Women in sports: the applicability of common national reference intervals for inflammatory and coagulation biomarkers (HemSter Study)

IntroductionIntensive physical activity causes functional and metabolic changes in the athlete’s organism. The study aimed to verify the common national available reference intervals (RIs) for common inflammatory and screening coagulation tests in a population of healthy young female athletes.Materials and methodsOne hundred and twenty-one female athletes (age range: 16–34), from various sports disciplines (water polo, handball, volleyball, football, basketball), were included in the study. All participants completed the international physical activity short-form questionnaire. Blood samples were collected between 8–10 am, after an overnight fast, before any physical activity. Reference intervals were determined according to Clinical & Laboratory Standards Institute EP28-A3C Guidelines.ResultsCalculated RIs for white blood cell count (WBC), prothrombin time (PT), and activated partial thromboplastin time (APTT) ratio were in accordance with the common national RIs. Calculated RI for C-reactive protein (CRP) was lower (< 2.9 mg/L) than the proposed cut-off for a healthy population (< 5.0 mg/L). Reference interval for fibrinogen was higher (1.9–4.4 g/L), than the available RIs (1.8–3.5 g/L). D-dimer cut-off value was set at 852 µg/L fibrinogen equivalent units (FEU), higher than the proposed 500 µg/L FEU for venous thromboembolism (VTE) exclusion.ConclusionsThe applicability of the available RIs for WBC count, PT, and APTT-ratio was confirmed. However, RIs for CRP and fibrinogen differed significantly than the available common national RIs for the healthy non-athletes’ population. A higher cut-off for D-dimers should be extensively verified before implementation for VTE diagnosis exclusion in a group of healthy young female athletes.     

Long pentraxin 3 as a marker of COVID-19 severity: evidences and perspectives

IntroductionSeveral laboratory tests are characteristically altered in Coronavirus Disease 2019 (COVID-19), but are not totally accurate in predicting the disease outcome. The long pentraxin 3 (PTX3) is quickly released directly at inflammation sites by many immune cell types. Previous studies have shown that PTX3 correlated with disease severity in various inflammatory conditions. Our study investigated the use of PTX3 as a potential marker of COVID-19 severity and compared its performance in detecting a more severe form of the disease with that of routine laboratory parameters.Materials and methodsStored serum samples of RT-PCR confirmed COVID-19 cases that had been obtained at hospital admission were retrospectively analysed. Intensive care unit (ICU) stay was considered a surrogate endpoint of severe COVID-19. Pentraxin 3 was measured by a commercial enzyme-linked immunosorbent assay.ResultsA total of 96 patients were recruited from May 1st, 2020 to June 30th, 2020; 75/96 were transferred to ICU. Pentraxin 3 was higher in ICU vs non-ICU patients (35.86 vs 10.61 ng/mL, P < 0.001). Univariate and multivariate logistic regression models demonstrated that the only significant laboratory predictor of ICU stay was PTX3 (OR: 1.68 (1.19-2.29), P = 0.003), after controlling for comorbidities. The Receiver Operator Characteristic curve analysis showed that PTX3 had a higher accuracy compared to C-reactive protein (CRP), lactate dehydrogenase (LD), ferritin in identifying ICU patients (AUC of PTX3 = 0.98; CRP = 0.66; LD = 0.70; ferritin = 0.67, P < 0.001). A cut-off of PTX3 > 18 ng/mL yielded a sensitivity of 96% and a specificity of 100% in identifying patients requiring ICU.ConclusionHigh values of PTX3 predict a more severe COVID-19.     

Clinical Significance of Ischemia Modified Albumin in Critically Ill Patients with Sepsis

The study was conducted on 38 patients admitted into the intensive care unit with a provisional diagnosis of sepsis and 25 apparently healthy volunteers as controls. Serum procalcitonin (PCT) was assayed by an electrochemiluminescence method. Serum ischemia modified albumin (IMA), expressed as absorbance units was assayed by the albumin cobalt binding test. Patients with sepsis had significantly higher IMA levels (1.087 ± 0.786) as compared with those without sepsis (0.085 ± 0.234) with a p value <0.0001. The receiver operator characteristic (ROC) plot showed a sensitivity of 100 % and a specificity of 86.2 %. The area under the curve of the ROC plot was 0.917 with a p value of <0.0001. The higher levels of IMA serve to highlight the occurrence of ischemic damage which could be a prelude to poorer prognosis. The performance characteristics of IMA warrants its inclusion along with PCT as a parameter in the diagnosis of sepsis.     

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis

Introduction

Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis.

Materials and methods

Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed.

Results

Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test.

Conclusions

We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation.Key words: diagnostic marker, prostatitis, urinary asparagine-linked glycosylation     

Assay validity of point-of-care platelet function tests in thrombocytopenic blood samples

IntroductionPoint-of-care (POC) platelet function tests are faster and easier to perform than in-depth assessment by flow cytometry. At low platelet counts, however, POC tests are prone to assess platelet function incorrectly. Lower limits of platelet count required to obtain valid test results were defined and a testing method to facilitate comparability between different tests was established.Materials and methodsWe assessed platelet function in whole blood samples of healthy volunteers at decreasing platelet counts (> 100, 80-100, 50-80, 30-50 and < 30 x10⁹/L) using two POC tests: impedance aggregometry and in-vitro bleeding time. Flow cytometry served as the gold standard. The number of platelets needed to reach 50% of the maximum function (ED₅₀) and the lower reference limit (ED_ref) were calculated to define limits of test validity.ResultsThe minimal platelet count required for reliable test results was 100 x10⁹/L for impedance aggregometry and in-vitro bleeding time but only 30 x10⁹/L for flow cytometry. Comparison of ED₅₀ and ED_ref showed significantly lower values for flow cytometry than either POC test (P value < 0.05) but no difference between POC tests nor between the used platelet agonists within a test method.ConclusionCalculating the ED₅₀ and ED_ref provides an effective way to compare values from different platelet function assays. Flow cytometry enables correct platelet function testing as long as platelet count is > 30 x10⁹/L whereas impedance aggregometry and in-vitro bleeding time are inconsistent unless platelet count is > 100 x10⁹/L.     

Use of biochemical parameters for non-invasive screening of oesophageal varices in comparison to elastography-based approach in patients with compensated advanced chronic liver disease

IntroductionOesophageal varices are routinely diagnosed by esophagogastroduodenoscopy (EGD), and their bleeding has high mortality. We aimed to evaluate diagnostic performance of biochemical tests in comparison to elastography-based approaches, as non-invasive alternatives to EGD, for ruling-out high risk oesophageal varices (HRV).Material and methodsRetrospective analysis of patients (N = 861) who underwent liver stiffness measurement (LSM) by transient elastography (TE) in a single centre over 5-year period, with available results of EGD (within 3 months from LSM). Only patients with suspicion of compensated advanced chronic liver disease (cACLD) defined by LSM ≥ 10 kPa were included comprising the final cohort of 73 subjects. Original and expanded Baveno VI criteria (B6C), controlled attenuation parameter (CAP), platelet count (PLT), aspartate aminotransferase to PLT ratio index (APRI), Fibrosis-4 index (FIB4), model for end stage liver disease (MELD) score were evaluated against the results of EGD that served as the reference method.ResultsAnalysed patients had median age 62 years, 59/73 (0.81) were males, 54/73 (0.74) had alcoholic/non-alcoholic fatty liver disease, and 21/73 (0.29) had HRV. In multivariate logistic regression analysis only LSM and PLT were independently associated with HRV. The best performing tests for ruling-out HRV (% of spared EGD; % of missed HRV) were respectively: LSM < 20 kPa (53.4%; 0%), B6C (38%; 0%), Expanded B6C (47.9%; 4.8%); PLT > 214x10⁹/L (21.9%; 0%); FIB4 ≤ 1.8 (21.4%; 0%), APRI ≤ 0.34 (12.3%; 0%). CAP, MELD = 6 alone or combined with PLT > 150(x10⁹/L) did not show acceptable performance.ConclusionThe best performing biochemical tests for ruling-out HRV in our cohort of patients were PLT and FIB-4, but they were still outperformed by elastography-based approaches.Keyword: portal hypertension, cirrhosis, platelet count, esophageal varices, non-invasive tests     

Indirect reference intervals for haematological parameters in capillary blood of pre-school children

IntroductionIndirect estimation of reference intervals (RIs) is straightforward and inexpensive procedure for determination of intra-laboratory RIs. We applied the indirect approach to assess RIs for haematological parameters in capillary blood of pre-school children, using results stored in our laboratory database.Materials and methodsWe extracted data from laboratory information system, for the results obtained by automatic haematology analyser in capillary blood of 154 boys and 146 girls during pre-school medical examination. Data distribution was tested, and logarithmic transformation was applied if needed. Reference intervals were calculated by the nonparametric percentile method.ResultsReference intervals were calculated for: RBC count (4.2-5.4 x10¹²/L), haemoglobin (114-146 g/L), MCH (25.0-29.4 pg), MCHC (321-368 g/L), RDW-SD (36.1-43.5 fL), WBC count (4.5-12.3 x10⁹/L), neutrophils count (1.7-6.9 x10⁹/L) and percentage (29.0-69.0%), lymphocytes count (1.6-4.4 x10⁹/L) and percentage (21.9-60.7%), PLT (165-459 x10⁹/L), MPV (8.1-11.4 fL) and PDW (9.2-14.4%). Gender specific RIs were calculated for monocytes count (male (M): 0.2-1.6 x10⁹/L; female (F): 0.1-1.4 x10⁹/L) and percentage (M: 2.5-18.3%; F: 1.8-16.7%), haematocrit (M: 0.34-0.42 L/L; F: 0.34-0.43 L/L), MCV (M: 73.4-84.6 fL; F: 75.5-84.2 fL) and RDW (M: 12.1-14.3%; F: 11.7-13.9%), due to observed gender differences in these parameters (P = 0.031, 0.028, 0.020, 0.012 and 0.001; respectively). Estimated RIs markedly varied from the literature based RIs that are used in the laboratory.ConclusionsIndirect method employed in this study enables straightforward assessment of RIs in pre-school children. Herein derived RIs differed from the literature-based ones, indicating the need for intra-laboratory determination of RIs for specific populations and sample types.     

Effects of specimen haemolysis on complete blood count results by Abbott Alinity hq System

IntroductionThe current study aimed to assess the interference of in vitro haemolysis on complete blood count (CBC) using Abbott Alinity hq system, and to determine which haemolysis levels affect the reliability of sample results.Materials and methodsBlood samples obtained from 25 volunteers in K3-EDTA tubes were divided into four aliquots. The first aliquot was not subjected to any intervention. The second, third and fourth aliquots were passed through a fine needle 2, 4 and 6 times, respectively. Complete blood count was performed by multi-angle polarized scatter separation technology and haemolysis index (HI) was assessed from the plasma samples separated by centrifugation. Five groups were formed according to the HI values. The percentage biases between the results of non-haemolysed and haemolysed groups were compared with the desirable bias limits from The European Federation of Clinical Chemistry and Laboratory Medicine database and reference change values (RCVs).ResultsIn groups 1 to 4, the effects of haemolysis on CBC parameters were acceptable comparing to the analytical bias except for lymphocytes (7.26%-7.42%), MCH (2.59%), and MCHC (0.47%-2.81%). Results of group 5 (gross haemolysis) showed decreases in HCT(- 4.56%), RBC (- 4.07%) count and increase in lymphocyte (11.60%) count higher than the analytical performance specifications. Moreover, variations in MCH (4.65%) and MCHC (5.24%) were exceeding the RCVs.ConclusionsGross haemolysis (haemoglobin concentration > 10 g/L) is likely to produce unreliable CBC results on non-pathological samples. Further studies including pathological specimens are needed.     

Serum Urea:Albumin Ratio as a Prognostic Marker in Critical Patients With Non-Chronic Kidney Disease

Routine laboratory investigations play an important role in estimating the risk of mortality in intensive care unit (ICU) patients. The significance of urea:albumin ratio (UAR) in predicting the stay and mortality of ICU patients is not known. It is a retrospective study of patients admitted to ICU (n = 412) with non-chronic kidney disease (non-CKD). Receiver-operating characteristics (ROC) analysis for predicting mortality was carried out to find area under curve (AUC) and threshold levels. Analysis of survival probability was carried out by Kaplan–Meier method and Log-rank test. The AUC to predict mortality were 0.695, 0.767 and 0.791 for serum albumin, urea and UAR, respectively. The threshold levels for albumin, urea and UAR were 2.8 g/dL, 53 mg/dL, and 23.44 mg/g, respectively. The highest odds ratio (OR) of 9.75 to predict mortality at threshold level was observed for UAR, while OR were 7.0 and 3.62 for serum urea and albumin, respectively. The serum urea above and albumin below threshold level were associated with increase in ICU stay of >3 days but the highest OR of 4.73 to predict stay of >3 days was observed for UAR. Kaplan–Meier survival analysis shows significant (p < 0.001) difference at the threshold value of UAR. Serum urea and albumin are found to be an independent predictor for the mortality and stay; however an increased UAR value is the best parameter in predicting mortality and stay in ICU patients with non-CKD illness.     

Assessment of Hematological Parameters in Pulmonary Tuberculosis Patients

The aim of the study was the assessment of hematological parameters in pulmonary tuberculosis patients. Forty patients diagnosed with tuberculosis were recruited from the Institute of Thoracic Medicine on the basis of history, clinical examination, chest radiography, sputum examination and related laboratory parameters and were compared with age and sex matched healthy volunteers (n = 40). Hematological parameters and CRP in tuberculosis patients were determined. The mean values for serum hemoglobin level, RBC count and platelet count in PTB was found to be less (p < 0.001). Erythrocyte sedimentation rate (ESR), plasma C-reactive protein, WBC count in PTB subjects was increased (p < 0.001 for ESR & CRP, p < 0.05 for WBCs) and all were statistically significant. This study demonstrated that serum hemoglobin level, RBC count and platelet count was decreased in tuberculosis patients whereas ESR, CRP and WBC count was increased when compared with healthy controls.     

The rise in preanalytical errors during COVID-19 pandemic

IntroductionThe COVID-19 pandemic has posed several challenges to clinical laboratories across the globe. Amidst the outbreak, errors occurring in the preanalytical phase of sample collection, transport and processing, can further lead to undesirable clinical consequences. Thus, this study was designed with the following objectives: (i) to determine and compare the blood specimen rejection rate of a clinical laboratory and (ii) to characterise and compare the types of preanalytical errors between the pre-pandemic and the pandemic phases.Materials and methodsThis retrospective study was carried out in a trauma-care hospital, presently converted to COVID-19 care centre. Data was collected from (i) pre-pandemic phase: 1^st October 2019 to 23^rd March 2020 and (ii) pandemic phase: 24^th March to 31^st October 2020. Blood specimen rejection rate was calculated as the proportion of blood collection tubes with preanalytical errors out of the total number received, expressed as percentage.ResultsTotal of 107,716 blood specimens were screened of which 43,396 (40.3%) were received during the pandemic. The blood specimen rejection rate during the pandemic was significantly higher than the pre-pandemic phase (3.0% versus 1.1%; P < 0.001). Clotted samples were the commonest source of preanalytical errors in both phases. There was a significant increase in the improperly labelled samples (P < 0.001) and samples with insufficient volume (P < 0.001), whereas, a significant decline in samples with inadequate sample-anticoagulant ratio and haemolysed samples (P < 0.001).ConclusionIn the ongoing pandemic, preanalytical errors and resultant blood specimen rejection rate in the clinical laboratory have significantly increased due to changed logistics. The study highlights the need for corrective steps at various levels to reduce preanalytical errors in order to optimise patient care and resource utilisation.     

Verification of a 6-part differential haematology analyser Siemens Advia 2120i

IntroductionThe aim of this study was to perform a comprehensive verification of a 6-part differential haematology analyser Siemens Advia 2120i (Erlangen, Germany), prior to its routine implementation.Materials and methodsOur verification protocol included: precision (within- and between-run), estimated bias (%) as measure of trueness, which was calculated from observed and manufacturers’ declared value, analytical measuring interval (AMI), carryover, confirmation of a limit of blank (LoB), determination of a limit of detection (LoD) and limit of quantitation (LoQ). The K₂ ethylenediaminetetraacetic acid (EDTA) patients’ leftover samples were used for verification of analyser Advia 2021i. Acceptance criteria were based on manufacturer technical specifications (Siemens), 2016 state-of-the-art criteria (Vis and Huisman), and EFLM Biological Variation Database.ResultsThe within- and between-run precision were acceptable for all parameters and the lowest coefficients of variation were observed for mean corpuscular volume (MCV) (0.3% and 0.6%, respectively). Estimated bias was within the acceptance criteria for all parameters except for MCV (the estimated bias was 2.2% (acceptance criteria 2.0%). AMI was confirmed for all tested parameters (r > 0.99). The carryover estimates ranged from 0.1% for platelet count (Plt) to 0.6% for red blood cell count and were within the manufacturers’ specifications (≤ 1%). Manufacturers’ claims for LoB were confirmed for leukocytes, erythrocytes, haemoglobin, and platelets. The estimated LoD and LoQ were 0.05 x10⁹/L and 0.1 x10⁹/L for white blood cell count, while for Plt values were 2 x10⁹/L and 3 x10⁹/L, respectively.ConclusionsAnalytical performance of the Siemens Advia 2120i meets predefined quality goals and is suitable for routine use in a clinical laboratory.Key words: verification, haematology analyser, haematology, blood cell count     

Activated Carbon Fabric Mask Reduces Lead Absorption and Improves the Heme Biosynthesis and Hematological Parameters of Battery Manufacturing Workers

Activated carbon fabrics (ACF) mask prevents the absorption of lead and reduce its adverse effects of human health. Aim of this study to know the blood lead level and its effects on heme biosynthesis and hematological parameters after using 2 months activated carbon fabric mask of battery manufacturing workers (BMW). Blood lead level, heme biosynthesis and hematological parameters were measured by using standard method. Blood lead level (P < 0.001, − 13.5%) was significantly decreased, activated δ-aminolevulinic acid dehydratase (P < 0.001, 11.97%) and non-activated δ- aminolevulinic acid dehydratase (P < 0.001, 23.17%) enzyme activity were significantly increased, however, the ratio of activated to Non-activated δ- ALAD (P < 0.001, − 10.13%) was significantly decreased, urinary excretion of δ- aminolevulinic acid (P < 0.001, − 10.49%) and porphobilinogen (P < 0.001, − 7.38%) were significantly decreased after using 2 months ACF mask as compared to before using mask of BMW. Hematological parameters i.e Hb (P < 0.05, 13.42%), PCV (P < 0.05, 7.23%), MCV (P < 0.05, 1.9%) were significantly increased and total WBC count (P < 0.05, − 5.18%) was significantly decreased after using 2 months ACF mask as compared to before using mask of BMW. Two months using ACF mask reduces the blood lead level and improves the δ-ALDH activity and hematological parameters, decreases the urinary excretion of δ-ALA, PBG of battery manufacturing workers. Therefore, the regular using of ACF mask is beneficial to prevent the lead absorption and its adverse effects on human health.     

Comparison of hyaluronic acid in patients with rheumatoid arthritis,systemic sclerosis and systemic lupus erythematosus

IntroductionThe aim of the present study was to determine and compare the concentration of hyaluronic acid (HA) in rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE), and its correlation with parameters of disease activity and duration. The hypothesis was that HA should be increased in rheumatic diseases. We also expected that HA could be a marker of disease activity and inflammation in some of these diseases.Materials and methodsThe study group comprised 149 patients with RA, SSc and SLE hospitalized in the Department of Rheumatology and Internal Diseases, Medical University of Bialystok (Bialystok, Poland) and 30 healthy controls. The concentrations of HA, C-reactive protein (CRP) and rheumatoid factor (RF) were measured using Architect ci8200; haemoglobin, platelets on Sysmex XS-800i; and erythrocyte sedimentation rate (ESR) on Sediplus S 2000 analysers. Statistical analysis was performed using Statistica 13.3 PL.ResultsHyaluronic acid was increased in RA, SLE and SSc when compared to controls (P < 0.001, P = 0.011, and P = 0.015, respectively). There were no differences in HA between rheumatic diseases (P = 0.840). Hyaluronic acid positively correlated with SLE activity (P = 0.025). In RA, HA positively correlated with ESR (P = 0.028) and CRP (P = 0.009). However, HA was not found to correlate with the duration of rheumatic diseases.ConclusionsHyaluronic acid concentration undergoes changes in rheumatic diseases with no difference between RA, SLE and SSc. In RA, HA concentration can be a marker of inflammation, while in SLE patients an indicator of disease activity.     

中华医学会系列杂志媒体融合发展实践

[目的]介绍中华医学会系列杂志媒体融合发展的实践,以期为国内科技期刊同行提供借鉴。[方法]以中华医学会系列杂志发展策略和多种媒体发展具体案例为例,介绍中华医学会系列杂志媒体融合发展现状。[结果]顺应媒体融合发展趋势,中华医学会系列杂志基于集群优势逐步实现了期刊出版全程的信息化管理、期刊资源整合、数字化平台和新媒体的融合发展。[结论]掌握并积极应用先进的数字出版技术,有助于实现期刊群内容资源的有效整合,提升展示效果。     

Interrelationship Between Procalcitonin and Organ Failure in Sepsis

Sepsis suffers from lack of specific clinical symptoms which contribute to one of the major causes of mortality. In the present study, our aim was to evaluate the role of a recent biomarker Procalcitonin (PCT) in predicting organ dysfunction. 71 patients admitted with sepsis were included in the study. PCT levels were measured at 0, 24, 72 h and 7th day and sequential organ failure assessment score (SOFA) scores were calculated. PCT levels significantly decreased (p < 0.001) in 89.3 % of surviving patients, whereas, in 60 % non surviving patients the PCT level increased significantly (p < 0.001). A significant positive correlation between PCT and SOFA score was observed in survivors at each hour. These observations indicate that PCT concentration is significantly associated with severity of multi organ dysfunction and also helps in determining the prognosis of septic patients.     

Reevaluation of von Willebrand disease diagnosis in a Croatian paediatric cohort combining bleeding scores,phenotypic laboratory assays and next generation sequencing: a pilot study

IntroductionThis study reevaluated von Willebrand disease (vWD) diagnosis in a Croatian paediatric cohort by combining bleeding scores (BS), phenotypic laboratory testing, and next-generation sequencing (NGS).Materials and methodsA total of 25 children (11 males and 14 females, median age 10 years, from 2 to 17) previously diagnosed with vWD were included. BS were calculated using an online bleeding assessment tool. Phenotypic laboratory analyses included platelet count, platelet function analyser closure times, prothrombin time, activated partial thromboplastin time, von Willebrand factor antigen (vWF:Ag), vWF gain-of-function mutant glycoprotein Ib binding activity (vWF:GPIbM), vWF collagen binding activity (vWF:CBA), factor VIII activity (FVIII:C) and multimeric analysis. Next-generation sequencing covered regions of both vWF and FVIII genes and was performed on MiSeq (Illumina, San Diego, USA).ResultsDisease-associated variants identified in 15 patients comprised 11 distinct heterozygous vWF gene variants in 13 patients and one novel FVIII gene variant (p.Glu2085Lys) in two male siblings. Four vWF variants were novel (p.Gln499Pro, p.Asp1277Tyr, p.Asp1277His, p.Lys1491Glu). Three patients without distinctive variants had vWF:GPIbM between 30 and 50%. Patients with identified vWF gene variants had statistically significant lower values of vWF:GPIbM (P = 0.002), vWF:Ag (P = 0.007), vWF:CBA (P < 0.001) and FVIII:C (P = 0.002), compared to those without. Correlations between BS and phenotypic laboratory test results were not statistically significant for either of the tests.ConclusionThe applied diagnostic approach confirmed the diagnosis of vWD in 13 patients and mild haemophilia A in two. Limited utility of BS in the paediatric population was evidenced.     

Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy

Standard chemotherapy regimens for remission induction of pediatric acute myeloid leukemia (AML) are associated with significant morbidity and mortality. We performed a cohort study to determine the impact of reducing the intensity of remission induction chemotherapy on the outcomes of selected children with AML treated with a low-dose induction regimen plus granulocyte colony stimulating factor (G-CSF) (low-dose chemotherapy (LDC)/G-CSF). Complete response (CR) after two induction courses was attained in 87.0% (40/46) of patients receiving LDC/G-CSF. Post-remission therapy was offered to all patients, and included standard consolidation and/or stem cell transplantation. During the study period, an additional 94 consecutive children with AML treated with standard chemotherapy (SDC) for induction (80/94 (85.1%) of the patients attained CR after induction II, P = 0.953) and post-remission. In this non-randomized study, there were no significant differences in 4-year event-free (67.4 vs. 70.7%; P = 0.99) and overall (70.3 vs. 74.6%, P = 0.69) survival in the LDC/G-CSF and SDC cohorts, respectively. After the first course of induction, recovery of white blood cell (WBC) and platelet counts were significantly faster in patients receiving LDC/G-CSF than in those receiving SDC (11.5 vs. 18.5 d for WBCs (P < 0.001); 15.5 vs. 22.0 d for platelets (P < 0.001)). To examine the quality of molecular response, targeted deep sequencing was performed. Of 137 mutations detected at diagnosis in 20 children who attained hematological CR after two courses of LDC/G-CSF (n = 9) or SDC (n = 11), all of the mutations were below the reference value (variant allelic frequency <2.5%) after two courses, irrespective of the treatment group. In conclusion, children with AML receiving LDC/G-CSF appear to have similar outcomes and mutation clearance levels, but significantly lower toxicity than those receiving SDC. Thus, LDC/G-CSF should be further evaluated as an effective alternative to remission induction in pediatric AML.     

Increased plasma vaspin concentration in patients with sepsis: an exploratory examination

Introduction

Vaspin (visceral adipose tissue-derived serpin) was first described as an insulin-sensitizing adipose tissue hormone. Recently its anti-inflammatory function has been demonstrated. Since no appropriate data is available yet, we sought to investigate the plasma concentrations of vaspin in sepsis.

Materials and methods

57 patients in intensive care, fulfilling the ACCP/SCCM criteria for sepsis, were prospectively included in our exploratory study. The control group consisted of 48 critically ill patients, receiving intensive care after trauma or major surgery. Patients were matched by age, sex, weight and existence of diabetes before statistical analysis. Blood samples were collected on the day of diagnosis. Vaspin plasma concentrations were measured using a commercially available enzyme-linked immunosorbent assay.

Results

Vaspin concentrations were significantly higher in septic patients compared to the control group (0.3 (0.1-0.4) ng/mL vs. 0.1 (0.0-0.3) ng/mL, respectively; P < 0.001). Vaspin concentration showed weak positive correlation with concentration of C-reactive protein (CRP) (r = 0.31, P = 0.002) as well as with SAPS II (r = 0.34, P = 0.002) and maximum of SOFA (r = 0.39, P < 0.001) scoring systems, as tested for the overall study population.

Conclusion

In the sepsis group, vaspin plasma concentration was about three-fold as high as in the median surgical control group. We demonstrated a weak positive correlation between vaspin and CRP concentration, as well as with two scoring systems commonly used in intensive care settings. Although there seems to be some connection between vaspin and inflammation, its role in human sepsis needs to be evaluated further.Key words: adipocytokine, inflammation, vaspin, CRP, intensive care