Pre-analytical quality indicators in laboratory medicine: Performance of laboratories participating in the IFCC working group "Laboratory Errors and Patient Safety" project.

Quality indicators (QIs) are key tools for improving the quality of laboratory services, by reducing error rates and safeguarding patient safety. A body of accumulated evidence confirms the relevance of QIs and their impact on the overall quality of laboratory information. The consensus achieved on a list of "harmonized" QIs, along with the system used for data collection and reporting throughout an international benchmarking programme, has enabled achieving realistic performance targets, based on knowledge of the state-of-the-art. Data collected in 2017 and 2018 have been analyzed and performance measures obtained by laboratories participating in the project are summarized in the present article. The laboratory performance measures have been classified into three levels (optimum, desirable or minimum) in agreement with the widely accepted model of analytical quality specifications.

Soluble sPD-L1 and Serum Amyloid A1 as Potential Biomarkers for Lung Cancer.

BACKGROUND: The objective of this prospective study was to evaluate whether soluble programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) and serum amyloid A1 (SAA1) are potential diagnostic, predictive or prognostic biomarkers in lung cancer. METHODS: Lung cancer patients (n=115) with advanced metastatic disease, 101 with non-small cell lung cancer, NSCLC (77 EGFR wild-type NSCLC patients on chemotherapy, 15 EGFR mutation positive adenocarcinoma patients, 9 patients with mPD-L1 Expression ≥50% NSCLC - responders to immunotherapy), and 14 patients with small cell lung cancer (SCLC) were examined. ELISA method was used to determine sPD-L1 and SAA1 concentrations in patients' plasma. RESULTS: Significantly higher blood concentrations of sPD-L1 and SAA1 were noted in lung cancer patients compared with a healthy control group. In PD-L1+ NSCLC patients, a significantly higher sPD-L1 level was noticed compared to any other lung cancer subgroup, as well as the highest average SAA1 value compared to other subgroups. CONCLUSIONS: It seems that sPD-1/PD-L1 might be a potential biomarker, prognostic and/ or predictive, particularly in patients treated with immunotherapy. Serum amyloid A1 has potential to act as a good predictor of patients' survival, as well as a biomarker of a more advanced disease, with possibly good capability to predict the course of disease measured at different time points.

Immunoglobulin Heavy Chain Gene Rearrangements in Patients with Gaucher Disease.

BACKGROUND: Several studies support the evidence of increased incidence of hematological complications in Gaucher disease including monoclonal and polyclonal gammopathies and blood malignancies, especially multiple myeloma. METHODS: Serum concentrations of immunoglobulins and PCR analysis of the IGH gene rearrangements were performed. The clonal PCR products were directly sequenced and analyzed with the appropriate database and tools. Serum monoclonal proteins were detected and identified by electrophoresis. RESULTS: Among 27 Gaucher patients, clonal IGH rearrangement was discovered in eight, with 5/8 having also serum monoclonal protein. Elevated immunoglobulins were detected in 9/27 patients. Follow-up data for 17 patients showed that the clonal rearrangement remained the same in four of them, however, in one patient it disappeared after the follow-up period. The remaining 12/17 patients were without previous IGH clonal rearrangement and remained so after the follow-up. CONCLUSIONS: Although clonal expansion may occur relatively early in the disease course, at least judging by the IGH gene rearrangements in Gaucher patients, the detected clones may be transient. A careful clinical follow-up in these patients is mandatory, including monitoring for lymphoid neoplasms, especially multiple myeloma.

Quality Indicators in Laboratory Medicine: the status of the progress of IFCC Working Group "Laboratory Errors and Patient Safety" project.

The knowledge of error rates is essential in all clinical laboratories as it enables them to accurately identify their risk level, and compare it with those of other laboratories in order to evaluate their performance in relation to the State-of-the-Art (i.e. benchmarking) and define priorities for improvement actions. Although no activity is risk free, it is widely accepted that the risk of error is minimized by the use of Quality Indicators (QIs) managed as a part of laboratory improvement strategy and proven to be suitable monitoring and improvement tools. The purpose of QIs is to keep the error risk at a level that minimizes the likelihood of patients. However, identifying a suitable State-of-the-Art is challenging, because it calls for the knowledge of error rates measured in a variety of laboratories throughout world that differ in their organization and management, context, and the population they serve. Moreover, it also depends on the choice of the events to keep under control and the individual procedure for measurement. Although many laboratory professionals believe that the systemic use of QIs in Laboratory Medicine may be effective in decreasing errors occurring throughout the total testing process (TTP), to improve patient safety as well as to satisfy the requirements of International Standard ISO 15189, they find it difficult to maintain standardized and systematic data collection, and to promote continued high level of interest, commitment and dedication in the entire staff. Although many laboratories worldwide express a willingness to participate to the Model of QIs (MQI) project of IFCC Working Group "Laboratory Errors and Patient Safety", few systematically enter/record their own results and/or use a number of QIs designed to cover all phases of the TTP. Many laboratories justify their inadequate participation in data collection of QIs by claiming that the number of QIs included in the MQI is excessive. However, an analysis of results suggests that QIs need to be split into further measurements. As the International Standard on Laboratory Accreditation and approved guidelines do not specify the appropriate number of QIs to be used in the laboratory, and the MQI project does not compel laboratories to use all the QIs proposed, it appears appropriate to include in the MQI all the indicators of apparent utility in monitoring critical activities. The individual laboratory should also be able to decide how many and which QIs can be adopted. In conclusion, the MQI project is proving to be an important tool that, besides providing the TTP error rate and spreading the importance of the use of QIs in enhancing patient safety, highlights critical aspects compromising the widespread and appropriate use of QIs.

Verifying Sarcoidosis Activity: Chitotriosidase versus ACE in Sarcoidosis - a Case-control Study.

BACKGROUND: Until now, a proper biomarker(s) to evaluate sarcoidosis activity has not been recognized. The aims of this study were to evaluate the sensitivity and specificity of the two biomarkers of sarcoidosis activity already in use (serum angiotensin converting enzyme - ACE and serum chitotriosidase) in a population of 430 sarcoidosis patients. The activities of these markers were also analyzed in a group of 264 healthy controls. METHODS: Four hundred and thirty biopsy positive sarcoidosis patients were divided into groups with active and inactive disease, and groups with acute or chronic disease. In a subgroup of 55 sarcoidosis patients, activity was also assessed by F-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis. RESULTS: Serum chitotriosidase activities were almost 6 times higher in patients with active sarcoidosis than in healthy controls and inactive disease. A serum chitotriosidase value of 100 nmol/mL/h had the sensitivity of .5% and specificity of 70.0%. A serum ACE activity cutoff value of 32.0 U/L had the sensitivity of 66.0% and the specificity of 54%. A statistically significant correlation was obtained between the focal granulomatous activity detected on 18F-FDG PET/CT and serum chitotriosidase levels, but no such correlation was found with ACE. The levels of serum chitotriosidase activity significantly correlated with the disease duration (P < 0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (ρ =0.272, P =0.001). CONCLUSIONS: Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.

Haemostatic abnormalities in treatment-naïve patients with Type 1 Gaucher's disease.

There is a paucity of data on the effects of enzyme replacement therapy (ERT) on the coagulation abnormalities and platelet function of patients with Gaucher's disease (GDPs) and much of this data are controversial. This study investigates the haemostatic parameters in treatment-naïve GDPs and the effects of ERT. 31 Serbian treatment-naïve type 1 GDPs (M/F 17/14; median age 49 years, splenectomized 9/31) were studied. The complete blood count, prothrombin time (PT), activated partial tromboplastin time (aPTT) and coagulation factors were measured using the standard methods. Platelet aggregation was assessed with a whole-blood aggregometer. Splenic volumes were assessed using computer tomography. Twenty-one patients were treated with ERT (Imiglucerase). The haemostatic parameters were assessed after 6, 12 and 24 months (ERT(6, 12, 24)). Initially bleeding episodes were registered in 10/31 GDPs. Median platelet count was 108 × 10(9)/L; 22/31 GDPs were thrombocytopenic. The PT and aPTT values were abnormal in 16/31 and 13/31 GDPs, respectively. Platelet aggregation abnormalities were recorded in 19/31GDPs. Median platelet aggregation was reduced in response to adenosine-diphosphate 5 µmol/L (ADP(5) 0.46) and collagen 5 µmol/L (Col(5) 0.47). Splenic volume inversely correlated with the platelet count and a reduced response to arachidonic acid (AA), Col(5) and ADP(5) (p < 0.05). The splenectomized GDPs had a significantly lower platelet aggregation to Col(10) (p < 0.05). Bleeding GDPs had a significantly lower platelet count, higher chitotriosidase levels and a greater splenic volume compared to non-bleeding patients (p < 0.01). ERT: The number of bleeding GDPs had significantly decreased by ERT(6) (1/10; p < 0.01). The platelet count had significantly increased by ERT(6) (ERT(6) 180 × 10(9)/L, p < 0.01). The PT increased significantly from ERT(0) to ERT(24) (PT(0) 65%, PT(24) 81%; p < 0.05). The von Willebrand factor had increased significantly by ERT(6) and ERT(24) (ERT(0) 56%, ERT(6) 70%, ERT(12) 70%, ERT(24) 86%; p < 0.01). The number of GDPs with abnormal platelet aggregation had decreased significantly by ERT(6) (10/19; p < 0.05). Platelet aggregation on ADP(10) and AA significantly increased by ERT(6) (ADP(10): ERT(0) 0.75, ERT(6) 0.8 p < 0.01; AA: ERT(0) 0.7, ERT(6) 0.8 p < 0.05). In conclusion, platelet dysfunction and coagulation abnormalities were found in a considerable number of our GDPs. The absence of severe bleeding episodes suggests that the haemostatic system is sufficiently balanced and therefore the exact mechanism of the etiology of these abnormalities need to be fully clarified. ERT resulted in the cessation of bleeding and marked increase in platelet count, PT, vWF and platelet aggregation.