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     

Laboratory professionals’ attitudes towards ISO 15189:2012 accreditation: an anonymous survey of three Croatian accredited medical laboratories

IntroductionEffective implementation and continual compliance with ISO 15189:2012 require ongoing commitment and active involvement of laboratory staff. Our aim was to assess attitudes regarding accreditation implementation by conducting a survey in three Croatian accredited medical laboratories.Materials and methodsAn anonymous survey consisting of 34 questions was distributed either electronically or in a paper form a week prior to scheduled annual audits. Distributions of answers regarding age, work experience, laboratory workplace, and education level and according to the respective laboratory were compared.ResultsThe overall response rate was 76% (225/297). Preference towards working in an accredited laboratory and a positive attitude were revealed by 70% and 56% participants, respectively, with better process documentation as the main advantage. Only 14% of responders considered themselves completely familiar with ISO 15189:2012. Total of 68% of responders felt that accreditation increases the usual workload, with excessive paperwork as the main contributor. Half of the responders declared partial agreement that accreditation requirements and expectations were clearly explained and claimed that their suggestions were taken into account only occasionally, which was especially emphasized by technical staff. The vast majority (89%) completely follow the prescribed protocols. Only 27% consider turnaround time monitoring useful. Competence assessment is considered efficient by 41% of responders. The majority (73%) prefer an online audit in times of COVID-19.ConclusionsDespite an overall positive attitude towards accreditation, further efforts are needed in providing better education about ISO 15189:2012 for technical staff and modifying formats of competence assessment, in order to achieve better adherence to ISO 15189:2012 requirements.     

Assessment of antinuclear antibodies (ANA): National recommendations on behalf of the Croatian society of medical biochemistry and laboratory medicine

Antinuclear antibodies (ANA) represent a family of autoantibodies targeting ubiquitous cellular constituents and are a hallmark of systemic inflammatory autoimmune rheumatic diseases named connective tissue diseases (CTD). The gold standard method for ANA determination is indirect immunofluorescence (IIF) on the human laryngeal epidermoid carcinoma cell line type 2 substrate (HEp-2), but with increasing demand for ANA testing, novel methods eased for automation emerged, which allows testing by staff less experienced in this specific field of laboratory diagnostic. In 2016 The working group (WG) for laboratory diagnostics of autoimmune diseases as part of the Committee for the Scientific Professional Development of the Croatian Society of Medical Biochemistry and Laboratory Medicine (CSMBLM) published the data of a survey regarding general practice in laboratory diagnostics of autoimmune diseases in Croatia. Results indicated high diversity in the performance of autoantibody testing as well as reporting of the results and indicated the need of creating recommendations for the assessment of ANA that would help harmonize diagnostics of systemic autoimmune rheumatic diseases in Croatia. This document encompasses twenty-seven recommendations for ANA testing created concerning indications for ANA testing, preanalytical, analytical, and postanalytical issues, including rational algorithm and quality control assurance. These recommendations are based on the relevant international recommendations and guidelines for the assessment of ANA testing and relevant literature search and should help to harmonize the approach in ANA testing and clarify differences in interpretation of the results obtained using different methods of determination.     

Endothelins -- clinical perspectives

Endothelins (ET) are a group of endogenous peptides, which have a strong and long-lasting vasoconstrictive effect. Three isoforms of endothelins coded by three different genes have been identified to date. Endothelin-1 (ET-1) is the most potent vasoconstrictive agent currently identified, and it was originally isolated and characterized from the culture media of aortic endothelial cells. Two other isoforms, named endothelin-2 (ET-2) and endothelin-3 (ET-3), were subsequently identified, along with structural homologues isolated from the venom ofActractapis engaddensis known as the sarafotoxins. The biological effects of endothelin production are determined via activation of one or two G-protein coupled receptors, endothelin receptors A (ETRA) and B (ETRB1 and ETRB2). Recently endothelin receptor C (ETRC) was discovered, however, its functions and distribution still remain unclear. The effects mediated by ET-1 via ETRA are vasoconstriction, bronchoconstriction and secretion of aldosterone. Agonists related to the ETRB1 activation cause vasodilatation by stimulating NO, PGI2 and endothelium-derived hyperpolarizing factor (EDHF). In contrast, coupling to ETRB2 causes vasoconstriction. Involvement of ET has been demonstrated in the pathophysiology of certain disorders. In this review, we discuss the physiological and pathophysiological role of endothelium-derived ET-1, the pharmacology of its two receptors, focusing on the role of ET-1 in the development of some pathophysiological conditions.