New ISO standards for medical biology laboratories, prescriptions and deviations / Nouvelles normes ISO pour les laboratoires de biologie médicale, prescriptions et déviations

ISO published the draft for final approval of the revision of ISO 15189 standard. Following ISO directives, ISO 15189 must be aligned with ISO/IEC 17025:2017 and should be less prescriptive. Draft ISO/DIS 15189 deviates in some points from ISO 17025 and the ISO indications to limit prescriptiveness: equipment, uncertainty, quality control. This do not seem to be justified by medical specificities and could complicate the understanding of the new requirements in medical laboratories.

ISO a publié le projet pour approbation finale de la révision de la norme ISO 15189. Conformément aux directives de l'ISO, la norme ISO 15189 doit être alignée sur la norme ISO/CEI 17025:2017 et doit être moins prescriptive. Le projet d'ISO/DIS 15189 s'écarte sur certains points de l'ISO 17025 et des indications de l'ISO pour limiter le caractère prescriptif : équipement, incertitude, contrôle de qualité. Cela ne semble pas justifié par les spécificités médicales et pourrait compliquer la compréhension des nouvelles exigences dans les laboratoires médicaux.

Guidance for faecal occult blood testing: quantitative immunochemical method (FIT-HB) in colorectal cancer screening programmes. / Guida per la determinazione del sangue occulto fecale: metodo immunochimico quantitativo (FIT-HB) nei programmi di screening per il carcinoma colorettale

BACKGROUND: in Italy, colorectal cancer screening is included as part of the Italian National Health Service - SSN (Servizio Sanitario Nazionale) Essential Levels of Care - LEA (Livelli Essenziali Assistenziali) and the European Guidelines, which specify quantitative FIT-Hb testing as the best strategy for organised screening programmes. To ensure consistent operating standards in Member States, European regulations require the implementation of certification and accreditation requirements for diagnostic and care-related processes. The requirement, based on ISO 17021 accreditation standards, includes ISO 9001 certification for systems and ISO 15189:2012 accreditation for laboratories. METHODOLOGY: various phases of the analytical process (pre-test, test, post-test) were evaluated in detail and provided operational guidelines for adjusting analytical and managerial procedures using: (a) feedback from members of GISCoR screening labs; (b) performance data obtained via a systematic review of the literature and the Osservatorio Nazionale Screening (ONS) Survey; (c) recommendations for laboratory practice issued by the World Endoscopy Organization "FIT for Screening" Working Group; (d) selected guidelines from the National Guidelines Clearinghouse database; and (e) Canadian, Australian and European screening programme websites. With respect to ISO 15189:2012 standards for accreditation of medical laboratories, GISCoR's guidance has been re-evaluated and revised by auditors from the Italian certification body (ACCREDIA) to assess its compliance and completeness with the aim of finalising operating procedures. CONCLUSIONS: the implementation and maintenance of operational standards required by complex systems (e.g. screening programmes) involving constant interaction between facilities and the supporting organisational structure are not easy to achieve. The guide aims to provide laboratories with the necessary guidance for proper process management.

Methodology to define biological reference values in the environmental and occupational fields: the contribution of the Italian Society for Reference Values (SIVR).

BACKGROUND: Biological reference values (RVs) explore the relationships between humans and their environment and habits. RVs are fundamental in the environmental field for assessing illnesses possibly associated with environmental pollution, and also in the occupational field, especially in the absence of established biological or environmental limits. OBJECTIVES: The Italian Society for Reference Values (SIVR) determined to test criteria and procedures for the definition of RVs to be used in the environmental and occupational fields. METHODS: The paper describes the SIVR methodology for defining RVs of xenobiotics and their metabolites. Aspects regarding the choice of population sample, the quality of analytical data, statistical analysis and control of variability factors are considered. The simultaneous interlaboratory circuits involved can be expected to increasingly improve the quality of the analytical data. RESULTS: Examples of RVs produced by SIVR are presented. In particular, levels of chromium, mercury, ethylenethiourea, 3,5,6-trichloro-2-pyridinol, 2,5-hexanedione, 1-hydroxypyrene and t,t-muconic acid measured in urine and expressed in micrograms/g creatinine (µg/g creat) or micrograms/L (µg/L) are reported. CONCLUSIONS: With the proposed procedure, SIVR intends to make its activities known to the scientific community in order to increase the number of laboratories involved in the definition of RVs for the Italian population. More research is needed to obtain further RVs in different biological matrices, such as hair, nails and exhaled breath. It is also necessary to update and improve the present reference values and broaden the portfolio of chemicals for which RVs are available. In the near future, SIVR intends to expand its scientific activity by using a multivariate approach for xenobiotics that may have a common origin, and to define RVs separately for children who may be exposed more than adults and be more vulnerable.

High prevalence of celiac disease in autoimmune hepatitis detected by anti-tissue tranglutaminase autoantibodies.

Celiac disease (CD) may be found in association with other autoimmune diseases. We investigated the relation between autoimmune hepatitis (AIH) and CD by assessing the prevalence of IgA and IgG anti-tissue transglutaminase (tTG) antibodies in AIH, and by verifying whether the findings were associated with clinical and histological features of CD. Forty-seven consecutive patients with AIH (type I: n = 39; type II: n = 8) were studied. One hundred patients with chronic hepatitis C, and 120 healthy blood donors were also studied as controls. We analyzed sera for the presence of IgA and IgG anti-tTG antibodies using a specific human recombinant tTG immunoenzymatic assay. Anti-tTG positive patients and controls were further tested for anti-endomysium antibodies (EMA) and HLA typing, and those found positive by either of these tests underwent duodenal biopsy to confirm a possible diagnosis of CD. Three of the 47 AIH patients (6.4%) were positive for IgA anti-tTG and EMA antibodies, and were subsequently confirmed to be affected with CD by small-bowel biopsy findings. No IgG anti-tTG positivity was found in the AIH patients. None of the controls were positive for IgA anti-tTG, and only one with chronic hepatitis C had a low positive reaction for IgG anti-tTG, which resulted as a false positive. The crude prevalence rate of CD in AIH was 63.8 per 1,000 (95% CI, 13.2-186.1), and it was significantly higher than that found in the general population in Italy (4.9 per 1,000; 95% CI, 2.8-7.8). The results of this study showed a high prevalence of CD in patients with AIH. For this reason, early serological screening testing for CD is strongly recommended for all AIH patients.

Immunoassay of anti-thyroid autoantibodies: high analytical variability in second generation methods.

The use of highly sensitive immunometric methods in clinical laboratories to assay anti-thyroid antibodies has progressively expanded in recent years but it is not known whether the new techniques have improved the analytical variability connected with the preceding methodologies. The Italian Society of Laboratory Medicine Study Group on Autoimmune Diseases conducted a collaborative study with the biomedical industry to evaluate the degree of standardization of the new analytical procedures. Twelve companies agreed to participate in the study on the search for anti-thyroglobulin (anti-Tg) and anti-thyroperoxidase (anti-TPO) antibodies in nine sera from patients with autoimmune thyroiditis, and in six sera from patients with non-autoimmune thyroid disease; ten immunometric and three immunofluorescence methods were employed. Agreement of qualitative results was close to 90% for anti-Tg and 97% for anti-TPO, with no important differences between the methods; variability of the quantitative results, expressed as CV% of absolute (in lU/ml) and relative (in cut-off concentration multiples) values was 93.9% and 102.3%, respectively, for anti-Tg, and 75.5% and 62.9%, respectively, for anti-TPO. These findings show that despite the progressive improvement in the analytical techniques, the variability between methods for the assay of anti-Tg and anti-TPO is still unexpectedly high, and probably due to several factors such as uncertainty in defining the positive cutoff concentration, absence of adequate international reference preparations, modality of autoantigen purification, and analytical variability in the assay procedures.

Guidelines for the laboratory use of autoantibody tests in the diagnosis and monitoring of autoimmune rheumatic diseases.

The Italian Society of Laboratory Medicine Study Group on the Diagnosis of Autoimmune Diseases has generated a series of guidelines for the laboratory diagnosis and monitoring of systemic autoimmune rheumatic diseases intendedfor the use of clinical pathologists and laboratory physicians. These guidelines are based on a systematic review of published works and expert panel discussion and consist of 13 recommendations for antinuclear antibodies, anti-double-stranded native DNA, and antinuclear specific antibodies. To improve analytic performances and help select the most appropriate test for specific autoantibodies, as well as provide education and guidance in the use of these tests, special emphasis is placed on laboratory methods.