Clostridioides difficile is a Gram-positive, spore-forming anaerobic enteropathogen responsible for a wide spectrum of clinical diseases ranging from mild diarrhoea to pseudomembranous colitis. It is the first cause of healthcare-associated diarrhoeas, but community-associated Clostridioides difficile infections (CDI) are increasingly reported in patients without the common risk factors (age > 65 years, previous antibiotic treatment). The main C. difficile virulence factors are toxins A (TcdA) and B (TcdB), and in some cases the binary toxin. The CDI incidence has increased in Europe since the early 2000s, then decreased to reach approximately 4 cases/10,000 patients/days. C. difficile should be tested only in diarrheal stools. Children less than 3 years old are frequently colonized, therefore CDI diagnosis should be carried out only in specific cases (outbreak, Hirschsprung disease). No stand-alone method can be used for the CDI diagnosis. The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) recommends a two-step algorithm with a sensitive screening test (molecular assay or glutamate dehydrogenase immunochromatographic assay). If the screening test is negative, the CDI diagnosis can be ruled out. If the screening test is positive, a second highly specific test should be used, such as toxin A/B immunochromatographic assay.

It is important that a clinical laboratory has implemented appropriate procedures for quality control, which includes both internal quality control (IQC) and external quality assessment (EQA) with the common goal to detect systematic errors and random errors. It is the case for both the Hemohub® Bayesian tools for IQC results interpretation and the ECAT EQA optimised bivariate z-scores analysis. On a concrete case study, we demonstrate both the higher sensitivity and specificity of optimised bivariate z-scores analysis than the univariate approach. The Bayesian IQC results interpretation like the ECAT analysis confirmed the explicit conclusion i.e. an increase of the random error corresponding to the increase of the inter assay coefficient of variation (CV) at the date of EQA samples runs. Improvement of repaired dysfunction could be then daily observed on IQC results and then confirmed on EQA results thanks to the complementarity of the two approaches.

This observation reports the case of an occupational allergic asthma in a laboratory technician, caused by exposure to formaldehyde. She experienced feelings of discomfort during low exposure, below the regulatory exposure thresholds. Sent to occupational medicine, signs of an asthma attack were noted by the doctor. Respiratory function tests showed bronchial hyperactivity. The diagnosis of formaldehyde asthma was made due to the recurrence of signs during exposure and the absence of other allergies. This type of occupational asthma is rare nowly and this case is an opportunity to recall what the different occupational asthmas are and which are the most common among laboratory technicians.

Urine drug screening is carried out on numerous automated analysis platforms using enzyme-linked immunosorbent assays. While these methods are rapid, they often lack specificity. We report the case of a 5-year-old child treated for Dravet disease and hospitalized for clonic seizures. During her hospitalization, 3 urine samples were sent to the Toxicology laboratory to rule out any toxic origin to these seizures. The first two were positive for ecstasy, and negative for other drugs. For the last sample, all tests were negative. The presence of ecstasy in the first 2 samples was not confirmed by gas chromatography-mass spectrometry, which identified stiripentol in all 3 urines. Stiripentol is an antiepileptic drug that shares a 3,4-methylenedioxy group with MDMA. We determined that the antibody in the kit crossed 20% with stiripentol, and were able to define a stiripentol cut-off concentration of 2,500 ng/mL. We checked this cut-off by measuring stiripentol in the 3 urine samples, finding concentrations of 47,600 and 5,800 ng/mL for the first and second samples respectively, and 1,900 ng/mL for the last. These concentrations explain the false positives in the first two urine samples, and the negative result in the last. This work underlines the need to remain critical of the results of immuno-screening methods, and to confirm them with a reference method.

The Working Group Preanalytical Phase of the European Federation of Clinical Chemistry and Laboratory Medicine advises suppressing haemolysis-sensitive tests when haemolysis is clinically significant, as improper specimen handling can rupture red blood cells, increasing potassium levels. Thus, a correctly repeated blood sample should show lower potassium levels than a haemolysed one. This study aimed to determine the prevalence of haemolysed samples with potassium levels below the reference range and whether this predicts hypokalemia in repeated collections. From March 2022 to March 2024, 396,640 non-haemolysed samples (H-index < 2 UA) were analyzed. Samples with an H-index ≥ 2 AU were classified as haemolysed, and potassium values were suppressed. Warnings were issued for haemolysed samples with potassium below the reference range (3.4-4.5 mmol/L), advising new sample collection. Twenty-five (0.01%) repeat samples were taken within 24 hours of a previously haemolysed sample with low potassium. Severe and moderate hypokalemia were more common in these repeats, with severe hypokalemia (≤2.5 mmol/L) found in 48% of repeat tests, compared to 0.3% in all samples. Though rare, a decrease in potassium in haemolysed samples often precedes hypokalemia diagnosis. Implementing a simple and cost-effective LIS algorithm to alert clinicians could potentially reduce diagnosis and treatment time.

While the latest WHO classification of hematological neoplasms helps refine the diagnostic criteria for anaplastic large cell lymphomas (ALCL), their diagnosis can still be challenging. This retrospective series of 10 ALCL cases illustrates the cytological appearance and immunological profile obtained through flow cytometry (FCM) from various sample types, including lymph node biopsies (LN), peripheral blood (PB), cerebrospinal fluid (CSF), and pleural fluid (PF). ALCL exhibits a polymorphic cytological appearance, ranging from "doughnut" cells to Hodgkin-like cells, very large cells, and small cells, with this polymorphism being particularly pronounced in ALK (-) forms. The detection of cytotoxic CD4+ T-cells by FCM aids in confirming the diagnosis, especially in small cell forms, which typically correspond to circulating phases. Cytological orientation, particularly for LNB, helps optimize the FCM panel to be used and ensures that ALCL, which frequently shows a loss of pan-T markers, is not overlooked. In conclusion, while the final diagnosis is histological, cytological analysis combined with FCM provides an initial diagnostic orientation for ALCL and guides complementary genetic analyses.

The diagnosis of subarachnoid hemorrhage (SAH) is extremely important for appropriate management. Cerebral computed tomography (CT), used as the first-line investigation to detect bleeding, has excellent sensitivity if performed promptly, but its sensitivity falls sharply with the time elapsed since the onset of SAH. Oxyhemoglobin and bilirubin, the breakdown products of heme, are detectable in cerebrospinal fluid (CSF) by spectrophotometric absorption, which defines the search for xanthochromia pigment in CSF. Both parameters can be sought when imaging is negative or doubtful with a strong suspicion of SAH based on clinical signs. In this context, our working group at the Société Française de Biologie Clinique (SFBC) is proposing recommendations to provide medical biologists with support for the implementation and validation of "oxyhemoglobin and bilirubin in CSF" test and enabling them to play their part in the diagnostic process. From the pre-analytical stages through to the delivery of results, we will summarize the pitfalls to be avoided, the main decision values and different physiological and pathological profiles.

Tuberculosis remains one of the leading causes of mortality worldwide. Microscopy and culture still the references of Tuberculosis diagnosis. Microscopy has a low sensitivity, specificity and culture is time consuming. For this reason, rapid and reliable diagnosis of the disease is required. We describe a retrospective comparison study of tuberculosis diagnosis by PCR IS6110 directly from blood samples of patients with suspected Tuberculosis with Acid-Fast-Bacilli and culture. From 80 patients enrolled, culture results were positive for 25, acid fast bacilli were positive for 15 and blood PCR were positive for 45. Comparing blood PCR result with acid fast bacilli, the sensitivity and specificity were respectively 35% and 87.5% (PPV = 9%, PNV = 21.1%) for PTB. The specificity of blood PCR was 100% (PNV = 72.73%), for EPTB. In comparison with culture blood PCR have a high sensitivity and specificity better than with the acid fast, they were respectively 57.89%, 100% for PTB and 50%, 100% for EPTB. This study is the first established in Tunisia and in Africa aiming to diagnose TB from blood. B-PCR results has shown a high correlation with culture that illustrates the usefulness of B-PCR as a rapid and early diagnostic, combined with others serological results B-PCR can be a solid, rapid and efficient TB diagnostic tools.

A new direction of research was established due to biofilms' infections caused by a mixture of fungal and bacterial species. Diagnosis of these infections becomes more difficult and high doses of drugs are used in treatment, especially in critically ill patients. The aim of the current study was to examine the effects of amphotericin B, in combination with imipenem or colistin against Candida albicans - Acinetobacter baumannii- Proteus mirabilis and Candida tropicalis - Acinetobacter baumannii -Proteus mirabilis polymicrobial biofilms. According to the microdilution method of the Clinical Laboratory Standards Institute (CLSI) published in documents M27-A3 (2008) and M07-A10 (2015) respectively, the susceptibility of the clinical isolates Candida yeasts to amphotericin B and Gram-negative bacteria to imipenem and colistin was determined. A Checkerboard assay was employed to evaluate the efficacy of drugs combinations. The 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT) reduction assay was used to quantify the biofilms. The combination amphotericin B/colistin and amphotericin B/imipenem did not produce obvious effects against the polymicrobial biofilms formed for 48 hours. Whereas colistin alone produced strong effects against Candida albicans-Acinetobacter baumannii and Candida albicans - Acinetobacter baumannii -Proteus mirabilis compared to Candida tropicalis - Acinetobacter baumannii and Candida tropicalis - Acinetobacter baumannii - Proteus mirabilis polymicrobial biofilms. For mixed Candida spp. bacterial biofilms, these results point to the difficulties in eradicating these biofilms, as well as in preventing their development.

Hemoglobin (Hb) measurement is a fundamental biological test, especially in emergency situations where rapid medical decisions are required. Portable hemoglobinometers, such as HemoCue®, provide a delocalized solution for capillary whole blood. The SFBC's POCT News and Issues working group designed and conducted two national surveys to assess the use and management of these devices, both on the clinical and biological side, with 306 and 160 responses respectively. The surveys revealed little effective or desired network connection, heterogeneity in management and training, and only 7% of sites fully accredited, although a quality approach is being structured in 45% of cases. Nearly 80% of biologists suggest reclassification as a rapid diagnostic test, citing difficult standards management and inadequate human resources. However, its daily use goes beyond the simple diagnostic orientation of anemia; blood transfusion decisions without laboratory verification are made by 53% of physicians, while 18% of users are unaware of minimum maintenance procedures, underscoring the need for a rigorous quality approach. The SFBC working group proposes a list of tips to help medical biologists implement this approach, a guarantee of reliable results, in the context of medical decision-making. The selected points are fleet mapping, relations with biomedical and clinical departments, quality documents and minimum method verification, user management, QC management and traceability of results.

The relevant and correct prescribing of medical biology is a major public health issue. Correct prescribing is a legal obligation under article L6211-8 of the French Public Health Code and is an integral part of the biologist's daily work, already specified in the 2012 (section 4.7) and 2022 (section 5.3.3) versions of the NF EN ISO 15189 standard. COFRAC document SH REF 02 v08 specifies the requirements for consultancy services. The adaptation of the prescriptions is a revision of the contract with the prescriber, which makes it possible to optimize patient care and ensure the satisfaction of the laboratory users. Although essential, accurate prescribing is time consuming. "Chronophage" is the term that has been used for almost a decade. At present, the work of biologists in this area is not valued. In fact, there is no evaluation system to highlight this regulation control activity. To date, no work has been published to estimate this time, this chronophagy, and to evaluate its impact. Cost measurement using Time-Driven Activity-Based Costing (TDABC), a variant of Activity-Based Costing (ABC), is based on a process approach. The main contribution of TDABC is that it uses a single cost driver: time. Serum immunofixation is a test used to confirm and monitor plasma cell dyscrasias, the archetype of which is multiple myeloma. The learned societies and the IMWG provide explicit diagnostic criteria, but the guidelines do not address the frequency of follow-up. In particular, the frequency of repeat and follow-up serum immunofixation remains unaddressed from an evidence-based medicine perspective. This work has made it possible to highlight the savings made between 1st January and 31th August 2023 thanks to the involvement of the biologist and to highlight his essential role in the process of controlling the overall expenditure (reagents, human resources, time and money) in the specialized biochemistry sector (bench: proteins) and to strengthen the role of the biologist within the institution. The various players in the healthcare sector - prescribing physicians, biologists, hospital administrators and, last but not least, patients - all have an essential role to play in maximizing value for patients and in the healthcare economy.

Detection of schistocytes is an important first step in the differential diagnosis of thrombotic microangiopathy. It is however labor intensive and prone to subjectivity. To improve and standardize the detection and quantification of schistocytes, we studied its automated analysis by digital microscopy DM1200 (CellaVision®) on 63 positive and 102 negative smears obtained from SP-50 (Sysmex®). Easy to use and very useful for staff training, it showed a lower between-observer coefficient of variation than usually described for manual counting (25% vs. 50%). Very sensitive (100%) in pre-classification, the detection of schistocytes was highly sensitive (98.4%) and specific (96.8%) after reclassification (AUCROC = 0.9929), showing a good correlation with manual microscopy. TAT was comparable to manual counting. For positive smears, the percentage of schistocytes was similar between pre- and post-classification. However, 29.6% of pre-classified schistocytes were removed and 21.8% were added. For negative smears a significative overestimation of schistocytes (292%) was observed. Except poikilocytosis, on negative smears, the most common error of the software (24.9%) was due to platelets classified in schistocytes. Were also observed for example erroneous divisions of the image (3.2%) or artifactual schistocytes resulting from scratches in the smear (2.6%). Another limit is the high number of red blood cells not analyzed (46.8% for high-density smears), which might false the schistocytes percentage. To conclude, CellaVision® technology showed many benefits, but also limits that the operator needs to know.

Since 1960, Williams and Trotman had dreamed of automating all technical manipulations in bacteriology. However, this switch to automation took several decades to realize. The high cost of instruments and the attachment to classical bacteriology were the main obstacles. Automation began with blood culture incubators, and paved the way for automation in other areas of bacteriology, notably cytology, culture, identification and antibiotic susceptibility testing. Medical laboratories have been quick to recognize the efficiency of these systems and their many advantages. The reduction in turnaround times for bacteriological examinations is one of the changes that have revolutionized laboratory practice. In addition, sensitivity, safety, traceability and quality are more assured with automation. The second revolution is the integration of artificial intelligence into the processing and interpretation of bacteriological analyses. We are currently witnessing the total automation of laboratories and a reduction in human intervention. In this article, we have attempted to address all aspects of bacteriology affected by automation, and the impact of this change on current laboratory practice and quality of healthcare.

Anti-Jo1 antibodies are usually known markers of myositis. However, they can be associated with different pathologies. We aimed to determine the immuno-clinical characteristics of patients with positive anti-Jo1. We enrolled 31 anti-Jo1 positive patients, selected from 10429 cases tested for antinuclear antibodies (ANA) by indirect immunofluorescence. The anti-Jo1 identification was motivated by the ANA pattern or the clinical data of patients. The average age of patients was 36.9 ± 10 years (F/M sex ratio: 3.4). The overall prevalence of anti-Jo1 was 0.3% among all ANA-tested cases. The ANA pattern associated with the presence of anti-Jo1 was heterogeneous with ANA negative in 38.7 % of cases. They were associated with different autoantibody specificities in 64.5 % of cases and were alone in 35.5% of cases. When confronted with clinical data, anti-Jo1 positivity was associated with autoimmune (77,4%) and non-autoimmune (22,6%) clinical conditions. Our study shows a low overall prevalence of anti-Jo1. These antibodies must be systematically tested for in the context of myositis even if ANA is negative. Nevertheless, their positivity in other systemic or even non-autoimmune diseases requires further studies to better understand their clinical significance.

Edoxaban is a direct oral anticoagulant available in Europe but not in France. Given the high tourist traffic in France, understanding the pharmacology of edoxaban and the availability of its laboratory testing seemed crucial in emergency situations. The aim of this work was to describe the methodology for measuring the anti-Xa activity of edoxaban, highlighting pre-analytical and analytical aspects, along with essential clinico-biological data for therapeutic guidance. The analysis was performed using the chromogenic method on the STAR-Max analyzer, with the STA®-Liquid ANTI-Xa kit (Diagnostica Stago®). Anti-Xa Edoxaban level measurement has a detection limit of 15 ng/mL, a quantification limit of 20 ng/mL and a linearity limit of 400 ng/mL. Repeatability, intermediate precision, accuracy, and measurement uncertainty studies were conducted to assess method performance, meeting quality requirements. The comparison between two STAR-Max® analyzers showed excellent results with linear regression and a low bias with good precision and no loss of dispersion regardless of edoxaban levels. In conclusion, although the measurement of edoxaban level may be rarely necessary in clinical practice, its implementation is straightforward. The availability of edoxaban in neighboring countries, underscores the importance of having its measurement available in hospital laboratories.

The single-specimen pneumatic tube (PTS) is a commonly used rapid specimen delivery system in modern clinical laboratories. However, its impact on sample integrity and laboratory test results remains controversial. The installation and configuration of single-specimen PTS are unique to their institution. We sought to validate our single-specimen PTS by comparing routine chemistry, immunology, and hematology results with a repeat sample integrity index for manual transport. In 2023, 30 employees were randomly selected from the company medical examination, and three tubes of procoagulant serum samples and three tubes of EDTA anticoagulant blood samples were collected from each of them. Group A uses a single specimen PTS at 8 m/s, Group B uses a single specimen PTS at 15 m/s, and Group C uses manual transfer. Specimens from all three groups were simultaneously analysed for ALT, AST, TG, TC, LDL, K, NA, CI, TSH, hs-cTnT, NSE, Cyfra21-1 and haematological analysis. The differences between the three groups of NSE and Cyfra21-1 were statistically significant (P < 0.05). The differences of the rest of the items were not statistically significant. The difference in NSE was not statistically significant between groups A and B (P = 0.401), B and C, and C and A (P < 0.05). The difference in Cyfra21-1 was not statistically significant between groups A and B (P = 0.897), B and C (P = 0.052), and C and A (P = 0.145). Individual sample PTS should be validated for testing prior to use to ensure the results' accuracy.

The susceptibility modules and characteristic genes of patients with osteoarthritis (OA) were determined by weighted gene co-expression network analysis (WGCNA), and the role of immune cells in OA related microenvironment was analyzed. GSE98918 and GSE117999 data sets are from GEO database. R language was used to conduct difference analysis for the new data set after merging. The formation of gene co-expression network, screening of susceptibility modules and screening of core genes are all through WGCNA. GO and KEGG enrichment analyses were used for Hub genes. The characteristic genes of the disease were obtained by Lasso regression screening. SSGSEA was used to estimate immune cell abundance in sample and a series of correlation analyses were performed. WGCNA was used to form 6 gene co-expression modules. The yellow-green module is identified as the susceptible module of OA. 202 genes were identified as core genes. Finally, RHOT2, FNBP4 and NARF were identified as the characteristic genes of OA. The results showed that the characteristic genes of OA were positively correlated with plasmacytoid dendritic cells, NKT cells and immature dendritic cells, but negatively correlated with active B cells. MDSC were the most abundant immune cells in cartilage. This study identified the Hippo signaling pathway, mTOR signaling pathway, and three characteristic genes (RHOT2, FNBP4, NARF) as being associated with osteoarthritis (OA). These three genes are downregulated in the cartilage of OA patients and may serve as biomarkers for early diagnosis and targeted therapy. Proper regulation of immune cells may aid in the treatment of OA. Future research should focus on developing tools to detect these genes and exploring their therapeutic applications.

Laboratory medicine plays a crucial role in patient care, contributing to approximately 70 % of clinical decisions. In collaboration with clinicians, laboratory medicine specialists perform analyses that are useful for diagnosis, screening and prevention. Laboratories are known for their efficiency, which is reached through a rigorous quality system. However, errors can occur, especially given the complexity of the total testing process. These errors may lead to severe consequences, such as incorrect diagnoses or delays in treatment. Errors can occur at every stage of the total testing process, those related to the pre-analytical phase being the most prevalent. To reduce medical errors related to laboratory processes, it is essential to provide training for medical and paramedical staff, optimize production automation, and leverage technological advancements. These considerations have led to the creation of a French Working Group on Sources of Errors in Laboratory Medicine, under the aegis of the French lean society of clinical chemistry and laboratory medicine (Société Française de Biologie Clinique - SFBC). The objectives of this working group are to produce an educational handbook on sources of errors in laboratory medicine, provide training for clinical chemists, and conducting applied research projects to better understand the mechanisms behind specific errors. Ultimately, the aim is to minimize errors and enhance the quality of laboratory tests.