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We assessed the humoral and cellular immune responses after two booster mRNA vaccine administrations [BNT162b2 (Pfizer-BioNTech vaccine)] in cohorts of immunocompromised patients (n = 199) and healthy controls (HC) (n = 54). All patients living with HIV (PLWH) and chronic kidney disease (CKD) patients and almost all (98.2%) of the primary immunodeficiency (PID) patients had measurable antibodies 3 and 6 months after administration of the third and fourth vaccine dose, comparable to the HCs. In contrast, only 53.3% and 83.3% of the multiple sclerosis (MS) and rheumatologic patients, respectively, developed a humoral immune response. Cellular immune response was observed in all PLWH after administration of four vaccine doses. In addition, cellular immune response was positive in 89.6%, 97.8%, 73.3% and 96.9% of the PID, MS, rheumatologic and CKD patients, respectively. Unlike the other groups, only the MS patients had a significantly higher cellular immune response compared to the HC group. Administration of additional vaccine doses results in retained or increased humoral and cellular immune response in patients with acquired or inherited immune disorders. [ABSTRACT FROM AUTHOR]

This letter discusses a case of interference in urinary particle counts using automated urinary fluorescence flow cytometry (UFFC) due to the presence of lipid droplets. The interference was identified in a urine sample from a patient who had used sesame oil as a lubrication agent during catheterization. Manual microscopy confirmed the presence of white blood cells but did not show an increased red blood cell or crystal count. Physicochemical analysis using infrared spectroscopy and surface tension analysis confirmed the presence of lipids in the urine sample. The authors suggest combining urinary particle analysis with urinary test strip analysis and implementing intelligent verification rules to reduce errors in automated urinary particle analysis. They also recommend avoiding the use of urethral lubricants like sesame oil before UFFC analysis. [Extracted from the article]

Urinary test strip and sediment analysis integrated with intelligent verification criteria can help to select samples that need manual review. This study aimed to evaluate the improvement in the diagnostic performance of combined urinary test strip and urinary sediment analysis using intelligent verification criteria on the latest generation automated test strip and urinary fluoresce flow cytometry (UFFC) analysers. Urine test strip and sediment analysis were performed using the Sysmex UC-3500 and UF-5000 (Kobe, Japan) on 828 urinary samples at the clinical laboratory of the Ghent University Hospital. The results were compared to manual microscopy using phase-contrast microscopy as a reference. After the application of the intelligent verification criteria, we determined whether the diagnostic performance of urine sediment analysis could be improved. Application of intelligent verification criteria resulted in an increase in specificity from 88.5 to 96.8% and from 88.2 to 94.9% for red blood cells and white blood cells, respectively. Implementing review rules for renal tubular epithelial cells and pathological casts increased the specificity from 66.7 to 74.2% and from 96.2 to 100.0%, respectively; and improved the diagnostic performance of urinary crystals and atypical cells. The implementation of review rules improved the diagnostic performance of UFFC, thereby increasing the reliability and quality of urine sediment results. [ABSTRACT FROM AUTHOR]

This document discusses the importance of accurately measuring sodium concentrations in the diagnosis of electrolyte disorders. It highlights the differences between direct and indirect methods of measuring sodium and how these differences can affect the diagnosis of hyponatremia and hypernatremia. The document emphasizes the need for corrective algorithms to account for variations in protein concentration and recommends using direct sodium measurements in patients with abnormal protein concentrations. It concludes by emphasizing the importance of awareness and corrective measures in sodium measurement methods. [Extracted from the article]

The early detection of gynecological cancers, which is critical for improving patient survival rates, is challenging because of the vague early symptoms and the diagnostic limitations of current approaches. This comprehensive review delves into the game-changing potential of infrared (IR) spectroscopy, a noninvasive technology used to transform the landscape of cancer diagnosis in gynecology. By collecting the distinctive vibrational frequencies of chemical bonds inside tissue samples, Fourier-transform infrared (FTIR) spectroscopy provides a 'molecular fingerprint' that outperforms existing diagnostic approaches. We highlight significant advances in this field, particularly the identification of discrete biomarker bands in the mid- and near-IR spectra. Proteins, lipids, carbohydrates, and nucleic acids exhibited different absorption patterns. These spectral signatures not only serve to distinguish between malignant and benign diseases, but also provide additional information regarding the cellular changes associated with cancer. To underscore the practical consequences of these findings, we examined studies in which IR spectroscopy demonstrated exceptional diagnostic accuracy. This review supports the use of IR spectroscopy in normal clinical practice, emphasizing its capacity to detect and comprehend the intricate molecular underpinnings of gynecological cancers. [ABSTRACT FROM AUTHOR]

Keywords: contrast media; refractory index; urinalysis; urinary fluorescence flow cytometry EN contrast media refractory index urinalysis urinary fluorescence flow cytometry e335 e337 3 07/01/21 20210801 NES 210801 To the Editor, Modern automated urinalysis uses advanced flow cytometers, in which urinary particles are counted and classified based on their impedance, forward scatter, side scatter, side fluorescence, and depolarized side scattered light characteristics [[1]], [[2]]. Next to the well-known effect of iodine containing contrast media on urinary specific gravity [[7]], we describe for the first time an effect on urinary fluorescence flow cytometric results due to the presence of high concentrations of contrast media in the urine. [Extracted from the article]

The article offers information on the multicenter study on the Sysmex XN-series analyzer for the establishment of common reference intervals for hematology parameters in adults. It mentions the analysis of complete blood count (CBC) including white blood cell (WBC) differentiation and reticulocyte count on an XN analyzer.

Background: Diagnosis of upper urinary tract infections (UTI) is challenging. We evaluated the analytical and diagnostic performance characteristics of renal tubular epithelial cells (RTECs) and transitional epithelial cells (TECs) on the Sysmex UF-5000 urine sediment analyzer. Methods: Urinary samples from 506 patients presenting with symptoms of a UTI were collected. Only samples for which a urinary culture was available were included. Analytical (imprecision, accuracy, stability and correlation with manual microscopy) and diagnostic performance (sensitivity and specificity) were evaluated. Results: The Sysmex UF-5000 demonstrated a good analytical performance. Depending on the storage time, storage conditions (2–8 °C or 20–25 °C) and urinary pH, RTECs and TECs were stable in urine for at least 4 h. Using Passing-Bablok and Bland-Altman analysis, an acceptable agreement was observed between the manual and automated methods. Compared to TECs, RTECs demonstrated an acceptable diagnostic performance for the diagnosis of upper UTI. Conclusions: While TECs do not seem to serve as a helpful marker, increased urinary levels of RTECs add value in the diagnosis of upper UTI and may be helpful in the discrimination between upper and lower UTIs. [ABSTRACT FROM AUTHOR]

Background: Urinary conductivity allows a coarse prediction of urinary osmolality in most cases but is insensitive to the osmolal contribution of uncharged particles and the presence of roentgen contrast media. Urinary osmolality can be estimated on the recently introduced Sysmex UF-5000 urine analyzer using conductivity. In this study, we evaluated the analytical performance of this research parameter. Secondly, we aimed to improve the manufacturer's algorithm for estimating urinary osmolality, based on standard urinalysis parameters (creatinine, glucose, relative density). Methods: The analytical performance was determined and a prediction model to estimate urinary osmolality based on urinalysis parameters was developed. We further developed and validated a prediction model using another set of routine urine samples. In addition, the influence of roentgen contrast media on urinary osmolality was studied. Results: The within-run and between imprecision for osmolality and conductivity measured on the Sysmex UF-5000 ranged from 1.1% to 4.9% and 0.7% to 4.8%, respectively. Multiple regression analysis revealed urinary creatinine, conductivity and relative density to be the strongest predictors to estimate urinary osmolality. A mean difference of 1.3 mOsm/kg between measured and predicted osmolality demonstrated that the predictive performance of our model was favorable. An excellent correlation between the relative density and % contrast media was demonstrated. Conclusions: Urinary osmolality is an important parameter for assessing specimen dilution in urinalysis. Urinary conductivity, along with relative density and urinary creatinine allows a coarse prediction of urinary osmolality and is insensitive to the osmolal contribution of uncharged particles and the presence of roentgen contrast media. [ABSTRACT FROM AUTHOR]

Keywords: albuminuria; proteinuria; urinalysis EN albuminuria proteinuria urinalysis e1 e2 2 11/28/22 20230101 NES 230101 To the Editor, With interest, we read the recent publication on estimating urinary albumin to creatinine ratio (ACR) from proteinuria to creatinine ratio (PCR) using same-day measurements [[1]]. In conclusion, care should be taken when estimating albuminuria out of proteinuria data, in particular in the case of low-range proteinuria or in patients presenting with Bence Jones proteinuria. When using economic arguments to avoid testing for albuminuria (proteinuria tests are less expensive than immunochemical albuminuria tests), it should be noted that quantitative albuminuria can be achieved using inexpensive common urine test strips in conjunction with a sensitive urine test reader [[8]]. [Extracted from the article]

Raman spectroscopy, a non-invasive diagnostic technique capturing molecular vibrations, offers significant advancements in skin cancer diagnostics. This review delineates the ascent of Raman spectroscopy from classical methodologies to the forefront of modern technology, emphasizing its precision in differentiating between malignant and benign skin tissues. Our study offers a detailed examination of distinct Raman spectroscopic signatures found in skin cancer, concentrating specifically on squamous cell carcinoma, basal cell carcinoma, and melanoma, across both in vitro and in vivo research. The discussion extends to future possibilities, spotlighting enhancements in portable Raman instruments, the adoption of machine learning for spectral data refinement, and the merging of Raman imaging with other diagnostic techniques. The review culminates by contemplating the broader implications of these advancements, suggesting a trajectory that may significantly optimize the accuracy and efficiency of skin cancer diagnostics. [ABSTRACT FROM AUTHOR]

Hematological diseases, due to their complex nature and diverse manifestations, pose significant diagnostic challenges in healthcare. The pressing need for early and accurate diagnosis has driven the exploration of novel diagnostic techniques. Infrared (IR) spectroscopy, renowned for its noninvasive, rapid, and cost-effective characteristics, has emerged as a promising adjunct in hematological diagnostics. This review delves into the transformative role of IR spectroscopy and highlights its applications in detecting and diagnosing various blood-related ailments. We discuss groundbreaking research findings and real-world applications while providing a balanced view of the potential and limitations of the technique. By integrating advanced technology with clinical needs, we offer insights into how IR spectroscopy may herald a new era of hematological disease diagnosis. [ABSTRACT FROM AUTHOR]

Results obtained with the most recent Roche Cobas 8000 c502 lipase application (in the period 01/05/2018-25/01/2019) are presented in Figure 1E. Remarkably, with this new lipase application, we could still observe a gap within the patient result distribution between 300 and 400 U/L. Non-linearity within the primary measurement range of a lipase assay as the cause of a gap in the interpatient lipase results distribution. [Extracted from the article]

Background: Recently, urine test strip readers have become available for automated test strip analysis. We explored the possibilities of the Sysmex UC-3500 automated urine chemistry analyzer based on complementary metal oxide semiconductor (CMOS) sensor technology with regard to accuracy of leukocyte esterase and hemoglobin peroxidase results. We studied the influence of possible confounders on these measurements. Methods: Reflectance data of leukocyte esterase and hemoglobin peroxidase were measured using CMOS technology on the Sysmex UC-3500 automated urine chemistry analyzer. Analytical performance (imprecision, LOQ) as well as the correlation with white blood cell (WBC) and red blood cell (RBC) counts (Sysmex UF-5000) were studied. Furthermore, the influence of urinary dilution, haptoglobin, pH and ascorbic acid as confounders was determined. Results: Within- and between-run imprecision (reflectance signal) ranged from 1.1% to 3.6% and 0.9% to 4.2% for peroxidase and 0.4% to 2.5% and 0.4% to 3.3% for leukocyte esterase. Good agreement was obtained between the UF-5000 for RBCs and peroxidase reflectance (r = 0.843) and for WBCs and leukocyte esterase (r = 0.821). Specific esterase activity decreased for WBC counts exceeding 100 cells/μL. Haptoglobin influenced the peroxidase activity, whereas leukocyte esterase and peroxidase activities showed a pH optimum between 5.0 and 6.5. A sigmoidal correlation was observed between urinary osmolality and peroxidase activity. Conclusions: CMOS technology allows to obtain high quality test strip results for assessing WBC and RBC in urine. Quantitative peroxidase and leukocyte esterase are complementary with flow cytometry and have an added value in urinalysis, which may form a basis for expert system development. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTI) are very common throughout life and account for the majority of the workload in the clinical microbiology laboratory. Clear instructions for the interpretation of urine cultures by the laboratory technicians are indispensable to obtain standardized, reliable, and clinically useful results. In literature, there is often a lack of evidence-based practice in processing urinary samples in the laboratory. In this consensus document, the BILULU Study Group presents a practical approach for the implementation of existing guidelines for the culture of urine in the microbiology laboratory and offers answers for issues where no clear solution is available in the guidelines. [ABSTRACT FROM AUTHOR]

Background Point-of-care blood gas test results may benefit therapeutic decision making by their immediate impact on patient care. We evaluated the (pre-)analytical performance of a novel cartridge-type blood gas analyzer, the GEM Premier 5000 (Werfen), for the determination of pH, partial carbon dioxide pressure (pCO 2 ), partial oxygen pressure (pO 2 ), sodium (Na + ), potassium (K + ), chloride (Cl − ), ionized calcium ( i Ca 2 + ), glucose, lactate, and total hemoglobin (tHb). Methods Total imprecision was estimated according to the CLSI EP5-A2 protocol. The estimated total error was calculated based on the mean of the range claimed by the manufacturer. Based on the CLSI EP9-A2 evaluation protocol, a method comparison with the Siemens RapidPoint 500 and Abbott i-STAT CG8 + was performed. Obtained data were compared against preset quality specifications. Interference of potential pre-analytical confounders on co-oximetry and electrolyte concentrations were studied. Results The analytical performance was acceptable for all parameters tested. Method comparison demonstrated good agreement to the RapidPoint 500 and i-STAT CG8 +, except for some parameters (RapidPoint 500: pCO 2 , K + , lactate and tHb; i-STAT CG8 +: pO 2 , Na + , i Ca 2 + and tHb) for which significant differences between analyzers were recorded. No interference of lipemia or methylene blue on CO-oximetry results was found. On the contrary, significant interference for benzalkonium and hemolysis on electrolyte measurements were found, for which the user is notified by an interferent specific flag. Conclusion Identification of sample errors from pre-analytical sources, such as interferences and automatic corrective actions, along with the analytical performance, ease of use and low maintenance time of the instrument, makes the evaluated instrument a suitable blood gas analyzer for both POCT and laboratory use. [ABSTRACT FROM AUTHOR]

Background: We evaluated the analytical performance of six different faecal calprotectin immunoassays together with their diagnostic accuracy in the discrimination between functional and organic bowel disorders. Methods: The faecal samples were obtained from inflammatory bowel disease patients (n = 27) at the time of diagnosis [Crohn's disease (n = 15), colitis ulcerosa (n = 12)], gastroenterologic disease control patients (n = 52) and rheumatologic disease control patients (n = 26). All individuals included in the study underwent a concurrent ileocolonoscopy. Analytical performance (imprecision, accuracy, carry-over, correlation and agreement) and diagnostic accuracy (sensitivity, specificity, likelihood ratios) of the different assays were evaluated. Results: All methods demonstrated good analytical performance, but within-run and total imprecision varied depending on the assay methodology used. Using Passing Bablok and Bland-Altman analyses, low quantitative agreement was observed between the assays. All assays showed excellent diagnostic accuracy, with areas under the receiver operating characteristic curves (ROC) ranging from 0.974 to 0.998. The AUCs were not significantly different between assays (p > 0.05). Diagnostic sensitivity at the cut-off at a fixed specificity of 75% ranged from 95.2% to 100%. Introduction of multiple result intervals increased the clinical interpretation of all the assays. Conclusions: Analytical and diagnostic performance of the evaluated faecal calprotectin assays is good, but numerical values differ substantially between the assays necessitating the use of different clinical cut-offs. Introduction of multiple result intervals aids in clinical decision-making. [ABSTRACT FROM AUTHOR]

Although lipase immunoassays are not a perfect diagnostic solution [[8]], these promising ELISA assays disappeared prematurely from the market when the practical colorimetric lipase methods were introduced approximately 30 years ago. Keywords: immunoassay; interference; isoenzymes; lipase EN immunoassay interference isoenzymes lipase 75 76 2 02/07/22 20220201 NES 220201 To the Editor, With interest we read the paper by Pasqualetti et al. [[1]] regarding the care of the laboratory community of pancreatic lipase. Furthermore, the lipase isoforms L1 and L2 are immunochemically distinct from isoform L3, which increases the diagnostic specificity of lipase immunoassays [[7]]. [Extracted from the article]

A letter to the editor is presented regarding the role and efficacy of Nova StatStrip® Glucose as accurate blood glucose measuring system (BGMS) for the management of dysglycemia through point-of-care blood glucose monitoring.

The article presents calculations for a large number of therapeutic drugs monitors in the laboratory using the calculated within-subject variations in a delta check algorithm to filter out results that can merit closer inspections. It provides proof-of-concept for vancomycin and tacrolimus representing 2 drug classes namely antibiotics and immunosuppressants. It suggests a review of all first patient values outside the therapeutic interval by a laboratory medicine specialist.

A letter to the editor is presented in response to the study which examined added value of indirect immunofluorescence intensity of automated antinuclear antibody testing in a secondary hospital setting, which previously published online on November 12, 2015.

Introduction: Mutations in the epidermal growth factor receptor ( EGFR) have been reported as predictive markers of tumour response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Although the 'common' EGFR mutations have been associated with response to EGFR-TKIs, the correlation with response to treatment for many other rare mutations is still unclear. The aim of this study was to investigate the clinical significance of rare and complex mutations, and the efficacy of EGFR-TKIs in this selected group of patients. Methods: Three hundred and thirty patients with stage IIIB/IV NSCLC (106 females aged 62.5 ± 1.1 years; 224 males aged 68.0 ± 0.6 years) were enrolled in the study. Formalin fixed paraffin embedded tissue samples were screened for mutations using a high resolution melting technique, followed by Sanger sequencing of exons 18-21 of the EGFR-gene. Mutation status was also tested using the Roche Cobas EGFR mutation test. Results: EGFR mutations were detected in 31 tumours (9.4 %). Eleven cases carried novel mutations, six of these patients were treated with erlotinib or gefitinib. A response rate (RR) of 50.0 % was obtained in the group with rare EGFR mutations, the PFS was 3.0 months [standard deviation (STD) = 5.4 months]. The RR to EGFR-TKIs in patients with conventional EGFR mutations was 85 % with a median PFS of 10.5 months (STD = 3.6 months). Conclusion: We reported six patients with rare EGFR mutations of unknown clinical significance and their association with EGFR-TKIs. Report of cases harbouring rare mutations can support the decision making progress in this subset of patients. [ABSTRACT FROM AUTHOR]

Background: The European Society for Pediatric Gastroenterology and Nutrition states that if IgA anti-tissue transglutaminase (tTG) exceeds 10 times the upper limit of normal (ULN), there is the possibility to diagnose celiac disease (CD) without duodenal biopsy, if supported by anti-endomysium testing and human leukocyte antigen (HLA) typing. We aimed to evaluate whether combining IgA tTG and IgG anti-deamidated gliadin peptide (DGP) antibody testing and taking into account the antibody levels improves clinical interpretation. Methods: We calculated likelihood ratios for various test result combinations using data obtained from newly diagnosed CD patients (n = 156) [13 children < 2 years, 45 children between 2 and 16 years, and 98 adults (> 16 years)] and 974 disease controls. All patients and controls underwent duodenal biopsy. IgA anti-tTG and IgG anti-DGP assays were from Thermo Fisher and Inova. Results: Likelihood ratios for CD markedly increased with double positivity and increasing antibody levels of IgA anti-tTG and IgG anti-DGP. Patients with double positivity and high antibody levels (> 3 times, > 10 times ULN) had a high probability for having CD (likelihood ratio e 649 for > 3 times ULN and ∞ for > 10 times ULN). The fraction of CD patients with double positivity and high antibody levels was 59%-67% (depending on the assay) for > 3 ULN and 33%-36% (depending on the assay) for > 10 ULN, respectively. This fraction was significantly higher in children with CD than in adults. Conclusions: Combining IgG anti-DGP with IgA anti-tTG and defining thresholds for antibody levels improves the serologic diagnosis of CD. [ABSTRACT FROM AUTHOR]

We retrospectively compared the long-term evolution of IgG anti-spike (S) and anti-nucleocapsid (N) levels (Abbott immunoassays) in 116 non-severe and 115 severe SARS-CoV-2 infected patients from 2 university hospitals up to 365 days post positive RT-PCR. IgG anti-S and anti-N antibody levels decayed exponentially up to 365 days after a peak 0 to 59 days after positive RT-PCR. Peak antibody level/cut-off ratio 0 to 59 days after positive RT-PCR was more than 70 for anti-S compared to less than 6 for anti-N (P < 0.01). Anti-S and anti-N were significantly higher in severe compared to non-severe patients up to 180 to 239 days and 300 to 365 days, respectively (P < 0.05). Despite similar half-lives, the estimated time to 50% seronegativity was more than 2 years for anti-S compared to less than 1 year for anti-N in non-severe and severe COVID-19 patients, due to the significantly higher peak antibody level/cut-off ratio for anti-S compared to anti-N. [ABSTRACT FROM AUTHOR]

Background Accurate quantification of vancomycin in plasma is important for adequate dose-adjustment. As literature suggests between-method differences, our first objective was to develop a novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for total vancomycin in human plasma and to compare frequently used immunoassays with this method. Secondly, we investigated the clinical impact of between-method quantification differences. Methods For LC–MS/MS, lithium heparin plasma was extracted by adding a precipitation reagent containing the internal standard (vancomycin-des-leucine). Analysis was performed on an Acquity TQD mass spectrometer equipped with an Acquity UPLC 2795 separations module. Our method was analytically validated and compared with four frequently used immunoassays from four different manufacturers. Vancomycin concentrations were clinically classified as toxic, therapeutic and sub-therapeutic. Clinical discordance was calculated using LC–MS/MS as a reference. Results A novel LC–MS/MS method using protein precipitation as sole pretreatment and an analysis time of 5.0 min was developed. The assay had a total imprecision of 2.6–8.5%, a limit of quantification of 0.3 mg/L and an accuracy ranging from 101.4 to 111.2%. Using LC–MS/MS as reference, three immunoassays showed a mean proportional difference within 10% and one showed a substantial mean proportional difference of > 20%. Clinical discordant interpretation of the obtained concentrations ranged from 6.1 to 22.2%. Conclusions We developed a novel LC–MS/MS method for rapid analysis of total vancomycin concentrations in human plasma. Correlation of the method with immunoassays showed a mean proportional difference > 20% for one of the assays, causing discordant clinical interpretation in more than 1 out of 5 samples. [ABSTRACT FROM AUTHOR]

Background: Symptoms of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can overlap. Faecal calprotectin has recently been established to be a non-invasive marker for neutrophilic intestinal inflammation. We compared two devices for extraction of faecal calprotectin. Based on these results, two immunoassays for measurement of faecal calprotectin were evaluated. Methods: Samples were extracted using the Thermo Fisher extraction device (Thermo Fisher Scientific) and Smart Pep extraction device (Roche Diagnostics) and measured with the EliA Calprotectin immunoassay (Thermo Fisher Scientific) on ImmunoCAP 250. The performance of both assays was investigated by enrolling 183 consecutive patients (79 males, 104 females; median age 32 years) with clinical suspicion of IBD. Faecal calprotectin was measured using a recently launched immunoassay, EliA Calprotectin in comparison with an established immunochomatographic point-of-care-test (POCT, Quantum Blue Calprotectin; Bühlmann). Results were compared with endoscopic and histological findings. Results: The use of the Thermo Fisher extraction device resulted in an underestimation of faecal calprotectin concentrations, especially in liquid stool samples. IBD was diagnosed in 51/183 patients (27.9%) [Crohn's disease (CD, n=37), ulcerative colitis (UC, n=14)]. After adjusting the optimal cut-off for detection of IBD using receiver operating curve analysis, a sensitivity of 94.1% and 90.2% and specificity of 87.9% and 90.9% for the EliA and POCT assay, respectively, were obtained. Conclusions: The Thermo Fisher device is not reliable for extraction of faecal calprotectin. The performance characteristics of the EliA Calprotectin assay are statistically equivalent to the Bühlmann POCT. [ABSTRACT FROM AUTHOR]

Keywords: glycerol; L-index; lipid particle size; triglycerides EN glycerol L-index lipid particle size triglycerides e128 e129 2 07/13/20 20200801 NES 200801 To the Editor, We read with interest the paper by Lippi et al. [[1]] dealing with serum indices. Therefore, the ratio between the logarithmic transformed values of the triglycerides and the L-index is an estimate of the average particle size of triglyceride-containing particles [[8]]. J Inherit Metab Dis 2016;39:S175-6. 8 De Haene H, Taes Y, Christophe A, Delanghe J. Comparison of triglyceride concentration with lipemic index in disorders of triglyceride and glycerol metabolism. [Extracted from the article]

• After two months SARS-CoV-2 anti-N IgG antibodies steadily decrease up to at least 8 months after positive PCR. • 22.2 % of mild versus 2.6 % of severe COVID-19 patients never seroconverted. • Antibody levels are significantly higher in severe COVID-19 patients compared to mild COVID-19 patients. • 70.6 % of severe compared to 38.9 % of mild COVID-19 patients remain seropostive up to 8 months after positive PCR. Most SARS-CoV-2 infected patients develop IgG antibodies within 2–3 weeks after symptom onset. Antibody levels have been shown to gradually decrease in the first months after infection, but few data are available at six months or later. A retrospective multi-center study was performed using 652 samples of 236 PCR-confirmed SARS-CoV-2 infected patients from 2 Belgian University hospitals. Patients were included if at least two samples were available (range 2–7 samples); including at least one sample collected 30 days or later after first positive PCR (range 0–240 days). Of those 236 patients, 19.1 % were classified as mild/asymptomatic (mild) and 80.9 % as moderate to critical (severe). IgG anti-nucleocapsid antibodies (anti-N) were measured using the Abbott Architect immunoassay. 22.2 % of mild and 2.6 % of severe COVID-19 cases never seroconverted (p < 0.001). Of the mild patients who seroconverted 0–59 days after PCR; 18.8 %, 40.0 % and 61.1 % were seronegative in the windows 60–119 days, 120–179 days and 180–240 days after PCR, respectively. In severe patients, these numbers were 1.9 %, 10.8 % and 29.4 % respectively (p < 0.05 each). Antibody levels were significantly higher in severe patients compared to mild patients in each 60 day window (p < 0.001 each). SARS-CoV-2 anti-N IgG antibody levels steadily decreased after 2 months up to 8 months post PCR. Of severe COVID-19 patients, 70.6 % remained positive up to eight months after infection. Antibody levels were significantly lower in mild SARS-CoV-2 infected patients and 61.1 % became seronegative within 6 months after the first positive PCR. [ABSTRACT FROM AUTHOR]

The article presents a case study of 44-year-old, HIV-negative female patient presented with night sweats and abdominal lymphadenopathies. She was further diagnosed with systemic lupus erythematosus (SLE) after treatment with multiple immunosuppressants and splenectomy. She was found evident to a kappa restricted clonal plasma cells (PC) population.

Automated storage and retrieval modules (SRM), as part of total lab automation (TLA) systems, offer tremendous practical and economic benefits. In contrast to manual storage systems, SRMs indicate continuous motion of samples and may leave samples prone to temperature fluctuations. This study investigates analyte stability in serum and heparin plasma within an automated storage module. The stability of 28 common biochemistry analytes was investigated using 57 freshly obtained routine serum samples and 42 lithium-heparin plasma samples. Following baseline measurement, samples were stored at 2–8 °C in the automated SRM of the Accelerator a3600 TLA and reanalyzed at fixed time points (2, 4, 8, 12, 24, 48 and 72 h) on the Abbott Architect c16000 chemistry analyzer. The concentration at each time point was expressed as %-difference to the baseline value and mean results were compared to the criteria for desirable bias derived from the biological variation database. Nine of the analytes exceeded the bias criterion within 72 h after initial measurement in either serum samples, plasma samples or both. Lithium-heparin plasma samples showed increasing values for phosphor, potassium and lactate dehydrogenase (LDH), which were only considered stable for respectively 24, 12 and 4 h, glucose was considered stable for 8 h. Electrolyte concentrations and LDH activity significantly increased in serum samples beyond 48 h. Bicarbonate should not be performed as add-on test at all. The presented data indicate that the conditions within an SRM have no clinical impact on sample stability and allow stable measurement of routine analytes within 72 h, comparable to manual storage facilities. [ABSTRACT FROM AUTHOR]

The EFLM Task and Finish Group Urinalysis has updated the ECLM European Urinalysis Guidelines (2000) on urinalysis and urine bacterial culture, to improve accuracy of these examinations in European clinical laboratories, and to support diagnostic industry to develop new technologies.Graded recommendations were built in the following areas:Strategies of urine testing are described to patients with complicated or uncomplicated urinary tract infection (UTI), and high or low-risk to kidney disease.Patient preparation, and urine collection are supported with two quality indicators: contamination rate (cultures), and density of urine (chemistry, particles).Measurements of both urine albumin and α1-microglobulin are recommended for sensitive detection of kidney disease in high-risk patients. Performance specifications are given for urine protein measurements and quality control of multiproperty strip tests.Procedures for microscopy are reviewed for diagnostic urine particles, including urine bacteria. Technologies in automated particle counting and visual microscopy are updated with advice how to verify new instruments with the reference microscopy.Chromogenic agar is recommended as primary medium in urine cultures. Limits of significant growth are reviewed, with an optimised workflow for routine specimens, using leukocyturia to reduce less important antimicrobial susceptibility testing. Automation in bacteriology is encouraged to shorten turn-around times. Matrix assisted laser desorption ionization time-of-flight mass spectrometry is applicable for rapid identification of uropathogens. Aerococcus urinae, A. sanguinicola and Actinotignum schaalii are taken into the list of uropathogens. A reference examination procedure was developed for urine bacterial cultures. [ABSTRACT FROM AUTHOR]

Die EFLM Task and Finish Group Urinalysis hat die ECLM European Urinalysis Guideline aus dem Jahr 2000 zur Urinanalyse und Urinbakterienkultur für Patient:innen mit Harnwegsinfektionen und mit unterschiedlichem Risiko für Nierenerkrankungen aktualisiert. Die Leitlinie unterstützt medizinisch begründete und wirtschaftlich ausgewogene Laborprozesse unter Berücksichtigung der Anforderungen der DIN EN ISO 15189:2022 sowie die Diagnostikindustrie bei Qualitätsspezifikationen für neue Technologien. [ABSTRACT FROM AUTHOR]

Well-standardized procedures in the pre-analytical phase of urine diagnostics is of utmost importance to obtain reliable results. We investigated the effect of different urine collection methods and the associated urine transfer tubes on urine test strip and particle results. In total, 146 selected urine samples were subdivided into three different collection containers and subsequently transferred into its accompanying transfer tube (BD, Greiner, Sarstedt vacuum and Sarstedt aspiration). As reference, the original urine sample was directly measured on the analyser. Both chemical test strip analysis (Sysmex UC-3500) and fluorescence flow cytometry particle analysis (Sysmex UF-5000) were performed on all samples. No statistically significant differences in test strip results were found between the studied transfer methods. On the contrary, transfer of urine samples to the secondary tubes affected their particle counts. Clinically significant reductions in counts of renal tubular epithelial cells and hyaline casts were observed using the BD and Greiner transfer tubes and in counts of pathological casts using the BD, Greiner and Sarstedt vacuum tubes. The results of this study indicate that the use of urine transfer tubes may impact counts of fragile urine particles. Clinical laboratories need to be aware about the variation that urine collection methods can induce on urine particle counts. [ABSTRACT FROM AUTHOR]

Uromodulin, also known as Tamm-Horsfall protein, represents the predominant urinary protein in healthy individuals. Over the years, studies have revealed compelling associations between urinary and serum concentrations of uromodulin and various parameters, encompassing kidney function, graft survival, cardiovascular disease, glucose metabolism, and overall mortality. Consequently, there has been a growing interest in uromodulin as a novel and effective biomarker with potential applications in diverse clinical settings. Reduced urinary uromodulin levels have been linked to an elevated risk of acute kidney injury (AKI) following cardiac surgery. In the context of chronic kidney disease (CKD) of different etiologies, urinary uromodulin levels tend to decrease significantly and are strongly correlated with variations in estimated glomerular filtration rate. The presence of uromodulin in the serum, attributable to basolateral epithelial cell leakage in the thick ascending limb, has been observed. This serum uromodulin level is closely associated with kidney function and histological severity, suggesting its potential as a biomarker capable of reflecting disease severity across a spectrum of kidney disorders. The UMOD gene has emerged as a prominent locus linked to kidney function parameters and CKD risk within the general population. Extensive research in multiple disciplines has underscored the biological significance of the top UMOD gene variants, which have also been associated with hypertension and kidney stones, thus highlighting the diverse and significant impact of uromodulin on kidney-related conditions. UMOD gene mutations are implicated in uromodulin-associated kidney disease, while polymorphisms in the UMOD gene show a significant association with CKD. In conclusion, uromodulin holds great promise as an informative biomarker, providing valuable insights into kidney function and disease progression in various clinical scenarios. The identification of UMOD gene variants further strengthens its relevance as a potential target for better understanding kidney-related pathologies and devising novel therapeutic strategies. Future investigations into the roles of uromodulin and regulatory mechanisms are likely to yield even more profound implications for kidney disease diagnosis, risk assessment, and management. [ABSTRACT FROM AUTHOR]

Vancomycin pharmacokinetic (PK) and pharmacodynamic (PD) data in neonates are based on total concentrations. However, only unbound vancomycin is pharmacologically active. The objective was to determine vancomycin protein binding and the covariates impacting unbound vancomycin concentration in neonates and young infants. In neonates and young infants to whom vancomycin was administered intermittently for medical indications, total and unbound vancomycin plasma concentrations were determined using LC-MS/MS. Sampling occurred randomly during vancomycin exposure, covering a broad range of concentrations. Impact of covariates on unbound vancomycin concentration was determined using linear regression. Significant results of the univariate regressions were entered in a stepwise multiple regression. Passing-Bablok regression and Bland-Altman were used to assess the difference between measured and calculated unbound vancomycin concentration. Thirty-seven samples in 33 patients (median (interquartile range) gestational age 35 (29-39) weeks) were collected. Median total and unbound vancomycin concentrations were 14.2 (7.4-20.6) and 13.6 (7.2-22.5) mg/L, respectively. Median unbound fraction was 0.90 (0.77-0.98). Multiple regression revealed total vancomycin concentration (β = 0.884, p < 0.001) and albumin (β = − 0.323, p = 0.007) as most important covariates of unbound vancomycin concentrations, with an R2 adjusted of 0.953 (p < 0.0001). Mean absolute difference between calculated and measured unbound vancomycin was − 0.008 (95% CI − 0.92-0.91) mg/L. The unbound vancomycin fraction in neonates is higher compared to that in children and adults, and total vancomycin concentration and albumin were the most important covariates of unbound vancomycin concentration. Integration of protein binding in future PK/PD analyses is appropriate to optimize vancomycin dosing and to determine population-specific vancomycin PD targets for neonates. [ABSTRACT FROM AUTHOR]

Detection of hemoglobin (Hb) and red blood cells in urine (hematuria) is characterized by a large number of pitfalls. Clinicians and laboratory specialists must be aware of these pitfalls since they often lead to medical overconsumption or incorrect diagnosis. Pre-analytical issues (use of vacuum tubes or urine tubes containing preservatives) can affect test results. In routine clinical laboratories, hematuria can be assayed using either chemical (test strips) or particle-counting techniques. In cases of doubtful results, Munchausen syndrome or adulteration of the urine specimen should be excluded. Pigmenturia (caused by the presence of dyes, urinary metabolites such as porphyrins and homogentisic acid, and certain drugs in the urine) can be easily confused with hematuria. The peroxidase activity (test strip) can be positively affected by the presence of non-Hb peroxidases (e.g. myoglobin, semen peroxidases, bacterial, and vegetable peroxidases). Urinary pH, haptoglobin concentration, and urine osmolality may affect specific peroxidase activity. The implementation of expert systems may be helpful in detecting preanalytical and analytical errors in the assessment of hematuria. Correcting for dilution using osmolality, density, or conductivity may be useful for heavily concentrated or diluted urine samples. [ABSTRACT FROM AUTHOR]

Cyclosporine A, immunoassay, immunosuppressant drugs, liquid chromatography-tandem mass spectrometry (LC-MS/MS), therapeutic drug monitoring Recently, the CsA immunoassay was reformulated (ref: LN 3R30) to improve assay imprecision of the previous on-market assay (ref: LK 1L75). Keywords: cyclosporine A; immunoassay; immunosuppressant drugs; liquid chromatography-tandem mass spectrometry (LC-MS/MS); therapeutic drug monitoring EN cyclosporine A immunoassay immunosuppressant drugs liquid chromatography-tandem mass spectrometry (LC-MS/MS) therapeutic drug monitoring e209 e212 4 04/12/21 20210501 NES 210501 To the Editor, Cyclosporine A (CsA) is an immunosuppressant drug (ISD) used to prevent transplant rejection after organ transplantation. Assay imprecision (within-run, between-run and total imprecision) was evaluated, both for the immunoassays as for the LC-MS/MS method, following the Clinical and Laboratory Standards Institute protocol EP5-A3 and using three Lyphocheck Whole Blood Immunosuppressant Controls, level 1, 2 and 3 (Bio-Rad Laboratories, Hercules, CA; LOT: 26270, EXP: 09/2021) [[10]]. [Extracted from the article]

Objectives: In this study, the possibilities of Fourier-transformed infrared spectroscopy (FTIR) for analysis of urine sediments and for detection of bacteria causing urinary tract infections (UTIs) were investigated. Methods: Dried urine specimens of control subjects and patients presenting with various nephrological and urological conditions were analysed using mid-infrared spectroscopy (4,000–400 cm−1). Urine samples from patients with a UTI were inoculated on a blood agar plate. After drying of the pure bacterial colonies, FTIR was applied and compared with the results obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Chemometric data analysis was used to classify the different species. Results: Due to the typical molecular assignments of lipids, proteins, nucleic acids and carbohydrates, FTIR was able to identify bacteria and showed promising results in the detection of proteins, lipids, white and red blood cells, as well as in the identification of crystals. Principal component analysis (PCA) allowed to differentiate between Gram-negative and Gram-positive species and soft independent modelling of class analogy (SIMCA) revealed promising classification ratios between the different pathogens. Conclusions: FTIR can be considered as a supplementary method for urine sediment examination and for detection of pathogenic bacteria in UTI. [ABSTRACT FROM AUTHOR]