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The programme of the German Congress for Laboratory Medicine 2022 was essentially designed by the divisions of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL). Almost all chairpersons of the divisions organised a 90-min symposium on current topics, i.e. conceptualised the symposia and invited speakers. For this article all chairpersons summarised the lectures that were given within the symposia. The DGKL’s work is structured into 5 areas of expertise: Molecular Diagnostics, Learning & Teaching, Quality & Management, Laboratory & Diagnostics and Biobanks & Informatics. The areas of expertise are in turn subdivided into divisions. About the history of the establishment of this new structure within the DGKL you can find information in the editorial of this issue.

Programmed cell death, accidental cell degradation and active extrusion constantly lead to the release of DNA fragments into human body fluids from virtually all cell and tissue types. It is widely accepted that these cell-free DNA (cfDNA) molecules retain the cell-type specific genetic and epigenetic features. Particularly, cfDNA in plasma or serum has been utilized for molecular diagnostics. The current clinically implemented liquid biopsy approaches are mostly based on detecting genetic differences in cfDNA molecules from healthy and diseased cells. Their diagnostic potential is limited to pathologies involving genetic alterations, by the low proportion of cfDNA molecules carrying the mutation(s) relative to the total cfDNA pool, and by the detection limit of employed techniques. Recently, research efforts turned to epigenetic features of cfDNA molecules and found that the tissue-of-origin of individual cfDNA molecules can be inferred from epigenetic characteristics. Analysis of, e.g., methylation patterns, nucleosome or transcription factor binding site occupancies, fragment size distribution or fragment end motifs, and histone modifications determined the cell or tissue-of-origin of individual cfDNA molecules. With this tissue-of origin-analysis, it is possible to estimate the contributions of different tissues to the total cfDNA pool in body fluids and find tissues with increased cell death (pathologic condition), expanding the portfolio of liquid biopsies beyond genetics and towards a wide range of pathologies, such as autoimmune disorders, cardiovascular diseases, and inflammation, among many others. In this review, we give an overview on the status of tissue-of-origin approaches and focus on what is needed to exploit the full potential of liquid biopsies towards minimally invasive screening methods with broad clinical applications.

Genomes of diverse origins are continuously shed into human body fluids in the form of fragmented cell-free DNA (cfDNA). These molecules maintain the genetic and epigenetic codes of their originating source, and often carry additional layers of unique information in newly discovered physico-chemical features. Characterization of cfDNA thus presents the opportunity to non-invasively reconstruct major parts of the host- and metagenome in silico. Data from a single specimen can be leveraged to detect a broad range of disease-specific signatures and has already enabled the development of many pioneering diagnostic tests. Moreover, data from serial sampling may allow unparalleled mapping of the scantily explored landscape of temporal genomic changes as it relates to various changes in different physiological and pathological states of individuals. In this review, we explore how this vast dimension of biological information accessible through cfDNA analysis is being tapped towards the development of increasingly powerful molecular assays and how it is shaping emerging technologies. We also discuss how this departure from traditional paradigms of snapshot genetic testing may pave the way for an onrush of new and exciting discoveries in human biology.

Early detection is crucial for optimal treatment and prognosis of cancer. New approaches for pan-cancer screening comprise the comprehensive characterization of circulating tumor DNA (ctDNA) in plasma by next generation sequencing and molecular profiling of mutations and methylation patterns, as well as fragmentation analysis. These promise the accurate detection and localization of multiple cancers in early disease stages. However, studies with real screening populations have to show their clinical utility and practicability.

* Context.--There is a need to avoid the overdiagnosis of prostate cancer (PCa) and to find more specific biomarkers. Objective.--To evaluate the clinical utility of [-2]proprostate-specific antigen ([-2]proPSA) derivatives in detecting clinically significant PCa (csPCa) and to compare it with prostate-specific antigen (PSA) and with the percentage of free PSA (%fPSA). Design.--Two hundred thirty-seven men (PSA: 2-10 ng/ mL) scheduled for a prostate biopsy were enrolled. Parametric and nonparametric tests, receiver operating characteristic curves, and logistic regression analysis were applied. Outcomes were csPCa and overall PCa. Results.--Both [-2]proPSA derivatives were significantly higher in csPCa and overall PCa (P < .001). The areas under the curves for the prediction of csPCa were higher for the percentage of [-2]proPSA (%[-2]proPSA) (0.781) and the prostate health index (PHI) (0.814) than for PSA (0.651) and %fPSA (0.724). There was a gain of 11% in diagnostic accuracy when %[-2]proPSA or PHI were added to a base model with PSA and %fPSA. Twenty-five percent to 29% of biopsies could have been spared with %[-2]proPSA (cutoff: [greater than or equal to] 1.25%) and PHI (cutoff: [greater than or equal to] 27), missing 10% of csPCas. The same results could have been achieved by using [-2]proPSA as a reflex test, when %fPSA was 25% or less (cutoffs: [greater than or equal to] 1.12% and [greater than or equal to] 24 for %[-2]proPSA and PHI, respectively). Conclusions.--The [-2]proPSA derivatives improve the diagnostic accuracy of csPCa when the PSA value is between 2 and 10 ng/mL, sparing unnecessary biopsies and selecting patients for active surveillance. [-2]proPSA can be used as a reflex test when %fPSA is 25% or less, without reducing the diagnostic accuracy for csPCa and the number of spared biopsies., Prostate cancer (PCa) is estimated to be the malignancy with the highest incidence in men in 2020, both in the United States and in Europe, (1,2) being the second leading [...]

Background/Objectives: We present a software package called reflimR (Version 1.0.6), which enables rapid and transparent verification of reference intervals from routine laboratory measurements. Our method makes it easy to compare the results with specified target values and facilitates the interpretation of deviations using traffic light colors. Methods: The algorithm includes three procedural steps: (a) definition of an appropriate distribution model, based on Bowley's quartile skewness, (b) iterative truncation, based on a modified boxplot method to obtain the central 95% of presumably inconspicuous results, and (c) extrapolation of reference limits from a truncated normal quantile–quantile plot. Results: All algorithms have been combined into one consolidated library, which can be called in the R environment with a single command reflim (x). Using an example dataset included in the package, we demonstrate that our method can be applied to mixed data containing a substantial proportion of pathological values. It leads to similar results as the direct guideline approach as well as the more sophisticated indirect refineR software package. As compared to the latter, reflimR works much faster and needs smaller datasets for robust estimates. For the interpretation of the results, we present an intuitive color scheme based on tolerance ranges (permissible uncertainty of laboratory results). We show that a relatively high number of published reference limits require careful reevaluation. Conclusions: The reflimR package closes the gap between direct guideline methods and the more sophisticated indirect refineR method. We recommend reflimR for the rapid routine verification of large amounts of reference limits and refineR for a careful analysis of unclear or doubtful results from this check. [ABSTRACT FROM AUTHOR]

Legal regulations and guidelines such as the Guidelines of the German Medical Association for the Quality Assurance of Laboratory Medical Examinations (Rili-BAEK) and ISO 15189 apply to electronic laboratory reports. However, many laboratories struggle with practical implementation of these regulations and guidelines.

Point-of-care antigen tests (PoC-AgTs) for the rapid detection of SARS-CoV-2 infection enable screening of additional populations with less effort, independent of laboratories and at a low cost. PoC-AgTs have therefore been included in national testing strategies with additional quality requirements to address limitations in specificity and sensitivity. Information given in the package inserts of the test providers should enable the user to evaluate the performance of a PoC-AgT in advance. The quality of this information has been independently assessed since the Corona Test Ordinance came into force in Germany in October 2020.

BackgroundThis meta-analysis evaluated whether pretherapy serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) are predictive of response to therapy in non-small cell lung cancer (NSCLC) and whether changes in these markers during vs pretherapy are indicative of response.MethodsOriginal peer-reviewed studies enrolling adults with untreated advanced NSCLC were identified using PubMed. Two reviewers independently extracted data from eligible studies and assessed study heterogeneity and the risk of study bias.ResultsFourteen studies were eligible; 11 had objective response as an end point and three evaluated clinical benefit (i.e., response and stable disease). Study bias was relatively low. Both markers showed comparable modest predictive value across studies, with baseline CYFRA 21-1 numerically better in predicting treatment benefit. A good performance in identifying objective response during treatment was seen (AUC 0.724 (95% CI 0.667-0.785) for CYFRA 21-1 and 0.728 (95% CI, 0.599-0.871) for CEA). A decline in CYFRA 21-1 levels during treatment was highly indicative for objective response (sensitivity 79.1% (95% CI 71.5-85.1)).ConclusionsComprehensive analysis of study heterogeneity and bias provides a high level of evidence for the clinical utility of CEA and CYFRA 21-1 for the prediction and monitoring of response in NSCLC.

Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs) were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. However, recent research has shown superior performance using a combination of multiple TMs as a panel for assessment, or as part of validated algorithms that also incorporate other clinical factors. In addition, newer TMs have been discovered that have an increased sensitivity and specificity profile for defined malignancies. The aim of this review is to provide a concise overview of the appropriate uses of both traditional and newer TMs and their roles in diagnosis, prognosis, and the monitoring of patients in current clinical practice. We also look at the future direction of TMs and their integration with other diagnostic modalities and other emerging serum based biomarkers, such as circulating nucleic acids, to ultimately advance diagnostic performance and improve patient management.