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Simplified preanalytical laboratory procedures for therapeutic drug monitoring (TDM) in patients treated with high-dose methotrexate (HD-MTX) and glucarpidase
24.10.24 | The administration of high-dose methotrexate (HD-MTX) in cancer patients occasionally leads to kidney damage, which necessitates the use of the enzyme glucarpidase to remove MTX. The established immunoassays for therapeutic drug monitoring (TDM) of MTX often show cross-reactivity, which affects the results and necessitates the use of chromatography-based methods. Employees of the Department of Laboratory Medicine & Toxicology were able to show that simplified pre-analytical processing of blood samples without an acidification step is sufficient for precise LC-MS/MS analysis (mass spectrometry), thus saving valuable time for the preparation of findings, whereby correct sample storage at specific temperatures is crucial for measurement accuracy.
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Therapy-related AML: long-term outcome in a large cohort of AML-patients with intensive and non-intensive therapy
02.10.24 | In a retrospective study of 1,133 patients, members of the Department of Haematology & Oncology were able to show that patients with therapy-related acute myeloid leukaemia (t-AML) have a poorer prognosis than de novo AML patients, which is reflected in shorter survival times with prognostically less favourable genetic changes. Intensively treated t-AML patients showed a significantly shorter median overall survival time. The results suggest that the treatment of t-AML should be guided in particular by genetic risk factors and not exclusively based on the t-AML diagnosis, taking into account the latest ELN 2022 recommendations.
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Amplification of autoimmune organ damage by NKp46-activated ILC1
04.09.24 | Staff from the Departments of Microbiology and Autoimmune Diagnostics, together with researchers from Charité, have shown in a high-ranking publication in the journal Nature that specialised immune cells, the innate lymphoid cells (ILC), play a central role in triggering kidney damage in lupus erythematosus, known as lupus nephritis. This finding challenges the previous assumption that autoantibodies alone are responsible for tissue damage in lupus and shows that activation of ILC by the receptor NKp46 triggers a cascade of inflammatory processes and tissue damage in the kidneys. The results could lead to new treatment options aimed at blocking this ILC and thus preventing severe kidney damage in lupus patients.
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Laboratory Reform 2025: Call for support
14.08.24 | Devaluations in laboratory diagnostics jeopardise comprehensive & local care! That’s why we need your help! Because it affects us all, we ask you to support the concerns of the Accredited Laboratories in Medicine e.V. for the Laboratory Reform 2025. You can access all the details, the open letter and the signature form via the link in the button.
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Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19
09.08.24| Staff from the Departments of Microbiology, Virology & Immunology, together with researchers from Charité, were able to use metagenome, metabolome, cytokine and transcriptome profiling of hospitalised COVID-19 patients compared to uninfected control subjects to identify associated changes in the microbiome and metabolome as a contribution to inflammatory dysregulation in COVID-19. For example, severe disease progression is associated with the loss of beneficial gut microbes and disturbances in the oropharyngeal microbiome were due to antibiotic use. Reduced concentrations of various metabolites in the blood were associated with a depletion of certain bacterial species in the gut, while higher concentrations were associated with an increase in pro-inflammatory cytokines. The study results provide a basis for understanding the role of the microbiome in other types of severe infections.
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Improvement of liquid handling and sample preparation
02.08.24 | In collaboration with Hamilton, Labor Berlin is expanding the automation and standardization of its workflows in sample preparation. This strategic partnership focuses on daily routines of IVD-R-compliant, laboratory-developed workflows.
Studies & Collaborations department
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Clinical presentation, diagnosis, and treatment of chronic granulomatous disease
05.07.24 | In a recent publication, members of the Department of Immunology provide a comprehensive overview of the congenital immunodeficiency of chronic granulomatosis (CGD), which is caused by an impaired respiratory burst reaction of phagocytes. The authors provide a comprehensive description of the molecular pathomechanism and state-of-the-art flow cytometric diagnostics for individual characterization and treatment selection in this X-linked or autosomal recessive disease, which is associated with an increased risk of severe bacterial and fungal infections. Apart from prophylactic antibiotics and immunosuppressive therapies to control excessive autoinflammatory reactions, allogeneic stem cell transplantation or gene therapies are the only curative options.
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SARS-CoV-2 rapid antigen test sensitivity and viral load in newly symptomatic hospital employees in Berlin, Germany, December, 2020 to February, 2022: an observational study
07.06.24 | Employees of the Department of Virology, together with clinicians from Charité, have examined the performance of antigen-based rapid tests (Ag-RDT) in symptomatic hospital employees with regard to various SARS-CoV-2 variants and immunization status in 7,675 employees of Charité Universitätsmedizin Berlin. It was found that the sensitivity of Ag-RDT was higher in immunologically naive individuals (82%) than in multiply immunized individuals (73%) and that the sensitivity decreased over time due to changing dominant virus variants and increasing vaccination rates. Despite higher SARS-CoV-2 RNA concentrations, the increased population immunity led to reduced clinical Ag-RDT sensitivity.
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Blood calprotectin as a biomarker for infection and sepsis – the prospective CASCADE trial
17.05.24 | In a prospective clinical study involving 395 patients in the emergency room, staff from the Department of Laboratory Medicine and clinicians from Charité determined the biomarker calprotectin, which is released by white blood cells (neutrophil granulocytes) in the event of a bacterial infection. The so-called ROC value (maximum 1.0) of calprotectin for the detection of bacterial infections was 0.90 (in diabetics even 0.94), for the detection of sepsis within 72 hours 0.83 and for the prediction of 30-day mortality 0.78. The results show that the serum biomarker calprotectin can be helpful in detecting bacterial infections, assessing their severity and predicting clinical deterioration.
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Screening Newborns for Low T Cell Receptor Excision Circles (TRECs) Fails to Detect Immunodeficiency, Centromeric Instability, and Facial Anomalies Syndrome
07.05.24 | Employees of the Immunology and Human Genetics departments at Labor Berlin, together with clinicians from Charité, have shown that the genetic determination of T-cell-rexeptor-excision-circles (TRECs) from the dried blood of newborns can reliably identify severely affected SCID patients (severe combined immunodeficiency) and provide them with immediate therapy. Nevertheless, only two thirds of patients with CID (combined immunodeficiency) could be identified who still have T cells at birth but lose them with increasing age and then fall ill. This shows that even in the case of inconspicuous newborn screening, early diagnosis for this patient group is of decisive importance for finding an adequate therapy.
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Surfing with laboratory plastic
02.05.24 | Labor Berlin meets Merijaan
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Together with the Berlin start-up Merijaan, we are focusing on innovative recycling on the way to a greener laboratory, because sustainability is important to us!
Read the interview with Katja Strunk, Head of Facility Management at Labor Berlin, to find out how this collaboration came about in 2022 and what surfboards made from laboratory plastic are all about. -
A Novel Variant in the WRN Gene Detected in a Case of early-onset Severe Insulin Resistance Displaying Some but Not All Hallmarks of Progeroid Werner Syndrome
15.04.24 | Using NGS sequencing (Next Generation Sequencing), employees of Labor Berlin, together with scientists from Charité, were able to identify a previously unknown pathogenic homozygous variant in the WRN gene that led to severe insulin resistance in a patient with early-onset diabetes. The result shows that Werner syndrome should be considered in the differential diagnosis of cases of severe insulin resistance and emphasizes the importance of NGS analysis for finding a diagnosis in selected cases.
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“Top 40 under 40” visit to Labor Berlin
04.04.24 | Since 2007, Capital has been selecting the “Top 40 under 40”: an award for young talents from business, politics and society. A network meeting is held once a month to provide insights into the different working environments and to share experiences and visions. Last week, Nina Beikert, Managing Director of Labor Berlin, welcomed some guests to our central laboratory.
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Strategies and solutions for recruiting skilled workers
26.03.24 | The effects of the shortage of skilled workers on the German labor market are becoming increasingly noticeable & are also putting further pressure on the healthcare industry. According to a recent study, around 1.8 million jobs in the healthcare sector could remain unfilled in 2035. How successful recruitment and long-term employee retention can be achieved in the future was discussed in detail last week at the Roche Laboratory Forum 2024 with experts including Fabian Raddatz, Managing Director of Labor Berlin.
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Underfilled blood collection tubes as pathologizing factor for measured laboratory parameters in older patients
20.03.24 | In hematology and cancer patients, high LDH (lactate dehydrogenase) levels are often correlated with advanced disease or tumor burden and aid in diagnosis, monitoring and prognosis. Employees of the Department of Laboratory Medicine were able to show in a study that increased LDH concentrations, especially in geriatric patients, can lead to unnecessary and extensive diagnostic procedures or even to misdiagnoses due to insufficiently filled sample tubes, e.g. due to difficulties in taking blood samples or due to vein problems. This pre-analytical error in LDH determination should be taken into account in order to avoid a considerable clinical burden or even patient damage.
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Value of hemophagocytosis in the diagnosis of hemophagocytic lymphohistiocytosis in critically ill patients
27.02.24 | Employees of the Department of Hematology/Oncology, together with scientists from Charité, were able to show in a study of over 250 critically ill adult intensive care patients with secondary HLH (hemophagocytic lymphohistiocytosis) that the determination of a significantly increased ferritin concentration quickly and reliably confirms the diagnosis of HLH. The results suggest that the diagnosis of HLH should be considered and treated in patients with high ferritin concentrations, even if only four HLH-2004 criteria are met and hemophagocytosis is not assessable or detectable by bone marrow aspiration.
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Mucosal microbiome of surgically treated terminal ileal Crohn’s disease
14.02.24 | In a molecular biological comparison of surgical CD versus non-CD patients in a study of Crohn’s disease (CD), members of the Department of Molecular Diagnostics, together with scientists from Charité, were able to determine that there were no differences in the diversity of species and diversity of the intestinal microbiome. However, CD patients showed significant taxonomic differences, in particular a decrease in Firmicutes at the genus level and an increase in Bacteroides, Escherichia, Shigella and Pseudescherichia at the genus level. The results show that Crohn’s disease is associated with changes in the gut microbiome and contributes to the understanding of the mucosal microbiome in surgical CD patients.
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Labor Berlin image video
02.02.24 | We have the well-being of our patients firmly in our sights – because every moment counts! Because rehearsals are filled with life for us. Life that we want to preserve. Watch our image video to find out what drives us and why passion is our credo!
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Digitalization in the medical laboratory
31.01.2024 | Medical laboratories are important data providers in the healthcare sector. Increasing digitization promises simpler, more efficient and more transparent workflows, from sampling to archiving. At the Roche Laboratory Forum 2023 in Mannheim, experts such as Nikolaus Wintrich, Chief Operating Officer of Labor Berlin, discussed the opportunities and challenges of digitalization for laboratories with a focus on optimizing processes and overcoming hurdles.
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Humoral immune escape by current SARS-CoV-2 variants BA.2.86 and JN.1, December 2023
24.01.24 | The SARS-CoV-2 variants BA.2.86 and its descendant JN.1 are currently spreading worldwide. Together with researchers from all over Europe, members of the Department of Virology were able to show through neutralization experiments with the virus isolates JN.1, BA.2.86, EG.5, XBB.1.5 and earlier variants on patient sera (vaccinated or recovered) obtained in autumn 2023 that although a clear neutralization escape was detectable, this effect did not differ in specificity from other newer variants in the two new variants. The neutralization escape thus generally corresponds to the increased occurrence of new virus variants, but does not explain the increase in JN.1 incidence.
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The Recurrent Atypical e8a2 BCR::ABL1 Transcript with Insertion of an Inverted 55 Base Pair ABL1 Intron 1b Sequence: A Detailed Molecular Analysis
08.01.24 | Detecting the unusual BCR::ABL1 transcripts in about 2% of chronic myeloid leukaemia (CML) cases in the laboratory is important so that these patients can also benefit from therapy with tyrosine kinase inhibitors. In the case of a rare variant called e8a2 BCR::ABL1, employees at Labor Berlin were able to elucidate the complex multi-stage development of this variant and determine the chromosomal breakpoint. The study also documents the course of the disease and provides recommendations for the future molecular analysis of similar cases.
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Simplified preanalytical laboratory procedures for therapeutic drug monitoring (TDM) in patients treated with high-dose methotrexate (HD-MTX) and glucarpidase
Franz L. Knörnschild, Sven Liebig, Peggy Kießling, Monika Prpic, Tehyung Kim, Ulrich Keller, Kai Kappert, Stefan Schwartz, Amir Jahic Blood Cancer Journal, 16 September 2024 doi: 10.1515/cclm-2024-052 PMID: 38997789
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Therapy-related AML: long-term outcome in a large cohort of AML-patients with intensive and non-intensive therapy
Sophia Gross, Jana Ihlow, Leonie Busack, Kacper Adamiak, Jens Schrezenmeier, Julia Jesse, Michaela Schwarz, Anne Flörcken, Lam Giang Vuong, Kathrin Rieger, Jan Krönke, Philipp le Coutre, Vivien Boldt, Ann-Christin von Brünneck, David Horst, Thomas Burmeister, Igor-Wolfgang Blau, Ulrich Keller, Lars Bullinger, Jörg Westermann Blood Cancer Journal, 16 September 2024 doi: 10.1038/s41408-024-01140-5 PMID: 39284846
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Amplification of autoimmune organ damage by NKp46-activated ILC
Stylianos-Iason Biniaris-Georgallis, Tom Aschman, Katerina Stergioula, Frauke Schreiber, Vajiheh Jafari, Anna Taranko, Tejal Karmalkar, Ana Kasapi, Tihana Lenac Rovis, Vedrana Jelencic, David A. Bejarano, Lea Fabry, Michail Papacharalampous, Irene Mattiola, Martina Molgora, Jinchao Hou, Karolin W. Hublitz, Frederik Heinrich, Gabriela Maria Guerra, Pawel Durek, Giannino Patone, Eric Lars-Helge Lindberg, Henrike Maatz, Oliver Hölsken, Gerhard Krönke, Arthur Mortha, Reinhard E. Voll, Alexander J. Clarke, Anja E. Hauser, Marco Colonna, Kevin Thurley, Andreas Schlitzer, Christoph Schneider, Efstathios G. Stamatiades, Mir-Farzin Mashreghi, Stipan Jonjic, Norbert Hübner, Andreas Diefenbach, Masatoshi Kanda & Antigoni Triantafyllopoulou Nature 2024 Aug 13 doi: 10.1038/s41586-024-07907-x PMID: 39137897
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Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19
Morgan Essex, Belén Millet Pascual-Leone, Ulrike Löber, Mathias Kuhring, Bowen Zhang, Ulrike Brüning, Raphaela Fritsche-Guenther, Marta Krzanowski, Facundo Fiocca Vernengo, Sophia Brumhard, Ivo Röwekamp, Agata Anna Bielecka, Till Robin Lesker, Emanuel Wyler, Markus Landthaler, Andrej Mantei, Christian Meisel, Sandra Caesar, Charlotte Thibeault, Victor M Corman, Lajos Marko, Norbert Suttorp, Till Strowig, Florian Kurth, Leif E Sander, Yang Li, Jennifer A Kirwan, Sofia K Forslund, Bastian Opitz NPJ Biofilms Microbiomes Aug 1, 2024 doi: 10.1038/s41522-024-00538-0 PMID: 39085233
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Clinical presentation, diagnosis, and treatment of chronic granulomatous disease
Olga Staudacher, Horst von Bernuth Frontiers in Pediatrics, June 28, 2024 doi: 10.3389/fped.2024.1384550
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Measurement uncertainty and quality assurance in the field of immunophenotyping of lymphocyte subpopulations in peripheral blood.
Nebe, Carl Thomas; Dorn-Beineke, Alexandra; Braun, Patrick; Daniel, Volker; Ilieva, Zhana; Kuling, Gudrun; Meisel, Christian; Oelschlägel, Uta; Sack, Ulrich Follow LaboratoriumsMedizin, Volume 37 (5) de Gruyter – Sep 1, 2013
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Congenital pneumonia and pustular skin lesions in a male infant.
Leisering J, Renner E.D, von Bernuth H, Wahn V, Rossi R Monthly Journal of Pediatrics 8. 2013, June
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Terminally differentiated CD8⁺ T cells negatively affect bone regeneration in humans.
Reinke S, Geissler S, Taylor WR, Schmidt-Bleek K, Juelke K, Schwachmeyer V, Dahne M, Hartwig T, Akyüz L, Meisel C, Unterwalder N, Singh NB, Reinke P, Haas NP, Volk HD, Duda GN Sci Transl Med. 2013 May 29;5(187):187er4. PMID:23515078
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Impaired thymic function and CD4+ T lymphopenia, but not mannose-binding lectin deficiency, are risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients.
Schürmann M, Schürmann D, Schindler R, Meisel C, Liman P, Kruse J, Enghard P, König J, Schmidt D, Reinke P, Nickel P Transpl Immunol. 2013 Jun;28(4):159-63. doi: 10.1016/j.trim.2013.05.003. Epub 2013 May 15. PMID:23684946
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Even in Pneumococcal Sepsis CD62L Shedding on Granulocytes Proves to be a Reliable Functional Test for the Diagnosis of Interleukin-1 Receptor Associated Kinase 4 Deficiency.
Andres O, Strehl K, Kölsch U, Kunzmann S, Lebrun AH, Stroh T, Schwarz K, Morbach H, von Bernuth H, Liese J Pediatr Infect Dis J. 2013 Mar 27. [Epub ahead of print] PMID:23538514
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