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1. The Clinical Decision Support System AMPEL for Laboratory Diagnostics: Implementation and Technical Evaluation

Author

Walter Costa, Maria Beatriz, Wernsdorfer, Mark, Kehrer, Alexander, Voigt, Markus, Cundius, Carina, Federbusch, Martin, Eckelt, Felix, Remmler, Johannes, Schmidt, Maria, Pehnke, Sarah, Gärtner, Christiane, Wehner, Markus, Isermann, Berend, Richter, Heike, Telle, Jörg, and Kaiser, Thorsten

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundLaboratory results are of central importance for clinical decision making. The time span between availability and review of results by clinicians is crucial to patient care. Clinical decision support systems (CDSS) are computational tools that can identify critical values automatically and help decrease treatment delay. ObjectiveWith this work, we aimed to implement and evaluate a CDSS that supports health care professionals and improves patient safety. In addition to our experiences, we also describe its main components in a general manner to make it applicable to a wide range of medical institutions and to empower colleagues to implement a similar system in their facilities. MethodsTechnical requirements must be taken into account before implementing a CDSS that performs laboratory diagnostics (labCDSS). These can be planned within the functional components of a reactive software agent, a computational framework for such a CDSS. ResultsWe present AMPEL (Analysis and Reporting System for the Improvement of Patient Safety through Real-Time Integration of Laboratory Findings), a labCDSS that notifies health care professionals if a life-threatening medical condition is detected. We developed and implemented AMPEL at a university hospital and regional hospitals in Germany (University of Leipzig Medical Center and the Muldental Clinics in Grimma and Wurzen). It currently runs 5 different algorithms in parallel: hypokalemia, hypercalcemia, hyponatremia, hyperlactatemia, and acute kidney injury. ConclusionsAMPEL enables continuous surveillance of patients. The system is constantly being evaluated and extended and has the capacity for many more algorithms. We hope to encourage colleagues from other institutions to design and implement similar CDSS using the theory, specifications, and experiences described in this work.

Published
2021
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2. Reference intervals and percentiles for soluble transferrin receptor and sTfR/log ferritin index in healthy children and adolescents.

Author

Prenzel, Freerk, Kaiser, Thorsten, Willenberg, Anja, vom Hove, Maike, Flemming, Gunter, Fischer, Lars, Kratzsch, Jürgen, Kiess, Wieland, and Vogel, Mandy

Subjects
*TRANSFERRIN receptors, *IRON in the body, *IRON deficiency, *BODY mass index, *IRON metabolism
Abstract

Soluble transferrin receptor (sTfR) is a marker of both erythropoiesis and iron status and is considered useful for detecting iron deficiency, especially in inflammatory conditions, but reference intervals covering the entire pediatric age spectrum are lacking. We studied 1,064 (48.5 % female) healthy children of the entire pediatric age spectrum to determine reference values and percentiles for sTfR and the ratio of sTfR to log-ferritin (sTfR-F index) using a standard immunoturbidimetric assay. Soluble TfR levels were highly age-specific, with a peak in infancy and a decline in adulthood, whereas the sTfR-F index was a rather constant parameter. There were positive linear relationships for sTfR with hemoglobin (Hb) (p=0.008) and transferrin (females p<0.001; males p=0.003). A negative association was observed between sTfR and ferritin in females (p<0.0001) and for transferrin saturation and mean corpuscular volume (MCV) in both sexes (both p<0.0001). We found a positive relationship between sTfR and body height, body mass index (BMI) and inflammatory markers (CrP p<0.0001; WBC p=0.0172), while sTfR-F index was not affected by inflammation. Soluble TfR values appear to reflect the activity of infant erythropoiesis and to be modulated by inflammation and iron deficiency even in a healthy cohort. [ABSTRACT FROM AUTHOR]

Published
2025
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7. Biomarkers for Non-Invasive Stratification of Coronary Artery Disease and Prognostic Impact on Long-Term Survival in Patients with Stable Coronary Heart Disease

Author

Netto, Jeffrey, Teren, Andrej, Burkhardt, Ralph, Willenberg, Anja, Beutner, Frank, Henger, Sylvia, Schuler, Gerhard, Thiele, Holger, Isermann, Berend, Thiery, Joachim, Scholz, Markus, Kaiser, Thorsten, Netto, Jeffrey, Teren, Andrej, Burkhardt, Ralph, Willenberg, Anja, Beutner, Frank, Henger, Sylvia, Schuler, Gerhard, Thiele, Holger, Isermann, Berend, Thiery, Joachim, Scholz, Markus, and Kaiser, Thorsten

Abstract

Knowledge about cardiac and inflammatory biomarkers in patients with stable coronary artery disease (CAD) is limited. To address this, we analyzed 3072 patients (36% female) with a median follow-up of 10 years in the Leipzig LIFE Heart Study with suspected CAD with coronary angiography. Selected biomarkers included troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, C-reactive protein (hsCRP), and interleukin-6 (IL-6). Patients were stratified by CAD severity: CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis < 50%), and CAD2 (one stenosis 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2; GC2: CAD0 vs. CAD1 + 2. CAD0, CAD1, and CAD2 were apparent in 1271, 631, and 1170 patients, respectively. Adjusted for classical risk factors, hs-cTnT, NT-proBNP, and IL-6 differed significantly in both GC and hsCRP only in GC2. After multivariate analysis, hs-cTnT, NT-proBNP, and IL-6 remained significant in GC1. In GC2, hs-cTnT (p < 0.001) and copeptin (p = 0.014) reached significance. Ten-year survival in groups CAD0, CAD1, and CAD2 was 88.3%, 77.3%, and 72.4%. Incorporation of hs-cTnT, NT-proBNP, copeptin, and IL-6 improved risk prediction (p < 0.001). The studied cardiac and inflammatory biomarkers enable fast and precise non-invasive identification of mortality risk in CAD patients, allowing the tailoring of primary and secondary CAD prevention.

Published
2024

10. Evidence-based cutoffs for total and adjusted calcium: a major factor in detecting severe hypo- and hypercalcemia.

Author

Schmidt, Maria, Steinbach, Daniel, Federbusch, Martin, Tönjes, Anke, Isermann, Berend, Kaiser, Thorsten, and Eckelt, Felix

Subjects
HYPERCALCEMIA, CALCIUM, COHEN'S kappa coefficient (Statistics), CLINICAL decision support systems
Abstract

Severe hypo- and hypercalcemia are common and urgent treatment is recommended. Free calcium (fCa) is the gold standard but needs blood gas tests with challenging preanalytics. Total calcium (tCa) and calculated adjusted calcium (aCa) are readily available, but their interpretation is hampered by identical tCa and aCa cutoffs, laborious local aCa calculation and difficult comparability of calcium biomarkers. Laboratory results from University Medicine Leipzig were evaluated over a five-year period (236,274 patients). A local aCa equation was derived by linear least squares regression, the agreement between fCa, tCa and aCa assessed with Cohen's κ and decision thresholds derived by this indirect method. The local aCa equation was created from data of 9,756 patients, each with one paired measurement of tCa, fCa and albumin. Derived aCa cutoffs (1.95/3.15 mmol/L) differ markedly from derived tCa cutoffs (1.6/2.9 mmol/L) and severe hypo- and hypercalcemia can be more accurately assessed by aCa (κ=0.489, 0.812) than by tCa (κ=0.445, 0.744). Comparing our approach to standard care (tCa, literature cutoff), a total 3,250 of 3,680 (88.3 %) misclassified measurements were correctly classified when using aCa with evidence-based cutoffs. Optimized cutoffs for aCa and tCa hold great potential for improved patient care. Locally derived aCa equations differ mostly in the chosen mean normal calcium and provide minimal overall improvement, but entail a close examination of the used cutoffs before application. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Higher troponin T serum concentrations in hospital patients without diagnosed cardiac diseases compared to a population-based cohort

Author

Gessner, Romy, primary, Gärtner, Christiane, additional, Schmidt, Maria, additional, Eckelt, Felix, additional, Wirkner, Kerstin, additional, Löffler, Markus, additional, Uhe, Tobias, additional, Isermann, Berend, additional, Laufs, Ulrich, additional, Kaiser, Thorsten, additional, and Wachter, Rolf, additional

Published
2023
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27. Revising the MELD Score to Address Sex-Bias in Liver Transplant Prioritization for a German Cohort

Author

Walter Costa, Maria Beatriz, Gärtner, Christiane, Schmidt, Maria, Berg, Thomas, Seehofer, Daniel, and Kaiser, Thorsten

Abstract

(1) Background: Prioritization of patients for liver transplantation in Germany relies on the MELD (model for end-stage liver disease) scoring system that does not consider the patient’s sex. Many studies have shown that women are disadvantaged by the MELD score. Using a large patient cohort from a German liver transplant centre, we investigated options to reduce gender inequality in the patient prioritization for liver transplantation. (2) Methods: We calculated female-as-male MELD scores in our cohort by substituting the serum creatinine of a female patient with that of their male equivalent to test for the fairness of the scores. We investigated the effects of the female-as-male scores compared to the original MELD score of 1759 patients listed for liver transplantation. (3) Results: Serum creatinine sex correction (female-as-male) for MELD scores added up to 5.4 points in females, while the median changed by +1.6 points for females. We identified 72 females with an original MELD score < 20, for whom the adjusted female-as-male MELD score would be >20, thus giving them a better chance to receive a liver transplant. (4) Conclusions: Mathematical conversion of female to male creatinine concentrations identified disadvantages in liver transplantation prioritization for females and ascertained MELD 3.0 as having high potential to compensate for these inequalities.

Published
2023
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34. Invasive Growth of Ailanthus altissima Trees is Associated with a High Rate of Sensitization in Atopic Patients

Author

Prenzel, Freerk, primary, Treudler, Regina, additional, Lipek, Tobias, additional, vom Hove, Maike, additional, Kage, Paula, additional, Kuhs, Simone, additional, Kaiser, Thorsten, additional, Bastl, Maximilian, additional, Bumberger, Jan, additional, Genuneit, Jon, additional, Hornick, Thomas, additional, Klotz, Stefan, additional, Zarnowski, Julia, additional, Boege, Maren, additional, Zebralla, Veit, additional, Simon, Jan-Christoph, additional, and Dunker, Susanne, additional

Published
2022
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35. Biomarkers for Non-Invasive Stratification of Coronary Artery Disease and Prognostic Impact on Long-Term Survival in Patients with Stable Coronary Heart Disease

Author

Netto, Jeffrey, primary, Teren, Andrej, additional, Burkhardt, Ralph, additional, Willenberg, Anja, additional, Beutner, Frank, additional, Henger, Sylvia, additional, Schuler, Gerhard, additional, Thiele, Holger, additional, Isermann, Berend, additional, Thiery, Joachim, additional, Scholz, Markus, additional, and Kaiser, Thorsten, additional

Published
2022
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36. Endgames

Author

Kaiser, Thorsten, Moessner, Joachim, Patel, Keyur, McHutchison, John G., Tillmann, Hans L., Fletcher, John, Fellows, Helen J., and Dalton, Harry R.

Published
2009

37. Body fat composition determines outcomes before and after liver transplantation in patients with cirrhosis

Author

Engelmann, Cornelius, Aehling, Niklas F., Schob, Stefan, Nonnenmacher, Ines, Handmann, Luise, Macnaughtan, Jane, Herber, Adam, Surov, Alexey, Kaiser, Thorsten, Denecke, Timm, Jalan, Rajiv, Seehofer, Daniel, Moche, MIchael, Berg, Thomas, Engelmann, Cornelius, Aehling, Niklas F., Schob, Stefan, Nonnenmacher, Ines, Handmann, Luise, Macnaughtan, Jane, Herber, Adam, Surov, Alexey, Kaiser, Thorsten, Denecke, Timm, Jalan, Rajiv, Seehofer, Daniel, Moche, MIchael, and Berg, Thomas

Abstract

Cachexia occurs in late stages of liver cirrhosis, and a low-fat mass is potentially associated with poor outcome. This study compared different computed tomography (CT)–derived fat parameters with respect to its prognostic impact on the development of complications and death before and after liver transplantation. Between 2001 and 2014, 612 patients with liver cirrhosis without hepatocellular carcinoma listed for liver transplantation met the inclusion criteria, including abdominal CT scan (±200 days to listing). A total of 109 patients without cirrhosis served as controls. The subcutaneous fat index (SCFI), the paraspinal muscle fat index, and the visceral fat index were assessed at L3/L4 level and normalized to the height (cm2/m2). Data were collected and analyzed retrospectively. Low SCFI was associated with a higher rate of ascites and increased C-reactive protein levels (p < 0.001). In addition, multivariate Cox regression analysis adjusting for sex, age, body mass index (BMI), and Model for End-Stage Liver Disease showed that decreasing SCFI was also associated with an increased risk of cirrhosis-related complications (p = 0.003) and death on the transplant wait list (p = 0.013). Increased paraspinal and visceral fat were not only positively correlated with creatinine levels (p < 0.001), BMI, and metabolic comorbidities (all p < 0.001) before transplantation, but also predictive for 1-year mortality after transplantation. Conclusion: The distribution of body fat is a major determinant for complications and outcome in cirrhosis before and after liver transplantation.

Published
2022

38. Invasive Growth of Ailanthus altissima Trees is Associated with a High Rate of Sensitization in Atopic Patients

Author

Prenzel,Freerk, Treudler,Regina, Lipek,Tobias, vom Hove,Maike, Kage,Paula, Kuhs,Simone, Kaiser,Thorsten, Bastl,Maximilian, Bumberger,Jan, Genuneit,Jon, Hornick,Thomas, Klotz,Stefan, Zarnowski,Julia, Boege,Maren, Zebralla,Veit, Simon,Jan-Christoph, Dunker,Susanne, Prenzel,Freerk, Treudler,Regina, Lipek,Tobias, vom Hove,Maike, Kage,Paula, Kuhs,Simone, Kaiser,Thorsten, Bastl,Maximilian, Bumberger,Jan, Genuneit,Jon, Hornick,Thomas, Klotz,Stefan, Zarnowski,Julia, Boege,Maren, Zebralla,Veit, Simon,Jan-Christoph, and Dunker,Susanne

Abstract

Freerk Prenzel1,2 &ast;, Regina Treudler1,3 &ast;, Tobias Lipek,1,2 Maike vom Hove,1,2 Paula Kage,1,3 Simone Kuhs,1,4 Thorsten Kaiser,1,4 Maximilian Bastl,5 Jan Bumberger,6– 8 Jon Genuneit,9,10 Thomas Hornick,8,11 Stefan Klotz,8,12 Julia Zarnowski,1,3 Maren Boege,1,13 Veit Zebralla,1,13 Jan-Christoph Simon,1,3 Susanne Dunker8,11 1Leipziger Interdisciplinary Center for Allergy (LICA), Comprehensive Allergy Center, Leipzig, Germany; 2University of Leipzig, Medical Center, Department of Pediatrics, Leipzig, Germany; 3University of Leipzig, Medical Center, Department of Dermatology, Venerology and Allergy, Leipzig, Germany; 4University of Leipzig, Medical Center, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig, Germany; 5Medical University of Vienna, Department of Otorhinolaryngology, Vienna, Austria; 6Helmholtz-Centre for Environmental Research (UFZ), Department Monitoring and Exploration Technologies, Leipzig, Germany; 7Helmholtz-Centre for Environmental Research (UFZ), Research Data Management, Leipzig, Germany; 8German Centre for Integrative Biodiversity Research (iDiv) Halle, Jena, Leipzig, Germany; 9Pediatric Epidemiology, Department of Pediatrics, Medical Faculty, Leipzig University, Leipzig, Germany; 10German Center for Child and Youth Health, Leipzig/ Dresden, Dresden, Germany; 11Helmholtz-Centre for Environmental Research (UFZ), Department Physiological Diversity, Leipzig, Germany; 12Helmholtz-Centre for Environmental Research (UFZ), Department Community Ecology, Halle, Germany; 13University of Leipzig, Medical Center, Department of Otorhinolaryngology, Head and Neck Surgery, Leipzig, Germany&ast;These authors contributed equally to this workCorrespondence: Susanne Dunker, Helmholtz Centre for Environmental Research – UFZ, Leipzig, Germany, Tel +49 341 9733170, Email susanne.dunker@ufz.dePurpose: Ailanthus altissima is one of the world’s most invasive species with a globally problematic spread. Pollen i

Published
2022

41. Body fat composition determines outcomes before and after liver transplantation in patients with cirrhosis

Author

Engelmann, Cornelius, primary, Aehling, Niklas F., additional, Schob, Stefan, additional, Nonnenmacher, Ines, additional, Handmann, Luise, additional, Macnaughtan, Jane, additional, Herber, Adam, additional, Surov, Alexey, additional, Kaiser, Thorsten, additional, Denecke, Timm, additional, Jalan, Rajiv, additional, Seehofer, Daniel, additional, Moche, Michael, additional, and Berg, Thomas, additional

Published
2022
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42. Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with newly diagnosed/untreated multiple myeloma

Author

Pönisch, Wolfram, Holzvogt, Bruno, Plötze, Madlen, Andrea, Marc, Bourgeois, Malvina, Heyn, Simone, Zehrfeld, Thomas, Hammerschmidt, Doreen, Schwarz, Maik, Edelmann, Thomas, Becker, Cornelia, Hoffmann, Franz Albert, Schwarzer, Andreas, Kreibich, Ute, Gutsche, Kerstin, Reifenrath, Kolja, Winkelmann, Cornelia, Krahl, Rainer, Remane, Yvonne, Hennig, Evelin, Schliwa, Thomas, Lindner, Tom, Kaiser, Thorsten, Vucinic, Vladan, Behre, Gerhard, and Niederwieser, Dietger

Published
2014
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44. Raman spectroscopy on blood serum samples of patients with end-stage liver disease

Author

Estrela-Lopis Irina, Kaiser Thorsten, Peter W. Hildebrand, Staritzbichler René, Isermann Berend, and Hunold Pascal

Subjects
Adult, Male, Raman Spectroscopy, Physiology, Science, Gastroenterology and Hepatology, Research and Analysis Methods, Spectrum Analysis, Raman, Biochemistry, End Stage Liver Disease, symbols.namesake, Liver disease, Spectrum Analysis Techniques, Blood serum, Diagnostic Medicine, Albumins, Medicine and Health Sciences, medicine, Bile, Humans, High potential, Aged, business.industry, Liver Diseases, Biology and Life Sciences, Proteins, Bilirubin, End stage liver disease, Middle Aged, Serum samples, medicine.disease, Body Fluids, Blood, Creatinine, symbols, Medicine, Female, Anatomy, Raman spectroscopy, business, Biomarkers, Algorithms, Research Article, Biomedical engineering
Abstract

Raman spectroscopy has shown to be a promising method for the examination of biomedical samples. However, until now, its efficacy has not been established in clinical diagnostics. In this study, Raman spectroscopy’s potential application in medical laboratories is evaluated for a large variety (38) of biomarkers. Given 234 serum samples from a cohort of patients with different stages of liver disease, we performed Raman spectroscopy at 780nm excitation wavelength. The Raman spectra were analyzed in combination with the results of routine diagnostics using specifically developed complex mathematical algorithms, including fluorescence filtering, frequency subset selection and several overfitting circumventing strategies, such as independent validation. With the results of this cohort, which were validated in 328 independent samples, a significant proof-of-concept study was completed. This study highlights the need to prevent overfitting and to use independent data for validation. The results reveal that Raman spectroscopy has high potential for use in medical laboratory diagnostics to simultaneously quantify multiple biomarkers.

Published
2021
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49. Acute kidney injury and its progression in hospitalized patients—Results from a retrospective multicentre cohort study with a digital decision support system

Author

Kister, Thea Sophie, primary, Remmler, Johannes, additional, Schmidt, Maria, additional, Federbusch, Martin, additional, Eckelt, Felix, additional, Isermann, Berend, additional, Richter, Heike, additional, Wehner, Markus, additional, Krause, Uwe, additional, Halbritter, Jan, additional, Cundius, Carina, additional, Voigt, Markus, additional, Kehrer, Alexander, additional, Telle, Jörg Michael, additional, and Kaiser, Thorsten, additional

Published
2021
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50. Sensitivity of SARS-CoV-2 antibody tests with late convalescent sera

Author

Kannenberg, Judith, primary, Schnurra, Carolin, additional, Reiners, Nina, additional, Henschler, Reinhard, additional, Buhmann, Raymund, additional, Kaiser, Thorsten, additional, Biemann, Ronald, additional, Hönemann, Mario, additional, Ackermann, Grit, additional, Trawinski, Henning, additional, and Jassoy, Christian, additional

Published
2021
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