Harden, Markus

[["dc.bibliographiccitation.firstpage","3869"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Knee Surgery, Sports Traumatology, Arthroscopy"],["dc.bibliographiccitation.lastpage","3877"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Balcarek, Peter"],["dc.contributor.author","Rehn, Stephan"],["dc.contributor.author","Howells, Nick R."],["dc.contributor.author","Eldridge, Jonathan D."],["dc.contributor.author","Kita, Keisuke"],["dc.contributor.author","Dejour, David"],["dc.contributor.author","Nelitz, Manfred"],["dc.contributor.author","Banke, Ingo J."],["dc.contributor.author","Lambrecht, Delphine"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Friede, Tim"],["dc.date.accessioned","2020-12-10T14:09:50Z"],["dc.date.available","2020-12-10T14:09:50Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1007/s00167-016-4365-x"],["dc.identifier.eissn","1433-7347"],["dc.identifier.issn","0942-2056"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70574"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Results of medial patellofemoral ligament reconstruction compared with trochleoplasty plus individual extensor apparatus balancing in patellar instability caused by severe trochlear dysplasia: a systematic review and meta-analysis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","282"],["dc.bibliographiccitation.journal","Journal of Clinical Anesthesia"],["dc.bibliographiccitation.lastpage","289"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Wetz, Anna J."],["dc.contributor.author","Perl, Thorsten"],["dc.contributor.author","Brandes, Ivo Florian"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Bauer, Martin"],["dc.contributor.author","Braeuer, Anselm"],["dc.date.accessioned","2018-11-07T10:06:45Z"],["dc.date.available","2018-11-07T10:06:45Z"],["dc.date.issued","2016"],["dc.description.abstract","Study objective: Perioperative hypothermia is a frequently observed phenomenon of general anesthesia and is associated with adverse patient outcome. Recently, a significant influence of core temperature before induction of anesthesia has been reported. However, there are still little existing data on core temperature before induction of anesthesia and no data regarding potential risk factors for developing preoperative hypothermia. The purpose of this investigation was to estimate the incidence of hypothermia before anesthesia and to determine if certain factors predict its incidence. Design/setting/patients: Data from 7 prospective studies investigating core temperature previously initiated at our department were analyzed. Patients undergoing a variety of elective surgical procedures were included. Interventions/measurements: Core temperature was measured before induction of anesthesia with an oral (314 patients), infrared tympanic (143 patients), or tympanic contact thermometer (36 patients). Available potential predictors included American Society of Anesthesiologists status, sex, age, weight, height, body mass index, adipose ratio, and lean body weight. Association with preoperative hypothermia was assessed separately for each predictor using logistic regression. Independent predictors were identified using multivariable logistic regression. Main results: A total of 493 patients were included in the study. Hypothermia was found in 105 patients (21.3%; 95% confidence interval, 17.8%-25.2%). The median core temperature was 36.3 degrees C (25th-75th percentiles, 36.0 degrees C-36.7 degrees C). Two independent factors for preoperative hypothermia were identified: male sex and age (>52 years). Conclusions: As a consequence of the high incidence of hypothermia before anesthesia, measuring core temperature should be mandatory 60 to 120 minutes before induction to identify and provide adequate treatment to hypothermic patients. (C) 2016 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.jclinane.2016.03.065"],["dc.identifier.isi","000384952700058"],["dc.identifier.pmid","27687393"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39155"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1873-4529"],["dc.relation.issn","0952-8180"],["dc.title","Unexpectedly high incidence of hypothermia before induction of anesthesia in elective surgical patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3437"],["dc.bibliographiccitation.issue","36"],["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.lastpage","3447"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Zabel, Markus"],["dc.contributor.author","Willems, Rik"],["dc.contributor.author","Lubinski, Andrzej"],["dc.contributor.author","Bauer, Axel"],["dc.contributor.author","Brugada, Josep"],["dc.contributor.author","Conen, David"],["dc.contributor.author","Flevari, Panagiota"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Zabel, Markus"],["dc.contributor.author","Lüthje, Lars"],["dc.contributor.author","Haarmann, Helge"],["dc.contributor.author","Bergau, Leonard"],["dc.contributor.author","Tichelbäcker, Tobias"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Zabel, Markus"],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Pieske, Burkert"],["dc.contributor.authorgroup","EU-CERT-ICD Study Investigators"],["dc.date.accessioned","2020-05-07T07:50:46Z"],["dc.date.accessioned","2021-10-27T13:22:10Z"],["dc.date.available","2020-05-07T07:50:46Z"],["dc.date.available","2021-10-27T13:22:10Z"],["dc.date.issued","2020"],["dc.description.abstract","Aims: The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy. Methods and results: We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537–0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class

[["dc.bibliographiccitation.artnumber","156"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Medical Research Methodology"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Friede, Tim"],["dc.date.accessioned","2019-07-09T11:49:34Z"],["dc.date.available","2019-07-09T11:49:34Z"],["dc.date.issued","2018"],["dc.description.abstract","Abstract Background Multi-centre randomized controlled clinical trials play an important role in modern evidence-based medicine. Advantages of collecting data from more than one site are numerous, including accelerated recruitment and increased generalisability of results. Mixed models can be applied to account for potential clustering in the data, in particular when many small centres contribute patients to the study. Previously proposed methods on sample size calculation for mixed models only considered balanced treatment allocations which is an unlikely outcome in practice if block randomisation with reasonable choices of block length is used. Methods We propose a sample size determination procedure for multi-centre trials comparing two treatment groups for a continuous outcome, modelling centre differences using random effects and allowing for arbitrary sample sizes. It is assumed that block randomisation with fixed block length is used at each study site for subject allocation. Simulations are used to assess operation characteristics such as power of the sample size approach. The proposed method is illustrated by an example in disease management systems. Results A sample size formula as well as a lower and upper boundary for the required overall sample size are given. We demonstrate the superiority of the new sample size formula over the conventional approach of ignoring the multi-centre structure and show the influence of parameters such as block length or centre heterogeneity. The application of the procedure on the example data shows that large blocks require larger sample sizes, if centre heterogeneity is present. Conclusion Unbalanced treatment allocation can result in substantial power loss when centre heterogeneity is present but not considered at the planning stage. When only few patients by centre will be recruited, one has to weigh the risk of imbalance between treatment groups due to large blocks and the risk of unblinding due to small blocks. The proposed approach should be considered when planning multi-centre trials."],["dc.identifier.doi","10.1186/s12874-018-0602-y"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15714"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59583"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Sample size calculation in multi-centre clinical trials"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1344"],["dc.bibliographiccitation.issue","10206"],["dc.bibliographiccitation.journal","The Lancet"],["dc.bibliographiccitation.lastpage","1351"],["dc.bibliographiccitation.volume","394"],["dc.contributor.author","Bauer, Axel"],["dc.contributor.author","Klemm, Mathias"],["dc.contributor.author","Rizas, Konstantinos D"],["dc.contributor.author","Hamm, Wolfgang"],["dc.contributor.author","von Stülpnagel, Lukas"],["dc.contributor.author","Dommasch, Michael"],["dc.contributor.author","Steger, Alexander"],["dc.contributor.author","Lubinski, Andrezej"],["dc.contributor.author","Flevari, Panagiota"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Platonov, Pyotr"],["dc.date.accessioned","2020-12-10T15:21:55Z"],["dc.date.available","2020-12-10T15:21:55Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/S0140-6736(19)31996-8"],["dc.identifier.issn","0140-6736"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73216"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Prediction of mortality benefit based on periodic repolarisation dynamics in patients undergoing prophylactic implantation of a defibrillator: a prospective, controlled, multicentre cohort study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1209"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","The Journal of Clinical Psychiatry"],["dc.bibliographiccitation.lastpage","1215"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Krasnianski, Anna"],["dc.contributor.author","Bohling, Geeske T."],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T09:52:06Z"],["dc.date.available","2018-11-07T09:52:06Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Psychiatric symptoms in sporadic Creutzfeldt-Jakob disease (sCJD) are still not sufficiently evaluated. Aim: To describe psychiatric symptoms in sCJD with respect to molecular subtype. Method: Patients in this retrospective study were classified according to established diagnostic criteria. 248 sCJD patients with known molecular subtype were recruited from January 1993 to December 2004 and investigated. Psychiatric symptoms were defined according to Mller and colleagues and the AMDP system (Study Group for Methods and Documentation in Psychiatry) and were collected by direct examination by study physicians or extracted from medical documentation. Our data were compared with published data on variant CJD (vCJD). Results: Psychiatric symptoms were common in sCJD patients (90%) and mostly found already at the disease onset (agitation in 64% of the patients, hallucinations in 45%, anxiety in 50%, depression in 37%). All psychiatric symptoms but illusions were found early in the disease course. Psychiatric symptoms in sCJD were less frequent than in vCJD. Conclusions: We provide the first detailed analysis of psychiatric symptoms in a large group of patients with sCJD with respect to differences concerning frequency and time point of occurrence of psychiatric symptoms between molecular subtypes. These data suggest that psychiatric symptoms occurring early in the disease course are common not only in vCJD but also in other CJD types."],["dc.identifier.doi","10.4088/JCP.13m08915"],["dc.identifier.isi","000365412500029"],["dc.identifier.pmid","25938948"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36044"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Physicians Postgraduate Press"],["dc.relation.issn","1555-2101"],["dc.relation.issn","0160-6689"],["dc.title","Psychiatric Symptoms in Patients With Sporadic Creutzfeldt-Jakob Disease in Germany"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","252"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Pulmonary Medicine"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Reinhardt, Christian"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Herrmann‐Lingen, Christoph"],["dc.contributor.author","Rittmeyer, Achim"],["dc.contributor.author","Andreas, Stefan"],["dc.date.accessioned","2022-07-01T07:35:22Z"],["dc.date.available","2022-07-01T07:35:22Z"],["dc.date.issued","2022"],["dc.date.updated","2022-07-25T11:18:48Z"],["dc.description.abstract","Purpose Smoking cessation in patients with diagnosed lung cancer has positive effects on cancer therapy and overall prognosis. Despite this, knowledge on smoking cessation in lung cancer patients is sparse. Methods This is an observational single centre, 12-week, prospective, single-arm trial at a tertiary lung cancer centre. Responsive patients were enrolled following confirmed lung cancer diagnosis. Smoking cessation intervention included counselling as well as pharmacotherapy. The primary endpoint was the point prevalence abstinence rate at week 12 based on biochemical verification. Secondary endpoints were the abstinence rate at week 26, quality of life and side effects. Results 80 patients were enrolled. Mean age was 62.6 ± 7.9 years. Most patients (63%) were treated with chemotherapy or radiochemotherapy. 39 patients used nicotine replacement therapy, 35 varenicline whereas six patients did not use pharmacotherapy. During the study period 13 patients died. Data were available in 72 patients after 12 weeks and 57 patients at week 24. Point prevalence abstinence rates were 37.5% (95% CI 26.4–49.7%) at week 12 and 32.8% (95% CI 21.8–45.4%) at week 26, respectively. Quality of life and side effects were not significantly affected by pharmacotherapy. Conclusion In conclusion, our results suggest that smoking cessation is feasible in patients with newly diagnosed lung cancer. The observed abstinence rate is comparable to other patient cohorts. Furthermore, pharmacotherapy in addition to cancer therapy was safe and did not show novel side effects in these seriously ill patients. Thus, smoking cessation should be an integral part of lung cancer treatment. Trial registration The study was conducted in accordance with good clinical practice standards (GCP) and approved by the local ethics committee (16/3/14), the European PAS registry (EUPAS8748) and the German BfArM (NIS-Studien-Nr. 5508). All patients provided written informed consent before study enrollment."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.citation","BMC Pulmonary Medicine. 2022 Jun 27;22(1):252"],["dc.identifier.doi","10.1186/s12890-022-02048-1"],["dc.identifier.pii","2048"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112152"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","1471-2466"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Smoking cessation"],["dc.subject","Lung cancer"],["dc.subject","Pharmacotherapy"],["dc.subject","Varenicline"],["dc.subject","Real life setting"],["dc.title","Smoking cessation by combined medication and counselling: a feasibility study in lung cancer patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1284"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Biometrical Journal"],["dc.bibliographiccitation.lastpage","1299"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Friede, Tim"],["dc.date.accessioned","2021-04-14T08:27:16Z"],["dc.date.available","2021-04-14T08:27:16Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Many late‐phase clinical trials recruit subjects at multiple study sites. This introduces a hierarchical structure into the data that can result in a power‐loss compared to a more homogeneous single‐center trial. Building on a recently proposed approach to sample size determination, we suggest a sample size recalculation procedure for multicenter trials with continuous endpoints. The procedure estimates nuisance parameters at interim from noncomparative data and recalculates the sample size required based on these estimates. In contrast to other sample size calculation methods for multicenter trials, our approach assumes a mixed effects model and does not rely on balanced data within centers. It is therefore advantageous, especially for sample size recalculation at interim. We illustrate the proposed methodology by a study evaluating a diabetes management system. Monte Carlo simulations are carried out to evaluate operation characteristics of the sample size recalculation procedure using comparative as well as noncomparative data, assessing their dependence on parameters such as between‐center heterogeneity, residual variance of observations, treatment effect size and number of centers. We compare two different estimators for between‐center heterogeneity, an unadjusted and a bias‐adjusted estimator, both based on quadratic forms. The type 1 error probability as well as statistical power are close to their nominal levels for all parameter combinations considered in our simulation study for the proposed unadjusted estimator, whereas the adjusted estimator exhibits some type 1 error rate inflation. Overall, the sample size recalculation procedure can be recommended to mitigate risks arising from misspecified nuisance parameters at the planning stage."],["dc.identifier.doi","10.1002/bimj.201900138"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82225"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1521-4036"],["dc.relation.issn","0323-3847"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Sample size recalculation in multicenter randomized controlled clinical trials based on noncomparative data"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2160"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Pain"],["dc.bibliographiccitation.lastpage","2172"],["dc.bibliographiccitation.volume","157"],["dc.contributor.author","Straube, Sebastian"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Schroeder, Heiko"],["dc.contributor.author","Arendacka, Barbora"],["dc.contributor.author","Fan, Xiangning"],["dc.contributor.author","Moore, R. Andrew"],["dc.contributor.author","Friede, Tim"],["dc.date.accessioned","2018-11-07T10:07:45Z"],["dc.date.available","2018-11-07T10:07:45Z"],["dc.date.issued","2016"],["dc.description.abstract","Back schools are interventions that comprise exercise and education components. We aimed to systematically review the randomized controlled trial evidence on back schools for the treatment of chronic low back pain. By searching MEDLINE, Embase, and Cochrane Central as well as bibliographies, we identified 31 studies for inclusion in our systematic review and 5 of these for inclusion in meta-analyses. Meta-analyses for pain scores and functional outcomes revealed statistical superiority of back schools vs no intervention for some comparisons but not others. No meta-analysis was feasible for the comparison of back schools vs other active treatments. Adverse events were poorly reported so that no reliable conclusions regarding the safety of back schools can be drawn, although some limited reassurance in this regard may be derived from the fact that few adverse events and no serious adverse events were reported in the back school groups in the studies that did report on safety. Overall, the evidence base for the use of back schools to treat chronic low back pain is weak; in nearly a half-century since back schools were first trialled, no unequivocal evidence of benefit has emerged."],["dc.description.sponsorship","Federal Ministry of Education and Research, Germany [01KG1409]"],["dc.identifier.doi","10.1097/j.pain.0000000000000640"],["dc.identifier.isi","000386015500006"],["dc.identifier.pmid","27257858"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39339"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1872-6623"],["dc.relation.issn","0304-3959"],["dc.title","Back schools for the treatment of chronic low back pain: possibility of benefit but no convincing evidence after 47 years of research-systematic review and meta-analysis"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1002286"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS Medicine"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Fischer, Anna"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Harden, Markus"],["dc.contributor.author","Koch, Martina"],["dc.contributor.author","Wuensch, Tilo"],["dc.contributor.author","Stockmann, Martin"],["dc.contributor.author","Nashan, Bjoern"],["dc.contributor.author","Kollmar, Otto"],["dc.contributor.author","Matthaei, Johannes"],["dc.contributor.author","Kanzow, Philipp"],["dc.contributor.author","Walson, Philip D."],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Oellerich, Michael"],["dc.date.accessioned","2018-11-07T10:25:24Z"],["dc.date.accessioned","2020-05-22T07:30:58Z"],["dc.date.available","2018-11-07T10:25:24Z"],["dc.date.available","2020-05-22T07:30:58Z"],["dc.date.issued","2017"],["dc.description.abstract","Background Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection. Methods and findings Traditional LFTs were performed and plasma GcfDNA was monitored in 115 adults post-LTx at three German transplant centers as part of a prospective, observational, multicenter cohort trial. GcfDNA percentage (graft cfDNA/total cfDNA) was measured using droplet digital PCR (ddPCR), based on a limited number of predefined single nucleotide polymorphisms, enabling same-day turn-around. The same method was used to quantify blood microchimerism. GcfDNA was increased >50% on day 1 post-LTx, presumably from ischemia/reperfusion damage, but rapidly declined in patients without graft injury within 7 to 10 d to a median <10%, where it remained for the 1-y observation period. Of 115 patients, 107 provided samples that met preestablished criteria. In 31 samples taken from 17 patients during biopsy-proven acute rejection episodes, the percentage of GcfDNA was elevated substantially (median 29.6%, 95% CI 23.6%-41.0%) compared with that in 282 samples from 88 patients during stable periods (median 3.3%, 95% CI 2.9%-3.7%; p < 0.001). Only slightly higher values (median 5.9%, 95% CI 4.4%-10.3%) were found in 68 samples from 17 hepatitis C virus (HCV)-positive, rejection-free patients. LFTs had low overall correlations (r = 0.28-0.62) with GcfDNA and showed greater overlap between patient subgroups, especially between acute rejection and HCV+ patients. Multivariable logistic regression modeling demonstrated that GcfDNA provided additional LFT-independent information on graft integrity. Diagnostic sensitivity and specificity were 90.3% (95% CI 74.2%-98.0%) and 92.9% (95% CI 89.3%-95.6%), respectively, for GcfDNA at a threshold value of 10%. The area under the receiver operator characteristic curve was higher for GcfDNA (97.1%, 95% CI 93.4%-100%) than for same-day conventional LFTs (AST: 95.7%; ALT: 95.2%; gamma-GT: 94.5%; bilirubin: 82.6%). An evaluation of microchimerism revealed that the maximum donor DNA in circulating white blood cells was only 0.068%. GcfDNA percentage can be influenced by major changes in host cfDNA (e.g., due to leukopenia or leukocytosis). One limitation of our study is that exact time-matched GcfDNA and LFT samples were not available for all patient visits. Conclusions In this study, determination of GcfDNA in plasma by ddPCR allowed for earlier and more sensitive discrimination of acute rejection in LTx patients as compared with conventional LFTs. Potential blood microchimerism was quantitatively low and had no significant influence on GcfDNA value. Further research, which should ideally include protocol biopsies, will be needed to establish the practical value of GcfDNA measurements in the management of LTx patients."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1371/journal.pmed.1002286"],["dc.identifier.isi","000400768500015"],["dc.identifier.pmid","28441386"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14418"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42852"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/65693"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1549-1676"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: A prospective, observational, multicenter cohort study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]