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"text": "\n161903\nPatterns of Change in Collaboration Are Associated with Baseline Characteristics and Predict Outcome and Dropout Rates in Treatment of Multi-Problem Families. A Validation Study.\n\nBachler, E\n\nFruehmann, A\n\nBachler, H\n\nAas, B\n\nNickel, M\n\nSchiepek, GK\n\nBeiträge in Fachzeitschriften\nISI:000406396200001\n28785232.0\n10.3389/fpsyg.2017.01221\nPMC5519618\nObjective: The present study validates the Multi-Problem Family (MPF)-Collaboration Scale), which measures the progress of goal directed collaboration of patients in the treatment of families with MPF and its relation to drop-out rates and treatment outcome. Method: Naturalistic study of symptom and competence-related changes in children of ages 4-18 and their caregivers. Setting: Integrative, structural outreach family therapy. Measures: The data of five different groups of goal directed collaboration (deteriorating collaboration, stable low collaboration, stable medium collaboration, stable high collaboration, improving collaboration) were analyzed in their relation to treatment expectation, individual therapeutic goals (ITG), family adversity index, severity of problems and global assessment of a caregiver's functioning, child, and relational aspects. Results: From N = 810 families, 20% displayed stable high collaboration (n = 162) and 21% had a pattern of improving collaboration. The families with stable high or improving collaboration rates achieved significantly more progress throughout therapy in terms of treatment outcome expectancy (d = 0.96; r = 0.43), reaching ITG (d = 1.17; r = 0.50), family adversities (d = 0.55; r = 0.26), and severity of psychiatric symptoms (d = 0.31; r = 0.15). Furthermore, families with stable high or improving collaboration maintained longer treatments and had a bigger chance of finishing the therapy as planned. The odds of having a stable low or deteriorating collaboration throughout treatment were significantly higher for subjects who started treatment with low treatment expectation or high family-related adversities. Conclusion: The positive outcomes of homebased interventions for multi-problem families are closely related to "stable high" and an "improving" collaboration as measured with the MPF-Collaboration Scale. Patients who fall into these groups have a high treatment outcome expectancy and reduce psychological stress. For therapeutic interventions with multi-problem families it seems beneficial to maintain a stable high collaboration or help the collaboration, e.g., by fostering treatment expectation.\n\nNickel, Marius\n\n\n"
},
{
"text": "\n169827\nP2Y6 deficiency limits vascular inflammation and atherosclerosis in mice.\n\nStachon, P\n\nPeikert, A\n\nMichel, NA\n\nHergeth, S\n\nMarchini, T\n\nWolf, D\n\nDufner, B\n\nHoppe, N\n\nAyata, CK\n\nGrimm, M\n\nCicko, S\n\nSchulte, L\n\nReinöhl, J\n\nvon zur Muhlen, C\n\nBode, C\n\nIdzko, M\n\nZirlik, A\n\nBeiträge in Fachzeitschriften\nISI:000344056100013\n25104800.0\n10.1161/ATVBAHA.114.303585\nNone\nNucleotides such as ATP, ADP, UTP, and UDP serve as proinflammatory danger signals via purinergic receptors on their release to the extracellular space by activated or dying cells. UDP binds to the purinergic receptor Y6 (P2Y6) and propagates vascular inflammation by inducing the expression of chemokines such as monocyte chemoattractant protein 1, interleukin-8, or its mouse homologsCCL1 (chemokine [C-C motif] ligand 1)/keratinocyte chemokine, CXCL2 (chemokine [C-X-C motif] ligand 2)/macrophage inflammatory protein 2, and CXCL5 (chemokine [C-X-C motif] ligand 5)/LIX, and adhesion molecules such as vascular cell adhesion molecule 1 and intercellular cell adhesion molecule 1. Thus, P2Y6 contributes to leukocyte recruitment and inflammation in conditions such as allergic asthma or sepsis. Because atherosclerosis is a chronic inflammatory disease driven by leukocyte recruitment to the vessel wall, we hypothesized a role of P2Y6 in atherogenesis.\n Intraperitoneal stimulation of wild-type mice with UDP induced rolling and adhesion of leukocytes to the vessel wall as assessed by intravital microscopy. This effect was not present in P2Y6-deficient mice. Atherosclerotic aortas of low-density lipoprotein receptor-deficient mice consuming high-cholesterol diet for 16 weeks expressed significantly more transcripts and protein of P2Y6 than respective controls. Finally, P2Y6 (-/-)/low-density lipoprotein receptor-deficient mice consuming high-cholesterol diet for 16 weeks developed significantly smaller atherosclerotic lesions compared with P2Y6 (+/+)/low-density lipoprotein receptor-deficient mice. Bone marrow transplantation identified a crucial role of P2Y6 on vascular resident cells, most likely endothelial cells, on leukocyte recruitment and atherogenesis. Atherosclerotic lesions of P2Y6-deficient mice contained fewer macrophages and fewer lipids as determined by immunohistochemistry. Mechanistically, RNA expression of vascular cell adhesion molecule 1 and interleukin-6 was decreased in these lesions and P2Y6-deficient macrophages took up less modified low-density lipoprotein cholesterol.\n We show for the first time that P2Y6 deficiency limits atherosclerosis and plaque inflammation in mice.\n © 2014 American Heart Association, Inc.\n\nAnto Michel, Nathaly\n\nZirlik, Andreas\n\n\n"
},
{
"text": "\n181970\nPsychometric properties of the Activities Scale for Kids-performance after allogeneic hematopoietic stem cell transplantation in adolescents and children : Results of a prospective study on behalf of the German-Austrian-Swiss GVHD Consortium.\n\nLawitschka, A\n\nBrunmair, M\n\nBauer, D\n\nZubarovskaya, N\n\nFelder-Puig, R\n\nStrahm, B\n\nBader, P\n\nStrauss, G\n\nAlbert, M\n\nvon Luettichau, I\n\nGreinix, H\n\nWolff, D\n\nPeters, C\n\nBeiträge in Fachzeitschriften\nISI:000523069300001\n32246210.0\n10.1007/s00508-020-01641-w\nPMC7840624\nThe psychometric properties of an instrument, the Activity Scale for Kids-performance (ASKp), were assessed which was proposed to capture physical functioning after allogeneic hematopoietic stem cell transplantation (HSCT). Additionally, this multicenter observational prospective study investigated the influence of clinical correlates focusing on chronic graft-versus-host disease (cGVHD).\n Patient-reported ASKp, clinician-reported Karnofsky/Lansky status (KPS/PSS), patient characteristics and cGVHD details were assessed of 55 patients with a median age of 12 years at baseline after day +100 post-HSCT and every 3 months during the next 18 months. The psychometric properties were evaluated and ASKp and KPS/PSS status was compared using ANOVAS and multiple regression models.\n The German version of the ASKp showed good psychometric properties except for ceiling effects. Discrimination ability of the ASKp was good regarding the need for devices but failed to predict cGVHD patients. Both the ASKp and the KPS/PSS were associated with patients after adoptive cell therapy being in need for devices, suffering from overlap cGVHD and from steroid side effects but not with patients' age and gender. In contrast to the KPS/PSS the ASKp only showed significant differences after merging moderate and severe cGHVD patients when comparing them to No-cGVHD (F = 4.050; p = 0.049), being outperformed by the KPS/PSS (F = 20.082; p < 0.001).\n The ASKp showed no clear advantages compared to KPS/PSS even though economical and patients' effort was higher. Further application range may be limited through ceiling effects. Both should be taken into consideration. Therefore, the results may not support the usage of ASKp after HSCT and rather suggest KPS/PSS, both patient and clinician reported.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n184033\nEducation, Implementation, and Teams: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.\n\nGreif, R\n\nBhanji, F\n\nBigham, BL\n\nBray, J\n\nBreckwoldt, J\n\nCheng, A\n\nDuff, JP\n\nGilfoyle, E\n\nHsieh, MJ\n\nIwami, T\n\nLauridsen, KG\n\nLockey, AS\n\nMa, MH\n\nMonsieurs, KG\n\nOkamoto, D\n\nPellegrino, JL\n\nYeung, J\n\nFinn, JC\n\nBaldi, E\n\nBeck, S\n\nBeckers, SK\n\nBlewer, AL\n\nBoulton, A\n\nCheng-Heng, L\n\nYang, CW\n\nCoppola, A\n\nDainty, KN\n\nDamjanovic, D\n\nDjärv, T\n\nDonoghue, A\n\nGeorgiou, M\n\nGunson, I\n\nKrob, JL\n\nKuzovlev, A\n\nKo, YC\n\nLeary, M\n\nLin, Y\n\nMancini, ME\n\nMatsuyama, T\n\nNavarro, K\n\nNehme, Z\n\nOrkin, AM\n\nPellis, T\n\nPflanzl-Knizacek, L\n\nPisapia, L\n\nSaviani, M\n\nSawyer, T\n\nScapigliati, A\n\nSchnaubelt, S\n\nScholefield, B\n\nSemeraro, F\n\nShammet, S\n\nSmyth, MA\n\nWard, A\n\nZace, D\n\nBaldi, E\n\nBeck, S\n\nBeckers, SK\n\nBlewer, AL\n\nBoulton, A\n\nCheng-Heng, L\n\nYang, CW\n\nCoppola, A\n\nDainty, KN\n\nDamjanovic, D\n\nDjärv, T\n\nDonoghue, A\n\nGeorgiou, M\n\nGunson, I\n\nKrob, JL\n\nKuzovlev, A\n\nKo, YC\n\nLeary, M\n\nLin, Y\n\nMancini, ME\n\nMatsuyama, T\n\nNavarro, K\n\nNehme, Z\n\nPellis, T\n\nPflanzl-Knizacek, L\n\nPisapia, L\n\nSaviani, M\n\nSawyer, T\n\nSchnaubelt, S\n\nScholefield, B\n\nSemeraro, F\n\nShammet, S\n\nSmyth, MA\n\nWard, A\n\nZace, D\n\nEducation Implementation and Teams Collaborators\n\nBeiträge in Fachzeitschriften\nISI:000581165500007\n33098918.0\n10.1016/j.resuscitation.2020.09.014\nNone\nFor this 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, the Education, Implementation, and Teams Task Force applied the population, intervention, comparator, outcome, study design, time frame format and performed 15 systematic reviews, applying the Grading of Recommendations, Assessment, Development, and Evaluation guidance. Furthermore, 4 scoping reviews and 7 evidence updates assessed any new evidence to determine if a change in any existing treatment recommendation was required. The topics covered included training for the treatment of opioid overdose; basic life support, including automated external defibrillator training; measuring implementation and performance in communities, and cardiac arrest centers; advanced life support training, including team and leadership training and rapid response teams; measuring cardiopulmonary resuscitation performance, feedback devices, and debriefing; and the use of social media to improve cardiopulmonary resuscitation application.\n Copyright © 2020. Published by Elsevier B.V.\n\nPflanzl-Knizacek, Lucas\n\n\n"
},
{
"text": "\n186002\nEffect of short-interval rituximab and high-dose corticosteroids on kidney function in systemic sclerosis: Long-term experience of a single centre.\n\nOdler, B\n\nHebesberger, C\n\nHoeflechner, L\n\nPregartner, G\n\nGressenberger, P\n\nJud, P\n\nZenz, S\n\nEller, K\n\nRosenkranz, AR\n\nMoazedi-Fuerst, F\n\nBeiträge in Fachzeitschriften\nISI:000618893700001\n33540483.0\n10.1111/ijcp.14069\nNone\nScleroderma renal crisis (SRC) is a rare but one of the most recognised complications of systemic sclerosis (SSc). Corticosteroid (CS) use has been considered as a major risk factor for SRC. Several studies reported the efficacy of rituximab (RTX) with an acceptable safety profile in SSc. However, data on the long-term effect of high-dose CS concomitant to RTX on kidney function are lacking.\n We retrospectively analysed SSc patients (n = 35) treated with a lower dosage and short-interval RTX and concomitant high-dose CS at the Department of Internal Medicine at the Medical University of Graz between 2010 and 2019. The kidney function was assessed using the estimated glomerular filtration rate (eGFR) at every RTX admission. The annual decline of kidney function was evaluated by linear mixed model analysis.\n At the RTX initiation, one patient had a decreased kidney function indicated by eGFR < 60 mL/min/1.73 m2 (median: 96 mL/min/1.73 m2 ; interquartile range (IQR): 43-136). Patients received RTX and complementary high-dose CS for a median follow-up time of 3.4 years (range 0.6-9.5). A linear mixed model analysis with the patient as random effect and time from first RTX as fixed effect estimated an annual decline of 1.98 mL/min/1.73 m2 of the eGFR (95% confidence interval: [-2.24, -1.72]; P <.001). During the follow-up period, no patient experienced SRC or a significant drop in kidney function.\n A regular, high-dose CS given contemporary to RTX seems to be a safe option for kidney function in patients with SSc. Our findings provide additional knowledge in risk evaluation and planning of individualised therapies or designing clinical studies using RTX.\n © 2021 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.\n\nEller, Kathrin\n\nGressenberger, Paul Georg\n\nHebesberger, Carina Sarah\n\nJud, Philipp\n\nMoazedi-Fürst, Florentine\n\nOdler, Balazs\n\nPregartner, Gudrun\n\nRosenkranz, Alexander\n\nZenz, Sabine\n\n\n"
},
{
"text": "\n187084\nLongitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome.\n\nVarosanec, M\n\nUher, T\n\nHorakova, D\n\nHagemeier, J\n\nBergsland, N\n\nTyblova, M\n\nSeidl, Z\n\nVaneckova, M\n\nKrasensky, J\n\nDwyer, MG\n\nHavrdova, E\n\nZivadinov, R\n\nBeiträge in Fachzeitschriften\nNone\n26113068.0\n10.3174/ajnr.A4330\nNone\nThe relationship between lesion formation and brain atrophy development in the early phase of multiple sclerosis is unclear. We investigated the association between new lesion accumulation and brain atrophy progression in patients with clinically isolated syndrome over 48 months.\n Patients with clinically isolated syndrome (n = 210) were evaluated with 1.5T MR imaging at baseline and at 6, 12, 24, 36, and 48 months as part of a multicenter observational study of early administration of intramuscular interferon β-1a. Mixed-effect model analyses, adjusted for age, sex, and treatment status, investigated the association between accumulation of contrast-enhancing and T2 lesions and brain-volume percent changes in a 48-month period.\n In patients with clinically isolated syndrome, the average whole-brain volume decreased 2.5%, the mean lateral ventricle volume increased 16.9%, and a mean of 7.7 new/enlarging T2 lesions accumulated over the follow-up period. Patients with clinically isolated syndrome who showed greater percentages of change in whole-brain, white and gray matter, cortical, and lateral ventricle volumes over the follow-up period had more severe lesion outcomes at baseline (all P < .007). There were significant associations between decreased individual brain-volume measures at baseline and greater percentages of change during follow-up (P < .05). We found a significant association between the total cumulative number of new/enlarging T2 lesions and the evolution of whole-brain (P < .001), lateral ventricle (P = .007), gray matter and thalamic (P = .013), subcortical deep gray matter (P = .015), and cortical (P = .036) volumes over the follow-up period.\n Lesion accumulation and brain-volume changes occur simultaneously in the early phase of clinically isolated syndrome. More severe lesion and brain-volume outcomes at baseline were associated with greater development of brain atrophy over the follow-up period in patients with clinically isolated syndrome.\n © 2015 by American Journal of Neuroradiology.\n\nVarosanec, Mihael\n\n\n"
},
{
"text": "\n187253\nTranscriptomic Profiling of <i>In Vitro</i> Tumor-Stromal Cell Paracrine Crosstalk Identifies Involvement of the Integrin Signaling Pathway in the Pathogenesis of Mesenteric Fibrosis in Human Small Intestinal Neuroendocrine Neoplasms.\n\nLaskaratos, FM\n\nLevi, A\n\nSchwach, G\n\nPfragner, R\n\nHall, A\n\nXia, D\n\nvon Stempel, C\n\nBretherton, J\n\nThanapirom, K\n\nAlexander, S\n\nOgunbiyi, O\n\nWatkins, J\n\nLuong, TV\n\nToumpanakis, C\n\nMandair, D\n\nCaplin, M\n\nRombouts, K\n\nBeiträge in Fachzeitschriften\nISI:000626908900001\n33718208.0\n10.3389/fonc.2021.629665\nPMC7943728\nAnalysis of the pathophysiology of mesenteric fibrosis (MF) in small intestinal neuroendocrine tumors (SI-NETs) in an in vitro paracrine model and in human SI-NET tissue samples.\n An indirect co-culture model of SI-NET cells KRJ-I and P-STS with stromal cells HEK293 was designed to evaluate the paracrine effects on cell metabolic activity, gene expression by RT2 PCR Profilers to analyse cancer and fibrosis related genes, and RNA sequencing. The integrin signaling pathway, a specific Ingenuity enriched pathway, was further explored in a cohort of human SI-NET tissues by performing protein analysis and immunohistochemistry.\n RT Profiler array analysis demonstrated several genes to be significantly up- or down-regulated in a cell specific manner as a result of the paracrine effect. This was further confirmed by employing RNA sequencing revealing multiple signaling pathways involved in carcinogenesis and fibrogenesis that were significantly affected in these cell lines. A significant upregulation in the expression of various integrin pathway - related genes was identified in the mesenteric mass of fibrotic SI-NET as confirmed by RT-qPCR and immunohistochemistry. Protein analysis demonstrated downstream activation of the MAPK and mTOR pathways in some patients with fibrotic SI-NETs.\n This study has provided the first comprehensive analysis of the crosstalk of SI-NET cells with stromal cells. A novel pathway - the integrin pathway - was identified and further validated and confirmed in a cohort of human SI-NET tissue featured by a dual role in fibrogenesis/carcinogenesis within the neoplastic fibrotic microenvironment.\n Copyright © 2021 Laskaratos, Levi, Schwach, Pfragner, Hall, Xia, von Stempel, Bretherton, Thanapirom, Alexander, Ogunbiyi, Watkins, Luong, Toumpanakis, Mandair, Caplin and Rombouts.\n\nSchwach, Gert\n\n\n"
},
{
"text": "\n187292\nGlobal burn care and the ideal burn dressing reloaded - A survey of global experts.\n\nNischwitz, SP\n\nLuze, H\n\nPopp, D\n\nWinter, R\n\nDraschl, A\n\nSchellnegger, M\n\nKargl, L\n\nRappl, T\n\nGiretzlehner, M\n\nKamolz, LP\n\nBeiträge in Fachzeitschriften\nNone\n33838957.0\n10.1016/j.burns.2021.02.008\nNone\nBurn care is a highly relevant medical specialty in every part of the world. Different infrastructure, healthcare systems and access to medical supplies lead to different needs, treatment strategies and outcomes. A fundamental tool in a burn care provider's armamentarium is the use of different dressings. Several studies have investigated the question of the ideal burn dressing, but none could achieve a proper global perspective. With advanced dressings being on the rise, we conducted this study to get a global understanding of the actual use and idea of the ideal burn dressing.\n The objective of this study was to investigate the understanding of an 'ideal burn dressing' on a global scale.\n A questionnaire about burn care and the ideal burn dressing has been created and translated to five of the most spoken languages world-wide (English, Spanish, French, Chinese, Indonesian). It has been uploaded to an online survey platform and sent out to burn experts worldwide. The voluntary participation was possible for a period of four weeks.\n In total, 196 respondents from 49 countries participated in the study, yielding a response rate of 24.5%. The most important burn dressing characteristics in a cumulative ranking were (1) lack of adhesion (80.54%), (2) pain-free dressing change (79.87%), (3) requirement of fewer dressing changes, while in a linear ranking they were (1) anti-infective (35.14% 1st), pain-reduction (24.14% 2nd), and high absorbency (23.49% 3rd). Silver-based dressings are the most used dressings for superficial (45.21%) and deep (52.78%). 94.81% believe that the choice of burn dressing affects the outcome.\n This investigation has delivered valuable insights into the global perspective of the ideal burn dressing. Yet, the question of the ideal burn dressing is still inconclusive. Wound dressing research is of fundamental interest for patients, healthcare providers and healthcare systems.\n Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.\n\nKamolz, Lars-Peter\n\nLuze, Hanna\n\nNischwitz, Sebastian Philipp\n\nPopp, Daniel\n\nRappl, Thomas\n\nSchellnegger, Marlies\n\nWinter, Raimund\n\n\n"
},
{
"text": "\n187699\nChronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA\n\nOrtiz, A\n\nCozzolino, M\n\nDuivenvoorden, R\n\nFliser, D\n\nFouque, D\n\nFranssen, CFM\n\nGoumenos, D\n\nHemmelder, MH\n\nHilbrands, LB\n\nJager, KJ\n\nMassy, ZA\n\nNoordzij, M\n\nRosenkranz, AR\n\nRychlik, I\n\nSoler, MJ\n\nStevens, K\n\nTorra, R\n\nTuglular, S\n\nVart, P\n\nWanner, C\n\nGansevoort, RT\n\nBeiträge in Fachzeitschriften\nISI:000646227800013\n33340043.0\n10.1093/ndt/gfaa314\nNone\nDiabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89], but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR<30mL/min/1.73 m(2)) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31-1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.\n\nRosenkranz, Alexander\n\n\n"
},
{
"text": "\n36005\nHow the molecule number is correctly quantified in two-color fluorescence cross-correlation spectroscopy: corrections for cross-talk and quenching in experiments.\n\nFöldes-Papp, Z\n\nBeiträge in Fachzeitschriften\nISI:000234501700003\n16375728.0\n10.2174/138920105775159296\nNone\nFluorescence correlation spectroscopy (FCS) and two-color fluorescence cross-correlation spectroscopy (FCCS) are among the cutting-edge technologies for measuring molecule numbers at the single-molecule level in liquid phases. Yet, even after single molecule technologies caught up with theory, the techniques remained tools only for specialists able to navigate the formulas that give meaning to their observations. This original article aims at the derivations of relevant and useful quantification of molecule numbers for researchers with more diverse backgrounds who have begun probing questions previously unanswerable, except on the level of the molecule. The quantitation depends on the exact conditions of measurement. To some extent these are arbitrary, so that standard procedures are necessary in for valid comparisons of measurements among different data sets. To agree on and specify such procedures is one of the further aims here. No matter what fluorophores, which have, of course, to meet photophysical and photochemical requirements for FCS/FCCS, and optical setups/devices are used, the primary measurement signal arises from fluctuations of the mean molecule number in a confocal femtoliter or smaller probe region. Since FCS/FCCS relies on fluorescence emission measurements of rare events, one is looking for small signals on essentially zero background. Optical separation by FCCS setups is usually defined in terms of cross-talk and cross-excitation/cross-emission, respectively, which can be calculated and minimized by the experimenter from readily measurable quantities of the absorption/emission scenario for single labels and multiple labels n and m bound to or incorporated into the two-color molecules. Furthermore, this article derives relevant formulas for the quantification of molecule numbers under different experimental conditions with substantial quenching of the two-color molecules such as single labels and multiple labels n and m bound to or incorporated into the two-color molecules, high-density labeling of two-color molecules with multiple n green labels and one red label. Here, we summarize and extend the formulas to make them more generally applicable.\n\n\n"
},
{
"text": "\n70995\nCytosolic energy reserves determine the effect of glycolytic sugar phosphates on sarcoplasmic reticulum Ca2+ release in cat ventricular myocytes.\n\nZima, AV\n\nKockskämper, J\n\nBlatter, LA\n\nBeiträge in Fachzeitschriften\nISI:000242240300022\n16945967.0\n10.1113/jphysiol.2006.117242\nPMC2000679\nLocalization of glycolytic enzymes in close proximity to Ca(2+) transport systems of the sarcoplasmic reticulum (SR) in cardiac cells suggests an important functional role for glycolysis in intracellular [Ca(2+)] regulation and, consequently, excitation-contraction coupling. Here, we investigated the mechanisms of regulation of SR Ca(2+) release by glycolytic sugar phosphate intermediates in cat ventricular myocytes. Experiments with permeabilized myocytes revealed that with normal cytosolic energy reserves (mm: ATP 5, ADP 0.01, phosphocreatine (CrP) 10) fructose-1, -bisphosphate (FBP; 1 mm) and fructose-6-phosphate (F6P; 1 mm) caused a transient increase of Ca(2+) spark frequency by 62 and 42%, respectively. This effect of sugar phosphates was associated with a 13% decrease in SR Ca(2+) load. Pretreatment of the cells with an inhibitor of glycolysis, iodoacetate (IAA; 0.5 mm), did not prevent the effects of FBP and F6P on Ca(2+) sparks. Recording of single ryanodine receptor (RyR) channel activity indicated that FBP and F6P significantly increased RyR open probability. Reduction of cytosolic energy reserves decreased Ca(2+) spark activity. Increasing [ADP] to 0.4 mm or removal of CrP ([ATP] was kept constant) caused a slowly developing decrease of Ca(2+) spark frequency by 29 and 42%, respectively. Changing [ADP] and [CrP] simultaneously decreased Ca(2+) spark frequency by 66%. This inhibition of Ca(2+) sparks was associated with a 40% decrease in SR Ca(2+) load. The subsequent addition of FBP (1 mm) partially restored Ca(2+) spark frequency and SR Ca(2+) load. This recovery of Ca(2+) sparks was blocked completely by IAA. These data suggest that at physiological ATP, ADP and CrP levels accumulation of sugar phosphates from glycolysis can stimulate SR Ca(2+) release. This effect does not require the activity of downstream glycolytic enzymes, but rather is the result of direct activation of RyRs. However, under conditions associated with depletion of cellular energy reserves (e.g. myocardial ischaemia), ATP generated from glycolysis may play an important role in maintaining myocardial Ca(2+) homeostasis by improving SR Ca(2+) uptake.\n\n\n"
},
{
"text": "\n130248\nIncidence and clinical course of radionecrosis in children with brain tumors. A 20-year longitudinal observational study.\n\nStrenger, V\n\nLackner, H\n\nMayer, R\n\nSminia, P\n\nSovinz, P\n\nMokry, M\n\nPilhatsch, A\n\nBenesch, M\n\nSchwinger, W\n\nSeidel, M\n\nSperl, D\n\nSchmidt, S\n\nUrban, C\n\nBeiträge in Fachzeitschriften\nISI:000323507900005\n23963155.0\n10.1007/s00066-013-0408-0\nNone\nRadionecrosis (RN) in children treated for brain tumors represents a potentially severe long-term complication. Its diagnosis is challenging, since magnetic resonance imaging (MRI) cannot clearly discriminate between RN and tumor recurrence. A retrospective single-center study was undertaken to describe the incidence and clinical course of RN in a cohort of 107 children treated with external radiotherapy (RT) for various brain tumors between 1992 and 2012. During a median follow-up of 4.6 years (range 0.29-20.1 years), RN was implied by suspicious MRI findings in in 5 children (4.7 %), 5-131 months after RT. Suspicion was confirmed histologically (1 patient) or substantiated by FDG positron-emission tomography (FDG-PET, 2 patients) or by FDG-PET and MR spectroscopy (1 patient). Before developing RN, all 5 patients had received cytotoxic chemotherapy in addition to RT. In addition to standard treatment protocols, 2 patients had received further chemotherapy for progression or relapse. Median radiation dose expressed as the biologically equivalent total dose applied in 2 Gy fractions (EQD2) was 51.7 Gy (range 51.0-60.0 Gy). At RN onset, 4 children presented with neurological symptoms. Treatment of RN included resection (n = 1), corticosteroids (n = 2) and a combination of corticosteroids, hyperbaric oxygen (HBO) and bevacizumab (n = 1). One patient with asymptomatic RN was not treated. Complete radiological regression of the lesions was observed in all patients. Clinical symptoms normalized in 3 patients, whereas 2 developed permanent severe neurological deficits. RN represents a severe long-term treatment complication in children with brain tumors. The spectrum of clinical presentation is wide; ranging from asymptomatic lesions to progressive neurological deterioration. FDG-PET and MR spectroscopy may be useful for distinguishing between RN and tumor recurrence. Treatment options in patients with symptomatic RN include conservative management (steroids, HBO, bevacizumab) and surgical resection.\n\nBenesch, Martin\n\nLackner, Herwig\n\nMokry, Michael\n\nRitter-Sovinz, Petra\n\nSchwinger, Wolfgang\n\nSeidel, Markus\n\nSperl, Daniela Ingrid\n\nStrenger, Volker\n\nUrban, Ernst-Christian\n\n\n"
},
{
"text": "\n139845\nPolygenic overlap between kidney function and large artery atherosclerotic stroke.\n\nHolliday, EG\n\nTraylor, M\n\nMalik, R\n\nBevan, S\n\nMaguire, J\n\nKoblar, SA\n\nSturm, J\n\nHankey, GJ\n\nOldmeadow, C\n\nMcEvoy, M\n\nSudlow, C\n\nRothwell, PM\n\nCoresh, J\n\nHamet, P\n\nTremblay, J\n\nTurner, ST\n\nde Andrade, M\n\nRao, M\n\nSchmidt, R\n\nCrick, PA\n\nRobino, A\n\nPeralta, CA\n\nJukema, JW\n\nMitchell, P\n\nRosas, SE\n\nWang, JJ\n\nScott, RJ\n\nDichgans, M\n\nMitchell, BD\n\nKao, WH\n\nFox, CS\n\nLevi, C\n\nAttia, J\n\nMarkus, HS\n\nCKDGen Consortium and the International Stroke Genetics Consortium\n\nBeiträge in Fachzeitschriften\nISI:000345516600237\n25352485.0\n10.1161/STROKEAHA.114.006609\nPMC4245455\nEpidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes.\n Polygenic models were derived using genome-wide association studies meta-analysis results for 3 kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: n=73 998), eGFR using cystatin C (eGFRcys: n=22 937), and urinary albumin to creatinine ratio (n=31 580). For each, single nucleotide polymorphisms passing 10 P value thresholds were used to form profile scores in 4561 IS cases and 7094 controls from the United Kingdom, Germany, and Australia. Scores were tested for association with IS and its 3 aetiological subtypes: large artery atherosclerosis, cardioembolism, and small vessel disease.\n Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of large artery atherosclerosis, with 5 scores reaching P<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher urinary albumin to creatinine ratio, of which 3 associated with large artery atherosclerosis (peak P=0.01) and all showed the expected directional association. One urinary albumin to creatinine ratio-based score also associated with small vessel disease (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02).\n This study suggests possible polygenic correlation between renal dysfunction and IS. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders seems merited.\n © 2014 American Heart Association, Inc.\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n140317\nWeight cycling in bipolar disorder.\n\nReininghaus, EZ\n\nLackner, N\n\nFellendorf, FT\n\nBengesser, S\n\nBirner, A\n\nReininghaus, B\n\nUnterweger, R\n\nPlatzer, M\n\nWallner-Liebmann, SJ\n\nZelzer, S\n\nMangge, H\n\nFuchs, D\n\nKapfhammer, HP\n\nMcIntyre, RS\n\nBeiträge in Fachzeitschriften\nISI:000344753000005\n25443762.0\n10.1016/j.jad.2014.09.006\nNone\nAn association between excess weight and/or weight fluctuations and cardiovascular morbidity and mortality is amply documented. Individuals with bipolar disorder (BD) are differentially affected by overweight/obesity, chaotic eating patterns (e.g., binge eating), as well as cardiovascular morbidity and mortality. Weight cycling (WCYC) is defined as a pattern of repetitive weight loss and gain.\n We sought to determine the relationship between course of illness and BD and WCYC retrospectively as well whether these co-occurring phenotypes identify a biologically distinct subpopulation on the basis of having a unique inflammatory biomarker/biosignature profile. Sociodemographic, clinical, and inflammatory markers were gathered from a well-characterized cohort of actual euthymic adults with BD (n=101) and a healthy control group (n=48).\n Individuals with BD with a history of WCYC were provided evidence of a greater frequency of prior episodes (i.e., both manic and depressed), as well as of significantly higher levels of circulating IL-6 concentrations when compared to non-WCYC individuals with BD. The association persisted after adjusting for relevant covariates (e.g., BMI, age, number of prior episodes).\n Include the small control group, differing medication status and that all data relies on personal information. Nevertheless we tried to verify all data as far as clinical disclosure was available.\n The results of this study indicate that adults with BD excessive in weight are not only more susceptible to a relapse-prone course of illness, but also are more likely to present with WCYC. The finding of elevated pro-inflammatory cytokines in this subpopulation may identify a separate subpopulation with greater susceptibility to cardiovascular disease. The overarching aim of personalized treatment and preventive strategies in BD begins with appropriate, empirically supported patient stratification. Our results provide preliminary support for stratifying BD cardiovascular risk on the basis of anthropometrics and WCYC.\n Copyright © 2014 Elsevier B.V. All rights reserved.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nFellendorf, Frederike\n\nHolasek, Sandra Johanna\n\nKapfhammer, Hans-Peter\n\nMangge, Harald\n\nPlatzer, Martina\n\nReininghaus, Eva\n\nUnterweger, Renate\n\nZelzer, Sieglinde\n\n\n"
},
{
"text": "\n148081\nHuman papillomavirus prevalence and type-distribution in cervical glandular neoplasias: Results from a European multinational epidemiological study.\n\nHoll, K\n\nNowakowski, AM\n\nPowell, N\n\nMcCluggage, WG\n\nPirog, EC\n\nCollas De Souza, S\n\nTjalma, WA\n\nRosenlund, M\n\nFiander, A\n\nCastro Sánchez, M\n\nDamaskou, V\n\nJoura, EA\n\nKirschner, B\n\nKoiss, R\n\nO'Leary, J\n\nQuint, W\n\nReich, O\n\nTorné, A\n\nWells, M\n\nRob, L\n\nKolomiets, L\n\nMolijn, A\n\nSavicheva, A\n\nShipitsyna, E\n\nRosillon, D\n\nJenkins, D\n\nBeiträge in Fachzeitschriften\nISI:000362843300012\n26096203.0\n10.1002/ijc.29651\nPMC5034816\nCervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type-distribution in CGN vary, providing uncertain evidence to support prophylactic vaccination and HPV screening. This study [108288/108290] assessed HPV prevalence and type-distribution in women diagnosed with cervical adenocarcinoma in situ (AIS, N = 49), adenosquamous carcinoma (ASC, N = 104), and various adenocarcinoma subtypes (ADC, N = 461) from 17 European countries, using centralised pathology review and sensitive HPV testing. The highest HPV-positivity rates were observed in AIS (93.9%), ASC (85.6%), and usual-type ADC (90.4%), with much lower rates in rarer ADC subtypes (clear-cell: 27.6%; serous: 30.4%; endometrioid: 12.9%; gastric-type: 0%). The most common HPV types were restricted to HPV16/18/45, accounting for 98.3% of all HPV-positive ADC. There were variations in HPV prevalence and ADC type-distribution by country. Age at diagnosis differed by ADC subtype, with usual-type diagnosed in younger women (median: 43 years) compared to rarer subtypes (medians between 57 and 66 years). Moreover, HPV-positive ADC cases were younger than HPV-negative ADC. The six years difference in median age for women with AIS compared to those with usual-type ADC suggests that cytological screening for AIS may be suboptimal. Since the great majority of CGN are HPV16/18/45-positive, the incorporation of prophylactic vaccination and HPV testing in cervical cancer screening are important prevention strategies. Our results suggest that special attention should be given to certain rarer ADC subtypes as most appear to be unrelated to HPV. \n © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.\n\nReich, Olaf\n\n\n"
},
{
"text": "\n160074\nHIV-1 Drug Resistance and Second-Line Treatment in Children Randomized to Switch at Low Versus Higher RNA Thresholds.\n\nHarrison, L\n\nMelvin, A\n\nFiscus, S\n\nSaidi, Y\n\nNastouli, E\n\nHarper, L\n\nCompagnucci, A\n\nBabiker, A\n\nMcKinney, R\n\nGibb, D\n\nTudor-Williams, G\n\nPENPACT-1 (PENTA 9PACTG 390) Study Team\n\nBeiträge in Fachzeitschriften\nISI:000360347900006\n26322666.0\n10.1097/QAI.0000000000000671\nPMC4556171\nThe PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold.\n PENPACT-1 had a 2 × 2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, and switch at a 1000 copies/mL versus 30, 00 copies/mL threshold. Switch criteria were not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or Center for Disease Control and Prevention stage C event. Resistance tests were performed on samples ≥1000 copies/mL before switch, resuppression, and at 4-years/trial end.\n Sixty-seven children started PI-based ART and were randomized to switch at 1000 copies/mL (PI-1000), 64 PIs and 30, 00 copies/mL (PI-30, 00), 67 NNRTIs and 1000 copies/mL (NNRTI-1000), and 65 NNRTI and 30, 00 copies/mL (NNRTI-30, 00). Ninety-four (36%) children reached the 1000 copies/mL switch criteria during 5-year follow-up. In 30, 00 copies/mL threshold arms, median time from 1000 to 30, 00 copies/mL switch criteria was 58 (PI) versus 80 (NNRTI) weeks (P = 0.81). In NNRTI-30, 00, more nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000 copies/mL (23% NNRTI-1000, 27% NNRTI-30, 00). Sixty-two children started abacavir + lamivudine, 166 lamivudine + zidovudine or stavudine, and 35 other NRTIs. The abacavir + lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30, 00, 64% NNRTI-1000, and 100% NNRTI-30, 00 were <400 copies/mL 24 weeks later.\n Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line. An abacavir + lamivudine NRTI combination seemed protective against development of NRTI resistance.\n\n\n"
},
{
"text": "\n161557\nGenome-scale analysis of the genes that contribute to Burkholderia pseudomallei biofilm formation identifies a crucial exopolysaccharide biosynthesis gene cluster.\n\nBorlee, GI\n\nPlumley, BA\n\nMartin, KH\n\nSomprasong, N\n\nMangalea, MR\n\nIslam, MN\n\nBurtnick, MN\n\nBrett, PJ\n\nSteinmetz, I\n\nAuCoin, DP\n\nBelisle, JT\n\nCrick, DC\n\nSchweizer, HP\n\nBorlee, BR\n\nBeiträge in Fachzeitschriften\nISI:000405080700062\n28658258.0\n10.1371/journal.pntd.0005689\nPMC5507470\nBurkholderia pseudomallei, the causative agent of melioidosis, is an important public health threat due to limited therapeutic options for treatment. Efforts to improve therapeutics for B. pseudomallei infections are dependent on the need to understand the role of B. pseudomallei biofilm formation and its contribution to antibiotic tolerance and persistence as these are bacterial traits that prevent effective therapy. In order to reveal the genes that regulate and/or contribute to B. pseudomallei 1026b biofilm formation, we screened a sequence defined two-allele transposon library and identified 118 transposon insertion mutants that were deficient in biofilm formation. These mutants include transposon insertions in genes predicted to encode flagella, fimbriae, transcriptional regulators, polysaccharides, and hypothetical proteins. Polysaccharides are key constituents of biofilms and B. pseudomallei has the capacity to produce a diversity of polysaccharides, thus there is a critical need to link these biosynthetic genes with the polysaccharides they produce to better understand their biological role during infection. An allelic exchange deletion mutant of the entire B. pseudomallei biofilm-associated exopolysaccharide biosynthetic cluster was decreased in biofilm formation and produced a smooth colony morphology suggestive of the loss of exopolysaccharide production. Conversely, deletion of the previously defined capsule I polysaccharide biosynthesis gene cluster increased biofilm formation. Bioinformatics analyses combined with immunoblot analysis and glycosyl composition studies of the partially purified exopolysaccharide indicate that the biofilm-associated exopolysaccharide is neither cepacian nor the previously described acidic exopolysaccharide. The biofilm-associated exopolysaccharide described here is also specific to the B. pseudomallei complex of bacteria. Since this novel exopolysaccharide biosynthesis cluster is retained in B. mallei, it is predicted to have a role in colonization and infection of the host. These findings will facilitate further advances in understanding the pathogenesis of B. pseudomallei and improve diagnostics and therapeutic treatment strategies.\n\nSteinmetz, Ivo\n\n\n"
},
{
"text": "\n164124\nDo time of birth, unit volume, and staff seniority affect neonatal outcome in deliveries at ≥34<sup>+0</sup> weeks of gestation?\n\nReif, P\n\nPichler, G\n\nGriesbacher, A\n\nLehner, G\n\nSchöll, W\n\nLang, U\n\nHofmann, H\n\nUlrich, D\n\nBeiträge in Fachzeitschriften\nISI:000433566700021\n29210161.0\n10.1111/1471-0528.15000\nNone\nWe investigated whether time of birth, unit volume, and staff seniority affect neonatal outcome in neonates born at ≥34+0 weeks of gestation.\n Population-based prospective cohort study.\n Ten public hospitals in the Austrian province of Styria.\n A total of 87 065 neonates delivered in the period 2004-2015.\n Based on short-term outcome data, generalised linear mixed models were used to calculate the risk for adverse and severely adverse neonatal outcomes according to time of birth, unit volume, and staff seniority.\n Neonatal composite adverse and severely adverse outcome measures.\n The odds ratio for severely adverse events during the night-time (22:01-07:29 hours) compared with the daytime (07:30-15:00 hours) was 1.35 (95% confidence interval, 95% CI 1.13-1.61). There were no significant differences in neonatal outcome comparing weekdays and weekends, and comparing office hours and shifts. Units with 500-1000 deliveries per year had the lowest risk for adverse events. Adverse and severely adverse neonatal outcomes were least common for midwife-guided deliveries, and became more frequent with the level of experience of the doctors attending the delivery. With increasing pregnancy risks, senior staff attending delivery and delivering in a tertiary centre reduce the odds ratio for adverse events.\n Different times of delivery were associated with increased adverse neonatal outcomes. The management of uncomplicated deliveries by less experienced staff showed no negative impact on perinatal outcome. In contrast, riskier pregnancies delivered by senior staff in a tertiary centre favour a better outcome. Achieving a better balance in the total number of labour ward staff during the day and the night appears to be a greater priority than increasing the continuous presence of senior obstetrical staff on the labour ward during the out-of-hours period.\n Deliveries during night time lead to a greater number of neonates experiencing severely adverse events.\n © 2017 Royal College of Obstetricians and Gynaecologists.\n\nGold ehem Ulrich, Daniela\n\nPichler, Gerhard\n\nReif, Philipp\n\nSchöll, Wolfgang\n\n\n"
},
{
"text": "\n164793\nNo erythropoietin-induced growth is observed in non-small cell lung cancer cells.\n\nFrille, A\n\nLeithner, K\n\nOlschewski, A\n\nOlschewski, H\n\nWohlkönig, C\n\nHrzenjak, A\n\nBeiträge in Fachzeitschriften\nISI:000423173400017\n29345289.0\n10.3892/ijo.2017.4225\nNone\nLung cancer patients have the highest incidence of anemia among patients with solid tumors. The use of recombinant human erythropoietin (Epo) has consistently been shown to reduce the need for blood transfusions and to increase hemoglobin levels in lung cancer patients with chemotherapy-induced anemia. However, clinical and preclinical studies have prompted concerns that Epo and the presence of its receptor, EpoR, in tumor cells may be responsible for adverse effects and, eventually, death. The question has been raised whether Epo promotes tumor growth and inhibits the death of cancer cells. In this study, we investigated the presence and functionality of EpoR, as well as the implications of Epo upon the proliferation and survival of lung cancer cells. Since the protein expression of both Epo and EpoR is induced by hypoxia, which is frequently present in lung cancer, the cells were treated with Epo under both normoxic and hypoxic conditions (1% O2). By using quantitative (real-time) PCR, western blot analysis, and immunocytochemical staining, three non-small cell lung cancer (NSCLC) cell lines (A427, A549 and NCI-H358) were analyzed for the expression of EpoR and its specific downstream signaling pathways [Janus kinase 2 (Jak2)-signal transducer and activator of transcription 5 (STAT5), phosphatidylinositol-3-kinase (PI3K)-Akt, mitogen-activated protein (MAP) kinase]. The effects of 100 U/ml Epo on cell proliferation and cisplatin-induced apoptosis were assessed. All NSCLC cell lines expressed EpoR mRNA and protein, while these levels differed considerably between the cell lines. We found the constitutive phosphorylation of EpoR and most of its downstream signaling pathways (STAT5, Akt and ERK1/2) independently of Epo administration. While Epo markedly enhanced the proliferation and reduced apoptosis of Epo-dependent UT-7/Epo leukemia cells, it did not affect tumor cell proliferation or the cisplatin-induced apoptosis of NSCLC cells. Thus, this in vitro study suggests that there are no tumor-promoting effects of Epo in the NSCLC cell lines studied, neither under normoxic nor under hypoxic conditions.\n\nHrzenjak, Andelko\n\nLeithner, Katharina\n\nOlschewski, Andrea\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n168552\nDiagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference.\n\nMunteanu, M\n\nTiniakos, D\n\nAnstee, Q\n\nCharlotte, F\n\nMarchesini, G\n\nBugianesi, E\n\nTrauner, M\n\nRomero Gomez, M\n\nOliveira, C\n\nDay, C\n\nDufour, JF\n\nBellentani, S\n\nNgo, Y\n\nTraussnig, S\n\nPerazzo, H\n\nDeckmyn, O\n\nBedossa, P\n\nRatziu, V\n\nPoynard, T\n\nFLIP Consortium and the FibroFrance Group\n\nBeiträge in Fachzeitschriften\nISI:000387151700010\n27549244.0\n10.1111/apt.13770\nPMC5113673\nBlood tests of liver injury are less well validated in non-alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis.\n To improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading.\n We pre-included new NAFLD patients with biopsy and blood tests from a single-centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary-ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing.\n A total of 600 patients with reliable tests and biopsies were included. The mean NonBinAUROCs (95% CI) of tests were all significant (P < 0.0001): 0.878 (0.864-0.892) for FibroTest and fibrosis stages, 0.846 (0.830-0.862) for ActiTest and activity grades, and 0.822 (0.804-0.840) for SteatoTest and steatosis grades. FibroTest had a higher NonBinAUROC than BARD (0.836; 0.820-0.852; P = 0.0001), FIB4 (0.845; 0.829-0.861; P = 0.007) but not significantly different than the NAFLD score (0.866; 0.850-0.882; P = 0.26). FibroTest had a significant difference in median values between adjacent stage F2 and stage F1 contrarily to BARD, FIB4 and NAFLD scores (Bonferroni test P < 0.05).\n In patients with NAFLD, SteatoTest, ActiTest and FibroTest are non-invasive tests that offer an alternative to biopsy, and they correlate with the simple grading/staging of the SAF scoring system across the three elementary features of NAFLD: steatosis, inflammatory activity and fibrosis.\n © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.\n\nLackner, Karoline\n\n\n"
}
]
}