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"text": "\n175087\nCerebral Oxygenation in Neonates Immediately after Cesarean Section and Mode of Maternal Anesthesia.\n\nWillfurth, I\n\nBaik-Schneditz, N\n\nSchwaberger, B\n\nMileder, L\n\nSchober, L\n\nUrlesberger, B\n\nPichler, G\n\nBeiträge in Fachzeitschriften\nISI:000483858600005\n31096224.0\n10.1159/000499046\nNone\nCerebral regional oxygen saturation (crSO2) during immediate transition and resuscitation immediately after birth is of increasing interest.\n The aim of the present study was to assess whether the type of maternal anesthesia during cesarean section (CS; general anesthesia vs. spinal anesthesia) has an influence on cerebral oxygenation during immediate neonatal transition after birth.\n Secondary outcome parameters of prospective observational studies were analyzed. Neonates born by CS from November 2009 to September 2016 at the Medical University of Graz (Austria) were eligible. Term and preterm neonates were included, provided that: (1) crSO2 was measured by near-infrared spectroscopy, and (2) peripheral arterial oxygen saturation (SpO2) and heart rate (HR) were measured by pulse oximetry during the first 15 min after birth. Administration of supplemental oxygen was recorded and cerebral fractional tissue oxygen extraction (cFTOE) was calculated out of crSO2 and SpO2. For comparison, term and preterm neonates with maternal general anesthesia were matched to neonates with maternal spinal anesthesia during CS.\n Out of 760 eligible neonates, 64 term (38.8 ± 0.9 weeks of gestation; 32 neonates in each group) and 54 preterm neonates (32.0 ± 2.9 weeks of gestation; 27 neonates in each group) were included. In term neonates, maternal general anesthesia was associated with lower initial SpO2, HR values, and Apgar scores. The fraction of inspired oxygen (FiO2) was statistically significantly higher in the general anesthesia group. Nevertheless, crSO2 and cFTOE did not differ statistically significantly between the groups. In preterm neonates there were no statistically significant differences in SpO2, HR, crSO2, and cFTOE between the general and spinal anesthesia groups. Apgar scores at 1 min were statistically significantly lower and FiO2 was statistically significantly higher in the general anesthesia group.\n Cerebral tissue oxygenation in neonates during immediate transition after birth was similar after maternal general and spinal anesthesia during CS, despite differences in SpO2, HR, and supplemental oxygen in term neonates and differences in supplemental oxygen in preterm neonates.\n © 2019 S. Karger AG, Basel.\n\nBaik-Schneditz, Nariae\n\nMileder, Lukas Peter\n\nPichler, Gerhard\n\nSchober, Lukas\n\nSchwaberger, Bernhard Christian\n\nUrlesberger, Berndt\n\n\n"
},
{
"text": "\n176551\nThe genetic relationship between educational attainment and cognitive performance in major psychiatric disorders.\n\nComes, AL\n\nSenner, F\n\nBudde, M\n\nAdorjan, K\n\nAnderson-Schmidt, H\n\nAndlauer, TFM\n\nGade, K\n\nHake, M\n\nHeilbronner, U\n\nKalman, JL\n\nReich-Erkelenz, D\n\nKlöhn-Saghatolislam, F\n\nSchaupp, SK\n\nSchulte, EC\n\nJuckel, G\n\nDannlowski, U\n\nSchmauß, M\n\nZimmermann, J\n\nReimer, J\n\nReininghaus, E\n\nAnghelescu, IG\n\nArolt, V\n\nBaune, BT\n\nKonrad, C\n\nThiel, A\n\nFallgatter, AJ\n\nNieratschker, V\n\nFigge, C\n\nvon Hagen, M\n\nKoller, M\n\nBecker, T\n\nWigand, ME\n\nJäger, M\n\nDietrich, DE\n\nStierl, S\n\nScherk, H\n\nSpitzer, C\n\nFolkerts, H\n\nWitt, SH\n\nDegenhardt, F\n\nForstner, AJ\n\nRietschel, M\n\nNöthen, MM\n\nWiltfang, J\n\nFalkai, P\n\nSchulze, TG\n\nPapiol, S\n\nBeiträge in Fachzeitschriften\nISI:000483954400001\n31462630.0\n10.1038/s41398-019-0547-x\nPMC6713703\nCognitive deficits are a core feature of psychiatric disorders like schizophrenia and bipolar disorder. Evidence supports a genome-wide polygenic score (GPS) for educational attainment (GPSEDU) can be used to explain variability in cognitive performance. We aimed to identify different cognitive domains associated with GPSEDU in a transdiagnostic clinical cohort of chronic psychiatric patients with known cognitive deficits. Bipolar and schizophrenia patients from the PsyCourse cohort (N = 730; 43% female) were used. Likewise, we tested whether GPSs for schizophrenia (GPSSZ) and bipolar disorder (GPSBD) were associated with cognitive outcomes. GPSEDU explained 1.5% of variance in the backward verbal digit span, 1.9% in the number of correctly recalled words of the Verbal Learning and Memory Test, and 1.1% in crystallized intelligence. These effects were robust to the influences of treatment and diagnosis. No significant associations between GPSSZ or GPSBD with cognitive outcomes were found. Furthermore, these risk scores did not confound the effect of GPSEDU on cognitive outcomes. GPSEDU explains a small fraction of cognitive performance in adults with psychiatric disorders, specifically for domains related to linguistic learning and working memory. Investigating such a proxy-phenotype longitudinally, could give intriguing insight into the disease course, highlighting at what time genes play a more influential role on cognitive performance. Better understanding the origin of these deficits might help identify those patients at risk for lower levels of functioning and poor social outcomes. Polygenic estimates may in the future be part of predictive models for more personalized interventions.\n\nReininghaus, Eva\n\n\n"
},
{
"text": "\n177818\nIn vivo functional requirement of the mouse Ifitm1 gene for germ cell development, interferon mediated immune response and somitogenesis.\n\nKlymiuk, I\n\nKenner, L\n\nAdler, T\n\nBusch, DH\n\nBoersma, A\n\nIrmler, M\n\nFridrich, B\n\nGailus-Durner, V\n\nFuchs, H\n\nLeitner, N\n\nMüller, M\n\nKühn, R\n\nSchlederer, M\n\nTreise, I\n\nde Angelis, MH\n\nBeckers, J\n\nBeiträge in Fachzeitschriften\nISI:000310310200005\n23115618.0\n10.1371/journal.pone.0044609\nPMC3480353\nThe mammalian Interferon induced transmembrane protein 1 (Ifitm1) gene was originally identified as a member of a gene family highly inducible by type I and type II interferons. Based on expression analyses, it was suggested to be required for normal primordial germ cell migration. The knockdown of Ifitm1 in mouse embryos provided evidence for a role in somitogenesis. We generated the first targeted knockin allele of the Ifitm1 gene to systematically reassess all inferred functions. Sperm motility and the fertility of male and female mutant mice are as in wild type littermates. Embryonic somites and the adult vertebral column appear normal in homozygous Ifitm1 knockout mice, demonstrating that Ifitm1 is not essential for normal segmentation of the paraxial mesoderm. Proportions of leucocyte subsets, including granulocytes, monocytes, B-cells, T-cells, NK-cells, and NKT-cells, are unchanged in mutant mice. Based on a normal immune response to Listeria monocytogenes infection, there is no evidence for a dysfunction in downstream IFNγ signaling in Ifitm1 mutant mice. Expression from the Ifitm1 locus from E8.5 to E14.5 is highly dynamic. In contrast, in adult mice, Ifitm1 expression is highly restricted and strong in the bronchial epithelium. Intriguingly, IFITM1 is highly overexpressed in tumor epithelia cells of human squamous cell carcinomas and in adenocarcinomas of NSCLC patients. These analyses underline the general importance of targeted in vivo studies for the functional annotation of the mammalian genome. The first comprehensive description of the Ifitm1 expression pattern provides a rational basis for the further examination of Ifitm1 gene functions. Based on our data, the fact that IFITM1 can function as a negative regulator of cell proliferation, and because the gene maps to chromosome band 11p15.5, previously associated with NSCLC, it is likely that IFITM1 in man has a key role in tumor formation.\n\nKlymiuk, Ingeborg\n\n\n"
},
{
"text": "\n180421\nFAHN/SPG35: a narrow phenotypic spectrum across disease classifications.\n\nRattay, TW\n\nLindig, T\n\nBaets, J\n\nSmets, K\n\nDeconinck, T\n\nSöhn, AS\n\nHörtnagel, K\n\nEckstein, KN\n\nWiethoff, S\n\nReichbauer, J\n\nDöbler-Neumann, M\n\nKrägeloh-Mann, I\n\nAuer-Grumbach, M\n\nPlecko, B\n\nMünchau, A\n\nWilken, B\n\nJanauschek, M\n\nGiese, AK\n\nDe Bleecker, JL\n\nOrtibus, E\n\nDebyser, M\n\nLopez de Munain, A\n\nPujol, A\n\nBassi, MT\n\nD'Angelo, MG\n\nDe Jonghe, P\n\nZüchner, S\n\nBauer, P\n\nSchöls, L\n\nSchüle, R\n\nBeiträge in Fachzeitschriften\nISI:000481419700017\n31135052.0\n10.1093/brain/awz102\nPMC6536916\nThe endoplasmic reticulum enzyme fatty acid 2-hydroxylase (FA2H) plays a major role in the formation of 2-hydroxy glycosphingolipids, main components of myelin. FA2H deficiency in mice leads to severe central demyelination and axon loss. In humans it has been associated with phenotypes from the neurodegeneration with brain iron accumulation (fatty acid hydroxylase-associated neurodegeneration, FAHN), hereditary spastic paraplegia (HSP type SPG35) and leukodystrophy (leukodystrophy with spasticity and dystonia) spectrum. We performed an in-depth clinical and retrospective neurophysiological and imaging study in a cohort of 19 cases with biallelic FA2H mutations. FAHN/SPG35 manifests with early childhood onset predominantly lower limb spastic tetraparesis and truncal instability, dysarthria, dysphagia, cerebellar ataxia, and cognitive deficits, often accompanied by exotropia and movement disorders. The disease is rapidly progressive with loss of ambulation after a median of 7 years after disease onset and demonstrates little interindividual variability. The hair of FAHN/SPG35 patients shows a bristle-like appearance; scanning electron microscopy of patient hair shafts reveals deformities (longitudinal grooves) as well as plaque-like adhesions to the hair, likely caused by an abnormal sebum composition also described in a mouse model of FA2H deficiency. Characteristic imaging features of FAHN/SPG35 can be summarized by the 'WHAT' acronym: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum. At least three of four imaging features are present in 85% of FA2H mutation carriers. Here, we report the first systematic, large cohort study in FAHN/SPG35 and determine the phenotypic spectrum, define the disease course and identify clinical and imaging biomarkers.\n © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.\n\nPlecko, Barbara\n\n\n"
},
{
"text": "\n183822\nEffect of ABCG2, OCT1, and ABCB1 (MDR1) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial.\n\nRinaldetti, S\n\nPfirrmann, M\n\nManz, K\n\nGuilhot, J\n\nDietz, C\n\nPanagiotidis, P\n\nSpiess, B\n\nSeifarth, W\n\nFabarius, A\n\nMüller, M\n\nPagoni, M\n\nDimou, M\n\nDengler, J\n\nWaller, CF\n\nBrümmendorf, TH\n\nHerbst, R\n\nBurchert, A\n\nJanβen, C\n\nGoebeler, ME\n\nJost, PJ\n\nHanzel, S\n\nSchafhausen, P\n\nPrange-Krex, G\n\nIllmer, T\n\nJanzen, V\n\nKlausmann, M\n\nEckert, R\n\nBüschel, G\n\nKiani, A\n\nHofmann, WK\n\nMahon, FX\n\nSaussele, S\n\nBeiträge in Fachzeitschriften\nISI:000428862400008\n29510895.0\n10.1016/j.clml.2018.02.004\nNone\nTyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated.\n RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial. Plasmid standards were designed including subgenic inserts of OCT1, ABCG2, and ABCB1 together with GUSB as reference gene. For expression analyses, quantitative real-time polymerase chain reaction was used. Multiple Cox regression analysis was performed. In addition, gene expression cutoffs for patient risk stratification were investigated.\n The TFR rate of 132 patients, 12 months after TKI discontinuation, was 54% (95% confidence interval [CI], 46%-62%). ABCG2 expression (‰) was retained as the only significant variable (P = .02; hazard ratio, 1.04; 95% CI, 1.01-1.07) in multiple Cox regression analysis. Only for the ABCG2 efflux transporter, a significant cutoff was found (P = .04). Patients with an ABCG2/GUSB transcript level >4.5‰ (n = 93) showed a 12-month TFR rate of 47% (95% CI, 37%-57%), whereas patients with low ABCG2 expression (≤4.5‰; n = 39) had a 12-month TFR rate of 72% (95% CI, 55%-82%).\n In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation.\n Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.\n\nJost, Philipp\n\n\n"
},
{
"text": "\n184847\nPharmacokinetics and Pharmacodynamics of Three Different Formulations of Insulin Aspart: A Randomized, Double-Blind, Crossover Study in Men With Type 1 Diabetes.\n\nSvehlikova, E\n\nMursic, I\n\nAugustin, T\n\nMagnes, C\n\nGerring, D\n\nJezek, J\n\nSchwarzenbacher, D\n\nRatzer, M\n\nWolf, M\n\nHowell, S\n\nZakrzewski, L\n\nUrschitz, M\n\nTschapeller, B\n\nGatschelhofer, C\n\nFeichtner, F\n\nLawrence, F\n\nPieber, TR\n\nBeiträge in Fachzeitschriften\nISI:000609407100027\n33328285.0\n10.2337/dc20-1017\nPMC7818330\nTo investigate the pharmacokinetic and pharmacodynamic properties and safety of a novel formulation of insulin aspart (AT247) versus two currently marketed insulin aspart formulations (NovoRapid [IAsp] and Fiasp [faster IAsp]).\n This single-center, randomized, double-blind, three-period, crossover study was conducted in 19 men with type 1 diabetes, receiving single dosing of trial products (0.3 units/kg) in a random order on three visits. Pharmacokinetics and pharmacodynamics were assessed during a euglycemic clamp lasting up to 8 h.\n Onset of insulin appearance was earlier for AT247 compared with IAsp (-12 min [95% CI -14; -8], P = 0.0004) and faster IAsp (-2 min [-5; -2], P = 0.0003). Onset of action was accelerated compared with IAsp (-23 min [-37; -15], P = 0.0004) and faster IAsp (-9 min [-11; -3], P = 0.0006). Within the first 60 min, a higher exposure was observed for AT247 compared with IAsp by the area under the curve (AUC) glucose infusion rate (GIR) from 0 to 60 min (AUCAsp0-60min: treatment ratio vs. IAsp 2.3 [1.9; 2.9] vs. faster IAsp 1.5 [1.3; 1.8]), which was underpinned by a greater early glucose-lowering effect (AUCGIR, -60min: treatment ratio vs. IAsp 2.8 [2.0; 5.5] vs. faster IAsp 1.7 [1.3; 2.3]). Furthermore, an earlier offset of exposure was observed for AT247 compared with IAsp (-32 min [-58; -15], P = 0.0015) and faster IAsp (-27 min [-85; -15], P = 0.0017), while duration of the glucose-lowering effect, measured by time to late half-maximum effect, did not differ significantly.\n AT247 exhibited an earlier insulin appearance, exposure, and offset, with corresponding enhanced early glucose-lowering effect compared with IAsp and faster IAsp. It therefore represents a promising candidate in the pursuit for second-generation prandial insulin analogs to improve postprandial glycemic control.\n © 2020 by the American Diabetes Association.\n\nGatschelhofer, Christina\n\nMursic, Ines\n\nNinaus, Daniela\n\nPieber, Thomas\n\nSvehlikova, Eva\n\nUrschitz, Martina\n\nWolf, Michael\n\n\n"
},
{
"text": "\n185388\nGeneral versus spinal anaesthesia in proximal femoral fracture surgery - treatment outcomes.\n\nLončarić-Katušin, M\n\nMišković, P\n\nLavrnja-Skolan, V\n\nKatušin, J\n\nBakota, B\n\nŽunić, J\n\nBeiträge in Fachzeitschriften\nNone\n29122123.0\n10.1016/S0020-1383(17)30740-4\nNone\nProximal femoral fractures are a major public health problem because of the increasing proportion of elderly individuals in the general population. The mode of choice for anaesthesia in surgical treatment of these fractures is still debated in terms of better postoperative outcome. The aim of our study was to compare the effect of general over spinal anaesthesia on mortality in proximal femoral fracture surgery.\n This study was a retrospective analysis of 115 patients aged at least 70 years who underwent surgery for proximal femoral fracture. The survey was conducted from 1 January to 31 December 2015 at the General Hospital Karlovac, Croatia. Patients were divided into two groups: group 1 - general anaesthesia and group 2 - spinal anaesthesia. The primary outcome measure was the effect of mode of anaesthesia, general versus spinal, on mortality within 30 days, six months and one year after surgery.\n General anaesthesia (EndoTracheal Anaesthesia) was administered in 77 patients (67%; group I - ETA) and spinal anaesthesia in 38 patients (33%; group 2 - SPIN). Both groups had more female than male patients: 69 patients (89.6%) in the ETA group and 32 patients (84.2%) in the SPIN group were female. The mean age in the ETA group was 82.91 years and in the SPIN group was 80.18 years. ASA II status was more common in patients in the SPIN group (25 patients [65.8%]). The average time from hospitalisation to surgery was 53.44 hours in the ETA group and 53.33 hours in the SPIN group. There was no significant difference between groups in the number of comorbidities, or intraoperative and postoperative complications. There was no statistically significant difference in mortality between the groups. Mortality after surgery in the ETA and SPIN groups, respectively, was as follows: 10.4% and 10.5% at 30 days, 23.4% and 15.8% at six months, and 32.5% and 31.6% at one year.\n The results indicate that the mode of anaesthesia (general vs spinal) has no effect on postoperative mortality, and that the mode of anaesthesia should be applied on an individual basis in correlation with associated comorbidities.\n © 2017 Elsevier Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n2985\nIn human hypercholesterolemia increased reactivity of vascular smooth muscle cells is due to altered subcellular Ca(2+) distribution.\n\nFleischhacker, E\n\nEsenabhalu, VE\n\nHolzmann, S\n\nSkrabal, F\n\nKoidl, B\n\nKostner, GM\n\nGraier, WF\n\nBeiträge in Fachzeitschriften\nISI:000085997300005\n10704612.0\n10.1016%2FS0021-9150%2899%2900290-7\nNone\nThere is evidence that, besides an attenuated endothelium-dependent relaxation, functional changes in smooth muscle contractility occur in experimental hypercholesterolemic animals. Unfortunately, little is known of the situation in human arteries, and the intracellular mechanisms involved in the modulation of vascular smooth muscle function in human hypercholesterolemia are still unclear. Thus, besides acetylcholine-induced endothelium-dependent relaxation, smooth muscle reactivity to KCl, norepinephrine (NE) and phenylephrine (PE) was evaluated in uterine arteries from 34 control individuals (CI) and 22 hypercholesterolemic patients (HC). Contractions to KCl, norepinephrine and phenylephrine were enhanced by 1.3-, 2.1- and 3.5-fold in vessels from HC. Furthermore, the Ca(2+) signaling in the perinuclear cytosol, which promotes cell contraction, and that of the subplasmalemmal region, which contributes to smooth muscle relaxation, were examined in freshly isolated smooth muscle cells. In cells from HC, increases in perinuclear Ca(2+) concentration ([Ca(2+)](peri)) in response to 30 mM KCl and 300 nM NE were increased by 67 and 93%, respectively. In contrast, the increase in the subplasmalemmal Ca(2+) concentration ([Ca(2+)](sub)) to 10 microM NE was reduced in cells from HC by 33%. No further differences in perinuclear and subplasmalemmal Ca(2+) signaling were found in cultured smooth muscle cells from CI and HC (primary culture 4-6 weeks after isolation). These data indicate a significant change in the subcellular Ca(2+) distribution in smooth muscle cells from HC. In addition, production of superoxide anions (O(2)(-)) was increased 3.8-fold in uterine arteries from HC. Treatment of smooth muscle cells with the O(2)(-)-generating mixture xanthine oxidase/hypoxanthine mimicked hypercholesterolemia on smooth muscle Ca(2+) signaling. From these findings, we conclude that during hypercholesterolemia, besides a reduced endothelium-dependent relaxation, changes in smooth muscle reactivity take place. Thereby, smooth muscle contractility is increased possibly due to the observed changes in subcellular Ca(2+) signaling. The observed increased O(2)(-) production in HC might play a crucial role in the alteration of smooth muscle function in hypercholesterolemia.\n\nGraier, Wolfgang\n\nKoidl, Bernd\n\nKostner, Gerhard\n\n\n"
},
{
"text": "\n3710\nA new rating scale for age-related white matter changes applicable to MRI and CT.\n\nWahlund, LO\n\nBarkhof, F\n\nFazekas, F\n\nBronge, L\n\nAugustin, M\n\nSjögren, M\n\nWallin, A\n\nAder, H\n\nLeys, D\n\nPantoni, L\n\nPasquier, F\n\nErkinjuntti, T\n\nScheltens, P\n\nEuropean Task Force on Age-Related White Matter Changes\n\nBeiträge in Fachzeitschriften\nISI:000169184600018\n11387493.0\n10.1161/01.STR.32.6.1318\nNone\nBACKGROUND AND PURPOSE: MRI is more sensitive than CT for detection of age-related white matter changes (ARWMC). Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI, and they differ in many aspects. This makes it difficult to compare CT and MRI studies. To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient samples, it is necessary to have a rating scale constructed for both MRI and CT. We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT. METHODS: Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination (MRI or CT) performed. The patients came from 4 centers in Europe, and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale. The interrater reliability was evaluated by using kappa statistics. The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas. RESULTS: Interrater reliability was good for MRI (kappa=0.67) and moderate for CT (kappa=0.48). MRI was superior in detection of small ARWMC, whereas larger lesions were detected equally well with both CT and MRI. In the parieto-occipital and infratentorial areas, MRI detected significantly more ARWMC than did CT. In the frontal area and basal ganglia, no differences between modalities were found. When a fluid-attenuated inversion recovery sequence was used, MRI detected significantly more lesions than CT in frontal and parieto-occipital areas. No differences were found in basal ganglia and infratentorial areas. CONCLUSIONS: We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity, except for certain regions. The interrater reliability was slightly better for MRI, as was the detectability of small lesions.\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n3818\nFetal DNA in maternal plasma: emerging clinical applications.\n\nPertl, B\n\nBianchi, DW\n\nBeiträge in Fachzeitschriften\nISI:000170657900023\n11530135.0\n10.1016%2FS0029-7844%2801%2901195-4\nNone\nOBJECTIVE: To review the potential clinical diagnostic applications of fetal DNA analysis in maternal plasma or serum for noninvasive prenatal diagnosis and screening. DATA SOURCES: We conducted a MEDLINE search of articles published between January 1970 and March 2000 using the key terms "fetal DNA, "plasma, and "serum." METHODS OF STUDY SELECTION: All 369 articles describing the detection of fetal DNA in maternal plasma were reviewed. RESULTS: The diagnostic use of circulating fetal DNA in maternal plasma is currently limited to genes that are present in the fetus but not in the mother. From a clinical perspective, the most advanced application is for noninvasive detection of fetal rhesus D (Rh[D]) genotype. The results of studies performed by four different groups showed that prenatal diagnosis of fetal Rh(D) status by molecular analysis of maternal plasma or serum is routinely possible beginning in the second trimester. Noninvasive fetal genotyping should be useful for the treatment of sensitized Rh(D)-negative women whose partners are heterozygous for the Rh(D) gene because no further diagnostic or therapeutic procedures are necessary if the fetus is Rh(D) negative. Future clinical applications of fetal DNA may be in its use as a screening test for Down syndrome, preeclampsia, or preterm labor. However, these applications currently rely on the detection of Y chromosomal sequences and consequently are limited presently to male fetuses. CONCLUSION: The recent discovery of high concentrations of fetal DNA in maternal plasma represents a promising noninvasive approach to prenatal diagnosis. Compared with the analysis of the cellular fraction of maternal blood, the analysis of fetal DNA extracted from maternal plasma has the advantage of being rapid, robust, and easy to perform. The fetal DNA detected is limited to the current pregnancy. However, universal fetal gene sequences must be identified that allow analysis of genetic material from both male and female fetuses. Study of fetal DNA in maternal plasma can improve our understanding of fetomaternal biology and physiology. The long-term effects of maternal exposure to relatively high amounts of foreign DNA are unknown but represent an exciting area for future inquiry.\n\nPertl, Barbara\n\n\n"
},
{
"text": "\n3887\nAdenovirus-mediated rescue of lipoprotein lipase-deficient mice. Lipolysis of triglyceride-rich lipoproteins is essential for high density lipoprotein maturation in mice.\n\nStrauss, JG\n\nFrank, S\n\nKratky, D\n\nHämmerle, G\n\nHrzenjak, A\n\nKnipping, G\n\nvon Eckardstein, A\n\nKostner, GM\n\nZechner, R\n\nBeiträge in Fachzeitschriften\nISI:000171194500007\n11432868.0\n10.1074/jbc.M104430200\nNone\nLipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of triglycerides and the subsequent uptake of free fatty acids in extrahepatic tissues. Deficiency of LPL in humans (Type I hyperlipoproteinemia) is associated with massive chylomicronemia, low high density lipoprotein (HDL) cholesterol levels, and recurrent attacks of pancreatitis when not controlled by a strict diet. In contrast to humans, homozygous LPL knock-out mice (L0) do not survive suckling and die between 18 and 24 h after birth. In this study, an adenovirus-based protocol was utilized for the transient expression of LPL during the suckling period in an effort to rescue L0 mice. After a single intraperitoneal injection of 5x10(9) plaque-forming units of LPL-expressing virus immediately after birth, more than 90% of L0 mice survived the first days of life. 3% of L0 mice survived the entire suckling period and lived for up to 20 months, although LPL activity in mouse tissues and postheparin plasma was undetectable in all animals after 6 weeks of age. Adult LPL-deficient mice were smaller than their littermates until 2-3 months of age and exhibited very high triglyceride levels in the fed (4997 +/- 1102 versus 113.4 +/- 18.7 mg/dl) and fasted state (2007 +/- 375 versus 65.5 +/- 7.4 mg/dl). Plasma total cholesterol levels, free fatty acids, and ketone bodies were elevated in L0 mice, whereas plasma glucose was normal. Most strikingly, L0 mice lacked apoA-I-containing prebeta-HDL particles as well as mature HDL resulting in undetectable HDL cholesterol and HDL-apoA-I levels. HDL deficiency in plasma was evident despite normal apoA-I mRNA levels in the liver and normal apoA-I protein levels in plasma, which were predominantly found in the chylomicron fraction. The absence of prebeta-HDL and mature HDL particles supports the concept that the lipolysis of triglyceride-rich lipoproteins is an essential step for HDL maturation.\n\nFrank, Sasa\n\nHrzenjak, Andelko\n\nKostner, Gerhard\n\nKratky, Dagmar\n\n\n"
},
{
"text": "\n4420\nWarty dyskeratoma--follicular dyskeratoma: analysis of clinicopathologic features of a distinctive follicular adnexal neoplasm.\n\nKaddu, S\n\nDong, H\n\nMayer, G\n\nKerl, H\n\nCerroni, L\n\nBeiträge in Fachzeitschriften\nISI:000177719100014\n12196754.0\n10.1067%2Fmjd.2002.122756\nNone\nBACKGROUND: The clinicopathologic spectrum of warty dyskeratoma (WD) is not well characterized and the pathogenesis of this unusual lesion is still unclear. OBJECTIVE: We reviewed the clinical and histopathologic spectrum of WD and investigated a possible involvement of human papillomavirus (HPV) infection in onset of this lesion. METHODS: A total of 46 cases of WD were analyzed clinically and histopathologically. Polymerase chain reaction (PCR) analysis for HPV-DNA was performed in 13 lesions of WD. RESULTS: A total of 46 lesions of WD from 45 patients (M/F ratio, 1:1.8; mean age 59.8 years, median 61 years, age range 3-88 years) presented as solitary papules or small nodules on the head and neck (32 cases), trunk (9 cases), lower extremities (4 cases), and upper extremities (1 case). One patient had 2 lesions. No patient had clinical signs of Darier's or Grover's disease. Histopathologically on scanning magnification, lesions showed mainly 3 architectural patterns, namely, cup-shaped (29 cases), cystic (6 cases), and nodular (2 cases). In 9 cases, a combination of two of these morphologic patterns was observed. Characteristically, the epithelial component in all WDs displayed foci of acantholytic dyskeratosis. Variable features suggestive of follicular differentiation toward the infundibular portion of a normal hair follicle were also observed, including a focal contiguity to pilosebaceous units in most cases (63%), and the presence of small infundibular cystic structures in a subset of lesions (46%). The majority of lesions (83%) also revealed a hyalinized or fibrous stroma with intrastromal clefts. PCR analysis for HPV-DNA performed in 13 cases inclusive of all representative architectural patterns was negative. CONCLUSION: We conclude that WD shows a wider spectrum of morphologic features than previously recognized. Despite some histopathologic similarities to viral warts, WD is not a manifestation of HPV infection. On the other hand, the majority of these lesions display overall histopathologic features consistent with a follicular adnexal neoplasm. On the basis of this finding, we propose the alternative term follicular dyskeratoma to better reflect the distinctive features of this peculiar lesion.\n\nCerroni, Lorenzo\n\nKaddu, Steven\n\nKerl, Helmut\n\n\n"
},
{
"text": "\n65907\nCigarette smoking is independently associated with markers of endothelial dysfunction and hyperinsulinaemia in nondiabetic individuals with coronary artery disease.\n\nWinkelmann, BR\n\nBoehm, BO\n\nNauck, M\n\nKleist, P\n\nMärz, W\n\nVerho, NK\n\nRanjith, N\n\nKneissl, G\n\nBeiträge in Fachzeitschriften\nISI:000172019800011\n11759183.0\n10.1185/0300799039117049\nNone\nBACKGROUND: Oxidative stress and endothelial dysfunction have been introduced as a unifying pathological mechanism for early atherosclerotic disease. They are caused by a variety of stimuli including cigarette smoking (environmental) and type 2 diabetes (disease factor). However, the role of hyperinsulinemia, a marker of insulin resistance, as a risk factor for atherosclerosis remains to be clarified. STUDY OBJECTIVES: To study the relationship of smoking, hyperinsulinaemia and biochemical markers of oxidative stress and endothelial dysfunction, in patients with coronary artery disease. DESIGN: Case-control study of 5-year survivor status in smokers, former smokers and nonsmokers with angiographically documented stable coronary artery disease classified by self-reporting of smoking status together with plasma cotinine measurements. SETTING: Cardiology and cardiac surgery unit of a tertiary care referral centre. PATIENTS AND METHODS: Plasma levels of vitamins C, E and selenium, and the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were assessed in 214 patients at baseline together with the glucose and insulin response to an oral glucose challenge. Sixty known or newly diagnosed type 2 diabetic patients (28%) were identified and excluded from further analysis. RESULTS: E-selectin and ICAM-1, serving as markers of endothelial dysfunction, significantly correlated with hyperinsulinaemia (p < 0.05). Circulating immunoreactive insulin was elevated in active smokers and former smokers as compared to non-smokers after an oral glucose load (p < 0.05 for the area under the insulin time curve), despite a similar glucose response. Smoking was associated with a decrease in antioxidant vitamins C (p = 0.02) and E (p = 0.03), and an increase of E-selectin (p < 0.05) and ICAM-1 (p < 0.001). Low baseline ICAM-1 and high vitamin C levels emerged as the most significant multivariate predictors of 5-year survival (p < 0.001). CONCLUSIONS: Hyperinsulinaemia in smokers is linked with markers of endothelial dysfunction. Impaired vascular reactivity can thus be a new possible mechanism linking insulin resistance and smoking.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n132744\nHomoarginine, kidney function and cardiovascular mortality risk.\n\nTomaschitz, A\n\nMeinitzer, A\n\nPilz, S\n\nRus-Machan, J\n\nGenser, B\n\nDrechsler, C\n\nGrammer, T\n\nKrane, V\n\nRitz, E\n\nKleber, ME\n\nPieske, B\n\nKraigher-Krainer, E\n\nFahrleitner-Pammer, A\n\nWanner, C\n\nBoehm, BO\n\nMärz, W\n\nBeiträge in Fachzeitschriften\nISI:000332381900029\n24398889.0\n10.1093/ndt/gft512\nNone\nHomoarginine is a novel biomarker for cardiovascular diseases. In the present large cohort study, we evaluate how homoarginine is linked to kidney function and examine the potential interaction of homoarginine and kidney function as predictors of cardiovascular outcomes.\n Serum homoarginine (mean: 2.41 ± 1.05 µmol/L), cystatin C and creatinine-based estimated GFR (eGFR, mean: 86.2 ± 23.0 mL/min per 1.73 m(2)) were measured in 3037 patients (mean age: 62.8 ± 10.6 years; 31.5% women) who were referred to coronary angiography.\n Homoarginine was positively associated with eGFR (age- and gender-adjusted partial correlation coefficient: 0.20, P < 0.001); using multiple regression analysis, eGFR emerged as an independent predictor of serum homoarginine (β = 0.10, SE 0.01, P < 0.001). Overall cardiovascular mortality was 18.5% (563 cardiovascular deaths) after 9.9 years. Multivariate Cox proportional hazard analysis revealed that compared with participants in the highest gender-specific homoarginine tertile, those in the lowest tertile were at increased risk of cardiovascular death [multivariate-adjusted HR 1.47; 95% confidence interval (95% CI) 1.15-1.87, P = 0.002]. After adjustment for confounders, both homoarginine and eGFR were associated independently with cardiovascular mortality, with a strong synergistic interaction (P for interaction 0.005). After stratifying the cohort into persons with eGFRs <60 and ≥60 mL/min per 1.73 m(2), there was a stronger association between homoarginine and cardiovascular mortality in patients within eGFR below 60 (mean: 46.5 ± 12.0 mL/min per 1.73 m(2); HR per log SD increment of homoarginine 0.78; 95% CI 0.65-0.95, P = 0.013) compared to those with eGFR values ≥60 mL/min per 1.73 m(2). Subgroup analysis revealed that homoarginine is exclusively associated with death due to heart failure in subjects with eGFR values <60 mL/min per 1.73 m(2) (HR per log SD 0.56; 95% CI 0.37-0.85; P = 0.006).\n Low homoarginine is strongly related to decreased kidney function, adverse cardiovascular events and death due to heart failure. The relationship between low homoarginine and adverse cardiovascular outcomes is most obvious when kidney function is impaired.\n\nFahrleitner-Pammer, Astrid\n\nMärz, Winfried\n\nMeinitzer, Andreas\n\nPilz, Stefan\n\n\n"
},
{
"text": "\n135755\nAdverse reactions of artificial bone graft substitutes: lessons learned from using tricalcium phosphate geneX®.\n\nFriesenbichler, J\n\nMaurer-Ertl, W\n\nSadoghi, P\n\nPirker-Fruehauf, U\n\nBodo, K\n\nLeithner, A\n\nBeiträge in Fachzeitschriften\nISI:000330976400032\n24078171.0\n10.1007/s11999-013-3305-z\nPMC3916599\nArtificial bone graft substitutes are widely used to fill bony defects after curettage of benign tumors. We sought to evaluate the efficacy of one such bone graft substitute, geneX®, which contains tricalcium phosphate and calcium sulphate; however, during the course of this study we observed a high number of complications.\n The primary aim of this prospective series was assessment of the effectiveness of geneX® concerning resorption profile and bone healing and remodeling after surgery. We present the types and frequencies of complications observed in patients treated for bone tumors by curettage and filling the defect using geneX®.\n We planned to study 40 patients; however, after enrollment of the first 31 patients, the study was stopped as a result of serious complications. There were 20 female and 11 male patients with a mean age at surgery of 40 years (range, 6–71 years). Plain radiographs were obtained at different intervals during followup and CT scans were obtained 6 and 12 months postoperatively. Complications were assessed using a 5-point scale according to Goslings and Gouma.\n Five of the 31 patients (16%) had complications develop after surgery. In three cases, a sterile inflammation adjacent to the geneX® occurred, with delayed wound healing in two patients and local pain. In the third patient, geneX® produced moderate to severe skin damage in the area of the scar, needing revision surgery. In two other patients, inflammatory cystic formations developed in the soft tissues with sizes up to 15 cm, which gradually reduced in size with time. Overall, there were four Grade 1 complications and one Grade 2 according to Goslings and Gouma.\n We concluded from this series of patients that geneX® causes soft tissue inflammation and pain with its use. Based on this experience we believe that this type of bone substitute should not be used in the treatment of bony defects.\n Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.\n\nFriesenbichler, Jörg\n\nLeithner, Andreas\n\nMaurer-Ertl, Werner\n\nSadoghi, Patrick\n\n\n"
},
{
"text": "\n137869\nRevisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3.\n\nMandorfer, M\n\nPayer, BA\n\nSchwabl, P\n\nSteiner, S\n\nFerlitsch, A\n\nAichelburg, MC\n\nStättermayer, AF\n\nFerenci, P\n\nObermayer-Pietsch, B\n\nGrabmeier-Pfistershammer, K\n\nTrauner, M\n\nPeck-Radosavljevic, M\n\nReiberger, T\n\nBeiträge in Fachzeitschriften\nISI:000349781900021\n24905495.0\n10.1111/liv.12615\nNone\nTo perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C-coinfected (HIV/HCV) patients.\n 25(OH)D deficiency (25(OH)DDEF), IR and low CD4(+) T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml(-1) , HOMA-IR >2 and CD4nadir <200 cells × μl(-1) respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group.\n Among 86 HIV/HCV, the median FPR was 0.167 units × years(-1) . While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05-8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05-15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV-genotype 3, CD4(+) nadir and 25(OH)D levels.\n Two potentially modifiable factors, CD4(+) nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV.\n © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.\n\nObermayer-Pietsch, Barbara\n\n\n"
},
{
"text": "\n142453\nKinetics of PBPC mobilization by cyclophosphamide, as compared with that by epirubicin/paclitaxel followed by G-CSF support: implications for optimal timing of PBPC harvest.\n\nDettke, M\n\nGreinix, HT\n\nKalhs, P\n\nKührer, I\n\nWorel, N\n\nHöcker, P\n\nBeiträge in Fachzeitschriften\nISI:000168716000021\n11346706.0\n10.1046/j.1537-2995.2001.41050681.x\nNone\nLimited information is available on the mobilization kinetics of autologous PBPCs after induction with various chemotherapy regimens. With PBPC mobilization in patients with breast cancer used as a model for chemotherapy-induced PBPC recruitment, the kinetics of progenitor cells mobilized either with cyclophosphamide (CY) or epirubicin/paclitaxel (EPI-TAX) followed by the administration of G-CSF was compared.\n The study included a total of 86 patients with breast cancer (stage II-IV) receiving either CY (n = 39) or EPI-TAX (n = 47), both followed by G-CSF support. The progenitor cell content in peripheral blood and apheresis components was monitored by flow cytometric enumeration of CD34+ cells. PBPC collection was started when the threshold of >20 x 10(6) CD34+ cells per L of peripheral blood was reached.\n The PBPC collection was begun a median of 9 days after the administration of EPI-TAX followed by G-CSF support, as compared to a median of 13 days after mobilization with CY plus G-CSF. After treatment with CY, the total numbers of PBPCs peaked on Day 1 of apheresis, and they rapidly declined thereafter. In contrast, treatment with EPI-TAX followed by G-CSF administration led to a steady mobilization of CD34+ cells during leukapheresis. The difference in the mobilization patterns with CY and EPI-TAX resulted in a greater yield of CD34+ cells per L of processed blood volume. Compared to EPI-TAX, mobilization with CY required the overall processing of 30 percent less whole-blood volume to reach the target yield of > or = 10 x 10(6) CD34+ cells per kg of body weight. After a median of three apheresis procedures, however, both CY+G-CSF and EPI-TAX+G-CSF were equally effective in obtaining this target yield.\n These results imply that specific PBPC mobilization as part of a given chemotherapy regimen should be taken into consideration before the planning of a PBPC harvest.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n144366\nOutcome of right-sided diaphragmatic hernia repair: a multicentre study.\n\nDuess, JW\n\nZani-Ruttenstock, EM\n\nGarriboli, M\n\nPuri, P\n\nPierro, A\n\nHoellwarth, ME\n\nBeiträge in Fachzeitschriften\nISI:000353218200006\n25801417.0\n10.1007/s00383-015-3695-y\nNone\nRight-sided congenital diaphragmatic hernia (R-CDH) occurs in 14 to 25% of all CDH cases. The current literature comparing the outcome of R-CDH vs left CDH (L-CDH) is inconsistent, with some studies reporting higher and others lower mortality in R-CDH compared to L-CDH. The aim of our multicentre study was to analyse characteristics and outcome of R-CDH.\n We retrospectively reviewed the medical records of 178 consecutive infants with CDH who underwent surgical repair of CDH at three European tertiary pediatric surgical centres from three different countries between 2000 and 2009. The analysis focused on demographic data, morbidity and mortality in R-CDH compared with L-CDH.\n Out of a total of 178 children, 32 (18.0%) right-sided and 146 (82.0 %) left-sided cases of CDH were identified. Prenatal diagnosis was made in 8 R-CDH vs 67 L-CDH (25.0 vs 45.9%, p = 0.030). Median gestational age in R-CDH was 39 weeks (range 29-42 weeks) and 39 weeks in L-CDH (range 28-43 weeks, p = 0.943). Median birth weight in R-CDH was 3233 g (range 905-4480 g) and in L-CDH was 3060 g (range 1065-5240 g, p = 0.184). Major associated anomalies were present in 19 R-CDH vs 46 L-CDH (59.4 vs 31.5%, p = 0.003). Extracorporeal membrane oxygenation (ECMO) was required in 3 R-CDH vs 19 L-CDH (9.4 vs 13.0%, p = 0.571). A diaphragmatic patch was used in 13 R-CDH and 59 L-CDH (40.6 vs 40.4%, p = 0.982). Fundoplication for GERD was required in 1 R-CDH and 19 L-CDH (3.1 vs 13.0 %, p = 0.109). No significant differences were observed in recurrence rate (9.4 vs 8.9%, p = 0.933). Postoperative mortality rate was significantly higher in R-CDH compared to L-CDH (21.9 vs 8.2%, p = 0.023). In R-CDH, prenatal diagnosis and patch repair correlated with mortality by univariate regression (p = 0.005 and p = 0.019).\n This multicentre study shows that prenatal diagnosis and patch repair were associated with an increased mortality rate in R-CDH. However, the morbidity following repair of R-CDH was not significantly different from that in L-CDH in survivors.\n\nHöllwarth, Michael\n\n\n"
},
{
"text": "\n174385\nIncidence and long-term risk of de novo malignancies after liver transplantation with implications for prevention and detection.\n\nSchrem, H\n\nKurok, M\n\nKaltenborn, A\n\nVogel, A\n\nWalter, U\n\nZachau, L\n\nManns, MP\n\nKlempnauer, J\n\nKleine, M\n\nBeiträge in Fachzeitschriften\nISI:000330122000010\n24106037.0\n10.1002/lt.23722\nNone\nThe goal of this study was the characterization of long-term cancer risks after liver transplantation (LT) with implications for prevention and detection. Site-specific cancer incidence rates and characteristics were compared retrospectively for 2000 LT patients from a single institution (January 1, 1983 to December 31, 2010) and the general German population with standardized incidence ratios (SIRs); the total follow-up at December 31, 2011 was 14, 90 person-years. The cancer incidence rates for the LT recipients were almost twice as high as those for the age- and sex-matched general population (SIR = 1.94, 95% CI = 1.63-2.31). Significantly increased SIRs were observed for vulvar carcinoma (SIR = 23.80), posttransplant lymphoproliferative disorder/non-Hodgkin lymphoma (SIR = 10.95), renal cell carcinoma (SIR = 2.65), lung cancer (SIR = 1.85), and colorectal cancer (SIR = 1.41). The mean time between transplantation and diagnosis was 6.8 years. The mean age at the time of diagnosis was significantly lower for the cohort versus the general population with similar malignancies [50 years (both sexes) versus 69 and 68 years (males and females), P ≤ 0.006]. Tumors were diagnosed at more advanced stages, and there was a trend of higher grading, which suggested more aggressive tumor growth. Tumor treatment was performed according to accepted guidelines. Surprisingly, 5-year survival was slightly better in the study cohort versus the general population for renal cell carcinoma, lung cancer, colorectal cancer, and thyroid cancer. Long-term immunosuppression with different protocols did not lead to significantly different SIRs, although patients treated with mycophenolate mofetil had the lowest SIR for de novo cancers (1.65, 95% CI = 1.2-2.4). Alcoholic liver disease (SIR = 2.30) and primary sclerosing cholangitis (SIR = 3.40) as indications for LT were associated with an increased risk of de novo malignancies. In conclusion, risk-adapted cancer surveillance is proposed. Tumor treatment performed according to accepted guidelines appears adequate. Mycophenolate may lead to lower long-term risks for de novo cancers.\n © 2013 American Association for the Study of Liver Diseases.\n\nSchrem, Harald Heinrich\n\n\n"
},
{
"text": "\n184539\nClinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK).\n\nNemes, K\n\nBens, S\n\nKachanov, D\n\nTeleshova, M\n\nHauser, P\n\nSimon, T\n\nTippelt, S\n\nWoessmann, W\n\nBeck, O\n\nFlotho, C\n\nGrigull, L\n\nDriever, PH\n\nSchlegel, PG\n\nKhurana, C\n\nHering, K\n\nKolb, R\n\nLeipold, A\n\nAbbink, F\n\nGil-Da-Costa, MJ\n\nBenesch, M\n\nKerl, K\n\nLowis, S\n\nMarques, CH\n\nGraf, N\n\nNysom, K\n\nVokuhl, C\n\nMelchior, P\n\nKröncke, T\n\nSchneppenheim, R\n\nKordes, U\n\nGerss, J\n\nSiebert, R\n\nFurtwängler, R\n\nFrühwald, MC\n\nBeiträge in Fachzeitschriften\nISI:000600546100011\n33249395.0\n10.1016/j.ejca.2020.10.004\nNone\nExtracranial rhabdoid tumours are rare, highly aggressive malignancies primarily affecting young children. The EU-RHAB registry was initiated in 2009 to prospectively collect data of rhabdoid tumour patients treated according to the EU-RHAB therapeutic framework.\n We evaluated 100 patients recruited within EU-RHAB (2009-2018). Tumours and matching blood samples were examined for SMARCB1 mutations by sequencing and cytogenetics.\n A total of 70 patients presented with extracranial, extrarenal tumours (eMRT) and 30 with renal rhabdoid tumours (RTK). Nine patients demonstrated synchronous tumours. Distant metastases at diagnosis (M+) were present in 35% (35/100), localised disease (M0) with (LN+) and without (LN-) loco-regional lymph node involvement in 65% (65/100). SMARCB1 germline mutations (GLM) were detected in 21% (17/81 evaluable) of patients. The 5-year overall survival (OS) and event-free survival (EFS) rates were 45.8 ± 5.4% and 35.2 ± 5.1%, respectively. On univariate analyses, age at diagnosis (≥12 months), M0-stage, absence of synchronous tumours, absence of a GLM, gross total resection (GTR), radiotherapy and achieving a CR were significantly associated with favourable outcomes. In an adjusted multivariate model presence of a GLM, M+ and lack of a GTR were the strongest significant negative predictors of outcome.\n We suggest to stratify patients with localised disease (M0), GTR+ and without proof of a GLM (5-year OS 72.2 ± 9.9%) as 'standard risk'. Patients presenting with one of the features M+ and/or GTR- and/or GLM+ belong to a high risk group (5-year, OS 32.5 ± 6.2%). These patients need novel therapeutic strategies such as combinations of targeted agents with conventional chemotherapy or novel experimental approaches ideally within international phase I/II trials.\n Copyright © 2020 Elsevier Ltd. All rights reserved.\n\nBenesch, Martin\n\n\n"
}
]
}