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"text": "\n66440\nGene therapy progress and prospects: stem cell plasticity.\n\nKashofer, K\n\nBonnet, D\n\nBeiträge in Fachzeitschriften\nISI:000231019700001\n15973440.0\n10.1038/sj.gt.3302571\nNone\nWith the identification of stem cell plasticity several years ago, multiple reports raised hopes that tissue repair by stem cell transplantation could be within reach in the near future. Krause et al reported that a single purified hematopoietic stem cell not only repopulated the bone marrow of a host animal, but also integrated into unrelated tissues. Lagasse et al demonstrated that in a genetic model of liver disease, purified hematopoietic stem cells can give rise to hepatocytes and rescue fatal liver damage. More recent work by Jiang et al demonstrated that cultured cells can retain their stem cell potential. There are a number of possible mechanisms that could explain these phenomena, and recent experiments have raised controversy about which mechanism is prevalent. One possibility is transdifferentiation of a committed cell directly into another cell type as a response to environmental cues. Transdifferentiation has been shown mainly in vitro, but some in vivo data also support this mechanism. Direct transdifferentiation would clinically be limited by the number of cells that can be introduced into an organ without removal of resident cells. If bone marrow cells could on the other hand give rise to stem cells of another tissue, then they could in theory repopulate whole organs from a few starting cells. This model of dedifferentiation is consistent with recent data from animal models. Genetic analysis of cells of donor origin in vivo and in vitro has brought to light another possible mechanism. The fusion of host and donor cells can give rise to mature tissue cells without trans- or dedifferentiation. The resulting heterokaryons are able to cure a lethal genetic defect and do not seem to be prone to give rise to cancer. All these models will clinically face the problem of accessibility of healthy primary cells for transplantation. This underlines the importance of the recent identification of a population of mesenchymal stem cells (MSCs) with stem cell properties similar to embryonic stem (ES) cells. These cells can be cultured and expanded in vitro without losing their stem cell potential making them an attractive target for cell therapy. Finally, it is still not clear if stem cells for various tissues are present in peripheral blood, or bone marrow and thus can be directly purified from these sources. Identification of putative tissue stem cells would be necessary before purification strategies can be devised. In this review, we discuss the evidence for these models, and the conflicting results obtained to date.\n\nKashofer, Karl\n\n\n"
},
{
"text": "\n103275\nIsolated GH deficiency (IGHD) type II: imaging of the pituitary gland by magnetic resonance reveals characteristic differences in comparison with severe IGHD of unknown origin.\n\nBinder, G\n\nNagel, BH\n\nRanke, MB\n\nMullis, PE\n\nBeiträge in Fachzeitschriften\nISI:000179848900006\n12457450.0\n10.1530/eje.0.1470755\nNone\nOBJECTIVE: To determine the specific morphology of the pituitary gland in children with severe isolated GH deficiency due to GH-1 gene mutations (IGHD type II). DESIGN: The pituitary gland morphology in magnetic resonance imaging (MRI) of children with IGHD type II was analyzed and compared with the findings in a group of children with comparably severe IGHD of unknown origin. In addition, the birth histories of both groups were studied. SUBJECTS: Thirteen children with IGHD type II were diagnosed in seven European children's hospitals and they carried a corresponding GH-1 gene mutation. For comparison, we selected from a group of 66 MRI-studied GH-insufficient subjects diagnosed in our clinic, all children with severe IGHD (all GH peaks <4 microg/l) who had no GH-1 gene mutation, no first-grade relative with IGHD and no septo-optic dysplasia. METHODS: Sagittal and coronal images of the brain were analyzed for the presence of any malformation of the pituitary gland and the intracranium. The height of each adenohypophysis was measured in a strict midline sagittal image for quantification of the gland's size. In addition, patients' files were reviewed for birth trauma or breech delivery. RESULTS: Normal MRI morphology of the pituitary gland was observed in all patients of the familial IGHD type II group (P<0.003) in which, however, five of thirteen patients (38%) exhibited a mild hypoplasia of their gland (mean sagittal adenohypophysial height -1.0+/-0.03 SD score (SDS)). In contrast, the pituitary gland in the idiopathic group showed a definitive malformation with hypoplasia of pituitary stalk and adenohypophysis in all cases, while ectopia of the neurohypophysis was present in nine of the ten cases. The adenohypophysis was significantly smaller in the idiopathic group (mean sagittal adenohypophysial height -3.2+/-0.3 SDS) (P<0.0001). All thirteen birth histories in the familial group (IGHD type II) were unremarkable while, in the idiopathic group, three of eight available birth histories recorded a breech delivery or traumatic birth (37.5%) (P<0.05). CONCLUSIONS: This study shows for the first time that MRI pituitary morphology may correlate with the etiology of severe IGHD: normal morphology suggests the presence of GH-1 gene mutations, while severe hypoplasia with malformation have other causes which might include so far unknown genetic defects as well as traumatic insults.\n\n\n"
},
{
"text": "\n157363\nComparative proteomics of paired vocal fold and oral mucosa fibroblasts.\n\nKarbiener, M\n\nDarnhofer, B\n\nFrisch, MT\n\nRinner, B\n\nBirner-Gruenberger, R\n\nGugatschka, M\n\nBeiträge in Fachzeitschriften\nISI:000395953200002\n28099887.0\n10.1016/j.jprot.2017.01.010\nPMC5389448\nInjuries of the vocal folds frequently heal with scar formation, which can have lifelong detrimental impact on voice quality. Current treatments to prevent or resolve scars of the vocal fold mucosa are highly unsatisfactory. In contrast, the adjacent oral mucosa is mostly resistant to scarring. These differences in healing tendency might relate to distinct properties of the fibroblasts populating oral and vocal fold mucosae. We thus established the in vitro cultivation of paired, near-primary vocal fold fibroblasts (VFF) and oral mucosa fibroblasts (OMF) to perform a basic cellular characterization and comparative cellular proteomics. VFF were significantly larger than OMF, proliferated more slowly, and exhibited a sustained TGF-β1-induced elevation of pro-fibrotic interleukin 6. Cluster analysis of the proteomic data revealed distinct protein repertoires specific for VFF and OMF. Further, VFF displayed a broader protein spectrum, particularly a more sophisticated array of factors constituting and modifying the extracellular matrix. Conversely, subsets of OMF-enriched proteins were linked to cellular proliferation, nuclear events, and protection against oxidative stress. Altogether, this study supports the notion that fibroblasts sensitively adapt to the functional peculiarities of their respective anatomical location and presents several molecular targets for further investigation in the context of vocal fold wound healing.\n Mammalian vocal folds are a unique but delicate tissue. A considerable fraction of people is affected by voice problems, yet many of the underlying vocal fold pathologies are sparsely understood at the molecular level. One such pathology is vocal fold scarring - the tendency of vocal fold injuries to heal with scar formation -, which represents a clinical problem with highly suboptimal treatment modalities. This study employed proteomics to obtain comprehensive insight into the protein repertoire of vocal fold fibroblasts, which are the cells that predominantly synthesize the extracellular matrix in both physiological and pathophysiological conditions. Protein profiles were compared to paired fibroblasts from the oral mucosa, a neighboring tissue that is remarkably resistant to scarring. Bioinformatic analyses of the data revealed a number of pathways as well as single proteins (e.g. ECM-remodeling factors, transcription factors, enzymes) that were significantly different between the two fibroblast types. Thereby, this study has revealed novel interesting molecular targets which can be analyzed in the future for their impact on vocal fold wound healing.\n Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.\n\nBirner-Grünberger, Ruth\n\nDarnhofer, Barbara\n\nFrisch, Marie-Therese\n\nGugatschka, Markus\n\nRinner, Beate\n\n\n"
},
{
"text": "\n76042\nLarge-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: the GENOMOS study.\n\nLangdahl, BL\n\nUitterlinden, AG\n\nRalston, SH\n\nTrikalinos, TA\n\nBalcells, S\n\nBrandi, ML\n\nScollen, S\n\nLips, P\n\nLorenc, R\n\nObermayer-Pietsch, B\n\nReid, DM\n\nArmas, JB\n\nArp, PP\n\nBassiti, A\n\nBustamante, M\n\nHusted, LB\n\nCarey, AH\n\nPérez Cano, R\n\nDobnig, H\n\nDunning, AM\n\nFahrleitner-Pammer, A\n\nFalchetti, A\n\nKarczmarewicz, E\n\nKruk, M\n\nvan Leeuwen, JP\n\nMasi, L\n\nvan Meurs, JB\n\nMangion, J\n\nMcGuigan, FE\n\nMellibovsky, L\n\nMosekilde, L\n\nNogués, X\n\nPols, HA\n\nReeve, J\n\nRenner, W\n\nRivadeneira, F\n\nvan Schoor, NM\n\nIoannidis, JP\n\nAPOSS investigators\n\nDOPS investigators\n\nEPOS investigators\n\nEPOLOS investigators\n\nFAMOS investigators\n\nLASA investigators\n\nERGO investigators\n\nfor the GENOMOS Study\n\nBeiträge in Fachzeitschriften\nISI:000255260100016\n18284942.0\n10.1016/j.bone.2007.11.007\nNone\nINTRODUCTION: The TGFB1 gene which encodes transforming growth factor beta 1, is a strong candidate for susceptibility to osteoporosis and several studies have reported associations between bone mineral density (BMD), osteoporotic fractures and polymorphisms of TGFB1, although these studies have yielded conflicting results. METHODS: We investigated associations between TGFB1 polymorphisms and BMD and fracture in the GENOMOS study: a prospective multicenter study involving 10 European research studies including a total of 28, 24 participants. Genotyping was conducted for known TGFB1 polymorphisms at the following sites: G-1639-A (G-800-A, rs1800468), C-1348-T (C-509-T, rs1800469), T29-C (Leu10Pro, rs1982073), G74-C (Arg25Pro, rs1800471) and C788-T (Thr263Ile, rs1800472). These polymorphisms were genotyped prospectively and methodology was standardized across research centers. Genotypes and haplotypes were related to BMD at the lumbar sine and femoral neck and fractures. RESULTS: There were no significant differences in either women or men at either skeletal site for any of the examined polymorphisms with the possible exception of a weak association with reduced BMD (-12 mg/cm2) in men with the T-1348 allele (p<0.05). None of the haplotypes was associated with BMD and none of the polymorphisms or haplotypes significantly affected overall risk of fractures, however, the odds ratio for incident vertebral fracture in carriers of the rare T788 allele was 1.64 (95% CI: 1.09-2.64), p<0.05. CONCLUSIONS: This study indicates that polymorphic variation in the TGFB1 gene does not play a major role in regulating BMD or susceptibility to fractures. The weak associations we observed between the C-1348-T and lumbar spine BMD in men and between C788-T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies.\n\nFahrleitner-Pammer, Astrid\n\nObermayer-Pietsch, Barbara\n\nRenner, Wilfried\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n118505\nTrisodium citrate induced protein precipitation in haemodialysis catheters might cause pulmonary embolism.\n\nSchilcher, G\n\nScharnagl, H\n\nHorina, JH\n\nRibitsch, W\n\nRosenkranz, AR\n\nStojakovic, T\n\nPolaschegg, HD\n\nBeiträge in Fachzeitschriften\nISI:000306669100050\n22467258.0\n10.1093/ndt/gfs048\nNone\nHypertonic citrate is bacteriocidal, and has been reported to reduce both dialysis catheter biofilm deposition and bacteraemia rates. However concentrated 46.7% citrate solutions are significantly hyperosmolar...(and) it had been suggested that this increased density led to increased losses of the line lock from the catheter tip, depending upon catheter design. Schilcher carried out both in-vitro and in-vivo studies to investigate whether hypertonic citrate solutions could increase the risk of catheter malfunction due to clot formation...The locking anticoagulant plays a decisive role in the patency of central venous catheters (CVCs) used for haemodialysis. During injection, the hydraulic effects inevitably cause lock solution to spill into the systemic circulation. Density differences between whole blood (WB) and the lock solution cause further gravity-induced seepage of lock solution. This is followed by an influx of WB into the catheter, also described for trisodium citrate, which is a common agent for serum protein precipitation. Embolic complications from haemodialysis catheters locked with hypertonic trisodium citrate have been reported. We aimed to investigate protein precipitation in trisodium citrate locked catheters as a possible cause of pulmonary embolisms. In vitro, WB and trisodium citrate (concentrations ranging from 4.7 to 46.7) mixtures in a ratio of 1:4 were used to assess protein precipitation. Additionally, WB/trisodium citrate mixture was pumped through a 20-m mesh filter, simulating pulmonary vessels, and filtrate pressure was measured. In vivo, listed filling volumes of haemodialysis catheters locked with trisodium citrate 4 (n 10), 10 (n 10), 20 (n 10) or 46.7 (n 10) were aspirated and then analysed for protein precipitation. In vitro, protein precipitation capable of causing filter occlusion was observed in test solutions containing trisodium citrate above a concentration of 12. In vivo, protein precipitation was detected in all samples from the CVCs filled with trisodium citrate 46.7 (n 10) and 20 (n 10). In contrast, there were no signs of precipitation in samples from the catheters filled with trisodium citrate 4 (n 10) or 10 (n 10). Our in vitro results demonstrate that protein precipitates inside haemodialysis catheters when trisodium citrate is used above the concentrations of 12. Precipitated protein may have contributed to the pathophysiology of reported embolisms from haemodialysis catheters filled with hypertonic trisodium citrate. Based on our findings, we suggest that trisodium citrate lock solution up to the concentration of 10 can be used safely.\n\nHorina, Joerg\n\nRibitsch, Werner\n\nRosenkranz, Alexander\n\nScharnagl, Hubert\n\nSchilcher, Gernot\n\n\n"
},
{
"text": "\n173004\nCost-effectiveness analysis of case management for optimized antithrombotic treatment in German general practices compared to usual care - results from the PICANT trial.\n\nUlrich, LR\n\nPetersen, JJ\n\nMergenthal, K\n\nBerghold, A\n\nPregartner, G\n\nHolle, R\n\nSiebenhofer, A\n\nBeiträge in Fachzeitschriften\nISI:000458183700001\n30729350.0\n10.1186/s13561-019-0221-2\nPMC6734317\nBy performing case management, general practitioners and health care assistants can provide additional benefits to their chronically ill patients. However, the economic effects of such case management interventions often remain unclear although how to manage the burden of chronic disease is a key question for policy-makers. This analysis aimed to compare the cost-effectiveness of 24 months of primary care case management for patients with a long-term indication for oral anticoagulation therapy with usual care.\n This analysis is part of the cluster-randomized controlled Primary Care Management for Optimized Antithrombotic Treatment (PICANT) trial. A sample of 680 patients with German statutory health insurance was initially considered for the cost analysis (92% of all participants at baseline). Costs included all disease-related direct health care costs from the payer's perspective (German statutory health insurers) plus case management costs for the intervention group. A-Quality Adjusted Life Year (QALY) measurement (EQ-5D-3 L instrument) was used to evaluate utility, and incremental cost-effectiveness ratio (ICER) to assess cost-effectiveness. Mean differences were calculated and displayed with 95%-confidence intervals (CI) from non-parametric bootstrapping (1000 replicates).\n N = 505 patients (505/680, 74%) were included in the cost analysis (complete case analysis with a follow-up after 12 and 24 months as well as information on cost and QALY). After two years, the mean difference of direct health care costs per patient (€115, 95% CI [- 201; 406]) and QALYs (0.03, 95% CI [- 0.04; 0.11]) in the two groups was small and not significant. The costs of case management in the intervention group caused mean total costs per patient in this group to rise significantly (mean difference €503, 95% CI [188; 794]). The ICER was €16, 67 per QALY. Regardless of the willingness of insurers to pay per QALY, the probability of the intervention being cost-effective never rose above 70%.\n A primary care case management for patients with a long-term indication for oral anticoagulation therapy improved QALYs compared to usual care, but was more costly. However, the results may help professionals and policy-makers allocate scarce health care resources in such a way that the overall quality of care is improved at moderate costs, particularly for chronically ill patients.\n Current Controlled Trials ISRCTN41847489 .\n\nBerghold, Andrea\n\nPregartner, Gudrun\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n177061\nIGF2 mRNA Binding Protein 2 Transgenic Mice Are More Prone to Develop a Ductular Reaction and to Progress Toward Cirrhosis\n\nCzepukojc, B\n\nAbuhaliema, A\n\nBarghash, A\n\nTierling, S\n\nNass, N\n\nSimon, Y\n\nKorbel, C\n\nCadenas, C\n\nvan Hul, N\n\nSachinidis, A\n\nHengstler, JG\n\nHelms, V\n\nLaschke, MW\n\nWalter, J\n\nHaybaeck, J\n\nLeclercq, I\n\nKiemer, AK\n\nKessler, SM\n\nBeiträge in Fachzeitschriften\nISI:000483799100001\n31555647.0\n10.3389/fmed.2019.00179\nPMC6737005\nThe insulin-like growth factor 2 (IGF2) mRNA binding proteins (IMPs/IGF2BPs) IMP1 and 3 are regarded as oncofetal proteins, whereas the hepatic IMP2 expression in adults is controversially discussed. The splice variant IMP2-2/p62 promotes steatohepatitis and hepatocellular carcinoma. Aim of this study was to clarify whether IMP2 is expressed in the adult liver and influences progression toward cirrhosis. IMP2 was expressed at higher levels in embryonic compared to adult tissues as quantified in embryonic, newborn, and adult C57BL/6J mouse livers and suggested by analysis of publicly available human data. In an IMP2-2 transgenic mouse model microarray and qPCR analyses revealed increased expression of liver progenitor cell (LPC) markers Bex1, Prom1, Spp1, and Cdh1 indicating a de-differentiated liver cell phenotype. Induction of these LPC markers was confirmed in human cirrhotic tissue datasets. The LPC marker SPP1 has been described to play a major role in fibrogenesis. Thus, DNA methylation was investigated in order to decipher the regulatory mechanism of Spp1 induction. In IMP2-2 transgenic mouse livers single CpG sites were differentially methylated, as quantified by amplicon sequencing, whereas human HCC samples of a human publicly available dataset showed promoter hypomethylation. In order to study the impact of IMP2 on fibrogenesis in the context of steatohepatitis wild-type or IMP2-2 transgenic mice were fed either a methionine-choline deficient (MCD) or a control diet for 2-12 weeks. MCD-fed IMP2-2 transgenic mice showed a higher incidence of ductular reaction (DR), accompanied by hepatic stellate cell activation, extracellular matrix (ECM) deposition, and induction of the LPC markers Spp1, Cdh1, and Afp suggesting the occurrence of de-differentiated cells in transgenic livers. In human cirrhotic samples IMP2 overexpression correlated with LPC marker and ECM component expression. Progression of liver disease was induced by combined MCD and diethylnitrosamine (DEN) treatment. Combined MCD-DEN treatment resulted in shorter survival of IMP2-2 transgenic compared to wild-type mice. Only IMP2-2 transgenic livers progressed to cirrhosis, which was accompanied by strong DR. In conclusion, IMP2 is an oncofetal protein in the liver that promotes DR characterized by de-differentiated cells toward steatohepatitis-associated cirrhosis development with poor survival.\n\nHaybäck, Johannes\n\n\n"
},
{
"text": "\n177075\n2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus.\n\nAringer, M\n\nCostenbader, K\n\nDaikh, D\n\nBrinks, R\n\nMosca, M\n\nRamsey-Goldman, R\n\nSmolen, JS\n\nWofsy, D\n\nBoumpas, DT\n\nKamen, DL\n\nJayne, D\n\nCervera, R\n\nCostedoat-Chalumeau, N\n\nDiamond, B\n\nGladman, DD\n\nHahn, B\n\nHiepe, F\n\nJacobsen, S\n\nKhanna, D\n\nLerstrøm, K\n\nMassarotti, E\n\nMcCune, J\n\nRuiz-Irastorza, G\n\nSanchez-Guerrero, J\n\nSchneider, M\n\nUrowitz, M\n\nBertsias, G\n\nHoyer, BF\n\nLeuchten, N\n\nTani, C\n\nTedeschi, SK\n\nTouma, Z\n\nSchmajuk, G\n\nAnic, B\n\nAssan, F\n\nChan, TM\n\nClarke, AE\n\nCrow, MK\n\nCzirják, L\n\nDoria, A\n\nGraninger, W\n\nHalda-Kiss, B\n\nHasni, S\n\nIzmirly, PM\n\nJung, M\n\nKumánovics, G\n\nMariette, X\n\nPadjen, I\n\nPego-Reigosa, JM\n\nRomero-Diaz, J\n\nRúa-Figueroa Fernández, Í\n\nSeror, R\n\nStummvoll, GH\n\nTanaka, Y\n\nTektonidou, MG\n\nVasconcelos, C\n\nVital, EM\n\nWallace, DJ\n\nYavuz, S\n\nMeroni, PL\n\nFritzler, MJ\n\nNaden, R\n\nDörner, T\n\nJohnson, SR\n\nBeiträge in Fachzeitschriften\nISI:000483727200005\n31385462.0\n10.1002/art.40930\nPMC6827566\nTo develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).\n This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1, 01 subjects and validation compared with previous criteria in a new validation cohort of 1, 70 subjects.\n The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.\n These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.\n © 2019, American College of Rheumatology.\n\nGraninger, Winfried\n\n\n"
},
{
"text": "\n180685\nOptimal predictors of prostate cancer on repeat prostate biopsy: a prospective study of 1,051 men.\n\nDjavan, B\n\nZlotta, A\n\nRemzi, M\n\nGhawidel, K\n\nBasharkhah, A\n\nSchulman, CC\n\nMarberger, M\n\nBeiträge in Fachzeitschriften\nISI:000085974000019\n10737484.0\n10.1016/S0022-5347(05)67711-7\nNone\nWe compare the ability of total prostate specific antigen (PSA), percent free PSA, PSA density and transition zone PSA density to predict the outcome of repeat prostatic biopsy in men with serum total PSA 4 to 10 ng./ml. who were diagnosed with benign prostatic hyperplasia after initial biopsy.\n In this prospective study 1, 51 men with total PSA 4 to 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy with 2 additional transition zone biopsies. In 254 subjects biopsy specimens were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All subjects with biopsy specimens negative for prostate cancer underwent repeat biopsy 6 weeks after initial biopsy. The ability of total PSA, percent free PSA, PSA density and transition zone PSA density to improve the diagnostic power of PSA testing was assessed with univariate and multivariate analyses as well as receiver operating characteristics (ROC) curves.\n Initial biopsy was positive (prostate cancer) in 231 and negative (benign prostatic hyperplasia) in 820 of the 1, 51 subjects. Prostate cancer was detected on repeat biopsy in 10% of subjects (83 of 820) with negative initial biopsy. Percent free PSA and transition zone PSA density were the most accurate predictors of prostate cancer in these subjects. At a cutoff of 30% percent free PSA would have detected 90% of cancers (sensitivity) and eliminated 50% of unnecessary repeat biopsies (specificity). Sensitivity and specificity of transition zone PSA density at a cutoff of 0.26 ng./ml./cc was 78% and 52%, respectively. ROC curve analysis also showed that percent free PSA was a significantly better predictor of repeat biopsy results than total PSA, PSA density and transition zone PSA density. The area under the ROC curve was 74.5% for percent free PSA, 69.1% for transition zone PSA density, 61.8% for PSA density and 60.3% for total PSA.\n At least 10% of patients with negative initial prostatic biopsy results will be diagnosed with prostate cancer on repeat biopsy. Percent free PSA and transition zone PSA density enhance the specificity of PSA testing compared to total PSA or PSA density when determining which patients should undergo repeat biopsy. Repeat biopsy should be performed in patients with percent free PSA less than 30% or transition zone PSA density 0.26 ng./ml./cc or greater. In our study percent free PSA was the most accurate predictor of prostate cancer in repeat biopsy specimens.\n\n\n"
},
{
"text": "\n187534\nThe diffuse-type tenosynovial giant cell tumor (dt-TGCT) patient journey: a prospective multicenter study.\n\nBernthal, NM\n\nSpierenburg, G\n\nHealey, JH\n\nPalmerini, E\n\nBauer, S\n\nTOPP Study Group\n\nGelderblom, H\n\nStaals, EL\n\nLopez-Bastida, J\n\nFronk, EM\n\nYe, X\n\nLaeis, P\n\nvan de Sande, MAJ\n\nBeiträge in Fachzeitschriften\nISI:000645646500001\n33926503.0\n10.1186/s13023-021-01820-6\nPMC8086070\nTenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm arising from the synovium of joints, bursae, and tendon sheaths affecting small and large joints. It represents a wide spectrum ranging from minimally symptomatic to massively debilitating. Most findings to date are mainly from small, retrospective case series, and thus the morbidity and actual impact of this rare disease remain to be elucidated. This study prospectively explores the management of TGCT in tertiary sarcoma centers.\n The TGCT Observational Platform Project registry was a multinational, multicenter, prospective observational study involving 12 tertiary sarcoma centers in 7 European countries, and 2 US sites. This study enrolled for 2 years all consecutive ≥ 18 years old patients, with histologically diagnosed primary or recurrent cases of diffuse-type TGCT. Patient demographic and clinical characteristics were collected at baseline and every 6 months for 24 months. Quality of life questionnaires (PROMIS-PF and EQ-5D) were also administered at the same time-points. Here we report baseline patient characteristics.\n 166 patients were enrolled between November 2016 and March 2019. Baseline characteristics were: mean age 44 years (mean age at disease onset: 39 years), 139/166 (83.7%) had prior treatment, 71/166 patients (42.8%) had ≥ 1 recurrence after treatment of their primary tumor, 76/136 (55.9%) visited a medical specialist ≥ 5 times, 66/116 (56.9%) missed work in the 24 months prior to baseline, and 17/166 (11.6%) changed employment status or retired prematurely due to disease burden. Prior treatment consisted of surgery (i.e., arthroscopic, open synovectomy) (128/166; 77.1%) and systemic treatments (52/166; 31.3%) with imatinib (19/52; 36.5%) or pexidartinib (27/52; 51.9%). Treatment strategies at baseline visits consisted mainly of watchful waiting (81/166; 48.8%), surgery (41/166; 24.7%), or targeted systemic therapy (37/166; 22.3%). Patients indicated for treatment reported more impairment compared to patients indicated for watchful waiting: worst stiffness NRS 5.16/3.44, worst pain NRS 6.13/5.03, PROMIS-PF 39.48/43.85, and EQ-5D VAS 66.54/71.85.\n This study confirms that diffuse-type TGCT can highly impact quality of life. A prospective observational registry in rare disease is feasible and can be a tool to collect curated-population reflective data in orphan diseases. Name of registry: Tenosynovial Giant Cell Tumors (TGCT) Observational Platform Project (TOPP).\n NCT02948088. Date of registration: 10 October 2016. URL of Trial registry record: https://clinicaltrials.gov/ct2/show/NCT02948088?term=NCT02948088&draw=2 .\n\nLeithner, Andreas\n\n\n"
},
{
"text": "\n80110\nControl of delayed nausea and vomiting with granisetron plus dexamethasone or dexamethasone alone in patients receiving highly emetogenic chemotherapy: a double-blind, placebo-controlled, comparative study.\n\nGoedhals, L\n\nHeron, JF\n\nKleisbauer, JP\n\nPagani, O\n\nSessa, C\n\nGiger, K\n\nCavalli, F\n\nLudwig, C\n\nAapro, M\n\nBleiberg, H\n\nDe Wash, G\n\nDicato, M\n\nTagnon, A\n\nVanstraelen, D\n\nVindevoghel, A\n\nAbratt, R\n\nFalkson, G\n\nBarley, V\n\nCarmichael, J\n\nColeman, R\n\nDavidson, N\n\nGrieve, R\n\nHarper, P\n\nRoberts, J\n\nRustin, G\n\nNaman, H\n\nSchneider, M\n\nNoble, A\n\nNetter, P\n\nCupissol, D\n\nBalmes, P\n\nCals, L\n\nKhayat, D\n\nCatimel, G\n\nDutin, JP\n\nBoufette, P\n\nAdenis, L\n\nMisset, J\n\nCollery, P\n\nNouvet, G\n\nChavaillon, JM\n\nBlanchon, F\n\nPoirier, R\n\nArnaud, A\n\nLecaer, H\n\nCarles, P\n\nMuir, J\n\nBonnaud, F\n\nMarqueste, L\n\nClavier, J\n\nGuerin, J\n\nTaytard, A\n\nKeizer, H\n\nNortier, J\n\nSlee, P\n\nWils, J\n\nRodenburg, C\n\nBurghouts, J\n\nDe Wit, R\n\nGarcia-Giron, C\n\nJimenez-Lacave, A\n\nCruz-Hernandez, J\n\nMassuti-Sureda, B\n\nHans, K\n\nFuchs, R\n\nKriegmair, M\n\nSchuller, J\n\nLahousen, M\n\nPannuti, F\n\nMonfardini, S\n\nNilsson, S\n\nBeiträge in Fachzeitschriften\nISI:000074815700020\n9681082.0\n10.1023/A:1008256115221\nNone\nBACKGROUND: The efficacies of granisetron plus dexamethasone and dexamethasone alone in controlling delayed nausea and vomiting after cisplatin chemotherapy (> or = 69 mg/m2) were compared in a multicentre, double-blind, placebo-controlled comparative study. PATIENTS AND METHODS: In all, 654 patients (of whom 619 were evaluable) received prophylactic granisetron plus dexamethasone before chemotherapy on day 0; on day 1 complete responders and non-responders were randomized separately to receive dexamethasone, 8 mg b.d. p.o., with either granisetron, 1 mg b.d. p.o., or matching placebo for six days. RESULTS: Over days 1-6 the complete response rates were 54.5% (dexamethasone group) and 52.1% (dexamethasone plus granisetron group). Response rates were higher over days 4-6 (71.8% and 70.7%, respectively) than over days 1-3 (60.4% and 57.9%, respectively). Significantly more patients who responded to antiemetic treatment during day 0 were responders over days 1-6 (63% vs. 17%; P < 0.001). No other treatment-related differences were found. Adverse events tended to be minor, with constipation and headache the most common. Overall, there were no significant differences in the safety profiles of the two regimens, but constipation and abdominal pain were significantly more common in the dexamethasone plus granisetron group. CONCLUSIONS: Granisetron plus dexamethasone did not appear to confer additional benefit over use of dexamethasone alone in controlling delayed nausea and vomiting following cisplatin chemotherapy. Control of acute nausea and vomiting, however, appeared to be an important factor influencing delayed nausea and vomiting.\n\n\n"
},
{
"text": "\n118366\nComplement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders.\n\nMader, S\n\nGredler, V\n\nSchanda, K\n\nRostasy, K\n\nDujmovic, I\n\nPfaller, K\n\nLutterotti, A\n\nJarius, S\n\nDi Pauli, F\n\nKuenz, B\n\nEhling, R\n\nHegen, H\n\nDeisenhammer, F\n\nAboul-Enein, F\n\nStorch, MK\n\nKoson, P\n\nDrulovic, J\n\nKristoferitsch, W\n\nBerger, T\n\nReindl, M\n\nBeiträge in Fachzeitschriften\nISI:000300342200001\n22204662.0\n10.1186/1742-2094-8-184\nPMC3278385\nSerum autoantibodies against the water channel aquaporin-4 (AQP4) are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO). However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM) remains unresolved.\n We analyzed patients with definite NMO (n = 45), HR-NMO (n = 53), ADEM (n = 33), clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32), MS (n = 71) and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects) for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC). AQP4-IgG was found in patients with NMO (n = 43, 96%), HR-NMO (n = 32, 60%) and in one CIS patient (3%), but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%), NMO (n = 3, 7%), HR-NMO (n = 7, 13%, 5 rON and 2 LETM), CIS (n = 2, 6%), MS (n = 2, 3%) and controls (n = 3, 3%, two SLE and one OND). Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33%) AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able to mediate CDC at high-titer levels.\n We could show for the first time that a subset of AQP4-IgG seronegative patients with NMO and HR-NMO exhibit a MOG-IgG mediated immune response, whereas MOG is not a target antigen in cases with an AQP4-directed humoral immune response.\n\n\n"
},
{
"text": "\n146613\nMaternal and neonatal outcomes in pregnant women with PCOS: comparison of different diagnostic definitions.\n\nKollmann, M\n\nKlaritsch, P\n\nMartins, WP\n\nGuenther, F\n\nSchneider, V\n\nHerzog, SA\n\nCraciunas, L\n\nLang, U\n\nObermayer-Pietsch, B\n\nLerchbaum, E\n\nRaine-Fenning, N\n\nBeiträge in Fachzeitschriften\nISI:000363052400019\n26223675.0\n10.1093/humrep/dev187\nNone\nDoes the prevalence of adverse maternal and neonatal outcomes vary in women diagnosed with polycystic ovary syndrome (PCOS) according to different definitions?\n A comparison of different criteria revealed that there is a substantial risk for perinatal complications in PCOS women, regardless of the used definition.\n Pregnant women with PCOS are susceptible to perinatal complications. At present, there are three main definitions for PCOS. So far, we are aware of only one study, which found that the elevated risk for complications varied widely depending on the different phenotypes and features but only considered a relatively small sample size for some of the phenotypes.\n Retrospective matched cohort study.\n Data of primiparous women with PCOS according to ESHRE/ASRM 2003 criteria and healthy controls giving birth to neonates ≥500 g were included. A total of 885 women were analysed: out of 177 women with PCOS, 85 (48.0%) met the National Institutes of Health (NIH) 1990 criteria, another 14 (7.9%) featured the additional phenotypes defined by The Androgen Excess and PCOS Society (AE-PCOS) 2006 criteria, 78 (44.1%) were classified as PCOS exclusively by the ESHRE/ASRM 2003 definition, and 708 represented the control group.\n The prevalence of adverse maternal (49.4 versus 64.3 versus 60.3%, P = 0.313) and neonatal (27.1 versus 35.7 versus 23.1%, P = 0.615) outcomes did not differ within the three PCOS groups (ESHRE/ASRM, NIH, AE-PCOS, respectively). Compared with healthy controls, the risk for maternal complications was increased in PCOS patients [odds ratio (OR) 2.57; 95% confidence interval (CI) 1.82-3.64; P < 0.001] while there was no difference in neonatal complications (OR 0.83; 95% CI 0.56-1.21; P = 0.343).\n A limitation of our study is its retrospective design and the relatively small sample size, particularly in the AE-PCOS subgroup.\n Since women with PCOS have, regardless of the used definition, a high risk of maternal and neonatal complications they should be informed and advised to follow regular checks in units where problems can be detected early to allow specialized care.\n Marietta Blau Grant (Austrian Agency for International Cooperation in Education and Research; OeAD-GmbH) and mobility scholarship (Medical University of Graz).\n © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.\n\nHerzog, Sereina Annik\n\nKlaritsch, Philipp\n\nKollmann, Martina\n\nLerchbaum, Elisabeth\n\nObermayer-Pietsch, Barbara\n\n\n"
},
{
"text": "\n149156\nPrognostic values of ETS-1, MMP-2 and MMP-9 expression and co-expression in breast cancer patients.\n\nPuzovic, V\n\nBrcic, I\n\nRanogajec, I\n\nJakic-Razumovic, J\n\nBeiträge in Fachzeitschriften\nISI:000342881700009\n24645837.0\n10.4149/neo_2014_054\nNone\nThe aim of this study was to analyse expression of ETS-1 protein and two gelatinases (MMP-2 and MMP-9) and their possible prognostic value in breast carcinoma patients, as well as correlation of their expression with other known prognostic factors such as tumor size, grade, vascular invasion, steroid receptor values, HER2 values and proliferative index. The expression of MMP-2, MMP-9 and ETS-1 was immunohistochemicaly analysed in 121 consecutive primary breast carcinoma patients who underwent surgery at the Clinical Hospital Centre Zagreb during 2002. Three representative areas from each tumor paraffin blocks were taken and arranged on a recipient paraffin block with predefined coordinates for simultaneous analyses of multiple tissue samples (TMA). ETS-1, MMP-2 and MMP-9 expression and co-expression were correlated with other clinico-pathological parameters and based on the available clinical follow up data survival analysis was performed. The ETS-1 protein is found to be expressed in tumor cell nuclei and cytoplasm as well as in stromal lymphocytes, fibroblasts and endothelial cells. MMP-2 and MMP-9 were found to be expressed in cytoplasm of both, tumor and stromal cells. For our analysis only tumor cell expression was used for statistical analysis. We found 56, % ETS-1 positive tumors, 77, % were MMP-2 positive, and MMP-9 was expressed in 90% of primary breast carcinomas. There were no significant correlations between MMP-s expression and other patohistological prognostic factors, but expression of ETS-1 was significantly correlated with higher tumor size and grade, as well as with negative steroid receptors. Co-expression of MMP-2, MMP-9 and ETS-1 was found in 40, % of tumors, and more commonly was found in tumors larger than 2 cm, high grade tumors, and steroid receptor negative tumors. In univariate analysis, statistically significant negative impact on overall survival (OS) had tumor size, nuclear and tumor grade, ETS-1 expression in tumor cells, co-expression of ETS-1 either with MMP-2 or MMP-9, as well as co-expression of ETS-1, MMP-2 and MMP-3. Disease free survival (DFS) was significantly shorter in patients with tumors greater than 2 cm, ETS-1 positive tumors, ETS-1 and MMP-2 or MMP-9 co-expressed tumors, and additionally in tumors with ETS-1, MMP-2 and MMP-9 co-expression. These results suggest that expression of ETS-1 as well as MMP-2, MMP-9 and ETS-1 co-expression might be used as a poor prognostic factor in breast cancer patients.\n\nBrcic, Iva\n\n\n"
},
{
"text": "\n152002\n[Position paper on medication-related osteonecrosis of the jaw (MRONJ)].\n\nSvejda, B\n\nMuschitz, Ch\n\nGruber, R\n\nBrandtner, Ch\n\nSvejda, Ch\n\nGasser, RW\n\nSantler, G\n\nDimai, HP\n\nBeiträge in Fachzeitschriften\nISI:000371428900014\n26847441.0\n10.1007/s10354-016-0437-2\nNone\nIt is now 12 years since the first article on medication-related osteonecrosis of the jaw (MRONJ) was reported in 2003. The recognition of MRONJ is still inconsistent between physicians and dentists but it is without doubt a severe disease with impairment of oral health-related quality of life. This position paper was developed by three Austrian societies for dentists, oral surgeons and osteologists involved in this topic. This update contains amendments on the incidence, pathophysiology, diagnosis, staging and treatment and provides recommendations for management based on a multidisciplinary international consensus. The MRONJ can be a medication-related side effect of treatment of malignant and benign bone diseases with bisphosphonates (Bp), bevacizumab and denosumab (Dmab) as antiresorptive therapy. The incidence of MRONJ is highest in the oncology patient population (range 1-15 %), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of MRONJ is estimated to be 0.001-0.01 %, marginally higher than the incidence in the general population (< 0.001 %). Other risk factors for MRONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, ill-fitting dentures as well as other drugs, including antiangiogenic agents. Prevention strategies for MRONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of MRONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of MRONJ is based on the stage of the disease, extent of the lesions and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Early data have suggested enhanced osseous wound healing with teriparatide in those patients without contraindications for its use. The MRONJ related to denosumab may resolve more quickly with a drug holiday than MRONJ related to bisphosphonates. Localized surgical debridement is indicated in advanced nonresponsive disease and has proven successful. More invasive surgical techniques are becoming increasingly more important. Prevention is the key for the management of MRONJ. This requires a close teamwork for the treating physician and the dentist. It is necessary that this information is disseminated to other relevant health care professionals and organizations.\n\nDimai, Hans\n\n\n"
},
{
"text": "\n186868\nThe avascular plane of the Achilles tendon: a quantitative anatomic and angiographic approach and a base for a possible new treatment option after rupture.\n\nWolff, KS\n\nWibmer, AG\n\nBinder, H\n\nGrissmann, T\n\nHeinrich, K\n\nSchauer, S\n\nNepp, R\n\nRois, S\n\nRitschl, H\n\nTeufelsbauer, H\n\nPretterklieber, ML\n\nBeiträge in Fachzeitschriften\nNone\n21444168.0\n10.1016/j.ejrad.2011.03.015\nNone\nAchilles tendon ruptures, especially ruptures caused by pathologic conditions and also by achillotendinitis are often attributed to the alleged hypovascularisation of the Achilles tendon. Anatomic studies often mention an avascular plane. The purpose of this study was to re-investigate the arterial supply of the Achilles tendon.\n Lower legs of 28 anatomic specimen were injected with a radiologic contrast agent and subsequently an arterial angiography was performed. Afterwards the legs were embalmed and later anatomically dissected. The origin of arteries entering the paratenon of the tendo calcanei branching off from either the anterior (TA) or the posterior tibial artery (TP) was determined. The distance between the points of commencement of these nutrient arteries and a specific reference point, i.e. the insertion of the Achilles tendon into the tuber calcanei, was measured digitally on the radiographs and again with a slide-gauge on the dissected specimens.\n As revealed by angiographic analysis, the TA gave off 5 vessels (v) at a frequency and median distance to the tuber calcanei (in cm) of v1: 50%, 6.01 cm; v2: 39.3%, 7.88 cm; v3: 35.7%, 9.71 cm; v4: 17.9%, 12.7 cm; v5: 10.7%, 14.6 cm. The TP contributed to the arterial supply of the Achilles tendon by means of 7 inserting arteries branching off at a frequency and mean distances of v1: 67.9%, 4.53 cm; v2: 60.7%, 6.97 cm, v3: 50%, 9.58 cm; v4: 35.7%, 10.89 cm; v5: 25%, 12.65 cm; v6: 10.7%, 16.94 cm; v7: 3.6%, 18.7 cm proximal to the tuber calcanei. However, due to the small diameter of these branches, by anatomic dissection no nutrient arteries commencing from the TA could be detected. On the other hand, a maximum of 7 vessels originating from the TP, larger than the former vessels, had been also revealed by anatomic dissection (frequency and mean distances, v1: 100%, 6.8 cm; v2: 82.1%, 7.7 cm; v3: 71.4%, 9.5cm; v4: 35.7%, 11.3 cm; v5: 17.9%, 9.9 cm; v6: 7.1, 10.5 cm; v7: 3.6%, 12.0 cm).\n A dense net of small arteries inserts into the paratenon of the Achilles tendon in its lower 20 cm. The angiographic method was more specific and showed vessels that could not be identified as arteries originating from the TA by macroscopic anatomic dissection.\n Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n187849\nEpithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts.\n\nStacchiotti, S\n\nMiah, AB\n\nFrezza, AM\n\nMessiou, C\n\nMorosi, C\n\nCaraceni, A\n\nAntonescu, CR\n\nBajpai, J\n\nBaldini, E\n\nBauer, S\n\nBiagini, R\n\nBielack, S\n\nBlay, JY\n\nBonvalot, S\n\nBoukovinas, I\n\nBovee, JVMG\n\nBoye, K\n\nBrodowicz, T\n\nCallegaro, D\n\nDe Alava, E\n\nDeoras-Sutliff, M\n\nDufresne, A\n\nEriksson, M\n\nErrani, C\n\nFedenko, A\n\nFerraresi, V\n\nFerrari, A\n\nFletcher, CDM\n\nGarcia Del Muro, X\n\nGelderblom, H\n\nGladdy, RA\n\nGouin, F\n\nGrignani, G\n\nGutkovich, J\n\nHaas, R\n\nHindi, N\n\nHohenberger, P\n\nHuang, P\n\nJoensuu, H\n\nJones, RL\n\nJungels, C\n\nKasper, B\n\nKawai, A\n\nLe Cesne, A\n\nLe Grange, F\n\nLeithner, A\n\nLeonard, H\n\nLopez Pousa, A\n\nMartin Broto, J\n\nMerimsky, O\n\nMerriam, P\n\nMiceli, R\n\nMir, O\n\nMolinari, M\n\nMontemurro, M\n\nOldani, G\n\nPalmerini, E\n\nPantaleo, MA\n\nPatel, S\n\nPiperno-Neumann, S\n\nRaut, CP\n\nRavi, V\n\nRazak, ARA\n\nReichardt, P\n\nRubin, BP\n\nRutkowski, P\n\nSafwat, AA\n\nSangalli, C\n\nSapisochin, G\n\nSbaraglia, M\n\nScheipl, S\n\nSchöffski, P\n\nStrauss, D\n\nStrauss, SJ\n\nSundby Hall, K\n\nTap, WD\n\nTrama, A\n\nTweddle, A\n\nvan der Graaf, WTA\n\nVan De Sande, MAJ\n\nVan Houdt, W\n\nvan Oortmerssen, G\n\nWagner, AJ\n\nWartenberg, M\n\nWood, J\n\nZaffaroni, N\n\nZimmermann, C\n\nCasali, PG\n\nDei Tos, AP\n\nGronchi, A\n\nBeiträge in Fachzeitschriften\nNone\n34090171.0\n10.1016/j.esmoop.2021.100170\nNone\nEpithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.\n Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.\n\nLeithner, Andreas\n\nScheipl, Susanne\n\n\n"
},
{
"text": "\n97902\nK-ATP channel subunits in rat dorsal root ganglia: alterations by painful axotomy.\n\nZoga, V\n\nKawano, T\n\nLiang, MY\n\nBienegraeber, M\n\nWeihrauch, D\n\nMcCallum, B\n\nGemes, G\n\nHogan, Q\n\nSarantopoulos, C\n\nBeiträge in Fachzeitschriften\nISI:000275044300001\n20102598.0\n10.1186/1744-8069-6-6\nPMC2825500\nBackground: ATP-sensitive potassium (K-ATP) channels in neurons mediate neuroprotection, they regulate membrane excitability, and they control neurotransmitter release. Because loss of DRG neuronal K-ATP currents is involved in the pathophysiology of pain after peripheral nerve injury, we characterized the distribution of the K-ATP channel subunits in rat DRG, and determined their alterations by painful axotomy using RT-PCR, immunohistochemistry and electron microscopy. Results: PCR demonstrated Kir6.1, Kir6.2, SUR1 and SUR2 transcripts in control DRG neurons. Protein expression for all but Kir6.1 was confirmed by Western blots and immunohistochemistry. Immunostaining of these subunits was identified by fluorescent and confocal microscopy in plasmalemmal and nuclear membranes, in the cytosol, along the peripheral fibers, and in satellite glial cells. Kir6.2 co-localized with SUR1 subunits. Kir6.2, SUR1, and SUR2 subunits were identified in neuronal subpopulations, categorized by positive or negative NF200 or CGRP staining. K-ATP current recorded in excised patches was blocked by glybenclamide, but preincubation with antibody against SUR1 abolished this blocking effect of glybenclamide, confirming that the antibody targets the SUR1 protein in the neuronal plasmalemmal membrane. In the myelinated nerve fibers we observed anti-SUR1 immunostaining in regularly spaced funneled-shaped structures. These structures were identified by electron microscopy as Schmidt-Lanterman incisures (SLI) formed by the Schwann cells. Immunostaining against SUR1 and Kir6.2 colocalized with anti-Caspr at paranodal sites. DRG excised from rats made hyperalgesic by spinal nerve ligation exhibited similar staining against Kir6.2, SUR1 or SUR2 as DRG from controls, but showed decreased prevalence of SUR1 immunofluorescent NF200 positive neurons. In DRG and dorsal roots proximal to axotomy SLI were smaller and showed decreased SUR1 immunofluorescence. Conclusions: We identified Kir6.2/SUR1 and Kir6.2/SUR2 K-ATP channels in rat DRG neuronal somata, peripheral nerve fibers, and glial satellite and Schwann cells, in both normal state and after painful nerve injury. This is the first report of K-ATP channels in paranodal sites adjacent to nodes of Ranvier and in the SLI of the Schwann cells. After painful axotomy K-ATP channels are downregulated in large, myelinated somata and also in SLI, which are also of smaller size compared to controls. Because K-ATP channels may have diverse functional roles in neurons and glia, further studies are needed to explore the potential of K-ATP channels as targets of therapies against neuropathic pain and neurodegeneration.\n\n\n"
},
{
"text": "\n116575\nPredicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.\n\nCha, EK\n\nShariat, SF\n\nKormaksson, M\n\nNovara, G\n\nChromecki, TF\n\nScherr, DS\n\nLotan, Y\n\nRaman, JD\n\nKassouf, W\n\nZigeuner, R\n\nRemzi, M\n\nBensalah, K\n\nWeizer, A\n\nKikuchi, E\n\nBolenz, C\n\nRoscigno, M\n\nKoppie, TM\n\nNg, CK\n\nFritsche, HM\n\nMatsumoto, K\n\nWalton, TJ\n\nEhdaie, B\n\nTritschler, S\n\nFajkovic, H\n\nMartinez-Salamanca, JI\n\nPycha, A\n\nLangner, C\n\nFicarra, V\n\nPatard, JJ\n\nMontorsi, F\n\nWood, CG\n\nKarakiewicz, PI\n\nMargulis, V\n\nBeiträge in Fachzeitschriften\nISI:000300838000047\n22284969.0\n10.1016/j.eururo.2012.01.021\nNone\nBackground: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. Objective: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. Design, setting, and participants: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n = 1273) and external validation (11 centers, n = 971). Interventions: All patients underwent RNU. Measurements: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping. Results and limitations: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p = 0.002), lymphovascular invasion (HR: 1.66; p < 0.001), sessile tumor architecture (HR: 1.76; p < 0.001), and concomitant CIS (HR: 1.33; p = 0.035) were associated with disease recurrence. Similarly, T classification (p for trend < 0.001), lymph node metastasis (HR: 2.23; p = 0.001), lymphovascular invasion (HR: 1.81; p < 0.001), and sessile tumor architecture (HR: 1.72; p = 0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination. Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nLangner, Cord\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n140757\nBone quality of the newest bone formed after two years of teriparatide therapy in patients who were previously treatment-naïve or on long-term alendronate therapy.\n\nHofstetter, B\n\nGamsjaeger, S\n\nVarga, F\n\nDobnig, H\n\nStepan, JJ\n\nPetto, H\n\nPavo, I\n\nKlaushofer, K\n\nPaschalis, EP\n\nBeiträge in Fachzeitschriften\nISI:000344810100004\n25037600.0\n10.1007/s00198-014-2814-2\nNone\nThe results of the present study, involving analysis of biopsies from patients who received teriparatide for 2 years and were previously either treatment-naïve or on long-term alendronate therapy, suggest that prior alendronate use does not blunt the favorable effects of teriparatide on bone quality.\n Examine the effect of 2 years of teriparatide (TPTD) treatment on mineral and organic matrix properties of the newest formed bone in patients who were previously treatment-naïve (TN) or on long-term alendronate (ALN) therapy.\n Raman and Fourier transform infrared microspectroscopic analyses were used to determine the mineral/matrix (M/M) ratio, the relative proteoglycan (PG) content, and the mineral maturity/crystallinity (MMC; determined by three methods: carbonate content, full width at half height of the v 1 PO4 band [FWHH], and wavelength at maxima of the v 1 PO4 band), as well as collagen maturity (ratio of pyridinoline/divalent cross-links), in paired iliac crest biopsies at trabecular, endosteal, and osteonal surfaces of newly formed bone in postmenopausal osteoporotic women who were previously either TN (n = 16) or receiving long-term ALN treatment (n = 24).\n Trabecular M/M ratio increased and matrix content decreased significantly in the ALN pretreated group. Collagen maturity decreased in both patient groups. Endosteal M/M ratio increased significantly in the TN group. Trabecular M/M ratio was higher at endpoint in the ALN pretreated group than in the TN group. Overall, no changes from baseline were observed in PG content, except that PG content was higher in the ALN pretreated group than in the TN group at endosteal surfaces at endpoint. The ability of TPTD treatment to reduce MMC in both patient groups and at the different bone surfaces depended on the measurement tool (relative carbonate content or wavelength at maxima of the v 1 PO4 band). None of the changes in MMC were different between the two patient groups.\n The results suggest some favorable impact of TPTD on bone mineral and organic matrix properties of in situ forming bone in terms of increased initial mineralization and decreased MMC and collagen maturity. Moreover, prior long-term ALN administration may have only limited influence on these properties in bone newly formed after 2 years of TPTD treatment.\n\n\n"
}
]
}