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"text": "\n50094\nPolymorphisms within the tumor necrosis factor-alpha promoter region in patients with HLA-B27-associated uveitis: association with susceptibility and clinical manifestations.\n\nEl-Shabrawi, Y\n\nWegscheider, BJ\n\nWeger, M\n\nRenner, W\n\nPosch, U\n\nUlrich, S\n\nArdjomand, N\n\nHermann, J\n\nBeiträge in Fachzeitschriften\nISI:000236538900027\n16581430.0\n10.1016/j.ophtha.2006.01.004\nNone\nPURPOSE: The existence of genetic variations in a number of cytokines has been considered to influence susceptibility or relate to disease severity in various autoimmune diseases. Among these, single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor alpha (TNF-alpha) promoter at nucleotides -308 and -238 are considered to be protective against inflammation in HLA-B27-positive individuals, whereas the SNP at position -857 has been associated with disease development in anterior uveitis. We investigate a hypothesized association between the TNF-alpha -857 C-to-T, -308 G-to-A, and the TNF-alpha -238 G-to-A SNPs and the presence of HLA-B27-associated uveitis. DESIGN: Retrospective case-control study. PARTICIPANTS: One hundred fourteen Caucasian patients with HLA-B27-associated uveitis were studied. Mean age of patients was 44.9+/-14 years (range, 16-81), and mean duration of HLA-B27-associated uveitis was 115.6+/-104 months (range, 6 months-51 years). Eighty-six patients (75.4%) suffered from an additional systemic manifestation of the disease. Sixty-three unrelated healthy HLA-B27-positive blood donors and 88 unrelated healthy HLA-B27-negative individuals served as controls. METHODS: Genotypes were determined by polymerase chain reaction. MAIN OUTCOME PARAMETERS: Association of genotypes at positions -857, -308, and -238 of the TNF-alpha gene with disease development. RESULTS: Frequencies of the TNF-alpha -308GA and TNF-alpha -238GA genotypes were significantly lower in patients with HLA-B27-associated uveitis (6.1% and 0%, respectively) when compared with the HLA-B27-negative control group, 23% at -308 (P = 0.003), and 7.9% at -238 (P = 0.0003). When compared with healthy HLA-B27-positive controls, a significantly lower frequency of the TNF-alpha -238GA genotype was found among patients (6.3%, P = 0.015). The frequency of the TNF-alpha -308GA genotype was also found to be lower in patients than among HLA-B27-positive control subjects, without, however, reaching statistical significance (6.1%, P = 0.07). No difference in frequencies was seen among the different groups for the SNPs at position -857. CONCLUSION: Our data suggest that HLA-B27-positive individuals show a higher susceptibility towards development of an intraocular inflammation in the presence of an A allele at nucleotide -238 and, to a lesser degree, at nucleotide -308 of the TNF-alpha gene promoter.\n\nArdjomand, Navid\n\nEl-Shabrawi, Yosuf\n\nHermann, Josef\n\nRenner, Wilfried\n\nWeger, Martin\n\n\n"
},
{
"text": "\n60776\nQuantitative assessment of tumour extraction from dermoscopy images and evaluation of computer-based extraction methods for an automatic melanoma diagnostic system.\n\nIyatomi, H\n\nOka, H\n\nSaito, M\n\nMiyake, A\n\nKimoto, M\n\nYamagami, J\n\nKobayashi, S\n\nTanikawa, A\n\nHagiwara, M\n\nOgawa, K\n\nArgenziano, G\n\nSoyer, HP\n\nTanaka, M\n\nBeiträge in Fachzeitschriften\nISI:000237269600011\n16567974.0\n10.1097/01.cmr.0000215041.76553.58\nNone\nThe aims of this study were to provide a quantitative assessment of the tumour area extracted by dermatologists and to evaluate computer-based methods from dermoscopy images for refining a computer-based melanoma diagnostic system. Dermoscopic images of 188 Clark naevi, 56 Reed naevi and 75 melanomas were examined. Five dermatologists manually drew the border of each lesion with a tablet computer. The inter-observer variability was evaluated and the standard tumour area (STA) for each dermoscopy image was defined. Manual extractions by 10 non-medical individuals and by two computer-based methods were evaluated with STA-based assessment criteria: precision and recall. Our new computer-based method introduced the region-growing approach in order to yield results close to those obtained by dermatologists. The effectiveness of our extraction method with regard to diagnostic accuracy was evaluated. Two linear classifiers were built using the results of conventional and new computer-based tumour area extraction methods. The final diagnostic accuracy was evaluated by drawing the receiver operating curve (ROC) of each classifier, and the area under each ROC was evaluated. The standard deviations of the tumour area extracted by five dermatologists and 10 non-medical individuals were 8.9% and 10.7%, respectively. After assessment of the extraction results by dermatologists, the STA was defined as the area that was selected by more than two dermatologists. Dermatologists selected the melanoma area with statistically smaller divergence than that of Clark naevus or Reed naevus (P = 0.05). By contrast, non-medical individuals did not show this difference. Our new computer-based extraction algorithm showed superior performance (precision, 94.1%; recall, 95.3%) to the conventional thresholding method (precision, 99.5%; recall, 87.6%). These results indicate that our new algorithm extracted a tumour area close to that obtained by dermatologists and, in particular, the border part of the tumour was adequately extracted. With this refinement, the area under the ROC increased from 0.795 to 0.875 and the diagnostic accuracy showed an increase of approximately 20% in specificity when the sensitivity was 80%. It can be concluded that our computer-based tumour extraction algorithm extracted almost the same area as that obtained by dermatologists and provided improved computer-based diagnostic accuracy.\n\n\n"
},
{
"text": "\n63503\nThe laying hen expresses two different low density lipoprotein receptor-related proteins.\n\nStifani, S\n\nBarber, DL\n\nAebersold, R\n\nSteyrer, E\n\nShen, X\n\nNimpf, J\n\nSchneider, WJ\n\nBeiträge in Fachzeitschriften\nISI:A1991GJ47200103\n1918027.0\nNone\nNone\nWe have identified, by a combination of ligand, 45Ca2+, and immunoblotting, two large membrane proteins akin to the mammalian so-called low density lipoprotein (LDL) receptor-related protein (LRP) in chicken tissues. LRP has thus far been demonstrated only in mammalian species where it is thought to act as a receptor for proteinase-alpha 2-macroglobulin complexes and/or chylomicron remnants, lipoproteins not produced in birds. One of the chicken LRPs was demonstrated in liver, and has the same apparent Mr and hallmark biochemical properties as rat liver LRP. The other chicken LRP is smaller (approximately 380 kDa) and is expressed in ovarian follicles, but is undetectable in liver. Immunological analysis demonstrated a lack of cross-reactivity between the two LRPs, as well as between them and the previously identified chicken oocyte-specific 95-kDa receptor for the yolk precursors, very low density lipoprotein, and vitellogenin (Stifani, S., Barber, D. L., Nimpf, J., and Schneider, W. J. (1989) Proc. Natl. Acad. Sci. U.S.A. 87, 1955-1959). As shown by ligand blotting, both chicken LRPs have the ability to interact with vitellogenin, a property they share not only with rat LRP, but also with mammalian LDL receptors. To obtain independent confirmation of the ligand blotting results, the smaller (follicular) LRP was purified and high-affinity binding of vitellogenin to it was demonstrated by a solid-phase filtration binding assay. Amino acid sequences of tryptic fragments of the smaller LRP were obtained, and its homology with human LRP demonstrated through unambiguous alignment of three fragments. Both chicken LRPs, the chicken oocyte 95-kDa receptor, as well as rat LRP, could be shown by ligand blotting to interact specifically with chicken serum alpha 2-macroglobulin. In addition, human apolipoprotein E, a ligand implicated in receptor-mediated metabolism of chylomicron remnants, also binds to the smaller chicken LRP, further emphasizing the similarities between LDL receptors and related proteins from a variety of species. In analogy to the known dichotomy of chicken LDL receptors, which is characterized by the production of the 95-kDa oocyte-specific receptor on one hand and a 130-kDa LDL receptor that is exclusively expressed in somatic cells (Hayashi, K., Nimpf, J., and Schneider, W. J. (1989) J. Biol. Chem. 264, 3131-3139), it appears that the smaller and larger chicken LRPs also may be restricted to the oocyte and somatic cells, respectively.\n\nSteyrer, Ernst\n\n\n"
},
{
"text": "\n112772\nDesign and development of a mobile computer application to reengineer workflows in the hospital and the methodology to evaluate its effectiveness.\n\nHolzinger, A\n\nKosec, P\n\nSchwantzer, G\n\nDebevc, M\n\nHofmann-Wellenhof, R\n\nFrühauf, J\n\nBeiträge in Fachzeitschriften\nISI:000297904700007\n21854873.0\n10.1016/j.jbi.2011.07.003\nNone\nThis paper describes a new method of collecting additional data for the purpose of skin cancer research from the patients in the hospital using the system Mobile Computing in Medicine Graz (MoCoMed-Graz). This system departs from the traditional paper-based questionnaire data collection methods and implements a new composition of evaluation methods to demonstrate its effectiveness. The patients fill out a questionnaire on a Tablet-PC (or iPad Device) and the resulting medical data is integrated into the electronic patient record for display when the patient enters the doctor's examination room. Since the data is now part of the electronic patient record, the doctor can discuss the data together with the patient making corrections or completions where necessary, thus enhancing data quality and patient empowerment. A further advantage is that all questionnaires are in the system at the end of the day - and manual entry is no longer necessary - consequently raising data completeness. The front end was developed using a User Centered Design Process for touch tablet computers and transfers the data in XML to the SAP based enterprise hospital information system. The system was evaluated at the Graz University Hospital - where about 30 outpatients consult the pigmented lesion clinic each day - following Bronfenbrenner's three level perspective: The microlevel, the mesolevel and the macrolevel: On the microlevel, the questions answered by 194 outpatients, evaluated with the System Usability Scale (SUS) resulted in a median of 97.5 (min: 50, max: 100) which showed that it is easy to use. On the mesolevel, the time spent by medical doctors was measured before and after the implementation of the system; the medical task performance time of 20 doctors (age median 43 (min: 29; max: 50)) showed a reduction of 90%. On the macrolevel, a cost model was developed to show how much money can be saved by the hospital management. This showed that, for an average of 30 patients per day, on a 250 day basis per year in this single clinic, the hospital management can save up to 40, 00 EUR per annum, proving that mobile computers can successfully contribute to workflow optimization. Copyright © 2011 Elsevier Inc. All rights reserved.\n\nHofmann-Wellenhof, Rainer\n\nHolzinger, Andreas\n\nSchwantzer, Gerold\n\n\n"
},
{
"text": "\n165747\nEuropean academy of dermatology and venereology European prurigo project: expert consensus on the definition, classification and terminology of chronic prurigo.\n\nPereira, MP\n\nSteinke, S\n\nZeidler, C\n\nForner, C\n\nRiepe, C\n\nAugustin, M\n\nBobko, S\n\nDalgard, F\n\nElberling, J\n\nGarcovich, S\n\nGieler, U\n\nGonçalo, M\n\nHalvorsen, JA\n\nLeslie, TA\n\nMetz, M\n\nReich, A\n\nŞavk, E\n\nSchneider, G\n\nSerra-Baldrich, E\n\nStänder, HF\n\nStreit, M\n\nWallengren, J\n\nWeller, K\n\nWollenberg, A\n\nBruland, P\n\nSoto-Rey, I\n\nStorck, M\n\nDugas, M\n\nWeisshaar, E\n\nSzepietowski, JC\n\nLegat, FJ\n\nStänder, S\n\nEADV Task Force Pruritus group members\n\nBeiträge in Fachzeitschriften\nISI:000436252800035\n28857299.0\n10.1111/jdv.14570\nNone\nThe term prurigo has been used for many decades in dermatology without clear definition, and currently used terminology of prurigo is inconsistent and confusing. Especially, itch-related prurigo remains unexplored regarding the epidemiology, clinical profile, natural course, underlying causes, available treatments and economic burden, although burdensome and difficult to treat.\n To address these issues, the multicentre European Prurigo Project (EPP) was designed to increase knowledge on chronic prurigo (CPG). In the first step, European experts of the EADV Task Force Pruritus (TFP) aimed to achieve a consensus on the definition, classification and terminology of CPG. Additionally, procedures of the cross-sectional EPP were discussed and agreed upon.\n Discussions and surveys between members of the TFP served as basis for a consensus conference. Using the Delphi method, consensus was defined as an agreement ≥75% among the present members.\n Twenty-four members of the TFP participated in the consensus conference. Experts consented that CPG should be used as an umbrella term for the range of clinical manifestations (e.g. papular, nodular, plaque or umbilicated types). CPG is considered a distinct disease defined by the presence of chronic pruritus for ≥6 weeks, history and/or signs of repeated scratching and multiple localized/generalized pruriginous skin lesions (whitish or pink papules, nodules and/or plaques). CPG occurs due to a neuronal sensitization to itch and the development of an itch-scratch cycle.\n This new definition and terminology of CPG should be implemented in dermatology to harmonize communication in the clinical routine, clinical trials and scientific literature. Acute/subacute forms of prurigo are separated entities, which need to be differentiated from CPG and will be discussed in a next step. In the near future, the cross-sectional EPP will provide relevant clinical data on various aspects of CPG leading to new directions in the scientific investigation of CGP.\n © 2017 European Academy of Dermatology and Venereology.\n\nLegat, Franz\n\n\n"
},
{
"text": "\n90735\nOxidative stress and epididymal sperm transport, motility and morphological defects.\n\nEl-Taieb, MA\n\nHerwig, R\n\nNada, EA\n\nGreilberger, J\n\nMarberger, M\n\nBeiträge in Fachzeitschriften\nISI:000265518400031\n19297071.0\n10.1016/j.ejogrb.2009.02.018\nNone\nObjectives: Radical oxidative species (ROS) have an important effect on sperm quality and quantity. Oxidative stress (OS) occurs when production of potentially destructive reactive oxygen species (ROS) exceeds the body's own natural antioxidant defenses, resulting in cellular damage. OS is a common pathology seen in approximately half of all infertile men. Increased ROS generation and reduced antioxidant capacity is negatively correlated with sperm concentration and motility in infertile men. For the first time, we used a more stable and reliable sensitive carbonyl protein (CP) detection method to determine ROS in seminal plasma than measuring ROS directly to clarify the effect of OS on spermatozoa in terms of protein dysfunction. This is the first report to measure CP in seminal plasma as an indicator of OS. Furthermore, for the first time we correlated the results of CP measurement with light microscopy in combination with ultrastructural analysis by electron microscopy. Material and Methods: 20 patients with idiopathic oligoasthenoteratozoospermia (iOAT) and 10 fertile controls were enrolled in this study. CP values were measured by enzyme-linked immuno sorbent assay (ELISA) to detect the level of OS. Transmission electron microscope (TEM) was used to detect axonemal anomalies. Results: Compared to fertile controls, statistically highly significant higher degrees of abnormal sperm parameters (P < 0.001) could be found in iOAT patients. CP values were highly significantly elevated in iOAT patients than in normal controls (P < 0.001). A statistically highly significant difference in different axonemal anomalies were found between iOAT patients and normal controls (P < 0.001). CP values have been found to be positively correlated with different axonemal anomalies (absence of axoneme (r(2) = 0.841), missing of central singlet tubules (r(2) = 0.702) and missing of outer doublet tubules (r(2) = 0.869). A statistically negative correlation were found between different axonemal anomalies (absent axoneme (r(2) = -0.780), missing of central singlet tubules (r(2) = -0.611), and missing of outer doublet tubules (r(2) = -0.738) and forward progressive sperm motility. Conclusion: High levels of CP can be measured in iOAT patients, indicating that OS could underlie the aetipopathogenesis of the syndrome. OS negatively affects flagellar axonemal structure with subsequent impairment of forward progressive sperm motility. This can put an attention for antioxidants as a therapy for iOAT syndrome and further research to find how to decrease ROS production. (C) 2009 Elsevier Ireland Ltd. All rights reserved.\n\nGreilberger, Joachim\n\n\n"
},
{
"text": "\n140775\nInfluence of Acute Normobaric Hypoxia on Physiological Variables and Lactate Turn Point Determination in Trained Men\n\nOfner, M\n\nWonisch, M\n\nFrei, M\n\nTschakert, G\n\nDomej, W\n\nKropfl, JM\n\nHofmann, P\n\nBeiträge in Fachzeitschriften\nISI:000345121400008\nNone\nNone\nNone\nThe goal of this study is to evaluate the response of physiological variables to acute normobaric hypoxia compared to normoxia and its influence on the lactate turn point determination according to the three-phase model of energy supply (Phase I: metabolically balanced at muscular level; Phase II: metabolically balanced at systemic level; Phase III: not metabolically balanced) during maximal incremental exercise. Ten physically active (VO(2)max 3.9 [0.49] l.min(-1)), healthy men (mean age [SD]: 25.3 [4.6] yrs.), participated in the study. All participants performed two maximal cycle ergometric exercise tests under normoxic as well as hypoxic conditions (FiO(2) = 14%). Blood lactate concentration, heart rate, gas exchange data, and power output at maximum and the first and the second lactate turn point (LTP1, LTP2), the heart rate turn point (HRTP) and the first and the second ventilatory turn point (VETP1, VETP2) were determined. Since in normobaric hypoxia absolute power output (P) was reduced at all reference points (max: 314 / 274 W; LTP2: 218 / 184 W; LTP1: 110 / 96 W), as well as VO2max (max: 3.90 / 3.23 l.min(-1); LTP2: 2.90 / 2.43 l.min(-1); LTP1: 1.66 / 1.52 l.min(-1)), percentages of P-max at LTP1, LTP2, HRTP and VETP1, VETP2 were almost identical for hypoxic as well as normoxic conditions. Heart rate was significantly reduced at P-max in hypoxia (max: 190 / 185 bpm), but no significant differences were found at submaximal control points. Blood lactate concentration was not different at maximum, and all reference points in both conditions. Respiratory exchange ratio (RER) (max: 1.28 / 1.08; LTP2: 1.13 / 0.98) and ventilatory equivalents for O-2 (max: 43.4 / 34.0; LTP2: 32.1 / 25.4) and CO2 (max: 34.1 / 31.6; LTP2: 29.1 / 26.1) were significantly higher at some reference points in hypoxia. Significant correlations were found between LTP1 and VETP1 (r = 0.778; p < 0.01), LTP2 and HRTP (r = 0.828; p < 0.01) and VETP2 (r = 0.948; p < 0.01) for power output for both conditions. We conclude that the lactate turn point determination according to the three-phase-model of energy supply is valid in normobaric, normoxic as well as hypoxic conditions. The turn points for La, HR, and V-E were reproducible among both conditions, but shifted left to lower workloads. The lactate turn point determination may therefore be used for the prescription of exercise performance in both environments.\n\nDomej, Wolfgang\n\n\n"
},
{
"text": "\n153938\nImpact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation.\n\nStyczynski, J\n\nTridello, G\n\nGil, L\n\nLjungman, P\n\nHoek, J\n\nIacobelli, S\n\nWard, KN\n\nCordonnier, C\n\nEinsele, H\n\nSocie, G\n\nMilpied, N\n\nVeelken, H\n\nChevallier, P\n\nYakoub-Agha, I\n\nMaertens, J\n\nBlaise, D\n\nCornelissen, J\n\nMichallet, M\n\nDaguindau, E\n\nPetersen, E\n\nPassweg, J\n\nGreinix, H\n\nDuarte, RF\n\nKröger, N\n\nDreger, P\n\nMohty, M\n\nNagler, A\n\nCesaro, S\n\nBeiträge in Fachzeitschriften\nISI:000378647000004\n27091716.0\n10.1200/JCO.2015.64.2405\nNone\nWe investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT).\n The study included 11, 64 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT.\n Patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors (hazard ratio [HR], 1.05; 95% CI, 0.97 to 1.12; P = .23). Seropositive donors also had no influence on relapse-free survival (HR, 1.04; 95% CI, 0.97 to 1.11; P = 0.31), relapse incidence (HR, 1.03; 95% CI, 0.94 to 1.12; P = .58), and nonrelapse mortality (HR, 1.05; 95% CI, 0.94 to 1.17; P = .37). However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P < .001; HR, 1.42; 95% CI, 1.30 to 1.56). When adjusting for confounders, higher risk was identified for both acute and chronic GVHD. In seronegative patients with seropositive donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P < .001) for chronic GVHD. Seropositive patients with seronegative donors did not have an increased risk of GVHD.\n Our data suggest that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT.\n © 2016 by American Society of Clinical Oncology.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n154991\nGenomic aberrations in spitzoid melanocytic tumours and their implications for diagnosis, prognosis and therapy.\n\nWiesner, T\n\nKutzner, H\n\nCerroni, L\n\nMihm, MC\n\nBusam, KJ\n\nMurali, R\n\nBeiträge in Fachzeitschriften\nISI:000383317900003\n27020384.0\n10.1016/j.pathol.2015.12.007\nPMC4817351\nHistopathological evaluation of melanocytic tumours usually allows reliable distinction of benign melanocytic naevi from melanoma. More difficult is the histopathological classification of Spitz tumours, a heterogeneous group of tumours composed of large epithelioid or spindle-shaped melanocytes. Spitz tumours are biologically distinct from conventional melanocytic naevi and melanoma, as exemplified by their distinct patterns of genetic aberrations. Whereas common acquired naevi and melanoma often harbour BRAF mutations, NRAS mutations, or inactivation of NF1, Spitz tumours show HRAS mutations, inactivation of BAP1 (often combined with BRAF mutations), or genomic rearrangements involving the kinases ALK, ROS1, NTRK1, BRAF, RET, and MET. In Spitz naevi, which lack significant histological atypia, all of these mitogenic driver aberrations trigger rapid cell proliferation, but after an initial growth phase, various tumour suppressive mechanisms stably block further growth. In some tumours, additional genomic aberrations may abrogate various tumour suppressive mechanisms, such as cell-cycle arrest, telomere shortening, or DNA damage response. The melanocytes then start to grow in a less organised fashion and may spread to regional lymph nodes, and are termed atypical Spitz tumours. Upon acquisition of even more aberrations, which often activate additional oncogenic pathways or alter cell differentiation, the neoplastic cells become entirely malignant and may colonise and take over distant organs (spitzoid melanoma). The sequential acquisition of genomic aberrations suggests that Spitz tumours represent a continuous biological spectrum, rather than a dichotomy of benign versus malignant, and that tumours with ambiguous histological features (atypical Spitz tumours) might be best classified as low-grade melanocytic tumours. The number of genetic aberrations usually correlates with the degree of histological atypia and explains why existing ancillary genetic techniques, such as array comparative genomic hybridisation (CGH) or fluorescence in situ hybridisation (FISH), are usually capable of accurately classifying histologically benign and malignant Spitz tumours, but are not very helpful in the diagnosis of ambiguous melanocytic lesions. Nevertheless, we expect that progress in our understanding of tumour progression will refine the classification of spitzoid melanocytic tumours in the near future. By integrating clinical, pathological, and genetic criteria, distinct tumour subsets will be defined within the heterogeneous group of Spitz tumours, which will eventually lead to improvements in diagnosis, prognosis and therapy. \n Copyright © 2015 The Royal College of Pathologists of Australasia. All rights reserved.\n\nCerroni, Lorenzo\n\n\n"
},
{
"text": "\n162465\nAcute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study.\n\nAzoulay, E\n\nPickkers, P\n\nSoares, M\n\nPerner, A\n\nRello, J\n\nBauer, PR\n\nvan de Louw, A\n\nHemelaar, P\n\nLemiale, V\n\nTaccone, FS\n\nMartin Loeches, I\n\nMeyhoff, TS\n\nSalluh, J\n\nSchellongowski, P\n\nRusinova, K\n\nTerzi, N\n\nMehta, S\n\nAntonelli, M\n\nKouatchet, A\n\nBarratt-Due, A\n\nValkonen, M\n\nLandburg, PP\n\nBruneel, F\n\nBukan, RB\n\nPène, F\n\nMetaxa, V\n\nMoreau, AS\n\nSouppart, V\n\nBurghi, G\n\nGirault, C\n\nSilva, UVA\n\nMontini, L\n\nBarbier, F\n\nNielsen, LB\n\nGaborit, B\n\nMokart, D\n\nChevret, S\n\nEfraim investigators and the Nine-I study group\n\nBeiträge in Fachzeitschriften\nISI:000417152700005\n28948369.0\n10.1007/s00134-017-4947-1\nNone\nIn immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV).\n To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers).\n A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86-0.99), day-1 SOFA (1.09/point, 1.06-1.13), day-1 PaO2/FiO2 (1.47, 1.05-2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42-3.14), invasive pulmonary aspergillosis (1.85, 1.21-2.85), and undetermined cause (1.46, 1.09-1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59-1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09-1.27), direct admission to the ICU (0.69, 0.54-0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08-1.16), PaO2/FiO2 < 100 (1.60, 1.03-2.48), and undetermined ARF etiology (1.43, 1.04-1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09-4.91), first-line IMV (2.55, 1.94-3.29), NIV failure (3.65, 2.05-6.53), standard oxygen failure (4.16, 2.91-5.93), and HFNC failure (5.54, 3.27-9.38).\n HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.\n\nAmrein, Karin\n\n\n"
},
{
"text": "\n173818\nNovel role of extracellular matrix protein 1 (ECM1) in cardiac aging and myocardial infarction.\n\nHardy, SA\n\nMabotuwana, NS\n\nMurtha, LA\n\nCoulter, B\n\nSanchez-Bezanilla, S\n\nAl-Omary, MS\n\nSenanayake, T\n\nLoering, S\n\nStarkey, M\n\nLee, RJ\n\nRainer, PP\n\nHansbro, PM\n\nBoyle, AJ\n\nBeiträge in Fachzeitschriften\nISI:000459330800021\n30789914.0\n10.1371/journal.pone.0212230\nPMC6383988\nThe prevalence of heart failure increases in the aging population and following myocardial infarction (MI), yet the extracellular matrix (ECM) remodeling underpinning the development of aging- and MI-associated cardiac fibrosis remains poorly understood. A link between inflammation and fibrosis in the heart has long been appreciated, but has mechanistically remained undefined. We investigated the expression of a novel protein, extracellular matrix protein 1 (ECM1) in the aging and infarcted heart.\n Young adult (3-month old) and aging (18-month old) C57BL/6 mice were assessed. Young mice were subjected to left anterior descending artery-ligation to induce MI, or transverse aortic constriction (TAC) surgery to induce pressure-overload cardiomyopathy. Left ventricle (LV) tissue was collected early and late post-MI/TAC. Bone marrow cells (BMCs) were isolated from young healthy mice, and subject to flow cytometry. Human cardiac fibroblast (CFb), myocyte, and coronary artery endothelial & smooth muscle cell lines were cultured; human CFbs were treated with recombinant ECM1. Primary mouse CFbs were cultured and treated with recombinant angiotensin-II or TGF-β1. Immunoblotting, qPCR and mRNA fluorescent in-situ hybridization (mRNA-FISH) were conducted on LV tissue and cells.\n ECM1 expression was upregulated in the aging LV, and in the infarct zone of the LV early post-MI. No significant differences in ECM1 expression were found late post-MI or at any time-point post-TAC. ECM1 was not expressed in any resident cardiac cells, but ECM1 was highly expressed in BMCs, with high ECM1 expression in granulocytes. Flow cytometry of bone marrow revealed ECM1 expression in large granular leucocytes. mRNA-FISH revealed that ECM1 was indeed expressed by inflammatory cells in the infarct zone at day-3 post-MI. ECM1 stimulation of CFbs induced ERK1/2 and AKT activation and collagen-I expression, suggesting a pro-fibrotic role.\n ECM1 expression is increased in ageing and infarcted hearts but is not expressed by resident cardiac cells. Instead it is expressed by bone marrow-derived granulocytes. ECM1 is sufficient to induce cardiac fibroblast stimulation in vitro. Our findings suggest ECM1 is released from infiltrating inflammatory cells, which leads to cardiac fibroblast stimulation and fibrosis in aging and MI. ECM1 may be a novel intermediary between inflammation and fibrosis.\n\nRainer, Peter\n\n\n"
},
{
"text": "\n184796\nSafety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial.\n\nFrey, BM\n\nBoutitie, F\n\nCheng, B\n\nCho, TH\n\nEbinger, M\n\nEndres, M\n\nFiebach, JB\n\nFiehler, J\n\nFord, I\n\nGalinovic, I\n\nKönigsberg, A\n\nPuig, J\n\nRoy, P\n\nWouters, A\n\nMagnus, T\n\nThijs, V\n\nLemmens, R\n\nMuir, KW\n\nNighoghossian, N\n\nPedraza, S\n\nSimonsen, CZ\n\nGerloff, C\n\nThomalla, G\n\nWAKE-UP investigators\n\nBeiträge in Fachzeitschriften\nNone\n33324940.0\n10.1186/s42466-020-00087-9\nPMC7678217\nOne quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial.\n WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0-1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase.\n Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years, p < 0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%, p = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome (p = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047-4.236).\n Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.\n © The Author(s) 2020.\n\nFandler-Höfler, Simon\n\nFazekas, Franz\n\nGattringer, Thomas\n\nPichler, Alexander\n\n\n"
},
{
"text": "\n6267\nIncidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS).\n\nFelsenberg, D\n\nSilman, AJ\n\nLunt, M\n\nArmbrecht, G\n\nIsmail, AA\n\nFinn, JD\n\nCockerill, WC\n\nBanzer, D\n\nBenevolenskaya, LI\n\nBhalla, A\n\nBruges, AJ\n\nCannata, JB\n\nCooper, C\n\nDequeker, J\n\nEastell, R\n\nFelsch, B\n\nGowin, W\n\nHavelka, S\n\nHoszowski, K\n\nJajic, I\n\nJanott, J\n\nJohnell, O\n\nKanis, JA\n\nKragl, G\n\nLopes, VA\n\nLorenc, R\n\nLyritis, G\n\nMasaryk, P\n\nMatthis, C\n\nMiazgowski, T\n\nParisi, G\n\nPoor ,G\n\nRaspe, HH\n\nReid, DM\n\nReisinger, W\n\nScheidt-Nave, C\n\nStepan, JJ\n\nTodd, CJ\n\nWeber, K\n\nWoolf ,AD\n\nYershova, OB\n\nReeve, J\n\nO'Neill, TW\r\n\n\nBeiträge in Fachzeitschriften\nISI:000174436200020\nNone\nNone\nNone\nVertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14, 11 men and women aged 50 years and over were recruited from population-based registers in 29 European centers and had an interviewer-administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films-plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey-Kanis method) in the follow-up film. There were 3174 men, mean age 63.1 years, and 3614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1000 person years (pyr) in women and 5.7/1000 pyr in men. The age-standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar-12.1/1000 pyr and 6.8/1000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population-based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n65923\nThe effect of anastrozole on the single-dose pharmacokinetics and anticoagulant activity of warfarin in healthy volunteers.\n\nYates, RA\n\nWong, J\n\nSeiberling, M\n\nMerz, M\n\nMärz, W\n\nNauck, M\n\nBeiträge in Fachzeitschriften\nISI:000168979400006\n11422000.0\n10.1046/j.1365-2125.2001.01358.x\nPMC2014464\nAIMS: The aims of this study were to determine the effects of the nonsteroidal, selective aromatase inhibitor, anastrozole, at steady-state concentrations, on the pharmacokinetics and pharmacodynamics of warfarin, and to assess whether or not anastrozole alone has any anticoagulant activity. METHODS: This was a randomized, double-blind, placebo-controlled, two-way crossover trial conducted at a single centre. The study comprised two treatment periods of 11 days, separated by a 3 week washout. Healthy male volunteers (n = 16, median age 28.5 years) were randomized to receive either anastrozole (7 mg loading dose on day 1, followed by 1 mg daily on days 2-11) in the first treatment period and placebo in the second treatment period, or vice versa. In addition to their randomized treatment, all volunteers received a single dose of 25 mg warfarin on day 3 of each treatment period. Blood samples for pharmacokinetic and pharmacodynamic assessment were taken at frequent intervals during each treatment period. The safety of volunteers was monitored throughout the study. RESULTS: Administration of anastrozole resulted in no clinically significant changes in the pharmacokinetics of either R- or S-warfarin compared with placebo for AUC (ng ml-1 h) (glsmean, R-warfarin; anastrozole 93619.9, placebo 91127.91, 95%CI 0.988-1.068; S-warfarin; anastrozole 57129.21, placebo 55676.34, 95%CI 0.979-1.076), CL/F (ml min-1) (glsmean, R-warfarin; anastrozole 2.23, placebo 2.29, 95%CI 0.937-1.012; S-warfarin; anastrozole 3.65, placebo 3.74, 95%CI 0.929-1.021) and t1/2 (h) (lsmean, R-warfarin; anastrozole 55.40, placebo 55.15, 95%CI-2.083-2.592; S-warfarin; anastrozole 39.38, placebo 40.98, 95%CI-6.189-2.996). In addition, anastrozole had no clinically significant effect on the pharmacodynamic effects of warfarin, as assessed 240 h after warfarin dosing by measurement of prothrombin time (s) (glsmean, anastrozole 11.56, placebo 11.31, 95%CI 0.987-1.059), thrombin time (s) (glsmean, anastrozole 19.06, placebo 18.75, 95%CI 0.980-1.054) activated partial thromboplastin time (s) (glsmean, anastrozole 29.94, placebo 29.74, 95%CI 0.968-1.047) and factor VII (%) (glsmean, anastrozole 97.81, placebo 107.26, 95%CI 0.821-1.012). Anastrozole alone had no effect on these indicators of the clotting process. CONCLUSIONS: Overall, there was no evidence to suggest that anastrozole has any clinically relevant effects on the pharmacokinetics of warfarin. Anastrozole had no effect on clotting mechanisms or on the pharmacodynamic activity of warfarin, as assessed by prothrombin time, thrombin time, activated partial thromboplastin time, and factor VII.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n67206\nDermoscopy report: proposal for standardization. Results of a consensus meeting of the International Dermoscopy Society.\n\nMalvehy, J\n\nPuig, S\n\nArgenziano, G\n\nMarghoob, AA\n\nSoyer, HP\n\nInternational Dermoscopy Society Board members\n\nBeiträge in Fachzeitschriften\nISI:000247577500010\n17482314.0\n10.1016/j.jaad.2006.02.051\nNone\nBACKGROUND: Dermoscopy can assist clinicians in the evaluation and diagnosis of skin tumors. Since dermoscopy is becoming widely accepted and used in the medical community, there is now the need for a standardized method for documenting dermoscopic findings so as to be able to effectively communicate such information among colleagues. OBJECTIVES: Toward this end, the International Dermoscopy Society embarked on creating a consensus document for the standardization and recommended criteria necessary to be able to effectively convey dermoscopic findings to consulting physicians and colleagues. METHODS: The Dermoscopy Report Steering Committee created an extensive list of dermoscopic criteria obtained from an exhaustive search of the literature. A preliminary document listing all the dermoscopic criteria that could potentially be included in a standardized dermoscopy report was elaborated and presented to the members of the International Dermoscopy Society Board in two meetings of the Society and subsequently discussed via Internet communications between members and the Steering Committee. RESULTS: A consensus document including 10 points categorized as either recommended or optional and a template of the dermoscopy report were obtained. The final items included in the document are as follows: (1) patient's age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); (2) clinical description of the lesion (recommended); (3) the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); (4) the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003. For new terms it would be helpful to provide a working definition (recommended); (5) the dermoscopic algorithm used should be mentioned (optional); (6) information on the imaging equipment and magnification (recommended); (7) clinical and dermoscopic images of the tumor (recommended); (8) a diagnosis or differential diagnosis (recommended); (9) decision concerning the management (recommended); (10) specific comments for the pathologist when excision and histopathologic examination are recommended (optional). LIMITATIONS: The limitations of this study are those that are intrinsic of a consensus document obtained from critical review of the literature and discussion by opinion leaders in the field. CONCLUSIONS: Although it may be acceptable for a consulting physician to only state the dermoscopic diagnosis, the proposed standardized reporting system, if accepted and utilized, will make it easier for consultants to communicate with each other more effectively.\n\nZalaudek, Iris\n\n\n"
},
{
"text": "\n118813\nLong-term outcomes of web creep, scar quality, and function after simple syndactyly surgical treatment.\n\nLumenta, DB\n\nKitzinger, HB\n\nBeck, H\n\nFrey, M\n\nBeiträge in Fachzeitschriften\nISI:000280822800016\n20638200.0\n10.1016/j.jhsa.2010.04.033\nNone\nPURPOSE: Syndactyly is the second most common congenital malformation of the hand, and reports of the incidence of web creep after surgery vary. To evaluate our outcomes of simple syndactyly surgical release, we conducted a retrospective analysis of patients treated between January 1965 and December 2007. METHODS: After matching for inclusion criteria, we recruited 19 patients with 26 affected web spaces for clinical examination. Outcomes evaluation included grading of web creep, Vancouver Scar Scale, assessment of complications and subjective patient analysis, range of motion, degree of finger abduction, power, and 2-point discrimination. Mean age at follow-up was 18 years (range, 6-50 y), with a mean age of 4.4 years (range, 7 mo to 15 y) at surgery and mean follow-up of 11.5 years (range, 5-35 y). Surgical management consisted of palmar and dorsal triangular skin flaps for creation of the new commissure, and multiple zigzag incisions for separation of digits. For tension-free closure, full-thickness skin grafts were harvested as needed. RESULTS: We observed web creep up to the proximal third of the distance between palmar metacarpophalangeal and proximal interphalangeal joint crease in 2 web spaces. All other web spaces had either a soft web equivalent to the contralateral (unaffected) side (n = 13) or no web advancement with thickening of the interdigital space (n = 11). The scar quality as assessed with the Vancouver Scar Scale revealed a height below 2 mm in 24 of 26 web spaces, with close to normal to supple pliability in 20 of 26 web spaces. There were no considerable differences for range of motion, degree of finger abduction, power, or 2-point discrimination between the affected and unaffected sides. In 17 of 24 cases in which full-thickness skin grafts from the groin region were used, patients reported commissural hair growth in the grafted region. CONCLUSIONS: Evaluation of the long-term outcomes of surgical treatment for simple syndactyly at our institution demonstrated a low incidence of web creep. When choosing the groin as a donor area for full thickness skin grafts, we recommend harvesting from the lateral third of the inguinal crease, to avoid esthetic compromise associated with the beginning of hair growth in puberty. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. Copyright 2010 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.\n\nLumenta, David Benjamin\n\n\n"
},
{
"text": "\n162556\nIs a motivational interviewing based lifestyle intervention for obese pregnant women across Europe implemented as planned? Process evaluation of the DALI study.\n\nJelsma, JGM\n\nSimmons, D\n\nGobat, N\n\nRollnick, S\n\nBlumska, K\n\nJans, G\n\nGaljaard, S\n\nDesoye, G\n\nCorcoy, R\n\nJuarez, F\n\nKautzky-Willer, A\n\nHarreiter, J\n\nvan Assche, A\n\nDevlieger, R\n\nTimmerman, D\n\nHill, D\n\nDamm, P\n\nMathiesen, ER\n\nWender-Ożegowska, E\n\nZawiejska, A\n\nLapolla, A\n\nDalfrà, MG\n\nDel Prato, S\n\nBertolotto, A\n\nDunne, F\n\nJensen, DM\n\nAndersen, L\n\nSnoek, FJ\n\nvan Poppel, MNM\n\nBeiträge in Fachzeitschriften\nISI:000409558800002\n28882133.0\n10.1186/s12884-017-1471-9\nPMC5590191\nProcess evaluation is an essential part of designing and assessing complex interventions. The vitamin D and lifestyle intervention study (DALI) study is testing different strategies to prevent development of gestational diabetes mellitus among European obese pregnant women with a body mass index ≥29 kg/m2. The intervention includes guidance on physical activity and/or healthy eating by a lifestyle coach trained in motivational interviewing (MI). The aim of this study was to assess the process elements: reach, dose delivered, fidelity and satisfaction and to investigate whether these process elements were associated with changes in gestational weight gain (GWG).\n Data on reach, dose delivered, fidelity, and satisfaction among 144 participants were collected. Weekly recruitment reports, notes from meetings, coach logs and evaluation questionnaires (n = 110) were consulted. Fidelity of eight (out of twelve) lifestyle coach practitioners was assessed by analysing audio recorded counselling sessions using the MI treatment integrity scale. Furthermore, associations between process elements and GWG were assessed with linear regression analyses.\n A total of 20% of the possible study population (reach) was included in this analysis. On average 4.0 (of the intended 5) face-to-face sessions were delivered. Mean MI fidelity almost reached 'expert opinion' threshold for the global scores, but was below 'beginning proficiency' for the behavioural counts. High variability in quality of MI between practitioners was identified. Participants were highly satisfied with the intervention, the lifestyle coach and the intervention materials. No significant associations were found between process elements and GWG.\n Overall, the intervention was well delivered and received by the study population, but did not comply with all the principles of MI. Ensuring audio recording of lifestyle sessions throughout the study would facilitate provision of individualized feedback to improve MI skills. A larger sample size is needed to confirm the lack of association between process elements and GWG.\n ISRCTN registry: ISRCTN70595832 ; Registered 12 December 2011.\n\nDesoye, Gernot\n\n\n"
},
{
"text": "\n181667\nComprehensive Molecular and Pathologic Evaluation of Transitional Mesothelioma Assisted by Deep Learning Approach: A Multi-Institutional Study of the International Mesothelioma Panel from the MESOPATH Reference Center.\n\nGalateau Salle, F\n\nLe Stang, N\n\nTirode, F\n\nCourtiol, P\n\nNicholson, AG\n\nTsao, MS\n\nTazelaar, HD\n\nChurg, A\n\nDacic, S\n\nRoggli, V\n\nPissaloux, D\n\nMaussion, C\n\nMoarii, M\n\nBeasley, MB\n\nBegueret, H\n\nChapel, DB\n\nCopin, MC\n\nGibbs, AR\n\nKlebe, S\n\nLantuejoul, S\n\nNabeshima, K\n\nVignaud, JM\n\nAttanoos, R\n\nBrcic, L\n\nCapron, F\n\nChirieac, LR\n\nDamiola, F\n\nSequeiros, R\n\nCazes, A\n\nDamotte, D\n\nFoulet, A\n\nGiusiano-Courcambeck, S\n\nHiroshima, K\n\nHofman, V\n\nHusain, AN\n\nKerr, K\n\nMarchevsky, A\n\nPaindavoine, S\n\nPicquenot, JM\n\nRouquette, I\n\nSagan, C\n\nSauter, J\n\nThivolet, F\n\nBrevet, M\n\nRouvier, P\n\nTravis, WD\n\nPlanchard, G\n\nWeynand, B\n\nClozel, T\n\nWainrib, G\n\nFernandez-Cuesta, L\n\nPairon, JC\n\nRusch, V\n\nGirard, N\n\nBeiträge in Fachzeitschriften\nISI:000550011000017\n32165206.0\n10.1016/j.jtho.2020.01.025\nNone\nHistologic subtypes of malignant pleural mesothelioma are a major prognostic indicator and decision denominator for all therapeutic strategies. In an ambiguous case, a rare transitional mesothelioma (TM) pattern may be diagnosed by pathologists either as epithelioid mesothelioma (EM), biphasic mesothelioma (BM), or sarcomatoid mesothelioma (SM). This study aimed to better characterize the TM subtype from a histological, immunohistochemical, and molecular standpoint. Deep learning of pathologic slides was applied to this cohort.\n A random selection of 49 representative digitalized sections from surgical biopsies of TM was reviewed by 16 panelists. We evaluated BAP1 expression and CDKN2A (p16) homozygous deletion. We conducted a comprehensive, integrated, transcriptomic analysis. An unsupervised deep learning algorithm was trained to classify tumors.\n The 16 panelists recorded 784 diagnoses on the 49 cases. Even though a Kappa value of 0.42 is moderate, the presence of a TM component was diagnosed in 51%. In 49% of the histological evaluation, the reviewers classified the lesion as EM in 53%, SM in 33%, or BM in 14%. Median survival was 6.7 months. Loss of BAP1 observed in 44% was less frequent in TM than in EM and BM. p16 homozygous deletion was higher in TM (73%), followed by BM (63%) and SM (46%). RNA sequencing unsupervised clustering analysis revealed that TM grouped together and were closer to SM than to EM. Deep learning analysis achieved 94% accuracy for TM identification.\n These results revealed that the TM pattern should be classified as non-EM or at minimum as a subgroup of the SM type.\n Copyright © 2020. Published by Elsevier Inc.\n\nBrcic, Luka\n\n\n"
},
{
"text": "\n185308\nPerinatal Outcomes of Subjects Enrolled in a Multicenter Trial with a Waiver of Antenatal Consent.\n\nKatheria, AC\n\nAllman, P\n\nSzychowski, JM\n\nEssers, J\n\nCarlo, WA\n\nSchmölzer, GM\n\nDempsey, E\n\nYanowitz, T\n\nKaempf, J\n\nVora, F\n\nBhat, S\n\nArnell, K\n\nRich, W\n\nVarner, M\n\nBeiträge in Fachzeitschriften\nNone\n33142340.0\n10.1055/s-0040-1719184\nNone\nThis study aimed to determine whether outcomes differed between infants enrolled in the PREMOD2 trial and those otherwise eligible but not enrolled, and whether the use of waiver effected these differences.\n The multicenter PREMOD2 (PREmature infants receiving Milking Or Delayed cord clamping) trial was approved for waiver of antenatal consent by six of the nine sites institutional review boards, while three sites exclusively used antenatal consent. Every randomized subject delivered at a site with a waiver of consent was approached for postnatal consent to allow for data collection. Four of those six sites' IRBs required the study team to attempt antenatal consent when possible. Three sites exclusively used antenatal consent.\n Enrolled subjects had higher Apgar scores, less use of positive pressure ventilation, a lower rate of bronchopulmonary dysplasia, and a less frequent occurrence of the combined outcome of severe intraventricular hemorrhage or death. A significantly greater number of infants were enrolled at sites with an option of waiver of consent (66 vs. 26%, risk ratio = 2.54, p < 0.001). At sites with an option of either approaching families before delivery or after delivery with a waiver of antenatal consent, those approached prior to delivery refused consent 40% (range 15-74% across six sites) of the time.\n PREMOD2 trial demonstrated analytical validity limitations because of the variable mix of antenatal consent and waiver of consent. A waiver of antenatal consent for minimal risk interventional trials conducted during the intrapartum period will be more successful in enrolling a representative sample of low and high-risk infants if investigators are able to enroll all eligible subjects.\n ClinicalTrials.gov identifier: NCT03019367.\n · Waiver of consent is when informed consent cannot be obtained prior to delivery.. · Cord milking is a procedure in which blood is pushed (stripped) two to four times towards the newborn.. · Delayed clamping means the umbilical cord is not clamped immediately after birth..\n The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).\n\n\n"
},
{
"text": "\n186068\nVitamin D Concentrations at Term Do Not Differ in Newborns and Their Mothers with and without Polycystic Ovary Syndrome.\n\nKollmann, M\n\nObermayer-Pietsch, B\n\nLerchbaum, E\n\nFeigl, S\n\nHochstätter, R\n\nPregartner, G\n\nTrummer, C\n\nKlaritsch, P\n\nBeiträge in Fachzeitschriften\nISI:000615286600001\n33540556.0\n10.3390/jcm10030537\nPMC7867163\nStudies suggest that non-pregnant women with polycystic ovary syndrome (PCOS) may be at elevated risk of 25 hydroxyvitamin D (25(OH)D) deficiency. Furthermore, there is evidence suggesting that 25(OH)D may also play an important role during pregnancy. Data regarding 25(OH)D deficiency during pregnancy in PCOS patients and its association with perinatal outcome is scarce. The aim of the study was to investigate whether mothers with and without PCOS have different 25(OH)D levels at term, how maternal 25(OH)D levels are reflected in their offspring, and if 25(OH)D levels are associated with an adverse perinatal outcome. Therefore, we performed a cross-sectional observational study and included 79 women with PCOS according to the ESHRE/ASRM 2003 definition and 354 women without PCOS and an ongoing pregnancy ≥ 37 + 0 weeks of gestation who gave birth in our institution between March 2013 and December 2015. Maternal serum and cord blood 25(OH)D levels were analyzed at the day of delivery. Maternal 25(OH)D levels did not differ significantly in women with PCOS and without PCOS (p = 0.998), nor did the 25(OH)D levels of their respective offspring (p = 0.692). 25(OH)D deficiency (<20 ng/mL) was found in 26.9% and 22.5% of women with and without PCOS (p = 0.430). There was a strong positive correlation between maternal and neonatal 25(OH)D levels in both investigated groups (r ≥ 0.79, p < 0.001). Linear regression estimates of cord blood 25(OH)D levels are about 77% of serum 25(OH)D concentrations of the mother. Compared to healthy controls, the risk for maternal complications was increased in PCOS women (48% vs. 65%; p = 0.009), while there was no significant difference in neonatal complications (22% and 22%; p = 1.0). However, 25(OH)D levels were similar between mothers and infants with and without perinatal complications. Although the share of women and infants with 25(OH)D deficiency was high in women with PCOS and without PCOS, it seems that the incidence of adverse perinatal outcome was not affected. The long-term consequences for mothers and infants with a 25(OH)D deficiency have to be investigated in future studies.\n\nFeigl, Sarah\n\nHochstätter, Rüdiger\n\nKlaritsch, Philipp\n\nKollmann, Martina\n\nLerchbaum, Elisabeth\n\nObermayer-Pietsch, Barbara\n\nPregartner, Gudrun\n\nTrummer, Christian\n\n\n"
}
]
}