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"text": "\n181734\nGlobal and Regional Development of the Human Cerebral Cortex: Molecular Architecture and Occupational Aptitudes.\n\nShin, J\n\nMa, S\n\nHofer, E\n\nPatel, Y\n\nVosberg, DE\n\nTilley, S\n\nRoshchupkin, GV\n\nSousa, AMM\n\nJian, X\n\nGottesman, R\n\nMosley, TH\n\nFornage, M\n\nSaba, Y\n\nPirpamer, L\n\nSchmidt, R\n\nSchmidt, H\n\nCarrion-Castillo, A\n\nCrivello, F\n\nMazoyer, B\n\nBis, JC\n\nLi, S\n\nYang, Q\n\nLuciano, M\n\nKarama, S\n\nLewis, L\n\nBastin, ME\n\nHarris, MA\n\nWardlaw, JM\n\nDeary, IE\n\nScholz, M\n\nLoeffler, M\n\nWitte, AV\n\nBeyer, F\n\nVillringer, A\n\nArmstrong, NJ\n\nMather, KA\n\nAmes, D\n\nJiang, J\n\nKwok, JB\n\nSchofield, PR\n\nThalamuthu, A\n\nTrollor, JN\n\nWright, MJ\n\nBrodaty, H\n\nWen, W\n\nSachdev, PS\n\nTerzikhan, N\n\nEvans, TE\n\nAdams, HHHH\n\nIkram, MA\n\nFrenzel, S\n\nAuwera-Palitschka, SV\n\nWittfeld, K\n\nBülow, R\n\nGrabe, HJ\n\nTzourio, C\n\nMishra, A\n\nMaingault, S\n\nDebette, S\n\nGillespie, NA\n\nFranz, CE\n\nKremen, WS\n\nDing, L\n\nJahanshad, N\n\nENIGMA Consortium\n\nSestan, N\n\nPausova, Z\n\nSeshadri, S\n\nPaus, T\n\nneuroCHARGE Working Group\n\nBeiträge in Fachzeitschriften\nISI:000574296400019\n32198502.0\n10.1093/cercor/bhaa035\nPMC7947185\nWe have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade-albeit in a very limited manner-to behaviors as complex as the choice of one's occupation.\n © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.\n\nHofer, Edith\n\nPirpamer, Lukas\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n640\nCytochrome P450 mono-oxygenase-regulated signalling of Ca2+ entry in human and bovine endothelial cells.\n\nGraier, WF\n\nSimecek, S\n\nSturek, M\n\nBeiträge in Fachzeitschriften\nISI:A1995QD73200002\n7536247.0\n10.1113/jphysiol.1995.sp020515\nPMC1157726\n1. We tested the hypothesis that agonist-stimulated Ca2+ entry, and thus formation of endothelium-derived nitric oxide (EDNO) in vascular endothelial cells, is related to activation of microsomal P450 mono-oxygenase (P450 MO) and the biosynthesis of 5, -epoxyeicosatrienoic acid (5, -EET). 2. Several P450 inhibitors diminished the sustained [Ca2+]i plateau response to agonist or intracellular Ca2+ store depletion with ATPase inhibitors by 31-69% (fura-2 technique). Mn2+ influx stimulated by agonists or ATPase inhibitors was prevented by P450 inhibitors. 3. Histamine- or ATPase inhibitor-stimulated formation of EDNO was strongly attenuated (50-83%) by P450 inhibitors, without any effect on EDNO formation by the Ca2+ ionophore A23187, indicating that decreased EDNO synthesis is due specifically to the inhibition of Ca2+ entry by these compounds. 4. Induction of P450 MO by beta-naphthoflavone potentiated agonist-induced Ca2+ and Mn2+ influx by 60 and 53%, respectively. Intracellular Ca2+ release remained unchanged. 5. The P450 MO product, 5, -EET (< 156 nmol l-1), activated Ca2+/Mn2+ entry without any depletion of intracellular Ca2+ stores. The 5, -EET-stimulated Ca2+/Mn2+ entry was not affected by P450 inhibitors. 6. As with the bradykinin-stimulated Ca2+ entry pathway, the 5, -EET-activated Ca2+ entry pathway was permeable to Mn2+ and Ba2+, sensitive to Ni2+, La3+ and membrane depolarization, and insensitive to the removal of extracellular Na+ or the organic Ca2+ antagonist, nitrendipine. 7. In the presence of 5, -EET, stimulation with bradykinin only transiently increased [Ca2+]i. Vice versa, 5, -EET failed to increase [Ca2+]i further in bradykinin-stimulated cells. The sustained [Ca2+]i plateau phase induced by a co-stimulation with bradykinin and 5, -EET was identical to that observed with bradykinin or 5, -EET alone. 8. These results demonstrate that Ca2+ entry induced by the P450 MO product, 5, -EET, is indistinguishable to that observed by stimulation with bradykinin. 9. All data support our hypothesis that depletion of endothelial Ca2+ stores activates microsomal P450 MO which in turn synthesizes 5, -EET. We propose that the arachidonic acid metabolite 5, -EET or one of its metabolites is a second messenger for activation of endothelial Ca2+ entry.\n\nGraier, Wolfgang\n\n\n"
},
{
"text": "\n3820\nUltraviolet exposure as the main initiator of p53 mutations in basal cell carcinomas from psoralen and ultraviolet A-treated patients with psoriasis.\n\nSeidl, H\n\nKreimer-Erlacher, H\n\nBäck, B\n\nSoyer, HP\n\nHöfler, G\n\nKerl, H\n\nWolf, P\n\nBeiträge in Fachzeitschriften\nISI:000170668300027\n11511317.0\n10.1046/j.0022-202x.2001.01413.x\nNone\nBasal cell carcinoma, the most frequent skin cancer in humans, is often linked to chronic sun exposure. In psoralen and ultraviolet A-treated psoriatic patients, basal cell carcinomas may occur even more frequently; however, the exact etiology and mechanisms of tumorigenesis in psoriatic patients are unclear because psoralen and ultraviolet A is not only a carcinogen but also an immunosuppressor and because psoralen and ultraviolet A-treated psoriatic patients often have other (co)carcinogenic risk factors (e.g, therapeutic exposure to ultraviolet B, X-ray radiation, arsenic, tar, and/or chemotherapeutic agents such as methotrexate). In this study, we analyzed the DNA of 13 basal cell carcinomas from five psoralen and ultraviolet A-treated psoriatic patients for mutations of the p53 tumor suppressor gene. DNA sequencing revealed a total of 11 mis-sense, two non-sense, and four silent mutations in seven of the 13 basal cell carcinomas (54%). Of the 13 total mis-sense or non-sense mutations, 12 (92%) occurred at dipyrimidine sites and nine (69%) were of the ultraviolet fingerprint type (eight C-->T transitions and one CC-->TT transition). Three of the C-->T transitions occurred at dipyrimidine sites opposite a 5'-TpG sequence (a potential psoralen-binding site and target for psoralen and ultraviolet A mutagenesis). Thus, whether these mutations were induced by ultraviolet or psoralen and ultraviolet A was not clear. In addition, two other mutations (15%) occurred at 5'-TpG sites, one (8%) occurred at a 5'-TpA site (the most frequent site of psoralen binding and mutagenesis in cell and murine studies), and one (8%) involved a G-->T transversion. These results suggest that (i) the major initiator of p53 mutations in basal cell carcinoma in psoralen and ultraviolet A-treated psoriasis patients is environmental and/or therapeutic ultraviolet(B) exposure, and that (ii) psoralen and ultraviolet A itself causes only a smaller portion of p53 mutations in psoralen and ultraviolet A-associated basal cell carcinomas.\n\nHöfler, Gerald\n\nKerl, Helmut\n\nWolf, Peter\n\n\n"
},
{
"text": "\n4191\nHormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle.\n\nHaemmerle, G\n\nZimmermann, R\n\nStrauss, JG\n\nKratky, D\n\nRiederer, M\n\nKnipping, G\n\nZechner, R\n\nBeiträge in Fachzeitschriften\nISI:000175036300060\n11809748.0\n10.1074/jbc.M108640200\nNone\nHormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (-40%) and TG (-63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (-90%) and strongly decreased ketone body concentrations in plasma (-80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an "anti-atherogenic" lipoprotein profile.\n\nKratky, Dagmar\n\n\n"
},
{
"text": "\n166769\nThe Health Care Transition of Youth With Liver Disease Into the Adult Health System: Position Paper From ESPGHAN and EASL.\n\nVajro, P\n\nFischler, B\n\nBurra, P\n\nDebray, D\n\nDezsofi, A\n\nGuercio Nuzio, S\n\nHadzic, N\n\nHierro, L\n\nJahnel, J\n\nLamireau, T\n\nMcKiernan, P\n\nMcLin, V\n\nNobili, V\n\nSocha, P\n\nSmets, F\n\nBaumann, U\n\nVerkade, HJ\n\nBeiträge in Fachzeitschriften\nISI:000441420000034\n29570559.0\n10.1097/MPG.0000000000001965\nNone\nMedical advances have dramatically improved the long-term prognosis of children and adolescents with once-fatal hepatobiliary diseases. However, there is no generally accepted optimal pathway of care for the transition from paediatric care to the adult health system.\n The purpose of this position paper is to propose a transition process for young people with paediatric onset hepatobiliary diseases from child-centred to adult-centred healthcare services.\n Seventeen ESPGHAN/EASL physicians from 13 countries (Austria, Belgium, France, Germany, Hungary, Italy, the Netherlands, Norway, Poland, Spain, Sweden, Switzerland, and United Kingdom) formulated and answered questions after examining the currently published literature on transition from childhood to adulthood. PubMed and Google Scholar were systematically searched between 1980 and January 2018. Quality of evidence was assessed by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) system. Expert opinions were used to support recommendations whenever the evidence was graded weak. All authors voted on each recommendation, using the nominal voting technique.\n We reviewed the literature regarding the optimal timing for the initiation of the transition process and the transfer of the patient to adult services, principal documents, transition multi-professional team components, main barriers, and goals of the general transition process. A transition plan based on available evidence was agreed focusing on the individual young people's readiness and on coordinated teamwork, with transition monitoring continuing until the first year of adult services.We further agreed on selected features of transitioning processes inherent to the most frequent paediatric-onset hepatobiliary diseases. The discussion highlights specific clinical issues that will probably present to adult gastrointestinal specialists and that should be considered, according to published evidence, in the long-term tracking of patients.\n Transfer of medical care of individuals with paediatric onset hepatobiliary chronic diseases to adult facilities is a complex task requiring multiple involvements of patients and both paediatric and adult care providers.\n\nJahnel, Jörg\n\n\n"
},
{
"text": "\n176259\nCurrent approaches to identify sections within clinical narratives from electronic health records: a systematic review.\n\nPomares-Quimbaya, A\n\nKreuzthaler, M\n\nSchulz, S\n\nBeiträge in Fachzeitschriften\nISI:000476487300003\n31319802.0\n10.1186/s12874-019-0792-y\nPMC6637496\nThe identification of sections in narrative content of Electronic Health Records (EHR) has demonstrated to improve the performance of clinical extraction tasks; however, there is not yet a shared understanding of the concept and its existing methods. The objective is to report the results of a systematic review concerning approaches aimed at identifying sections in narrative content of EHR, using both automatic or semi-automatic methods.\n This review includes articles from the databases: SCOPUS, Web of Science and PubMed (from January 1994 to September 2018). The selection of studies was done using predefined eligibility criteria and applying the PRISMA recommendations. Search criteria were elaborated by using an iterative and collaborative keyword enrichment.\n Following the eligibility criteria, 39 studies were selected for analysis. The section identification approaches proposed by these studies vary greatly depending on the kind of narrative, the type of section, and the application. We observed that 57% of them proposed formal methods for identifying sections and 43% adapted a previously created method. Seventy-eight percent were intended for English texts and 41% for discharge summaries. Studies that are able to identify explicit (with headings) and implicit sections correspond to 46%. Regarding the level of granularity, 54% of the studies are able to identify sections, but not subsections. From the technical point of view, the methods can be classified into rule-based methods (59%), machine learning methods (22%) and a combination of both (19%). Hybrid methods showed better results than those relying on pure machine learning approaches, but lower than rule-based methods; however, their scope was more ambitious than the latter ones. Despite all the promising performance results, very few studies reported tests under a formal setup. Almost all the studies relied on custom dictionaries; however, they used them in conjunction with a controlled terminology, most commonly the UMLSⓇ metathesaurus.\n Identification of sections in EHR narratives is gaining popularity for improving clinical extraction projects. This study enabled the community working on clinical NLP to gain a formal analysis of this task, including the most successful ways to perform it.\n\nKreuzthaler, Markus Eduard\n\nSchulz, Stefan\n\n\n"
},
{
"text": "\n183551\nEuropean dermatology forum: Updated guidelines on the use of extracorporeal photopheresis 2020 - Part 2.\n\nKnobler, R\n\nArenberger, P\n\nArun, A\n\nAssaf, C\n\nBagot, M\n\nBerlin, G\n\nBohbot, A\n\nCalzavara-Pinton, P\n\nChild, F\n\nCho, A\n\nFrench, LE\n\nGennery, AR\n\nGniadecki, R\n\nGollnick, HPM\n\nGuenova, E\n\nJaksch, P\n\nJantschitsch, C\n\nKlemke, C\n\nLudvigsson, J\n\nPapadavid, E\n\nScarisbrick, J\n\nSchwarz, T\n\nStadler, R\n\nWolf, P\n\nZic, J\n\nZouboulis, C\n\nZuckermann, A\n\nGreinix, H\n\nBeiträge in Fachzeitschriften\nISI:000607303300076\n32964529.0\n10.1111/jdv.16889\nPMC7821314\nFollowing the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multidisciplinary setting. It has confirmed recognition in well-known documented conditions such as graft-vs.-host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease.\n In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added.\n These updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines were divided into two parts: PART I covers Cutaneous T-cell lymphoma, chronic graft-vs.-host disease and acute graft-vs.-host disease, while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatric patients, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.\n © 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.\n\nGreinix, Hildegard\n\nWolf, Peter\n\n\n"
},
{
"text": "\n184003\nProtocol for a multicentre, prospective cohort study of clinical, proteomic and genomic patterns associated with osteoporosis to develop a multidimensional fracture assessment tool: the PoCOsteo Study.\n\nKhashayar, P\n\nDimai, HP\n\nMoradi, N\n\nFahimfar, N\n\nGharibzadeh, S\n\nOstovar, A\n\nNabipour, I\n\nLarijani, B\n\nBeiträge in Fachzeitschriften\nISI:000578438500008\n32998914.0\n10.1136/bmjopen-2019-035363\nPMC7528352\nThe HORIZON 2020 project PoCOsteo aims (1) to develop a multidimensional fracture risk assessment tool which would take into account all factors known to be related to an individual's fracture risk. The fracture risk model is intended to be developed in two different populations, namely a European and a Middle Eastern one; (2) to develop a medical device, which would measure and/or quantify proteomic as well as genomic factors as present in whole blood samples collected through finger prick; (3) to test the clinical applicability and the validity of prototypes of the to be developed point of care device at both clinical centres.\n This article presents the protocol of this prospective cohort that will be carried out independently at two different centres (Division of Endocrinology and Diabetology at the Medical University of Graz (MUG) as a clinic-based cohort, and Endocrinology and Metabolism Research Institute (EMRI) at the Tehran University of Medical Sciences (TUMS) as a population-based cohort). The final aim is to develop a fracture risk assessment model, which would include clinical risk factors, biochemical markers of bone turnover, as well as specific genomic factors. The derivation cohorts will consist of individuals aged 50 years and above. The period of observation for each patient will be 12 months; an extension phase, which would last for another 2 years, is also planned.\n These studies are conducted in accordance with the World Medical Association Declaration of Helsinki. The Iranian part was approved by the Research Ethics Committee of EMRI, TUMS. The Austrian part was approved by the Ethics Committee of the Medical University of Graz. Based on the gathered information, a multidimensional fracture assessment tool will be designed which will later be added to the PoCOsteo device.\n © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\nDimai, Hans\n\n\n"
},
{
"text": "\n2471\nSynchronous radiochemotherapy in unfavorable brain tumors of children and young adults.\n\nUrban, C\n\nBenesch, M\n\nPakisch, B\n\nLackner, H\n\nKerbl, R\n\nSchwinger, W\n\nOberbauer, R\n\nBeiträge in Fachzeitschriften\nISI:000075844300007\n9760072.0\n10.1023%2FA%3A1005966407408\nNone\nThe prognosis of patients with incompletely resected malignant brain tumors is almost fatal. In an attempt to improve the outcome of children and young adults with unfavorable brain tumors an intensive multimodal therapeutic strategy was developed combining simultaneous (hyper)fractionated external beam irradiation and conventional adjuvant chemotherapy after initial surgery. 17 patients aged between 2.10 and 25.11 years were entered into the study. 16/17 patients were treated according to the German/Austrian Pediatric Brain Tumor Study Group multicenter trial HIT '91. They are not protocol patients of this HIT '91 trial. Induction chemotherapy consisted of 2 courses of ifosfamide (3 g/m2/d) on days 1-3, etoposide (150 mg/m2/d) on days 4-6, methotrexate (5 g/m2) on days 15 and 22, cisplatin (40 mg/m2/d) and cytarabine (400 mg/m2/d) on days 29-31. Three weeks after the last dose of cisplatin/cytarabine the second course of chemotherapy was started. The last patient entered into the study received a modified therapy containing ifosfamide, cisplatin and etoposide. Synchronously at a median of 12 days after initiation of chemotherapy 12/17 patients received local radiotherapy (6000-7040 cGy) to the brain and 5/17 patients craniospinal irradiation (3520 cGy with a tumor boost of 1400-2000 cGy). 4-6 weeks after completion of the second course of chemotherapy maintenance therapy was started with carmustine (CCNU) (75 mg/m2) and carboplatin (400 mg/m2) each on day 1 and vincristine (1.5 mg/m2) on day 1, 8, 15. This course was repeated eight times every six weeks. 9/17 patients are alive at a median follow-up of 25 months (range 5-50) with 4 complete remissions, 2 partial remissions and 1 stable disease lasting 42+ months. Two patients, who initially had stable disease, progressed, but are still alive at 31+ and 41+ months after diagnosis. Median progression-free survival and median overall survival is 19 and 36 months, respectively. Hematologic and methotrexate-induced toxicity were severe and resulted in one therapy-related death. However, radiotherapy concomitant to chemotherapy appears to be an effective method of treatment for brain tumors with poor prognosis, though toxicity is severe in some cases.\n\nBenesch, Martin\n\nKerbl, Reinhold\n\nLackner, Herwig\n\nSchwinger, Wolfgang\n\nUrban, Ernst-Christian\n\n\n"
},
{
"text": "\n103049\nDiagnostic terminology for reporting thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009\n\nKocjan, G\n\nCochand-Priollet, B\n\nde Agustin, PP\n\nBourgain, C\n\nChandra, A\n\nDaneshbod, Y\n\nDeery, A\n\nDuskova, J\n\nErsoz, C\n\nFadda, G\n\nFassina, A\n\nFirat, P\n\nJimenez-Ayala, B\n\nKarakitsos, P\n\nKoperek, O\n\nMatesa, N\n\nPoller, D\n\nThienpont, L\n\nRyska, A\n\nSchenck, U\n\nSauer, T\n\nSchmitt, F\n\nTani, E\n\nToivonen, T\n\nTotsch, M\n\nTroncone, G\n\nVass, L\n\nVielh, P\n\nBeiträge in Fachzeitschriften\nISI:000275214200003\n21054822.0\n10.1111/j.1365-2303.2010.00751.x\nNone\nA European Federation of Cytology Societies (EFCS) working party of 28 members from 14 European countries met at the European Congress of Cytology in Lisbon in September 2009, with two observers from the USA, to discuss the need for standardising thyroid FNA nomenclature in the light of the National Institute of Cancer (NCI) recommendations resulting from the State of the Science conference in Bethesda in 2007. The data were obtained through two questionnaires sent by email and a transcript of the live discussion at the congress, which is presented in full. The surveys and discussion showed that there were currently no national terminologies for reporting thyroid FNA in the different European countries except in Italy and the UK. Personal, 'local', surgical pathology and descriptive terminologies were in use. All but one of the working party members agreed that thyroid FNA reporting should be standardised. Whilst almost a third would adopt the NCI Bethesda terminology, which offers the advantages of a 'risk of cancer' correlation and is linked to clinical recommendations, more than half favoured a translation of local terminology as the first step towards a unified nomenclature, as has been done recently in the UK. There was some disagreement about the use of: a) the six-tiered as opposed to four or five-tiered systems, b) the use of an indeterminate category and c) the 'follicular neoplasm' category, which was felt by some participants not to be different from the 'suspicious of malignancy' category. The conclusions will be passed to the different national societies of cytology for discussion, who will be asked to map their local terminologies to the Bethesda classification, observe its acceptance by clinicians and audit its correlation with outcome.\n\n\n"
},
{
"text": "\n121386\nDifferences in Fabry Cardiomyopathy Between Female and Male Patients Consequences for Diagnostic Assessment\n\nNiemann, M\n\nHerrmann, S\n\nHu, K\n\nBreunig, F\n\nStrotmann, J\n\nBeer, M\n\nMachann, W\n\nVoelker, W\n\nErtl, G\n\nWanner, C\n\nWeidemann, F\n\nBeiträge in Fachzeitschriften\nISI:000292042900005\n21679893.0\n10.1016/j.jcmg.2011.01.020\nNone\nOBJECTIVES We hypothesized that Fabry cardiomyopathy in female patients might differ substantially from that in male patients and sought to prove this hypothesis in a large cohort consisting of 104 patients with Fabry disease. BACKGROUND Fabry cardiomyopathy in male patients is characterized by left ventricular (LV) hypertrophy, impaired myocardial function, and subsequent progressive myocardial fibrosis. In contrast, the occurrence of these 3 cardiomyopathic hallmarks in female patients remains unknown. METHODS In 104 patients (58 females, age 42 +/- 16 years; 46 males, age 42 +/- 13 years) with genetically proven Fabry disease, LV hypertrophy, regional myocardial deformation and myocardial fibrosis were assessed by standard echocardiography, strain rate imaging, and cardiac magnetic resonance (CMR) imaging-guided late enhancement (LE). RESULTS In men, end-diastolic left ventricular wall thickness (LVWT) ranged from 6 to 19.5 mm (LV mass CMR 55 to 200 g/m(2)), and LE was never seen with LVWT <12 mm (LV mass <99 g/m(2)). In contrast in female patients, LVWT ranged from 5 to 15.5 mm, LV mass ranged from 39 to 146 g/m(2), and LE was already detectable with an LVWT of 9 mm (LV mass 56 g/m(2)). When LV mass was examined in CMR, LE was detected in 23% of the female patients without hypertrophy (n = 9), whereas LE was never seen in male patients with normal LV mass. LE was always associated with low systolic strain rate, but the severity of impairment was independent of LVWT in female patients (lateral strain rate in patients with LV hypertrophy with LE -0.7 +/- 0.2 s(-1); patients without LV hypertrophy with LE -0.8 +/- 0.2 s(-1); p = 0.45). CONCLUSIONS In contrast to male patients, the loss of myocardial function and the development of fibrosis do not necessarily require myocardial hypertrophy in female patients with Fabry disease. Thus, in contrast to actual recommendations, initial cardiac staging and monitoring should be based on LV hypertrophy and on replacement fibrosis in female patients with Fabry disease. (J Am Coll Cardiol Img 2011; 4: 592-601) (C) 2011 by the American College of Cardiology Foundation\n\n\n"
},
{
"text": "\n124066\nThiomer-coated liposomes harbor permeation enhancing and efflux pump inhibitory properties.\n\nGradauer, K\n\nDünnhaupt, S\n\nVonach, C\n\nSzöllösi, H\n\nPali-Schöll, I\n\nMangge, H\n\nJensen-Jarolim, E\n\nBernkop-Schnürch, A\n\nPrassl, R\n\nBeiträge in Fachzeitschriften\nISI:000315680100006\n23228848.0\n10.1016/j.jconrel.2012.12.001\nPMC3560037\nAn ideal oral drug carrier should facilitate drug delivery to the gastrointestinal tract and its absorption into the systemic circulation. To meet these requirements, we developed a thiomer-coated liposomal delivery system composed of 1, -dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and a maleimide-functionalized lipid, to which chitosan-thioglycolic acid (CS-TGA) was covalently coupled. In addition to conventional 77 kDa CS-TGA (CS-TGA77), we tested the 150 kDa homologue (CS-TGA150) as well as an S-protected version of this polymer (CS-TGA150-MNA), in which some of the free SH-groups are conjugated with 6-mercaptonicotinamide to protect them from oxidation. Coupling of CS-TGA to the liposomal surface led to an increase in the particle size of at least 150 nm and an increase in the zeta potential from approximately -33 mV to a maximum of about +36 mV, depending on the polymer. As revealed by fluorescence dequenching the formulations have a storage stability of at least two weeks without releasing any encapsulated compounds. In simulated gastric fluid, the system was shown to be stable over 24 h, while in simulated intestinal fluid, a slow, sustained release of encapsulated compounds was observed. According to our experiments, thiomer-coated liposomes did not induce immunogenic reactions after an oral administration to mice. To evaluate the permeation enhancing and efflux pump inhibiting properties of CS-TGA coated liposomes we monitored the transport of fluoresceinisothiocyanate-dextran (FD(4)) and rhodamine-123 (Rho-123), respectively, through rat small intestine. Permeation studies showed a 2.8-fold higher permeation of FD(4) in the presence of CS-TGA77 coated liposomes and an even 4-fold higher permeation in the presence of CSA-TGA150-MNA coated liposomes. The latter also performed best when we evaluated P-glycoprotein inhibiting properties by monitoring the transport of Rho-123, revealing a 4.2-fold enhancement respective to the buffer control. Taken together, thiomer-coated liposomes were shown to protect encapsulated drugs in the stomach, slowly release them in the small intestine and enhance their absorption through the intestinal tissue by opening tight junctions and inhibiting efflux pumps.\n\nMangge, Harald\n\nPrassl, Ruth\n\n\n"
},
{
"text": "\n149999\nAnatomically accurate high resolution modeling of human whole heart electromechanics: A strongly scalable algebraic multigrid solver method for nonlinear deformation.\n\nAugustin, CM\n\nNeic, A\n\nLiebmann, M\n\nPrassl, AJ\n\nNiederer, SA\n\nHaase, G\n\nPlank, G\n\nBeiträge in Fachzeitschriften\nISI:000366156600032\n26819483.0\n10.1016/j.jcp.2015.10.045\nPMC4724941\nElectromechanical (EM) models of the heart have been used successfully to study fundamental mechanisms underlying a heart beat in health and disease. However, in all modeling studies reported so far numerous simplifications were made in terms of representing biophysical details of cellular function and its heterogeneity, gross anatomy and tissue microstructure, as well as the bidirectional coupling between electrophysiology (EP) and tissue distension. One limiting factor is the employed spatial discretization methods which are not sufficiently flexible to accommodate complex geometries or resolve heterogeneities, but, even more importantly, the limited efficiency of the prevailing solver techniques which are not sufficiently scalable to deal with the incurring increase in degrees of freedom (DOF) when modeling cardiac electromechanics at high spatio-temporal resolution. This study reports on the development of a novel methodology for solving the nonlinear equation of finite elasticity using human whole organ models of cardiac electromechanics, discretized at a high para-cellular resolution. Three patient-specific, anatomically accurate, whole heart EM models were reconstructed from magnetic resonance (MR) scans at resolutions of 220 μm, 440 μm and 880 μm, yielding meshes of approximately 184.6, 24.4 and 3.7 million tetrahedral elements and 95.9, 13.2 and 2.1 million displacement DOF, respectively. The same mesh was used for discretizing the governing equations of both electrophysiology (EP) and nonlinear elasticity. A novel algebraic multigrid (AMG) preconditioner for an iterative Krylov solver was developed to deal with the resulting computational load. The AMG preconditioner was designed under the primary objective of achieving favorable strong scaling characteristics for both setup and solution runtimes, as this is key for exploiting current high performance computing hardware. Benchmark results using the 220 μm, 440 μm and 880 μm meshes demonstrate efficient scaling up to 1024, 4096 and 8192 compute cores which allowed the simulation of a single heart beat in 44.3, 87.8 and 235.3 minutes, respectively. The efficiency of the method allows fast simulation cycles without compromising anatomical or biophysical detail.\n\nAugustin, Christoph\n\nNeic, Aurel-Vasile\n\nPlank, Gernot\n\nPrassl, Anton\n\n\n"
},
{
"text": "\n171500\nThe Data Registry of the European Competence Network on Mastocytosis (ECNM): Set Up, Projects, and Perspectives.\n\nValent, P\n\nOude Elberink, JNG\n\nGorska, A\n\nLange, M\n\nZanotti, R\n\nvan Anrooij, B\n\nBonifacio, M\n\nBonadonna, P\n\nGleixner, KV\n\nHadzijusufovic, E\n\nPerkins, C\n\nHartmann, K\n\nIllerhaus, A\n\nMerante, S\n\nElena, C\n\nShoumariyeh, K\n\nvon Bubnoff, N\n\nParente, R\n\nTriggiani, M\n\nSchwaab, J\n\nJawhar, M\n\nCaroppo, F\n\nFortina, AB\n\nBrockow, K\n\nDavid Fuchs, K\n\nGreul, R\n\nYavuz, AS\n\nDoubek, M\n\nMattsson, M\n\nHagglund, H\n\nPanse, J\n\nSabato, V\n\nAberer, E\n\nAl-Ali, HK\n\nMorren, MA\n\nVarkonyi, J\n\nZink, A\n\nNiedoszytko, M\n\nNiederwieser, D\n\nMalcovati, L\n\nReiter, A\n\nKennedy, V\n\nGotlib, J\n\nLortholary, O\n\nHermine, O\n\nArock, M\n\nKluin-Nelemans, H\n\nSperr, WR\n\nStudy Group of the European Competence Network on Mastocytosis (ECNM)\n\nBeiträge in Fachzeitschriften\nISI:000454522500010\n30416055.0\n10.1016/j.jaip.2018.09.024\nPMC7115815\nMastocytosis is a unique hematologic neoplasm with complex biology and pathology and a variable clinical course. The disease can essentially be divided into cutaneous mastocytosis (CM) and systemic mastocytosis (SM). In adults, SM is diagnosed in most cases and manifests as either indolent or advanced disease. Patients with advanced SM have an unfavorable prognosis with reduced survival. However, so far, little is known about the prevalence of various categories of SM and about prognostic factors. In an attempt to learn more about the behavior and evolution of various forms of CM and SM, the European Competence Network on Mastocytosis (ECNM) initiated a mastocytosis registry in 2012. In this article, the set up and start phase of this registry are described. Until 2018, more than 3000 patients from 12 countries and 25 centers have been enrolled. In a majority of all patients, robust follow-up data and relevant clinical end points are available. Using this data set, a series of registry projects have been launched, with the aim to validate previously identified diagnostic and prognostic variables and to identify new disease-related and patient-related parameters in various forms of mastocytosis. Moreover, the core data set of the registry will be useful to establish multiparametric scoring systems through which prognostication and individualized management of patients with mastocytosis should improve in the foreseeable future.\n Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.\n\n\n"
},
{
"text": "\n177993\nFacing privacy in neuroimaging: removing facial features degrades performance of image analysis methods.\n\nde Sitter, A\n\nVisser, M\n\nBrouwer, I\n\nCover, KS\n\nvan Schijndel, RA\n\nEijgelaar, RS\n\nMüller, DMJ\n\nRopele, S\n\nKappos, L\n\nRovira, Á\n\nFilippi, M\n\nEnzinger, C\n\nFrederiksen, J\n\nCiccarelli, O\n\nGuttmann, CRG\n\nWattjes, MP\n\nWitte, MG\n\nde Witt Hamer, PC\n\nBarkhof, F\n\nVrenken, H\n\nMAGNIMS Study Group and Alzheimer’s Disease Neuroimaging Initiative\n\nBeiträge in Fachzeitschriften\nISI:000494507500003\n31691120.0\n10.1007/s00330-019-06459-3\nPMC6957560\nRecent studies have created awareness that facial features can be reconstructed from high-resolution MRI. Therefore, data sharing in neuroimaging requires special attention to protect participants' privacy. Facial features removal (FFR) could alleviate these concerns. We assessed the impact of three FFR methods on subsequent automated image analysis to obtain clinically relevant outcome measurements in three clinical groups.\n FFR was performed using QuickShear, FaceMasking, and Defacing. In 110 subjects of Alzheimer's Disease Neuroimaging Initiative, normalized brain volumes (NBV) were measured by SIENAX. In 70 multiple sclerosis patients of the MAGNIMS Study Group, lesion volumes (WMLV) were measured by lesion prediction algorithm in lesion segmentation toolbox. In 84 glioblastoma patients of the PICTURE Study Group, tumor volumes (GBV) were measured by BraTumIA. Failed analyses on FFR-processed images were recorded. Only cases in which all image analyses completed successfully were analyzed. Differences between outcomes obtained from FFR-processed and full images were assessed, by quantifying the intra-class correlation coefficient (ICC) for absolute agreement and by testing for systematic differences using paired t tests.\n Automated analysis methods failed in 0-19% of cases in FFR-processed images versus 0-2% of cases in full images. ICC for absolute agreement ranged from 0.312 (GBV after FaceMasking) to 0.998 (WMLV after Defacing). FaceMasking yielded higher NBV (p = 0.003) and WMLV (p ≤ 0.001). GBV was lower after QuickShear and Defacing (both p < 0.001).\n All three outcome measures were affected differently by FFR, including failure of analysis methods and both "random" variation and systematic differences. Further study is warranted to ensure high-quality neuroimaging research while protecting participants' privacy.\n • Protecting participants' privacy when sharing MRI data is important. • Impact of three facial features removal methods on subsequent analysis was assessed in three clinical groups. • Removing facial features degrades performance of image analysis methods.\n\nEnzinger, Christian\n\nRopele, Stefan\n\n\n"
},
{
"text": "\n73211\nSurfactant treatment of neonates with respiratory failure and group B streptococcal infection. Members of the Collaborative European Multicenter Study Group.\n\nHerting, E\n\nGefeller, O\n\nLand, M\n\nvan Sonderen, L\n\nHarms, K\n\nRobertson, B and Members of the Collaborative European Multicenter Study Group (with Pichler, G\n\nMueller, W)\n\nBeiträge in Fachzeitschriften\nISI:000165052300001\n11061760.0\n10.1542/peds.106.5.957\nNone\nOBJECTIVE: Connatal pneumonia caused by group B streptococcal (GBS) infection may be associated with surfactant dysfunction. We investigated the effects of surfactant treatment in term and preterm neonates with GBS infection and respiratory failure, in comparison with corresponding data from a control population of noninfected infants treated with surfactant for respiratory distress syndrome (RDS). DESIGN/METHODS: The study comprised 118 infants with respiratory failure, clinical and/or laboratory signs of acute inflammatory disease, and GBS infection proven by culture results. They were recruited retrospectively from a database of patients treated with surfactant at 28 neonatology units participating in European multicenter trials (1987-1993) and prospectively from the same units in the following years. A nonrandomized control group of 236 noninfected infants was selected from the same database. The primary parameters evaluated were oxygen requirement, ventilator settings, and incidence of complications. RESULTS: Median birth weight in the GBS study group was 1468 g (25th-75th percentiles: 1015-2170), and median gestational age was 30 (27-33) weeks. Thirty-one percent of the infants weighed >2000 g. Median age at surfactant treatment was 6 hours. The mean initial surfactant dose was 142 mg/kg (standard deviation: 53). Ninety of the infants were treated with Curosurf (Chiesi Farmaceutici, Parma, Italy), 13 with Survanta (Abboth GmbH, Wiesbaden, Germany), 12 with Alveofact (Dr Karl Thomae GmbH, Biberach, Germany), and 3 with Exosurf (Wellcome GmbH, Burgwedel, Germany). Within 1 hour of surfactant treatment, median fraction of inspiratory oxygen was reduced from .84 (25th-75th percentiles:.63-1.0) to.50 (.35-.80). The incidence of complications in the study group (mortality: 30%; pneumothorax: 16%; intracranial hemorrhage: 42%) was high, compared with infants with RDS. CONCLUSIONS: Surfactant therapy improves gas exchange in the majority of patients with GBS pneumonia. The response to surfactant is slower than in infants with RDS, and repeated surfactant doses are often needed. The mortality and morbidity are substantial, considering the relatively high mean birth weight of the treated infants.\n\nMüller, Wilhelm\n\nPichler, Gerhard\n\n\n"
},
{
"text": "\n115582\nThe role of myoendothelial cell contact in non-nitric oxide-, non-prostanoid-mediated endothelium-dependent relaxation of porcine coronary artery.\n\nKühberger, E\n\nGroschner, K\n\nKukovetz, WR\n\nBrunner, F\n\nBeiträge in Fachzeitschriften\nISI:A1994PU18700036\n7889285.0\nNone\nPMC1510476\n1. Experiments were designed to analyse the requirement of myoendothelial junctions by bradykinin-induced endothelium-dependent relaxations resistant to NG-nitro-L-arginine (L-NOARG) and indomethacin porcine coronary arteries. 2. Rings of porcine coronary arteries were contracted with the thromboxane receptor agonist, U46619 and relaxations to bradykinin recorded isometrically. All experiments were performed in the presence of indomethacin. Nitric oxide (NO)-mediated effects were blocked by the NO synthase inhibitor L-NOARG (250 microM) and myoendothelial contacts inhibited by treatment with hypertonic solution containing D-mannitol or sucrose (each 180 mM) or the gap junctional uncoupling agent 1-heptanol (2 mM). High [K+] solutions (40 mM) were used to probe a possible contribution of endothelium-derived hyperpolarizing factor (EDHF). 3. In the presence of endothelium, bradykinin induced concentration-dependent relaxations with a mean EC50 of 3.2 nM and a maximum response of 95 +/- 1% of papaverine-induced relaxation (control curve). 4. In the absence of endothelium, bradykinin failed to induce relaxations. Addition of cultured porcine aortic endothelial cells to the organ bath resulted in some relaxation and restored in part the relaxant effect of bradykinin. This endothelial cell-mediated relaxant effect was completely abolished in the presence of 250 microM L-NOARG. 5. Bradykinin-induced relaxations in endothelium-preserved rings were only slightly suppressed by L-NOARG (86% of control). In vessels partially depolarized by high extracellular [K+] (40 mM) relaxation was reduced to 72% of control. In the presence of L-NOARG, bradykinin failed to relax partially depolarized vessels. 6. In the presence of 2 mM -heptanol, 180 mM mannitol or 180 mM sucrose maximum relaxation to bradykinin was reduced to ~70%, i.e. to the same extent as in the presence of high [K+]. The remaining relaxation was sensitive to blockade by L-NOARG.7. Tissue cyclic GMP content which reflects NO activity, was increased about 4 fold by bradykinin(300 nM). This increase was unaffected by high [K+], heptanol or sucrose but blocked by L-NOARG.8 Our results suggest that non-nitric oxide- and non-prostanoid-mediated endothelium-dependent relaxation of porcine coronary artery requires functionally intact myoendothelial junctions.\n\nGroschner, Klaus\n\n\n"
},
{
"text": "\n131853\nPolymorphisms of interferon-λ4 and IL28B - effects on treatment response to interferon/ribavirin in patients with chronic hepatitis C.\n\nStättermayer, AF\n\nStrassl, R\n\nMaieron, A\n\nRutter, K\n\nStauber, R\n\nStrasser, M\n\nBeinhardt, S\n\nDatz, C\n\nScherzer, TM\n\nSteindl-Munda, P\n\nGschwantler, M\n\nTrauner, M\n\nHofer, H\n\nFerenci, P\n\nBeiträge in Fachzeitschriften\nISI:000327659000010\n24205831.0\n10.1111/apt.12547\nNone\nThe IL28B genotype in rs12979860 predicts success of peginterferon/ribavirin (PEG/RBV) therapy in patients with chronic hepatitis C (CHC). Recently, a dinucleotide frame shift variant in ss469415590 (TT or ΔG) was described, which generates the novel interferon lambda 4 protein (IFNL4). IFNL4 ss469415590 (ΔG) allele carriers have an impaired clearance of HCV infection and response to IFN-α therapy. In this study, we compared the role of IFNL4 polymorphism with the two commonly used IL28B SNPs rs12979860 and rs8099917 on response to PEG/RBV in patients with CHC.\n To compare the role of IFNL4 polymorphism with the two commonly used IL28B SNPs rs12979860 and rs8099917 on response to PEG/RBV in patients with CHC.\n A total of 754 PEG/RBV patients treated (male/female = 484/270; Caucasians: 98.8%; mean age: 42.8 [CI 95%: 42.0-43.6] y; genotype (GT)1: n = 435, GT2: n = 23, GT3: n = 185, GT4: n = 114) were investigated. Liver fibrosis was assessed by liver biopsy in 456 patients. Single nucleotide polymorphisms (SNPs) in ss469415590, rs12979860 and rs8099917 were analysed by RT-PCR system.\n Of the patients, 12.9% (n = 97) had the ss469415590 ΔG/ΔG genotype (IFNL4), 51.3% (n = 387) were heterozygous (TT/ΔG) and 35.8% (n = 270) had TT/TT. IFNL4 polymorphism was independently associated with SVR in GT1 (OR: 2.539, CI 95%: 1.629-3.021, P < 0.001) and GT4 (OR: 12.573, CI 95%: 3.427-46.133, P < 0.001), but not in GT3 (OR: 1.514, CI 95%: 0.933-2.458, P = 0.093). IFNL4 correlated strongly with rs12979860 (ρ = 0.988, P < 0.001), but only moderately with rs8099917 (ρ = 0.598, P < 0.001).\n These findings underscore the role of IFNL4 for treatment response in patients with CHC genotypes 1 and 4. However, due to its strong correlation with rs12979860 in IL28B, there is no benefit in additional testing for IFNL4 for treatment prediction in Caucasian patients. By contrast, IFNL4 improves prediction of response to interferon-based therapies, if SNP rs8099917 is used.\n © 2013 John Wiley & Sons Ltd.\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n138497\nPathologic nodal staging scores in patients treated with radical prostatectomy: a postoperative decision tool.\n\nKluth, LA\n\nAbdollah, F\n\nXylinas, E\n\nRieken, M\n\nFajkovic, H\n\nSun, M\n\nKarakiewicz, PI\n\nSeitz, C\n\nSchramek, P\n\nHerman, MP\n\nBecker, A\n\nLoidl, W\n\nPummer, K\n\nNonis, A\n\nLee, RK\n\nLotan, Y\n\nScherr, DS\n\nSeiler, D\n\nChun, FK\n\nGraefen, M\n\nTewari, A\n\nGönen, M\n\nMontorsi, F\n\nShariat, SF\n\nBriganti, A\n\nBeiträge in Fachzeitschriften\nISI:000340260900014\n23850255.0\n10.1016/j.eururo.2013.06.041\nNone\nNodal metastasis is the strongest risk factor of disease recurrence in patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP).\n To develop a model that allows quantification of the likelihood that a pathologically node-negative patient is indeed free of nodal metastasis.\n Data from patients treated with RP and pelvic lymph node dissection (PLND; n=7135) for PCa between 2000 and 2011 were analyzed. For external validation, we used data from patients (n=4209) who underwent an anatomically defined extended PLND.\n RP and PLND.\n We developed a novel pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative based on the number of examined nodes and the patient's characteristics.\n In the development and validation cohorts, the probability of missing a positive node decreases with an increasing number of nodes examined. Whereas in pT2 patients, a 90% pNSS was achieved with one single examined node in both the development and validation cohort, a similar level of nodal staging accuracy was achieved in pT3a patients by examining five and nine nodes, respectively. The pT3b/T4 patients achieved a pNSS of 80% and 70% when 17 and 20 nodes in the development and validation cohort were examined, respectively. This study is limited by its retrospective design and multicenter nature. The number of nodes removed was not directly correlated with the extent/template of PLND.\n Every patient needs PLND for accurate nodal staging. However, a one-size-fits-all approach is too inaccurate. We developed a tool that indicates a node-negative patient is indeed free of lymph node metastasis by evaluating the number of examined nodes, pT stage, RP Gleason score, surgical margins, and prostate-specific antigen. This tool may help in postoperative decision making.\n Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nPummer, Karl\n\n\n"
},
{
"text": "\n138508\nOverlapping and continued alendronate or raloxifene administration in patients on teriparatide: effects on areal and volumetric bone mineral density--the CONFORS Study.\n\nMuschitz, C\n\nKocijan, R\n\nFahrleitner-Pammer, A\n\nPavo, I\n\nHaschka, J\n\nSchima, W\n\nKapiotis, S\n\nResch, H\n\nBeiträge in Fachzeitschriften\nISI:000340243900010\n24619763.0\n10.1002/jbmr.2216\nNone\nNine month teriparatide (TPTD) monotherapy followed by co-administration of raloxifene (RAL) or alendronate (ALN) for another nine 9 months resulted in incremental bone mineral density (BMD) increase. The aim of this study was to investigate the effects of continued antiresorptive treatments for 12 months in the extension phase. Postmenopausal women (n = 125) with severe osteoporosis on ongoing TPTD treatment for 9 months were randomized into three open-label groups for another 9 months: ALN (70 mg/week, n = 41), RAL (60 mg/d, n = 37) in addition to TPTD or no additional medication (n = 47) except Ca and vitamin D. After discontinuation of TPTD the respective antiresorptives were continued for a further 12 months, while patients in the TPTD monotherapy group received Ca and vitamin D. Amino-terminal propeptide of type I procollagen (P1NP) and cross-linked C-telopeptide (CTX), areal and volumetric BMD at the lumbar spine (LS) and hip were assessed. ALN resulted in continued BMD increase in LS (4.3 ± 1.5%; mean ± SD), femoral neck (4.2 ± 1.6%) and total hip (4 ± 1.6%; p < 0.001 for all), while RAL was only effective at the LS (2.4 ± 1.7%, p < 0.001) but no changes at the femoral neck (0.4 ± 1.4%) or total hip (-0.8 ± 1.5%) were observed. Cortical bone only increased in the ALN group (femoral neck 6.7 ± 2.7% and -1.3 ± 2.5%; total hip 13.8 ± 2.9% and -2.3 ± 2.5% for ALN and RAL, p < 0.001 for all; respectively). Analyzing the entire 30 months of therapy, the ALN group revealed the largest BMD increase in all regions. Our results suggest that the addition of ALN to ongoing TPTD and continuing ALN after TPTD was stopped may be beneficial for patients in terms of areal and volumetric BMD increase. Further research is warranted to determine the optimal timing of the initiation of the combination treatment, the respective antiresorptive medication and the potential benefit of this BMD increase regarding fracture prevention.\n © 2014 American Society for Bone and Mineral Research.\n\nFahrleitner-Pammer, Astrid\n\n\n"
}
]
}