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"text": "\n91929\nComparison of Oncologic Outcomes for Open and Laparoscopic Nephroureterectomy: A Multi-Institutional Analysis of 1249 Cases\n\nCapitanio, U\n\nShariat, SF\n\nIsbarn, H\n\nWeizer, A\n\nRemzi, M\n\nRoscigno, M\n\nKikuchi, E\n\nRaman, JD\n\nBolenz, C\n\nBensalah, K\n\nKoppie, TM\n\nKassouf, W\n\nFernandez, MI\n\nStrobel, P\n\nWheat, J\n\nZigeuner, R\n\nLangner, C\n\nWaldert, M\n\nOya, M\n\nGuo, CC\n\nNg, C\n\nMontorsi, F\n\nWood, CG\n\nMargulis, V\n\nLarakiewicz, PI\n\nBeiträge in Fachzeitschriften\nISI:000267234100001\nNone\n10.1016/j.eururo.2009.03.072\nNone\nBackground: Data regarding the oncologic efficacy of laparoscopic nephroureterectomy (LNU) compared to open nephroureterectomy (ONU) are scarce. Objective: We compared recurrence and cause-specific mortality rates of ONU and LNU. Design, setting, and participants: Thirteen centers from three continents contributed data on 1249 patients with nonmetastatic upper tract urothelial carcinoma (UTUC). Measurements: Univariable and multivariable survival models tested the effect of procedure type (ONU [n = 979] vs LNU [n = 270]) on cancer recurrence and cancer-specific mortality. Covariables consisted of institution, age, Eastern Cooperative Oncology Group (ECOG) performance status score, pT stage, pN stage, tumor grade, lymphovascular invasion, tumor location, concomitant carcinoma in situ, Ureteralcuff management, previous urothelial bladder cancer, and previous endoscopic treatment. Results and limitations: Median follow-up for censored cases was 49 mo (mean: 62). Relative to ONU, LNU patients had more favorable pathologic stages (pT0/Ta/Tis: 38.1% vs 20.8%, p < 0.001) and less lymphovascular invasion (14.8% vs 21.3%, p=0.02) and less frequently had tumors located in the ureter (64.5 vs 71.1%, p=0.04). In univariable recurrence and cancer-specific mortality models, ONU was associated with higher cancer recurrence and mortality rates compared to LNU (hazard ratio [HR]: 2.1 [p < 0.001] and 2.0 [p = 0.008], respectively). After adjustment for all covariates, ONU and LNU had no residual effect on cancer recurrence and mortality (p = 0.1 for both). Conclusions: Short-term oncologic data on LNU are comparable to ONU. Since LNU was selectively performed in favorable-risk patients, we cannot state with certainty that ONU and LNU have the same oncologic efficacy in poor-risk patients. Longterm follow-up data and morbidity data are necessary before LNU can be considered as the standard of care in patients with muscle-invasive or high-grade UTUC. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nLangner, Cord\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n108154\nThe effect of PTH(1-84) or strontium ranelate on bone formation markers in postmenopausal women with primary osteoporosis: results of a randomized, open-label clinical trial.\n\nQuesada-Gómez, JM\n\nMuschitz, C\n\nGómez-Reino, J\n\nGreisen, H\n\nAndersen, HS\n\nDimai, HP\n\nBeiträge in Fachzeitschriften\nISI:000293636500013\n21052638.0\n10.1007/s00198-010-1460-6\nNone\nWe explored the effects of PTH(1-84) compared with strontium ranelate on bone remodeling as measured by bone remodeling markers in postmenopausal women with osteoporosis. Biochemical markers of bone formation were significantly increased after treatment with PTH(1-84) but not strontium ranelate, indicating a different mechanism of action between these agents. Introduction PTH(1-84) and strontium ranelate (SR) are both known to reduce fracture risk in osteoporosis. Measuring changes in biochemical markers of bone turnover induced by these agents can help in characterizing the action of PTH(1-84) and SR on bone remodeling. Methods A 24-week, randomized, open-label, parallel group, phase IV trial was conducted in 81 postmenopausal women with primary osteoporosis (>= 50 years of age, lumbar spine, or total hip T-score <=-2.5 SD) to assess the effect of SR as compared to PTH(1-84) on bone formation markers P1NP and BSAP. The bone resorption marker CTX was also measured. Subjects were randomly assigned to receive daily either 100 mu g PTH(1-84) (n = 41) (subcutaneous injection) or oral 2 g SR (n = 40) for 24 weeks with daily supplements of 800 IU vitamin D(3) and 1, 00 mg calcium. Patient-reported outcomes were collected to investigate the effect of treatment on quality of life (QoL). Results Percentage changes from baseline in P1NP and BSAP were significantly increased for PTH(1-84) by week 24 compared with SR (p < 0.0001). Significant changes from baseline in P1NP and BSAP were noted for PTH(1-84) from week 4 onwards; no significant changes were noted for SR. A trend towards a positive impact on QoL was seen with PTH(1-84) treatment. Safety profiles concur with previous analyses. Conclusions PTH(1-84) had a more rapid and higher effect on bone formation markers compared to SR, indicating that SR has a different mode of action on bone remodeling than the bone building agent PTH(1-84) in postmenopausal women with osteoporosis.\n\nDimai, Hans\n\n\n"
},
{
"text": "\n112405\nThe predictive ability of pre-operative B-type natriuretic Peptide in vascular patients for major adverse cardiac events an individual patient data meta-analysis.\n\nRodseth, RN\n\nLurati Buse, GA\n\nBolliger, D\n\nBurkhart, CS\n\nCuthbertson, BH\n\nGibson, SC\n\nMahla, E\n\nLeibowitz, DW\n\nBiccard, BM\n\nBeiträge in Fachzeitschriften\nISI:000292955500013\n21777751.0\n10.1016/j.jacc.2011.04.018\nNone\nObjectives The aims of this study were to perform an individual patient data meta-analysis of studies using B-type natriuretic peptides (BNPs) to predict the primary composite endpoint of cardiac death and nonfatal myocardial infarction (MI) within 30 days of vascular surgery and to determine: 1) the cut points for a natriuretic peptide (NP) diagnostic, optimal, and screening test; and 2) if pre-operative NPs improve the predictive accuracy of the revised cardiac risk index (RCRI). Background NPs are independent predictors of cardiovascular events in noncardiac and vascular surgery. Their addition to clinical risk indexes may improve pre-operative risk stratification. Methods Studies reporting the association of pre-operative NP concentrations and the primary study endpoint, post-operative major adverse cardiovascular events (defined as cardiovascular death and nonfatal MI) in vascular surgery, were identified by electronic database search. Secondary study endpoints included all-cause mortality, cardiac death, and nonfatal MI. Results Six data sets were obtained, 5 for BNP (n = 632) and 1 for N-terminal pro-BNP (n = 218). An NP level higher than the optimal cut point was an independent predictor for the primary composite endpoint (odds ratio: 7.9; 95% confidence interval: 4.7 to 13.3). BNP cut points were 30 pg/ml for screening (95% sensitivity, 44% specificity), 116 pg/ml for optimal (highest accuracy point; 66% sensitivity, 82% specificity), and 372 pg/ml for diagnostic (32% sensitivity, 95% specificity). Subsequent to revised cardiac risk index stratification, reclassification using the optimal cut point significantly improved risk prediction in all groups (net reclassification improvement 58%, p < 0.000001), particularly in the intermediate-risk group (net reclassification improvement 84%, p < 0.001). Conclusions Pre-operative NP levels can be used to independently predict cardiovascular events in the first 30 days after vascular surgery and to significantly improve the predictive performance of the revised cardiac risk index. (J Am Coll Cardiol 2011; 58: 522-9) (C) 2011 by the American College of Cardiology Foundation\n\nMahla, Elisabeth\n\n\n"
},
{
"text": "\n132362\nWeight loss surgery improves the metabolic status in an obese rat model but does not affect bladder fibrosis associated with high fat diet feeding.\n\nOberbach, A\n\nSchlichting, N\n\nHeinrich, M\n\nLehmann, S\n\nTill, H\n\nMohr, FW\n\nMannello, F\n\nStolzenburg, JU\n\nNeuhaus, J\n\nBeiträge in Fachzeitschriften\nISI:000340666900006\n24166068.0\n10.1038/ijo.2013.199\nNone\nBladder dysfunction has one of the highest prevalences as a comorbidity of obesity in industrialized countries. The aetiopathogenesis of obesity-associated bladder dysfunction is still obscure, but there is growing evidence that general metabolic changes in obese patients may be in part responsible. As demonstrated recently, high fat diet (HFD) significantly alters the protein expression in the urinary bladder, activates multiple signalling pathways associated with cell survival and inflammation and ultimately provokes bladder fibrosis in an obese rat model. The study aimed to elucidate the role of matrix metalloproteases (MMPs) and their specific tissue inhibitors of metalloproteases (TIMPs) in obesity-related bladder extracellular matrix (ECM) remodelling and the effect of weight loss surgery via sleeve gastrectomy (SG) on phenotype and molecular parameters.\n Twenty-four male Sprague-Dawley rats were used for (i) characterization of the HFD phenotype and (ii) evaluation of alterations following SG. Metabolic status, the degree of bladder fibrosis and tissue expression and activity of MMP2, MMP9, MMP14, TIMP1 and TIMP2 were analysed by immunohistochemistry, enzyme-linked immunosorbent assay and activity assays. Statistical differences were calculated by analysis of variance or independent Student's t-test. A P-value <0.05 was considered statistically significant.\n In HFD rats, we found significant alterations in lipid metabolism, fat mass, free fatty acid profile, insulin resistance and inflammatory markers. Voided volume was significantly decreased, and bladder showed marked fibrosis. MMPs and TIMPs were differentially regulated depending on animal status (controls, chow diet, HFD, and SG- and sham-operated animals) in both urothelium and detrusor smooth muscle. Although animal weight and most metabolic parameters were positively affected by SG, bladder fibrosis persisted. The limitations of this study were 1 month follow-up and lack of direct measurement of bladder function.\n Early diagnosis of the bladder dysfunction associated with obesity is essential to allow targeted early intervention, that is, before manifestation of potentially irreversible ECM fibrotic alterations.\n\nTill, Holger\n\n\n"
},
{
"text": "\n138402\nAccuracy of two continuous glucose monitoring systems: a head-to-head comparison under clinical research centre and daily life conditions.\n\nKropff, J\n\nBruttomesso, D\n\nDoll, W\n\nFarret, A\n\nGalasso, S\n\nLuijf, YM\n\nMader, JK\n\nPlace, J\n\nBoscari, F\n\nPieber, TR\n\nRenard, E\n\nDeVries, JH\n\nBeiträge in Fachzeitschriften\nISI:000350969500004\n25132320.0\n10.1111/dom.12378\nPMC4409843\nTo assess the accuracy and reliability of the two most widely used continuous glucose monitoring (CGM) systems.\n We studied the Dexcom®G4 Platinum (DG4P; Dexcom, San Diego, CA, USA) and Medtronic Paradigm Veo Enlite system (ENL; Medtronic, Northridge, CA, USA) CGM systems, in 24 patients with type 1 diabetes. The CGM systems were tested during 6-day home use and a nested 6-h clinical research centre (CRC) visit. During the CRC visit, frequent venous blood glucose samples were used as reference while patients received a meal with an increased insulin bolus to induce an aggravated postprandial glucose nadir. At home, patients performed at least six reference capillary blood measurements per day. A Wilcoxon signed-rank test was performed using all data points ≥15 min apart.\n The overall mean absolute relative difference (MARD) value [standard deviation (s.d.)] measured at the CRC was 13.6 (11.0)% for the DG4P and 16.6 (13.5)% for the ENL [p < 0.0002, confidence interval of difference (CI Δ) 1.7-4.3%, n = 530]. The overall MARD assessed at home was 12.2 (12.0)% for the DG4P and 19.9 (20.5)% for the ENL (p < 0.0001, CI Δ = 5.8-8.7%, n = 839). During the CRC visit, the MARD in the hypoglycaemic range [≤3.9 mmol/l (70 mg/dl)], was 17.6 (12.2)% for the DG4P and 24.6 (18.8)% for the ENL (p = 0.005, CI Δ 3.1-10.7%, n = 117). Both sensors showed higher MARD values during hypoglycaemia than during euglycaemia [3.9-10 mmol/l (70-180 mg/dl)]: for the DG4P 17.6 versus 13.0% and for the ENL 24.6 versus 14.2%.\n During circumstances of intended use, including both a CRC and home phase, the ENL was noticeably less accurate than the DG4P sensor. Both sensors showed lower accuracy in the hypoglycaemic range. The DG4P was less affected by this negative effect of hypoglycaemia on sensor accuracy than was the ENL.\n © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.\n\nMader, Julia\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n140627\n[Recommendations for the use of faecal microbiota transplantation "stool transplantation": consensus of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) in cooperation with the Austrian Society of Infectious Diseases and Tropical Medicine].\n\nKump, PK\n\nKrause, R\n\nSteininger, C\n\nGröchenig, HP\n\nMoschen, A\n\nMadl, C\n\nNovacek, G\n\nAllerberger, F\n\nHögenauer, C\n\nBeiträge in Fachzeitschriften\nNone\n25474284.0\n10.1055/s-0034-1385562\nNone\nThe intestinal microbiota has a pivotal role in the maintenance of health of the human organism, especially in the defense against pathogenic microorganisms. Alterations in the microbiota, also termed dysbiosis, seem to be involved in the pathogenesis of a variety of intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT), also known as stool transplantation, is a therapeutic procedure aiming at restoring an altered intestinal microbiota by administration of stool microorganisms from a healthy donor into the intestinal tract of a patient. FMT is most commonly used for recurrent forms of Clostridium difficile infections (CDI). There are currently many cohort studies in a large number of patients and a randomized controlled trial showing a dramatic effect of FMT for this indication. Therefore FMT is recommended by international medical societies for the treatment of recurrent CDI with high scientific evidence. Other potential indications are the treatment of fulminant CDI or the treatment of inflammatory bowel diseases. In the practical utilization of FMT there are currently several open questions regarding the screening of stool donors, the processing of stool and the mode of FMT application. Different modes of FMT application have been described, the application into the colon has to be preferred due to less reported side effects than the application into the upper gastrointestinal tract. So far only very few side effects due to FMT have been reported, nevertheless the use and risks of FMT are currently intensely debated in the medical community. This consensus report of the Austrian society of gastroenterology and hepatology (ÖGGH) in cooperation with the Austrian society of infectious diseases and tropical medicine provides instructions for physicians who want to use FMT which are based on the current medical literature.\n © Georg Thieme Verlag KG Stuttgart · New York.\n\nHoegenauer, Christoph\n\nKrause, Robert\n\nKump, Patrizia\n\n\n"
},
{
"text": "\n140930\nA computational procedure for identifying master regulator candidates: a case study on diabetes progression in Goto-Kakizaki rats.\n\nPiao, G\n\nSaito, S\n\nSun, Y\n\nLiu, ZP\n\nWang, Y\n\nHan, X\n\nWu, J\n\nZhou, H\n\nChen, L\n\nHorimoto, K\n\nBeiträge in Fachzeitschriften\nISI:000306568400002\n23046543.0\n10.1186/1752-0509-6-S1-S2\nPMC3403593\nWe have recently identified a number of active regulatory networks involved in diabetes progression in Goto-Kakizaki (GK) rats by network screening. The networks were quite consistent with the previous knowledge of the regulatory relationships between transcription factors (TFs) and their regulated genes. To study the underlying molecular mechanisms directly related to phenotype changes, such as diseases, we also previously developed a computational procedure for identifying transcriptional master regulators (MRs) in conjunction with network screening and network inference, by effectively perturbing the phenotype states.\n In this work, we further improved our previous method for identifying MR candidates, by listing them in a more reliable manner, and applied the method to reveal the MR candidates for diabetes progression in GK rats from the active networks. Specifically, the active TF-gene pairs for different time periods in GK rats were first extracted from the networks by network screening. Another set of active TF-gene pairs was selected by network inference, by considering the gene expression signatures for those periods between GK and Wistar-Kyoto (WKY) rats. The TF-gene pairs extracted by the two methods were then further selected, from the viewpoints of the emergence specificity of TF in GK rats and the regulated-gene coverage of TF in the expression signature. Finally, we narrowed all of the genes down to only 5 TFs (Etv4, Fus, Nr2f1, Sp2, and Tcfap2b) as the candidates of MRs, with 54 regulated genes, by merging the selected TF-gene pairs.\n The present method has successfully identified biologically plausible MR candidates, including the TFs related to diabetes in previous reports. Although the experimental verifications of the candidates and the present procedure are beyond the scope of this study, we narrowed down the candidates to 5 TFs, which can be used to perform the verification experiments relatively easily. The numerical results showed that our computational method is an efficient way to detect the key molecules responsible for biological phenomena.\n\n\n"
},
{
"text": "\n142798\nThe impact of interleukin 28B rs12979860 single nucleotide polymorphism and liver fibrosis stage on response-guided therapy in HIV/HCV-coinfected patients.\n\nMandorfer, M\n\nNeukam, K\n\nReiberger, T\n\nPayer, BA\n\nRivero, A\n\nPuoti, M\n\nBoesecke, C\n\nBaumgarten, A\n\nGrzeszczuk, A\n\nZangerle, R\n\nMeyer-Olson, D\n\nRockstroh, JK\n\nTrauner, M\n\nPineda, JA\n\nPeck-Radosavljevic, M\n\nBeiträge in Fachzeitschriften\nISI:000326841800005\n23835502.0\n10.1097/01.aids.0000432460.44593.ef\nNone\nAccording to the European AIDS Clinical Society (EACS) guidelines for response-guided therapy (RGT) of chronic hepatitis C virus (HCV) infection in HIV-positive patients, HCV-genotype (GT) and rapid virologic response (RVR) exclusively determine the duration of antiviral therapy with pegylated interferon and ribavirin (PEGIFN+RBV). The aim of this study was to investigate the impact of interleukin 28B rs12979860 single nucleotide polymorphism (IL28B) and liver fibrosis stage on RGT in HIV/HCV-coinfected patients.\n Four hundred and thirty HIV/HCV-coinfected patients treated with PEGIFN+RBV were included in this multinational, retrospective analysis.\n Advanced liver fibrosis was defined as either METAVIR F3/F4 or liver stiffness more than 9.5 kPa.\n In patients with GT1/4 without RVR (GT1/4-noRVR), higher sustained virologic response (SVR) rates were observed in patients with extended treatment duration (48 weeks: 35% vs. 72 weeks: 60%; P = 0.008). In GT1/4-noRVR patients without advanced liver fibrosis (48 weeks: 45% vs. 72 weeks: 61%; P = 0.176), or with IL28B C/C (48 weeks: 48% vs. 72 weeks: 69%; P = 0.207), SVR rates did not vary significantly throughout the treatment duration subgroups. In contrast, in patients with advanced liver fibrosis (48 weeks: 11% vs. 72 weeks: 45%; P = 0.031), or IL28B non-C/C (48 weeks: 28% vs. 72 weeks: 56%; P = 0.011), extended treatment duration was associated with substantially higher SVR rates. GT2/3 patients with RVR (GT2/3-RVR) with shortened treatment duration (24 weeks) displayed SVR rates ranging from 83 to 100%, regardless of IL28B and liver fibrosis stage.\n Our study confirms the concept of RGT in HIV/HCV coinfection and supports the extension of therapy duration to 72 weeks for patients with GT1/4-noRVR, especially in patients with IL28B non-C/C or advanced liver fibrosis. The results of our study strongly support the shortening of therapy duration to 24 weeks in GT2/3-RVR patients, regardless of IL28B and advanced liver fibrosis.\n\n\n"
},
{
"text": "\n144396\nClinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein.\n\nBaumann, M\n\nSahin, K\n\nLechner, C\n\nHennes, EM\n\nSchanda, K\n\nMader, S\n\nKarenfort, M\n\nSelch, C\n\nHäusler, M\n\nEisenkölbl, A\n\nSalandin, M\n\nGruber-Sedlmayr, U\n\nBlaschek, A\n\nKraus, V\n\nLeiz, S\n\nFinsterwalder, J\n\nGotwald, T\n\nKuchukhidze, G\n\nBerger, T\n\nReindl, M\n\nRostásy, K\n\nBeiträge in Fachzeitschriften\nISI:000349720800007\n25121570.0\n10.1136/jnnp-2014-308346\nNone\nMyelin oligodendrocyte glycoprotein (MOG) antibodies have been recently described in children with acute disseminating encephalomyelitis (ADEM), but the clinical and neuroradiological characterisation of this subgroup is lacking.\n To compare the clinical and neuroradiological features of paediatric ADEM with and without MOG antibodies.\n Clinical course, cerebrospinal fluid (CSF)-, MRI studies, outcome and MOG status of 33 paediatric ADEM prospectively studied were reviewed.\n MOG antibodies (median 1:2560; range 1:160-1:20 480) were detected in 19 children with ADEM. The majority of children showed a decline of serum MOG-IgG titres over time. Children with MOG antibodies did not differ in their age at presentation, sex ratio, the presence of oligoclonal bands, clinical symptoms or initial severity, apart from a higher CSF cell count (p=0.038), compared with children without MOG antibodies. In addition, further relapsing demyelinating episodes associated with MOG antibodies were observed only in children with MOG antibodies. All 19 children with MOG antibodies had a uniform MRI pattern, characterised by large, hazy and bilateral lesions and the absence of atypical MRI features (eg, mainly small lesions, well-defined lesions), which was significantly different compared to that of children without MOG antibodies (p=0.003; and p=0.032, respectively). In addition, children with MOG antibodies had involvement of more anatomical areas (p=0.035) including the myelon characterised by a longitudinally extensive transverse myelitis (p=0.003), more often a complete resolution of lesions (p=0.036) and a better outcome (p=0.038).\n Patients with ADEM with MOG antibodies in our cohort had a uniform MRI characterised by large, bilateral and widespread lesions with an increased frequency of longitudinal extensive transverse myelitis and a favourable clinical outcome in contrast to children lacking MOG antibodies.\n Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.\n\n\n"
},
{
"text": "\n161895\nIntraoperative optical coherence tomography assisted analysis of pars Plana vitrectomy for retinal detachment in morning glory syndrome: a case report.\n\nLytvynchuk, LM\n\nGlittenberg, CG\n\nAnsari-Shahrezaei, S\n\nBinder, S\n\nBeiträge in Fachzeitschriften\nISI:000406859100001\n28764684.0\n10.1186/s12886-017-0533-0\nPMC5540621\nThe pathogenesis of non-rhegmatogenous retinal detachment (non-RRD) associated with morning glory syndrome (MGS) is not established, as well as best surgical approach to treat RD. Our purpose was to analyse intraoperative optical coherence tomography data (iOCT) in all steps of pars plana vitrectomy (PPV) for non-RRD in MGS, in order to follow pathophysiological aspects of the disease and to understand the tissues behaviour during surgical workflow.\n Intraoperative spectral domain optical coherent tomography (iSD-OCT) assisted PPV using Rescan 700 (Carl Zeiss Meditech, Jena, Germany) with epiretinal membrane (ERM) and internal retinal membrane (ILM) peeling, and air endotamponade was performed on the only eye of a 21 years old female with non-RRD associated with MGS. BCVA, pre-, intra- and postoperative OCT were performed along with standard ocular examination. iOCT video and snapshots were analysed intra- and postoperatively using post-processing approach using graphic software. The progression of non-RRD resulted in best corrected visual acuity (BCVA) decrease from 0.8 to 0.2. Triamcinolone enhanced iOCT imaging revealed strong vitreous traction and adhesion above the macula and optic disc. Internal limiting membrane was peeled under iOCT control to prevent the peeling of inner layers of the retinal schisis. No retinal break was detected, and only air endotamponade was performed. The retina reattached during first 4 weeks of follow-up with gradual resolution of intraretinal- and subretinal fluid, and remained stable in 12 months. BCVA improved to 0.8.\n Based on iSD-OCT findings we assume that non-RRD in this case of MGS is caused primarily by the vitreous traction with further possible formation of the retinal breaks. Retinal reattachment reached only with air endotamponade strongly advocates the tractional component of non-RRD and retinal schisis assotiated with MGS. Early PPV for central non-RRD and retinal schisis with the use of iOCT can be performed in more safe and controlled manner and has to be considered to reduce the risk of retinal break formation and to prevent the central vision loss.\n\n\n"
},
{
"text": "\n168532\nSurgery for metachronous metastasis of soft tissue sarcoma - A magnitude of benefit analysis using propensity score methods.\n\nSmolle, MA\n\nvan Praag, VM\n\nPosch, F\n\nBergovec, M\n\nLeitner, L\n\nFriesenbichler, J\n\nHeregger, R\n\nRiedl, JM\n\nPichler, M\n\nGerger, A\n\nSzkandera, J\n\nStöger, H\n\nSmolle-Jüttner, FM\n\nLiegl-Atzwanger, B\n\nFiocco, M\n\nvan de Sande, MA\n\nLeithner, A\n\nBeiträge in Fachzeitschriften\nISI:000458224600025\n30031674.0\n10.1016/j.ejso.2018.06.019\nNone\nMetastasectomy is hypothesised to improve OS in metastatic STS, but evidence in favour of this approach derives from non-controlled single-arm cohorts affected by selection bias. The objective was to quantify the effect of metastasectomy vs. non-surgical management on overall survival (OS) in patients with metachronous metastases from extremity- and trunk soft tissue sarcoma (STS).\n From a population of 1578 STS patients, 135 patients who underwent surgery for localised STS at two European centres between 1998 and 2015 and developed metachronous STS metastases were included. Propensity score analyses with inverse-probability-of-treatment-weights (IPTW) and landmark analyses were performed to control for selection and immortal time bias, respectively.\n OS was significantly longer in the 68 patients undergoing metastasectomy than in the 67 patients who were treated non-invasively for their metastasis (10-year OS: 23% vs. 4%; hazard ratio (HR) = 0.34, 95% CI: 0.22-0.53, p < 0.0001). This association prevailed after IPTW-weighting of the data to control for the higher prevalence of favourable prognostic factors in the surgery group (adjusted 10-year OS: 17% vs. 3%, log-rank p < 0.0001; HR = 0.33, 95% CI: 0.20-0.52, p < 0.0001). Five-year OS estimates were 27.8% in patients who had and 14.5% in patients who had not undergone metastasectomy within the first 3 months after diagnosis of a metastasis (p < 0.0001).\n In this observational bi-centre study, metastasectomy was associated with prolonged survival in patients with metachronous STS metastases. In the absence of randomized studies, our results indicate that metastasectomy should be considered as an important treatment option for metachronous STS metastases.\n Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.\n\nBergovec, Marko\n\nFriesenbichler, Jörg\n\nGerger, Armin\n\nLeithner, Andreas\n\nLeitner, Lukas\n\nLiegl-Atzwanger, Bernadette\n\nPichler, Martin\n\nPosch, Florian\n\nRiedl, Jakob\n\nSmolle, Maria Anna\n\nSmolle-Juettner, Freyja-Maria\n\nStoeger, Herbert\n\nSzkandera, Joanna\n\n\n"
},
{
"text": "\n174097\nCardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts.\n\nHeras-Bautista, CO\n\nMikhael, N\n\nLam, J\n\nShinde, V\n\nKatsen-Globa, A\n\nDieluweit, S\n\nMolcanyi, M\n\nUvarov, V\n\nJütten, P\n\nSahito, RGA\n\nMederos-Henry, F\n\nPiechot, A\n\nBrockmeier, K\n\nHescheler, J\n\nSachinidis, A\n\nPfannkuche, K\n\nBeiträge in Fachzeitschriften\nISI:000466258600015\n30862552.0\n10.1016/j.actbio.2019.03.017\nNone\nPathophysiological conditions, such as myocardial infarction and mechanical overload affect the mammalian heart integrity, leading to a stiffened fibrotic tissue. With respect to the pathophysiology of cardiac fibrosis but also in the limelight of upcoming approaches of cardiac cell therapy it is of interest to decipher the interaction of cardiomyocytes with fibrotic matrix. Therefore, we designed a hydrogel-based model to engineer fibrotic tissue in vitro as an approach to predict the behavior of cardiomyocytes facing increased matrix rigidity. Here, we generated pure induced pluripotent stem cell-derived cardiomyocytes and cultured them on engineered polyacrylamide hydrogels matching the elasticities of healthy as well as fibrotic cardiac tissue. Only in cardiomyocytes cultured on matrices with fibrotic-like elasticity, transcriptional profiling revealed a substantial up-regulation of a whole panel of cardiac fibrosis-associated transcripts, including collagen I and III, decorin, lumican, and periostin. In addition, matrix metalloproteinases and their inhibitors, known to be essential in cardiac remodeling, were found to be elevated as well as insulin-like growth factor 2. Control experiments with primary cardiac fibroblasts were analyzed and did not show comparable behavior. In conclusion, we do not only present a snapshot on the transcriptomic fingerprint alterations in cardiomyocytes under pathological conditions but also provide a new reproducible approach to study the effects of fibrotic environments to various cell types. STATEMENT OF SIGNIFICANCE: The ageing population in many western countries is faced with an increasing burden of ageing-related diseases such as heart failure which is associated with cardiac fibrosis. A deeper understanding of the interaction of organotypic cells with altered extracellular matrix mechanical properties is of pivotal importance to understand the underlying mechanisms. Here, we present a strategy to combine hydrogel matrices with induced pluripotent stem cell derived cardiomyocytes to study the effect of matrix stiffening on these cells. Our findings suggest an active role of matrix stiffening on cardiomyocyte function and heart failure progression.\n Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n175376\nHealth effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.\n\nGBD 2017 Diet Collaborators\n\nBeiträge in Fachzeitschriften\nISI:000467698100031\n30954305.0\n10.1016/S0140-6736(19)30041-8\nPMC6899507\nSuboptimal diet is an important preventable risk factor for non-communicable diseases (NCDs); however, its impact on the burden of NCDs has not been systematically evaluated. This study aimed to evaluate the consumption of major foods and nutrients across 195 countries and to quantify the impact of their suboptimal intake on NCD mortality and morbidity.\n By use of a comparative risk assessment approach, we estimated the proportion of disease-specific burden attributable to each dietary risk factor (also referred to as population attributable fraction) among adults aged 25 years or older. The main inputs to this analysis included the intake of each dietary factor, the effect size of the dietary factor on disease endpoint, and the level of intake associated with the lowest risk of mortality. Then, by use of disease-specific population attributable fractions, mortality, and disability-adjusted life-years (DALYs), we calculated the number of deaths and DALYs attributable to diet for each disease outcome.\n In 2017, 11 million (95% uncertainty interval [UI] 10-12) deaths and 255 million (234-274) DALYs were attributable to dietary risk factors. High intake of sodium (3 million [1-5] deaths and 70 million [34-118] DALYs), low intake of whole grains (3 million [2-4] deaths and 82 million [59-109] DALYs), and low intake of fruits (2 million [1-4] deaths and 65 million [41-92] DALYs) were the leading dietary risk factors for deaths and DALYs globally and in many countries. Dietary data were from mixed sources and were not available for all countries, increasing the statistical uncertainty of our estimates.\n This study provides a comprehensive picture of the potential impact of suboptimal diet on NCD mortality and morbidity, highlighting the need for improving diet across nations. Our findings will inform implementation of evidence-based dietary interventions and provide a platform for evaluation of their impact on human health annually.\n Bill & Melinda Gates Foundation.\n Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n177591\nHypoglycaemia leads to a delayed increase in platelet and coagulation activation markers in people with type 2 diabetes treated with metformin only: Results from a stepwise hypoglycaemic clamp study.\n\nAberer, F\n\nPferschy, PN\n\nTripolt, NJ\n\nSourij, C\n\nObermayer, AM\n\nPrüller, F\n\nNovak, E\n\nReitbauer, P\n\nKojzar, H\n\nPrietl, B\n\nKofler, S\n\nBrunner, M\n\nSvehlikova, E\n\nStojakovic, T\n\nScharnagl, H\n\nOulhaj, A\n\nAziz, F\n\nRiedl, R\n\nSourij, H\n\nBeiträge in Fachzeitschriften\nISI:000493725200001\n31595635.0\n10.1111/dom.13889\nPMC6972619\nTo investigate the effect of hypoglycaemia on platelet and coagulation activation in people with type 2 diabetes.\n This monocentric, open, single-arm, mechanistic trial included 14 people with established type 2 diabetes (four women, 10 men, age 55 ± 7 years, glycated haemoglobin concentration 51 ± 7 mmol/mol) receiving metformin monotherapy. A stepwise hyperinsulinaemic-hypoglycaemic clamp experiment (3.5 and 2.5 mmol/L, for 30 minutes respectively) was performed, aiming to investigate platelet and coagulation activity during predefined plateaus of hypoglycaemia, as well as 1 day and 7 days later.\n While platelet activation assessed by light transmittance aggregometry did not significantly increase after the hypoglycaemic clamp procedure, the more sensitive flow cytometry-based measurement of platelet surface activation markers showed hypoglycaemia-induced activation 24 hours (PAC1pos CD62Ppos , PAC1pos CD63Ppos and PAC1pos CD62Ppos CD63pos ; P < .01) and 7 days after the hypoglycaemic clamp (P < .001 for PAC1pos CD63pos ; P < .01 for PAC1pos CD62Ppos and PAC1pos CD62Ppos CD63pos ) in comparison to baseline. Coagulation markers, such as fibrinogen, D-dimer, plasminogen activator inhibitor-1, von Willebrand factor activity and factor VIII, were also significantly increased, an effect that was most pronounced 24 hours after the hypoglycaemic clamp.\n A single event of insulin-induced hypoglycaemia led to an increase in markers of platelet activation and coagulation in people with early stages of type 2 diabetes on metformin therapy. However, the activation occurred with a delay and was evident 24 hours and 7 days after the actual hypoglycaemic episode.\n © 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.\n\nAberer, Felix\n\nBrunner, Martina\n\nKofler, Selina\n\nKojzar, Harald\n\nNovak, Eva\n\nObermayer, Anna\n\nPferschy, Peter\n\nPrietl, Barbara\n\nPrüller, Florian\n\nRiedl, Regina\n\nScharnagl, Hubert\n\nSourij, Caren\n\nSourij, Harald\n\nSvehlikova, Eva\n\nTripolt, Norbert\n\n\n"
},
{
"text": "\n185386\nComplications in leg lengthening using an Ilizarov external fixator and intramedullary alignment in children: comparative study during a fourteen-year period.\n\nBukva, B\n\nVrgoč, G\n\nRakovac, I\n\nDučić, S\n\nSindik, J\n\nČoklo, M\n\nMarinović, M\n\nBakota, B\n\nBeiträge in Fachzeitschriften\nNone\n26613631.0\n10.1016/j.injury.2015.10.058\nNone\nThe purpose of this retrospective study was to evaluate the complications associated with leg lengthening in children treated with the Ilizarov external fixator (IEF) and compare them between two groups of patients: one group was treated using an IEF alone and the other group was treated using an IEF in association with intramedullary alignment (IA).\n The study was performed at the University Children's Hospital in Belgrade, Serbia during a fourteen-year period (from 2000 to 2014). Complications occurred in 73 paediatric patients who underwent the leg lengthening procedure. Complications were classified according to the Caton classification and compared between two groups. Group I comprised 39 patients who underwent the limb lengthening procedure using IEF alone. Group II consisted of 34 patients who were treated with the combination of IEF and IA using two Kirschner wires (K-wires) or Titanium Elastic Nails (TEN). The duration of hospital treatment was also compared between the two groups and the impact of the type of IA on the occurrence of complications was assessed.\n There was a high rate of complications in patients treated using an IEF compared with those treated using the combination of IEF and IA, but there was no statistically significant difference between the two groups. There was a statistically significant difference in the duration of initial hospitalisation between the two groups, particularly when comparing TEN usage in IA. A comparison of the group of patients treated using an IEF in association with K-wires and patients treated using IEF and TEN showed there was no statistically significant difference in complication rate and duration of initial hospitalisation.\n IA has multiple advantages as a method of treatment of leg length inequality. The major effect of applying IA in association with a circular IEF is significantly reduced complication rate and duration of initial hospitalisation, particularly when using TEN as a method of IA. This method of treatment also decreases hospital costs.\n Copyright © 2015 Elsevier Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n256\nAPOLIPOPROTEIN-E GENE-EXPRESSION IN MOUSE 3T3-L1 ADIPOCYTES AND HUMAN ADIPOSE-TISSUE AND ITS REGULATION BY DIFFERENTIATION AND LIPID-CONTENT.\n\nZECHNER, R\n\nMOSER, R\n\nNEWMAN, TC\n\nFRIED, SK\n\nBRESLOW, JL\n\nBeiträge in Fachzeitschriften\nISI:A1991FP08600087\nNone\nNone\nNone\nApolipoprotein E (apoE) is an important constituent of plasma lipoproteins and a ligand for several lipoprotein receptors. It is produced mainly in the liver but also in several peripheral tissues like brain, adrenal glands, kidney, and macrophages. Some of these tissues also coexpress lipoprotein lipase (LPL), an important enzyme in the metabolism of lipids and lipoproteins. This suggested a possible coordinate expression of these genes and led us to analyze whether adipocytes, a major source of LPL, could also synthesize apoE. Northern blotting experiments showed that apoE mRNA is found in differentiated mouse 3T3-L1 adipocytes as well as biopsies of human adipose tissue maintained in organ culture but not in undifferentiated 3T3-L1 preadipocytes. [S-35]Methionine pulse-labeling experiments revealed that apoE protein is produced in human adipose tissue and differentiated mouse 3T3-L1 adipocytes but not in preadipocytes. In biosynthetic labeling experiments, most apoE was found to be cell associated even after prolonged chase periods. Heparin treatment of the cultured cells did not enhance apoE secretion. During differentiation of 3T3-L1 cells, the onset of apoE gene expression was later than that of LPL. The apoE mRNA and intracellular apoE protein concentrations increased linearly with time of differentiation, at least through day 11, whereas LPL showed highest expression at day 7 and then declined. The increase in apoE mRNA correlated with the cellular lipid content. Inhibition of lipid accumulation in differentiated cells by biotin deprivation decreased apoE expression. Cholesterol-loading experiments suggested that apoE mRNA expression is regulated by the intracellular free cholesterol content of 3T3-L1 adipocytes. In contrast, the LPL mRNA level was not influenced by biotin deprivation or cholesterol loading. Human recombinant tumor necrosis factor, a potent inhibitor of LPL gene transcription, had no effect on adipocyte apoE mRNA levels. Therefore, although apoE and LPL are both expressed in adipocytes in a differentiation-dependent manner, the time course of their expression differs as do their responses to cellular lipid content and tumor necrosis factor. We conclude that these genes are not coordinately regulated in adipocytes.\n\n\n"
},
{
"text": "\n6273\nValidity of self-report of fractures: results from a prospective study in men and women across Europe. EPOS Study Group. European Prospective Osteoporosis Study Group.\n\nIsmail, AA\n\nO'Neill, TW\n\nCockerill, W\n\nFinn, JD\n\nCannata, JB\n\nHoszowski, K\n\nJohnell, O\n\nMatthis, C\n\nRaspe, H\n\nRaspe, A\n\nReeve, J\n\nSilman, AJ\n\nand and the EPOS Study Group\n\nBeiträge in Fachzeitschriften\nISI:000086769700009\n10824241.0\n10.1007/s001980050288\nNone\nIn population-based studies of osteoporosis, ascertainment of fractures is typically based on self-report, with subsequent verification by medical records. The aim of this analysis was to assess the validity of self-report of incident nonspine fractures using a postal questionnaire. The degree of overreporting of fracture (false positives) was assessed by comparing self-reports of new fracture from respondents in the multicenter European Prospective Osteoporosis Study with data from other sources including radiographs and medical records. In the analysis, 563 subjects reported nonspine fractures. Verification of the presence of fracture was possible in 510 subjects. Of these, fractures were not confirmed in 11% (false positives). The percentage of false positives was greater in men than in women (15% vs 9%, p = 0.04), and less for fractures of the distal forearm and hip than for fractures at other sites. In a separate study, the degree of underreporting (false negatives) was assessed by follow-up of 251 individuals with confirmed fracture ascertained from the records of fracture clinics in three European centers (Lubeck, Oviedo, Warsaw). Questionnaire responses were received from 174 (69%) subjects. Of these, 12 (7%) did not recall sustaining a fracture (false negatives). The percentage of false negatives was lower for hip and distal forearm fractures with only 3 of 90 (3%) such fractures not recalled. Using the combined data from both studies, of those who reported a 'date' of fracture on the questionnaire, 91% of subjects were correct to within 1 month of the actual date of the fracture. A postal questionnaire is a relatively simple and accurate method for obtaining information about the occurrence of hip and distal forearm fractures, including their timing. Accuracy of ascertainment of fractures at other sites is less good and where possible self-reported fractures at such sites should be verified from other sources.\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n88059\nTelmisartan to prevent recurrent stroke and cardiovascular events.\n\nYusuf, S\n\nDiener, HC\n\nSacco, RL\n\nCotton, D\n\nOunpuu, S\n\nLawton, WA\n\nPalesch, Y\n\nMartin, RH\n\nAlbers, GW\n\nBath, P\n\nBornstein, N\n\nChan, BP\n\nChen, ST\n\nCunha, L\n\nDahlöf, B\n\nDe Keyser, J\n\nDonnan, GA\n\nEstol, C\n\nGorelick, P\n\nGu, V\n\nHermansson, K\n\nHilbrich, L\n\nKaste, M\n\nLu, C\n\nMachnig, T\n\nPais, P\n\nRoberts, R\n\nSkvortsova, V\n\nTeal, P\n\nToni, D\n\nVanderMaelen, C\n\nVoigt, T\n\nWeber, M\n\nYoon, BW\n\nPRoFESS Study Group\n\nBeiträge in Fachzeitschriften\nISI:000259259900006\n18753639.0\n10.1056/NEJMoa0804593\nPMC2714258\nBACKGROUND: Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. METHODS: In a multicenter trial involving 20, 32 patients who recently had an ischemic stroke, we randomly assigned 10, 46 to receive telmisartan (80 mg daily) and 10, 86 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. RESULTS: The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). CONCLUSIONS: Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)\n\nHorner, Susanna\n\n\n"
},
{
"text": "\n138491\nSElf-gated Non-Contrast-Enhanced FUnctional Lung imaging (SENCEFUL) using a quasi-random fast low-angle shot (FLASH) sequence and proton MRI.\n\nFischer, A\n\nWeick, S\n\nRitter, CO\n\nBeer, M\n\nWirth, C\n\nHebestreit, H\n\nJakob, PM\n\nHahn, D\n\nBley, T\n\nKöstler, H\n\nBeiträge in Fachzeitschriften\nISI:000339570700006\n24820869.0\n10.1002/nbm.3134\nNone\nObtaining functional information on the human lung is of tremendous interest in the characterization of lung defects and pathologies. However, pulmonary ventilation and perfusion maps usually require contrast agents and the application of electrocardiogram (ECG) triggering and breath holds to generate datasets free of motion artifacts. This work demonstrates the possibility of obtaining highly resolved perfusion-weighted and ventilation-weighted images of the human lung using proton MRI and the SElf-gated Non-Contrast-Enhanced FUnctional Lung imaging (SENCEFUL) technique. The SENCEFUL technique utilizes a two-dimensional fast low-angle shot (FLASH) sequence with quasi-random sampling of phase-encoding (PE) steps for data acquisition. After every readout, a short additional acquisition of the non-phase-encoded direct current (DC) signal necessary for self-gating was added. By sorting the quasi-randomly acquired data according to respiratory and cardiac phase derived from the DC signal, datasets of representative respiratory and cardiac cycles could be accurately reconstructed. By application of the Fourier transform along the temporal dimension, functional maps (perfusion and ventilation) were obtained. These maps were compared with dynamic contrast-enhanced (DCE, perfusion) as well as standard Fourier decomposition (FD, ventilation) reference datasets. All datasets were additionally scored by two experienced radiologists to quantify image quality. In addition, one initial patient examination using SENCEFUL was performed. Functional images of healthy volunteers and a patient diagnosed with hypoplasia of the left pulmonary artery and left-sided pulmonary fibrosis were successfully obtained. Perfusion-weighted images corresponded well to DCE-MRI data; ventilation-weighted images offered a significantly better depiction of the lung periphery compared with standard FD. Furthermore, the SENCEFUL technique hints at a potential clinical relevance by successfully detecting a perfusion defect in the patient scan. It can be concluded that SENCEFUL enables highly resolved ventilation- and perfusion-weighted maps of the human lung to be obtained using proton MRI, and might be interesting for further clinical evaluation.\n Copyright © 2014 John Wiley & Sons, Ltd.\n\n\n"
},
{
"text": "\n139749\nPLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry.\n\nCasas, JP\n\nNinio, E\n\nPanayiotou, A\n\nPalmen, J\n\nCooper, JA\n\nRicketts, SL\n\nSofat, R\n\nNicolaides, AN\n\nCorsetti, JP\n\nFowkes, FG\n\nTzoulaki, I\n\nKumari, M\n\nBrunner, EJ\n\nKivimaki, M\n\nMarmot, MG\n\nHoffmann, MM\n\nWinkler, K\n\nMärz, W\n\nYe, S\n\nStirnadel, HA\n\nBoekholdt, SM\n\nKhaw, KT\n\nHumphries, SE\n\nSandhu, MS\n\nHingorani, AD\n\nTalmud, PJ\n\nBeiträge in Fachzeitschriften\nISI:000278213100005\n20479152.0\n10.1161/CIRCULATIONAHA.109.923383\nPMC3377948\nHigher lipoprotein-associated phospholipase A(2)(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal.\n A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2) PLA2G7 single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3) PLA2G7 single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17).\n Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD.\n\nMärz, Winfried\n\n\n"
}
]
}