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"text": "\n130213\nThe comparative cost-effectiveness of an equity-focused approach to child survival, health, and nutrition: a modelling approach.\n\nCarrera, C\n\nAzrack, A\n\nBegkoyian, G\n\nPfaffmann, J\n\nRibaira, E\n\nO'Connell, T\n\nDoughty, P\n\nAung, KM\n\nPrieto, L\n\nRasanathan, K\n\nSharkey, A\n\nChopra, M\n\nKnippenberg, R\n\nUNICEF Equity in Child Survival, Health and Nutrition Analysis Team\n\nBeiträge in Fachzeitschriften\nISI:000309931400033\n22999434.0\n10.1016/S0140-6736(12)61378-6\nNone\nProgress on child mortality and undernutrition has seen widening inequities and a concentration of child deaths and undernutrition in the most deprived communities, threatening the achievement of the Millennium Development Goals. Conversely, a series of recent process and technological innovations have provided effective and efficient options to reach the most deprived populations. These trends raise the possibility that the perceived trade-off between equity and efficiency no longer applies for child health--that prioritising services for the poorest and most marginalised is now more effective and cost effective than mainstream approaches. We tested this hypothesis with a mathematical-modelling approach by comparing the cost-effectiveness in terms of child deaths and stunting events averted between two approaches (from 2011-15 in 14 countries and one province): an equity-focused approach that prioritises the most deprived communities, and a mainstream approach that is representative of current strategies. We combined some existing models, notably the Marginal Budgeting for Bottlenecks Toolkit and the Lives Saved Tool, to do our analysis. We showed that, with the same level of investment, disproportionately higher effects are possible by prioritising the poorest and most marginalised populations, for averting both child mortality and stunting. Our results suggest that an equity-focused approach could result in sharper decreases in child mortality and stunting and higher cost-effectiveness than mainstream approaches, while reducing inequities in effective intervention coverage, health outcomes, and out-of-pocket spending between the most and least deprived groups and geographic areas within countries. Our findings should be interpreted with caution due to uncertainties around some of the model parameters and baseline data. Further research is needed to address some of these gaps in the evidence base. Strategies for improving child nutrition and survival, however, should account for an increasing prioritisation of the most deprived communities and the increased use of community-based interventions.\n\n\n"
},
{
"text": "\n131796\nTime to recurrence is a significant predictor of cancer-specific survival after recurrence in patients with recurrent renal cell carcinoma--results from a comprehensive multi-centre database (CORONA/SATURN-Project).\n\nBrookman-May, SD\n\nMay, M\n\nShariat, SF\n\nNovara, G\n\nZigeuner, R\n\nCindolo, L\n\nDe Cobelli, O\n\nDe Nunzio, C\n\nPahernik, S\n\nWirth, MP\n\nLongo, N\n\nSimonato, A\n\nSerni, S\n\nSiracusano, S\n\nVolpe, A\n\nMorgia, G\n\nBertini, R\n\nDalpiaz, O\n\nStief, C\n\nFicarra, V\n\nMembers of the CORONA-Project\n\nMembers of the SATURN-Project\n\nYoung Academic Urologists Renal Cancer Group\n\nBeiträge in Fachzeitschriften\nISI:000325556600017\n23890378.0\n10.1111/bju.12246\nNone\nObjectives To assess the prognostic impact of time to recurrence (TTR) on cancer-specific survival (CSS) after recurrence in patients with renal cell carcinoma (RCC) undergoing radical nephrectomy or nephron-sparing surgery. To analyse differences in clinical and histopathological criteria between patients with early and late recurrence. Patients and Methods Of 13107 patients with RCC from an international multicentre database, 1712 patients developed recurrence in the follow-up (FU), at a median (interquartile range) of 50.1 (25-106) months. In all, 1402 patients had recurrence at 5 years (Group A) and 310 patients beyond this time (Group B). Differences in clinical and histopathological variables between patients with early and late recurrence were analysed. The influence of TTR and further variables on CSS after recurrence was assessed by Cox regression analysis. Results Male gender, advanced age, tumour diameter and stage, Fuhrman grade 3-4, lymphovascular invasion (LVI), and pN + stage were significantly more frequent in patients with early recurrence, who had a significantly reduced 3-year CSS of 30% compared with patients in Group B (41%; P = 0.001). Age, gender, tumour histology, pT stage, and continuous TTR (hazard ratio 0.99, P = 0.006; monthly interval) independently predicted CSS. By inclusion of dichotomised TTR in the multivariable model, a significant influence of this variable on CSS was present until 48 months after surgery, but not beyond this time. Conclusions Advanced age, male gender, larger tumour diameters, LVI, Fuhrman grade 3-4, pN + stage, and advanced tumour stages are associated with early recurrence. Up to 4 years from surgery, a shorter TTR independently predicts a reduced CSS after recurrence.\n\nDalpiaz, Orietta\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n137581\nAzacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group.\n\nPleyer, L\n\nBurgstaller, S\n\nGirschikofsky, M\n\nLinkesch, W\n\nStauder, R\n\nPfeilstocker, M\n\nSchreder, M\n\nTinchon, C\n\nSliwa, T\n\nLang, A\n\nSperr, WR\n\nKrippl, P\n\nGeissler, D\n\nVoskova, D\n\nSchlick, K\n\nThaler, J\n\nMachherndl-Spandl, S\n\nTheiler, G\n\nEckmüllner, O\n\nGreil, R\n\nBeiträge in Fachzeitschriften\nISI:000342491800003\n24951123.0\n10.1007/s00277-014-2126-9\nPMC4176957\nData on efficacy and safety of azacitidine in acute myeloid leukemia (AML) with >30 % bone marrow (BM) blasts are limited, and the drug can only be used off-label in these patients. We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry (clinicaltrials.gov identifier NCT01595295). We herein update this report with a population almost twice as large (n = 302). This cohort included 172 patients with >30 % BM blasts; 93 % would have been excluded from the pivotal AZA-001 trial (which led to European Medicines Agency (EMA) approval of azacitidine for high-risk myelodysplastic syndromes (MDS) and AML with 20-30 % BM blasts). Despite this much more unfavorable profile, results are encouraging: overall response rate was 48 % in the total cohort and 72 % in patients evaluable according to MDS-IWG-2006 response criteria, respectively. Median OS was 9.6 (95 % CI 8.53-10.7) months. A clinically relevant OS benefit was observed with any form of disease stabilization (marrow stable disease (8.1 months), hematologic improvement (HI) (9.7 months), or the combination thereof (18.9 months)), as compared to patients without response and/or without disease stabilization (3.2 months). Age, white blood cell count, and BM blast count at start of therapy did not influence OS. The baseline factors LDH >225 U/l, ECOG ≥2, comorbidities ≥3, monosomal karyotype, and prior disease-modifying drugs, as well as the response-related factors hematologic improvement and further deepening of response after first response, were significant independent predictors of OS in multivariate analysis. Azacitidine seems effective in WHO-AML, including patients with >30 % BM blasts (currently off-label use). Although currently not regarded as standard form of response assessment in AML, disease stabilization and/or HI should be considered sufficient response to continue treatment with azacitidine.\n\n\n"
},
{
"text": "\n146808\nExpert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease--Clinical practice recommendations.\n\nTrenkwalder, C\n\nChaudhuri, KR\n\nGarcía Ruiz, PJ\n\nLeWitt, P\n\nKatzenschlager, R\n\nSixel-Döring, F\n\nHenriksen, T\n\nSesar, Á\n\nPoewe, W\n\nExpert Consensus Group for Use of Apomorphine in Parkinson's Disease\n\nBaker, M\n\nCeballos-Baumann, A\n\nDeuschl, G\n\nDrapier, S\n\nEbersbach, G\n\nEvans, A\n\nFernandez, H\n\nIsaacson, S\n\nvan Laar, T\n\nLees, A\n\nLewis, S\n\nMartínez Castrillo, JC\n\nMartinez-Martin, P\n\nOdin, P\n\nO'Sullivan, J\n\nTagaris, G\n\nWenzel, K\n\nBeiträge in Fachzeitschriften\nISI:000361576600003\n26189414.0\n10.1016/j.parkreldis.2015.06.012\nNone\nExtensive published evidence supports the use of subcutaneously-administered apomorphine as an effective therapy for Parkinson's disease (PD) but to date no consensus recommendations have been available to guide healthcare professionals in the optimal application of apomorphine therapy in clinical practice. This document outlines best-practice recommendations for selecting appropriate candidates for apomorphine intermittent injection (the pen-injection formulation) or apomorphine continuous infusion (the pump formulation), for initiating patients onto therapy and for managing their ongoing treatment. Apomorphine is a suitable therapeutic option for PD patients who experience troublesome 'off' periods despite optimized treatment with oral PD medications. Due to its speed of onset, apomorphine injection is particularly suited to those patients requiring rapid, reliable relief of both unpredictable and predictable 'off' periods, those who require reliable and fast relief when anticipating an 'off', those with levodopa absorption or gastric emptying problems resulting in delayed or failed 'on', or for rapid relief of early morning dystonia or akinesia. Apomorphine infusion(1) is suited for patients whose 'off' periods can no longer be adequately controlled by standard oral PD treatment or for those in whom rescue doses of apomorphine injection are effective but either needed too frequently (more than 4-6 times per day), or are associated with increasing dyskinesia. In addition to treating motor fluctuations, there is evidence that apomorphine infusion may be effective for the management of specific non-motor symptoms of PD associated with 'off' periods. Apomorphine infusion is less invasive than other non-oral treatment options for advancing disease, intrajejunal levodopa infusion and deep-brain stimulation. \n Copyright © 2015 Elsevier Ltd. All rights reserved.\n\nWenzel, Karoline\n\n\n"
},
{
"text": "\n151080\nDetermination of Eligibility in Related Pediatric Hematopoietic Cell Donors: Ethical and Clinical Considerations. Recommendations from a Working Group of the Worldwide Network for Blood and Marrow Transplantation Association.\n\nBitan, M\n\nvan Walraven, SM\n\nWorel, N\n\nBall, LM\n\nStyczynski, J\n\nTorrabadella, M\n\nWitt, V\n\nShaw, BE\n\nSeber, A\n\nYabe, H\n\nGreinix, HT\n\nPeters, C\n\nGluckman, E\n\nRocha, V\n\nHalter, J\n\nPulsipher, MA\n\nBeiträge in Fachzeitschriften\nISI:000368218800015\n26307344.0\n10.1016/j.bbmt.2015.08.017\nNone\nRelated donors for hematopoietic cell (HC) transplantation are a growing population in recent years because of expanding indications for allogeneic transplantation. The safety and welfare of the donor are major concerns for the transplantation community, especially for related sibling donors of young recipients who are children and, thus, not able to fully consent. Because donation of HC does not improve the donor's own physical health and carries a risk of side effects, careful assessment of medical risks specific to the individual donor, as well as consideration of ethical and legal aspects associated with donation from a child, must be considered. In addition, donor centers must balance the needs of both the donor and the recipient, understanding the inherent conflict parents may have as they can be overly focused on the very sick child receiving a transplant, rather than on the relatively less significant health or emotional problems that a sibling donor may have, which could impact risk with donation. Likewise, consideration must be made regarding the nature of the relationship of the sibling donor to the recipient and also aspects of performing research on pediatric HC donors. In this article, as members of the Donor Issues Committee of the Worldwide Network for Blood and Marrow Transplantation, we review key ethical concerns associated with pediatric donation and then give recommendations for screening potential child donors with underlying health conditions. These recommendations are aimed at protecting the physical and emotional well-being of childhood donors and arise out of the Third International Conference on Health and Safety of Donors sponsored by the Worldwide Network for Blood and Marrow Transplantation. \n Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n152003\nLong-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension: Results From an International Prospective Registry.\n\nDelcroix, M\n\nLang, I\n\nPepke-Zaba, J\n\nJansa, P\n\nD'Armini, AM\n\nSnijder, R\n\nBresser, P\n\nTorbicki, A\n\nMellemkjaer, S\n\nLewczuk, J\n\nSimkova, I\n\nBarberà, JA\n\nde Perrot, M\n\nHoeper, MM\n\nGaine, S\n\nSpeich, R\n\nGomez-Sanchez, MA\n\nKovacs, G\n\nJaïs, X\n\nAmbroz, D\n\nTreacy, C\n\nMorsolini, M\n\nJenkins, D\n\nLindner, J\n\nDartevelle, P\n\nMayer, E\n\nSimonneau, G\n\nBeiträge in Fachzeitschriften\nISI:000371348900005\n26826181.0\n10.1161/CIRCULATIONAHA.115.016522\nNone\nChronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension.\n A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospectively included over a 24-month period. Estimated survival at 1, 2, and 3 years was 93% (95% confidence interval [CI], 90-95), 91% (95% CI, 87-93), and 89% (95% CI, 86-92) in operated patients (n=404), and only 88% (95% CI, 83-91), 79% (95% CI, 74-83), and 70% (95% CI, 64-76) in not-operated patients (n=275). In both operated and not-operated patients, pulmonary arterial hypertension-targeted therapy did not affect survival estimates significantly. Mortality was associated with New York Heart Association functional class IV (hazard ratio [HR], 4.16; 95% CI, 1.49-11.62; P=0.0065 and HR, 4.76; 95% CI, 1.76-12.88; P=0.0021), increased right atrial pressure (HR, 1.34; 95% CI, 0.95-1.90; P=0.0992 and HR, 1.50; 95% CI, 1.20-1.88; P=0.0004), and a history of cancer (HR, 3.02; 95% CI, 1.36-6.69; P=0.0065 and HR, 2.15; 95% CI, 1.18-3.94; P=0.0129) in operated and not-operated patients, respectively. Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension-targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients.\n The long-term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients.\n © 2016 American Heart Association, Inc.\n\nKovacs, Gabor\n\n\n"
},
{
"text": "\n152027\nEffect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: results from the EPATH randomized, placebo-controlled trial.\n\nTomaschitz, A\n\nVerheyen, N\n\nMeinitzer, A\n\nPieske, B\n\nBelyavskiy, E\n\nBrussee, H\n\nHaas, J\n\nMärz, W\n\nPieske-Kraigher, E\n\nVerheyen, S\n\nOfner-Ziegenfuss, L\n\nHartaigh, BÓ\n\nSchwetz, V\n\nAberer, F\n\nGrübler, M\n\nLang, F\n\nAlesutan, I\n\nVoelkl, J\n\nGaksch, M\n\nHorina, JH\n\nDimai, HP\n\nRus-Machan, J\n\nStiegler, C\n\nRitz, E\n\nFahrleitner-Pammer, A\n\nPilz, S\n\nBeiträge in Fachzeitschriften\nISI:000379448000017\n27065001.0\n10.1097/HJH.0000000000000927\nNone\nAccumulating evidence points toward mutual interaction between parathyroid hormone (PTH) and aldosterone as potential mechanism for increasing cardiovascular risk in primary hyperparathyroidism (pHPT).\n The Eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism (EPATH) trial is a single-center, randomized, double-blind, parallel-group, placebo-controlled trial. The primary aim is to evaluate the effects of the mineralocorticoid receptor antagonist eplerenone on plasma intact PTH (iPTH) concentration in patients with pHPT. Secondary end points comprised surrogate parameters of cardiovascular health [24-h ambulatory SBP and DBP and echocardiographic parameters related to systolic/diastolic function as well as to cardiac dimensions].\n We enrolled 110 study participants with pHPT, 25-hydroxyvitamin D at least 20 ng/ml and estimated glomerular filtration rate more than 50 ml/min per 1.73 m. Patients were 1 : 1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or matching placebo for a treatment period of 8 weeks.The study was completed by 97 participants [mean (SD) age: 67.5 ± 9.5 years; 78.4% women). The mean treatment effect (95% confidence interval) for iPTH was 1.0 (0.9-1.1; P = 0.777) pg/ml. Mean 24-h ambulatory SBP and DBP decreased significantly [mean change (95% confidence interval) -6.3 (-9.4 to -3.3) and -3.7 (-5.7 to -1.7) mmHg, respectively; P < 0.001]. No differences were seen in any further secondary outcomes or frequency of adverse events.\n In pHPT, treatment with eplerenone compared with placebo had no effect on circulating iPTH levels. Eplerenone treatment was well tolerated and safe and followed by significant decrease of ambulatory blood pressure.\n\nAberer, Felix\n\nBrussee, Helmut\n\nDimai, Hans\n\nFahrleitner-Pammer, Astrid\n\nHaas, Josef\n\nHorina, Joerg\n\nMärz, Winfried\n\nMeinitzer, Andreas\n\nOfner-Ziegenfuss, Lisa\n\nPilz, Stefan\n\nTheiler-Schwetz, Verena\n\nVerheyen, Nicolas Dominik\n\nVerheyen, Sarah\n\n\n"
},
{
"text": "\n158665\n3DSpectra: A 3-dimensional quantification algorithm for LC-MS labeled profile data.\n\nNasso, S\n\nHartler, J\n\nTrajanoski, Z\n\nDi Camillo, B\n\nMechtler, K\n\nToffolo, GM\n\nBeiträge in Fachzeitschriften\nISI:000347021100012\n25218586.0\n10.1016/j.jprot.2014.08.017\nNone\nMass spectrometry-based proteomics can generate highly informative datasets, as profile three-dimensional (3D) LC-MS data: LC-MS separates peptides in two dimensions (time, m/z) minimizing their overlap, and profile acquisition enhances quantification. To exploit both data features, we developed 3DSpectra, a 3D approach embedding a statistical method for peptide border recognition. 3DSpectra efficiently accesses profile data by means of mzRTree, and makes use of a priori metadata, provided by search engines, to quantify the identified peptides. An isotopic distribution model, shaped by a bivariate Gaussian Mixture Model (GMM), which includes a noise component, is fitted to the peptide peaks using the expectation-maximization (EM) approach. The EM starting parameters, i.e., the centers and shapes of the Gaussians, are retrieved from the metadata. The borders of the peaks are delimited by the GMM iso-density curves, and noisy or outlying data are discarded from subsequent analysis. The 3DSpectra program was compared to ASAPRatio for a controlled mixture of Isotope-Coded Protein Labels (ICPL) labeled proteins, which were mixed at predefined ratios and acquired in enhanced profile mode, in triplicate. The 3DSpectra software showed significantly higher linearity, quantification accuracy, and precision than did ASAPRatio in this real use case simulation where the true ratios are known, and it also achieved wider peptide coverage and dynamic range.\n Quantitative proteomics is pivotal for many systems biology related fields, such as biomarker discovery. The quantification quality provided by the adopted software is crucial for the success of protein differential expression studies. To determine the reliability of a quantitative computational method, we suggest evaluating performance parameters like accuracy and precision of the quantifications, robustness to outliers and proteome coverage. A quantitative comparison of these parameters is highly desirable since it enables to benchmark software performance. We applied this strategy to 3DSpectra, a 3-dimensional approach to spectra analysis for MS1 peptide quantification. It distinguishes peptide peaks from spurious peaks interfering in the survey scan. 3DSpectra was compared to ASAPRatio in terms of quantification quality performance parameters and showed an overall improvement.\n Copyright © 2014 Elsevier B.V. All rights reserved.\n\n\n"
},
{
"text": "\n168643\nAdverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract.\n\nMach, F\n\nRay, KK\n\nWiklund, O\n\nCorsini, A\n\nCatapano, AL\n\nBruckert, E\n\nDe Backer, G\n\nHegele, RA\n\nHovingh, GK\n\nJacobson, TA\n\nKrauss, RM\n\nLaufs, U\n\nLeiter, LA\n\nMärz, W\n\nNordestgaard, BG\n\nRaal, FJ\n\nRoden, M\n\nSantos, RD\n\nStein, EA\n\nStroes, ES\n\nThompson, PD\n\nTokgözoglu, L\n\nVladutiu, GD\n\nGencer, B\n\nStock, JK\n\nGinsberg, HN\n\nChapman, MJ\n\nEuropean Atherosclerosis Society Consensus Panel\n\nBeiträge in Fachzeitschriften\nISI:000439059000006\n29718253.0\n10.1093/eurheartj/ehy182\nPMC6047411\nTo objectively appraise evidence for possible adverse effects of long-term statin therapy on glucose homeostasis, cognitive, renal and hepatic function, and risk for haemorrhagic stroke or cataract.\n A literature search covering 2000-2017 was performed. The Panel critically appraised the data and agreed by consensus on the categorization of reported adverse effects. Randomized controlled trials (RCTs) and genetic studies show that statin therapy is associated with a modest increase in the risk of new-onset diabetes mellitus (about one per thousand patient-years), generally defined by laboratory findings (glycated haemoglobin ≥6.5); this risk is significantly higher in the metabolic syndrome or prediabetes. Statin treatment does not adversely affect cognitive function, even at very low levels of low-density lipoprotein cholesterol and is not associated with clinically significant deterioration of renal function, or development of cataract. Transient increases in liver enzymes occur in 0.5-2% of patients taking statins but are not clinically relevant; idiosyncratic liver injury due to statins is very rare and causality difficult to prove. The evidence base does not support an increased risk of haemorrhagic stroke in individuals without cerebrovascular disease; a small increase in risk was suggested by the Stroke Prevention by Aggressive Reduction of Cholesterol Levels study in subjects with prior stroke but has not been confirmed in the substantive evidence base of RCTs, cohort studies and case-control studies.\n Long-term statin treatment is remarkably safe with a low risk of clinically relevant adverse effects as defined above; statin-associated muscle symptoms were discussed in a previous Consensus Statement. Importantly, the established cardiovascular benefits of statin therapy far outweigh the risk of adverse effects.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n168807\nComparison of a resorbable magnesium implant in small and large growing-animal models.\n\nGrün, NG\n\nHolweg, P\n\nTangl, S\n\nEichler, J\n\nBerger, L\n\nvan den Beucken, JJJP\n\nLöffler, JF\n\nKlestil, T\n\nWeinberg, AM\n\nBeiträge in Fachzeitschriften\nISI:000445990200032\n30059798.0\n10.1016/j.actbio.2018.07.044\nNone\nFracture treatment in children needs new implant materials to overcome disadvantages associated with removal surgery. Magnesium-based implants constitute a biocompatible and bioresorbable alternative. In adults and especially in children, implant safety needs to be evaluated. In children the bone turnover rate is higher and implant material might influence growth capacity, and the long-term effect of accumulated particles or ions is more critical due to the host's prolonged post-surgery lifespan. In this study we aimed to investigate the degradation behavior of ZX00 (Mg-0.45Zn-0.45Ca; in wt.%) in a small and a large animal model to find out whether there is a difference between the two models (i) in degradation rate and (ii) in bone formation and in-growth. Our results 6, 12 and 24 weeks after ZX00 implantation showed no negative effects on bone formation and in-growth, and no adverse effects such as fibrotic or sclerotic encapsulation. The degradation rate did not significantly differ between the two growing-animal models, and both showed slow and homogeneous degradation performance. Our conclusion is that small animal models may be sufficient to investigate degradation rates and provide preliminary evidence on bone formation and in-growth of implant materials in a growing-animal model.\n The safety of implant material is of the utmost importance, especially in children, who have enhanced bone turnover, more growth capacity and longer postoperative lifespans. Magnesium (Mg)-based implants have long been of great interest in pediatric orthopedic and trauma surgery, due to their good biocompatibility, biodegradability and biomechanics. In the study documented in this manuscript we investigated Mg-Zn-Ca implant material without rare-earth elements, and compared its outcome in a small and a large growing-animal model. In both models we observed bone formation and in-growth which featured no adverse effects such as fibrotic or sclerotic encapsulation, and slow homogeneous degradation performance of the Mg-based implant material.\n Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.\n\nHolweg, Patrick Lukas\n\nSommer, Nicole\n\nWeinberg, Annelie-Martina\n\n\n"
},
{
"text": "\n183848\nValidating Comprehensive Next-Generation Sequencing Results for Precision Oncology: The NCT/DKTK Molecularly Aided Stratification for Tumor Eradication Research Experience\n\nLier, A\n\nPenzel, R\n\nHeining, C\n\nHorak, P\n\nFrohlich, M\n\nUhrig, S\n\nBudczies, J\n\nKirchner, M\n\nVolckmar, AL\n\nHutter, B\n\nKreutzfeldt, S\n\nEndris, V\n\nRichter, D\n\nWolf, S\n\nPfutze, K\n\nNeumann, O\n\nBuchhalter, I\n\nde Oliveira, CMM\n\nSinger, S\n\nLeichsenring, J\n\nHerpel, E\n\nKlauschen, F\n\nJost, PJ\n\nMetzeler, KH\n\nSchulze-Osthoff, K\n\nKopp, HG\n\nKindler, T\n\nRieke, DT\n\nLamping, M\n\nBrandts, C\n\nFalkenhorst, J\n\nBauer, S\n\nSchrock, E\n\nFolprecht, G\n\nBoerries, M\n\nvon Bubnoff, N\n\nWeichert, W\n\nBrors, B\n\nLichter, P\n\nvon Kalle, C\n\nSchirmacher, P\n\nGlimm, H\n\nFrohling, S\n\nStenzinger, A\n\nBeiträge in Fachzeitschriften\nISI:000462187300001\nNone\n10.1200/PO.18.00171\nNone\nPurpose Rapidly evolving genomics technologies, in particular comprehensive next-generation sequencing (NGS), have led to exponential growth in the understanding of cancer biology, shifting oncology toward personalized treatment strategies. However, comprehensive NGS approaches, such as whole-exome sequencing, have limitations that are related to the technology itself as well as to the input source. Hence, clinical implementation of comprehensive NGS in a quality-controlled diagnostic workflow requires both the standardization of sequencing procedures and continuous validation of sequencing results by orthogonal methods in an ongoing program to enable the determination of key test parameters and continuous improvement of NGS and bioinformatics pipelines. Patients and Methods We present validation data on 220 patients who were enrolled between 2013 and 2016 in a multi-institutional, genomics-guided precision oncology program (Molecularly Aided Stratification for Tumor Eradication Research) of the National Center for Tumor Diseases Heidelberg and the German Cancer Consortium. Results More than 90% of clinically actionable genomic alterations identified by combined whole-exome sequencing and transcriptome sequencing were successfully validated, with varying frequencies of discordant results across different types of alterations (fusions, 3.7%; single-nucleotide variants, 2.6%; amplifications, 1.1%; overexpression, 0.9%; deletions, 0.6%). The implementation of new computational methods for NGS data analysis led to a substantial improvement of gene fusion calling over time. Conclusion Collectively, these data demonstrate the value of a rigorous validation program that partners with comprehensive NGS to successfully implement and continuously improve cancer precision medicine in a clinical setting. (C) 2018 by American Society of Clinical Oncology\n\nJost, Philipp\n\n\n"
},
{
"text": "\n1882\nOxidation of lipoprotein Lp(a). A comparison with low-density lipoproteins.\n\nSattler, W\n\nKostner, GM\n\nWaeg, G\n\nEsterbauer, H\n\nBeiträge in Fachzeitschriften\nISI:A1991ET43300008\n1825020.0\n10.1016/0005-2760(91)90251-C\nNone\nAimed at identifying possible mechanisms of the suggested high atherogenicity of Lp(a), its susceptibility for Cu(II)-induced oxidation was studied and compared with that of LDL. Since the content of antioxidants as well as the fatty acid pattern of a lipoprotein greatly affects its oxidizability, Lp(a) and LDL were characterized first with respect to these substances. Paired samples of low-density lipoproteins (LDL) and Lp(a) were isolated from seven individual donors and compared with each other. This study showed that LDL and Lp(a) are very similar with respect to their fatty acid and antioxidant composition. LDL contains approx. 1132 nmol of total fatty acids/mg lipoprotein and LDL 1466 nmol total fatty acids/mg lipoprotein. Analysis of the fatty acid composition of individual lipid classes (cholesteryl esters, phospholipids and triacylglycerols) revealed also a high similarity in the composition of these lipid classes between the two lipoproteins. A comparison of the antioxidant composition showed that Lp(a) contains less alpha-tocopherol than LDL (1.6 +/- 0.35 nmol/mg vs. 2.1 +/- 0.25 nmol/mg LDL). In copper(II)-induced lipid peroxidation experiments we found a striking difference in the susceptibility of individual lipoprotein classes between all donors. In addition, Lp(a) exhibited a 1.2 to 2.4 longer lag-phase than the corresponding LDL preparation from the same blood donor. Treatment of Lp(a) with neuraminidase resulted in a drastic decrease of the lag-phase of Lp(a). Neuraminidase treatment of LDL on the other hand had no significant effects on its susceptibility to oxidation. Supplementation of neuraminidase-treated Lp(a) with N-acetylneuraminic acid (NANA) at concentrations comparable to the naturally occurring amounts of NANA in the Lp(a) protein moiety led to an increase of the lag-phase yielding values which were comparable to those observed with native Lp(a). These results demonstrate that the fatty acid composition as well as the antioxidant concentrations of Lp(a) and LDL are quite similar; despite this fact, Cu2(+)-mediated oxidation of Lp(a) is retarded in comparison to LDL which might be due to the higher content of NANA in Lp(a).\n\nKostner, Gerhard\n\nSattler, Wolfgang\n\n\n"
},
{
"text": "\n11613\nIntragastric capsaicin enhances rat gastric acid elimination and mucosal blood flow by afferent nerve stimulation.\n\nLippe, IT\n\nPabst, MA\n\nHolzer, P\n\nBeiträge in Fachzeitschriften\nISI:A1989R617600014\n2924079.0\n10.1111/j.1476-5381.1989.tb11788.x\nPMC1854317\n1. This study investigated the effects of intragastric capsaicin on acid output, clearance of aniline, potential difference, and morphology of the mucosa in the rat stomach. The experiments were carried out on rats anaesthetized with urethane in which the stomachs were continuously perfused with saline. 2. When the stomach was perfused with normal saline (pH approximately 6), intragastric capsaicin (32-640 microM) had no effect on the output of titratable acid. In contrast, when acid output was stimulated by pentagastrin or when the stomach was perfused with acid saline (pH 3), capsaicin reduced acid output. Acid loss which occurred during perfusion with saline of pH 2 was not significantly increased by capsaicin. This suggests that capsaicin does not enhance acid back-diffusion but facilitates acid elimination by other means. 3. The gastric clearance of [14C]-aniline, which is an indirect index of gastric mucosal blood flow, was estimated while the stomach was perfused with saline of pH 3. The clearance of aniline rose by 50-60% following intragastric administration of capsaicin (160 microM) whereas the mean arterial blood pressure was increased by about 2.5 mmHg only. Combined pretreatment of the rats with atropine, phentolamine, and propranolol did not alter the effect of capsaicin on the gastric clearance of aniline. 4. The gastric potential difference was not altered by capsaicin (160 microM) administered together with saline of pH 3. This and the finding that there were no signs of mucosal damage by light and scanning electron microscopy indicate that intragastric capsaicin does not irritate the gastric mucosa. 5. The effects of intragastric capsaicin on gastric acid output and aniline clearance and on blood pressure were absent in rats in which capsaicin-sensitive afferent neurones had been ablated by neonatal treatment with a neurotoxic dose of capsaicin, which indicates that they result from stimulation of afferent nerve endings in the stomach. It is concluded that facilitation of acid elimination and mucosal blood flow may contribute to the previously reported protective action of capsaicin on the gastric mucosa.\n\nHolzer, Peter\n\nLippe, Irmgard\n\nPabst, Maria-Anna\n\n\n"
},
{
"text": "\n123728\nThe angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial.\n\nSolomon, SD\n\nZile, M\n\nPieske, B\n\nVoors, A\n\nShah, A\n\nKraigher-Krainer, E\n\nShi, V\n\nBransford, T\n\nTakeuchi, M\n\nGong, JJ\n\nLefkowitz, M\n\nPacker, M\n\nMcMurray, JJV\n\n\n\nBeiträge in Fachzeitschriften\nISI:000310196500028\n22932717.0\n10.1016/S0140-6736(12)61227-6\nNone\nBackground Heart failure with preserved ejection fraction is associated with substantial morbidity and mortality, but effective treatments are lacking. We assessed the efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), in patients with this disorder. Methods PARAMOUNT was a phase 2, randomised, parallel-group, double-blind multicentre trial in patients with New York Heart Association (NYHA) class II-III heart failure, left ventricular ejection fraction 45% or higher, and NT-proBNP greater than 400 pg/mL. Participants were randomly assigned (1: 1) by central interactive voice response system to LCZ696 titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily, and treated for 36 weeks. Investigators and participants were masked to treatment assignment. The primary endpoint was change in NT-proBNP, a marker of left ventricular wall stress, from baseline to 12 weeks; analysis included all patients randomly assigned to treatment groups who had a baseline and at least one postbaseline assessment. This trial is registered at Clinicaltrials.gov, number NCT00887588. Findings 149 patients were randomly assigned to LCZ696 and 152 to valsartan; 134 in the LCZ696 group and 132 in the valsartan group were included in analysis of the primary endpoint. NT-proBNP was significantly reduced at 12 weeks in the LCZ696 group compared with the valsartan group (LCZ696: baseline, 783 pg/mL [95% CI 670-914], 12 weeks, 605 pg/mL [512-714]; valsartan: baseline, 862 pg/mL [733-1012], 12 weeks, 835 [710-981]; ratio LCZ696/valsartan, 0.77, 95% CI 0.64-0.92, p=0.005). LCZ696 was well tolerated with adverse effects similar to those of valsartan; 22 patients (15%) on LCZ696 and 30 (20%) on valsartan had one or more serious adverse event. Interpretation In patients with heart failure with preserved ejection fraction, LCZ696 reduced NT-proBNP to a greater extent than did valsartan at 12 weeks and was well tolerated. Whether these effects would translate into improved outcomes needs to be tested prospectively.\n\n\n"
},
{
"text": "\n135055\nInhibition of N-type calcium channels: the only mechanism by which presynaptic alpha 2-autoreceptors control sympathetic transmitter release.\n\nBoehm, S\n\nHuck, S\n\nBeiträge in Fachzeitschriften\nISI:A1996VK34400014\n8921283.0\n10.1111/j.1460-9568.1996.tb01336.x\nNone\nAlpha 2-Adrenoceptors are known to inhibit voltage-dependent Ca2+ channels located at neuronal cell bodies; the present study investigated whether this or alternative mechanisms, possibly downstream of Ca2+ entry, underlie the presynaptic alpha 2-adrenergic modulation of transmitter release from chick sympathetic neurons. Using chick sympathetic neurons, overflow of previously incorporated [3H]noradrenaline was elicited in the presence of extracellular Ca2+ by electrical pulses, 25 mM K+ or 10 microM nicotine, or by adding Ca2+ to otherwise Ca(2+)-free medium when cells had been made permeable by the calcium ionophore A23187 or by alpha-latrotoxin. Pretreatment of neurons with the N-type Ca2+ channel blocker omega-conotoxin GVIA and application of the alpha 2-adrenergic agonist UK 14304 reduced the overflow elicited by electrical pulses, K+ or nicotine, but not the overflow caused by Ca2+ after permeabilization with alpha-latrotoxin or A23187. In contrast, the L-type Ca2+ channel blocker nitrendipine reduced the overflow due to K+ and nicotine, but not the overflow following electrical stimulation or alpha-latrotoxin- and A23187-permeabilization. The inhibition of electrically evoked overflow by UK 14304 persisted in the presence of nitrendipine and the L-type Ca2+ channel agonist BayK 8644, which per se enhanced overflow. In omega-conotoxin GVIA-treated cultures, electrically evoked overflow was also enhanced by BayK 8644 and almost reached the value obtained in untreated neurons. However, UK 14304 lost its effect under these conditions. Whole-cell recordings of voltage-activated Ca2+ currents corroborated these results: UK 14304 inhibited Ca2+ currents by 33%, nitrendipine caused a 7% reduction, and BayK 8644 increased the currents by 30%. Moreover, the dihydropyridines failed to abolish the inhibition by UK 14304, but pretreatment with omega-conotoxin GVIA, which reduced mean amplitude from 0.95 to 0.23 nA, entirely prevented alpha 2-adrenergic effects. Our results indicate that the alpha 2-autoreceptor-mediated modulation of noradrenaline release from chick sympathetic neurons relies exclusively on the inhibition of omega-conotoxin GVIA-sensitive N-type Ca2+ channels. Mechanisms downstream of these channels and voltage-sensitive Ca2+ channels other than N-type appear not to be important.\n\n\n"
},
{
"text": "\n137032\nNovel genetic approach to investigate the role of plasma secretory phospholipase A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian randomization analysis using PLA2G5 expression levels.\n\nHolmes, MV\n\nExeter, HJ\n\nFolkersen, L\n\nNelson, CP\n\nGuardiola, M\n\nCooper, JA\n\nSofat, R\n\nBoekholdt, SM\n\nKhaw, KT\n\nLi, KW\n\nSmith, AJ\n\nVan't Hooft, F\n\nEriksson, P\n\nFranco-Cereceda, A\n\nAsselbergs, FW\n\nBoer, JM\n\nOnland-Moret, NC\n\nHofker, M\n\nErdmann, J\n\nKivimaki, M\n\nKumari, M\n\nReiner, AP\n\nKeating, BJ\n\nHumphries, SE\n\nHingorani, AD\n\nMallat, Z\n\nSamani, NJ\n\nTalmud, PJ\n\nCARDIoGRAM Consortium\n\nBeiträge in Fachzeitschriften\nISI:000334510200008\n24563418.0\n10.1161/CIRCGENETICS.113.000271\nPMC4212409\nSecretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis.\n Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotide polymorphism in PLA2G5 showing the strongest association with PLA2G5 mRNA expression levels as a proxy for sPLA2-V levels. We tested the association of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 case-control studies with 27 230 events and 70 500 controls. rs525380C>A showed the strongest association with PLA2G5 mRNA expression (P=5.1×10(-6)). There was no association of rs525380C>A with plasma sPLA2 activity (difference in geometric mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidence intervals [-0.9%, 1.6%]; P=0.56). In meta-analyses, the odds ratio for CHD per A-allele was 1.02 (95% confidence intervals [0.99, 1.04]; P=0.20).\n This novel approach for single-nucleotide polymorphism selection for this modified Mendelian randomization analysis showed no association between rs525380 (the lead single-nucleotide polymorphism for PLA2G5 expression, a surrogate for sPLA2-V levels) and CHD events. The evidence does not support a causal role for sPLA2-V in CHD.\n\n\n"
},
{
"text": "\n146431\nTherapy for unhealed gastrocutaneous fistulas in rats as a model for analogous healing of persistent skin wounds and persistent gastric ulcers: stable gastric pentadecapeptide BPC 157, atropine, ranitidine, and omeprazole.\n\nSkorjanec, S\n\nDolovski, Z\n\nKocman, I\n\nBrcic, L\n\nBlagaic Boban, A\n\nBatelja, L\n\nCoric, M\n\nSever, M\n\nKlicek, R\n\nBerkopic, L\n\nRadic, B\n\nDrmic, D\n\nKolenc, D\n\nIlic, S\n\nCesarec, V\n\nTonkic, A\n\nZoricic, I\n\nMise, S\n\nStaresinic, M\n\nIvica, M\n\nLovric Bencic, M\n\nAnic, T\n\nSeiwerth, S\n\nSikiric, P\n\nBeiträge in Fachzeitschriften\nISI:000261653400010\n18649140.0\n10.1007/s10620-008-0332-9\nNone\nThis study focused on unhealed gastrocutaneous fistulas to resolve whether standard drugs that promote healing of gastric ulcers may simultaneously have the same effect on cutaneous wounds, and corticosteroid aggravation, and to demonstrate why peptides such as BPC 157 exhibit a greater healing effect. Therefore, with the fistulas therapy, we challenge the wound/growth factors theory of the analogous nonhealing of wounds and persistent gastric ulcers.\n The healing rate of gastrocutaneous fistula in rat (2-mm-diameter stomach defect, 3-mm-diameter skin defect) validates macro/microscopically and biomechanically a direct skin wound/stomach ulcer relation, and identifies a potential therapy consisting of: (i) stable gastric pentadecapeptide BPC 157 [in drinking water (10 microg/kg) (12 ml/rat/day) or intraperitoneally (10 microg/kg, 10 ng/kg, 10 pg/kg)], (ii) atropine (10 mg/kg), ranitidine (50 mg/kg), and omeprazole (50 mg/kg), (iii) 6-alpha-methylprednisolone (1 mg/kg) [intraperitoneally, once daily, first application at 30 min following surgery; last 24 h before sacrifice (at postoperative days 1, 2, 3, 7, 14, and 21)].\n Greater anti-ulcer potential and efficiency in wound healing compared with standard agents favor BPC 157, efficient in inflammatory bowel disease (PL-14736, Pliva), given in drinking water or intraperitoneally. Even after 6-alpha-methylprednisolone aggravation, BPC 157 promptly improves both skin and stomach mucosa healing, and closure of fistulas, with no leakage after up to 20 ml water intragastrically. Standard anti-ulcer agents, after a delay, improve firstly skin healing and then stomach mucosal healing, but not fistula leaking and bursting strength (except for atropine).\n We conclude that BPC 157 may resolve analogous nonhealing of wounds and persistent gastric ulcers better than standard agents.\n\nBrcic, Luka\n\n\n"
},
{
"text": "\n146914\nDevelopment and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure.\n\nJalan, R\n\nSaliba, F\n\nPavesi, M\n\nAmoros, A\n\nMoreau, R\n\nGinès, P\n\nLevesque, E\n\nDurand, F\n\nAngeli, P\n\nCaraceni, P\n\nHopf, C\n\nAlessandria, C\n\nRodriguez, E\n\nSolis-Muñoz, P\n\nLaleman, W\n\nTrebicka, J\n\nZeuzem, S\n\nGustot, T\n\nMookerjee, R\n\nElkrief, L\n\nSoriano, G\n\nCordoba, J\n\nMorando, F\n\nGerbes, A\n\nAgarwal, B\n\nSamuel, D\n\nBernardi, M\n\nArroyo, V\n\nCANONIC study investigators of the EASL-CLIF Consortium\n\nBeiträge in Fachzeitschriften\nISI:000343839900011\n24950482.0\n10.1016/j.jhep.2014.06.012\nNone\nAcute-on-chronic liver failure (ACLF) is a frequent syndrome (30% prevalence), characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality. This study develops and validates a specific prognostic score for ACLF patients.\n Data from 1349 patients included in the CANONIC study were used. First, a simplified organ function scoring system (CLIF Consortium Organ Failure score, CLIF-C OFs) was developed to diagnose ACLF using data from all patients. Subsequently, in 275 patients with ACLF, CLIF-C OFs and two other independent predictors of mortality (age and white blood cell count) were combined to develop a specific prognostic score for ACLF (CLIF Consortium ACLF score [CLIF-C ACLFs]). A concordance index (C-index) was used to compare the discrimination abilities of CLIF-C ACLF, MELD, MELD-sodium (MELD-Na), and Child-Pugh (CPs) scores. The CLIF-C ACLFs was validated in an external cohort and assessed for sequential use.\n The CLIF-C ACLFs showed a significantly higher predictive accuracy than MELDs, MELD-Nas, and CPs, reducing (19-28%) the corresponding prediction error rates at all main time points after ACLF diagnosis (28, 90, 180, and 365 days) in both the CANONIC and the external validation cohort. CLIF-C ACLFs computed at 48 h, 3-7 days, and 8-15 days after ACLF diagnosis predicted the 28-day mortality significantly better than at diagnosis.\n The CLIF-C ACLFs at ACLF diagnosis is superior to the MELDs and MELD-Nas in predicting mortality. The CLIF-C ACLFs is a clinically relevant, validated scoring system that can be used sequentially to stratify the risk of mortality in ACLF patients.\n Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.\n\n\n"
},
{
"text": "\n154860\nFunctional Metagenomics of Spacecraft Assembly Cleanrooms: Presence of Virulence Factors Associated with Human Pathogens.\n\nBashir, M\n\nAhmed, M\n\nWeinmaier, T\n\nCiobanu, D\n\nIvanova, N\n\nPieber, TR\n\nVaishampayan, PA\n\nBeiträge in Fachzeitschriften\nISI:000382820300001\n27667984.0\n10.3389/fmicb.2016.01321\nPMC5017214\nStrict planetary protection practices are implemented during spacecraft assembly to prevent inadvertent transfer of earth microorganisms to other planetary bodies. Therefore, spacecraft are assembled in cleanrooms, which undergo strict cleaning and decontamination procedures to reduce total microbial bioburden. We wanted to evaluate if these practices selectively favor survival and growth of hardy microorganisms, such as pathogens. Three geographically distinct cleanrooms were sampled during the assembly of three NASA spacecraft: The Lockheed Martin Aeronautics' Multiple Testing Facility during DAWN, the Kennedy Space Center's Payload Hazardous Servicing Facility (KSC-PHSF) during Phoenix, and the Jet Propulsion Laboratory's Spacecraft Assembly Facility during Mars Science Laboratory. Sample sets were collected from the KSC-PHSF cleanroom at three time points: before arrival of the Phoenix spacecraft, during the assembly and testing of the Phoenix spacecraft, and after removal of the spacecraft from the KSC-PHSF facility. All samples were subjected to metagenomic shotgun sequencing on an Illumina HiSeq 2500 platform. Strict decontamination procedures had a greater impact on microbial communities than sampling location Samples collected during spacecraft assembly were dominated by Acinetobacter spp. We found pathogens and potential virulence factors, which determine pathogenicity in all the samples tested during this study. Though the relative abundance of pathogens was lowest during the Phoenix assembly, potential virulence factors were higher during assembly compared to before and after assembly, indicating a survival advantage. Decreased phylogenetic and pathogenic diversity indicates that decontamination and preventative measures were effective against the majority of microorganisms and well implemented, however, pathogen abundance still increased over time. Four potential pathogens, Acinetobacter baumannii, Acinetobacter lwoffii, Escherichia coli and Legionella pneumophila, and their corresponding virulence factors were present in all cleanroom samples. This is the first functional metagenomics study describing presence of pathogens and their corresponding virulence factors in cleanroom environments. The results of this study should be considered for microbial monitoring of enclosed environments such as schools, homes, hospitals and more isolated habitation such the International Space Station and future manned missions to Mars.\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n165000\nRandomized, controlled clinical two-centre study using xenogeneic block grafts loaded with recombinant human bone morphogenetic protein-2 or autogenous bone blocks for lateral ridge augmentation.\n\nThoma, DS\n\nPayer, M\n\nJakse, N\n\nBienz, SP\n\nHüsler, J\n\nSchmidlin, PR\n\nJung, UW\n\nHämmerle, CHF\n\nJung, RE\n\nBeiträge in Fachzeitschriften\nISI:000419830500012\n29150957.0\n10.1111/jcpe.12841\nNone\nTo test whether or not the use of a xenogeneic block loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) results in different bone quantity and quality compared to an autogenous bone block.\n Twenty-four patients with insufficient bone volume for implant placement were randomly assigned to two treatment modalities: a xenogeneic bone block loaded with rhBMP-2 (test) and an autogenous bone block (control). The horizontal ridge width was evaluated prior to augmentation, after augmentation and at 4 months. Patient-reported outcome measures (PROMs) were assessed at suture removal and at 4 months. Biopsies were obtained at 4 months and histologically evaluated. Intergroup comparisons were tested by a two-sided Wilcoxon-Mann-Whitney test, intra-group comparisons were performed with Wilcoxon-signed rank test, and all categorical variables were tested with Chi-squared tests.\n One autogenous bone block failed. This patient was replaced, and in all subsequently treated 24 patients, implant placement was possible 4 months later. The median ridge width increased from 4.0 mm (Q1 = 2.0; Q3 = 4.0) (test) and 2.0 mm (Q1 = 2.0; Q3 = 3.0) (control) to 7.0 mm (Q1 = 6.0; Q3 = 8.0) (test) and 7.0 mm (Q1 = 6.0; Q3 = 8.0) (control) at 4 months (intergroup p > .05). A higher morbidity was reported at the augmented site in the control group during surgery. Sensitivity was more favourable in the test than that in the control group at 4 months. The biopsies revealed more mineralized tissue in the control group (p < .0043).\n Both treatment modalities were successful in regenerating bone to place dental implants. PROMs did not reveal any significant differences between the groups except for pain during surgery at the recipient site (in favour of the test group). Histologically, a higher amount of mineralized tissue was observed for the control group at 4 months.\n © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.\n\nJakse, Norbert\n\nPayer, Michael\n\n\n"
}
]
}