HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 127182,
"next": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=126640",
"previous": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=126600",
"results": [
{
"text": "\n107411\nTime to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.\n\nLees, KR\n\nBluhmki, E\n\nvon Kummer, R\n\nBrott, TG\n\nToni, D\n\nGrotta, JC\n\nAlbers, GW\n\nKaste, M\n\nMarler, JR\n\nHamilton, SA\n\nTilley, BC\n\nDavis, SM\n\nDonnan, GA\n\nHacke, W\n\nECASS, ATLANTIS, NINDS and EPITHET rt-PA Study Group\n\nAllen, K\n\nMau, J\n\nMeier, D\n\ndel Zoppo, G\n\nDe Silva, DA\n\nButcher, KS\n\nParsons, MW\n\nBarber, PA\n\nLevi, C\n\nBladin, C\n\nByrnes, G\n\nBeiträge in Fachzeitschriften\nISI:000277890200031\n20472172.0\n10.1016/S0140-6736(10)60491-6\nNone\nBackground Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. Methods We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (on) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. Findings Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. Interpretation Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit.\n\n\n"
},
{
"text": "\n162215\nPerformance of five research-domain automated WM lesion segmentation methods in a multi-center MS study.\n\nde Sitter, A\n\nSteenwijk, MD\n\nRuet, A\n\nVersteeg, A\n\nLiu, Y\n\nvan Schijndel, RA\n\nPouwels, PJW\n\nKilsdonk, ID\n\nCover, KS\n\nvan Dijk, BW\n\nRopele, S\n\nRocca, MA\n\nYiannakas, M\n\nWattjes, MP\n\nDamangir, S\n\nFrisoni, GB\n\nSastre-Garriga, J\n\nRovira, A\n\nEnzinger, C\n\nFilippi, M\n\nFrederiksen, J\n\nCiccarelli, O\n\nKappos, L\n\nBarkhof, F\n\nVrenken, H\n\nMAGNIMS study group and for neuGRID\n\nBeiträge in Fachzeitschriften\nISI:000418641800010\n28899746.0\n10.1016/j.neuroimage.2017.09.011\nNone\nIn vivoidentification of white matter lesions plays a key-role in evaluation of patients with multiple sclerosis (MS). Automated lesion segmentation methods have been developed to substitute manual outlining, but evidence of their performance in multi-center investigations is lacking. In this work, five research-domain automated segmentation methods were evaluated using a multi-center MS dataset.\n 70 MS patients (median EDSS of 2.0 [range 0.0-6.5]) were included from a six-center dataset of the MAGNIMS Study Group (www.magnims.eu) which included 2D FLAIR and 3D T1 images with manual lesion segmentation as a reference. Automated lesion segmentations were produced using five algorithms: Cascade; Lesion Segmentation Toolbox (LST) with both the Lesion growth algorithm (LGA) and the Lesion prediction algorithm (LPA); Lesion-Topology preserving Anatomical Segmentation (Lesion-TOADS); and k-Nearest Neighbor with Tissue Type Priors (kNN-TTP). Main software parameters were optimized using a training set (N = 18), and formal testing was performed on the remaining patients (N = 52). To evaluate volumetric agreement with the reference segmentations, intraclass correlation coefficient (ICC) as well as mean difference in lesion volumes between the automated and reference segmentations were calculated. The Similarity Index (SI), False Positive (FP) volumes and False Negative (FN) volumes were used to examine spatial agreement. All analyses were repeated using a leave-one-center-out design to exclude the center of interest from the training phase to evaluate the performance of the method on 'unseen' center.\n Compared to the reference mean lesion volume (4.85 ± 7.29 mL), the methods displayed a mean difference of 1.60 ± 4.83 (Cascade), 2.31 ± 7.66 (LGA), 0.44 ± 4.68 (LPA), 1.76 ± 4.17 (Lesion-TOADS) and -1.39 ± 4.10 mL (kNN-TTP). The ICCs were 0.755, 0.713, 0.851, 0.806 and 0.723, respectively. Spatial agreement with reference segmentations was higher for LPA (SI = 0.37 ± 0.23), Lesion-TOADS (SI = 0.35 ± 0.18) and kNN-TTP (SI = 0.44 ± 0.14) than for Cascade (SI = 0.26 ± 0.17) or LGA (SI = 0.31 ± 0.23). All methods showed highly similar results when used on data from a center not used in software parameter optimization.\n The performance of the methods in this multi-center MS dataset was moderate, but appeared to be robust even with new datasets from centers not included in training the automated methods.\n Copyright © 2017 Elsevier Inc. All rights reserved.\n\nEnzinger, Christian\n\nRopele, Stefan\n\n\n"
},
{
"text": "\n182203\nQuantum biology in low level light therapy: death of a dogma.\n\nSommer, AP\n\nSchemmer, P\n\nPavláth, AE\n\nFörsterling, HD\n\nMester, ÁR\n\nTrelles, MA\n\nBeiträge in Fachzeitschriften\nISI:000527389200022\n32395484.0\n10.21037/atm.2020.03.159\nPMC7210155\nIt is shown that despite exponential increase in the number of clinically exciting results in low level light therapy (LLLT), scientific progress in the field is retarded by a wrong fundamental model employed to explain the photon-cell interaction as well as by an inadequate terminology. This is reflected by a methodological stagnation in LLLT, persisting since 1985. The choice of the topics is, by necessity, somewhat arbitrary. Obviously, we are writing more about the fields we know more about. In some cases, there are obvious objective reasons for the choice. Progress in LLLT is currently realized by a trial and error process, as opposed to a systematic approach based on a valid photon-cell interaction model.\n The strategy to overcome the current problem consists in a comprehensive analysis of the theoretical foundation of LLLT, and if necessary, by introducing new interaction models and checking their validity on the basis of the two pillars of scientific advance (I) agreement with experiment and (II) predictive capability. The list of references used in this work, does contain a representative part of what has been done in the photon-cell interaction theory in recent years, considered as ascertained by the scientific community.\n Despite the immense literature on the involvement of cytochrome c oxidase (COX) in LLLT, the assumption that COX is the main mitochondrial photoacceptor for R-NIR photons no longer can be counted as part of the theoretical framework proper, at least not after we have addressed the misleading points in the literature. Here, we report the discovery of a coupled system in mitochondria whose working principle corresponds to that of field-effect transistor (FET). The functional interplay of cytochrome c (emitter) and COX (drain) with a nanoscopic interfacial water layer (gate) between the two enzymes forms a biological FET in which the gate is controlled by R-NIR photons. By reducing the viscosity of the nanoscopic interfacial water layers within and around the mitochondrial rotary motor in oxidatively stressed cells R-NIR light promotes the synthesis of extra adenosine triphosphate (ATP).\n Based on the results of our own work and a review of the published literature, we present the effect of R-NIR photons on nanoscopic interfacial water layers in mitochondria and cells as a novel understanding of the biomedical effects R-NIR light. The novel paradigm is in radical contrast to the theory that COX is the main absorber for R-NIR photons and responsible for the increase in ATP synthesis, a dogma propagated for more than 20 years.\n 2020 Annals of Translational Medicine. All rights reserved.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n185593\nRestraint use in the acute-care hospital setting: A cross-sectional multi-centre study.\n\nThomann, S\n\nZwakhalen, S\n\nRichter, D\n\nBauer, S\n\nHahn, S\n\nBeiträge in Fachzeitschriften\nISI:000612179400002\n33217663.0\n10.1016/j.ijnurstu.2020.103807\nNone\nRestraints are likely to negatively affect patients' health and therefore a reduction in their usage is recommended for all health-care settings. To date, research on restrictive practices has concentrated on mental health and long-term care settings. In the acute-care hospital setting few studies have been published and these studies mainly focus on physical/mechanical restraints in specific subpopulations and/or on intensive care units. However, to ensure restraints are used as little as possible in the acute-care hospital setting, it seems important to investigate more comprehensively the use of restraints, to include all types of restraints irrespective of ward type or subpopulations and to identify factors associated with restraint use.\n The aim of this study was to investigate restraint use regardless of ward type in the acute-care hospital setting, including restraint type, reasons for restraint use, process indicators when using restraints and restraint use-associated patient characteristics.\n Using a cross-sectional multi-centre design, data were collected by means of an annual international prevalence measurement in acute-care hospitals in Switzerland and Austria. All hospitalised patients aged 18+ who gave informed consent were included. Data were collected at three measurement points between 2016 and 2018. Descriptive and multivariate logistic regression analyses were performed.\n A total of 29, 77 patients hospitalised in 140 hospitals were included in this study. The prevalence rate for the use of at least one restraint over a 30-day period was 8.7% (n = 2577), with mechanical restraints representing the highest proportion of restraint type used (55.0%, n = 1417). The main reason for restraint use was fall prevention (43.8%, n = 1129), followed by confusion or delirious behaviour (20.4%, n = 525). In 64.3% of the cases (n = 1657), restraint use was documented in the patient file. Regular evaluation occurred in 42.9% of the cases (n = 1105). Care dependency had the strongest association with restraint use (odds ratio [OR] 25.00, 95% confidence interval [CI] 21.01-29.78 for completely dependant patients in comparison to completely independent patients), followed by mental and behavioural disorders (OR 2.36, 95% CI 2.15-2.59).\n Restraints are often utilised in hospitals in complex care situations such as with patients at risk of falling or with delirium. When using restraints the consideration of processes like documentation and evaluation shows great potential for improvement. Standardisation of these processes and education of the interprofessional team could be beneficial for raising awareness and for the sustainable reduction of restraint use. Tweetable abstract: In hospitals restraints are often used in complex care situations. However, their use seems to be insufficiently documented and evaluated.\n Copyright © 2020. Published by Elsevier Ltd.\n\nBauer, Silvia\n\n\n"
},
{
"text": "\n4422\nEvaluation of the effect of routine packed red blood cell transfusion in anemic cervix cancer patients treated with radical radiotherapy.\n\nKapp, KS\n\nPoschauko, J\n\nGeyer, E\n\nBerghold, A\n\nOechs, AC\n\nPetru, E\n\nLahousen, M\n\nKapp, DS\n\nBeiträge in Fachzeitschriften\nISI:000177780900008\n12182975.0\n10.1016/S0360-3016(02)02896-1\nNone\nPURPOSE: It is well established that anemia predicts diminished radiocurability in cervix cancer. However, the therapeutic benefit of measures to correct the anemia remains controversial. The objective of this study was to determine the impact of routine transfusion in patients with hemoglobin level (hb-l) < or =11 g/dl. METHODS AND MATERIALS: Since 1985, it has been departmental policy to attempt to correct hb-l < or =11 g/dl before and/or during radiotherapy by red blood cell transfusion (RBCT) in patients undergoing radical radiotherapy for primary cervix cancer. To assess the benefit of RBCT, the charts of 204 patients (FIGO: IB-IV) treated until 1997 were reviewed. Parameters analyzed for their impact on disease-specific survival (DSS), pelvic control (PC), and metastases-free survival (MFS) included pretreatment hb-l, treatment hb-l, stage, tumor size, and lymph node status. To determine any differences in outcome according to type of anemia, a separate analysis was performed, grouping patients by cause of anemia (tumor vs. other medical illness related). RESULTS: Each of the parameters tested was significantly correlated with the end points studied in univariate analysis. Patients whose hb-l were corrected (18.5%) had an outcome that did not differ significantly from that of nontransfused patients, whereas DSS, PC, and MFS (all: p < 0.001) were significantly decreased in nonresponders to RBCT. Subgroup analysis showed no impact of hb-l in patients with other medical illness-related anemia (n = 12). In multivariate analysis treatment, but not pretreatment, hb-l remained predictive for DSS, PC, and MFS. Persistent anemia was associated with a significantly increased risk of death (relative risk: 2.1) and pelvic failure (relative risk: 2.4) compared with nontransfused patients. If only patients with tumor anemia were considered, the respective risks increased (2.7; 3.6). None of the patients with other causes of anemia recurred, whether or not their hb-l was maintained. Assessment of the therapeutic gain in patients who responded to RBCT showed improved PC (p = 0.02) and a trend toward increased DSS (p = 0.06), but no effect on MFS after adjustment for tumor size and lymph node status. CONCLUSION: Treatment hb-l, in addition to tumor size and lymph node status, independently predicted outcome. Although our final multivariate analysis showed a therapeutic benefit for patients whose hb-l was corrected, the response to RBCT was disappointing. Results of our subgroup analysis suggest that the cause of anemia in patients with cervical cancer warrants in-depth investigation.\n\nBerghold, Andrea\n\nPetru, Edgar\n\n\n"
},
{
"text": "\n123195\nData-based theoretical identification of subcellular calcium compartments and estimation of calcium dynamics in cardiac myocytes.\n\nLivshitz, L\n\nAcsai, K\n\nAntoons, G\n\nSipido, K\n\nRudy, Y\n\nBeiträge in Fachzeitschriften\nISI:000308871100003\n22547631.0\n10.1113/jphysiol.2012.228791\nPMC3477750\nIn cardiac cells, Ca(2+) release flux (J(rel)) via ryanodine receptors (RyRs) from the sarcoplasmic reticulum (SR) has a complex effect on the action potential (AP). Coupling between J(rel) and the AP occurs via L-type Ca(2+) channels (I(Ca)) and the Na(+)/Ca(2+) exchanger (I(NCX)). We used a combined experimental and modelling approach to study interactions between J(rel), I(Ca) and I(NCX) in porcine ventricular myocytes.We tested the hypothesis that during normal uniform J(rel), the interaction between these fluxes can be represented as occurring in two myoplasmic subcompartments for Ca(2+) distribution, one (T-space) associated with RyR and enclosed by the junctional portion of the SR membrane and corresponding T-tubular portion of the sarcolemma, the other (M-space) encompassing the rest of the myoplasm. I(Ca) and I(NCX) were partitioned into subpopulations in the T-space and M-space sarcolemma. We denoted free Ca(2+) concentrations in T-space and M-space Ca(t) and Ca(m), respectively. Experiments were designed to allow separate measurements of I(Ca) and I(NCX) as a function of J(rel). Inclusion of T-space in themodel allowed us to reproduce in silico the following important experimental results: (1) hysteresis of I(NCX) dependence on Ca(m); (2) delay between peak I(NCX) and peak Ca(m) during caffeine application protocol; (3) delay between I(NCX) and Ca(m) during Ca(2+)-induced-Ca(2+)-release; (4) rapid I(Ca) inactivation (within 2 ms) due to J(rel), with magnitude graded as a function of the SR Ca(2+) content; (5) time delay between I(Ca) inactivation due to J(rel) and Ca(m). Partition of 25% NCX in T-space and 75% in M-space provided the best fit to the experimental data. Measured Ca(m) and I(Ca) or I(NCX) were used as input to the model for estimating Ca(t). The actual model-computed Ca(t), obtained by simulating specific experimental protocols, was used as a gold standard for comparison. The model predicted peak Ca(t) in the range of 6–25 μM, with time to equilibrium of Ca(t) with Ca(m) of ~350 ms. These Ca(t) values are in the range of LCC and RyR sensitivity to Ca(2+). An increase of the SR Ca(2+) load increased the time to equilibrium. The I(Ca)-based estimation method was most accurate during the ascending phase of Ca(t). The I(NCX)-based method provided a good estimate for the descending phase of Ca(t). Thus, application of both methods in combination provides the best estimate of the entire Ca(t) time course.\n\n\n"
},
{
"text": "\n177353\nNorursodeoxycholic acid versus placebo in the treatment of non-alcoholic fatty liver disease: a double-blind, randomised, placebo-controlled, phase 2 dose-finding trial.\n\nTraussnigg, S\n\nSchattenberg, JM\n\nDemir, M\n\nWiegand, J\n\nGeier, A\n\nTeuber, G\n\nHofmann, WP\n\nKremer, AE\n\nSpreda, F\n\nKluwe, J\n\nPetersen, J\n\nBoettler, T\n\nRainer, F\n\nHalilbasic, E\n\nGreinwald, R\n\nPröls, M\n\nManns, MP\n\nFickert, P\n\nTrauner, M\n\nAustrian/German NAFLD-norUDCA study group\n\nBeiträge in Fachzeitschriften\nISI:000485108300019\n31345778.0\n10.1016/S2468-1253(19)30184-0\nNone\nNorursodeoxycholic acid is an orally administered side chain-shortened homologue of ursodeoxycholic acid that undergoes hepatic enrichment with hepatoprotective, anti-inflammatory, and antifibrotic activity. We assessed the efficacy of two doses of norursodeoxycholic acid versus placebo for the treatment of non-alcoholic fatty liver disease.\n We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 dose-finding clinical trial in tertiary referral hospitals and medical centres in Austria (n=6) and Germany (n=23) for patients with non-alcoholic fatty liver disease with or without diabetes. Patients with a clinical diagnosis of non-alcoholic fatty liver disease and serum alanine aminotransferase (ALT) concentrations of more than 0·8 times the upper limit of normal were randomly assigned (1:1:1) using a computer-generated central randomisation. Patients were randomly assigned to receive either norursodeoxycholic acid capsules at 500 mg per day or 1500 mg per day, or placebo, for 12 weeks with a subsequent 4-week follow-up period. All individuals involved in the trial were masked to treatment allocation. The primary efficacy endpoint was the mean relative percentage change in ALT concentrations between baseline and end of treatment assessed in the intention-to-treat population. This trial is registered with EudraCT, number 2013-004605-38.\n Between March 30, 2015, and Sept 20, 2016, of 198 individuals included in the analysis, 67 patients were randomly assigned to receive 500 mg norursodeoxycholic acid, 67 to 1500 mg norursodeoxycholic acid, and 64 to placebo. A dose-dependent reduction in serum ALT between baseline and end of treatment was observed with norursodeoxycholic acid versus placebo, with a significant effect in the 1500 mg group (mean change -27·8%, 95% repeated CI -34·7 to -14·4; p<0·0001). Serious adverse events (n=6) and treatment-emergent adverse events (n=314) were reported in a similar proportion of patients across groups. 112 treatment-emergent adverse events occurred in the 1500 mg group, 99 in the 500 mg group, and 103 in the placebo group. The most frequent adverse events were headache, gastrointestinal disorders, and infections (eg, diarrhoea, abdominal pain, or nasopharyngitis).\n Norursodeoxycholic acid at 1500 mg resulted in a significant reduction of serum ALT within 12 weeks of treatment when compared with placebo. Norursodeoxycholic acid was safe and well tolerated encouraging further studies.\n Dr Falk Pharma GmbH.\n Copyright © 2019 Elsevier Ltd. All rights reserved.\n\nFickert, Peter\n\nRainer, Florian\n\n\n"
},
{
"text": "\n184095\nEnhancing early detection of neurological and developmental disorders and provision of intervention in low-resource settings in Uttar Pradesh, India: study protocol of the G.A.N.E.S.H. programme.\n\nToldo, M\n\nVarishthananda, S\n\nEinspieler, C\n\nTripathi, N\n\nSingh, A\n\nVerma, SK\n\nVishwakarma, K\n\nZhang, D\n\nDwivedi, A\n\nGupta, R\n\nKarn, S\n\nKerketta, N\n\nNarayan, R\n\nNikam Singh, K\n\nRani, S\n\nSingh, A\n\nSingh, D\n\nSingh, KP\n\nSingh, N\n\nSingh, N\n\nSingh, R\n\nSingh, SP\n\nSrivastava, R\n\nSrivastava, S\n\nSrivastava, S\n\nYadav, G\n\nYadav, P\n\nYadav, S\n\nYadav, S\n\nMarschik, PB\n\nBeiträge in Fachzeitschriften\nISI:000591360100020\n33148727.0\n10.1136/bmjopen-2020-037335\nPMC7640505\nAround 9% of India's children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants <5 months. In addition, children with developmental delay, intellectual disabilities, late detected genetic disorders or autism spectrum disorder show abnormal general movements (GMs) during infancy. General Movement Assessment in Neonates for Early Identification and Intervention, Social Support and Health Awareness (G.A.N.E.S.H.) aims to (1) provide evidence as to whether community health workers can support the identification of infants at high-risk for neurological and developmental disorders and disabilities, (2) monitor further development in those infants and (3) initiate early and targeted intervention procedures.\n This 3-year observational cohort study will comprise at least 2000 infants born across four districts of Uttar Pradesh, India. Community health workers, certified for GMA, video record and assess the infants' GMs twice, that is, within 2 months after birth and at 3-5 months. In case of abnormal GMs and/or reduced MOSs, infants are further examined by a paediatrician and a neurologist. If necessary, early intervention strategies (treatment as usual) are introduced. After paediatric and neurodevelopmental assessments at 12-24 months, outcomes are categorised as normal or neurological/developmental disorders. Research objective (1): to relate the GMA to the outcome at 12-24 months. Research objective (2): to investigate the impact of predefined exposures. Research objective (3): to evaluate the interscorer agreement of GMA.\n G.A.N.E.S.H. received ethics approval from the Indian Government Chief Medical Officers of Varanasi and Mirzapur and from the Ramakrishna Mission Home of Service in Varanasi. GMA is a worldwide used diagnostic tool, approved by the Ethics Committee of the Medical University of Graz, Austria (27-388 ex 14/15). Apart from peer-reviewed publications, we are planning to deploy G.A.N.E.S.H. in other vulnerable settings.\n © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.\n\nEinspieler, Christa\n\nMarschik, Dajie\n\nMarschik, Peter\n\n\n"
},
{
"text": "\n186969\n5'UTR polymorphism in the serotonergic receptor HTR3A gene is differently associated with striatal Dopamine D2/D3 receptor availability in the right putamen in Fibromyalgia patients and healthy controls-Preliminary evidence.\n\nLedermann, K\n\nHasler, G\n\nJenewein, J\n\nSprott, H\n\nSchnyder, U\n\nMartin-Soelch, C\n\nBeiträge in Fachzeitschriften\nISI:000505971900001\n31868947.0\n10.1002/syn.22147\nNone\nExtensive literature has investigated the role of serotonin (5-HT) in the control of the central dopamine (DA) systems, and their dysfunction in the pathological conditions. 5-HT stimulates the local DA release in striatal regions via activation of various receptors including serotonin receptor-3 (5-HT3). Several studies have related polymorphisms (SNPs) in the serotonin receptor-3 (HTR3) genes to be associated with the pain modulation and endogenous pain suppression. A few studies suggested a functional role of 5'UTR SNP in the serotonergic receptor HTR3A gene (rs1062613) in the development of the chronic pain and Fibromyalgia syndrome (FMS) in particular. Here, we investigated the effect of a 5'UTR SNP in the serotonergic receptor HTR3A gene (rs1062613) on striatal dopamine D2/D3 receptor (DRD2) availability and reward-associated DA release in response to unpredictable monetary rewards in 23 women with FMS and 17 age-matched healthy female controls. Furthermore, we aimed to examine if SNP rs1062613 is associated with thermal pain and pain tolerance thresholds.\n We used PET and [11 C]raclopride to assess the DRD2 availability. In the same participants we used the [11 C]raclopride PET bolus-plus-infusion method to measure the [11 C]raclopride receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition. DRD2 availability and ΔBP were assessed in MRI-based striatal regions of interest. Thermal pain and pain tolerance thresholds were assessed outside the scanner.\n The frequency of SNP rs1062613 genotype differed significantly between groups, indicating that CC homozygotes were more frequent in FMS patients (82.6%) than in healthy controls (41.3%). Our results showed a significant main effect of SNP rs1062613 on [11 C]raclopride binding potential in the right caudate nucleus indicating a higher DRD2 receptor availability for CC-genotype of this SNP. Furthermore, we found a significant group × SNP interaction on [11 C]raclopride binding potential in the right putamen, indicating a higher DRD2 availability in T-carriers compared to CC genotype of SNP rs1062613 in FMS patients, whereas this effect was not present in healthy controls. However, we did not find an influence of SNP rs1062613 on reward-related DA release. In addition, there was no association between SNP rs1062613 and pain threshold or pain tolerance threshold in our data.\n These preliminary results indicate that SNP rs1062613 in the serotonergic receptor HTR3A gene possibly modulates the DRD2 receptor availability.\n © 2019 Wiley Periodicals, Inc.\n\nJenewein, Josef\n\n\n"
},
{
"text": "\n81493\nEscalating immunomodulatory therapy of multiple sclerosis. Update (September 2006)\n\nBassetti, C\n\nBeer, K\n\nBeer, S\n\nBuettner, U\n\nChofflon, M\n\nGass, A\n\nGoebels, N\n\nGotschi-Fuchs, M\n\nKappos, L\n\nKesselring, J\n\nLudin, HP\n\nMattle, H\n\nSchluep, M\n\nVaney, C\n\nBaumhackl, U\n\nBerger, T\n\nDeisenhammer, F\n\nFazekas, F\n\nFreimuller, M\n\nKollegger, H\n\nKristoferitsch, W\n\nLassmann, H\n\nMarkut, H\n\nStrasser-Fuchs, S\n\nVass, K\n\nAltenkirch, H\n\nBamborschke, S\n\nBaum, K\n\nBayas, A\n\nBenecke, R\n\nBruck, W\n\nButtmann, M\n\nChan, A\n\nDaumer, M\n\nDommasch, D\n\nElias, WG\n\nFasshauer, E\n\nFlachenecker, P\n\nGehlen, W\n\nGold, R\n\nHaas, J\n\nHaferkamp, G\n\nHaller, P\n\nHartung, HP\n\nHeesen, C\n\nHeibel, M\n\nHeidenreich, F\n\nHemmer, B\n\nHenze, T\n\nHohlfeld, R\n\nJanzen, RWC\n\nJapp, G\n\nJung, S\n\nJugelt, E\n\nKallmann, B\n\nKieseier, BC\n\nKleinschnitz, C\n\nKohler, J\n\nKohler, W\n\nKolmel, W\n\nKonig, N\n\nLehrieder, G\n\nLeussink, V\n\nLowitzsch, K\n\nMaurer, M\n\nManegold, U\n\nMelms, A\n\nMertin, J\n\nNeuhaus, O\n\nOschmann, P\n\nPetereit, HF\n\nPette, M\n\nPohlau, D\n\nPohl, D\n\nRieckmann, P\n\nRuprecht, K\n\nSailer, M\n\nSchipper, H\n\nSchmidt, S\n\nSchock, G\n\nSchulz, M\n\nSchwarz, S\n\nSchwendemann, G\n\nSeidel, D\n\nSommer, N\n\nStangel, M\n\nStark, E\n\nSteinbrecher, A\n\nStoll, G\n\nToyka, KV\n\nTumani, H\n\nVoltz, R\n\nWandinger, KP\n\nWeber, F\n\nWeilbach, F\n\nWeinrich, W\n\nWeissert, R\n\nWiendl, H\n\nWietholter, H\n\nWildemann, B\n\nZettl, UK\n\nZiemssen, T\n\nZipp, F\n\nZschenderlein, R\n\nRieckmann, P\n\nToyka, KV\n\nBeiträge in Fachzeitschriften\nISI:000243486600014\n17136556.0\n10.1007/s00115-006-2220-x\nNone\nThe updated recommendations presented here reflect new developments in the diagnostic work-up and immunotherapy of multiple sclerosis (MS) as well as optimization of medical care for MS patients. Monoclonal antibodies provide considerable improvement of treatment, but their use in basic therapy is restricted by their side effect profile. Thus, for the time being, natalizumab is only approved for monotherapy after basic treatment has failed or for rapidly progressive relapsing-remitting MS. In contrast, long-term data on recombinant beta-interferons and glatiramer acetate (Copaxone) show that even after several years no unexpected side effects occur and that a prolonged therapeutic effect can be assumed which correlates with the dose or frequency of treatment. Recently IFN-beta1b (Betaferon) was approved for prophylactic treatment after the first attack (clinically isolated syndrome, CIS). During treatment with beta-interferons, neutralizing antibodies can emerge with possible loss of effectivity. In contrast, antibodies play no role in treatment with glatiramer acetate. During or after therapy with mitoxantrone, serious side effects (cardiomyopathy, acute myeloid leukemia) appeared in 0.2-0.4% of cases. Plasmapheresis is limited to individual curative attempts in escalating therapy of a severe attack. According to the revised McDonald criteria, the diagnosis of MS can be made as early as the occurrence of the first attack (CIS). Recommendations for optimized care of MS patients are also new, thus implementing a resolution of the European Parliament.\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n177360\nEligibility and subsequent burden of cardiovascular disease of four strategies for blood pressure-lowering treatment: a retrospective cohort study\n\nZweiker, R\n\nBeiträge in Fachzeitschriften\nISI:000485980400006\nNone\nNone\nNone\nBackground: Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example. Methods: We did a retrospective cohort study in primary care patients aged 30-79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality. We assessed and compared four different strategies to determine eligibility for treatment: using 2011 UK National Institute for Health and Care Excellence (NICE) guideline, or proposed 2019 NICE guideline, or blood pressure alone (threshold > 140/90 mmHg), or predicted 10-year cardiovascular risk alone (QRISK2 score >= 10%). Patients were followed up until the earliest occurrence of a cardiovascular disease diagnosis, death, or end of follow-up period (March 31, 2016). For each strategy, we estimated the proportion of patients eligible for treatment and number of cardiovascular events that could be prevented with treatment. We then estimated eligibility and number of events that would occur during 10 years in the UK general population. Findings: Between Jan 1, 2011, and March 31, 2016, 1, 22.670 patients in the cohort were followed up for a median of 4.3 years (IQR 2.5-5.2). 271.963 (22.2%) patients were eligible for treatment under the 2011 NICE guideline, 327.429 (26.8%) under the proposed 2019 NICE guideline, 481.859 (39.4%) on the basis of a blood pressure threshold of 140/90 mmHg or higher, and 357.840 (29.3%) on the basis of a QRISK2 threshold of 10% or higher. During follow-up, 32.183 patients were diagnosed with cardiovascular disease (overall rate 7.1 per 1000 person-years, 95% CI 7.0-7.2). Cardiovascular event rates in patients eligible for each strategy were 15.2 per 1000 person-years (95% CI 15.0-15.5) under the 2011 NICE guideline, 14.9 (14.7-15.1) under the proposed 2019 NICE guideline, 11.4 (11.3-11.6) with blood pressure threshold alone, and 16.9 (16.7-17.1) with QRISK2 threshold alone. Scaled to the UK population, we estimated that 233.152 events would be avoided under the 2011 NICE guideline (28 patients needed to treat for 10 years to avoid one event), 270.233 under the 2019 NICE guideline (29 patients), 301.523 using a blood pressure threshold (38 patients), and 322.921 using QRISK2 threshold (27 patients). Interpretation: A cardiovascular risk-based strategy (QRISK2 >= 10%) could prevent over a third more cardiovascular disease events than the 2011 NICE guideline and a fifth more than the 2019 NICE guideline, with similar efficiency regarding number treated per event avoided.\n\nZweiker, Robert\n\n\n"
},
{
"text": "\n127095\nTonsillotomy and adenotonsillectomy in childhood. Study on postoperative pain therapy.\n\nPlatzer, M\n\nLikar, R\n\nStettner, H\n\nJost, R\n\nWutti, C\n\nLeipold, H\n\nBreschan, C\n\nBeiträge in Fachzeitschriften\nISI:000293135400004\n21607780.0\n10.1007/s00101-011-1855-6\nNone\nThe primary aim of this study was to determine whether the combination of i.v. ketoprofen and i.v. paracetamol provides superior postoperative analgesia in children undergoing adenoidectomy or tonsillotomy compared to either drug alone. The secondary goal was to assess the time until rescue analgesia was needed, propofol requirements and the incidence of vomiting and time of discharge from the postanaesthesia recovery unit (PARU). This double-blinded study included 120 children (aged 3-13 years) scheduled for elective tonsillectomy, adenoidectomy or adenotonsillectomy. The children were randomly assigned to one of 3 groups of 40 children each, using the sealed envelope method. The children received i.v. ketoprofen 2 mg/kgBW (group 1) or paracetamol 15 mg/kgBW (group 2) or the combination of these 2 drugs (group 3) after induction of anaesthesia. Standardized general anaesthesia consisted of sevoflurane and fentanyl at a dose of 2-3 mu g/kgBW. Pain was assessed using a 5-point scoring system based on the Smiley scale. The Smiley scale shows various faces from a laughing face which corresponds to the state of no pain to a very unhappy face which corresponds to the situation of worst pain (1: no pain, 2: mild pain, 3: moderate pain, 4: severe pain, 5: worst pain). Pain was assessed at 30 min, 1 h, 2 h, 3 h and 4 h after arriving in the PACU. If the pain score exceeded 2 an i.v. dose of 0.1 mg/kgBW morphine was administered as rescue analgesia. During the stay in the PACU the children in the combination group required significantly less supplementary rescue analgesia than children in the ketoprofen and paracetamol groups (17.5% versus 30.8% versus 45%, respectively, chi(2) analysis < 0.05). Pain scoring was highest after paracetamol, however, this difference was only significant when compared to the group receiving the combination of paracetamol and ketoprofen (U-test p < 0.05). Rescue analgesia was administered earliest in group 2 (paracetamol) reaching statistical significance, however, only when compared to group 3 (logrank test p < 0.05). Propofol requirements and time to discharge from the PACU did not differ significantly between the 3 groups (chi(2) analysis; U-test; p > 0.05). The overall incidence of vomiting was very low in this study with 6.4% (9/139). Significantly more children in the paracetamol group compared to ketoprofen group and combination group suffered from vomiting (17.5% versus 2.6% versus 2.5%; chi(2) analysis; p < 0.05). The time to discharge from PACU did not differ significantly between the 3 groups (U-test: p > 0.05). The combination of i.v. paracetamol and i.v. ketoprofen provides superior postoperative analgesia compared to the single use of paracetamol.\n\nBreschan, Christian\n\n\n"
},
{
"text": "\n103573\nB vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.\n\nVITATOPS Trial Study Group\n\nBeiträge in Fachzeitschriften\nISI:000281465900006\n20688574.0\n10.1016/S1474-4422(10)70187-3\nNone\nBackground Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye. Methods In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444. Findings Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups. Interpretation Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins.\n\nRopele, Stefan\n\nSchmidt, Reinhold\n\nStögerer-Oberschmid, Eva Maria\n\n\n"
},
{
"text": "\n171614\nInduction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.\n\nDietz, A\n\nWichmann, G\n\nKuhnt, T\n\nPfreundner, L\n\nHagen, R\n\nScheich, M\n\nKölbl, O\n\nHautmann, MG\n\nStrutz, J\n\nSchreiber, F\n\nBockmühl, U\n\nSchilling, V\n\nFeyer, P\n\nde Wit, M\n\nMaschmeyer, G\n\nJungehülsing, M\n\nSchroeder, U\n\nWollenberg, B\n\nSittel, C\n\nMünter, M\n\nLenarz, T\n\nKlussmann, JP\n\nGuntinas-Lichius, O\n\nRudack, C\n\nEich, HT\n\nFoerg, T\n\nPreyer, S\n\nWesthofen, M\n\nWelkoborsky, HJ\n\nEsser, D\n\nThurnher, D\n\nRemmert, S\n\nSudhoff, H\n\nGörner, M\n\nBünzel, J\n\nBudach, V\n\nHeld, S\n\nKnödler, M\n\nLordick, F\n\nWiegand, S\n\nVogel, K\n\nBoehm, A\n\nFlentje, M\n\nKeilholz, U\n\nBeiträge in Fachzeitschriften\nISI:000455165100014\n30412221.0\n10.1093/annonc/mdy332\nNone\nThe German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC).\n Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B.\n Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%.\n Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS.\n NCT00508664.\n\nThurnher, Dietmar\n\n\n"
},
{
"text": "\n183331\nAssociation of common genetic variants with brain microbleeds: A genome-wide association study.\n\nKnol, MJ\n\nLu, D\n\nTraylor, M\n\nAdams, HHH\n\nRomero, JRJ\n\nSmith, AV\n\nFornage, M\n\nHofer, E\n\nLiu, J\n\nHostettler, IC\n\nLuciano, M\n\nTrompet, S\n\nGiese, AK\n\nHilal, S\n\nvan den Akker, EB\n\nVojinovic, D\n\nLi, S\n\nSigurdsson, S\n\nvan der Lee, SJ\n\nJack, CR\n\nWilson, D\n\nYilmaz, P\n\nSatizabal, CL\n\nLiewald, DCM\n\nvan der Grond, J\n\nChen, C\n\nSaba, Y\n\nvan der Lugt, A\n\nBastin, ME\n\nWindham, BG\n\nCheng, CY\n\nPirpamer, L\n\nKantarci, K\n\nHimali, JJ\n\nYang, Q\n\nMorris, Z\n\nBeiser, AS\n\nTozer, DJ\n\nVernooij, MW\n\nAmin, N\n\nBeekman, M\n\nKoh, JY\n\nStott, DJ\n\nHoulden, H\n\nSchmidt, R\n\nGottesman, RF\n\nMacKinnon, AD\n\nDeCarli, C\n\nGudnason, V\n\nDeary, IJ\n\nvan Duijn, CM\n\nSlagboom, PE\n\nWong, TY\n\nRost, NS\n\nJukema, JW\n\nMosley, TH\n\nWerring, DJ\n\nSchmidt, H\n\nWardlaw, JM\n\nIkram, MA\n\nSeshadri, S\n\nLauner, LJ\n\nMarkus, HS\n\nAlzheimer's Disease Neuroimaging Initiative\n\nBeiträge in Fachzeitschriften\nISI:000607315800029\n32913026.0\n10.1212/WNL.0000000000010852\nPMC7836652\nTo identify common genetic variants associated with the presence of brain microbleeds (BMBs).\n We performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMBs were rated on susceptibility-weighted or T2*-weighted gradient echo MRI sequences, and further classified as lobar or mixed (including strictly deep and infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs.\n BMBs were detected in 3, 56 of the 25, 62 participants, of which 2, 79 were strictly lobar and 1, 93 mixed. One locus in the APOE region reached genome-wide significance for its association with BMB (lead single nucleotide polymorphism rs769449; odds ratio [OR]any BMB [95% confidence interval (CI)] 1.33 [1.21-1.45]; p = 2.5 × 10-10). APOE ε4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19-1.50]; p = 1.0 × 10-6) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86-1.25]; p = 0.68). APOE ε2 alleles did not show associations with BMB counts. Variants previously related to deep intracerebral hemorrhage and lacunar stroke, and a risk score of cerebral white matter hyperintensity variants, were associated with BMB.\n Genetic variants in the APOE region are associated with the presence of BMB, most likely due to the APOE ε4 allele count related to a higher number of strictly lobar BMBs. Genetic predisposition to small vessel disease confers risk of BMB, indicating genetic overlap with other cerebral small vessel disease markers.\n Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.\n\nHofer, Edith\n\nPirpamer, Lukas\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n187418\nTreatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient(R) in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06)\n\nPink, D\n\nAndreou, D\n\nBauer, S\n\nBrodowicz, T\n\nKasper, B\n\nReichardt, P\n\nRichter, S\n\nLindner, LH\n\nSzkandera, J\n\nGruenwald, V\n\nKebenko, M\n\nKirchner, M\n\nHohenberger, P\n\nBeiträge in Fachzeitschriften\nISI:000634327600001\nNone\n10.3390/cancers13061223\nNone\nSimple Summary There are very few systemic treatment options for patients with advanced angiosarcomas. We therefore examined whether combined treatment with paclitaxel and pazopanib was active and well tolerated. However, we did not meet a preplanned interim target of 6/14 patients without progression of the disease at 6 months, after which finding we stopped recruitment, having enrolled a total of 26 patients. Of the patients enrolled, 46% were progression-free at 6 months. Two patients showed a complete and seven patients a partial tumor response to treatment. The progression-free survival of patients with superficial tumors was significantly longer compared to the patients with visceral tumors. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. The results in patients with superficial tumors appear promising. Future studies should evaluate the safety and efficacy of vascular endothelial growth factor receptor (VEGFR) and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting. We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7-15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, p = 0.0247) and PFS (11.3 vs. 2.7 months, p < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.\n\nSzkandera, Joanna\n\n\n"
},
{
"text": "\n16738\nQuantitative patch and repeated open application testing in methyldibromo glutaronitrile-sensitive patients.\n\nSchnuch, A\n\nKelterer, D\n\nBauer, A\n\nSchuster, Ch\n\nAberer, W\n\nMahler, V\n\nKatzer, K\n\nRakoski, J\n\nJappe, U\n\nKrautheim, A\n\nBircher, A\n\nKoch, P\n\nWorm, M\n\nLöffler, H\n\nHillen, U\n\nFrosch, PJ\n\nUter, W\n\nBeiträge in Fachzeitschriften\nISI:000228744700005\n15859992.0\n10.1111/j.0105-1873.2005.00529.x\nNone\nContact allergy to methyldibromo glutaronitrile (MDBGN), often combined with phenoxyethanol (PE) (e.g., Euxyl K 400), increased throughout the 1990s in Europe. Consequently, in 2003, the European Commission banned its use in leave-on products, where its use concentration was considered too high and the non-sensitizing use concentration as yet unknown. The 2 objectives of the study are (a) to find a maximum non-eliciting concentration in a leave-on product in MDBGN/PE-sensitized patients, which could possibly also be considered safe regarding induction and (b) to find the best patch test concentration for MDBGN. We, therefore, performed a use-related test (ROAT) in patients sensitized to MDBGN/PE (n = 39) with 3 concentrations of MDBGN/PE (50, 100 and 250 p.p.m. MDBGN, respectively). A subset of these patients (n = 24) was later patch-tested with various concentrations (0.1, 0.2, 0.3 and 0.5% MDBGN, respectively). 15 patients (38%, 95% confidence interval (CI) = 23-55%) had a negative and 24 (62%; 95% CI = 45-77%) a positive overall repeated open application test (ROAT) result. 13 reacted to the lowest (50 p.p.m.), 8 to the middle (100 p.p.m.) and 3 to the highest concentration (250 p.p.m.) only. In those 13 reacting to the lowest ROAT concentration, dermatitis developed within a few days (1-7). The strength of the initial and the confirmatory patch test result, respectively, and the outcome of the ROAT were positively associated. Of the 24 patients with a use and confirmatory patch test, 15 reacted to 0.1% MDBGN, 16 to 0.2%, 17 to 0.3% and 22 to 0.5%. With the patch test concentration of 0.5%, the number of ROAT-negative patients but patch-test-positive patients increases considerably, particularly due to + reactions. A maximum sensitivity of 94% (95% CI = 70-100%) is reached with a patch test concentration of 0.2%, and is not further improved by increasing the concentration. However, the specificity decreases dramatically from 88 (95% CI = 47-100%) with 0.2% to a mere 12.5% (95% CI = 0-53%) with 0.5%. It can be concluded (a) that for MDBGN 0.2% is very likely the best patch test concentration and (b) that 50 p.p.m. in a leave-on product can elicit contact dermatitis in sensitized persons. We were, therefore, unable to find a safe, still microbicidal, concentration for leave-on products. By contrast, with other contact allergens, dose-response use tests may be able to identify a non-eliciting concentration, which could give valuable clues to a non-inducing (i.e., safe) concentration in products.\n\nAberer, Werner\n\nSchuster, Christian Josef\n\n\n"
},
{
"text": "\n127822\nThe Foker Technique (FT) and Kimura Advancement (KA) for the Treatment of Children with Long-Gap Esophageal Atresia (LGEA): Lessons Learned at Two European Centers.\n\nSroka, M\n\nWachowiak, R\n\nLosin, M\n\nSzlagatys-Sidorkiewicz, A\n\nLandowski, P\n\nCzauderna, P\n\nFoker, J\n\nTill, H\n\n\n\nBeiträge in Fachzeitschriften\nISI:000315021100002\n23378143.0\n10.1055/s-0033-1333891\nNone\nIntroduction We present the experiences from two European centers performing the Foker technique (FT) of esophageal lengthening by axial traction and the Kimura advancement (KA) method of lengthening the upper pouch by extrathoracic resiting a spit fistula (SF) in children with long-gap esophageal atresia (LGEA, gap length > 5 cm). Materials and Methods A total of 15 children were treated (8 pure EA, 6 lower tracheoesophageal fistula [TEF], and 1 upper TEF). Gaps ranged from 5 to 14 cm. Nine children already had a SF. Patients were grouped according to the presence of a SF and the subsequent surgical strategy: Group A (no SF, n = 6) received FT on both pouches. Group B (with SF, n = 6) received KA of SF and FT of the lower pouch. Group C (with SF, n = 3) received closure of the SF and subsequent Foker traction (CSFT) on both pouches. Results Group A: Primary repairs for all six children (mean age 3 months, gap length 6.5 cm) after a mean traction time of 3 weeks and amean of 2.1 thoracotomies (range 2 to 3). Dilations were required in three out of six for anastomotic strictures with one perforation during the second dilation. Group B: All six children (mean age 16.4 months, gap length 9.5 cm) had a primary anastomosis, although for two it was significantly delayed (48 and 143 weeks traction time) because of infections. The number of thoracotomies ranged from 2 to 8 (mean 3.6). Leaks occurred in five out of six anastomoses (responsive to conservative management). Two children developed severe strictures, which required the anastomosis to be redone. In group C (mean age 10.6 months, gap length 6.5 cm), several major complications occurred. The three SF closures leaked (one iatrogenic) causing severe mediastinitis. CSFT was successful in only one case and the other two children had an esophageal replacement (stomach, jejunum). No deaths occurred in the series. Conclusion FT of both pouches (group A) resulted in primary repairs of all six LGEA patients. The combination of KA and FT (group B) resulted in an equivalent rate of primary repairs, but with an increased number of thoracotomies and rate of complications compared with group A. CSFT (group C) resulted in a high failure rate. More data are needed (we propose a multicenter registry) to elucidate the safety and efficacy of each elongation technique and to establish an algorithm with clearer inclusion and exclusion criteria.\n\nTill, Holger\n\n\n"
},
{
"text": "\n168638\nBaseline Characteristics of Patients With Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial.\n\nSolomon, SD\n\nRizkala, AR\n\nLefkowitz, MP\n\nShi, VC\n\nGong, J\n\nAnavekar, N\n\nAnker, SD\n\nArango, JL\n\nArenas, JL\n\nAtar, D\n\nBen-Gal, T\n\nBoytsov, SA\n\nChen, CH\n\nChopra, VK\n\nCleland, J\n\nComin-Colet, J\n\nDuengen, HD\n\nEcheverría Correa, LE\n\nFilippatos, G\n\nFlammer, AJ\n\nGalinier, M\n\nGodoy, A\n\nGoncalvesova, E\n\nJanssens, S\n\nKatova, T\n\nKøber, L\n\nLelonek, M\n\nLinssen, G\n\nLund, LH\n\nO'Meara, E\n\nMerkely, B\n\nMilicic, D\n\nOh, BH\n\nPerrone, SV\n\nRanjith, N\n\nSaito, Y\n\nSaraiva, JF\n\nShah, S\n\nSeferovic, PM\n\nSenni, M\n\nSibulo, AS\n\nSim, D\n\nSweitzer, NK\n\nTaurio, J\n\nVinereanu, D\n\nVrtovec, B\n\nWidimský, J\n\nYilmaz, MB\n\nZhou, J\n\nZweiker, R\n\nAnand, IS\n\nGe, J\n\nLam, CSP\n\nMaggioni, AP\n\nMartinez, F\n\nPacker, M\n\nPfeffer, MA\n\nPieske, B\n\nRedfield, MM\n\nRouleau, JL\n\nVan Veldhuisen, DJ\n\nZannad, F\n\nZile, MR\n\nMcMurray, JJV\n\nBeiträge in Fachzeitschriften\nISI:000438926500008\n29980595.0\n10.1161/CIRCHEARTFAILURE.118.004962\nNone\nTo describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality.\n We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease.\n PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics.\n URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.\n © 2018 American Heart Association, Inc.\n\nZweiker, Robert\n\n\n"
},
{
"text": "\n693\nDetection of pulmonary nodules with helical CT: comparison of cine and film-based viewing.\n\nTillich, M\n\nKammerhuber, F\n\nReittner, P\n\nRiepl, T\n\nStoeffler, G\n\nSzolar, DH\n\nBeiträge in Fachzeitschriften\nISI:A1997YH01000028\n9393175.0\n10.2214/ajr.169.6.9393175\nNone\nOBJECTIVE: The purpose of our study was to determine whether cine viewing of helical CT scans of the chest improves the detection of pulmonary nodules in patients with known extrathoracic malignancy. SUBJECTS AND METHODS: Identical helical CT studies of the chest of 60 patients with known extrathoracic malignancy were reviewed for detection of pulmonary nodules. Four radiologists interpreted the helical CT studies. Pulmonary nodules were divided into four groups according to maximum diameter: group 1, nodules smaller than or equal to 5 mm; group 2, nodules larger than 5 mm but smaller than or equal to 10 mm; group 3, nodules larger than 10 mm but smaller than or equal to 20 mm; group 4, nodules larger than 20 mm. Interpreters also assigned a lesion conspicuity score of pulmonary nodules based on a four-point scale: one point for poor visibility, two points for adequate visibility, three points for good visibility, and four points for excellent visibility. Static film-based images printed on a laser printer were viewed on a light box. Cine viewing of helical CT scans from the same examinations was done on a commercially available workstation. The number, diameter, and conspicuity scores of pulmonary nodules detected at lung window settings were documented. RESULTS: Interpreters saw 266 nodules on cine viewing, whereas 237 nodules were seen with static film-based viewing. A significantly higher percentage of nodules that were smaller than or equal to 5 mm in diameter was found with cine viewing (n = 106) than with static film-based viewing (n = 81) (p < .05). Cine viewing (n = 105) also allowed a slightly but not significantly higher detection rate of nodules that were larger than 5 mm but smaller than or equal to 10 mm in diameter than did static film-based viewing (n = 101). We found no differences between cine (n = 55) and static film-based viewing (n = 55) in the detection of pulmonary nodules that were larger than 10 mm in diameter. The mean conspicuity score of nodules was significantly higher with cine viewing (2.9 +/- 0.2) than with film-based viewing (2.4 +/- 0.2) (p < .05). CONCLUSION: Cine viewing of helical CT scans significantly increases the detection rate of pulmonary nodules that are smaller than or equal to 5 mm in diameter. However, we found no significant difference between cine and film-based viewing in the detection rate of pulmonary nodules that were larger than 5 mm in diameter. The advantages of cine viewing may be attributed to both the larger image size and the ability to scroll through images for improved differentiation between vessels and nodules.\n\nStoeffler, Gerharde\n\n\n"
}
]
}