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"text": "\n151269\nAccuracy of treatment planning based on stereolithography in computer assisted surgery.\n\nSchicho, K\n\nFigl, M\n\nSeemann, R\n\nEwers, R\n\nLambrecht, JT\n\nWagner, A\n\nWatzinger, F\n\nBaumann, A\n\nKainberger, F\n\nFruehwald, J\n\nKlug, C\n\nBeiträge in Fachzeitschriften\nISI:000240694400039\n17022237.0\n10.1118/1.2242014\nNone\nThree-dimensional stereolithographic models (SL models), made of solid acrylic resin derived from computed-tomography (CT) data, are an established tool for preoperative treatment planning in numerous fields of medicine. An innovative approach, combining stereolithography with computer-assisted point-to-point navigation, can support the precise surgical realization of a plan that has been defined on an SL model preoperatively. The essential prerequisites for the application of such an approach are: (1) The accuracy of the SL models (including accuracy of the CT scan and correspondence of the model with the patient's anatomy) and (2) the registration method used for the transfer of the plan from the SL model to the patient (i.e., whether the applied registration markers can be added to the SL model corresponding to the markers at the patient with an accuracy that keeps the "cumulative error" at the end of the chain of errors, in the order of the accuracy of contemporary navigation systems). In this study, we focus on these two topics: By applying image-matching techniques, we fuse the original CT data of the patient with the corresponding CT data of the scanned SL model, and measure the deviations of defined parameter (e.g., distances between anatomical points). To evaluate the registration method used for the planning transfer, we apply a point-merge algorithm, using four marker points that should be located at exactly corresponding positions at the patient and at connective bars that are added to the surface of the SL model. Again, deviations at defined anatomical structures are measured and analyzed statistically. Our results prove sufficient correspondence of the two data sets and accuracy of the registration method for routine clinical application. The evaluation of the SL model accuracy revealed an arithmetic mean of the relative deviations from 0.8% to 5.4%, with an overall mean deviation of 2.2%. Mean deviations of the investigated anatomical structures ranged from 0.8 mm to 3.2 mm. An overall mean (comprising all structures) of 2.5 mm was found. The fiducial registration error of the point-merge algorithm ranged from 1.0 mm to 1.4 mm. The evaluated chain of errors showed a mean deviation of 2.5 mm. This study verifies that preoperative planning on SL models and intraoperative transfer of this plan with computer assisted navigation is a suitable and sufficiently reliable method for clinical applications.\n\n\n"
},
{
"text": "\n171360\nAdherence to treatment in allergic rhinitis using mobile technology. The MASK Study.\n\nMenditto, E\n\nCosta, E\n\nMidão, L\n\nBosnic-Anticevich, S\n\nNovellino, E\n\nBialek, S\n\nBriedis, V\n\nMair, A\n\nRajabian-Soderlund, R\n\nArnavielhe, S\n\nBedbrook, A\n\nCzarlewski, W\n\nAnnesi-Maesano, I\n\nAnto, JM\n\nDevillier, P\n\nDe Vries, G\n\nKeil, T\n\nSheikh, A\n\nOrlando, V\n\nLarenas-Linnemann, D\n\nCecchi, L\n\nDe Feo, G\n\nIllario, M\n\nStellato, C\n\nFonseca, J\n\nMalva, J\n\nMorais-Almeida, M\n\nPereira, AM\n\nTodo-Bom, AM\n\nKvedariene, V\n\nValiulis, A\n\nBergmann, KC\n\nKlimek, L\n\nMösges, R\n\nPfaar, O\n\nZuberbier, T\n\nCardona, V\n\nMullol, J\n\nPapadopoulos, NG\n\nProkopakis, EP\n\nBewick, M\n\nRyan, D\n\nRoller-Wirnsberger, RE\n\nTomazic, PV\n\nCruz, AA\n\nKuna, P\n\nSamolinski, B\n\nFokkens, WJ\n\nReitsma, S\n\nBosse, I\n\nFontaine, JF\n\nLaune, D\n\nHaahtela, T\n\nToppila-Salmi, S\n\nBachert, C\n\nHellings, PW\n\nMelén, E\n\nWickman, M\n\nBindslev-Jensen, C\n\nEller, E\n\nO'Hehir, RE\n\nCingi, C\n\nGemicioğlu, B\n\nKalayci, O\n\nIvancevich, JC\n\nBousquet, J\n\nMASK group\n\nBeiträge in Fachzeitschriften\nISI:000463761700007\n30597673.0\n10.1111/cea.13333\nNone\nMobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries.\n To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App.\n An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach.\n A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users.\n Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.\n © 2019 John Wiley & Sons Ltd.\n\nRoller-Wirnsberger, Regina\n\nTomazic, Peter Valentin\n\n\n"
},
{
"text": "\n174150\nRespiratory Syncytial Virus Associated Hospitalizations in Infants of 33 to 42 Weeks' Gestation: Does Gestational Age Matter?\n\nResch, B\n\nWörner, C\n\nÖzdemir, S\n\nHubner, M\n\nPuchas, C\n\nUrlesberger, B\n\nBeiträge in Fachzeitschriften\nISI:000477670800005\n30887492.0\n10.1055/a-0868-0004\nNone\nTo evaluate rates and characteristics of respiratory syncytial virus hospitalizations (RSV-H) in infants of 33 to 42 weeks of gestational age (GA).\n All infants with a history of neonatal hospitalization and a GA of 33 to 42 weeks born between 2005 and 2015 and follow-up at least over one RSV season (first year of life). Infants with congenital heart disease and other congenital anomalies were excluded.\n Retrospective single-center cohort STROBE compliant study. Data were collected regarding demographic data and re-hospitalization characteristics due to respiratory illness and due to RSV infection; and data were compared between moderate-late preterm, near term, term, and post term infants, respectively.\n A total of 81.656 live born infants were registered in our catchment area with gestational age from 33 to 42 weeks during the study period; and 2188 of 2356 preterm infants and 1004 of 1168 term infants with history of neonatal hospitalization were included for analysis. Rehospitalizations due to respiratory illness occurred in 301 preterm (13.8%) and 136 term (13.5%) infants for 381 and 183 times, respectively. In total 84 of 3192 infants (2.6%) were tested RSV positive, 61 of 2188 preterm (2.8%) and 23 of 1004 term (2.3%). Preterm infants without history of neonatal hospitalization had a RSV hospitalization (RSV-H) rate of 1.7% (61/3488) and term infants of 1.3% (967/74.644) that were significantly lower compared to study infants (p=0.004 and 0.002, respectively). Moderate and late preterm (2.8%), near term (3.1%) and post term (3.5%) infants had significantly higher RSV-H rates compared to term infants (1.2%). Risk factors for RSV-H in preterm infants included discharge during RSV season (4.2 vs. 2.0%, p=0.017) and presence of older siblings (4.2 vs. 2.1%, p=0.023), in term infants presence of older siblings (p=0.019). The course of RSV disease did not differ between groups.\n Interestingly, we did not observe decreasing RSV-H rates with increasing GA. Term infants represented the group with lowest RSV-H rates. Neonatal hospitalization was a risk factor for RSV-H for both preterm and term infants. Near term infants do more resemble the late preterm than term infants regarding RSV-H rates.\n We found comparable higher RSV-H rates in all groups compared to term infants without differences in the course of disease and identified neonatal hospitalization as an independent risk factor.\n © Georg Thieme Verlag KG Stuttgart · New York.\n\nResch, Bernhard\n\nUrlesberger, Berndt\n\n\n"
},
{
"text": "\n5181\nTopical methyl aminolaevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment.\n\nHorn, M\n\nWolf, P\n\nWulf, HC\n\nWarloe, T\n\nFritsch, C\n\nRhodes, LE\n\nKaufmann, R\n\nDe Rie, M\n\nLegat, FJ\n\nStender, IM\n\nSolér, AM\n\nWennberg, AM\n\nWong, GA\n\nLarkö, O\n\nBeiträge in Fachzeitschriften\nISI:000187154400018\n14674903.0\n10.1111/j.1365-2133.2003.05600.x\nNone\nConventional treatment of basal cell carcinoma (BCC) causes morbidity and/or disfigurement in some patients because of the location (e.g. mid-face) and size of the lesion.\n Following reports that such difficult-to-treat BCC lesions have been treated successfully with topical methyl aminolaevulinate (MAL) photodynamic therapy (PDT), a multicentre study was performed to determine the response of such BCC to MAL-PDT.\n An open, uncontrolled, prospective, multicentre study was conducted comprising patients with superficial and/or nodular BCC who were at risk of complications, poor cosmetic outcome, disfigurement and/or recurrence using conventional therapy. Patients were given one or two cycles within 3 months of topical MAL-PDT, each consisting of two treatments 1 week apart. Tumour response was assessed clinically at 3 months after the last PDT, with histological confirmation of all lesions in clinical remission. The cosmetic outcome was rated. Patients with a BCC in remission will be followed up for 5 years for recurrence, of which the 24-month follow-up is reported here. Ninety-four patients with 123 lesions were enrolled and treated with MAL-PDT at nine European primary care and referral university hospitals. An independent blinded study review board (SRB) retrospectively excluded nine patients and a total of 15 lesions from the efficacy analysis, for not having a difficult-to-treat BCC according to the protocol.\n The lesion remission rate at 3 months was 92% (45 of 49) for superficial BCC, 87% (45 of 52) for nodular BCC, and 57% (four of seven) for mixed BCC, as assessed by clinical examination, and 85% (40 of 47), 75% (38 of 51), and 43% (three of seven), respectively, as assessed by histological examination and verified by the SRB. At 24 months after treatment, the overall lesion recurrence rate was 18% (12 of 66). The cosmetic outcome was graded as excellent or good by the investigators in 76% of the cases after 3 months follow-up, rising to 85% at 12 months follow-up, and 94% at 24 months follow-up.\n Topical MAL-PDT is effective in treating BCC at risk of complications and poor cosmetic outcome using conventional therapy. MAL-PDT preserves the skin and shows favourable cosmetic results.\n\nHorn, Michael\n\nLegat, Franz\n\nWolf, Peter\n\n\n"
},
{
"text": "\n136370\nThe central nervous system effects, pharmacokinetics and safety of the NAALADase-inhibitor GPI 5693.\n\nvan der Post, JP\n\nde Visser, SJ\n\nde Kam, ML\n\nWoelfler, M\n\nHilt, DC\n\nVornov, J\n\nBurak, ES\n\nBortey, E\n\nSlusher, BS\n\nLimsakun, T\n\nCohen, AF\n\nvan Gerven, JM\n\nBeiträge in Fachzeitschriften\nISI:000230600800003\n16042665.0\n10.1111/j.1365-2125.2005.02396.x\nPMC1884920\nThe aim was to assess the central nervous system (CNS) effects, pharmacokinetics and safety of GPI 5693, an inhibitor of a novel CNS-drug target, NAALADase which is being evaluated for the treatment of neuropathic pain.\n This was a double-blind, placebo-controlled, exploratory study in healthy subjects receiving oral GPI 5693 single ascending doses of 100, 300, 750, 1125 mg with a placebo treatment randomly interspersed. An open-label, parallel extension examined the effects of food and sex on the pharmacokinetics of 750, 1125 and 1500 mg doses. Blood samples were collected for pharmacokinetic and biochemical/haematological safety analysis, vital signs, ECG and adverse event checks were performed regularly up to 48 h postdose. Postdose CNS effects were assessed using eye movements, adaptive tracking, electroencephalography (EEG), body sway and Visual Analogue Scales (VAS).\n CNS effects were mainly observed after the 1125 mg dose, showing a significant decrease of adaptive tracking performance, VAS alertness and VAS mood, and an increase of EEG occipital alpha and theta power. Gastro-intestinal (GI) adverse effects were frequent at higher doses. No clinically significant changes in vital signs or ECG were noted during any of the treatments. The therapeutically relevant concentration range (950-11 100 ng ml(-1)) as determined from animal experiments was already reached after the 300 mg dose. C(max) after the 300 mg and 750 mg dose was 2868 and 9266 ng ml(-1) with a t(1/2) of 2.54 and 4.78 h, respectively. Concomitant food intake (with the 750 mg and 1125 mg doses) reduced C(max) by approximately 66% and AUC by approximately 40%. With concomitant food intake, the dose-normalized C(max) also decreased significantly by -5.6 (CI: -2.6 to -8.7) ng ml(-1) mg(-1). The pharmacokinetic variability was largest after the 300 mg and 750 mg dose, resulting in a SD of approximately 50% of the C(max).\n NAALADase inhibition with GPI 5693 was safe and tolerable in healthy subjects. Plasma concentrations that were effective in the reversal of hyperalgesia in the chronic constrictive injury animal model of neuropathic pain were obtained at doses of 300, 750 and 1125 mg in the fasted state. Comcomitant food intake reduced C(max) and AUC. CNS effects and GI AEs increased in incidence over placebo only at the 1125 mg dose.\n\nWölfler, Monika Martina\n\n\n"
},
{
"text": "\n154453\nHypertension and coronary artery disease: epidemiology, physiology, effects of treatment, and recommendations : A joint scientific statement from the Austrian Society of Cardiology and the Austrian Society of Hypertension.\n\nWeber, T\n\nLang, I\n\nZweiker, R\n\nHorn, S\n\nWenzel, RR\n\nWatschinger, B\n\nSlany, J\n\nEber, B\n\nRoithinger, FX\n\nMetzler, B\n\nBeiträge in Fachzeitschriften\nISI:000380123500001\n27278135.0\n10.1007/s00508-016-0998-5\nNone\nHigh blood pressure is a major modifiable risk factor for all clinical manifestations of coronary artery disease (CAD). In people without known cardiovascular disease, the lowest systolic (down to 90-114 mmHg) and the lowest diastolic (down to 60-74 mmHg) pressures are associated with the lowest risk for developing CAD. Although diastolic blood pressure is the strongest predictor of CAD in younger and middle-aged people, this relationship becomes inverted and pulse pressure shows the strongest direct relationship with CAD in people above 60 years of age.Pathophysiological mechanisms of blood pressure as a risk factor for CAD are complex and include the influence of blood pressure as a physical force on the development of the atherosclerotic plaque, and the relationship between pulsatile hemodynamics/arterial stiffness and coronary perfusion. Treatment of arterial hypertension has been proven to prevent coronary events in patients without clinical CAD. In patients with established CAD, the effect of blood pressure lowering per se is beneficial, probably more than specific drugs or drug classes. The important exceptions are beta blockers (BBs), which are superior to all other drug classes for use after a recent myocardial infarction. Blood pressure targets in patients with established CAD have created controversy in the light of the so-called J-curve phenomenon, which describes an increase in coronary events at lower diastolic blood pressures. One explanation for this observation is that perfusion of the left ventricle occurs predominantly during diastole, and that coronary autoregulation may be exhausted with low diastolic blood pressure in the setting of left ventricular hypertrophy and atherosclerotic narrowing of the epicardial coronaries. The worst situation is a high systolic blood pressure in the presence of a low diastolic blood pressure, both a hallmark of increased aortic stiffness. However, the lowering of systolic blood pressure is clearly beneficial in this setting, even at the price of further lowering diastolic pressure. Primary blood pressure goal in patients with established CAD is below 140/90 mmHg. Recent studies suggest that a lower systolic blood pressure may be appropriate, whereas caution is advised with diastolic blood pressure below 60 mmHg.\n\nHorn, Sabine\n\nZweiker, Robert\n\n\n"
},
{
"text": "\n167140\nQuality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters-patient-centered end points in trials of maintenance therapy.\n\nFriedlander, M\n\nRau, J\n\nLee, CK\n\nMeier, W\n\nLesoin, A\n\nKim, JW\n\nPoveda, A\n\nBuck, M\n\nScambia, G\n\nShimada, M\n\nHilpert, F\n\nKing, MT\n\nDebruyne, P\n\nBologna, A\n\nMalander, S\n\nMonk, BJ\n\nPetru, E\n\nCalvert, P\n\nHerzog, TJ\n\nBarrett, C\n\ndu Bois, A\n\nBeiträge in Fachzeitschriften\nISI:000429455000032\n29267856.0\n10.1093/annonc/mdx796\nNone\nHealth-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points.\n HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ.\n There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI - 0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P < 0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P [hazard ratio (HR) 0.72, 95% CI 0.69-0.86, P = 0.0001].\n There were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS.\n NCT00866697.\n\nPetru, Edgar\n\n\n"
},
{
"text": "\n181722\nRepresentation of patients with a migration background in studies on antithrombotic treatment. An analysis of recruitment data from a cluster randomized controlled trial.\n\nMergenthal, K\n\nSiebenhofer, A\n\nUlrich, LR\n\nGuethlin, C\n\nGerlach, FM\n\nPetersen, JJ\n\nBeiträge in Fachzeitschriften\nISI:000535291800023\n32176711.0\n10.1371/journal.pone.0230297\nPMC7075549\nThe health status, health awareness and health behavior of persons with a migration background often differ from the autochthonous population. Little is known about the proportion of patients with a migration background (PMB) that participate in primary care studies on oral antithrombotic treatment (OAT) in Germany, and whether the quality of their antithrombotic care differs from patients without a migration background. The aim of this paper was to use the results of a cluster-randomized controlled trial (PICANT) to determine the proportion of PMB at different stages of recruitment, and to compare the results in terms of sociodemographic characteristics and antithrombotic treatment.\n This study used screening and baseline data from the PICANT trial on oral anticoagulation management in GP practices. For this analysis, we determined the proportion of PMB during the recruitment period at stage 1 (screening of potentially eligible patients), stage 2 (eligible patients invited to participate in the trial), and stage 3 (assessment of baseline characteristics of patients participating in the PICANT trial). In addition, we compared patients in terms of sociodemographic characteristics and quality of anticoagulant treatment. Statistical analysis comprised descriptive and bivariate analyses.\n The proportion of PMB at each recruitment stage declined from 9.1% at stage 1 to 7.9% at stage 2 and 7.3% at stage 3). A lack of German language skills led to the exclusion of half the otherwise eligible PMB. At stages 1 and 3, PMB were younger (stage 1: 70.7 vs. 75.0 years, p<0.001; stage 3: 70.2 vs. 73.5 years, p = 0.013), but did not differ in terms of gender. The quality of their anticoagulant care was comparable (100.0% vs. 99.1% were receiving appropriate OAT, 94.4% vs. 95.7% took phenprocoumon, or warfarin, and the most recent INR measurement of 60.8% vs. 69.3% was within their individual INR range).\n In the potentially eligible population and among participants at baseline, the quality of anticoagulant care was high in all groups of patients, which is reassuring. To enable the inclusion of more PMB, future primary care research on OAT in Germany should address how best to overcome language barriers. This will be challenging, particularly because the heterogeneity of PMB means the resulting sample sizes for each specific language group are small.\n Current Controlled Trials ISRCTN41847489.\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n183939\nTargeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis.\n\nLópez-Vicario, C\n\nCheca, A\n\nUrdangarin, A\n\nAguilar, F\n\nAlcaraz-Quiles, J\n\nCaraceni, P\n\nAmorós, A\n\nPavesi, M\n\nGómez-Cabrero, D\n\nTrebicka, J\n\nOettl, K\n\nMoreau, R\n\nPlanell, N\n\nArroyo, V\n\nWheelock, CE\n\nClària, J\n\nBeiträge in Fachzeitschriften\nISI:000572079900017\n32294533.0\n10.1016/j.jhep.2020.03.046\nNone\nAcute-on-chronic liver failure (ACLF) is a newly described syndrome, which develops in patients with acute decompensation of cirrhosis, and is characterized by intense systemic inflammation, multiple organ failures and high short-term mortality. The profile of circulating lipid mediators, which are endogenous signaling molecules that play a major role in inflammation and immunity, is poorly characterized in ACLF.\n In the current study, we assessed the profile of lipid mediators by liquid chromatography coupled to tandem mass spectrometry in plasma from patients with acute decompensation of cirrhosis, with (n = 119) and without (n = 127) ACLF, and from healthy controls (n = 18). Measurements were prospectively repeated in 191 patients with acute decompensation of cirrhosis during a 28-day follow-up period.\n Fifty-nine lipid mediators (out of 100) were detected in plasma from cirrhotic patients, of which 16 were significantly associated with disease status. Among these, 11 lipid mediators distinguished patients at any stage from healthy controls, whereas 2 lipid mediators (LTE4 and 12-HHT, both derived from arachidonic acid) shaped a minimal plasma fingerprint that discriminated patients with ACLF from those without. Levels of LTE4 distinguished ACLF grade 3 from ACLF grades 1 and 2, followed the clinical course of the disease (increased with worsening and decreased with improvement) and positively correlated with markers of inflammation and non-apoptotic cell death. Moreover, LTE4 together with LXA5 (derived from eicosapentaenoic acid) and EKODE (derived from linoleic acid) were associated with short-term mortality. LXA5 and EKODE formed a signature associated with coagulation and liver failures.\n Taken together, these findings uncover specific lipid mediator profiles associated with disease severity and prognosis in patients with acute decompensation of cirrhosis.\n Acute-on-chronic liver failure (ACLF) is characterized by intense systemic inflammation, multiple organ failures and high short-term mortality. In the current study, we assessed the plasma lipid profile of 100 bioactive lipid mediators in healthy controls, patients with decompensated cirrhosis, and those who had developed ACLF. We identified lipid mediator signatures associated with inflammation and non-apoptotic cell death that discriminate disease severity and evolution, short-term mortality and organ failures.\n Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.\n\nÖttl, Karl\n\n\n"
},
{
"text": "\n187334\nIndacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD.\n\nWedzicha, JA\n\nBanerji, D\n\nChapman, KR\n\nVestbo, J\n\nRoche, N\n\nAyers, RT\n\nThach, C\n\nFogel, R\n\nPatalano, F\n\nVogelmeier, CF\n\nFLAME Investigators\n\nBeiträge in Fachzeitschriften\nNone\n27181606.0\n10.1056/NEJMoa1516385\nNone\nMost guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear.\n We conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily. The primary outcome was the annual rate of all COPD exacerbations.\n A total of 1680 patients were assigned to the indacaterol-glycopyrronium group, and 1682 to the salmeterol-fluticasone group. Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11% lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P=0.003). The indacaterol-glycopyrronium group had a longer time to the first exacerbation than did the salmeterol-fluticasone group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95% CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (hazard ratio, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95% CI, 0.66 to 1.00; P=0.046). The effect of indacaterol-glycopyrronium versus salmeterol-fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P=0.02).\n Indacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.).\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n149750\nNon-anesthesiologist administration of propofol for gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy, European Society of Gastroenterology and Endoscopy Nurses and Associates Guideline--Updated June 2015.\n\nDumonceau, JM\n\nRiphaus, A\n\nSchreiber, F\n\nVilmann, P\n\nBeilenhoff, U\n\nAparicio, JR\n\nVargo, JJ\n\nManolaraki, M\n\nWientjes, C\n\nRácz, I\n\nHassan, C\n\nPaspatis, G\n\nBeiträge in Fachzeitschriften\nISI:000368414900015\n26561915.0\n10.1055/s-0034-1393414\nNone\nMain Recommendations 1 We recommend that the type of endoscopic procedure and the patient's American Society of Anesthesiologists (ASA) physical status, age, body mass index, Mallampati's classification, and risk factors for obstructive sleep apnea (OSA) be assessed before each procedure with non-anesthesiologist administration of propofol (NAAP) (strong recommendation, moderate quality evidence). 2 We suggest primary involvement of an anesthesiologist in patients of ASA class >= 3, with a Mallampati's class >= 3 or other conditions that put them at risk of airway obstruction (e.g. pharyngolaryngeal tumors), in patients who chronically receive significant amounts of narcotic analgesics, or in cases where a long-lasting procedure is anticipated (weak recommendation, low quality evidence). 3 We suggest consideration of capnographic monitoring during NAAP in specific situations including high risk patients, intended deep sedation, and long procedures (weak recommendation, high quality evidence). 4 We suggest propofol monotherapy except in particular situations (weak recommendation, high quality evidence). 5 We recommend administering propofol through intermittent bolus infusion or perfusor systems, including target-controlled infusion (TCI), and consideration of patient-controlled sedation (PCS) in particular situations (strong recommendation, high quality evidence). 6 We suggest that patients listen to self-selected music during upper and lower GI endoscopy procedures (weak recommendation, moderate quality evidence). 7 We do not suggest using pharyngeal anesthesia during propofol sedation for upper GI endoscopy (weak recommendation, moderate quality evidence). 8 We suggest using the post-anesthetic discharge scoring system (PADSS) to determine when patient recovery is sufficient to allow discharge (weak recommendation, low quality evidence). 9 Minimum discharge criteria should be fulfilled before discharging a patient. We recommend that patients who have received combined regimens, and all patients of ASA class >2, should upon discharge be accompanied by a responsible person and refrain for 24 hours from driving, drinking alcohol, operating heavy machinery, or engaging in legally binding decisions. Advice should be provided verbally and in written form to the patient, including a 24-hour contact phone number (strong recommendation, low quality evidence). 10 For patients of ASA classes 1-2 who have received low dose propofol monotherapy, a 6-hour limit is suggested (weak recommendation, low quality evidence).\n\n\n"
},
{
"text": "\n166448\nStudy protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).\n\nMcNally, D\n\nAmrein, K\n\nO'Hearn, K\n\nFergusson, D\n\nGeier, P\n\nHenderson, M\n\nKhamessan, A\n\nLawson, ML\n\nMcIntyre, L\n\nRedpath, S\n\nWeiler, HA\n\nMenon, K\n\nCanadian Critical Care Trials Group\n\nBeiträge in Fachzeitschriften\nNone\n29234503.0\n10.1186/s40814-017-0214-z\nPMC5721544\nClinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD.\n The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10, 00 IU/kg, maximum of 400, 00 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding).\n Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017.\n Clinicaltrials.gov NCT02452762.\n\nAmrein, Karin\n\n\n"
},
{
"text": "\n171364\nAssociations of event-related brain potentials and Alzheimer's disease severity: A longitudinal study.\n\nFruehwirt, W\n\nDorffner, G\n\nRoberts, S\n\nGerstgrasser, M\n\nGrossegger, D\n\nSchmidt, R\n\nDal-Bianco, P\n\nRansmayr, G\n\nGarn, H\n\nWaser, M\n\nBenke, T\n\nBeiträge in Fachzeitschriften\nISI:000466837000004\n30582941.0\n10.1016/j.pnpbp.2018.12.013\nNone\nSo far, no cost-efficient, widely-used biomarkers have been established to facilitate the objectivization of Alzheimer's disease (AD) diagnosis and monitoring. Research suggests that event-related potentials (ERPs) reflect neurodegenerative processes in AD and might qualify as neurophysiological AD markers.\n First, to examine which ERP component correlates the most with AD severity, as measured by the Mini-Mental State Examination (MMSE). Then, to analyze the temporal change of this component as AD progresses.\n Sixty-three subjects (31 with possible, 32 with probable AD diagnosis) were recruited as part of the cohort study Prospective Dementia Registry Austria (PRODEM). For a maximum of 18 months patients revisited every 6 months for follow-up assessments. ERPs were elicited using an auditory oddball paradigm. P300 and N200 latency was determined with regard to target as well as difference wave ERPs, whereas P50 amplitude was measured from standard stimuli waveforms.\n P300 latency exhibited the strongest association with AD severity (e.g., r = -0.512, p < 0.01 at Pz for target stimuli in probable AD subjects). Further, there were significant Pearson correlations for N200 latency (e.g., r = -0.407, p = 0.026 at Cz for difference waves in probable AD subjects). P50 amplitude, as measured by different detection methods and at various scalp sites, did not significantly correlate with disease severity - neither in probable AD, possible AD, nor in both subgroups of patients combined. ERP markers for the group of possible AD patients did not show any significant correlations with MMSE scores. Post-hoc pairwise comparisons between baseline and 18-months follow-up assessment revealed significant P300 latency differences (e.g., p < 0.001 at Cz for difference waves in probable AD subjects). However, there were no significant correlations between the change rates of P300 latency and MMSE score.\n P300 and N200 latency significantly correlated with disease severity in probable AD, whereas P50 amplitude did not. P300 latency, which showed the highest correlation coefficients with MMSE, significantly increased over the course of the 18 months study period in probable AD patients. The magnitude of the observed prolongation is in line with other longitudinal AD studies and substantially higher than in normal ageing, as reported in previous trials (no healthy controls were included in our study).\n Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n183940\nIs kidney function associated with cognition and mood in late life? : The Screening for CKD among Older People across Europe (SCOPE) study.\n\nTap, L\n\nCorsonello, A\n\nFormiga, F\n\nMoreno-Gonzalez, R\n\nÄrnlöv, J\n\nCarlsson, AC\n\nRoller-Wirnsberger, R\n\nWirnsberger, G\n\nZiere, G\n\nFreiberger, E\n\nSieber, C\n\nKostka, T\n\nGuligowska, A\n\nGil, P\n\nMartinez, SL\n\nArtzi-Medvedik, R\n\nYehoshua, I\n\nFabbietti, P\n\nLattanzio, F\n\nMattace-Raso, F\n\nSCOPE investigators\n\nBeiträge in Fachzeitschriften\nISI:000576901000006\n33008359.0\n10.1186/s12877-020-01707-4\nPMC7531080\nChronic kidney disease (CKD), cognitive impairment and depression share common risk factors. Previous studies did not investigate the possible association between kidney function and cognitive and mood disorders in older persons in a broad range of kidney function. The present study explored associations between kidney function, cognition and mood in outpatients of 75 years and over.\n Baseline data of 2252 participants of the SCOPE study, an international multicenter cohort observational study, ere used in which community-dwelling persons of 75 years and over were enrolled to screen for CKD Kidney function was estimated with the BIS1-eGFR equation, cognition was assessed with the Mini-Mental State Examination (MMSE) and mood with the Geriatric Depression Scale 15 items (GDS-15). Characteristics were compared across stages of CKD. Mean eGFR values were also compared across categories of MMSE (< 24, 24-26, ≥27) and between groups with high and low score on the GDS-15 (> 5/≤5).\n In total, 63% of the population had an eGFR < 60 mL/min. In advanced stages of CKD, participants were older and more often men than in earlier stages (p < 0.001). Cardiovascular diseases and diabetes mellitus were more often found in those in advanced stages of CKD (p < 0.001), and also cumulative comorbidity scores were higher than in those in earlier stages (p < 0.001). Median MMSE was 29 in CKD stage 1-2 and 3, and 30 in CKD stage 4, whereas median GDS-15 score was 2 in all stages of CKD. Mean values of eGFR did not differ across categories of MMSE or between groups with high and low score on the GDS-15. Stratification for albuminuria did not change these results.\n Older persons in more advanced stages of CKD did not have lower cognitive scores or higher rates of depressive symptoms than older persons in earlier stages. Future longitudinal studies might give information on the possible effect of kidney function on cognition and mood in late life.\n This study was registered prospectively on 25th February 2016 at clinicaltrials.gov ( NCT02691546 ).\n\nRoller-Wirnsberger, Regina\n\nWirnsberger, Gerhard\n\n\n"
},
{
"text": "\n110025\nApixaban in patients with atrial fibrillation.\n\nConnolly, SJ\n\nEikelboom, J\n\nJoyner, C\n\nDiener, HC\n\nHart, R\n\nGolitsyn, S\n\nFlaker, G\n\nAvezum, A\n\nHohnloser, SH\n\nDiaz, R\n\nTalajic, M\n\nZhu, J\n\nPais, P\n\nBudaj, A\n\nParkhomenko, A\n\nJansky, P\n\nCommerford, P\n\nTan, RS\n\nSim, KH\n\nLewis, BS\n\nVan Mieghem, W\n\nLip, GY\n\nKim, JH\n\nLanas-Zanetti, F\n\nGonzalez-Hermosillo, A\n\nDans, AL\n\nMunawar, M\n\nO'Donnell, M\n\nLawrence, J\n\nLewis, G\n\nAfzal, R\n\nYusuf, S\n\nAVERROES Steering Committee and Investigators\n\nBeiträge in Fachzeitschriften\nISI:000287928400006\n21309657.0\n10.1056/NEJMoa1007432\nNone\nBACKGROUND: Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients.\r\n\r\nMETHODS: In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mg per day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism.\r\n\r\nRESULTS: Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P=0.07). There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P=0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups.\r\n\r\nCONCLUSIONS: In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00496769.).\n\n\n"
},
{
"text": "\n156047\nDietary juniper berry oil minimizes hepatic reperfusion injury in the rat.\n\nJones, SM\n\nZhong, Z\n\nEnomoto, N\n\nSchemmer, P\n\nThurman, RG\n\nBeiträge in Fachzeitschriften\nISI:000076180000019\n9755241.0\n10.1002/hep.510280419\nNone\nJuniper berry oil is rich in 5, 1, 4-eicosatrienoic acid, a polyunsaturated fatty acid similar to one found in fish oil, yet less prone to peroxidation. Dietary fish oil treatment has been shown to effectively reduce reperfusion injury; therefore, the effects of a diet containing juniper berry oil on hepatic reperfusion injury in a low-flow, reflow reperfusion model were investigated in the rat. Rats were fed semisynthetic diets containing either juniper berry oil, fish oil, or corn oil for 14 to 16 days. Daily food consumption averaged around 20 g/d in both the control and treatment groups; average daily weight gain was around 4 g per 100 g rat weight in all three groups studied, and there were no significant differences in these parameters. Livers were initially perfused at low-flow rates to induce pericentral hypoxia followed by a 40-minute reperfusion period. Peak lactate dehydrogenase (LDH) release during reflow averaged 44 U/g/h in the corn oil group and 32 U/g/h in the fish oil group, but was only 21 U/g/h as a result of juniper berry oil treatment. Malondialdehyde (MDA), an end-product of lipid peroxidation, reached a maximum value of 62 nmol/g/h in the corn oil group, but only reached 43 nmol/g/h and 34 nmol/g/h in the fish oil and juniper berry oil groups, respectively. Both juniper berry oil and fish oil treatment improved rates of bile flow from 25 microL/g/h (corn oil) to 36 and 38 microL/g/h, respectively. Importantly, juniper berry oil reduced cell death in pericentral regions of the liver lobule by 75%. Trypan blue distribution time, an indicator of the hepatic microcirculation, was reduced by approximately 25% with fish oil and over 50% by juniper berry oil diets compared with corn oil controls. The rates of entry of fluorescein-dextran, a dye confined to the vascular space, were increased 1.8- and 2.6-fold, and rates of outflow were increased 4.4- and 4.3-fold by fish oil and juniper berry oil, respectively, also reflecting improved microcirculation. Juniper berry oil also blunted increases in intracellular calcium and release of prostaglandin E2 (PGE2) by cultured Kupffer cells stimulated by endotoxin. These results are consistent with the hypothesis that feeding a diet containing juniper berry oil reduces reperfusion injury by inhibiting activation of Kupffer cells, thus reducing vasoactive eicosanoid release and improving the hepatic microcirculation in livers undergoing oxidant stress.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n160081\nPostoperative Complications and Functional Outcome after Esophageal Atresia Repair: Results from Longitudinal Single-Center Follow-Up.\n\nFriedmacher, F\n\nKroneis, B\n\nHuber-Zeyringer, A\n\nSchober, P\n\nTill, H\n\nSauer, H\n\nHöllwarth, ME\n\nBeiträge in Fachzeitschriften\nISI:000402076800001\n28424985.0\n10.1007/s11605-017-3423-0\nNone\nEsophageal atresia (EA) and tracheoesophageal fistula (TEF) represent major therapeutic challenges, frequently associated with serious morbidities following surgical repair. The aim of this longitudinal study was to assess temporal changes in morbidity and mortality of patients with EA/TEF treated in a tertiary-level center, focusing on postoperative complications and their impact on long-term gastroesophageal function.\n One hundred nine consecutive patients with EA/TEF born between 1975 and 2011 were followed for a median of 9.6 years (range, 3-27 years). Comparative statistics were used to evaluate temporal changes between an early (1975-1989) and late (1990-2011) study period.\n Gross types of EA were A (n = 6), B (n = 5), C (n = 89), D (n = 7), and E (n = 2). Seventy (64.2%) patients had coexisting anomalies, 13 (11.9%) of whom died before EA correction was completed. In the remaining 96 infants, surgical repair was primary (n = 66) or delayed (n = 25) anastomosis, closure of TEF in EA type E (n = 2), and esophageal replacement with colon interposition (n=2) or gastric transposition (n=1). Long-gap EA was diagnosed in 23 (24.0%) cases. Postoperative mortality was 4/96 (4.2%). Overall survival increased significantly between the two study periods (42/55 vs. 50/54; P = 0.03). Sixty-nine (71.9%) patients presented postoperatively with anastomotic strictures requiring a median of 3 (range, 1-15) dilatations. Revisional surgery was required for anastomotic leakage (n = 5), recurrent TEF with (n = 1) or without (n=9) anastomotic stricture, undetected proximal TEF (n = 4), and refractory anastomotic strictures with (n = 1) or without (n = 2) fistula. Normal dietary intake was achieved in 89 (96.7%) patients, while 3 (3.3%) remained dependent on gastrostomy feedings. Manometry showed esophageal dysmotility in 78 (84.8%) infants at 1 year of age, increasing to 100% at 10-year follow-up. Fifty-six (60.9%) patients suffered from dysphagia with need for endoscopic foreign body removal in 12 (13.0%) cases. Anti-reflux medication was required in 43 (46.7%) children and 30 (32.6%) underwent fundoplication. The rate of gastroesophageal reflux increased significantly between the two study periods (29/42 vs. 44/50; P = 0.04). Twenty-two (23.9%) cases of endoscopic esophagitis and one Barrett's esophagus were identified.\n Postoperative complications after EA/TEF repair are common and should be expertly managed to reduce the risk of long-term morbidity. Regular multidisciplinary surveillance with transitional care into adulthood is recommended in all patients with EA/TEF.\n\nHöllwarth, Michael\n\nTill, Holger\n\n\n"
},
{
"text": "\n166432\nTick-Borne Encephalitis Virus Vaccine-Induced Human Antibodies Mediate Negligible Enhancement of Zika Virus Infection<i>In</i><i>Vitro</i>and in a Mouse Model.\n\nDuehr, J\n\nLee, S\n\nSingh, G\n\nFoster, GA\n\nKrysztof, D\n\nStramer, SL\n\nBermúdez González, MC\n\nMenichetti, E\n\nGeretschläger, R\n\nGabriel, C\n\nSimon, V\n\nLim, JK\n\nKrammer, F\n\nBeiträge in Fachzeitschriften\nISI:000425277500001\n29435494.0\n10.1128/mSphereDirect.00011-18\nPMC5806211\nRecent reports in the scientific literature have suggested that anti-dengue virus (DENV) and anti-West Nile virus (WNV) immunity exacerbates Zika virus (ZIKV) pathogenesisin vitroandin vivoin mouse models. Large populations of immune individuals exist for a related flavivirus (tick-borne encephalitis virus [TBEV]), due to large-scale vaccination campaigns and endemic circulation throughout most of northern Europe and the southern Russian Federation. As a result, the question of whether anti-TBEV immunity can affect Zika virus pathogenesis is a pertinent one. For this study, we obtained 50 serum samples from individuals vaccinated with the TBEV vaccine FSME-IMMUN (Central European/Neudörfl strain) and evaluated their enhancement capacityin vitrousing K562 human myeloid cells expressing CD32 andin vivousing a mouse model of ZIKV pathogenesis. Among the 50 TBEV vaccinee samples evaluated, 29 had detectable reactivity against ZIKV envelope (E) protein by enzyme-linked immunosorbent assay (ELISA), and 36 showed enhancement of ZIKV infectionin vitro. A pool of the most highly reacting and enhanced samples resulted in no significant change in the morbidity/mortality of ZIKV disease in immunocompromisedStat2\n-/-\nmice. Our results suggest that humoral immunity against TBEV is unlikely to enhance Zika virus pathogenesis in humans. No clinical reports indicating that TBEV vaccinees experiencing enhanced ZIKV disease have been published so far, and though the epidemiological data are sparse, our findings suggest that there is little reason for concern. This study also displays a clear relationship between the phylogenetic distance between two flaviviruses and their capacity for pathogenic enhancement.IMPORTANCEThe relationship between serial infections of two different serotypes of dengue virus and more severe disease courses is well-documented in the literature, driven by so-called antibody-dependent enhancement (ADE). Recently, studies have shown the possibility of ADE in cells exposed to anti-DENV human plasma and then infected with ZIKV and also in mouse models of ZIKV pathogenesis after passive transfer of anti-DENV human plasma. In this study, we evaluated the extent to which this phenomenon occurs using sera from individuals immunized against tick-borne encephalitis virus (TBEV). This is highly relevant, since large proportions of the European population are vaccinated against TBEV or otherwise seropositive.\n\n\n"
},
{
"text": "\n856\nEffects of FR173657, a non-peptide B2 antagonist, on kinin-induced hypotension, visceral and peripheral oedema formation and bronchoconstriction.\n\nGriesbacher, T\n\nLegat, FJ\n\nBeiträge in Fachzeitschriften\nISI:A1997WL16100028\n9138701.0\n10.1038/sj.bjp.0700966\nPMC1564532\n1. Kinins are believed to play a key role in many inflammatory conditions. Therefore, bradykinin antagonists are being developed for potential therapeutic applications. In the present investigation we describe the pharmacology, in vivo, of (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2, -dichloro-3-[2-methyl-8-quinoliny l) oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide (FR173657), a novel, non-peptide bradykinin antagonist. 2. The hypotensive effects of i.v. injections of bradykinin (50 pmol) in captopril-pre-treated anaesthetized rats were significantly inhibited by 100 nmol kg-1 FR173657 s.c., and completely abolished by 300 nmol kg-1. The full inhibitory effect developed within 60 min and remained unchanged for at least 4 h. However, the effect was reversible, since 24 h after an injection of 300 nmol kg-1 FR173657 no inhibitory effect could be observed. 3. The plasma protein extravasation into the pancreas and duodenum induced by an i.v. infusion of bradykinin (11 nmol kg-1 within 20 min) in captopril-treated anaesthetized rats was completely abolished by FR173657 at doses of 30 nmol kg-1 s.c. and above, given 60 min before bradykinin. FR173657 3 nmol kg-1 was ineffective, while a dose of 10 nmol kg-1 produced an intermediate effect. 4. The paw oedema induced by the subplantar injection of bradykinin (30 nmol) in anaesthetized rats was inhibited slightly by s.c. injection of FR173657 0.3 mumol kg-1, whereas 1 and 3 mumol kg-1 produced significant inhibition of the bradykinin-induced oedema. The maximum inhibition amounted to about 50% and could not be increased even when the dose of FR173657 was increased to 30 mumol kg-1. FR173657 did not effect the oedema caused by histamine or 5-hydroxytryptamine. 5. Bradykinin (20 nmol kg-1, i.v.) caused increases in pulmonary inflation pressure by 300-600 Pa in anaesthetized, respirated guinea-pigs. The effect was reduced to 58 +/- 9% of the initial value 60 min after the s.c. injection of FR173657 1 mumol kg-1, whereas only 9 +/- 7% remained after 10 mumol kg-1. The bronchoconstrictor actions of histamine remained unaffected by FR173657. 6. In summary, FR173657 is a highly potent and selective bradykinin antagonist. The inhibitory action in vivo lasts for longer than 4 h but is fully reversible. FR173657, or similar compounds, will be a useful tool for the pharmacological investigation of pathophysiological states and may possess a therapeutic potential in diseases involving the endogenous release of kinins.\n\nGriesbacher, Thomas\n\nLegat, Franz\n\n\n"
},
{
"text": "\n107188\nBrain- and heart-type fatty acid-binding proteins in the brain: tissue distribution and clinical utility.\n\nPelsers, MM\n\nHanhoff, T\n\nVan der Voort, D\n\nArts, B\n\nPeters, M\n\nPonds, R\n\nHonig, A\n\nRudzinski, W\n\nSpener, F\n\nde Kruijk, JR\n\nTwijnstra, A\n\nHermens, WT\n\nMenheere, PP\n\nGlatz, JF\n\nBeiträge in Fachzeitschriften\nISI:000223503800014\n15217991.0\n10.1373/clinchem.2003.030361\nNone\nBACKGROUND: Detection of brain injury by serum markers is not a standard procedure in clinical practice, although several proteins, such as S100B, neuron-specific enolase (NSE), myelin basic protein, and glial fibrillary acidic protein, show promising results. We investigated the tissue distribution of brain- and heart-type fatty acid-binding proteins (B-FABP and H-FABP) in segments of the human brain and the potential of either protein to serve as plasma marker for diagnosis of brain injury. METHODS: B-FABP and H-FABP were measured immunochemically in autopsy samples of the brain (n = 6) and in serum samples from (a) patients with mild traumatic brain injury (MTBI; n = 130) and (b) depressed patients undergoing bilateral electroconvulsive therapy (ECT; n = 14). The protein markers S100B and NSE were measured for comparison. Reference values of B-FABP and H-FABP were established in healthy individuals (n = 92). RESULTS: The frontal, temporal, and occipital lobes, the striatum, the pons, and the cerebellum had different tissue concentrations of B-FABP and of H-FABP. B-FABP ranged from 0.8 microg/g wet weight in striatum tissue to 3.1 microg/g in frontal lobe. H-FABP was markedly higher, ranging from 16.2 microg/g wet weight in cerebellum tissue to 39.5 microg/g in pons. No B-FABP was detected in serum from healthy donors. H-FABP serum reference value was 6 microg/L. In the MTBI study, serum B-FABP was increased in 68% and H-FABP in 70% of patients compared with S100B (increased in 45%) and NSE (increased in 51% of patients). In ECT, serum B-FABP was increased in 6% of all samples (2 of 14 patients), whereas H-FABP was above its upper reference limit (6 microg/L) in 17% of all samples (8 of 14 patients), and S100B was above its upper reference limit (0.3 microg/L) in 0.4% of all samples. CONCLUSIONS: B-FABP and H-FABP patterns differ among brain tissues, with the highest concentrations in the frontal lobe and pons, respectively. However, in each part of the brain, the H-FABP concentration was at least 10 times higher than that of B-FABP. Patient studies indicate that B-FABP and H-FABP are more sensitive markers for minor brain injury than the currently used markers S100B and NSE.\n\n\n"
}
]
}