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"text": "\n89895\nCricoid cartilage and esophagus: CT scan study of the dynamic variability of their relative positions.\n\nBenkhadra, M\n\nLenfant, F\n\nBry, J\n\nAstruc, K\n\nTrost, O\n\nRicolfi, F\n\nGirard, C\n\nTrouilloud, P\n\nFeigl, G\n\nBeiträge in Fachzeitschriften\nISI:000268712900008\n19277448.0\n10.1007/s00276-009-0481-3\nNone\nIntroduction Cricoid pressure occludes the esophagus (E) by compressing it between the cricoid cartilage (CC) and the body of the sixth cervical vertebra (C6). This technique is used to prevent passive regurgitation during the induction of anesthesia in patients at high risk for regurgitation. Failures of this technique had been described and a possible displacement of the E relative to the CC had been reported, but there is no study about displacement during antero-posterior movements of the head. Aim The aim of our study was to evaluate the displacement of the CC relative to the cervical E, during flexion and extension movements of the head. Materials and methods We retrospectively studied X-ray computed tomography (CT) images of 21 patients with suspected cervical trauma. Patients were in the supine position. In the first series of images, the head was positioned at maximal flexion by means of a support placed under the external occipital protuberance. In the second series of images, the head was maintained in extension by means of a support placed under the shoulders. Each position was obtained as far as possible within the limits of pain and restricted movement. In flexion and extension, we used the lowest slice from the cricoid cartilage. The variables measured were: diameters of CC (CD) and E (OD), left and right lateral displacements of E. Results A total of 13 CT were analyzed. CD and OD as well as OD/OC ratios did not vary significantly in flexion and extension. We noticed 61.5 and 92.3% (respectively in flexion and in extension) of left or right displacement: 23% of patients presented right displacement in both Xexion and extension; 38.5% of patients did not present any right displacement in Xexion or in extension; 61.5% of patients presented left displacement in both Xexion and extension. More generally, almost 92% of patients presented displacement either in Xexion or extension, or both. Discussion In our study, it can be seen that the E is clearly displaced with regard to the CC, that this displacement is favored by extension. Only 2/13 patients have an "over than 3 mm" displacement in extension whereas 5/13 in flexion. So, even if there are more displacements in extension, they are inferior to 3 mm and may not be considered as significant considering the occlusion of E. According to our results, the extension position of the head produces more displacement of the E but should preserve the containment of the cricoid pressure if we consider the thickness of the E wall.\n\n\n"
},
{
"text": "\n161282\nMacular Sensitivity Measured With Microperimetry in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 7.\n\nSchönbach, EM\n\nWolfson, Y\n\nStrauss, RW\n\nIbrahim, MA\n\nKong, X\n\nMuñoz, B\n\nBirch, DG\n\nCideciyan, AV\n\nHahn, GA\n\nNittala, M\n\nSunness, JS\n\nSadda, SR\n\nWest, SK\n\nScholl, HPN\n\nProgStar Study Group\n\nBeiträge in Fachzeitschriften\nISI:000405531700007\n28542693.0\n10.1001/jamaophthalmol.2017.1162\nPMC6584711\nNew outcome measures for treatment trials for Stargardt disease type 1 (STGD1) and other macular diseases are needed. Microperimetry allows mapping of light sensitivity of the macula and provides topographic information on visual function beyond visual acuity.\n To measure and analyze retinal light sensitivity of the macula in STGD1 using fundus-controlled perimetry (microperimetry).\n This was a multicenter prospective cohort study. A total of 199 patients and 326 eyes with molecularly confirmed (ABCA4) STGD1 underwent testing with the Nidek MP-1 microperimeter as part of the multicenter, prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study. Sensitivity of 68 retinal loci was tested, and the mean sensitivity (MS) was determined; each point was categorized as "normal, "relative, or "deep" scotoma.\n Mean sensitivity and the number of points with normal sensitivity, relative, or deep scotomas.\n Mean (SD) patient age was 34.2 (14.7) years, mean (SD) best-corrected visual acuity of all eyes was 47.8 (16.9) Early Treatment Diabetic Retinopathy Study letter score (approximately 20/100 Snellen equivalent), and mean MS of all eyes of all 68 points was 11.0 (5.0) dB. The median number of normal points per eye was 49 (mean [SD], 41.3 [20.8]; range, 0-68); abnormal sensitivity and deep scotomas were more prevalent in the central macula. Mean sensitivity was lower in the fovea (mean [SD], 2.7 [4.4] dB) than in the inner (mean [SD], 6.8 [5.8] dB) and outer ring (mean [SD], 12.7 [5.3] dB). Overall MS per eye was 0.086 dB lower per year of additional age (95% CI, -0.13 to -0.041; P < .001) and 0.21 dB lower per additional year of duration of STGD1 (95% CI, -0.28 to -0.14; P < .001). Longer duration of STGD1 was associated with worse MS (β = -0.18; P < .001), with a lower number of normal test points (β = -0.71; P < .001), and with a higher number of deep scotoma points (β = -0.70; P < .001). We found 11 eyes with low MS (<6 dB) but very good best-corrected visual acuity of at least 72 Early Treatment Diabetic Retinopathy Study letter score (20/40 Snellen equivalent).\n We provide an extensive analysis of macular sensitivity parameters in STGD1 and demonstrate their association with demographic characteristics and vision. These data suggest microperimetry testing provides a more comprehensive assessment of retinal function and will be an important outcome measure in future clinical trials.\n\nStrauß, Rupert\n\n\n"
},
{
"text": "\n180029\nHuman C-terminal CUBN variants associate with chronic proteinuria and normal renal function.\n\nBedin, M\n\nBoyer, O\n\nServais, A\n\nLi, Y\n\nVilloing-Gaudé, L\n\nTête, MJ\n\nCambier, A\n\nHogan, J\n\nBaudouin, V\n\nKrid, S\n\nBensman, A\n\nLammens, F\n\nLouillet, F\n\nRanchin, B\n\nVigneau, C\n\nBouteau, I\n\nIsnard-Bagnis, C\n\nMache, CJ\n\nSchäfer, T\n\nPape, L\n\nGödel, M\n\nHuber, TB\n\nBenz, M\n\nKlaus, G\n\nHansen, M\n\nLatta, K\n\nGribouval, O\n\nMorinière, V\n\nTournant, C\n\nGrohmann, M\n\nKuhn, E\n\nWagner, T\n\nBole-Feysot, C\n\nJabot-Hanin, F\n\nNitschké, P\n\nAhluwalia, TS\n\nKöttgen, A\n\nAndersen, CBF\n\nBergmann, C\n\nAntignac, C\n\nSimons, M\n\nBeiträge in Fachzeitschriften\nISI:000505205000036\n31613795.0\n10.1172/JCI129937\nPMC6934218\nBACKGROUNDProteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding.METHODSWe used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling, and epidemiological methods.RESULTSWe identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset. Since the proteinuria in these patients had a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and the use of proteinuria-lowering treatments. However, renal function was normal in all cases. By contrast, we did not found any biallelic CUBN variants in proteinuric patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that 4 C-terminal CUBN variants are associated with albuminuria and slightly increased GFR in meta-analyses of large population-based cohorts.CONCLUSIONCollectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsy.FUNDINGATIP-Avenir program, Fondation Bettencourt-Schueller (Liliane Bettencourt Chair of Developmental Biology), Agence Nationale de la Recherche (ANR) Investissements d'avenir program (ANR-10-IAHU-01) and NEPHROFLY (ANR-14-ACHN-0013, to MS), Steno Collaborative Grant 2018 (NNF18OC0052457, to TSA and MS), Heisenberg Professorship of the German Research Foundation (KO 3598/5-1, to AK), Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) KIDGEM 1140 (project 246781735, to CB), and Federal Ministry of Education and Research (BMB) (01GM1515C, to CB).\n\nMache, Christoph\n\n\n"
},
{
"text": "\n112584\nFood-induced anaphylaxis and cofactors - data from the anaphylaxis registry\n\nWorm, M\n\nScherer, K\n\nKohli-Wiesner, A\n\nRueff, F\n\nMahler, V\n\nLange, L\n\nTreudler, R\n\nRietschel, E\n\nSzepfalusi, Z\n\nLang, R\n\nRabe, U\n\nReese, T\n\nSchwerk, N\n\nBeyer, K\n\nHompes, S\n\nBircher, A\n\nPrzybilla, B\n\nHawranek, T\n\nHansen, G\n\nFriedrichs, F\n\nMerk, H\n\nTenbrock, K\n\nLehmann, S\n\nGerstlauer, M\n\nKleine-Tebbe, J\n\nNiggemann, B\n\nDickel, H\n\nBucheler, M\n\nBieber, T\n\nHanfland, J\n\nSchmitt-Grohe, S\n\nVlajnic, D\n\nHeckmann, V\n\nNemat, K\n\nSchakel, K\n\nNordwig, A\n\nSchuster, A\n\nSchweitzer-Krantz, S\n\nHillen, U\n\nKopp, M\n\nSzliska, C\n\nKlinge, J\n\nNeustadter, I\n\nFuchs, T\n\nBruns, R\n\nMarsch, C\n\nKreft, B\n\nCoors, E\n\nRebien, W\n\nWedi, B\n\nPfohler, C\n\nRett, M\n\nHenzgen, M\n\nVohringer, P\n\nFolster-Holst, R\n\nHunzelmann, N\n\nSiebenhaar, G\n\nNestoris, S\n\nSchirpke, C\n\nGrabbe, J\n\nStichtenoth, G\n\nRing, J\n\nBrockow, K\n\nBrehler, R\n\nYildiz, I\n\nVolkmuth, S\n\nGeissler, M\n\nPolz, M\n\nRiffelmann, F\n\nThies, S\n\nLepp, U\n\nRabe, U\n\nRebmann, H\n\nSpindler, T\n\nKlimek, L\n\nPfaar, O\n\nBrosi, W\n\nAberer, W\n\nVarga, E\n\nReider, N\n\nHuttegger, I\n\nKinaciyan, T\n\nHoffmann-Sommergruber, K\n\nEng, P\n\nHelbling, A\n\nEigenmann, P\n\nGuggenheim, R\n\nSchmid-Grendelmeier, P\n\nBeiträge in Fachzeitschriften\nISI:000293310900002\nNone\n10.5414/ALP34329\nNone\nFood-induced anaphylaxis and cofactors - data from the anaphylaxis registry Food allergens are frequent causes of anaphylaxis. In particular in children and adults they are frequent elicitors of severe allergic reactions, whereas in adults food allergens range among venom and drugs. Since 2006 severe allergic reactions from Germany, Austria and Switzerland are collected in the anaphylaxis registry. Currently 78 hospitals and private practises are connected. From July 2006 until February 2009 1, 56 severe allergic reactions were registered. Among children and adolescents (n = 187, age range from 3 months to 17 years) food allergens were with 58% the most frequent elicitors. In the adult group (n = 968, 18 85 years) food allergens were on the third position (16.3%) following venom and drugs. In children legumes (31%) and in particular peanuts were frequently responsible food allergens, followed by tree nuts (25%) where hazelnut was the most frequent elicitor. In adults fruits (13.4%) induced most often severe food dependent anaphylaxis, but also animal products (12.2%); among these most frequently crustaceans and mussels. Cofactors were often suspected in food dependent anaphylaxis, namely in 39% of the adult group and in 14% of the children and adolescence group. In adults drugs (22%) and physical activity (10%) were reported as the most frequent cofactors, in children physical activity was suspected in 8.7% and drugs in 2.6%. Concomitant diseases like atopic dermatitis, allergic asthma or allergic rhinoconjunctivitis were reported in 78% of children and adolescents and in 67% of the adults. In conclusion food-induced anaphylaxis, their cofactors and concomitant diseases in affected patients are age-dependent. The data offers to identify risk factors of anaphylaxis.\n\nAberer, Werner\n\nVarga, Eva-Maria\n\n\n"
},
{
"text": "\n173823\nAtlanto-occipital dislocation in a patient presenting with out-of-hospital cardiac arrest: a case report and literature review.\n\nRief, M\n\nZoidl, P\n\nZajic, P\n\nHeschl, S\n\nOrlob, S\n\nSilbernagel, G\n\nMetnitz, P\n\nPuchwein, P\n\nPrause, G\n\nBeiträge in Fachzeitschriften\nNone\n30803441.0\n10.1186/s13256-018-1926-2\nPMC6390378\nAtlanto-occipital dislocation is a rare and severe injury of the upper spine associated with a very poor prognosis.\n We report the case of a 59-year-old European man who suffered from out-of-hospital cardiac arrest following a motor vehicle accident. Cardiopulmonary resuscitation was initiated immediately by bystanders and continued by emergency medical services. After 30 minutes of cardiopulmonary resuscitation with a total of five shocks following initial ventricular fibrillation, return of spontaneous circulation was achieved. An electrocardiogram recorded after return of spontaneous circulation at the scene showed signs of myocardial ischemia as a possible cause for the cardiac arrest. No visible signs of injury were found. He was transferred to the regional academic trauma center. Following an extended diagnostic and therapeutic workup in the emergency room, including extended focused assessment with sonography for trauma ultrasound, whole-body computed tomography, and magnetic resonance imaging (of his head and neck), a diagnosis of major trauma (atlanto-occipital dislocation, bilateral serial rip fractures and pneumothoraces, several severe intracranial bleedings, and other injuries) was made. An unfavorable outcome was initially expected due to suspected tetraplegia and his inability to breathe following atlanto-occipital dislocation. Contrary to initial prognostication, after 22 days of intensive care treatment and four surgical interventions (halo fixation, tracheostomy, intracranial pressure probe, chest drains) he was awake and oriented, spontaneously breathing, and moving his arms and legs. Six weeks after the event he was able to walk without aid. After 2 months of clinical treatment he was able to manage all the activities of daily life on his own. It remains unclear, whether cardiac arrest due to a cardiac cause resulted in complete atony of the paravertebral muscles and caused this extremely severe lesion (atlanto-occipital dislocation) or whether cardiac arrest was caused by apnea due the paraplegia following the spinal injury of the trauma.\n A plausible cause for the trauma was myocardial infarction which led to the car accident and the major trauma in relation to the obviously minor trauma mechanism. With this case report we aim to familiarize clinicians with the mechanism of injury that will assist in the diagnosis of atlanto-occipital dislocation. Furthermore, we seek to emphasize that patients presenting with electrocardiographic signs of myocardial ischemia after high-energy trauma should primarily be transported to a trauma facility in a percutaneous coronary intervention-capable center rather than the catheterization laboratory directly.\n\nHeschl, Stefan\n\nMetnitz, Philipp\n\nOrlob, Simon\n\nPrause, Gerhard\n\nPuchwein, Paul\n\nRief, Martin\n\nSilbernagel, Günther\n\nZajic, Paul\n\nZoidl, Philipp\n\n\n"
},
{
"text": "\n122954\nPredictive ability of the 2002 and 2010 versions of the Tumour-Node-Metastasis classification system regarding metastasis-free, cancer-specific and overall survival in a European renal cell carcinoma single-centre series.\n\nPichler, M\n\nHutterer, GC\n\nChromecki, TF\n\nJesche, J\n\nKampel-Kettner, K\n\nGroselj-Strele, A\n\nPummer, K\n\nZigeuner, R\n\nBeiträge in Fachzeitschriften\nISI:000316690500010\n23107473.0\n10.1111/j.1464-410X.2012.11584.x\nNone\nWhat's known on the subject? and What does the study add? As different and heterogenous populations of patients with RCC can be found in different geographic regions, newly proposed cancer staging systems need an independent validation of their clinical usefulness and prognostic significance. Only a few published studies have compared the old' 2002 version of the TNM classification system for RCC with the recent 2010 version, all of them using cancer-specific survival as their endpoint, and controversial results were reported regarding the potential superiority of the 2010 version over the 2002 version of this cancer staging system. The aim of the study was to validate and compare the predictive ability of the 2010 with the 2002 version of the TNM classification system regarding metastasis-free, overall and cancer-specific survival in a large central European cohort of patients with RCC. According to our data, the predictive ability of the 2010 version of the TNM classification system regarding the evaluated endpoints is not superior to the 2002 version. OBJECTIVE center dot To compare the predictive ability of the Tumour-Node-Metastasis (TNM) classification systems for renal cell carcinoma (RCC) using three different endpoints: metastasis-free (MFS); overall (OS); and cancer-specific survival (CSS). PATIENTS AND METHODS center dot Data from 2739 consecutive patients with RCC, who underwent surgery at a single academic centre, were evaluated using multivariate Cox proportional models, Harrell's concordance (c)-index and by applying decision curve analysis (DCA) with regard to MFS, OS and CSS. RESULTS center dot According to TNM 2010, significant differences for MFS were observed for pT1a vs pT1b, pT1b vs pT2a, pT3a vs pT3b and pT3b vs pT3c stages, respectively (all P<0.05). center dot With regard to OS, significant differences could be observed in pT1a vs pT1b and pT3a vs pT3b stages, respectively (all P<0.05). center dot The c-index for CSS, OS and MFS was slightly higher for the 2002 than for the 2010 version of the TNM classification system. center dot Non-inferiority of the 2002 TNM system is supported by the results of the DCA. CONCLUSION center dot According to our data, the predictive ability of the 2010 version of the TNM classification system regarding three different clinical endpoints is not superior to the 2002 version of this staging system.\n\nGroselj-Strele, Andrea\n\nHutterer, Georg\n\nPichler, Martin\n\nPummer, Karl\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n159804\nA framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS).\n\nvan Vollenhoven, R\n\nVoskuyl, A\n\nBertsias, G\n\nAranow, C\n\nAringer, M\n\nArnaud, L\n\nAskanase, A\n\nBalážová, P\n\nBonfa, E\n\nBootsma, H\n\nBoumpas, D\n\nBruce, I\n\nCervera, R\n\nClarke, A\n\nConey, C\n\nCostedoat-Chalumeau, N\n\nCzirják, L\n\nDerksen, R\n\nDoria, A\n\nDörner, T\n\nFischer-Betz, R\n\nFritsch-Stork, R\n\nGordon, C\n\nGraninger, W\n\nGyöri, N\n\nHoussiau, F\n\nIsenberg, D\n\nJacobsen, S\n\nJayne, D\n\nKuhn, A\n\nLe Guern, V\n\nLerstrøm, K\n\nLevy, R\n\nMachado-Ribeiro, F\n\nMariette, X\n\nMissaykeh, J\n\nMorand, E\n\nMosca, M\n\nInanc, M\n\nNavarra, S\n\nNeumann, I\n\nOlesinska, M\n\nPetri, M\n\nRahman, A\n\nRekvig, OP\n\nRovensky, J\n\nShoenfeld, Y\n\nSmolen, J\n\nTincani, A\n\nUrowitz, M\n\nvan Leeuw, B\n\nVasconcelos, C\n\nVoss, A\n\nWerth, VP\n\nZakharova, H\n\nZoma, A\n\nSchneider, M\n\nWard, M\n\nBeiträge in Fachzeitschriften\nISI:000394513300015\n27884822.0\n10.1136/annrheumdis-2016-209519\nNone\nTreat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.\n An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%.\n The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life.\n The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.\n Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.\n\nGraninger, Winfried\n\n\n"
},
{
"text": "\n152697\nOC-16 - Neutrophil extracellular traps and tissue factor-bearing microvesicles: a liaison dangereuse causing overt DIC in cancer patients?\n\nHell, L\n\nThaler, J\n\nMartinod, K\n\nAy, C\n\nPosch, F\n\nWagner, DD\n\nPabinger, I\n\nBeiträge in Fachzeitschriften\nISI:000373731900046\n27161688.0\n10.1016/S0049-3848(16)30133-5\nNone\nOvert disseminated intravascular coagulation (DIC) is a systemic process characterized by excessive coagulation activation and fibrinolysis that may occur in cancer patients. The underlying pathomechanisms are still poorly understood. Recent experimental studies found an important role for the interaction between procoagulant neutrophil extracellular traps (NETs) and tissue factor (TF) in the pathogenesis of thrombosis.\n To investigate whether NETs and TF-bearing microvesicles (MVs) play a central role in cancer-related overt DIC.\n Twenty-eight cancer patients with overt DIC (ISTH score ≥5, 14 females, median age: 62 years [range: 21-80], 13 with solid tumors, 15 with acute leukemia) and 28 matched healthy controls were included. NET formation parameters (plasma DNA and nucleosomes), MVassociated TF activity, and routine coagulation parameters were determined at study inclusion. In 11 patients with acute myeloid leukemia (AML), follow-up measurements were also performed.\n Plasma DNA, nucleosomes, and MV-TF activity were highly elevated in patients with cancer-related DIC compared to healthy individuals (all p-values<0.001). Strong correlations were found between plasma DNA and nucleosomes (Spearman correlation-coefficient: r=0.68), nucleosomes and MV-TF activity (r=0.62), and DNA and MV-TF activity (r=0.57). In multivariate regression, altered routine coagulation parameters were highly associated with NET parameters and MV-TF activity. In detail, a doubling in plasma DNA was associated with a 7.6% decrease in fibrinogen (p=0.012), a 15.3% decrease in platelet count (p=0.002), a 3.9% decrease in prothrombin time (p=0.014), and a 41.0% increase in D-dimer (p<0.001). A 10% increase in nucleosomes was associated with a 3.1% decrease in fibrinogen (p<0.001), a 5.0% decrease in platelet count (p<0.001), a 1.0% decrease in prothrombin time (p<0.009), and a 112.7% increase in D-dimer (p<0.001). A 10% increase in MV-TF activity was associated with a 4.9% decrease in fibrinogen (p<0.001), a 7.1% decrease in platelet count (p<0.001), a 1.3% decrease in prothrombin time (p<0.001), and a 15.5% increase in D-dimer (p<0.001). After initiation of chemotherapy in AML patients, NET parameters and MV-TF activity decreased significantly (nucleosomes: 3.3-fold decrease and normalization after 1 week; DNA: 1.2-fold decrease after 1 week and 1.5-fold decrease after 1 month; MV-TF activity: 10-fold decease after 1 week and normalization after 1 month) (Figure 1), and routine coagulation parameters improved.\n Our results add to experimental studies that have investigated the interaction between NETs and TF. Taken together, evidence indicates the presence of a liaison dangereuse between NETs and TF-bearing MVs, which could be the underlying cause of cancer-related overt DIC.\n © 2016 Elsevier Ltd. All rights reserved.\n\nPosch, Florian\n\n\n"
},
{
"text": "\n154308\nEAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016.\n\nBabjuk, M\n\nBöhle, A\n\nBurger, M\n\nCapoun, O\n\nCohen, D\n\nCompérat, EM\n\nHernández, V\n\nKaasinen, E\n\nPalou, J\n\nRouprêt, M\n\nvan Rhijn, BW\n\nShariat, SF\n\nSoukup, V\n\nSylvester, RJ\n\nZigeuner, R\n\nBeiträge in Fachzeitschriften\nISI:000396333700028\n27324428.0\n10.1016/j.eururo.2016.05.041\nNone\nThe European Association of Urology (EAU) panel on Non-muscle-invasive Bladder Cancer (NMIBC) released an updated version of the guidelines on Non-muscle-invasive Bladder Cancer.\n To present the 2016 EAU guidelines on NMIBC.\n A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines published between April 1, 2014, and May 31, 2015, was performed. Databases covered by the search included Medline, Embase, and the Cochrane Libraries. Previous guidelines were updated, and levels of evidence and grades of recommendation were assigned.\n Tumours staged as TaT1 or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection of the bladder (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis. If the initial resection is incomplete, there is no muscle in the specimen, or a high-grade or T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour and intermediate-risk patients at a lower risk of recurrence, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy (RC) should be considered. RC is recommended in BCG-refractory tumours. The long version of the guidelines is available at the EAU Web site (www.uroweb.org/guidelines).\n These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice.\n The European Association of Urology has released updated guidelines on Non-muscle-invasive Bladder Cancer (NMIBC). Stratification of patients into low-, intermediate-, and high-risk groups is essential for decisions about adjuvant intravesical instillations. Risk tables can be used to estimate risks of recurrence and progression. Radical cystectomy should be considered only in case of failure of instillations or in NMIBC with the highest risk of progression.\n Copyright © 2016. Published by Elsevier B.V.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n134934\nGenome-wide association study for radiographic vertebral fractures: a potential role for the 16q24 BMD locus.\n\nOei, L\n\nEstrada, K\n\nDuncan, EL\n\nChristiansen, C\n\nLiu, CT\n\nLangdahl, BL\n\nObermayer-Pietsch, B\n\nRiancho, JA\n\nPrince, RL\n\nvan Schoor, NM\n\nMcCloskey, E\n\nHsu, YH\n\nEvangelou, E\n\nNtzani, E\n\nEvans, DM\n\nAlonso, N\n\nHusted, LB\n\nValero, C\n\nHernandez, JL\n\nLewis, JR\n\nKaptoge, SK\n\nZhu, K\n\nCupples, LA\n\nMedina-Gómez, C\n\nVandenput, L\n\nKim, GS\n\nHun Lee, S\n\nCastaño-Betancourt, MC\n\nOei, EH\n\nMartinez, J\n\nDaroszewska, A\n\nvan der Klift, M\n\nMellström, D\n\nHerrera, L\n\nKarlsson, MK\n\nHofman, A\n\nLjunggren, Ö\n\nPols, HA\n\nStolk, L\n\nvan Meurs, JB\n\nIoannidis, JP\n\nZillikens, MC\n\nLips, P\n\nKarasik, D\n\nUitterlinden, AG\n\nStyrkarsdottir, U\n\nBrown, MA\n\nKoh, JM\n\nRichards, JB\n\nReeve, J\n\nOhlsson, C\n\nRalston, SH\n\nKiel, DP\n\nRivadeneira, F\n\nBeiträge in Fachzeitschriften\nISI:000329558600004\n24516880.0\n10.1016/j.bone.2013.10.015\nPMC4102322\nVertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged > 55 years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p < 5 × 10− 8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p = 4.6 × 10− 8. However, the association was not significant across 5720 cases and 21, 91 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p = 0.17), displaying high degree of heterogeneity (I2 = 57%; Qhet p = 0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size > 1.25) may still be consistent with an effect size < 1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.\n\nObermayer-Pietsch, Barbara\n\n\n"
},
{
"text": "\n135953\nEvaluation of cerebral metabolism and quantitative electroencephalography after hypothermic circulatory arrest and low-flow cardiopulmonary bypass at different temperatures.\n\nMezrow, CK\n\nMidulla, PS\n\nSadeghi, AM\n\nGandsas, A\n\nWang, W\n\nDapunt, OE\n\nZappulla, R\n\nGriepp, RB\n\nBeiträge in Fachzeitschriften\nISI:A1994NF01600004\n8159021.0\n10.1016/S0022-5223(94)70375-2\nNone\nAlthough widely used for repair of complex cardiovascular pathologic conditions, long intervals of hypothermic circulatory arrest and low flow cardiopulmonary bypass may both result in cerebral injury. This study examines cerebral hemodynamics, metabolism, and electrical activity to evaluate the risks of cerebral injury after 60 minutes of hypothermic circulatory arrest at 8 degrees C, 13 degrees C, and 18 degrees C, compared with 60 minutes of low flow cardiopulmonary bypass at 18 degrees C. Thirty-two puppies were randomly assigned to one of four experimental groups and centrally cooled to the appropriate temperature. Serial evaluations of quantitative electroencephalography, radioactive microsphere determinations of cerebral blood flow, calculations of cerebral oxygen consumption, cerebral glucose consumption, cerebral vascular resistance, cerebral oxygen extraction, systemic oxygen metabolism, and systemic vascular resistance were done. Measurements were obtained at baseline (37 degrees C), at the end of cooling, at 30 degrees C during rewarming, and at 2, 4, and 8 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass. At the end of cooling, cerebral vascular resistance remained at baseline levels in all groups, but systemic vascular resistance was increased in all groups. Cerebral oxygen consumption became progressively lower as temperature was reduced: it was only 5% of baseline at 8 degrees C; 20% at 13 degrees C; and 34% and 39% at 18 degrees C. Quantitative electroencephalography was silent in the 8 degrees C and 13 degrees C groups, but significant slow wave activity was present at 18 degrees C. Systemic vascular resistance and cerebral oxygen consumption returned to baseline values in all groups by 2 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass, but cerebral vascular resistance remained elevated at 2 and 4 hours, not returning to baseline until 8 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass. All but two of the long-term survivors (27 of 32) appeared neurologically normal; after hypothermic circulatory arrest at 8 degrees and 18 degrees C two animals had an unsteady gait. Comparison of quantitative electroencephalography before operation and 6 days after operation showed a significant increase in slow wave activity (delta activity) after hypothermic circulatory arrest and low flow cardiopulmonary bypass at 18 degrees C, a change that suggests possible cerebral injury. Although undetected after operation by simple behavioral and neurologic assessment, significant differences in cerebral metabolism, vasomotor responses, and quantitative electroencephalography do exist during and after hypothermic circulatory arrest and low flow cardiopulmonary bypass at various temperatures and may be implicated in the occurrence of cerebral injury.(ABSTRACT TRUNCATED AT 400 WORDS)\n\n\n"
},
{
"text": "\n173468\nAssociation of CA27.29 and Circulating Tumor Cells Before and at Different Times After Adjuvant Chemotherapy in Patients with Early-stage Breast Cancer - The SUCCESS Trial.\n\nHepp, P\n\nAndergassen, U\n\nJäger, B\n\nTrapp, E\n\nAlunni-Fabbroni, M\n\nFriedl, TW\n\nHecker, N\n\nLorenz, R\n\nFasching, P\n\nSchneeweiss, A\n\nFehm, T\n\nJanni, W\n\nRack, B\n\nBeiträge in Fachzeitschriften\nISI:000384001800054\n27630326.0\n10.21873/anticanres.11034\nNone\nEvidence for the prognostic value of circulating tumor cells (CTCs) in early-stage breast cancer is swiftly increasing. An alternative approach for identifying patients at risk for recurrence is based on the detection of the mucin-1 (MUC1)-based tumor marker CA27.29. Here we report the association of these two prognostic markers before and immediately after chemotherapy (CHT), as well as after 2 and 5 years of follow-up.\n The SUCCESS trial compared fluorouracil, epirubicin and cyclophosphamide followed by docetaxel vs. FEC followed by docetaxel plus gemcitabine, and 2 vs. 5 years of treatment with zoledronic acid in 3, 54 patients with node-positive or high-risk node-negative early-stage breast cancer. CA27.29 was measured with the ST AIA-PACK CA27.29 reagent (Tosoh Bioscience, Belgium). The cutoff for CA27.29 positivity was >31 U/ml. CTCs were assessed with the CellSearch System (Veridex, USA). The cutoff for CTC positivity was ≥1 CTC/15 ml whole blood. The relationship between CTC positivity and CA27.29 positivity was assessed based on Chi-square statistics and Cramer's V, which varies from 0 (no association between the variables) to 1 (complete association). Samples for CA27.29 and CTC determinations during follow-up were only drawn from patients that had no relapse.\n Both CA27.29 and CTC data were available for 1, 81, 1, 02, 1, 59 and 707 patients before, immediately after and at 2 and 5 years after CHT, respectively. Positivity rates for CTC were 21.3%, 22.8%, 18.6% and 8.5%, respectively. CA27.29 was positive in 7.9%, 21.0%, 2.8%and 7.5%, respectively. Positivity for both CA27.29 and CTC was found in 2.4%, 4.2%, 0.7% and 1.8% of patients, respectively. The association between CA27.29 and CTC was significant but weak before CHT (p=0.0015; Cramer's V=0.063) and 5 years after CHT (p<0.001; Cramer's V=0.164), and not significant immediately after CHT (p=0.162; Cramer's V=0.035) and 2 years after (p=0.349; Cramer's V=0.028).\n We showed that CTC and CA27.29 positivity were significantly, but only weakly associated before CHT and 5 years after CHT, while no significant association was found immediately or 2 years after CHT during the course of early-stage breast cancer. It, therefore, seems reasonable to further evaluate the prognostic value of CTCs and CA27.29 as a combined prognostic test of two potentially independent markers that might provide complementary prognostic information.\n Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.\n\nTrapp, Elisabeth Katharina\n\n\n"
},
{
"text": "\n184881\nConceptual understanding and applicability of shared decision-making in psychiatric care: An integrative review.\n\nGurtner, C\n\nSchols, JMGA\n\nLohrmann, C\n\nHalfens, RJG\n\nHahn, S\n\nBeiträge in Fachzeitschriften\nISI:000594681500001\n33191536.0\n10.1111/jpm.12712\nNone\nWHAT IS KNOWN ON THE SUBJECT?: Shared decision-making is a concept originating in the medical field, and it is ideally based on a trustful relationship between the patient and the health professionals involved. Shared decision-making shows potential to strengthen patient autonomy and encourages patients to become involved in decisions regarding their treatment. WHAT DOES THE PAPER ADD TO EXISTING KNOWLEDGE?: A universal concept and understanding of shared decision-making with relevance specifically to psychiatric clinical practice could not be identified in the analysed literature. Shared decision-making refers to a process, and how and whether the patient wishes to participate in the decision-making process should be clarified from the very beginning. On the basis of this synthesizing review, a process model for psychiatric practice was specified and illustrated to help lead health professionals, patients and other supporters through the decision-making process. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The process of shared decision-making should be made visible to all persons involved, and it should be stated at the beginning that a decision must be made. Decisions regarding treatment are usually not limited to a single consultation. A collaborative approach including multiple health professionals and other supporters, such as peer workers and family members, is required. Psychiatric nurses could support patients during the process of decision-making and provide additional information, if requested.\n INTRODUCTION: Patient involvement in decisions regarding treatment has increasingly been supported in health care, and therefore, shared decision-making (SDM), as an informative and participative approach, is promoted in the scientific literature.\n To review the current state of research regarding the conceptual understanding and implementation of SDM in psychiatric clinical practice.\n An integrative review that included empirical, theoretical and conceptual research published between 1997 and 2019 was conducted. For this, five health-related databases were searched.\n Fourteen articles were included in the synthesis. No universal conceptual understanding of SDM regarding psychiatric care could be identified, although several articles highlighted the link with other concepts, such as autonomy and patient-centeredness. Furthermore, four additional key themes with relevance for the successful implementation of SDM in clinical practice were determined.\n SDM refers to a process and is usually not limited to a single consultation. SDM shows the potential to enhance patient-centred and recovery-oriented care. A collaborative approach including multiple health professionals, peer workers and family members is required.\n The process of SDM should be made visible for all parties involved. Nurses in particular could play a key role by collecting information regarding patient's preferences and by providing support.\n © 2020 John Wiley & Sons Ltd.\n\nLohrmann, Christa\n\n\n"
},
{
"text": "\n187883\nImmunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27 & ndash;45 years of age compared to women 16 & ndash;26 years of age: An open-label phase 3 study\n\nJoura, EA\n\nUlied, A\n\nVandermeulen, C\n\nFigueroa, MR\n\nSeppa, I\n\nAguado, JJH\n\nAhonen, A\n\nReich, O\n\nVirta, M\n\nPerino, A\n\nTuser, MP\n\nPeters, K\n\nOrigoni, M\n\nRaspagliesi, F\n\nTjalma, WAA\n\nTummers, P\n\nWoelber, L\n\nNieminen, P\n\nvan Damme, P\n\nSehouli, J\n\nRuiz, GF\n\nBrucker, S\n\nFehm, T\n\nCheon, K\n\nRawat, S\n\nLuxembourg, A\n\nWittke, F\n\nBeiträge in Fachzeitschriften\nISI:000645426400009\n33676783.0\n10.1016/j.vaccine.2021.01.074\nNone\nBackground: Efficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16 & ndash;26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27 & ndash;45 versus 16 & ndash;26 years of age. Methods: This international, open-label study (NCT03158220) was conducted in women 16 & ndash;45 years of age. Participants (16 & ndash;26 years, n = 570 and 27 & ndash;45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study. Results: At month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27 & ndash;45 years were compared to those in women 16 & ndash;26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27 & ndash;45 years to 16 & ndash;26 years) was 0.60 & ndash;0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27 & ndash; 45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16 & ndash;26 years, and 85.2% and 24.1% of women 27 & ndash; 45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study. Conclusions: The 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27 & ndash;45 years compared with women 16 & ndash;26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16 & ndash;26 years to women 27 & ndash;45 years of age. Clinical trial registration NCT03158220. (c) 2021 Elsevier Ltd. All rights reserved.\n\nReich, Olaf\n\n\n"
},
{
"text": "\n1259\nImbalance between the endothelial cell-derived contracting factors prostacyclin and angiotensin II and nitric oxide/cyclic GMP in human primary varicosis.\n\nSchuller-Petrovic, S\n\nSiedler, S\n\nKern, T\n\nMeinhart, J\n\nSchmidt, K\n\nBrunner, F\n\nBeiträge in Fachzeitschriften\nISI:A1997YB24700024\n9375976.0\n10.1038/sj.bjp.0701437\nPMC1564992\n1. The role of the endothelium in the vasomotor control of human veins in the lower extremity is little understood. We tested the hypothesis that the production of relaxing and contracting factors is altered in endothelial cells from varicose saphenous veins which may predispose to the decreased vessel tone observed in primary varicosis. 2. We determined the intracellular accumulation of guanosine 3':5'-cyclic monophosphate cyclic GMP; a measure of nitric oxide production and the release of endothelin and prostacyclin (measured as its stable metabolite 6-keto-prostaglandin F1alpha) from cultured cells derived from the long saphenous veins of patients with primary varicosis (Varicose saphena group, n = 27) or from patients undergoing coronary artery bypass surgery (Healthy saphena group, n = 22). In addition, levels of endothelin, angiotensin II, bradykinin, cyclic GMP and cyclic AMP in plasma from patients with primary varicosis and healthy volunteers (n = 8-11 in each group) were determined. 3. Although basal cyclic GMP levels were similar, more cyclic GMP accumulated in response to histamine (1-100 micromol l[-1]) in cells from varicose saphenous veins (0.75 +/- 0.1 pmol per well) than in cells from veins without varicosis (0.27 +/- 0.05 pmol per well). Furthermore, the relaxant potency of nitroprusside (1 nmol l(-1) - 300 micromol l[-1]) in vitro was higher for varicose veins (mean EC50 = 5.9 micromol l(-1); n = 8) than healthy veins (mean EC50 = 20.0 micromol l(-1); n = 7). 4. The production of prostacyclin was significantly less in cells from varicose than healthy saphenous veins (66 +/- 8.7 and 121 +/- 20.1 nmol g(-1) protein), but the production of endothelin was similar in both groups. Prostacyclin (3 nmol l(-1) 30 micromol l[-1]) consistently contracted rings of varicose saphenous vein in vitro with a mean EC50 value of 10-20 micromol l(-1) (n = 7); the maximum tension generated was approximately 50% of that of a completely depolarizing solution of K+ (120 mmol l[-1]). 5. In plasma from patients with varicose veins, levels of cyclic GMP were higher than in healthy controls (9.2 +/- 0.03 and 7.2 +/- 0.02 nmol l[-1]), levels of angiotensin II were lower (81 +/- 11.5 and 147 +/- 21.7 pmol l[-1]), and levels of endothelin, cyclic AMP, and bradykinin were not different. 6. It is concluded that endothelial cells from diseased saphenous veins secrete less constrictor mediators than cells from healthy veins and that in diseased veins the nitric oxide/cyclic GMP system is up-regulated which may shift the balance of vasoactive factors towards vasodilatation and contribute to the development of primary varicosis.\n\nSchuller-Petrovic, Sanja\n\n\n"
},
{
"text": "\n129417\nManpower and portfolio of European ENT.\n\nLuxenberger, W\n\nLahousen, T\n\nMollenhauer, H\n\nFreidl, W\n\nBeiträge in Fachzeitschriften\nISI:000331706100027\n23771279.0\n10.1007/s00405-013-2582-1\nNone\nThe aim of this study is to evaluate highly variable ENT manpower among European countries. A descriptive study design is used. Manpower in medicine is highly variable among European countries. EU and associated countries are keeping officially appointed representatives to the European Union of medical specialists--otorhinolaryngology section (UEMS--ORL section). UEMS--ORL section is running a working group for manpower in ENT collecting data regarding demographics and ENT manpower in European countries. These ENT manpower data are presented in this paper and compared to available data concerning manpower in European medicine in general. To further evaluate these huge differences, representatives of the particular countries were also asked to fill out a questionnaire concerning specifics of ENT healthcare in their country. Furthermore, typical tasks of ENT doctors based on the official UEMS logbook for ENT training were listed and could be rated regarding their frequency, performed in everyday routine of an average ENT doctor of the country. Divergences in doctors/inhabitants ratios were remarkable within European countries, but disparities in ENT manpower were even more so. The ratio of ENT doctors/inhabitants was the lowest in Ireland (1:80, 00) and Great Britain (1:65, 00). Greece (1:10, 00), Italy, Czech Republic, Lithuania, Poland and Slovakia (1:12, 00) were--at the time of the study--the countries with the highest density of ENT doctors. The EU average for 2009 was (1:21, 00). The presence of non-surgical working ENT doctors was significantly associated with higher densities of ENT doctors, whereas the necessity of being referred to an ENT doctor (gatekeeping or similar measures) was not. Estimated average waiting times for an appointment in non-urgent, chronic conditions, respectively, diseases were highly variable and predominantly showed a significant correlation to the ENT doctors/inhabitants ratio in the investigated countries. But also for acute conditions like acute hypacusis, dysphonia and hemoptysis, significant differences correlating to the ENT doctors/inhabitants ratio in waiting times for an ENT appointment were found. Estimated frequencies of different ENT tasks in everyday routine were extremely diverse as well, however, without detectable correlations to the ENT doctors/inhabitants ratio. In countries like Great Britain, Ireland, Malta and The Netherlands ENT doctors are primarily seen and serving as surgeons. In most Central European countries like Germany, Austria, Czech Republic, Poland and Slovakia, ENT doctors aside of surgery are also dealing with high percentages of conservative medicine, which may include vast fields like the management of Allergology, Phoniatrics, Audiology, etc. In some countries ENT doctors are even playing a significant role in primary health care as well. These various portfolios of ENT may be one explanation for the huge difference in numbers of European ENT manpower.\n\nFreidl, Wolfgang\n\nLahousen-Luxenberger, Theresa\n\nLuxenberger, Wolfgang\n\n\n"
},
{
"text": "\n135732\nAge dependency of successful recanalization in anterior circulation stroke: the ENDOSTROKE study.\n\nSinger, OC\n\nHaring, HP\n\nTrenkler, J\n\nNolte, CH\n\nBohner, G\n\nReich, A\n\nWiesmann, M\n\nBussmeyer, M\n\nMpotsaris, A\n\nNeumann-Haefelin, T\n\nHohmann, C\n\nNiederkorn, K\n\nDeutschmann, H\n\nStoll, A\n\nBormann, A\n\nJander, S\n\nTurowski, B\n\nBrenck, J\n\nSchlamann, MU\n\nPetzold, GC\n\nUrbach, H\n\nLiebeskind, DS\n\nBerkefeld, J\n\nBeiträge in Fachzeitschriften\nISI:000330857000018\n24281318.0\n10.1159/000356213\nNone\nClinical outcome after endovascular stroke therapy (EVT) for proximal anterior circulation stroke is often disappointing despite high recanalization rates. The ENDOSTROKE study aims to determine predictors of clinical outcome in patients undergoing EVT. Here we focus on the impact of age and recanalization on proximal middle cerebral artery (M1-MCA) or carotid T occlusion.\n ENDOSTROKE is an investigator-initiated, industrially independent multicenter registry launched in January, 2011, for consecutive patients undergoing EVT for large-vessel stroke. This analysis focuses on patients treated in 11 academic and nonacademic stroke centers with angiographically proven M1-MCA (n = 259) or carotid T occlusion (n = 103). Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) score 2 or 3, and in patients with available Thrombolysis in Cerebral Ischemia (TICI) data (n = 309) as TICI scores 2b-3. Good outcome was defined as modified Rankin Scale (mRS) score of 0-2 assessed after 3 months or later.\n The median age was 68 years (25th and 75th percentiles: 56, 76 years), and the median National Institutes of Health Stroke Scale (NIHSS) score at admission was 16 (13, 19); 41% of the patients had a favorable (mRS scores 0-2), and 59% had an unfavorable (mRS scores 3-6) outcome; 83% reached TIMI 2-3 flow. Independent predictors of good outcome were younger age, lower initial NIHSS scores, TIMI 2/3 recanalization and lower serum glucose levels. Outcome was highly dependent on patients' age: 60% of the patients within the lowest age quartile (range: 18-56 years) experienced good clinical outcome, decreasing stepwise over 47% (57-68 years) and 37% (69-76 years) to 17% in the highest age quartile (77-94 years). The proportion of patients with poor clinical outcome despite TIMI 2/3 recanalization ('futile recanalization') increased dramatically from only 29% in the lowest age quartile over 34% and 40% (2nd and 3rd age quartiles) up to 53% in the highest age quartile. Results were similar in patients with available TICI scores, with 'futile recanalization' rates increasing from 24% to 46% (lowest to highest age quartile).\n This study emphasizes the dramatic impact of patients' age on outcome in EVT for M1-MCA or carotid T occlusion, even in the presence of recanalization. Reasons for this age-related decrease in clinically successful recanalization rates urgently need clarification and may comprise patient-related factors (age-related increase in cardioembolic strokes, collateral status, comorbidities) as well as periprocedural issues (tortuous vessel anatomy in the elderly, age-dependent negative impact of general anesthesia in EVT).\n\nDeutschmann, Hannes\n\n\n"
},
{
"text": "\n187131\nTreatment of early-stage mycosis fungoides: results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.\n\nQuaglino, P\n\nPrince, HM\n\nCowan, R\n\nVermeer, M\n\nPapadavid, E\n\nBagot, M\n\nServitjie, O\n\nBerti, E\n\nGuenova, E\n\nStadler, R\n\nQuerfeld, C\n\nBusschots, AM\n\nHodak, E\n\nPatsatsi, A\n\nSanches, J\n\nMaule, M\n\nYoo, J\n\nKevin, M\n\nFava, P\n\nRibero, S\n\nZocchi, L\n\nRubatto, M\n\nFierro, MT\n\nWehkamp, U\n\nMarshalko, M\n\nMitteldorf, C\n\nAkilov, O\n\nOrtiz-Romero, P\n\nEstrach, T\n\nVakeva, L\n\nEnz, PA\n\nWobser, M\n\nBayne, M\n\nJonak, C\n\nRubeta, M\n\nForbes, A\n\nBates, A\n\nBattistella, M\n\nAmel-Kashipaz, R\n\nVydianath, B\n\nCombalia, A\n\nGeorgiou, E\n\nHauben, E\n\nHong, EK\n\nJost, M\n\nKnobler, R\n\nAmitay-Laish, I\n\nMiyashiro, D\n\nCury-Martins, J\n\nMartinez, X\n\nMuniesa, C\n\nPrag-Naveh, H\n\nStratigos, A\n\nNikolaou, V\n\nQuint, K\n\nRam-Wolff, C\n\nRieger, K\n\nStranzenbach, R\n\nSzepesi, Á\n\nAlberti-Violetti, S\n\nFelicity, E\n\nCerroni, L\n\nKempf, W\n\nWhittaker, S\n\nWillemze, R\n\nKim, Y\n\nScarisbrick, JJ\n\nBeiträge in Fachzeitschriften\nISI:000619162500001\n32479678.0\n10.1111/bjd.19252\nPMC7704558\nThe PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF).\n To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures.\n In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review.\n The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease.\n Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.\n © 2020 British Association of Dermatologists.\n\nCerroni, Lorenzo\n\n\n"
},
{
"text": "\n187337\nNintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease.\n\nDistler, O\n\nHighland, KB\n\nGahlemann, M\n\nAzuma, A\n\nFischer, A\n\nMayes, MD\n\nRaghu, G\n\nSauter, W\n\nGirard, M\n\nAlves, M\n\nClerisme-Beaty, E\n\nStowasser, S\n\nTetzlaff, K\n\nKuwana, M\n\nMaher, TM\n\nSENSCIS Trial Investigators\n\nBeiträge in Fachzeitschriften\nNone\n31112379.0\n10.1056/NEJMoa1903076\nNone\nInterstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD.\n We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52.\n A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was -52.4 ml per year in the nintedanib group and -93.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P = 0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of -0.21 (95% CI, -0.94 to 0.53; P = 0.58) and 1.69 (95% CI, -0.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group.\n Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo. (Funded by Boehringer Ingelheim; SENSCIS ClinicalTrials.gov number, NCT02597933.).\n Copyright © 2019 Massachusetts Medical Society.\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n1146\nGlucocorticoid-recognizing and -effector sites in rat liver plasma membrane. Kinetics of corticosterone uptake by isolated membrane vesicles. III. Specificity and stereospecificity.\n\nLackner, C\n\nDaufeldt, S\n\nWildt, L\n\nAlléra, A\n\nBeiträge in Fachzeitschriften\nISI:000072878300008\n9569012.0\n10.1016/S0960-0760(97)00141-6\nNone\nIn previous papers we provided evidence for a glucocorticoid (GC) responsive site in a highly purified rat liver plasma membrane (PM) fraction, which has proved to be osmotically active, 'right side-out' vesicles, free of CBG, glucocorticoid receptors (GR) and ATP (J. Steroid Biochem. Molec. Biol. 42 (1992) 737-756 and 757-771). This site, now called 'GC importer', mediates active transmembrane transport of corticosterone (B). Pronounced specificity, including stereo- and enantiomeric specificity, of ligand-GC importer interaction was demonstrated by competition assays using 54 different steroidal hormones and molecules. Important structural prerequisites for ligands with high specificity for the GC importer are plane C21-steroid hormones with 1-ene and/or 4-ene or 5alpha-reduced configuration, and/or OH-group(s) at C11beta>C17alpha>C21. Unexpectedly, other preferred ligands are C17alpha-ethynyl steroids like estrogens with an OH- or OCH3-group at C3 (EE2, mestranol) as well as progestins with C3-OH and 4-ene configuration (ethynodiol). C21-steroids with 11alpha-OH, 11-keto, 16alpha-CH3, 16beta-CH3, 16alpha-OH or 5beta-reduced configuration are low specificity ligands. The importer even displays different specificity for enantiomers (levonorgestrel>L-norgestrel). Altogether, the GC importer preferentially recognizes active GC and natural progestins which act as GC-antagonist (e.g. prednisolone>11beta-cortisol = B > or = progestins). Synthetic GC-agonists (e.g. dexamethasone, betamethasone, triamcinolone), most synthetic progestins, biologically inactive GC (e.g. 11alpha-cortisol, prednisone, cortisone, 11-dehydro-B), mineralocorticoids (aldosterone), natural estrogens (e.g. E1, E2, E3), DES and vitamin D3 derivatives do not interact with the GC importer. Osmotic shrinkage experiments revealed that interaction of high as well as low specificity ligands with the GC importer comprises reversible binding and transport through the PM. The ligand specificity profile of the GC importer and the GR exhibit pronounced differences, suggesting that both GC recognizing sites are different proteins. Performing immunoblotting, using specific mono- and polyclonal antibodies directed against the intracellular rat GR, of the PM pretreated with the membrane protein solubilizing detergent CHAPSO, we found that specific steroid binding to the PM site is not due to contamination with GR. Colchicine, daunorubicine, quinine, reserpine, verapamil and vinblastine, representatives of lipophilic xenobiotics which are known to be transported out of cells by the glycoprotein P170, did not compete with B for uptake into PM-vesicles, indicating that the GC importer is not a member of the ABC/mdr superfamily. The GC importer seems to be an additional link in the chain of steroid signal transduction and may be functionally involved in the action of natural GC-agonists and GC-antagonists.\n\nLackner, Karoline\n\n\n"
}
]
}