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"text": "\n139851\nReproducibility of histological assessments of disease activity in UC.\n\nMosli, MH\n\nFeagan, BG\n\nZou, G\n\nSandborn, WJ\n\nD'Haens, G\n\nKhanna, R\n\nBehling, C\n\nKaplan, K\n\nDriman, DK\n\nShackelton, LM\n\nBaker, KA\n\nMacDonald, JK\n\nVandervoort, MK\n\nSamaan, MA\n\nGeboes, K\n\nValasek, MA\n\nPai, R\n\nLangner, C\n\nRiddell, R\n\nHarpaz, N\n\nSewitch, M\n\nPeterson, M\n\nStitt, LW\n\nLevesque, BG\n\nBeiträge in Fachzeitschriften\nISI:000362593700013\n25360036.0\n10.1136/gutjnl-2014-307536\nNone\nHistopathology is potentially an important outcome measure in UC. Multiple histological disease activity (HA) indices, including the Geboes score (GS) and modified Riley score (MRS), have been developed; however, the operating properties of these instruments are not clearly defined. We assessed the reproducibility of existing measures of HA.\n Five experienced pathologists with GI pathology fellowship training and expertise in IBD evaluated, on three separate occasions at least two weeks apart, 49 UC colon biopsies and scored the GS, MRS and a global rating of histological severity using a 100 mm visual analogue scale (VAS). The reproducibility of each grading system and for individual instrument items was quantified by estimates of intraclass correlation coefficients (ICCs) based on two-way random effects models. Uncertainty of estimates was quantified by 95% two-sided CIs obtained using the non-parametric cluster bootstrap method. Biopsies responsible for the greatest disagreement based on the ICC estimates were identified. A consensus process was used to determine the most common sources of measurement disagreement. Recommendations for minimising disagreement were subsequently generated.\n Intrarater ICCs (95% CIs) for the total GS, MRS and VAS scores were 0.82 (0.73 to 0.88), 0.71 (0.63 to 0.80) and 0.79 (0.72 to 0.85), respectively. Corresponding inter-rater ICCs were substantially lower: 0.56 (0.39 to 0.67), 0.48 (0.35 to 0.66) and 0.61 (0.47 to 0.72). Correlation between the GS and VAS was 0.62 and between the MRS and VAS was 0.61.\n Although 'substantial' to 'almost perfect' ICCs for intrarater agreement were found in the assessment of HA in UC, ICCs for inter-rater agreement were considerably lower. According to the consensus process results, standardisation of item definitions and modification of the existing indices is required to create an optimal UC histological instrument.\n Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.\n\nLangner, Cord\n\n\n"
},
{
"text": "\n145205\nFractional flow reserve and coronary bifurcation anatomy: a novel quantitative model to assess and report the stenosis severity of bifurcation lesions.\n\nTu, S\n\nEchavarria-Pinto, M\n\nvon Birgelen, C\n\nHolm, NR\n\nPyxaras, SA\n\nKumsars, I\n\nLam, MK\n\nValkenburg, I\n\nToth, GG\n\nLi, Y\n\nEscaned, J\n\nWijns, W\n\nReiber, JH\n\nBeiträge in Fachzeitschriften\nISI:000353345300014\n25819180.0\n10.1016/j.jcin.2014.12.232\nNone\nThe aim of this study was to develop a new model for assessment of stenosis severity in a bifurcation lesion including its core. The diagnostic performance of this model, powered by 3-dimensional quantitative coronary angiography to predict the functional significance of obstructive bifurcation stenoses, was evaluated using fractional flow reserve (FFR) as the reference standard.\n Development of advanced quantitative models might help to establish a relationship between bifurcation anatomy and FFR.\n Patients who had undergone coronary angiography and interventions in 5 European cardiology centers were randomly selected and analyzed. Different bifurcation fractal laws, including Murray, Finet, and HK laws, were implemented in the bifurcation model, resulting in different degrees of stenosis severity.\n A total of 78 bifurcation lesions in 73 patients were analyzed. In 51 (65%) bifurcations, FFR was measured in the main vessel. A total of 34 (43.6%) interrogated vessels had an FFR≤0.80. Correlation between FFR and diameter stenosis was poor by conventional straight analysis (ρ=-0.23, p<0.001) but significantly improved by bifurcation analyses: the highest by the HK law (ρ=-0.50, p<0.001), followed by the Finet law (ρ=-0.49, p<0.001), and the Murray law (ρ=-0.41, p<0.001). The area under the receiver-operating characteristics curve for predicting FFR≤0.80 was significantly higher by bifurcation analysis compared with straight analysis: 0.72 (95% confidence interval: 0.61 to 0.82) versus 0.60 (95% confidence interval: 0.49 to 0.71; p=0.001). Applying a threshold of ≥50% diameter stenosis, as assessed by the bifurcation model, to predict FFR≤0.80 resulted in 23 true positives, 27 true negatives, 17 false positives, and 11 false negatives.\n The new bifurcation model provides a comprehensive assessment of bifurcation anatomy. Compared with straight analysis, identification of lesions with preserved FFR values in obstructive bifurcation stenoses was improved. Nevertheless, accuracy was limited by using solely anatomical parameters.\n Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.\n\nToth-Gayor, Gabor\n\n\n"
},
{
"text": "\n148533\nMonoglyceride lipase deficiency modulates endocannabinoid signaling and improves plaque stability in ApoE-knockout mice.\n\nVujic, N\n\nSchlager, S\n\nEichmann, TO\n\nMadreiter-Sokolowski, CT\n\nGoeritzer, M\n\nRainer, S\n\nSchauer, S\n\nRosenberger, A\n\nWoelfler, A\n\nDoddapattar, P\n\nZimmermann, R\n\nHoefler, G\n\nLass, A\n\nGraier, WF\n\nRadovic, B\n\nKratky, D\n\nBeiträge in Fachzeitschriften\nISI:000367375100040\n26584135.0\n10.1016/j.atherosclerosis.2015.10.109\nPMC4704137\nMonoglyceride lipase (MGL) catalyzes the final step of lipolysis by degrading monoglyceride (MG) to glycerol and fatty acid. MGL also hydrolyzes and thereby deactivates 2-arachidonoyl glycerol (2-AG), the most abundant endocannabinoid in the mammalian system. 2-AG acts as full agonist on cannabinoid receptor type 1 (CB1R) and CB2R, which are mainly expressed in brain and immune cells, respectively. Thus, we speculated that in the absence of MGL, increased 2-AG concentrations mediate CB2R signaling in immune cells to modulate inflammatory responses, thereby affecting the development of atherosclerosis.\n We generated apolipoprotein E (ApoE)/MGL double-knockout (DKO) mice and challenged them with Western-type diet for 9 weeks. Despite systemically increased 2-AG concentrations in DKO mice, CB2R-mediated signaling remains fully functional, arguing against CB2R desensitization. We found increased plaque formation in both en face aortae (1.3-fold, p = 0.028) and aortic valve sections (1.5-fold, p = 0.0010) in DKO mice. Interestingly, DKO mice also presented reduced lipid (12%, p = 0.031) and macrophage content (18%, p = 0.061), elevated intraplaque smooth muscle staining (1.4-fold, p = 0.016) and thicker fibrous caps (1.8-fold, p = 0.0032), together with a higher ratio of collagen to necrotic core area (2.5-fold, p = 0.0003) and expanded collagen content (1.6-fold, p = 0.0007), which suggest formation of less vulnerable atherosclerotic plaques. Treatment with a CB2R inverse agonist prevents these effects in DKO mice, demonstrating that the observed plaque phenotype in DKO mice originates from CB2R activation.\n Loss of MGL modulates endocannabinoid signaling in CB2R-expressing cells, which concomitantly affects the pathogenesis of atherosclerosis. We conclude that despite larger lesion size loss of MGL improves atherosclerotic plaque stability. Thus, pharmacological MGL inhibition may be a novel intervention to reduce plaque rupture.\n Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.\n\nGöritzer, Madeleine\n\nGraier, Wolfgang\n\nHöfler, Gerald\n\nKratky, Dagmar\n\nMadreiter-Sokolowski, Corina\n\nRadovic, Branislav\n\nRainer, Silvia\n\nSchauer, Silvia\n\nSchlacher, Angelika\n\nVujic, Nemanja\n\nWoelfler, Albert\n\n\n"
},
{
"text": "\n150829\nPrevalence, Clinical Characteristics, and Risk Factors for Non-recording of Alcohol Use in Hospitals across Europe: The ALCHIMIE Study.\n\nRosón, B\n\nCorbella, X\n\nPerney, P\n\nSantos, A\n\nStauber, R\n\nLember, M\n\nArutyunov, A\n\nRuza, I\n\nVaclavik, J\n\nGarcía, L\n\nPujol, R\n\nStauber, R\n\nVogel, W\n\nVaclavik, J\n\nGajdová, J\n\nSmrzova, A\n\nLiberdová, A\n\nCibickova, L\n\nPlasek, J\n\nSvarcova, T\n\nSalupere, R\n\nLember, M\n\nRosón, B\n\nGuillem, MN\n\nFernández-Sola, J\n\nZapatero, A\n\nMonte, R\n\nPuerta, RB\n\nGamallo, R\n\nDurán, C\n\nPerney, P\n\nOuakli, A\n\nOziol, E\n\nBastide, D\n\nTourneaire, P\n\nAllard, G\n\nCros, H\n\nPiala, JM\n\nQuere, I\n\nCondouret, S\n\nRuža, I\n\nFunka, K\n\nZarina, L\n\nBarata, J\n\nGonsalves, O\n\nSantos, A\n\nOliveira, N\n\nYakushin, S\n\nPetrovicheva, L\n\nSleptsov, A\n\nArutyunov, A\n\nMitkhat, G\n\nMarusenko, I\n\nALCHIMIE Study Group\n\nBeiträge in Fachzeitschriften\nISI:000379699000012\n26818195.0\n10.1093/alcalc/agv142\nNone\nTo determine the detection rates, clinical features, and risk factors for lack of registration of alcohol use in medical patients admitted in European hospitals.\n A point-prevalence, cross-sectional, multicenter survey involving 2100 medical inpatients from 43 hospitals from 8 European countries. Patients were screened for current alcohol use, using standardized questionnaires. Alcohol use recording in medical records was assessed.\n Of the 2100, more than a half reported alcohol use. Significant differences were shown in the prevalence of drinking and the recording rates of alcohol use among the hospitals and countries involved. Overall, 346 patients (16%) fulfilled criteria for alcohol use disorder. Alcohol use was registered in 909 (43%) of medical records, with quantification in 143 (7%). Multivariate analysis showed that women (OR 1.49), older age patients (OR 1.23), patients from the Northern European countries (OR 4.79) and from hospitals with high local alcohol prevalence (OR 1.59) were more likely to have lack of alcohol use registration in their medical files.\n A considerable proportion of medical patients admitted in European hospitals fulfill criteria for alcohol use disorders. These patients are frequently overlooked during hospitalization and not appropriately registered in medical records. Women, older patients, and inpatients from European areas with high local alcohol use prevalence are at higher risk associated with a non-recording of alcohol use.\n © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n152726\nThe Added Value of Analyzing Pooled Health-Related Quality of Life Data: A Review of the EORTC PROBE Initiative.\n\nZikos, E\n\nCoens, C\n\nQuinten, C\n\nEdiebah, DE\n\nMartinelli, F\n\nGhislain, I\n\nKing, MT\n\nGotay, C\n\nRingash, J\n\nVelikova, G\n\nReeve, BB\n\nGreimel, E\n\nCleeland, CS\n\nFlechtner, H\n\nTaphoorn, MJ\n\nWeis, J\n\nSchmucker-von Koch, J\n\nSprangers, MA\n\nBottomley, A\n\nEORTC PROBE\n\nBeiträge in Fachzeitschriften\nISI:000375404600020\n26714759.0\n10.1093/jnci/djv391\nNone\nThe European Organisation for Research and Treatment of Cancer (EORTC) Patient-Reported Outcomes and Behavioural Evidence (PROBE) initiative was established to investigate critical topics to better understand health-related quality of life (HRQOL) of cancer patients and to educate clinicians, policy makers, and healthcare providers.\n The aim of this paper is to review the major research outcomes of the pooled analysis of HRQOL data along with the clinical data. We identified 30 pooled EORTC randomized controlled trials (RCTs), 18 NCIC-Clinical Trials Group RCTs, and two German Ovarian Cancer Study Group RCTs, all using the EORTC QLQ-C30. All statistical tests were two-sided.\n Evidence was found that HRQOL data can offer prognostic information beyond clinical measures and improve prognostic accuracy in cancer RCTs (by 5.9%-8.3%). Moreover, models that considered both patient- and clinician-reported scores gained more prognostic overall survival accuracy for fatigue (P < .001), vomiting (P = .01), nausea (P < .001), and constipation (P = .01). Greater understanding of the association between symptom and/or functioning scales was developed by identifying physical, psychological, and gastrointestinal clusters. Additionally, minimally important differences in interpreting HRQOL changes for improvement and deterioration were found to vary across different patient populations and disease stages. Finally, HRQOL scores are statistically significantly affected by deviations from the intended time point at which the questionnaire is completed.\n The use of existing pooled data shows that it is possible to learn about general aspects of cancer HRQOL and methodology. Our work shows that setting up international pooled datasets holds great promise for understanding patients' unmet psychosocial needs and calls for additional empirical investigation to improve clinical care and understand cancer through retrospective HRQOL analyses.\n © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.\n\nGreimel, Elfriede Renate\n\n\n"
},
{
"text": "\n155438\nPancreatic resection for intraductal papillary mucinous neoplasm- a thirteen-year single center experience.\n\nMarsoner, K\n\nHaybaeck, J\n\nCsengeri, D\n\nWaha, JE\n\nSchagerl, J\n\nLangeder, R\n\nMischinger, HJ\n\nKornprat, P\n\nBeiträge in Fachzeitschriften\nISI:000387643600001\n27809876.0\n10.1186/s12885-016-2887-8\nPMC5096332\nThe purpose of this study is to review our results for pancreatic resection in patients with intraductal papillary mucinous neoplasm (IPMN) with and without associated carcinoma.\n A total of 54 patients undergoing pancreatic resection for IPMN in a single university surgical center (Medical University of Graz) were reviewed retrospectively. Their survival rates were compared to those of patients with pancreatic ductal adenocarcinoma.\n Twenty-four patients exhibit non-invasive IPMN and thirty patients invasive IPMN with associated carcinoma. The mean age is 67 (+/-11) years, 43 % female. Surgical strategies include classical or pylorus-preserving Whipple procedure (n = 30), distal (n = 13) or total pancreatectomy (n = 11), and additional portal venous resection in three patients (n = 3). Median intensive care stay is three days (range 1 - 87), median in hospital stay is 23 days (range 7 - 87). Thirty-day mortality is 3.7 %. Median follow up is 42 months (range 0 - 127). One-, five- and ten-year overall actuarial survival is 87 %; 84 % and 51 % respectively. Median overall survival is 120 months. Patients with non-invasive IPMN have significantly better survival than patients with invasive IPMN and IPMN-associated carcinoma (p < 0.008). In the subgroup of invasive IPMN with associated carcinoma, a positive nodal state, perineural invasion as well as lymphovascular infiltration are associated with poor outcome (p < 0.0001; <0.0001 and =0.001, respectively). Elevated CA 19-9(>37 U/l) as well as elevated lipase (>60 U/l) serum levels are associated with unfavorable outcome (p = 0.009 and 0.018; respectively). Patients operated for pancreatic ductal adenocarcinoma show significantly shorter long-term survival than patients with IPMN associated carcinoma (p = 0.001).\n Long-term outcome after pancreatic resection for non-invasive IPMN is excellent. Outcome after resection for invasive IPMN with invasive carcinoma is significantly better than for pancreatic ductal adenocarcinoma. In low- and intermediate risk IPMN with no clear indication for immediate surgical resection, a watchful waiting strategy should be evaluated carefully against surgical treatment individually for each patient.\n\nHaybäck, Johannes\n\nKornprat, Peter\n\nMarsoner, Katharina\n\nMischinger, Hans-Joerg\n\nWaha, James Elvis\n\n\n"
},
{
"text": "\n157299\nMicrostructure and mechanics of healthy and aneurysmatic abdominal aortas: experimental analysis and modelling.\n\nNiestrawska, JA\n\nViertler, C\n\nRegitnig, P\n\nCohnert, TU\n\nSommer, G\n\nHolzapfel, GA\n\nBeiträge in Fachzeitschriften\nISI:000389816300008\n27903785.0\n10.1098/rsif.2016.0620\nPMC5134013\nSoft biological tissues such as aortic walls can be viewed as fibrous composites assembled by a ground matrix and embedded families of collagen fibres. Changes in the structural components of aortic walls such as the ground matrix and the embedded families of collagen fibres have been shown to play a significant role in the pathogenesis of aortic degeneration. Hence, there is a need to develop a deeper understanding of the microstructure and the related mechanics of aortic walls. In this study, tissue samples from 17 human abdominal aortas (AA) and from 11 abdominal aortic aneurysms (AAA) are systematically analysed and compared with respect to their structural and mechanical differences. The collagen microstructure is examined by analysing data from second-harmonic generation imaging after optical clearing. Samples from the intact AA wall, their individual layers and the AAA wall are mechanically investigated using biaxial stretching tests. A bivariate von Mises distribution was used to represent the continuous fibre dispersion throughout the entire thickness, and to provide two independent dispersion parameters to be used in a recently proposed material model. Remarkable differences were found between healthy and diseased tissues. The out-of-plane dispersion was significantly higher in AAA when compared with AA tissues, and with the exception of one AAA sample, the characteristic wall structure, as visible in healthy AAs with three distinct layers, could not be identified in AAA samples. The collagen fibres in the abluminal layer of AAAs lost their waviness and exhibited rather straight and thick struts of collagen. A novel set of three structural and three material parameters is provided. With the structural parameters fixed, the material model was fitted to the mechanical experimental data, giving a very satisfying fit although there are only three material parameters involved. The results highlight the need to incorporate the structural differences into finite-element simulations as otherwise simulations of AAA tissues might not be good predictors for the actual in vivo stress state.\n © 2016 The Author(s).\n\nCohnert, Tina Ulrike\n\nNiestrawska, Justyna Anna\n\nRegitnig, Peter\n\nViertler, Christian\n\n\n"
},
{
"text": "\n178223\nContrast Induced Acute Kidney Injury and its Impact on Mid-Term Kidney Function, Cardiovascular Events and Mortality.\n\nRibitsch, W\n\nHorina, JH\n\nQuehenberger, F\n\nRosenkranz, AR\n\nSchilcher, G\n\nBeiträge in Fachzeitschriften\nISI:000496714900015\n31729409.0\n10.1038/s41598-019-53040-5\nPMC6858434\nThe existence and clinical relevance of contrast induced acute kidney injury (CI-AKI) is still heavily debated and angiographic procedures are often withheld in fear of CI-AKI, especially in CKD-patients. We investigated the incidence of CI-AKI in cardiovascular high risk patients undergoing intra-arterial angiography and its impact on mid-term kidney function, cardiovascular events and mortality. We conducted a prospective observational trial on patients undergoing planned intra-arterial angiographic procedures. All subjects received standardized intravenous hydration prior to contrast application. CI-AKI was defined according to a ≥25% increase of creatinine from baseline to either 24hrs or 48hrs after angiography. Plasma creatinine and eGFR were recorded from the institutional medical record system one and three months after hospital discharge. Patients were followed up for two years to investigate the long term effects of CI-AKI on cardiovascular events and mortality. We studied 706 (317 female) patients with a mean eGFR of 52.0 ± 15 ml·min-1·1.73 m-2. The incidence of CI-AKI was 10.2% (72 patients). In 94 (13.3%) patients serum creatinine decreased ≥25% either 24 or 48 hours after angiography. Patients with CI-AKI had a lower creatinine and a higher eGFR at baseline, but no other independent predictors of CI-AKI could be identified. Kidney function was not different between both groups one and three months after discharge. After a two year follow up the overall incidence of cardiovascular events was 56.5% in the CI-AKI group and 58.8% in the Non CI-AKI group (p = 0.8), the incidence of myocardial infarctions, however, was higher in CI-AKI-patients. Overall survival was also not different between patients with CI-AKI (88.6%) and without CI-AKI (84.7%, p = 0.48). The occurrence of CI-AKI did not have any negative impact on mid-term kidney function, the incidence of cardiovascular events and mortality. Considerable fluctuations of serum creatinine interfere with the presumed diagnosis of CI-AKI. Necessary angiographic procedures should not be withheld in fear of CI-AKI.\n\nHorina, Joerg\n\nQuehenberger, Franz\n\nRibitsch, Werner\n\nRosenkranz, Alexander\n\nSchilcher, Gernot\n\n\n"
},
{
"text": "\n183102\nDistribution and prognostic significance of gluconeogenesis and glycolysis in lung cancer.\n\nSmolle, E\n\nLeko, P\n\nStacher-Priehse, E\n\nBrcic, L\n\nEl-Heliebi, A\n\nHofmann, L\n\nQuehenberger, F\n\nHrzenjak, A\n\nPopper, HH\n\nOlschewski, H\n\nLeithner, K\n\nBeiträge in Fachzeitschriften\nISI:000564462000001\n32777161.0\n10.1002/1878-0261.12780\nPMC7607181\nInhibition of glycolysis has been considered as a therapeutic approach in aggressive cancers including lung cancer. Abbreviated gluconeogenesis, mediated by phosphoenolpyruvate carboxykinase (PEPCK), was recently discovered to partially circumvent the need for glycolysis in lung cancer cells. However, the interplay of glycolysis and gluconeogenesis in lung cancer is still poorly understood. Here we analyzed the expression of GLUT1, the prime glucose transporter, and of PCK1 and PCK2, the cytoplasmic and mitochondrial isoforms of PEPCK, in 450 samples of non-small cell lung cancer (NSCLC) and in 54 NSCLC metastases using tissue microarrays and whole tumor sections. Spatial distribution was assessed by automated image analysis. Additionally, glycolytic and gluconeogenic gene expression was inferred from The Cancer Genome Atlas (TCGA) datasets. We found that PCK2 was preferentially expressed in the lung adenocarcinoma subtype, while GLUT1 expression was higher in squamous cell carcinoma. GLUT1 and PCK2 were inversely correlated, GLUT1 showing elevated expression in larger tumors while PCK2 was highest in smaller tumors. However, a mixed phenotype showing the presence of both, glycolytic and gluconeogenic cancer cells was frequent. In lung adenocarcinoma, PCK2 expression was associated with significantly improved overall survival, while the opposite was found for GLUT1. The metabolic tumor microenvironment and the 3-dimensional context play an important role in modulating both pathways, since PCK2 expression preferentially occurred at the tumor margin and hypoxia regulated both, glycolysis and gluconeogenesis, in NSCLC cells in vitro, albeit in opposite directions. PCK1/2 expression was enhanced in metastases compared to primary tumors, possibly related to the different environment. The results of this study show that glycolysis and gluconeogenesis are activated in NSCLC in a tumor size and oxygenation modulated manner and differentially correlate with outcome. The frequent co-activation of gluconeogenesis and glycolysis in NSCLC should be considered in potential future therapeutic strategies targeting cancer cell metabolism.\n This article is protected by copyright. All rights reserved.\n\nBonstingl, Lilli\n\nBrcic, Luka\n\nEl-Heliebi, Amin\n\nHrzenjak, Andelko\n\nLeithner, Katharina\n\nOlschewski, Horst\n\nPopper, Helmuth\n\nQuehenberger, Franz\n\nTaucher, Elisabeth\n\n\n"
},
{
"text": "\n1223\nHuman diabetes is associated with hyperreactivity of vascular smooth muscle cells due to altered subcellular Ca2+ distribution.\n\nFleischhacker, E\n\nEsenabhalu, VE\n\nSpitaler, M\n\nHolzmann, S\n\nSkrabal, F\n\nKoidl, B\n\nKostner, GM\n\nGraier, WF\n\nBeiträge in Fachzeitschriften\nISI:000080567900017\n10342823.0\n10.2337/diabetes.48.6.1323\nNone\nAlterations of vascular smooth muscle function have been implicated in the development of vascular complications and circulatory dysfunction in diabetes. However, little is known about changes in smooth muscle contractility and the intracellular mechanisms contributing to altered responsiveness of blood vessels of diabetic patients. Therefore, smooth muscle and endothelial cell function were assessed in 20 patients with diabetes and compared with 41 age-matched control subjects. In rings from uterine arteries, smooth muscle sensitivity to K+, norepinephrine (NE), and phenylephrine (PE) was enhanced by 1.4-, 2.3-, and 9.7-fold, respectively, and endothelium-dependent relaxation was reduced by 64% in diabetic patients, as compared with control subjects. In addition, in freshly isolated smooth muscle cells from diabetic patients, an increased perinuclear Ca2+ signaling to K+ (30 mmol/l >73%; 60 mmol/l >68%) and NE (300 nmol/l >86%; 10 micromol/l >67%) was found. In contrast, subplasmalemmal Ca2+ response, which favors smooth muscle relaxation caused by activation of Ca2+-activated K+ channels, was reduced by 38% in diabetic patients as compared with control subjects, indicating a significant change in the subcellular Ca2+ distribution in vascular smooth muscle cells in diabetic patients. In contrast to the altered Ca2+ signaling found in freshly isolated cells from diabetic patients, in cultured smooth muscle cells isolated from control subjects and diabetic patients, no difference in the intracellular Ca2+ signaling to stimulation with either K+ or NE was found. Furthermore, production of superoxide anion (*O2-) in intact and endothelium-denuded arteries from diabetic patients was increased by 150 and 136%, respectively. Incubation of freshly isolated smooth muscle cells from control subjects with the *O2- -generating system xanthine oxidase/hypoxanthine mimicked the effect of diabetic patients on subcellular Ca2+ distribution in a superoxide dismutase-sensitive manner. We conclude that in diabetic subjects, smooth muscle reactivity is increased because of changes in subcellular Ca2+ distribution on cell activation. Increased *O2- production may play a crucial role in the alteration of smooth muscle function.\n\nGraier, Wolfgang\n\nKoidl, Bernd\n\nKostner, Gerhard\n\n\n"
},
{
"text": "\n119274\nTamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group.\n\nDubsky, PC\n\nJakesz, R\n\nMlineritsch, B\n\nPöstlberger, S\n\nSamonigg, H\n\nKwasny, W\n\nTausch, C\n\nStöger, H\n\nHaider, K\n\nFitzal, F\n\nSinger, CF\n\nStierer, M\n\nSevelda, P\n\nLuschin-Ebengreuth, G\n\nTaucher, S\n\nRudas, M\n\nBartsch, R\n\nSteger, GG\n\nGreil, R\n\nFilipcic, L\n\nGnant, M\n\nBeiträge in Fachzeitschriften\nISI:000302625400014\n22271481.0\n10.1200/JCO.2011.36.8993\nNone\nAnastrozole (ANA) alone delivers significant disease-free survival benefits over tamoxifen (TAM) monotherapy in postmenopausal women with early estrogen receptor-positive breast cancer. The ABCSG-8 (Austrian Breast and Colorectal Cancer Study Group 8) study is a large phase III clinical trial addressing the sequence strategy containing ANA in comparison with 5 years of TAM in a low- to intermediate-risk group of postmenopausal patients.\n Endocrine receptor-positive patients with G1 or G2 tumors were eligible. After surgery, patients were randomly assigned to 5 years of TAM or 2 years of TAM followed by 3 years of ANA. Adjuvant chemotherapy and G3 and T4 tumors were exclusion criteria. Intention-to-treat and censored analyses of on-treatment recurrence-free survival (RFS) were performed, and exploratory survival end points and toxicity were investigated.\n Information from 3, 14 patients, including 17, 63 woman-years, with a median of 60 months of follow-up was available for this analysis. Median age was 63.8 years, 75% were node negative, and 75% had T1 tumors. Sequencing of ANA after identical 2-year treatment with TAM in both arms did not result in a statistically significant improvement of RFS (hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.01; P = .06). Exploratory analyses of distant relapse-free survival indicated a 22% improvement (HR, 0.78; 95% CI, 0.60 to 1.00). On-treatment adverse events and serious adverse events were consistent with known toxicity profiles of ANA and TAM treatment.\n Despite a low overall rate of recurrence in a population with breast cancer at limited risk of relapse, the a priori sequence strategy of 2 years of TAM followed by 3 years of ANA led to small outcome and toxicity benefits.\n\nLuschin-Ebengreuth, Gero\n\nSamonigg, Hellmut\n\nStoeger, Herbert\n\n\n"
},
{
"text": "\n132810\nFood foreign body injuries.\n\nSebastian van As, AB\n\nYusof, AM\n\nMillar, AJ\n\nSusy Safe Working Group\n\nBeiträge in Fachzeitschriften\nISI:000303901500005\n22376998.0\n10.1016/j.ijporl.2012.02.005\nNone\nThe purpose of this study is to acquire a better understanding of Food Foreign Bodies (FFB) injuries in children characterizing the risk of complications and prolonged hospitalization due to food items according to patients' characteristics, circumstances of the accident, Foreign Body (FB) features and FB location, as emerging from the SUSY Safe Web-Registry.\n The present study uses data provided by the SUSY Safe Project, a DG SANCO co-funded project started in February 2005, which was aimed at establishing an international registry of cases of Foreign Bodies (FB) injuries in children aged 0-14 years. The analysis was carried out on injuries due to a food item. FB location was reported according to ICD9-CM code: ears (ICD931), nose (ICD932), pharynx and larynx (ICD933) trachea, bronchi and lungs (ICD934), mouth, esophagus and stomach (ICD935). Age and gender injury distributions were assessed. Data regarding adult supervision and activity before injury were also evaluated. FBs which most frequently cause complications were identified. The association between children age, adult presence, object characteristics and hospitalization/complications was computed using unweighted odds ratios and the related 95% confidence intervals.\n 16, 78 FB injuries occurred in children aged 0-14 years have been recorded in the SUSY Safe databases. FB type was specified in 10, 64 cases; among them 2744 (26%) were due to a food item. FB site was recorded in 1344 cases: FB was located in the ears in 99 patients, while 1140 occurred in the upper and lower respiratory tract; finally, 105 food items were removed from mouth, esophagus and stomach. Complications occurred in 176 cases and the most documented was pulmonary or bronchial infections (23%) followed emphysema or atelectasis and by and asthma (7%). Bones were the commonest retrieved FFB encountered in this study, while nuts seem to be the FFB most frequently associated to complications.\n On the basis of this study we make the strong recommendation that parents should be adequately educated and provide age-appropriate food to their children and be present in order to supervise them during eating especially during a critical period ranging from 2 to 3 years of age.\n Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.\n\nZaupa, Paola\n\n\n"
},
{
"text": "\n147376\nExenatide exerts a PKA-dependent positive inotropic effect in human atrial myocardium: GLP-1R mediated effects in human myocardium.\n\nWallner, M\n\nKolesnik, E\n\nAblasser, K\n\nKhafaga, M\n\nWakula, P\n\nLjubojevic, S\n\nThon-Gutschi, EM\n\nSourij, H\n\nKapl, M\n\nEdmunds, NJ\n\nKuzmiski, JB\n\nGriffith, DA\n\nKnez, I\n\nPieske, B\n\nvon Lewinski, D\n\nBeiträge in Fachzeitschriften\nISI:000367417400030\n26432951.0\n10.1016/j.yjmcc.2015.09.018\nNone\nGlucagon-like peptide-1 receptor (GLP-1R) agonists are a rapidly growing class of drugs developed for treating type-2 diabetes mellitus. Patients with diabetes carry an up to 5-fold greater mortality risk compared to non-diabetic patients, mainly as a result of cardiovascular diseases. Although beneficial cardiovascular effects have been reported, exact mechanisms of GLP-1R-agonist action in the heart, especially in human myocardium, are poorly understood. The effects of GLP-1R-agonists (exenatide, GLP-1(7-36)NH2, PF-06446009, PF-06446667) on cardiac contractility were tested in non-failing atrial and ventricular trabeculae from 72 patients. The GLP-1(7-36)NH2 metabolite, GLP-1(9-36)NH2, was also examined. In electrically stimulated trabeculae, the effects of compounds on isometric force were measured in the absence and presence of pharmacological inhibitors of signal transduction pathways. The role of β-arrestin signaling was examined using a β-arrestin partial agonist, PF-06446667. Expression levels were tested by immunoblots. Translocation of GLP-1R downstream molecular targets, Epac2, GLUT-1 and GLUT-4, were assessed by fluorescence microscopy. All tested GLP-1R-agonists significantly increased developed force in human atrial trabeculae, whereas GLP-1(9-36)NH2 had no effect. Exendin(9-39)NH2, a GLP-1R-antagonist, and H-89 blunted the inotropic effect of exenatide. In addition, exenatide increased PKA-dependent phosphorylation of phospholamban (PLB), GLUT-1 and Epac2 translocation, but not GLUT-4 translocation. Exenatide failed to enhance contractility in ventricular myocardium. Quantitative real-time PCR (qRT-PCR) revealed a significant higher GLP-1R expression in the atrium compared to ventricle. Exenatide increased contractility in a dose-dependent manner via GLP-1R/cAMP/PKA pathway and induced GLUT-1 and Epac2 translocation in human atrial myocardium, but had no effect in ventricular myocardium. Therapeutic use of GLP-1R-agonists may therefore impart beneficial effects on myocardial function and remodelling.\n Copyright © 2015 Elsevier Ltd. All rights reserved.\n\nAblasser, Klemens\n\nHolzer, Senka\n\nKnez, Igor\n\nKolesnik, Ewald\n\nSourij, Harald\n\nvon Lewinski, Dirk\n\nWallner, Markus\n\n\n"
},
{
"text": "\n155411\nRare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies.\n\nAuer-Grumbach, M\n\nToegel, S\n\nSchabhüttl, M\n\nWeinmann, D\n\nChiari, C\n\nBennett, DLH\n\nBeetz, C\n\nKlein, D\n\nAndersen, PM\n\nBöhme, I\n\nFink-Puches, R\n\nGonzalez, M\n\nHarms, MB\n\nMotley, W\n\nReilly, MM\n\nRenner, W\n\nRudnik-Schöneborn, S\n\nSchlotter-Weigel, B\n\nThemistocleous, AC\n\nWeishaupt, JH\n\nLudolph, AC\n\nWieland, T\n\nTao, F\n\nAbreu, L\n\nWindhager, R\n\nZitzelsberger, M\n\nStrom, TM\n\nWalther, T\n\nScherer, SS\n\nZüchner, S\n\nMartini, R\n\nSenderek, J\n\nBeiträge in Fachzeitschriften\nISI:000383114800007\n27588448.0\n10.1016/j.ajhg.2016.07.008\nPMC5011077\nAxonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade β-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment.\n Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.\n\nFink-Puches, Regina\n\nRenner, Wilfried\n\n\n"
},
{
"text": "\n166396\nWhat are Barriers of Nutritional Therapy in Malnourished Medical Inpatients? An Observational Study\n\nTribolet, P\n\nFehr, R\n\nBachli, V\n\nGeiser, M\n\nToplak, H\n\nStanga, Z\n\nSchuetz, P\n\nBeiträge in Fachzeitschriften\nISI:000409130200011\nNone\n10.1055/s-0043-109233\nNone\nBackground Malnutrition is a frequent problem in daily clinical practice and associated with complications, longer hospitalisation and poor outcomes. Use of clinical nutrition is important to prevent these negative aspects, but the efficiency of nutritional therapy is variable and may have several barriers in clinical practice. Herein, the aim of this paper was to examine the feasibility of a new-established nutritional algorithm in everyday clinical practice in a hospital setting and to study potential barriers for the success of nutritional therapy. Methods This is an observational sub-study of the EFFORT-trial, a Swiss-wide, multicenter, randomized, controlled intervention study, which is investigating the effect of nutritional therapy on malnourished, hospitalized, medical patients. The patients were treated according to a clearly defined nutritional algorithm, with the aim of an accurate supply of energy and protein. Based on food diaries the energy and protein target were calculated. To associate not-achieved energy and protein goals and predefined predictors, a multivariate, logistical regression has been used for calculation. Results A total of 581 patients were included in this analysis, whereas most of them reached the nutritional goals (83.3% of all patients reached the energy target and 78.7% the protein target on at least one of the first five days in hospital). According to the multivariate, regression analysis, there was no difference reaching the goals, in regard of age, gender, main diagnosis and comorbidities. Only the loss of appetite has been shown to be a protective factor reaching the energy goals (Odds Ratio [OR] loss of appetite, yes: 0.53, 95% CI, 0.3 to 0.94; p = 0.03). A higher BMI was considered to be a risk factor to not-achieve protein goals (OR per BMI unit [kg/m(2)]: 1.05, 95% CI 1.01 to 1.09; p = 0.02). Conclusions This study shows the feasibility of the nutritional algorithm, as most patients reached their nutritional goals with oral nutrition and without the need for further escalation of enteral or parenteral nutrition. If goals are not reached, an individual assessment is necessary to improve the nutritional care.\n\nToplak, Hermann\n\n\n"
},
{
"text": "\n173298\nSpatially clustering de novo variants in CYFIP2, encoding the cytoplasmic FMRP interacting protein 2, cause intellectual disability and seizures.\n\nZweier, M\n\nBegemann, A\n\nMcWalter, K\n\nCho, MT\n\nAbela, L\n\nBanka, S\n\nBehring, B\n\nBerger, A\n\nBrown, CW\n\nCarneiro, M\n\nChen, J\n\nCooper, GM\n\nDeciphering Developmental Disorders (DDD) Study\n\nFinnila, CR\n\nGuillen Sacoto, MJ\n\nHenderson, A\n\nHüffmeier, U\n\nJoset, P\n\nKerr, B\n\nLesca, G\n\nLeszinski, GS\n\nMcDermott, JH\n\nMeltzer, MR\n\nMonaghan, KG\n\nMostafavi, R\n\nÕunap, K\n\nPlecko, B\n\nPowis, Z\n\nPurcarin, G\n\nReimand, T\n\nRiedhammer, KM\n\nSchreiber, JM\n\nSirsi, D\n\nWierenga, KJ\n\nWojcik, MH\n\nPapuc, SM\n\nSteindl, K\n\nSticht, H\n\nRauch, A\n\nBeiträge in Fachzeitschriften\nISI:000464137100010\n30664714.0\n10.1038/s41431-018-0331-z\nPMC6461771\nCYFIP2, encoding the evolutionary highly conserved cytoplasmic FMRP interacting protein 2, has previously been proposed as a candidate gene for intellectual disability and autism because of its important role linking FMRP-dependent transcription regulation and actin polymerization via the WAVE regulatory complex (WRC). Recently, de novo variants affecting the amino acid p.Arg87 of CYFIP2 were reported in four individuals with epileptic encephalopathy. We here report 12 independent patients harboring a variety of de novo variants in CYFIP2 broadening the molecular and clinical spectrum of a novel CYFIP2-related neurodevelopmental disorder. Using trio whole-exome or -genome sequencing, we identified 12 independent patients carrying a total of eight distinct de novo variants in CYFIP2 with a shared phenotype of intellectual disability, seizures, and muscular hypotonia. We detected seven different missense variants, of which two occurred recurrently (p.(Arg87Cys) and p.(Ile664Met)), and a splice donor variant in the last intron for which we showed exon skipping in the transcript. The latter is expected to escape nonsense-mediated mRNA decay resulting in a truncated protein. Despite the large spacing in the primary structure, the variants spatially cluster in the tertiary structure and are all predicted to weaken the interaction with WAVE1 or NCKAP1 of the actin polymerization regulating WRC-complex. Preliminary genotype-phenotype correlation indicates a profound phenotype in p.Arg87 substitutions and a more variable phenotype in other alterations. This study evidenced a variety of de novo variants in CYFIP2 as a novel cause of mostly severe intellectual disability with seizures and muscular hypotonia.\n\nPlecko, Barbara\n\n\n"
},
{
"text": "\n176125\nLow cardiac lipolysis reduces mitochondrial fission and prevents lipotoxic heart dysfunction in Perilipin 5 mutant mice.\n\nKolleritsch, S\n\nKien, B\n\nSchoiswohl, G\n\nDiwoky, C\n\nSchreiber, R\n\nHeier, C\n\nMaresch, LK\n\nSchweiger, M\n\nEichmann, TO\n\nStryeck, S\n\nKrenn, P\n\nTomin, T\n\nSchittmayer, M\n\nKolb, D\n\nRülicke, T\n\nHoefler, G\n\nWolinski, H\n\nMadl, T\n\nBirner-Gruenberger, R\n\nHaemmerle, G\n\nBeiträge in Fachzeitschriften\nISI:000515095600019\n31166588.0\n10.1093/cvr/cvz119\nPMC7338219\nLipotoxic cardiomyopathy in diabetic and obese patients typically encompasses increased cardiac fatty acid (FA) uptake eventually surpassing the mitochondrial oxidative capacity. Lowering FA utilization via inhibition of lipolysis represents a strategy to counteract the development of lipotoxic heart dysfunction. However, defective cardiac triacylglycerol (TAG) catabolism and FA oxidation in humans (and mice) carrying mutated ATGL alleles provokes lipotoxic heart dysfunction questioning a therapeutic approach to decrease cardiac lipolysis. Interestingly, decreased lipolysis via cardiac overexpression of Perilipin 5 (Plin5), a binding partner of ATGL, is compatible with normal heart function and lifespan despite massive cardiac lipid accumulation. Herein, we decipher mechanisms that protect Plin5 transgenic mice from the development of heart dysfunction.\n We generated mice with cardiac-specific overexpression of Plin5 encoding a serine-155 to alanine exchange (Plin5-S155A) of the protein kinase A phosphorylation site, which has been suggested as a prerequisite to stimulate lipolysis and may play a crucial role in the preservation of heart function. Plin5-S155A mice showed a substantial increase in cardiac TAG and ceramide levels, which was comparable to mice overexpressing non-mutated Plin5. Lipid accumulation was compatible with normal heart function even under mild stress. Plin5-S155A mice showed reduced cardiac FA oxidation but normal ATP production and changes in the Plin5-S155A phosphoproteome compared to Plin5 transgenic mice. Interestingly, mitochondrial recruitment of dynamin-related protein 1 (Drp1) was markedly reduced in cardiac muscle of Plin5-S155A and Plin5 transgenic mice accompanied by decreased phosphorylation of mitochondrial fission factor, a mitochondrial receptor of Drp1.\n This study suggests that low cardiac lipolysis is associated with reduced mitochondrial fission and may represent a strategy to combat the development of lipotoxic heart dysfunction.\n © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.\n\nBirner-Grünberger, Ruth\n\nHöfler, Gerald\n\nKolb, Dagmar\n\nMadl, Tobias\n\nTomin, Tamara\n\n\n"
},
{
"text": "\n182695\nLevosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.\n\nPapp, Z\n\nAgostoni, P\n\nAlvarez, J\n\nBettex, D\n\nBouchez, S\n\nBrito, D\n\nČerný, V\n\nComin-Colet, J\n\nCrespo-Leiro, MG\n\nDelgado, JF\n\nÉdes, I\n\nEremenko, AA\n\nFarmakis, D\n\nFedele, F\n\nFonseca, C\n\nFruhwald, S\n\nGirardis, M\n\nGuarracino, F\n\nHarjola, VP\n\nHeringlake, M\n\nHerpain, A\n\nHeunks, LMA\n\nHusebye, T\n\nIvancan, V\n\nKarason, K\n\nKaul, S\n\nKivikko, M\n\nKubica, J\n\nMasip, J\n\nMatskeplishvili, S\n\nMebazaa, A\n\nNieminen, MS\n\nOliva, F\n\nPapp, JG\n\nParissis, J\n\nParkhomenko, A\n\nPõder, P\n\nPölzl, G\n\nReinecke, A\n\nRicksten, SE\n\nRiha, H\n\nRudiger, A\n\nSarapohja, T\n\nSchwinger, RHG\n\nToller, W\n\nTritapepe, L\n\nTschöpe, C\n\nWikström, G\n\nLewinski, DV\n\nVrtovec, B\n\nPollesello, P\n\nBeiträge in Fachzeitschriften\nISI:000563273900002\n32639325.0\n10.1097/FJC.0000000000000859\nPMC7340234\nLevosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.\n\nFruhwald, Sonja\n\nToller, Wolfgang\n\nvon Lewinski, Dirk\n\n\n"
},
{
"text": "\n183518\nPulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome : Results From a Prospective, Single-Center, Clinicopathologic Case Series.\n\nLax, SF\n\nSkok, K\n\nZechner, P\n\nKessler, HH\n\nKaufmann, N\n\nKoelblinger, C\n\nVander, K\n\nBargfrieder, U\n\nTrauner, M\n\nBeiträge in Fachzeitschriften\nISI:000567080900009\n32422076.0\n10.7326/M20-2566\nPMC7249507\nCoronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.\n To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.\n Prospective autopsy study.\n Single pathology department.\n 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).\n Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.\n Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.\n The sample was small.\n COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory and imaging studies, and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.\n None.\n\nKessler, Harald\n\n\n"
},
{
"text": "\n183789\nHematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome.\n\nWolska-Kusnierz, B\n\nPastorczak, A\n\nFendler, W\n\nWakulinska, A\n\nDembowska-Baginska, B\n\nHeropolitanska-Pliszka, E\n\nPiątosa, B\n\nPietrucha, B\n\nKałwak, K\n\nUssowicz, M\n\nPieczonka, A\n\nDrabko, K\n\nLejman, M\n\nKoltan, S\n\nGozdzik, J\n\nStyczynski, J\n\nFedorova, A\n\nMiakova, N\n\nDeripapa, E\n\nKostyuchenko, L\n\nKrenova, Z\n\nHlavackova, E\n\nGennery, AR\n\nSykora, KW\n\nGhosh, S\n\nAlbert, MH\n\nBalashov, D\n\nEapen, M\n\nSvec, P\n\nSeidel, MG\n\nKilic, SS\n\nTomaszewska, A\n\nWiesik-Szewczyk, E\n\nKreins, A\n\nGreil, J\n\nBuechner, J\n\nLund, B\n\nGregorek, H\n\nChrzanowska, K\n\nMlynarski, W\n\nBeiträge in Fachzeitschriften\nISI:000617323400025\n33082212.0\n10.1158/1078-0432.CCR-20-2574\nNone\nNijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematologic malignancies.\n We describe the natural history of NBS, including cancer incidence, risk of death, and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency.\n Among 241 patients with NBS enrolled in the study from 11 countries, 151 (63.0%) patients were diagnosed with cancer. Incidence rates for primary and secondary cancer, tumor characteristics, and risk factors affecting overall survival (OS) were estimated. The cumulative cancer incidence was 40.21% ± 3.5% and 77.78% ± 3.4% at 10 years and 20 years of follow-up, respectively. Most of the tumors n = 95 (62.9%) were non-Hodgkin lymphomas. Overall, 20 (13.2%) secondary malignancies occurred at a median age of 18 (interquartile range, 13.7-21.5) years. The probability of 20-year overall survival (OS) for the whole cohort was 44.6% ± 4.5%. Patients who developed cancer had a shorter 20-year OS than those without malignancy (29.6% vs. 86.2%; P < 10-5). A total of 49 patients with NBS underwent HSCT, including 14 patients transplanted before malignancy. Patients with NBS with diagnosed cancer who received HSCT had higher 20-year OS than those who did not (42.7% vs. 30.3%; P = 0.038, respectively). In the group of patients who underwent preemptive transplantation, only 1 patient developed cancer, which is 6.7 times lower as compared with nontransplanted patients [incidence rate ratio 0.149 (95% confidence interval, 0.138-0.162); P < 0.0001].\n There is a beneficial effect of HSCT on the long-term survival of patients with NBS transplanted in their first complete remission of cancer.\n ©2020 American Association for Cancer Research.\n\nSeidel, Markus\n\n\n"
}
]
}