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"text": "\n139840\nLymphocyte-to-monocyte ratio: a novel marker for critical limb ischemia in PAOD patients.\n\nGary, T\n\nPichler, M\n\nBelaj, K\n\nEller, P\n\nHafner, F\n\nGerger, A\n\nBrodmann, M\n\nBeiträge in Fachzeitschriften\nISI:000345460000011\n25359092.0\n10.1111/ijcp.12495\nNone\nThe lymphocyte-to-monocyte ratio (LMR) is easily determined from the white blood cell count. Lymphocytes were previously investigated as a part of the neutrophil-to-lymphocyte ratio (NLR) in patients with atherosclerotic disease and an elevated NLR was negatively associated with cardiovascular endpoints. As monocytes play a leading role in the progression of atherosclerosis, especially in peripheral arterial occlusive disease (PAOD), we investigated LMR and its association with critical limb ischemia and other vascular endpoints in PAOD patients.\n We evaluated 2121 PAOD patients treated at our institution from 2005 to 2010. LMR was calculated and the cohort was divided into tertiles according to the LMR. An optimal cut-off value for the continuous LMR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI. In our cohort occurrence of CLI decreased significantly with an increase in LMR. An LMR of 3.1 was identified as an optimal cut-off. Two groups were categorized, one with 1021 patients (LMR < 3.1) and a second one with 1100 patients (LMR ≥ 3.1). CLI was more frequent in LMR < 3.1 patients [426 (41.7%)] than in LMR ≥ 3.1 patients [254 (23.1%)] (p < 0.001), as was also the case with prior myocardial infarction [60 (9.5%) vs. 35 (3.2%), p = 0.003] and congestive heart failure [136 (13.3%) vs. 66 (6.0%), p < 0.001). As to inflammatory parameters, C-reactive protein [median 9.0 mg/l (4.0-30.0) vs. median 4.0 mg/l (2.0-8.0)] and fibrinogen (median 438 mg/dl (350-563) vs. 372 mg/dl (316-459.5)] also differed significantly in the two patient groups (both p < 0.001). A LMR < 3.1 was associated with an odds ratio (OR) of 2.0 (95% CI 1.8-2.2, p < 0.001) for CLI, even after adjustment for other vascular risk factors.\n A decreased LMR is significantly associated with a high risk for CLI and other vascular endpoints. The LMR is an easily determinable, broadly available and inexpensive marker that could be used to identify patients at high risk for vascular endpoints.\n © 2014 John Wiley & Sons Ltd.\n\nBrodmann, Marianne\n\nEller, Philipp\n\nGary, Thomas\n\nGerger, Armin\n\nHafner, Franz\n\nPichler, Martin\n\n\n"
},
{
"text": "\n142449\nLong-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia.\n\nReiter, E\n\nGreinix, HT\n\nKeil, F\n\nBrugger, S\n\nRabitsch, W\n\nSchulenburg, A\n\nMannhalter, C\n\nSchwarzinger, I\n\nWorel, N\n\nVolc-Platzer, B\n\nFischer, G\n\nDieckmann, K\n\nHinterberger, W\n\nSchneider, B\n\nHaas, OA\n\nGeissler, K\n\nKalhs, P\n\nBeiträge in Fachzeitschriften\nISI:000084007900003\n10602894.0\n10.1007/s002770050547\nNone\nBetween January 1983 and December 1997, 88 patients (36 female, 52 male, median age 37 years, range 19-57) with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) at the University Hospital of Vienna. Sixty patients were in chronic phase, 18 in accelerated phase, and ten in blast crisis. Marrow donors were HLA-identical siblings for 64 patients (BM 58, PBSC 6), 2-antigen-mismatched related donors (RD) for two, HLA-identical unrelated donors (URD) for 17, and 1-antigen-mismatched URD for five. The median time from diagnosis to BMT was 22 months (range 2-91), and 63 patients had received prior interferon (IFN)-alpha therapy, 46 (73%) for more than 6 months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation (TBI) in 71 patients and CY and busulfan (BU) in 16. One patient received etoposide and TBI. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) was given to 12 patients, MTX and cyclosporin A (CSA) to 67, CSA alone to four, and CSA and methylprednisolone to five. Durable engraftment was documented in 80 of 82 patients (98%). As of December 31, 1997, 52 patients (59%) were alive, 38 (58%) after sibling transplantation with a median observation time of 73 months and 14 (64%) after URD transplantation with a median observation time of 12 months. Probability of overall survival is 59%, for patients undergoing transplantation in chronic phase and 44% for patients undergoing transplantation in advanced stage CML. Probability of disease-free survival (DFS) after sibling and URD BMT is 55% and 59%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 32% both after RD and after URD transplantation. Acute GVHD occurred in 53 of 80 evaluable patients (66%), consisting of grade III or IV in 14 patients (18%). Chronic GVHD developed in 40 of 63 eligible patients (63%), including extensive disease in 26 patients (41%). Thus, sibling and URD BMT offer high cure rates with acceptable toxicity to patients with CML.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n149395\nIncreased S100A4 expression in the vasculature of human COPD lungs and murine model of smoke-induced emphysema.\n\nReimann, S\n\nFink, L\n\nWilhelm, J\n\nHoffmann, J\n\nBednorz, M\n\nSeimetz, M\n\nDessureault, I\n\nTroesser, R\n\nGhanim, B\n\nKlepetko, W\n\nSeeger, W\n\nWeissmann, N\n\nKwapiszewska, G\n\nBeiträge in Fachzeitschriften\nISI:000363085700001\n26483185.0\n10.1186/s12931-015-0284-5\nPMC4612429\nChronic obstructive lung disease (COPD) is a common cause of death in industrialized countries often induced by exposure to tobacco smoke. A substantial number of patients with COPD also suffer from pulmonary hypertension that may be caused by hypoxia or other hypoxia-independent stimuli - inducing pulmonary vascular remodeling. The Ca(2+) binding protein, S100A4 is known to play a role in non-COPD-driven vascular remodeling of intrapulmonary arteries. Therefore, we have investigated the potential involvement of S100A4 in COPD induced vascular remodeling.\n Lung tissue was obtained from explanted lungs of five COPD patients and five non-transplanted donor lungs. Additionally, mice lungs of a tobacco-smoke-induced lung emphysema model (exposure for 3 and 8 month) and controls were investigated. Real-time RT-PCR analysis of S100A4 and RAGE mRNA was performed from laser-microdissected intrapulmonary arteries. S100A4 immunohistochemistry was semi-quantitatively evaluated. Mobility shift assay and siRNA knock-down were used to prove hypoxia responsive elements (HRE) and HIF binding within the S100A4 promoter.\n Laser-microdissection in combination with real-time PCR analysis revealed higher expression of S100A4 mRNA in intrapulmonary arteries of COPD patients compared to donors. These findings were mirrored by semi-quantitative analysis of S100A4 immunostaining. Analogous to human lungs, in mice with tobacco-smoke-induced emphysema an up-regulation of S100A4 mRNA and protein was observed in intrapulmonary arteries. Putative HREs could be identified in the promoter region of the human S100A4 gene and their functionality was confirmed by mobility shift assay. Knock-down of HIF1/2 by siRNA attenuated hypoxia-dependent increase in S100A4 mRNA levels in human primary pulmonary artery smooth muscle cells. Interestingly, RAGE mRNA expression was enhanced in pulmonary arteries of tobacco-smoke exposed mice but not in pulmonary arteries of COPD patients.\n As enhanced S100A4 expression was observed in remodeled intrapulmonary arteries of COPD patients, targeting S100A4 could serve as potential therapeutic option for prevention of vascular remodeling in COPD patients.\n\nKwapiszewska-Marsh, Grazyna\n\n\n"
},
{
"text": "\n168356\nSelf-reported perinatal depressive symptoms and postnatal symptom severity after treatment with antidepressants in pregnancy: a cross-sectional study across 12 European countries using the Edinburgh Postnatal Depression Scale.\n\nLupattelli, A\n\nTwigg, MJ\n\nZagorodnikova, K\n\nMoretti, ME\n\nDrozd, M\n\nPanchaud, A\n\nRieutord, A\n\nJuraski, RG\n\nOdalovic, M\n\nKennedy, D\n\nRudolf, G\n\nJuch, H\n\nNordeng, H\n\nBeiträge in Fachzeitschriften\nISI:000434801300001\n29922092.0\n10.2147/CLEP.S156210\nPMC5997125\nThis study aimed at exploring the prevalence of self-reported antenatal and postnatal depressive symptoms by severity across multiple countries and the association between antidepressant treatment in pregnancy and postnatal symptom severity.\n This was a multinational web-based study conducted across 12 European countries (n=8069). Uniform data collection was ensured via an electronic questionnaire. Pregnant women at any gestational week and mothers of children with <1 year of age could participate. We used the Edinburgh Postnatal Depression Scale (EPDS) to measure the prevalence of antenatal and postnatal depressive symptoms according to severity, which were corrected by survey weight adjustment (descriptive analysis). Within mothers with a psychiatric disorder (n=173), we estimated the association between antidepressant treatment in pregnancy and postnatal depressive symptom severity, as standardized EPDS mean scores, via the inverse probability of treatment weight (association analysis).\n In the descriptive analysis (n=8069), the period prevalence of moderate-to-very severe depressive symptoms was higher in the western and eastern regions relative to the northern region, both in the antenatal period (6.8%-7.5% vs 4.3%) and in the postnatal period (7.6% vs 4.7%). One in two mothers with psychiatric disorders used an antidepressant in pregnancy (86 of 173). In the association analysis, women medicated at any time during pregnancy (adjusted β=-0.34, 95% confidence interval [CI] =-0.66, -0.02) had a significant postnatal symptom severity reduction compared with the nonmedicated counterpart. This effect was larger (β=-0.74, 95% CI =-1.24, -0.24) when the analysis was restricted to mothers within 6 months after childbirth.\n The prevalence of self-reported antenatal and postnatal depressive symptoms differs across European countries. Among women with psychiatric disorders, those who had been on treatment with antidepressants during pregnancy were less likely to report postnatal depressive symptoms, particularly within the 6-month period after childbirth, compared with the nonmedicated counterpart.\n\nJuch, Herbert\n\n\n"
},
{
"text": "\n168610\nThe European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology guidelines for the management of patients with cervical cancer.\n\nCibula, D\n\nPötter, R\n\nPlanchamp, F\n\nAvall-Lundqvist, E\n\nFischerova, D\n\nHaie Meder, C\n\nKöhler, C\n\nLandoni, F\n\nLax, S\n\nLindegaard, JC\n\nMahantshetty, U\n\nMathevet, P\n\nMcCluggage, WG\n\nMcCormack, M\n\nNaik, R\n\nNout, R\n\nPignata, S\n\nPonce, J\n\nQuerleu, D\n\nRaspagliesi, F\n\nRodolakis, A\n\nTamussino, K\n\nWimberger, P\n\nRaspollini, MR\n\nBeiträge in Fachzeitschriften\nISI:000437110000011\n29728273.0\n10.1016/j.radonc.2018.03.003\nNone\nDespite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer.\n The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide.\n The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives.\n The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.\n Copyright © 2018 European Society for Gynaecological Oncology, European Society for Radiotherapy and Oncology, and the European Society of Pathology. Published by Elsevier B.V. All rights reserved.\n\nTamussino, Karl\n\n\n"
},
{
"text": "\n183436\nGenetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.\n\nHofer, E\n\nRoshchupkin, GV\n\nAdams, HHH\n\nKnol, MJ\n\nLin, H\n\nLi, S\n\nZare, H\n\nAhmad, S\n\nArmstrong, NJ\n\nSatizabal, CL\n\nBernard, M\n\nBis, JC\n\nGillespie, NA\n\nLuciano, M\n\nMishra, A\n\nScholz, M\n\nTeumer, A\n\nXia, R\n\nJian, X\n\nMosley, TH\n\nSaba, Y\n\nPirpamer, L\n\nSeiler, S\n\nBecker, JT\n\nCarmichael, O\n\nRotter, JI\n\nPsaty, BM\n\nLopez, OL\n\nAmin, N\n\nvan der Lee, SJ\n\nYang, Q\n\nHimali, JJ\n\nMaillard, P\n\nBeiser, AS\n\nDeCarli, C\n\nKarama, S\n\nLewis, L\n\nHarris, M\n\nBastin, ME\n\nDeary, IJ\n\nVeronica Witte, A\n\nBeyer, F\n\nLoeffler, M\n\nMather, KA\n\nSchofield, PR\n\nThalamuthu, A\n\nKwok, JB\n\nWright, MJ\n\nAmes, D\n\nTrollor, J\n\nJiang, J\n\nBrodaty, H\n\nWen, W\n\nVernooij, MW\n\nHofman, A\n\nUitterlinden, AG\n\nNiessen, WJ\n\nWittfeld, K\n\nBülow, R\n\nVölker, U\n\nPausova, Z\n\nBruce Pike, G\n\nMaingault, S\n\nCrivello, F\n\nTzourio, C\n\nAmouyel, P\n\nMazoyer, B\n\nNeale, MC\n\nFranz, CE\n\nLyons, MJ\n\nPanizzon, MS\n\nAndreassen, OA\n\nDale, AM\n\nLogue, M\n\nGrasby, KL\n\nJahanshad, N\n\nPainter, JN\n\nColodro-Conde, L\n\nBralten, J\n\nHibar, DP\n\nLind, PA\n\nPizzagalli, F\n\nStein, JL\n\nThompson, PM\n\nMedland, SE\n\nENIGMA consortium\n\nSachdev, PS\n\nKremen, WS\n\nWardlaw, JM\n\nVillringer, A\n\nvan Duijn, CM\n\nGrabe, HJ\n\nLongstreth, WT\n\nFornage, M\n\nPaus, T\n\nDebette, S\n\nArfan Ikram, M\n\nSchmidt, H\n\nSchmidt, R\n\nSeshadri, S\n\nBeiträge in Fachzeitschriften\nISI:000573752500003\n32963231.0\n10.1038/s41467-020-18367-y\nPMC7508833\nCortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22, 24 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.\n\nHofer, Edith\n\nPirpamer, Lukas\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n17132\nKeratan sulphate levels in mucopolysaccharidoses and mucolipidoses.\n\nTomatsu, S\n\nOkamura, K\n\nMaeda, H\n\nTaketani, T\n\nCastrillon, SV\n\nGutierrez, MA\n\nNishioka, T\n\nFachel, AA\n\nOrii, KO\n\nGrubb, JH\n\nCooper, A\n\nThornley, M\n\nWraith, E\n\nBarrera, LA\n\nLaybauer, LS\n\nGiugliani, R\n\nSchwartz, IV\n\nFrenking, GS\n\nBeck, M\n\nKircher, SG\n\nPaschke, E\n\nYamaguchi, S\n\nUllrich, K\n\nHaskins, M\n\nIsogai, K\n\nSuzuki, Y\n\nOrii, T\n\nKondo, N\n\nCreer, M\n\nOkuyama, T\n\nTanaka, A\n\nNoguchi, A\n\nBeiträge in Fachzeitschriften\nISI:000228973600010\n15877208.0\n10.1007/s10545-005-5673-3\nNone\nThe mucopolysaccharidoses (MPS) is characterized by accumulation of glycosaminoglycans (GAGs), and mucolipidosis (ML) by accumulation of GAGs and sphingolipids. Each type of MPS accumulates specific GAGs. The lysosomal enzymes N-acetylgalactosamine-6-sulphate sulphatase and beta-galactosidase involve the stepwise degradation of keratan sulphate (KS). Deficiency of these enzymes results in elevation of KS levels in the body fluids and in tissues, leading to MPS IV disease. In this study, we evaluated blood and urine KS levels in types of MPS and ML other than MPS IV. Eighty-five plasma samples came from MPS I (n = 18), MPS II (n = 28), MPS III (n = 20), MPS VI (n = 3), MPS VII (n = 5) and ML (n = 11) patients while 127 urine samples came from MPS I (n = 34), MPS II (n = 34), MPS III (n = 32), MPS VI (n = 7), MPS VII (n = 9) and ML (n = 11) patients. KS levels were determined using the ELISA method. Plasma KS levels varied with age in both control and patient populations. In all age groups, the mean values of plasma KS in MPS and ML patients were significantly higher than those in the age-matched controls. Plasma KS values in four newborn patients were above the mean + 2SD of the age-matched controls (mean, 41 ng/ml). Overall, 85.9% of individual values in non-type IV MPS and ML patients were above the mean + 2SD of the age-matched controls. For urine KS levels, 24.4% of individual values in patients were above the mean + 2SD of the age-matched controls. In conclusion, KS in blood is elevated in each type of non-type IV MPS examined, in contrast to the conventional understanding. This finding suggests that measurement of KS level provides a new diagnostic biomarker in a wide variety of mucopolysaccharidoses and mucolipidoses in addition to MPS IV.\n\n\n"
},
{
"text": "\n130448\nAnterior cruciate ligament repair augmented with a synthetic intraarticular ligament. The importance of the through-the-condyle augmentation technique for postoperative rehabilitation\n\nSeitz, H\n\nWielke, B\n\nSchlenz, I\n\nPichl, W\n\nVecsei, V\n\nBeiträge in Fachzeitschriften\nISI:A1996TT08900003\n8717169.0\nNone\nNone\nThe rupture of the anterior cruciate ligament (ACL) near its femoral origin is a common injury of the knee and can lead to lesions of the meniscus due to instability and to early gonarthrosis. One procedure applied in current orthopaedic practice to prevent such impairment of knee joint function is ACL repair reinforced with a synthetic intraarticular ligament. In this study we used twelve knees of cadavers and after sectioning the ACL in each repaired it according the Marshall technique with USP 1 PDS II sutures. We augmented the repair in each case with a 3-mm PET (Trevira hochfest) band inserted by the through-the-condyle (TTC) procedure and attached without preload to the femoral and tibial condyle with a 4-mm staple. We then measured the length of the ACL, the length of the Marshall sutures-ACL complex, the partial lengths, and the deviation angles and adherence-friction force of the 3-mm PET augmentation device, and applied the law of Hooke to calculate the load-sharing between the USP 1 PDS II sutures-ACL complex and the 3-mm PET band and between the ACL and the 3-mm PET band, respectively. We also evaluated the load on the femoral and the tibial fixation of the augmentation device. The results showed that the 3-mm PET band took over 60% of an externally applied load on the knee during the hypothetic period of ACL healing and 27% of the force acting on the knee thereafter. It was calculated that a maximum of 75% of the load taken over by the augmentation device was at the tibial staple and only up to 45% of the force at the femoral one. With due consideration for the requirement for absolute protection ("stress shielding") of the healing ACL but also for the aim of early postoperative accelerated functional rehabilitation without casts, splints or other restrictions of joint movement, we believe that a pretensioned 3-mm PET band is the best choice, since augmentation without preload cannot fulfil these requirements.\n\n\n"
},
{
"text": "\n132369\nTryptophan breakdown is increased in euthymic overweight individuals with bipolar disorder: a preliminary report.\n\nReininghaus, EZ\n\nMcIntyre, RS\n\nReininghaus, B\n\nGeisler, S\n\nBengesser, SA\n\nLackner, N\n\nHecht, K\n\nBirner, A\n\nKattnig, F\n\nUnterweger, R\n\nKapfhammer, HP\n\nZelzer, S\n\nFuchs, D\n\nMangge, H\n\nBeiträge in Fachzeitschriften\nISI:000337517600009\n24330408.0\n10.1111/bdi.12166\nNone\nIndividuals with bipolar disorder (BD) are disproportionately affected by symptoms of being overweight and metabolic syndrome when compared to the general population. The pertinence of this observation is underscored by observations that excess weight is associated with a more complex illness presentation, course, and outcome in BD. We present the first preliminary report of our BIPFAT study, which explored shared hypothesized pathophysiological pathways between being overweight and having BD.\n We investigated the tryptophan-kynurenine metabolism pathway as a proxy of dysregulated inflammatory homeostasis in euthymic, overweight individuals with BD (n = 78) compared to healthy controls (n = 156).\n Both blood kynurenine concentrations and the kynurenine to tryptophan ratio [(Kyn:Trp); an estimate of tryptophan breakdown] were significantly higher in the total sample of euthymic patients with BD, with greater increases noted in both parameters in the subsample of overweight patients with BD. When compared to controls, peripheral neopterin concentrations were significantly lower. Within the BD group, there were also significant between-group differences in neopterin concentrations, with higher levels in those who were overweight and in subjects with BD in the later stages of illness compared to earlier stages.\n Increased tryptophan breakdown, as well as neopterin levels in BD, may be an indirect mediator of immune-mediated inflammation. In BD, this may account for the high prevalence of medical comorbidities and increased mortality. The observation of increased kynurenine levels and Kyn:Trp, and altered circulating neopterin levels provides indirect evidence of increased activity of tryptophan-degrading indoleamine 2, -dioxygenase in euthymic individuals with BD, underscoring the role of inflammatory mediators as a causative and/or consequent factor. More robust abnormalities in the overweight subsample underscore the additional inflammatory burden of medical comorbidity and suggest a shared pathophysiology as well as a mechanism mediating BD and cardiovascular disease.\n © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nKapfhammer, Hans-Peter\n\nMangge, Harald\n\nReininghaus, Eva\n\nUnterweger, Renate\n\nZelzer, Sieglinde\n\n\n"
},
{
"text": "\n140377\nDrug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial.\n\nZeller, T\n\nBaumgartner, I\n\nScheinert, D\n\nBrodmann, M\n\nBosiers, M\n\nMicari, A\n\nPeeters, P\n\nVermassen, F\n\nLandini, M\n\nSnead, DB\n\nKent, KC\n\nRocha-Singh, KJ\n\nIN.PACT DEEP Trial Investigators\n\nBeiträge in Fachzeitschriften\nISI:000343470400005\n25301459.0\n10.1016/j.jacc.2014.06.1198\nNone\nDrug-eluting balloons (DEB) may reduce infrapopliteal restenosis and reintervention rates versus percutaneous transluminal angioplasty (PTA) and improve wound healing/limb preservation.\n The goal of this clinical trial was to assess the efficacy and safety of IN.PACT Amphirion drug-eluting balloons (IA-DEB) compared to PTA for infrapopliteal arterial revascularization in patients with critical limb ischemia (CLI).\n Within a prospective, multicenter, randomized, controlled trial with independent clinical event adjudication and angiographic and wound core laboratories 358 CLI patients were randomized 2:1 to IA-DEB or PTA. The 2 coprimary efficacy endpoints through 12 months were clinically driven target lesion revascularization (CD-TLR) and late lumen loss (LLL). The primary safety endpoint through 6 months was a composite of all-cause mortality, major amputation, and CD-TLR.\n Clinical characteristics were similar between the 2 groups. Significant baseline differences between the IA-DEB and PTA arms included mean lesion length (10.2 cm vs. 12.9 cm; p = 0.002), impaired inflow (40.7% vs. 28.8%; p = 0.035), and previous target limb revascularization (32.2% vs. 21.8%; p = 0.047). Primary efficacy results of IA-DEB versus PTA were CD-TLR of 9.2% versus 13.1% (p = 0.291) and LLL of 0.61 ± 0.78 mm versus 0.62 ± 0.78 mm (p = 0.950). Primary safety endpoints were 17.7% versus 15.8% (p = 0.021) and met the noninferiority hypothesis. A safety signal driven by major amputations through 12 months was observed in the IA-DEB arm versus the PTA arm (8.8% vs. 3.6%; p = 0.080).\n In patients with CLI, IA-DEB had comparable efficacy to PTA. While primary safety was met, there was a trend towards an increased major amputation rate through 12 months compared to PTA. (Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733).\n Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.\n\nBrodmann, Marianne\n\n\n"
},
{
"text": "\n149655\nVasoactive Therapy in Systemic Sclerosis: Real-life Therapeutic Practice in More Than 3000 Patients.\n\nMoinzadeh, P\n\nRiemekasten, G\n\nSiegert, E\n\nFierlbeck, G\n\nHenes, J\n\nBlank, N\n\nMelchers, I\n\nMueller-Ladner, U\n\nFrerix, M\n\nKreuter, A\n\nTigges, C\n\nLahner, N\n\nSusok, L\n\nGuenther, C\n\nZeidler, G\n\nPfeiffer, C\n\nWorm, M\n\nKarrer, S\n\nAberer, E\n\nBretterklieber, A\n\nGenth, E\n\nSimon, JC\n\nDistler, JH\n\nHein, R\n\nSchneider, M\n\nSeitz, CS\n\nHerink, C\n\nSteinbrink, K\n\nSárdy, M\n\nVarga, R\n\nMensing, H\n\nMensing, C\n\nLehmann, P\n\nNeeck, G\n\nFiehn, C\n\nWeber, M\n\nGoebeler, M\n\nBurkhardt, H\n\nBuslau, M\n\nAhmadi-Simab, K\n\nHimsel, A\n\nJuche, A\n\nKoetter, I\n\nKuhn, A\n\nSticherling, M\n\nHellmich, M\n\nKuhr, K\n\nKrieg, T\n\nEhrchen, J\n\nSunderkoetter, C\n\nHunzelmann, N\n\nGerman Network for Systemic Scleroderma\n\nBeiträge in Fachzeitschriften\nISI:000367459200011\n26568599.0\n10.3899/jrheum.150382\nNone\nVasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry.\n The data of 3248 patients with SSc were analyzed.\n Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005.\n These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed.\n\n\n"
},
{
"text": "\n155694\nChoosing Wisely: assessment of current US top five list recommendations' trustworthiness using a pragmatic approach.\n\nHorvath, K\n\nSemlitsch, T\n\nJeitler, K\n\nAbuzahra, ME\n\nPosch, N\n\nDomke, A\n\nSiebenhofer, A\n\nBeiträge in Fachzeitschriften\nISI:000391303200070\n27855098.0\n10.1136/bmjopen-2016-012366\nPMC5073530\nIdentification of sufficiently trustworthy top 5 list recommendations from the US Choosing Wisely campaign.\n Not applicable.\n All top 5 list recommendations available from the American Board of Internal Medicine Foundation website.\n Compilation of US top 5 lists and search for current German highly trustworthy (S3) guidelines. Extraction of guideline recommendations, including grade of recommendation (GoR), for suggestions comparable to top 5 list recommendations. For recommendations without guideline equivalents, the methodological quality of the top 5 list development process was assessed using criteria similar to that used to judge guidelines, and relevant meta-literature was identified in cited references. Judgement of sufficient trustworthiness of top 5 list recommendations was based either on an 'A' GoR of guideline equivalents or on high methodological quality and citation of relevant meta-literature.\n 412 top 5 list recommendations were identified. For 75 (18%), equivalents were found in current German S3 guidelines. 44 of these recommendations were associated with an 'A' GoR, or a strong recommendation based on strong evidence, and 26 had a 'B' or a 'C' GoR. No GoR was provided for 5 recommendations. 337 recommendations had no equivalent in the German S3 guidelines. The methodological quality of the development process was high and relevant meta-literature was cited for 87 top 5 list recommendations. For a further 36, either the methodological quality was high without any meta-literature citations or meta-literature citations existed but the methodological quality was lacking. For the remaining 214 recommendations, either the methodological quality was lacking and no literature was cited or the methodological quality was generally unsatisfactory.\n 131 of current US top 5 list recommendations were found to be sufficiently trustworthy. For a substantial number of current US top 5 list recommendations, their trustworthiness remains unclear. Methodological requirements for developing top 5 lists are recommended.\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\nAbuzahra, Muna\n\nHorvath, Karl\n\nJeitler, Klaus\n\nPosch, Nicole\n\nSemlitsch, Thomas\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n160408\nFrom the evaluation of existing solutions to an all-inclusive package for biobanks.\n\nMüller, H\n\nMalservet, N\n\nQuinlan, P\n\nReihs, R\n\nPenicaud, M\n\nChami, A\n\nZatloukal, K\n\nDagher, G\n\nBeiträge in Fachzeitschriften\nISI:000398975200015\n28344915.0\n10.1007/s12553-016-0175-x\nPMC5346419\nThe domain of biobanking has gone through many stages and as a result there are a wide range of commercial and open source software solutions available. The utilization of these software tools requires different levels of domain and technical skills for installation, configuration and ultimate us of these biobank software tools. To compound this complexity the biobanking community are required to work together in order to share knowledge and jointly build solutions to underpin the research infrastructure. We have evaluated the available tools, described them in a catalogue (BiobankApps) and made a selection of tools available to biobanks in a reference toolbox (BIBBOX) that are use-case driven. In the BiobankApps tool catalogue, both commercial and open source software solutions related to the biobanking domain are included, classified and evaluated. The evaluation covers: 1) "user review" by an authenticated user 2) domain expert: quick analysis by BBMRI members and 3) domain expert: detailed analysis and test installation with real world data. The evaluation is paired with a survey across the more "advanced" (from a technology perspective) biobanks to investigate what tools are currently used and summarises known benefits/drawbacks of the respective packages. In the second step we recommend tools for specific use cases, and install, configure and connect these in the BIBBOX framework. This service also builds on the existing work in the United Kingdom in seeking to establish the motivations for different stakeholders to become involved and therefore assisting in prioritising the use-cases based on the level of need and support within the research community. All tools associated to a use-case are available as BIBBOX applications (technically this is achieved by docker containers), which are integrated in the BIBBOX framework with central identification and user management. In future work we plan to share the acquired knowledge with other networks, develop an Application Programmable Interface (API) for the exchange of metadata with other tool catalogues and work on an ontology for the evaluation of biobank software.\n\nMüller, Heimo\n\nReihs, Robert\n\nZatloukal, Kurt\n\n\n"
},
{
"text": "\n165017\nTreatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries: Long-Term Results of the IN.PACT SFA Randomized Trial.\n\nSchneider, PA\n\nLaird, JR\n\nTepe, G\n\nBrodmann, M\n\nZeller, T\n\nScheinert, D\n\nMetzger, C\n\nMicari, A\n\nSachar, R\n\nJaff, MR\n\nWang, H\n\nHasenbank, MS\n\nKrishnan, P\n\nIN.PACT SFA Trial Investigators\n\nBeiträge in Fachzeitschriften\nISI:000422638400012\n29326153.0\n10.1161/CIRCINTERVENTIONS.117.005891\nPMC5771683\nRandomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term.\n IN.PACT SFA is a single-blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with symptomatic (Rutherford 2-4) femoropopliteal lesions up to 18 cm in length. Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month assessments included primary patency, freedom from clinically driven target lesion revascularization, major adverse events, and functional outcomes. At 36 months, primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; log rank P<0.001). The rates of clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002) for the DCB and PTA groups, respectively. Functional outcomes were similarly improved between treatment groups even though subjects in the DCB group required significantly fewer reinterventions versus those in the PTA group (P<0.001 for target lesion revascularization, P=0.001 for target vessel revascularization). There were no device- or procedure-related deaths as adjudicated by an independent Clinical Events Committee.\n Three-year results demonstrate a durable and superior treatment effect among patients treated with DCB versus standard PTA, with significantly higher primary patency and lower clinically driven target lesion revascularization, resulting in similar functional improvements with reduced need for repeat interventions.\n URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for IN.PACT SFA phase II in the United States.\n © 2018 The Authors.\n\nBrodmann, Marianne\n\n\n"
},
{
"text": "\n168656\nWhole-Body Lung Function Test-Derived Outcome Predictors in Allogenic Stem Cell Transplantation.\n\nScheidl, S\n\nZinke-Cerwenka, W\n\nFlick, H\n\nGaal, S\n\nAvian, A\n\nGreinix, H\n\nOlschewski, H\n\nBeiträge in Fachzeitschriften\nISI:000455691600017\n30064013.0\n10.1016/j.bbmt.2018.07.036\nNone\nDespite clinical advances, late onset pulmonary complications in adult recipients of allogenic stem cell transplantation are a major cause of morbidity and mortality. Reported incidence and risk factors in the literature vary broadly and are partly contradictory. Identification of pretransplant factors associated with major complications would be helpful to define individual treatment strategies and early initiation of preventive measures. To evaluate incidence and risk factors of late onset noninfectious pulmonary complications, with special regard to small airways disease (SAD) and bronchiolitis obliterans syndrome (BOS), indicating graft-versus-host disease, following myeloablative versus nonmyeloablative allogenic stem cell transplantation. We reviewed the clinical records and assessed the course of lung function and pulmonary complications in adults who underwent allogenic stem cell transplantation for hematological malignancies between 1999 and 2015 using nonmyeloablative (n = 179) or myeloablative (n = 130) conditioning at the Division of Hematology of the Medical University of Graz. All patients underwent body plethysmography pulmonary function test (PFT), diffusion capacity for carbon monoxide, and arterial blood gas analysis before and repeatedly after transplant. SAD was defined as maximal expiratory flow at 50% and 25% of forced vital capacity <70% predicted. Ventilatory disorders and gas transfer abnormalities were common before and after allogenic stem cell transplantation, independent of conditioning regimen. SAD was common in the nonmyeloablative (34%) and myeloablative (29%) groups. The 100-day post-transplant mortality was significantly associated with reduced pretransplant total lung capacity <80%. Mortality 100 days post-transplant was significantly associated with pretransplant SAD and a pretransplant smoking history. In this subset, a smoking history was independently associated with increased mortality, with a 5-year mortality of 45% compared with 26% in never-smokers. Pretransplant SAD was not predictive for the later development of BOS. Smoking history, pretransplant restrictive PFT, and pre-existing SAD are important risk factors for death following allogenic stem cell transplantation. However, pretransplant SAD is not a predictor of long-term complications, including BOS.\n Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.\n\nAvian, Alexander\n\nFlick, Holger\n\nGreinix, Hildegard\n\nOlschewski, Horst\n\nScheidl, Stefan\n\n\n"
},
{
"text": "\n169802\nActivated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody.\n\nHeidt, T\n\nDeininger, F\n\nPeter, K\n\nGoldschmidt, J\n\nPethe, A\n\nHagemeyer, CE\n\nNeudorfer, I\n\nZirlik, A\n\nWeber, WA\n\nBode, C\n\nMeyer, PT\n\nBehe, M\n\nvon Zur Mühlen, C\n\nBeiträge in Fachzeitschriften\nISI:000289055700058\n21479193.0\n10.1371/journal.pone.0018446\nPMC3068185\nActivated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis.\n LIBS as well as an unspecific control single-chain antibody were labeled with (111)Indium ((111)In) via bifunctional DTPA ( = (111)In-LIBS/(111)In-control). Autoradiography after incubation with (111)In-LIBS on activated platelets in vitro (mean 3866 ± 28 DLU/mm(2), 4010 ± 630 DLU/mm(2) and 4520 ± 293 DLU/mm(2)) produced a significantly higher ligand uptake compared to (111)In-control (2101 ± 76 DLU/mm(2), 1181 ± 96 DLU/mm(2) and 1866 ± 246 DLU/mm(2)) indicating a specific binding to activated platelets; P<0.05. Applying these findings to an ex vivo mouse model of carotid artery thrombosis revealed a significant increase in ligand uptake after injection of (111)In-LIBS in the presence of small thrombi compared to the non-injured side, as confirmed by histology (49630 ± 10650 DLU/mm(2) vs. 17390 ± 7470 DLU/mm(2); P<0.05). These findings could also be reproduced in vivo. SPECT-CT analysis of the injured carotid artery with (111)In-LIBS resulted in a significant increase of the target-to-background ratio compared to (111)In-control (1.99 ± 0.36 vs. 1.1 ± 0.24; P < 0.01).\n Nuclear imaging with (111)In-LIBS allows the detection of platelet activation in vitro and ex vivo with high sensitivity. Using SPECT-CT, wall-adherent activated platelets in carotid arteries could be depicted in vivo. These results encourage further studies elucidating the role of activated platelets in plaque pathology and atherosclerosis and might be of interest for further developments towards clinical application.\n\nZirlik, Andreas\n\n\n"
},
{
"text": "\n176076\nImpact on the assessment of fine needle biopsy of the thyroid after the introduction of NIFTP\n\nTotsch, M\n\nSchmid, KW\n\nBeiträge in Fachzeitschriften\nISI:000472526100006\nNone\n10.1007/s00761-019-0593-2\nNone\nBackgroundThe explicit aim of the introduction of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in the 4th edition of the WHO classification of tumors of the thyroid gland (2017) was to spare patients with the diagnosis of this subgroup of encapsulated follicular variants of PTC with indolent clinical course, both overtreatment and the psychological burden of a cancer diagnosis; however, the establishment of NIFTP has deprived the characteristic nuclear features of PTC of their status as astand-alone malignancy criterion, necessitating not only aredefinition of the diagnostic criteria for PTC (WHO 2017) but also fundamental changes in the cytological assessment of thyroid FNB.Results and conclusionCytologically, PTC can nowadays only be reliably diagnosed (diagnostic groupV according to Ting etal.) if, besides the characteristic nuclear features, true papillary structures, psammoma bodies and/or aBRAF V600E mutation can be demonstrated immunohistochemically or molecular pathologically. This results in an increase of cases within the diagnostic groupIV (suspected malignancy). In this group (a)neoplasms with PTC-equivalent nuclear changes (histologically corresponding to aNIFTP or aPTC) and (b)rarely the suspicion for medullary, poorly differentiated or anaplastic carcinoma, malignant lymphomas or metastases have to be assigned. In addition, for groupIV cases the probability that amalignant tumor is diagnosed in the postoperative histological preparation is less than before (previously 60-75%, now 45-60%). The introduction of NIFTP has already resulted in areassessment of the risk of malignancy in the Bethesda classification. The Bethesda classification groupsIII (atypical with unclear significance AUS, follicular alterations with unclear significance, FLUS) andIV (follicular neoplasm, FN, suspicion of follicular neoplasm, SFN) now show avery similar risk of malignancy. As already pointed out earlier, the still existing (arbitrary) separation of these two diagnostic groups for the management of the affected patients, in particular with respect to the expectations of its role in the preoperative FNB of the thyroid gland in Germany and Austria, has to be critically called into question. By contrast, the necessary adaptation of the cytological conditions following the introduction of NIFTP can be implemented without problems in the 5-stage diagnostic scheme used by the authors.\n\n\n"
},
{
"text": "\n179969\nFXR-dependent Rubicon induction impairs autophagy in models of human cholestasis.\n\nPanzitt, K\n\nJungwirth, E\n\nKrones, E\n\nLee, JM\n\nPollheimer, M\n\nThallinger, GG\n\nKolb-Lenz, D\n\nXiao, R\n\nThorell, A\n\nTrauner, M\n\nFickert, P\n\nMarschall, HU\n\nMoore, DD\n\nWagner, M\n\nBeiträge in Fachzeitschriften\nISI:000537372900015\n32001325.0\n10.1016/j.jhep.2020.01.014\nNone\nCholestasis comprises a spectrum of liver diseases characterized by the accumulation of bile acids. Bile acids and activation of the farnesoid X receptor (FXR) can inhibit autophagy, a cellular self-digestion process necessary for cellular homeostasis and regeneration. In mice, autophagy appears to be impaired in cholestasis and induction of autophagy may reduce liver injury.\n Herein, we explored autophagy in human cholestasis in vivo and investigated the underlying molecular mechanisms in vitro. FXR chromatin immunoprecipitation-sequencing and qPCR were performed in combination with luciferase promoter studies to identify functional FXR binding targets in a human cholestatic liver sample.\n Autophagic processing appeared to be impaired in patients with cholestasis and in individuals treated with the FXR ligand obeticholic acid (OCA). In vitro, chenodeoxycholic acid and OCA inhibited autophagy at the level of autophagosome to lysosome fusion in an FXR-dependent manner. Rubicon, which inhibits autophago-lysosomal maturation, was identified as a direct FXR target that is induced in cholestasis and by FXR-agonistic bile acids. Genetic inhibition of Rubicon reversed the bile acid-induced impairment of autophagic flux. In contrast to OCA, ursodeoxycholic acid (UDCA), which is a non-FXR-agonistic bile acid, induced autophagolysosome formation independently of FXR, enhanced autophagic flux and was associated with reduced Rubicon levels.\n In models of human cholestasis, autophagic processing is impaired in an FXR-dependent manner, partly resulting from the induction of Rubicon. UDCA is a potent inducer of hepatic autophagy. Manipulating autophagy and Rubicon may represent a novel treatment concept for cholestatic liver diseases.\n Autophagy, a cellular self-cleansing process, is impaired in various forms of human cholestasis. Bile acids, which accumulate in cholestatic liver disease, induce Rubicon, a protein that inhibits proper execution of autophagy. Ursodeoxycholic acid, which is the first-line treatment option for many cholestatic liver diseases, induces hepatic autophagy along with reducing Rubicon.\n Copyright © 2020 European Association for the Study of the Liver. All rights reserved.\n\nFickert, Peter\n\nJungwirth, Emilian Rudolf\n\nKolb, Dagmar\n\nPanzitt, Katrin\n\nPollheimer, Marion\n\nTatscher, Elisabeth\n\nWagner, Martin\n\n\n"
},
{
"text": "\n183330\nAutogenous mitochondria transplantation for treatment of right heart failure.\n\nWeixler, V\n\nLapusca, R\n\nGrangl, G\n\nGuariento, A\n\nSaeed, MY\n\nCowan, DB\n\nDel Nido, PJ\n\nMcCully, JD\n\nFriehs, I\n\nBeiträge in Fachzeitschriften\nNone\n32919774.0\n10.1016/j.jtcvs.2020.08.011\nNone\nRight ventricular hypertrophy and failure are major causes of cardiac morbidity and mortality. A key event in the progression to right ventricular hypertrophy and failure is cardiomyocyte apoptosis due to mitochondrial dysfunction. We sought to determine whether localized intramyocardial injection of autologous mitochondria from healthy muscle treats heart failure.\n Mitochondria transplanted from different sources were initially tested in cultured hypertrophic cardiomyocytes. A right ventricular hypertrophy/right ventricular failure model created through banding of the pulmonary artery in immature piglets was used for treatment with autologous mitochondria (pulmonary artery banded mitochondria injected/treated n = 6) from calf muscle, versus vehicle (pulmonary artery banded vehicle injected/treated n = 6) injected into the right ventricular free-wall, and compared with sham-operated controls (sham, n = 6). Animals were followed for 8 weeks by echocardiography (free-wall thickness, contractility), and dp/dt max was measured concomitantly with cardiomyocyte hypertrophy, fibrosis, and apoptosis at study end point.\n Internalization of mitochondria and adenosine triphosphate levels did not depend on the source of mitochondria. At 4 weeks, banded animals showed right ventricular hypertrophy (sham: 0.28 ± 0.01 cm vs pulmonary artery banding: 0.4 ± 0.02 cm wall thickness; P = .001), which further increased in pulmonary artery banded mitochondria injected/treated but declined in pulmonary artery banded vehicle injected/treated (0.47 ± 0.02 cm vs 0.348 ± 0.03 cm; P = .01). Baseline contractility was not different but was significantly reduced in pulmonary artery banded vehicle injected/treated compared with pulmonary artery banded mitochondria injected/treated and so was dp/dtmax. There was a significant difference in apoptotic cardiomyocyte loss and fibrosis in sham versus hypertrophied hearts with most apoptosis in pulmonary artery banded vehicle injected/treated hearts (sham: 1 ± 0.4 vs calf muscle vs vehicle: 13 ± 1.7; P = .001 and vs pulmonary artery banded mitochondria injected/treated: 8 ± 1.9, P = .01; pulmonary artery banded vehicle injected/treated vs pulmonary artery banded mitochondria injected/treated, P = .05).\n Mitochondrial transplantation allows for prolonged physiologic adaptation of the pressure-loaded right ventricular and preservation of contractility by reducing apoptotic cardiomyocyte loss.\n Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.\n\nGrangl, Gernot\n\n\n"
},
{
"text": "\n187877\nHigh-Throughput and Site-Specific N-Glycosylation Analysis of Human Alpha-1-Acid Glycoprotein Offers a Great Potential for New Biomarker Discovery\n\nKeser, T\n\nTijardovic, M\n\nGornik, I\n\nLukic, E\n\nLauc, G\n\nGornik, O\n\nNovokmet, M\n\nBeiträge in Fachzeitschriften\nISI:000651577500001\n33493676.0\n10.1074/mcp.RA120.002433\nNone\nAlpha-1-acid glycoprotein (AGP) is an acute phase glycoprotein in blood, which is primarily synthetized in the liver and whose biological role is not completely understood. It consists of 45% carbohydrates that are present in the form of five N-linked complex glycans. AGP N-glycosylation was shown to be changed in many different diseases and some changes appear to be disease-specific, thus it has a great diagnostic and prognostic potential. However, AGP glycosylation was mainly analyzed in small cohorts and without detailed site-specific glycan information. Here, we developed a cost-effective method for a high-throughput and site-specific N-glycosylation LC-MS analysis of AGP which can be applied on large cohorts, aid in search for novel disease biomarkers and enable better understanding of AGP's role and function in health and disease. The method does not require isolation of AGP with antibodies and affinity chromatography, but AGP is enriched by acid precipitation from 5 μl of bloodplasma in a 96 well format. After trypsinization, AGP glycopeptides are purified using a hydrophilic interaction chromatography based solid-phase extraction and analyzed by RP-LC-ESI-MS. We used our method to show for the first time that AGP N-glycan profile is stable in healthy individuals (14 individuals in 3 time points), which is a requirement for evaluation of its diagnostic potential. Furthermore, we tested our method on a population including individuals with registered hyperglycemia in critical illness (59 cases and 49 controls), which represents a significantly increased risk of developing type 2 diabetes. Individuals at higher risk of diabetes presented increased N-glycan branching on AGP's second glycosylation site and lower sialylation of N-glycans on AGP's third and AGP1's fourth glycosylation site. Although this should be confirmed on a larger prospective cohort, it indicates that site-specific AGP N-glycan profile could help distinguish individuals who are at risk of type 2 diabetes.\n Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.\n\nLukic, Edita\n\n\n"
}
]
}