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"text": "\n154433\nFractional flow reserve-guided PCI versus medical therapy in stable coronary disease.\n\nDe Bruyne, B\n\nPijls, NH\n\nKalesan, B\n\nBarbato, E\n\nTonino, PA\n\nPiroth, Z\n\nJagic, N\n\nMöbius-Winkler, S\n\nMobius-Winckler, S\n\nRioufol, G\n\nWitt, N\n\nKala, P\n\nMacCarthy, P\n\nEngström, T\n\nOldroyd, KG\n\nMavromatis, K\n\nManoharan, G\n\nVerlee, P\n\nFrobert, O\n\nCurzen, N\n\nJohnson, JB\n\nJüni, P\n\nFearon, WF\n\nFAME 2 Trial Investigators\n\nBeiträge in Fachzeitschriften\nISI:000308649100005\n22924638.0\n10.1056/NEJMoa1205361\nNone\nThe preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.\n In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.\n Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary end-point event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event.\n In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.).\n\nToth-Gayor, Gabor\n\n\n"
},
{
"text": "\n181771\nThe leading role of pathology in assessing the somatic molecular alterations of cancer: Position Paper of the European Society of Pathology.\n\nMatias-Guiu, X\n\nStanta, G\n\nCarneiro, F\n\nRyska, A\n\nHoefler, G\n\nMoch, H\n\nEuropean Society of Pathology (ESP)\n\nBeiträge in Fachzeitschriften\nISI:000517704200001\n32124002.0\n10.1007/s00428-020-02757-0\nPMC7156353\nMolecular pathology is an essential part of pathology complementing conventional morphological tools to obtain a correct integrated diagnosis with appropriate assessment of prognosis and prediction of response to therapy, particularly in cancer. There is a concern about the situation of molecular pathology in some areas of Europe, namely, regarding the central role of pathologists in assessing somatic genomic alterations in cancer. In some countries, there are attempts that other laboratory medicine specialists perform the molecular analysis of somatic alterations in cancer, particularly now when next generation sequencing (NGS) is incorporated into clinical practice. In this scenario, pathologists may play just the role of "tissue providers, and other specialists may take the lead in molecular analysis. Geneticists and laboratory medicine specialists have all background and skills to perform genetic analysis of germline alterations in hereditary disorders, including familial forms of cancers. However, interpretation of somatic alterations of cancer belongs to the specific scientific domain of pathology. Pathologists are necessary to guarantee the quality of the results, for several reasons: (1) The identified molecular alterations should be interpreted in the appropriate morphologic context, since most of them are context-specific; (2) pre-analytical issues must be taken into consideration; (3) it is crucial to check the proportion of tumor cells in the sample subjected to analysis and presence of inflammatory infiltrate and necrosis should be monitored; and 4) the role of pathologists is crucial to select the most appropriate methods and to control the turnaround time in which the molecular results are delivered in the context of an integrated diagnosis. Obviously, there is the possibility of having core facilities for NGS in a hospital to perform the sequence analysis that are open to other specialties (microbiologists, geneticists), but also in this scenario, pathologists should have the lead in assessing somatic alterations of cancer. In this article, we emphasize the importance of interpreting somatic molecular alterations of the tumors in the context of morphology. In this Position Paper of the European Society of Pathology, we strongly support a central role of pathology departments in the process of analysis and interpretation of somatic molecular alterations in cancer.\n\nHöfler, Gerald\n\n\n"
},
{
"text": "\n182510\nA lean magnesium-zinc-calcium alloy ZX00 used for bone fracture stabilization in a large growing-animal model.\n\nHolweg, P\n\nBerger, L\n\nCihova, M\n\nDonohue, N\n\nClement, B\n\nSchwarze, U\n\nSommer, NG\n\nHohenberger, G\n\nvan den Beucken, JJJP\n\nSeibert, F\n\nLeithner, A\n\nLöffler, JF\n\nWeinberg, AM\n\nBeiträge in Fachzeitschriften\nISI:000558174200048\n32553919.0\n10.1016/j.actbio.2020.06.013\nNone\nOver the last decade, demand has increased for developing new, alternative materials in pediatric trauma care to overcome the disadvantages associated with conventional implant materials. Magnesium (Mg)-based alloys seem to adequately fulfill the vision of a homogeneously resorbable, biocompatible, load-bearing and functionally supportive implant. The aim of the present study is to introduce the high-strength, lean alloy Mg‒0.45Zn‒0.45Ca, in wt% (ZX00), and for the first time investigate the clinical applicability of screw osteosynthesis using this alloy that contains no rare-earth elements. The alloy was applied in a growing sheep model with osteotomized bone (simulating a fracture) and compared to a non-osteotomy control group regarding degradation behavior and fracture healing. The alloy exhibits an ultimate tensile strength of 285.7 ± 3.1 MPa, an elongation at fracture of 18.2 ± 2.1%, and a reduced in vitro degradation rate compared to alloys containing higher amounts of Zn. In vivo, no significant difference between the osteotomized bone and the control group was found regarding the change in screw volume over implantation time. Therefore, it can be concluded that the fracture healing process, including its effects on the surrounding area, has no significant influence on degradation behavior. There was also no negative influence from hydrogen-gas formation on fracture healing. Despite the proximal and distal screws showing chronologically different gas release, the osteotomy showed complete consolidation. STATEMENT OF SIGNIFICANCE: Conventional implants involve several disadvantages in pediatric trauma care. Magnesium-based alloys seem to overcome these issues as discussed in the recent literature. This study evaluates the clinical applicability of high-strength lean Mg‒0.45Zn‒0.45Ca (ZX00) screws in a growing-sheep model. Two groups, one including a simulated fracture and one group without fracture, underwent implantation of the alloy and were compared to each other. No significant difference regarding screw volume was observed between the groups. There was no negative influence of hydrogen-gas formation on fracture healing and a complete fracture consolidation was found after 12 weeks for all animals investigated.\n Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.\n\nHohenberger, Gloria\n\nHolweg, Patrick Lukas\n\nLeithner, Andreas\n\nSchwarze, Uwe Yacine\n\nSeibert, Franz\n\nSommer, Nicole\n\nWeinberg, Annelie-Martina\n\n\n"
},
{
"text": "\n182893\nPrognostic value of histopathological DCIS features in a large-scale international interrater reliability study.\n\nGroen, EJ\n\nHudecek, J\n\nMulder, L\n\nvan Seijen, M\n\nAlmekinders, MM\n\nAlexov, S\n\nKovács, A\n\nRyska, A\n\nVarga, Z\n\nAndreu Navarro, FJ\n\nBianchi, S\n\nVreuls, W\n\nBalslev, E\n\nBoot, MV\n\nKulka, J\n\nChmielik, E\n\nBarbé, E\n\nde Rooij, MJ\n\nVos, W\n\nFarkas, A\n\nLeeuwis-Fedorovich, NE\n\nRegitnig, P\n\nWestenend, PJ\n\nKooreman, LFS\n\nQuinn, C\n\nFloris, G\n\nCserni, G\n\nvan Diest, PJ\n\nLips, EH\n\nSchaapveld, M\n\nWesseling, J\n\nGrand Challenge PRECISION consortium\n\nBeiträge in Fachzeitschriften\nISI:000554057400001\n32734520.0\n10.1007/s10549-020-05816-x\nPMC7497690\nFor optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk.\n Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff's alpha (KA) and Gwet's AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression.\n Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05-6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35-5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34-10.23) were independently associated with a higher iIBC risk.\n Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.\n\nRegitnig, Peter\n\n\n"
},
{
"text": "\n187929\nAssessment of trimethylamine N-oxide (TMAO) as a potential biomarker of severe stress in patients vulnerable to posttraumatic stress disorder (PTSD) after acute myocardial infarction.\n\nBaranyi, A\n\nEnko, D\n\nvon Lewinski, D\n\nRothenhäusler, HB\n\nAmouzadeh-Ghadikolai, O\n\nHarpf, H\n\nHarpf, L\n\nTraninger, H\n\nObermayer-Pietsch, B\n\nSchweinzer, M\n\nBraun, CK\n\nMeinitzer, A\n\nBeiträge in Fachzeitschriften\nNone\n34104352.0\n10.1080/20008198.2021.1920201\nPMC8168738\nBackground: Posttraumatic stress disorder (PTSD) is a frequently observed stress-related disorder after acute myocardial infarction (AMI) and it is characterized by numerous symptoms, such as flashbacks, intrusions and anxiety, as well as uncontrollable thoughts and feelings related to the trauma. Biological correlates of severe stress might contribute to identifying PTSD-vulnerable patients at an early stage. Objective: Aims of the study were (1) to determine whether blood levels of trimethylamine N-oxide (TMAO) vary immediately after AMI in patients with/without AMI-induced PTSD symptomatology, (2) to investigate whether TMAO is a potential biomarker that might be useful in the prediction of PTSD and the PTSD symptom subclusters re-experiencing, avoidance and hyperarousal, and (3) to investigate whether TMAO varies immediately after AMI in patients with/without depression 6 months after AMI. Method: A total of 114 AMI patients were assessed with the Hamilton-Depression Scale after admission to the hospital and 6 months later. The Clinician Administered PTSD Scale for DSM-5 was used to explore PTSD-symptoms at the time of AMI and 6 months after AMI. To assess patients' TMAO status, serum samples were collected at hospitalization and 6 months after AMI. Results: Participants with PTSD-symptomatology had significantly higher TMAO levels immediately after AMI than patients without PTSD-symptoms (ANCOVA: TMAO(PTSD x time), F = 4.544, df = 1, p = 0.035). With the inclusion of additional clinical predictors in a hierarchical logistic regression model, TMAO became a significant predictor of PTSD-symptomatology. No significant differences in TMAO levels immediately after AMI were detected between individuals with/without depression 6 months after AMI. Conclusions: An elevated TMAO level immediately after AMI might reflect severe stress in PTSD-vulnerable patients, which might also lead to a short-term increase in gut permeability to trimethylamine, the precursor of TMAO. Thus, an elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD.\n © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.\n\nBaranyi, Andreas\n\nEnko, Dietmar\n\nMeinitzer, Andreas\n\nObermayer-Pietsch, Barbara\n\nRothenhäusler, Hans-Bernd\n\nSchweinzer, Melanie Sonja\n\nvon Lewinski, Dirk\n\n\n"
},
{
"text": "\n3614\nInternational Child Care Practices Study: infant sleeping environment.\n\nNelson, EA\n\nTaylor, BJ\n\nJenik, A\n\nVance, J\n\nWalmsley, K\n\nPollard, K\n\nFreemantle, M\n\nEwing, D\n\nEinspieler, C\n\nEngele, H\n\nRitter, P\n\nHildes-Ripstein, GE\n\nArancibia, M\n\nJi, X\n\nLi, H\n\nBedard, C\n\nHelweg-Larsen, K\n\nSidenius, K\n\nKarlqvist, S\n\nPoets, C\n\nBarko, E\n\nKiberd, B\n\nMcDonnell, M\n\nDonzelli, G\n\nPiumelli, R\n\nLandini, L\n\nGiustardi, A\n\nNishida, H\n\nFukui, S\n\nSawaguchi, T\n\nIno, M\n\nHoriuchi, T\n\nOguchi, K\n\nWilliams, S\n\nPerk, Y\n\nTappin, D\n\nMilerad, J\n\nWennborg, M\n\nAryayev, N\n\nNepomyashchaya, V\n\nBeiträge in Fachzeitschriften\nISI:000167904000005\n11245994.0\n10.1016%2FS0378-3782%2801%2900116-5\nNone\nBACKGROUND: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.\n\nEinspieler, Christa\n\n\n"
},
{
"text": "\n6845\nHER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.\n\nDi Leo, A\n\nChan, S\n\nPaesmans, M\n\nFriedrichs, K\n\nPinter, T\n\nCocquyt, V\n\nMurray, E\n\nBodrogi, I\n\nWalpole, E\n\nLesperance, B\n\nKorec, S\n\nCrown, J\n\nSimmonds, P\n\nVon Minckwitz, G\n\nLeroy, JY\n\nDurbecq, V\n\nIsola, J\n\nAapro, M\n\nPiccart, MJ\n\nLarsimont, D\n\nBeiträge in Fachzeitschriften\nISI:000223095300002\n15567936.0\n10.1023/B:BREA.0000036783.88387.47\nNone\nPURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.\n\n\n"
},
{
"text": "\n112535\nWasting and Sudden Cardiac Death in Hemodialysis Patients: A Post Hoc Analysis of 4D (Die Deutsche Diabetes Dialyse Studie).\n\nDrechsler, C\n\nGrootendorst, DC\n\nPilz, S\n\nTomaschitz, A\n\nKrane, V\n\nDekker, F\n\nMärz, W\n\nRitz, E\n\nWanner, C\n\nBeiträge in Fachzeitschriften\nISI:000295379600016\n21820222.0\n10.1053/j.ajkd.2011.05.026\nNone\nBackground: Wasting is common in hemodialysis patients and often is accompanied by cardiovascular disease and inflammation. The cardiovascular risk profile meaningfully changes with the progression of kidney disease, and little is known about the impact of wasting on specific clinical outcomes. This study examined the effects of wasting on the various components of cardiovascular outcome and deaths caused by infection in hemodialysis patients. Study Design: Prospective cohort study. Setting & Participants: 1, 55 hemodialysis patients from 178 centers participating in Die Deutsche Diabetes Dialyse Studie (4D) in 1998-2004. Predictor: Moderate wasting was defined as body mass index, albumin, and creatinine values less than the median (26.7 kg/m(2), 3.8 g/dL, and 6.8 mg/dL, respectively) and C-reactive protein level less than the median (5 mg/L) at baseline. Severe wasting was defined as body mass index, albumin, and creatinine levels less than the median and C-reactive protein level greater than the median at baseline. Outcomes & Measurements: Risks of sudden cardiac death (SCD), myocardial infarction (MI), stroke, combined cardiovascular events, deaths due to infection, and all-cause mortality were determined using Cox regression analyses during a median of 4 years of follow-up. Results: 196 patients had wasting (severe, n = 109; and moderate, n = 87). Overall, 617 patients died (160 of SCD and 128 of infectious deaths). Furthermore, 469 patients experienced a cardiovascular event, with MI and stroke occurring in 200 and 103 patients, respectively. Compared with patients without wasting (n = 1, 59), patients with severe wasting had significantly increased risks of SCD (adjusted HR, 1.8; 95% CI, 1.1-3.1), all-cause mortality (adjusted HR, 1.8; 95% CI, 1.4-2.4), and deaths due to infection (adjusted HR, 2.3; 95% CI, 1.2-4.3). In contrast, MI was not affected. The increased risk of cardiovascular events (adjusted HR, 1.5; 95% CI, 1.0-2.1) was explained mainly by the effect of wasting on SCD. Limitations: Selective patient cohort. Conclusions: Wasting was associated strongly with SCD, but not MI, in diabetic hemodialysis patients. Nonatherosclerotic cardiac disease potentially has a major role to account for the increased cardiovascular events in patients with wasting, suggesting the need for novel treatment strategies. Am J Kidney Dis. 58(4): 599-607. (C) 2011 by the National Kidney Foundation, Inc.\n\nMärz, Winfried\n\nPilz, Stefan\n\n\n"
},
{
"text": "\n119813\nProbabilistic classification learning with corrective feedback is selectively impaired in early Huntington's disease-Evidence for the role of the striatum in learning with feedback.\n\nHoll, AK\n\nWilkinson, L\n\nTabrizi, SJ\n\nPainold, A\n\nJahanshahi, M\n\nBeiträge in Fachzeitschriften\nISI:000307368100005\n22659110.0\n10.1016/j.neuropsychologia.2012.05.021\nNone\nIn general, declarative learning is associated with the activation of the medial temporal lobes (MTL), while the basal ganglia (BG) are considered the substrate for procedural learning. More recently it has been demonstrated the distinction of these systems may not be as absolute as previously thought and that not only the explicit or implicit nature of the memory task alone is important for the distinction of MTL or BG systems. Nevertheless, patients with BG dysfunction - such as patients with Parkinson's disease (PD) or Huntington's disease (HD) - are considered to be impaired at implicit learning. However, a more recent study demonstrated that one implicit learning task, probabilistic classification learning (examples include the weather prediction (WPT) and Mr. Potato Head tasks) is only impaired in PD when it involves learning with corrective feedback (FB) but not when it involves learning in a paired associate (PA) manner, without feedback. Therefore, it has been argued that the presence of feedback rather than the implicit nature of these tasks determines whether or not the BG are recruited. As patients with HD as well as those with PD, have also been shown to be impaired on the standard FB based version of probabilistic classification learning, the question remains as to whether or not there is a similar selective deficit in FB but not PA based probabilistic classification learning in HD. 18 patients with early HD and 18 healthy controls completed FB and PA versions of the WPT task. Relative to controls, HD patients were selectively impaired at WPT learning with feedback. These findings are consistent with previous evidence from studies of probabilistic classification learning in PD. Unlike PD, selective deficits in WPT learning in HD cannot be attributed to the effects of dopaminergic medication and must be directly related to BG dysfunction; for instance even in early HD, only 50% of the neurons in the medial head of caudate remain. We conclude that the striatum is important for WPT learning with feedback. Our findings are consistent with imaging evidence showing recruitment of the caudate during FB based WPT learning, while the MTL is associated with PA based learning.\n\nHoll, Anna\n\nPainold, Annamaria\n\n\n"
},
{
"text": "\n156776\nCardiovascular risk and endothelial function in people living with HIV/AIDS: design of the multi-site, longitudinal EndoAfrica study in the Western Cape Province of South Africa.\n\nStrijdom, H\n\nDe Boever, P\n\nWalzl, G\n\nEssop, MF\n\nNawrot, TS\n\nWebster, I\n\nWestcott, C\n\nMashele, N\n\nEverson, F\n\nMalherbe, ST\n\nStanley, K\n\nKessler, HH\n\nStelzl, E\n\nGoswami, N\n\nBeiträge in Fachzeitschriften\nISI:000391327100003\n28061822.0\n10.1186/s12879-016-2158-y\nPMC5219697\nThere is growing evidence of an interaction between HIV-infection, anti-retroviral therapy (ART) and cardiovascular diseases (CVD). Epidemiological studies in Europe and North America have been observing a shift towards an increased incidence of coronary heart disease and acute myocardial infarctions in HIV-infected populations compared to the general population even after adjusting for traditional cardiovascular risk factors. Despite South Africa (and sub-Saharan Africa, SSA) being regarded as the epicentre of the global HIV epidemic, very little is known about the prevalence of cardiovascular risk factors and precursors of vascular disease in HIV-infected populations in this region. The knowledge gap is further widened by the paucity of data from prospective studies. We present the rationale, objectives and key methodological features of the EndoAfrica study, which aims to determine whether HIV-infection and ART are associated with altered cardiovascular risk and changes in vascular endothelial structure and function in adults living in the Western Cape Province of South Africa.\n In this longitudinal study, comprehensive cardiovascular assessments of HIV-negative and HIV-positive (with and without ART) study participants are performed by clinical and biochemical screening for traditional cardiovascular risk factors and biomarkers of CVD. Vascular and endothelial function is determined by brachial artery flow-mediated dilatation (FMD), carotid-intima-thickness (IMT) measurements and quantitative retinal blood vessel analyses, complemented by vascular endothelial biomarker assays. Finally, we aim to statistically determine whether HIV-infection and/or ART are associated with increased cardiovascular risk and vascular endothelial dysfunction, and determine whether there is progression/regression in these endpoints 18 months after the baseline assessments.\n The EndoAfrica study provides a unique opportunity to recruit a cohort of HIV-infected patients and HIV-negative controls who will be comprehensively and longitudinally assessed for cardiovascular risk and disease profile with vascular endothelial function as a potentially important intermediate cardiovascular phenotype. To our knowledge, it is the first time that such a systematic study has been established in the context of SSA and South Africa.\n\nGoswami, Nandu\n\nKessler, Harald\n\nStelzl, Evelyn\n\n\n"
},
{
"text": "\n170863\nOpen reduction and internal fixation of proximal humeral fractures with use of the locking proximal humerus plate. Results of a prospective, multicenter, observational study.\n\nSüdkamp, N\n\nBayer, J\n\nHepp, P\n\nVoigt, C\n\nOestern, H\n\nKääb, M\n\nLuo, C\n\nPlecko, M\n\nWendt, K\n\nKöstler, W\n\nKonrad, G\n\nBeiträge in Fachzeitschriften\nISI:000266569800004\n19487508.0\n10.2106/JBJS.H.00006\nNone\nThe treatment of unstable displaced proximal humeral fractures, especially in the elderly, remains controversial. The objective of the present prospective, multicenter, observational study was to evaluate the functional outcome and the complication rate after open reduction and internal fixation of proximal humeral fractures with use of a locking proximal humeral plate.\n One hundred and eighty-seven patients (mean age, 62.9 +/- 15.7 years) with an acute proximal humeral fracture were managed with open reduction and internal fixation with a locking proximal humeral plate. At the three-month, six-month, and one-year follow-up examinations, 165 (88%), 158 (84%), and 155 (83%) of the 187 patients were assessed with regard to pain, shoulder mobility, and strength. The Constant score was determined at each interval, and the Disabilities of the Arm, Shoulder and Hand (DASH) score was determined for the injured and contralateral extremities at the time of the one-year follow-up.\n Between three months and one year, the mean range of motion and the mean Constant score for the injured shoulders improved substantially. Twelve months after surgery, the mean Constant score for the injured side was 70.6 +/- 13.7 points, corresponding to 85.1% +/- 14.0% of the score for the contralateral side. The mean DASH score at the time of the one-year follow-up was 15.2 +/- 16.8 points. Sixty-two complications were encountered in fifty-two (34%) of 155 patients at the time of the one-year follow-up. Twenty-five complications (40%) were related to incorrect surgical technique and were present at the end of the operative procedure. The most common complication, noted in twenty-one (14%) of 155 patients, was intraoperative screw perforation of the humeral head. Twenty-nine patients (19%) had an unplanned second operation within twelve months after the fracture.\n Surgical treatment of displaced proximal humeral fractures with use of the locking proximal humeral plate that was evaluated in the present study can lead to a good functional outcome provided that the correct surgical technique is used. Because many of the complications were related to incorrect surgical technique, it behooves the treating surgeon to perform the operation correctly to avoid iatrogenic errors.\n\nPlecko, Michael\n\n\n"
},
{
"text": "\n181675\nLeukocyte Telomere Length Is Related to Brain Parenchymal Fraction and Attention/Speed in the Elderly: Results of the Austrian Stroke Prevention Study.\n\nGampawar, P\n\nSchmidt, R\n\nSchmidt, H\n\nBeiträge in Fachzeitschriften\nISI:000526652500001\n32180739.0\n10.3389/fpsyt.2020.00100\nPMC7059269\nThere are controversial results if leukocyte telomere length (LTL) is related to structural brain changes and cognitive decline in aging. Here, we investigated the association between LTL and 1) global MRI correlates of brain aging such as brain parenchymal fraction (BPF) and white matter hyperintensities (WMH) load and Fazekas score as well as 2) global (g-factor) and domain-specific cognition such as attention/speed, conceptualization, memory, and visuopractical skills. In total, 909 participants of the Austrian Stroke Prevention Study with LTL, MRI, and cognitive tests were included. There were 388 (42.7%) men, and the mean age was 65.9 years. Longer LTL was significantly associated with larger BPF (β = 0.43, p < 0.001), larger WMH load (β = 0.03, p = 0.04), and score (β = 0.05, p = 0.04) after adjusting for age, sex, vascular risk factors, and ApoE4 carrier status. The effect on BPF was more significant in the subgroups of women (β = 0.51, p = 0.001), age >65 years (β = 0.58, p = 0.002), BMI ≥ 25 (β = 0.40, p = 0.004), education ≤10 years (β = 0.42, p = 0.002), hypertensives (β = 0.51, p = 0.001), cardiovascular disease (CVD) (β = 0.58, p = 0.005), non-diabetics (β = 0.42, p < 0.001), and Apoe4 non-carriers (β = 0.49, p < 0.001). The effect on WMH was significant within the hypertensives (load: β = 0.04, p = 0.02), non-diabetics (load:β = 0.03, p = 0.01; score: β = 0.06, p = 0.02), in those with education ≤10 years (load: β = 0.03, p = 0.04; score: β = 0.07, p = 0.02), in ApoE4 non-carriers (load: β = 0.03, p = 0.02; score: β = 0.07, p = 0.01) and in subjects without CVD (score: β = 0.06, p = 0.05). We only observed a significant association between LTL and the cognitive domain of attention/speed, which was confined to the subgroups of BMI ≥ 25 (β = 0.04, p = 0.05) and education ≤10 years (β = 0.04, p = 0.05). The effect of LTL on attention/speed was partly mediated in both subgroups by BPF (β = 0.02, 95% CI = 0.01:0.03) when tested by bootstrapping. Our results support a strong protective role of longer LTL on global brain volume which in turn may contribute to better cognitive functions, especially in the attention/speed domain in the elderly.\n Copyright © 2020 Gampawar, Schmidt and Schmidt.\n\nGampawar, Piyush Gajananrao\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n182639\nAdjuvant therapy with pegylated interferon-alfa2b vs observation in stage II B/C patients with ulcerated primary: Results of the European Organisation for Research and Treatment of Cancer 18081 randomised trial.\n\nEggermont, AMM\n\nRutkowski, P\n\nDutriaux, C\n\nHofman-Wellenhof, R\n\nDziewulski, P\n\nMarples, M\n\nGrange, F\n\nLok, C\n\nPennachioli, E\n\nRobert, C\n\nvan Akkooi, ACJ\n\nBastholt, L\n\nMinisini, A\n\nMarshall, E\n\nSalès, F\n\nGrob, JJ\n\nBechter, O\n\nSchadendorf, D\n\nMarreaud, S\n\nKicinski, M\n\nSuciu, S\n\nTestori, AAE\n\nBeiträge in Fachzeitschriften\nISI:000540721200013\n32470710.0\n10.1016/j.ejca.2020.04.015\nNone\nSubgroup analyses of two large EORTC adjuvant interferon-alpha2b (IFNα-2b) vs observation randomised trials demonstrated that a treatment benefit was observed only in patients with an ulcerated melanoma without palpable nodes (hazard ratio [HR] for recurrence-free survival [RFS] was 0.69). This was confirmed by a meta-analysis of 15 adjuvant IFN trials (HR: 0.79).\n In the EORTC 18081 trial, sentinel node-negative stage II patients with an ulcerated primary melanoma were 1:1 randomised between pegylated (PEG)-IFNα-2b at 3 μg/kg/week subcutaneously and observation, for 2 years, or until disease recurrence or unacceptable toxicity in spite of dose adjustments to maintain an Eastern Cooperative Oncology Group performance status of 0 or 1. Main end-point was RFS. Secondary end-points included distant metastasis-free survival (DMFS), overall survival, and safety (EudraCT Number: 2009-010273-20).\n Between February 2013 and January 2017, only 112 patients were randomised, 56 in each arm. The trial was stopped early for lack of recruitment. At a 3.4-year median follow-up, the estimated HR for the PEG-IFNα-2b group compared with the observation group regarding RFS was 0.66 (95% confidence interval [CI]: 0.32-1.37), and the 3-year RFS rate was 80.0% (95% CI: 65.7-88.8%) and 72.9% (95% CI: 58.3-83.0%), respectively. DMFS was prolonged: HR: 0.39 (95% CI: 0.15-0.97), and the 3-year DMFS rate was 90.6% (95% CI: 78.9-96.0%) vs 76.4% (95% CI: 62.1-85.9%). One patient in the PEG-IFNα-2b group died compared with 4 in the observation group. Fifty-four patients started PEG-IFNα-2b treatment, 16 (29%) completed 2 years of treatment, 2 (4%) stopped due to recurrence, 23 (43%) due to toxicity and 14 (25%) due to other reasons.\n The EORTC 18081 PEG-IFNα-2b randomised trial, observed a similar HR (0.69) for RFS as the previous EORTC trials (0.69). In countries without access to new drugs, adjuvant (PEG)-IFNα-2b treatment is an option for patients with ulcerated melanomas without palpable nodes.\n Copyright © 2020 Elsevier Ltd. All rights reserved.\n\nHofmann-Wellenhof, Rainer\n\n\n"
},
{
"text": "\n184249\nThe Positive Association between Plasma Myristic Acid and ApoCIII Concentrations in Cardiovascular Disease Patients Is Supported by the Effects of Myristic Acid in HepG2 Cells.\n\nOlivieri, O\n\nSpeziali, G\n\nCastagna, A\n\nPattini, P\n\nUdali, S\n\nPizzolo, F\n\nLiesinger, L\n\nGindlhuber, J\n\nTomin, T\n\nSchittmayer, M\n\nBirner-Gruenberger, R\n\nCecconi, D\n\nGirelli, D\n\nFriso, S\n\nMartinelli, N\n\nBeiträge in Fachzeitschriften\nISI:000579408700016\n32710763.0\n10.1093/jn/nxaa202\nNone\nIn the settings of primary and secondary prevention for coronary artery disease (CAD), a crucial role is played by some key molecules involved in triglyceride (TG) metabolism, such as ApoCIII. Fatty acid (FA) intake is well recognized as a main determinant of plasma lipids, including plasma TG concentration.\n The aim was to investigate the possible relations between the intakes of different FAs, estimated by their plasma concentrations, and circulating amounts of ApoCIII.\n Plasma samples were obtained from 1370 subjects with or without angiographically demonstrated CAD (mean ± SD age: 60.6 ± 11.0 y; males: 75.8%; BMI: 25.9 ± 4.6 kg/m2; CAD: 73.3%). Plasma lipid, ApoCIII, and FA concentrations were measured. Data were analyzed by regression models adjusted for FAs and other potential confounders, such as sex, age, BMI, diabetes, smoking, and lipid-lowering therapies. The in vitro effects of FAs were tested by incubating HepG2 hepatoma cells with increasing concentrations of selected FAs, and the mRNA and protein contents in the cells were quantified by real-time RT-PCR and LC-MS/MS analyses.\n Among all the analyzed FAs, myristic acid (14:0) showed the most robust correlations with both TGs (R = 0.441, P = 2.6 × 10-66) and ApoCIII (R = 0.327, P = 1.1 × 10-31). By multiple regression analysis, myristic acid was the best predictor of both plasma TG and ApoCIII variability. Plasma TG and ApoCIII concentrations increased progressively at increasing concentrations of myristic acid, independently of CAD diagnosis and gender. Consistent with these data, in the in vitro experiments, an ∼2-fold increase in the expression levels of the ApoCIII mRNA and protein was observed after incubation with 250 μM myristic acid. A weaker effect (∼30% increase) was observed for palmitic acid, whereas incubation with oleic acid did not affect ApoCIII protein or gene expression.\n Plasma myristic acid is associated with increased ApoCIII concentrations in cardiovascular patients. In vitro experiments indicated that myristic acid stimulates ApoCIII expression in HepG2 cells.\n Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.\n\nBirner-Grünberger, Ruth\n\nGindlhuber, Jürgen\n\nLiesinger, Laura\n\nSchittmayer-Schantl, Matthias\n\nTomin, Tamara\n\n\n"
},
{
"text": "\n186798\nCoronary computed tomography and triple rule out CT in patients with acute chest pain and an intermediate cardiac risk for acute coronary syndrome: part 2: economic aspects.\n\nHenzler, T\n\nGruettner, J\n\nMeyer, M\n\nRothhaar, B\n\nApfaltrer, P\n\nMetzger, F\n\nBorggrefe, M\n\nSchoepf, UJ\n\nSchoenberg, SO\n\nFink, C\n\nBeiträge in Fachzeitschriften\nNone\n22835878.0\n10.1016/j.ejrad.2012.06.012\nNone\nTo evaluate the economic impact of integrating coronary CT angiography (cCTA) or whole chest "triple-rule-out" CTA (TRO-CTA) in the work-up of patients with acute chest pain.\n 100 consecutive emergency department patients with acute chest pain and an intermediate cardiac risk for ACS underwent cCTA or TRO-CTA (cCTA group). Diagnostic performance, rate and length of hospitalization, hospital costs, hospital reimbursement and hospital profit were analyzed. All findings were compared to those of 100 different patients with acute chest pain that were evaluated with a standard of care (SOC) diagnostic algorithm (SOC group) that did not include cCTA. Diagnostic performance ("safety") of both algorithms was defined as the absence of major adverse cardiac events (MACE) over a 90-day follow-up period.\n In the cCTA group 60/100 patients were safely discharged at the same day. 19/100 patients were hospitalized due to significant coronary stenosis on cCTA, which was confirmed by invasive coronary catheterization (ICC) in 17/19 patients. Relevant non-coronary disease that led to hospitalization were found in 21 patients of the cCTA group. In the SOC group all patients were hospitalized. 87 of these hospitalized patients underwent ICC for exclusion of coronary artery stenosis. A significant coronary artery stenosis was found in only 25 of these patients. Within the cCTA group no patient suffered from MACE over the 90-day follow-up period. In the SOC group 2 patients were rehospitalized during the 90-day follow-up period due to recurrent chest pain and 1 patient because of a pseudoaneurym of the left femoral artery after ICC. The median hospital costs per patient were significantly lower in the cCTA group than in the SOC group (428.9€ vs. 1575.0€, p<0.001). The median reimbursement of the cCTA group was less compared to the SOC group (589.8€ vs. 2412.1€, p<0.001) and patients in the cCTA group gained less profit than patients in the SOC group (57.0€ vs. 448.4€, p<0.001).\n Integrating cCTA or TRO-CTA in a SOC algorithm can safely reduce the number of hospitalized patients and reduce total health care costs.\n Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.\n\nApfaltrer, Paul\n\n\n"
},
{
"text": "\n163096\nPrognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non-muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review.\n\nSoukup, V\n\nČapoun, O\n\nCohen, D\n\nHernández, V\n\nBabjuk, M\n\nBurger, M\n\nCompérat, E\n\nGontero, P\n\nLam, T\n\nMacLennan, S\n\nMostafid, AH\n\nPalou, J\n\nvan Rhijn, BWG\n\nRouprêt, M\n\nShariat, SF\n\nSylvester, R\n\nYuan, Y\n\nZigeuner, R\n\nBeiträge in Fachzeitschriften\nISI:000412685300035\n28457661.0\n10.1016/j.eururo.2017.04.015\nNone\nTumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications.\n To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC.\n A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist.\n Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias.\n Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression.\n This article summarises the utility of two different grading systems for non-muscle-invasive bladder cancer. Both systems predict progression and recurrence, although pathologists vary in their reporting; suggestions for further improvements are made.\n Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n187328\nBayesian Inference Associates Rare <i>KDR</i> Variants with Specific Phenotypes in Pulmonary Arterial Hypertension.\n\nSwietlik, EM\n\nGreene, D\n\nZhu, N\n\nMegy, K\n\nCogliano, M\n\nRajaram, S\n\nPandya, D\n\nTilly, T\n\nLutz, KA\n\nWelch, CCL\n\nPauciulo, MW\n\nSouthgate, L\n\nMartin, JM\n\nTreacy, CM\n\nPenkett, CJ\n\nStephens, JC\n\nBogaard, HJ\n\nChurch, C\n\nCoghlan, G\n\nColeman, AW\n\nCondliffe, R\n\nEichstaedt, CA\n\nEyries, M\n\nGall, H\n\nGhio, S\n\nGirerd, B\n\nGrünig, E\n\nHolden, S\n\nHoward, L\n\nHumbert, M\n\nKiely, DG\n\nKovacs, G\n\nLordan, J\n\nMachado, RD\n\nMackenzie Ross, RV\n\nMcCabe, C\n\nMoledina, S\n\nMontani, D\n\nOlschewski, H\n\nPepke-Zaba, J\n\nPrice, L\n\nRhodes, CJ\n\nSeeger, W\n\nSoubrier, F\n\nSuntharalingam, J\n\nToshner, MR\n\nVonk Noordegraaf, A\n\nWharton, J\n\nWild, JM\n\nWort, SJ\n\nLawrie, A\n\nWilkins, MR\n\nTrembath, RC\n\nShen, Y\n\nChung, WK\n\nSwift, AJ\n\nNichols, WC\n\nMorrell, NW\n\nGräf, S\n\nBeiträge in Fachzeitschriften\nNone\n33320693.0\n10.1161/CIRCGEN.120.003155\nPMC7892262\nBackground - Approximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics. Methods - We analyzed 13, 37 participants enrolled in the NIHR BioResource - Rare Diseases (NBR) study, of which 1, 48 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension (PH), we used the Bayesian rare-variant association method BeviMed. Results - Heterozygous, high impact, likely loss-of-function variants in the Kinase Insert Domain Receptor (KDR) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (KCO, posterior probability (PP)=0.989) and older age at diagnosis (PP=0.912). We also provide evidence for familial segregation of a rare nonsense KDR variant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the five patients harboring these predicted deleterious variants in KDR. Four additional PAH cases with rare likely loss-of-function variants in KDR were independently identified in the US PAH Biobank cohort with similar phenotypic characteristics. Conclusions - The Bayesian inference approach allowed us to independently validate KDR, which encodes for the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence for KDR being a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.\n\nKovacs, Gabor\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n65910\nLipid-lowering medication for secondary prevention of coronary heart disease in a German outpatient population: the gap between treatment guidelines and real life treatment patterns.\n\nRuof, J\n\nKlein, G\n\nMärz, W\n\nWollschläger, H\n\nNeiss, A\n\nWehling, M\n\nBeiträge in Fachzeitschriften\nISI:000176611400007\n12079440.0\n10.1006/pmed.2002.1050\nNone\nBACKGROUND: Few published data in particular from the United States indicate that the implementation of guidelines for prevention of coronary heart disease (CHD) is far from optimal. The objective of our study was to identify the type and prevalence of lipid-lowering medications in a German outpatient CHD population and to examine the impact of applied treatment regimens on serum lipid levels. METHODS: Retrospective analysis of the washout phase of 2, 56 CHD patients requiring lipid-lowering medication. Data are derived from a multicenter, randomized, open-label, parallel group clinical trial comparing the safety and efficacy of atorvastatin versus simvastatin in 591 centers in Germany. Medical history, physical examination, and serum lipid levels were obtained at the beginning of the washout phase (Week -6) and at the end of the washout phase (Week -1, i.e., 5 weeks after the discontinuation of all prior lipid-lowering medications). The data at Week -6 represented the lipid levels under real life conditions. The difference from the data at Week -1 reflected the therapeutic effects achieved by the previous lipid-lowering treatment. RESULTS: The mean low-density lipoprotein cholesterol (LDL-C) level at Week -6 was 173.4 +/- 42.5 mg/dl. Only 176 (6.2%) of 2, 56 CHD patients were found to meet the target LDL-C level of <115 mg/dl at Week -6, only 76 (2.7%) patients had LDL-C levels <100 mg/dl, and 363 (12.7%) patients had LDL-C levels <130 mg/dl. After discontinuation of all prior lipid-lowering medications, mean LDL-C increased to 187.2 +/- 44.0 mg. This means that only a marginal 7.4% reduction in LDL-C level was achieved under real life treatment conditions. This limited LDL-C reduction was due mainly to the low prevalence of lipid-lowering treatment (65.5% of patients did not receive any medication at all) and inadequate dosing. With respect to the effect on LDL-C and total cholesterol, statins alone were superior to fibrates. CONCLUSION: The study shows that there is a wide gap between treatment guidelines and real life treatment patterns in Germany. Awareness of the risks of high cholesterol levels has to be increased among both patients and physicians. Available treatment guidelines should be better implemented.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n69412\nCardiac resynchronization therapy in terminal heart failure: current status and prospects\n\nSack, S\n\nHeinzel, F\n\nDagres, N\n\nWieneke, H\n\nErbel, R\n\nBeiträge in Fachzeitschriften\nISI:000167188300012\n11258115.0\n10.1007/PL00002010\nNone\nBACKGROUND: With regard to epidemiological aspects, heart failure has been shown an increasing incidence in constrast to coronary artery disease which counts decreasingly due to secondary and primary prevention. The present data show an incidence for heart failure of 2% per year. 4-5 million people are newly affected by the disease. The prognosis is limited after diagnosis is confirmed. According to the US Framingham study, the median life expectancy is 3.2 and 5.4 after diagnosis for male and female, respectively. For patients in an advanced stage of the disease the mortality rate is 27% within 3 years. AV SEQUENTIAL PACING: The introduction of AV sequential pacing by the Austrian group of Margarete Hochleitner in 1992 showed an improved left ventricular systolic function, an improved clinical benefit in terms of NYHA classification, an enhanced left ventricular ejection fraction, an improved systolic and diastolic blood pressure, a reduction of the heart-chest relationship as well as a reduction of the resting hart rate and the echocardiographic dimension parameters. STUDIES: First experimental approach for biventricular stimulation, which means the simultaneous activation of the right and the left chamber, relied on the observation of a distorted ventricular activation due to the presence of a bundle branch block. The bundle branch block is a result of the dilatation of the myocardial fibers, death of myocardial cells which are replaced by fibrous tissue. Resynchronization of both ventricles was associated with an improved left ventricular function and improved diastolic relaxation. Clinical studies of patients with heart failure, severe left ventricular systolic dysfunction, and left bundle branch block have shown that systolic function can be improved by electrically stimulating the site of late activation. The magnitude of the improvement seems to be associated with the duration of the intrinsic surface QRS complex and whether the ventricle ipsilateral with the conduction defect is stimulated. The effect of ventricular resynchronization therapy was optimized by timing of atrioventricular activation associated with a decrease in both systolic and diastolic mitral regurgitation. CONCLUSION: The prognosis of patients with end-stage heart failure is limited by two determinants: myocardial pump failure and sudden (arrhythmogenic) cardiac death. Due to the fact that the incidence for sudden cardiac death is considerably high in patients with end-stage heart failure it is reasonable to include the implantation of cardioverters/defibrillaters (ICD) in the concept of biventricular stimulation.\n\n\n"
},
{
"text": "\n107306\nCritical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging.\n\nAuprich, M\n\nChun, FK\n\nWard, JF\n\nPummer, K\n\nBabaian, R\n\nAugustin, H\n\nLuger, F\n\nGutschi, S\n\nBudäus, L\n\nFisch, M\n\nHuland, H\n\nGraefen, M\n\nHaese, A\n\nBeiträge in Fachzeitschriften\nISI:000284575200018\n20980098.0\n10.1016/j.eururo.2010.10.024\nNone\nKnowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial.\n Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen.\n Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n=305) and computer-assisted planimetrically measured tumor volume data (n=160) were available.\n All patients were treated with RP.\n PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3.\n PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p=0.4) or SVI (p=0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p<0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size.\n PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3.\n Copyright © 2010 European Association of Urology. All rights reserved.\n\nAugustin, Herbert\n\nPummer, Karl\n\n\n"
}
]
}