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"text": "\n185594\nEvaluation of an implemented new insulin chart to improve quality and safety of diabetes care in a large university hospital: a follow-up study.\n\nKopanz, J\n\nSendlhofer, G\n\nLichtenegger, K\n\nSemlitsch, B\n\nRiedl, R\n\nPieber, TR\n\nTax, C\n\nBrunner, G\n\nPlank, J\n\nBeiträge in Fachzeitschriften\nISI:000614460700018\n33500281.0\n10.1136/bmjopen-2020-041298\nPMC7839871\nTo evaluate structure, documentation, treatment quality of a new implemented standardised insulin chart in adult medical inpatient wards at a university hospital.\n A before-after study (3 to 5 months after implementation) was used to compare the quality of old versus new insulin charts.\n University Hospital Graz, Austria.\n Healthcare professionals (n=237) were questioned regarding structure quality of blank insulin charts.\n A new standardised insulin chart was implemented and healthcare professionals were trained regarding features of this chart. Data from insulinised inpatients were evaluated regarding documentation and treatment quality of filled-in insulin charts (n=108 old insulin charts vs n=100 new insulin charts).\n The primary endpoint was documentation error for insulin administration.\n Healthcare professionals reported an improved structure quality of the new insulin chart with a Likert type response scale increase in all nine items. Documentation errors for insulin administration (primary endpoint) occurred more often on old than new insulin charts (77% vs 5%, p<0.001). Documentation errors for insulin prescription were more frequent on old insulin charts (100% vs 42%) whereas documentation errors for insulin management rarely occurred in any group (10% vs 8%). Patients of both chart evaluation groups (age: 71±11 vs 71±12 years, 47% vs 42% women, 75% vs 87% type 2 diabetes for old vs new charts, respectively) had a mean of 4±2 good diabetes days. Overall, 26 vs 18 hypoglycaemic episodes (blood glucose (BG) <4.0 mmol/L (72 mg/dL), p=0.28), including 7 vs 2 severe hypoglycaemic episodes (BG <3.0 mmol/L (54 mg/dL), p=0.17) were documented on old versus new insulin charts.\n The implementation of a structured documentation form together with training measures for healthcare professionals led to less documentation errors and safe management of glycaemic control in hospitalised patients in a short time follow-up. A rollout at further medical wards is recommended, and sustainability in the long-term has to be demonstrated.\n © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\nBrunner, Gernot\n\nKopanz, Julia\n\nLichtenegger, Katharina\n\nPieber, Thomas\n\nRiedl, Regina\n\nSemlitsch, Barbara\n\nSendlhofer, Gerald\n\n\n"
},
{
"text": "\n258\nApolipoprotein E polymorphism is not associated with longevity or disability in a sample of Italian octo- and nonagenarians.\n\nBader, G\n\nZuliani, G\n\nKostner, GM\n\nFellin, R\n\nBeiträge in Fachzeitschriften\nISI:000075466500008\n9693262.0\n10.1159/000022030\nNone\nBACKGROUND: Apolipoprotein E (apo E) is a protein associated with plasma lipoproteins. Apo E polymorphism has been related to significant modifications of lipoprotein profile, as well as to the incidence of different pathologies including cardiovascular disease, Alzheimer's disease, and vascular dementia. Furthermore, it was proposed that apo E polymorphism might be involved in the aging selection process. OBJECTIVE: The purposes of the present study were the following: (1) to evaluate apo E polymorphism in 'successful' and 'unsuccessful' aging, defined as the absence or presence of disability and severe chronic diseases (mainly cardiovascular disease and dementia), respectively; (2) to evaluate the impact of apo E polymorphism on plasma lipids in very old individuals free of or affected by disability. METHODS: 253 Italian subjects including 100 free-living healthy octo- and nonagenarians, 62 disabled octo- and nonagenarians, and 91 healthy adult controls, all matched for origin were studied. Apo E phenotypes were determined by PhastSystem (Pharmacia). Lipoprotein parameters (total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, lipoprotein (a), and apoprotein A-I and B) were measured by standardized methods. ADL were evaluated by the Katz index. RESULTS: The frequency of sigma2, sigma3, and sigma4 alleles was 0.062, 0.887, and 0.051 respectively in the entire sample; no differences in alleles distribution were found between the three groups. When the subjects were divided according to the E type (E2 type: E2/E2 and E2/E3; E3 type: E3/E3; E4 type: E3/E4 and E4/E4), no differences in lipoprotein parameters emerged, but a trend toward higher total and LDL-cholesterol from the E2 to the E4 type was observed. The sigma4 allele had a raising effect, while sigma2 had a lowering effect on total cholesterol levels, but these effects were much less profound in the disabled octo- and nonagenarians. CONCLUSIONS: We conclude that (1) the frequency of the sigma4 allele is very low in this sample of subjects from central Italy; (2) no differences emerged in sigma4 distribution between healthy and disabled octo- and nonagenarians, and adult controls; the very low frequency of sigma4 allele might contribute to this finding; (3) our data do not support the hypothesis of a possible association between apo E polymorphism and longevity or disability in this population.\n\nKostner, Gerhard\n\n\n"
},
{
"text": "\n2580\nThe pacemaker current I(f) in single human atrial myocytes and the effect of beta-adrenoceptor and A1-adenosine receptor stimulation.\n\nPorciatti, F\n\nPelzmann, B\n\nCerbai, E\n\nSchaffer, P\n\nPino, R\n\nBernhart, E\n\nKoidl, B\n\nMugelli, A\n\nBeiträge in Fachzeitschriften\nISI:A1997YC57200027\n9384516.0\n10.1038/sj.bjp.0701473\nPMC1565023\n1. We used single human atrial myocytes to study I(f) occurrence, properties and pharmacological modulation. Cells were obtained by chunk enzymatic digestion from samples of right atrial appendages of patients undergoing corrective cardiac surgery. 2. Patch-clamped cells in the whole-cell configuration were superfused with a modified Tyrode solution to reduce contamination by interfering currents and to amplify I(f). The average cell membrane capacitance was 85.06+/-2.41 pF (n=531). Data were consistent with the geometrical dimensions of the cells (length 94.2+/-1.89 microm, width 17.9+/-0.42 microm, n=126). 3. When hyperpolarizing to -120 mV from a holding potential of -40 mV, 252 of 306 tested cells (82%) expressed a hyperpolarization-activated inward current (I(f) density=3.77+/-0.25 pA pF(-1)); the current was considered to be present in a given cell if its density at -120 mV was larger than 0.5 pA pF(-1). 4. Current activation was sigmoidal and fitted a Boltzmann model; the average activation curve (n=25) showed a maximum current amplitude of 205.97+/-19.94 pA, corresponding to 3.87+/-0.63 pA pF(-1), voltage of half-maximal activation (V(1/2)) at -86.68+/-2.19 mV and a slope of -11.39+/-0.69 mV. The reversal potential of I(f) measured by tail-current analysis was -13.07+/-1.92 mV (n=6). The addition of CsCl (5 mM) fully and reversibly blocked the current. 5. In the presence of the beta-adrenoceptor agonist isoprenaline (Iso, 1 microM), V(1/2) was significantly shifted toward less negative potentials by 6.06+/-1.96 mV (n=16, P=0.0039). The selective A1-adenosine receptor agonist cyclopentyladenosine (CPA, 1 microM) caused a statistically significant shift of V(1/2) toward more negative potentials with respect to the control curve, both in the absence (-7.37+/-1.83 mV, P=0.0005, n=11) and in the presence of 1 microM Iso (-4.97+/-1.78, P=0.031, n=6). 6. These results demonstrate that a current with the properties of I(f) described in cardiac primary and secondary pacemakers occurs in the majority of human atrial cells. While the pathophysiological relevance of I(f) in human atrial tissue remains to be defined, our data clearly show that it is modulated through stimulation of beta-adrenoceptors and A1-adenosine receptors.\n\nBernhart, Eva Maria\n\nKoidl, Bernd\n\nPelzmann, Brigitte\n\nSchaffer, Peter\n\n\n"
},
{
"text": "\n71542\nShort-term effects of pulsed electromagnetic fields after physical exercise are dependent on autonomic tone before exposure.\n\nGrote, V\n\nLackner, H\n\nKelz, C\n\nTrapp, M\n\nAichinger, F\n\nPuff, H\n\nMoser, M\n\nBeiträge in Fachzeitschriften\nISI:000249781700011\n17674028.0\n10.1007/s00421-007-0520-x\nNone\nThe therapeutic application of pulsed electromagnetic fields (PEMFs) can accelerate healing after bone fractures and also alleviate pain according to several studies. However, no objective criteria have been available to ensure appropriate magnetic field strength or type of electromagnetic field. Moreover, few studies so far have investigated the physical principles responsible for the impact of electromagnetic fields on the human body. Existing studies have shown that PEMFs influence cell activity, the autonomic nervous system and the blood flow. The aim of this study is to examine the instantaneous and short-term effects of a PEMF therapy and to measure the impact of different electromagnetic field strengths on a range of physiological parameters, especially the autonomic nervous systems, determined by heart rate variability (HRV) as well as their influence on subjects' general feeling of well-being. The study comprised experimental, double-blind laboratory tests during which 32 healthy male adults (age: 38.4+/-6.5 years) underwent four physical stress tests at standardised times followed by exposure to pulsed magnetic fields of varying intensity [HPM, High Performance magnetic field; Leotec; pulsed signal; mean intensity increase: zero (placebo), 0.005, 0.03 and 0.09 T/s]. Exposure to electromagnetic fields after standardised physical effort significantly affected the very low frequency power spectral components of HRV (VLF; an indicator for sympathetically controlled blood flow rhythms). Compared to placebo treatment, exposure to 0.005 T/s resulted in accelerated recovery after physical strain. Subjects with lower baseline VLF power recovered more quickly than subjects with higher VLF when exposed to higher magnetic field strengths. The application of electromagnetic fields had no effect on subjects' general feeling of well-being. Once the magnetic field exposure was stopped, the described effects quickly subsided. PEMF exposure has a short-term dosage-dependent impact on healthy subjects. Exposure to PEMF for 20 min resulted in more rapid recovery of heart rate variability, especially in the very low frequency range after physical strain. The study also showed the moderating influence of the subjects' constitutional VLF power on their response to PEMF treatment. These findings have since been replicated in a clinical study and should be taken into consideration when PEMF treatment is chosen.\n\nLackner, Helmut Karl\n\nMoser, Maximilian\n\n\n"
},
{
"text": "\n98204\nEFQM business model enables process optimization within the subspeciality ocular oncology at the Department of Ophthalmology Graz\n\nLangmann, G\n\nFoussek, C\n\nGliebe, W\n\nKlug, U\n\nSchneider, M\n\nWackernagel, W\n\nTheisl, A\n\nLechner, H\n\nMaier, R\n\nKlein, A\n\nWedrich, A\n\nBeiträge in Fachzeitschriften\nISI:000273980700010\nNone\n10.1007/s00717-009-0372-3\nNone\nBACKGROUND: An increasing number of Austrian patients and patients from abroad leads to an increasing long time of waiting for an appointment at our ocular oncology service. Aim of this project is to optimize processes and shorten the stay of a patient in our outpatient clinic, without an increase of staff. Further aims of our activity are a definition of time for each diagnostic procedure, a shortening of the time of waiting and a realistic planning of the personal. METHOD: In November 2007 a first self assessment with a standardised EFQM questionaire by means of the workshop method was performed at the Department of Ophthalmology. Strengths and areas for improvement were defined, optimisation measures suggested and implemented. IMPROVEMENT MEASURES: A maximum number of new and control patients each day was defined as well as a minimum number of junior residents to examine the patients and senior residents to supervise the diagnostic and therapeutic decisions. Referring ophthalmologists were asked to send their patient's reports in advance to prioritisize patients according to their disease. As an example a retinoblastoma patient will be treated as an emergency patient, uveal melanomas will be diagnosed within one week and treated within 3 weeks. Processes were documented by means of the Adonis(A (R)) software procedures checked by the PDCA (Plan Do Act Check ) cycle according to Deming. SOPs (Standard operating procedures) were designed to optimize treatment procedures and guidelines were implemented. We try to fullfil requirements in resident's education according to ICO guidelines. RESULTS: The time of waiting of each patient could be shortened, patient's and physician's satisfaction improved. Appointments were organised according to the dignity of the tumor. A second day in the outpatient service had to be implemented in order to maintain a high quality of our patient's service. SUMMARY AND PERSPECTIVE: The EFQM business model provided our ocular oncology service with management tools like process formation and introduction of SOPs to improve the patient's flow. Next we intend to implement objectives (key figures) to monitor our process of improvement.\n\nKlein-Theyer, Angelika Karin\n\nLangmann, Gerald\n\nSchneider, Mona Regina\n\nWedrich, Andreas\n\n\n"
},
{
"text": "\n110884\nEfficacy of psoralen plus ultraviolet A therapy vs. biologics in moderate to severe chronic plaque psoriasis: retrospective data analysis of a patient registry.\n\nInzinger, M\n\nHeschl, B\n\nWeger, W\n\nHofer, A\n\nLegat, FJ\n\nGruber-Wackernagel, A\n\nTilz, H\n\nSalmhofer, W\n\nQuehenberger, F\n\nWolf, P\n\nBeiträge in Fachzeitschriften\nISI:000294362100030\n21564068.0\n10.1111/j.1365-2133.2011.10396.x\nNone\nFew studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis.\n To compare the clinical efficacy of PUVA and biologic therapies for psoriasis under daily life conditions.\n Data from a psoriasis registry (http://www.psoriasis-therapieregister.at) of 172 adult patients with moderate to severe chronic plaque psoriasis treated between 2003 and 2010 were analysed retrospectively. These patients had received oral PUVA [118 treatment courses including 5-methoxypsoralen (5-MOP; n = 32) and 8-methoxypsoralen (8-MOP; n = 86)] and/or biologic agents [130 treatment courses including adalimumab (n = 18), alefacept (n = 32), efalizumab (n = 17), etanercept (n = 38), infliximab (n = 7) and ustekinumab (n = 18)]. Treatment responses were analysed in terms of Psoriasis Area and Severity Index (PASI) improvement, including complete remission (CR) and reduction of PASI by at least 90% (PASI 90) or 75% (PASI 75), at treatment completion for PUVA (median time 10·3 and 9·2 weeks, for 8-MOP and 5-MOP, respectively) and at week 12 for biologics.\n Intention-to-treat-as observed CR, PASI 90 and PASI 75 rate was 22%, 69% and 86% for PUVA compared with 6%, 22% and 56% for adalimumab (P = 0·0034 by adapted Wilcoxon test), 3%, 3% and 25% for alefacept (P = 0·000000002), 6%, 6% and 59% for efalizumab (P = 0·000053), 6%, 29% and 39% for etanercept (P = 0·0000086), 29%, 71% and 100% for infliximab (P = 0·36) and 6%, 39% and 67% for ustekinumab (P = 0·028). When applying a more conservative post-hoc modified worst-case scenario analysis, with CR of 15%, PASI 90 of 58% and PASI 75 of 69%, PUVA was superior only to alefacept (P = 0·000013), efalizumab (P = 0·015) and etanercept (P = 0·0037). There were no statistically significant differences in PASI reduction rates between PUVA and infliximab.\n Retrospective analysis of registry data revealed that the primary efficacy of PUVA was superior to that of certain biologics. Prospective head-to-head studies of PUVA and biologics are warranted to confirm these observations.\n © 2011 The Authors. BJD © 2011 British Association of Dermatologists.\n\nGruber-Wackernagel, Alexandra\n\nHofer, Angelika\n\nLegat, Franz\n\nQuehenberger, Franz\n\nSalmhofer, Wolfgang\n\nWeger, Wolfgang\n\nWolf, Peter\n\n\n"
},
{
"text": "\n147503\nStandardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group.\n\nProvenzano, E\n\nBossuyt, V\n\nViale, G\n\nCameron, D\n\nBadve, S\n\nDenkert, C\n\nMacGrogan, G\n\nPenault-Llorca, F\n\nBoughey, J\n\nCurigliano, G\n\nDixon, JM\n\nEsserman, L\n\nFastner, G\n\nKuehn, T\n\nPeintinger, F\n\nvon Minckwitz, G\n\nWhite, J\n\nYang, W\n\nSymmans, WF\n\nResidual Disease Characterization Working Group of the Breast International Group-North American Breast Cancer Group Collaboration\n\nBeiträge in Fachzeitschriften\nISI:000360664200004\n26205180.0\n10.1038/modpathol.2015.74\nNone\nNeoadjuvant systemic therapy is being used increasingly in the treatment of early-stage breast cancer. Response, in the form of pathological complete response, is a validated and evaluable surrogate end point of survival after neoadjuvant therapy. Thus, pathological complete response has become a primary end point for clinical trials. However, there is a current lack of uniformity in the definition of pathological complete response. A review of standard operating procedures used by 28 major neoadjuvant breast cancer trials and/or 25 sites involved in such trials identified marked variability in specimen handling and histologic reporting. An international working group was convened to develop practical recommendations for the pathologic assessment of residual disease in neoadjuvant clinical trials of breast cancer and information expected from pathology reports. Systematic sampling of areas identified by informed mapping of the specimen and close correlation with radiological findings is preferable to overly exhaustive sampling, and permits taking tissue samples for translational research. Controversial areas are discussed, including measurement of lesion size, reporting of lymphovascular space invasion and the presence of isolated tumor cells in lymph nodes after neoadjuvant therapy, and retesting of markers after treatment. If there has been a pathological complete response, this must be clearly stated, and the presence/absence of residual ductal carcinoma in situ must be described. When there is residual invasive carcinoma, a comment must be made as to the presence/absence of chemotherapy effect in the breast and lymph nodes. The Residual Cancer Burden is the preferred method for quantifying residual disease in neoadjuvant clinical trials in breast cancer; other methods can be included per trial protocols and regional preference. Posttreatment tumor staging using the Tumor-Node-Metastasis system should be included. These recommendations for standardized pathological evaluation and reporting of neoadjuvant breast cancer specimens should improve prognostication for individual patients and allow comparison of treatment outcomes within and across clinical trials.\n\nPeintinger, Florentia\n\n\n"
},
{
"text": "\n156293\nDiverse action of lipoteichoic acid and lipopolysaccharide on neuroinflammation, blood-brain barrier disruption, and anxiety in mice.\n\nMayerhofer, R\n\nFröhlich, EE\n\nReichmann, F\n\nFarzi, A\n\nKogelnik, N\n\nFröhlich, E\n\nSattler, W\n\nHolzer, P\n\nBeiträge in Fachzeitschriften\nISI:000391908200020\n27751870.0\n10.1016/j.bbi.2016.10.011\nPMC5419569\nMicrobial metabolites are known to affect immune system, brain, and behavior via activation of pattern recognition receptors such as Toll-like receptor 4 (TLR4). Unlike the effect of the TLR4 agonist lipopolysaccharide (LPS), the role of other TLR agonists in immune-brain communication is insufficiently understood. We therefore hypothesized that the TLR2 agonist lipoteichoic acid (LTA) causes immune activation in the periphery and brain, stimulates the hypothalamic-pituitary-adrenal (HPA) axis and has an adverse effect on blood-brain barrier (BBB) and emotional behavior. Since LTA preparations may be contaminated by LPS, an extract of LTA (LTAextract), purified LTA (LTApure), and pure LPS (LPSultrapure) were compared with each other in their effects on molecular and behavioral parameters 3h after intraperitoneal (i.p.) injection to male C57BL/6N mice. The LTAextract (20mg/kg) induced anxiety-related behavior in the open field test, enhanced the circulating levels of particular cytokines and the cerebral expression of cytokine mRNA, and blunted the cerebral expression of tight junction protein mRNA. A dose of LPSultrapure matching the amount of endotoxin/LPS contaminating the LTAextract reproduced several of the molecular and behavioral effects of LTAextract. LTApure (20mg/kg) increased plasma levels of tumor necrosis factor-α (TNF-α), interleukin-6 and interferon-γ, and enhanced the transcription of TNF-α, interleukin-1β and other cytokines in the amygdala and prefrontal cortex. These neuroinflammatory effects of LTApure were associated with transcriptional down-regulation of tight junction-associated proteins (claudin 5, occludin) in the brain. LTApure also enhanced circulating corticosterone, but failed to alter locomotor and anxiety-related behavior in the open field test. These data disclose that TLR2 agonism by LTA causes peripheral immune activation and initiates neuroinflammatory processes in the brain that are associated with down-regulation of BBB components and activation of the HPA axis, although emotional behavior (anxiety) is not affected. The results obtained with an LTA preparation contaminated with LPS hint at a facilitatory interaction between TLR2 and TLR4, the adverse impact of which on long-term neuroinflammation, disruption of the BBB and mental health warrants further analysis.\n Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.\n\nFarzi, Aitak\n\nFröhlich, Eleonore\n\nHolzer, Peter\n\nReichmann, Florian\n\nSattler, Wolfgang\n\n\n"
},
{
"text": "\n167171\nMetabolic syndrome in hypertensive women in the age of menopause: a case study on data from general practice electronic health records.\n\nŠabanović, Š\n\nLjiljana, MT\n\nBabič, F\n\nVadovský, M\n\nParalič, J\n\nVčev, A\n\nHolzinger, A\n\nBeiträge in Fachzeitschriften\nISI:000428922800001\n29609615.0\n10.1186/s12911-018-0601-2\nPMC5880083\nThere is potential for medical research on the basis of routine data used from general practice electronic health records (GP eHRs), even in areas where there is no common GP research platform. We present a case study on menopausal women with hypertension and metabolic syndrome (MS). The aims were to explore the appropriateness of the standard definition of MS to apply to this specific, narrowly defined population group and to improve recognition of women at high CV risk.\n We investigated the possible uses offered by available data from GP eHRs, completed with patients interview, in goal of the study, using a combination of methods. For the sample of 202 hypertensive women, 47-59 years old, a data set was performed, consisted of a total number of 62 parameters, 50 parameters used from GP eHRs. It was analysed by using a mixture of methods: analysis of differences, cutoff values, graphical presentations, logistic regression and decision trees.\n The age range found to best match the emergency of MS was 51-55 years. Deviations from the definition of MS were identified: a larger cut-off value of the waist circumference measure (89 vs 80 cm) and parameters BMI and total serum cholesterol perform better as components of MS than the standard parameters waist circumference and HDL-cholesterol. The threshold value of BMI at which it is expected that most of hypertensive menopausal women have MS, was found to be 25.5. The other best means for recognision of women with MS include triglycerides above the threshold of 1.7 mmol/L and information on statins use. Prevention of CVD should focus on women with a new onset diabetes and comorbidities of a long-term hypertension with anxiety/depression.\n The added value of this study goes beyond the current paradigm on MS. Results indicate characteristics of MS in a narrowly defined, specific population group. A comprehensive view has been enabled by using heterogenoeus data and a smart combination of various methods for data analysis. The paper shows the feasibility of this research approach in routine practice, to make use of data which would otherwise not be used for research.\n\nHolzinger, Andreas\n\n\n"
},
{
"text": "\n181977\nImpact of Predilatation Prior to Transcatheter Aortic Valve Implantation With the Self-Expanding Acurate neo Device (from the Multicenter NEOPRO Registry).\n\nPagnesi, M\n\nKim, WK\n\nConradi, L\n\nBarbanti, M\n\nStefanini, GG\n\nSchofer, J\n\nHildick-Smith, D\n\nPilgrim, T\n\nAbizaid, A\n\nZweiker, D\n\nTesta, L\n\nTaramasso, M\n\nWolf, A\n\nWebb, JG\n\nSedaghat, A\n\nVan der Heyden, JAS\n\nZiviello, F\n\nMacCarthy, P\n\nHamm, CW\n\nBhadra, OD\n\nSchäfer, U\n\nCosta, G\n\nTamburino, C\n\nCannata, F\n\nReimers, B\n\nEitan, A\n\nAlsanjari, O\n\nAsami, M\n\nWindecker, S\n\nSiqueira, D\n\nSchmidt, A\n\nBianchi, G\n\nBedogni, F\n\nSaccocci, M\n\nMaisano, F\n\nJensen, CJ\n\nNaber, CK\n\nAlenezi, A\n\nWood, DA\n\nSinning, JM\n\nBrouwer, J\n\nTzalamouras, V\n\nVan Mieghem, NM\n\nColombo, A\n\nLatib, A\n\nBeiträge in Fachzeitschriften\nISI:000523600500012\n32098656.0\n10.1016/j.amjcard.2020.02.003\nNone\nSafety and feasibility of transfemoral Acurate neo implantation without systematic predilatation are not fully investigated. Our aim was to evaluate the use and impact of pre-implantation balloon aortic valvuloplasty (pre-BAV) before transcatheter aortic valve implantation (TAVI) with Acurate neo. The NEOPRO Registry retrospectively included 1, 63 patients who underwent transfemoral TAVI with Acurate neo at 18 centers between January 2012 and March 2018. Information on pre-BAV was available for 1, 62 patients (99.9%). Primary end points were pre-discharge moderate-to-severe paravalvular aortic regurgitation (PAR II+), 30-day new permanent pacemaker implantation, and 30-day all-cause mortality or stroke. A total of 1, 62 patients who underwent TAVI with (n = 1, 51) or without predilatation (n = 211) were included. A reduction in the pre-BAV rate was observed during the study period (from 95.7% in the first date quintile to 78.4% in the last date quintile). Patients who underwent pre-BAV had higher degrees of aortic valve (AV) and left ventricular outflow tract (LVOT) calcification. Primary endpoints were similar between pre-BAV and no pre-BAV groups (PAR II+ 5.5% vs 3.4%, p = 0.214; 30-day permanent pacemaker implantation 9.0% vs 8.0%, p = 0.660; 30-day death or stroke 4.9% vs 4.4%, p = 0.743). The need for postdilatation and other procedural outcomes were comparable between groups. Predilatation did not have a significant impact on primary endpoints across AV and LVOT calcification subgroups (subgroup analyses) and was not independently associated with primary endpoints (multivariate analyses). In conclusion, transfemoral Acurate neo implantation without predilatation appears to be feasible and safe, especially in patients with milder degrees of AV and LVOT calcification.\n Copyright © 2020 Elsevier Inc. All rights reserved.\n\nSchmidt, Albrecht\n\nZweiker, David\n\n\n"
},
{
"text": "\n185861\nAllogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides and Sézary syndrome. An updated experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.\n\nDomingo-Domenech, E\n\nDuarte, RF\n\nBoumedil, A\n\nOnida, F\n\nGabriel, I\n\nFinel, H\n\nArcese, W\n\nBrowne, P\n\nBeelen, D\n\nKobbe, G\n\nVeelken, H\n\nArranz, R\n\nGreinix, H\n\nLenhoff, S\n\nPoiré, X\n\nRibera, JM\n\nThompson, J\n\nZuckerman, T\n\nMufti, GJ\n\nCortelezzi, A\n\nOlavarria, E\n\nDreger, P\n\nSureda, A\n\nMontoto, S\n\nBeiträge in Fachzeitschriften\nISI:000606287700003\n33420392.0\n10.1038/s41409-020-01197-3\nNone\nAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option in advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS). This study presents an updated analysis of the initial experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT) describing the outcomes after allo-HSCT for MF and SS, with special emphasis on the impact of the use of unrelated donors (URD).\n Eligible for this study were patients with advanced-stage MF or SS who underwent a first allo-HSCT from matched HLA-identical related or URD between January/1997 and December/2011. Sixty patients have been previously reported.\n 113 patients were included [77 MF (68%)]; 61 (54%) were in complete or partial remission, 86 (76%) received reduced-intensity protocols and 44 (39%) an URD allo-HSCT. With a median follow up for surviving patients of 73 months, allo-HSCT resulted in an estimated overall survival (OS) of 38% at 5 years, and a progression-free survival (PFS) of 26% at 5 years. Multivariate analysis demonstrated that advanced-phase disease (complete remission/partial remission >3, primary refractory or relapse/progression in patients that had received 3 or more lines of systemic treatment prior to transplant or the number of treatment lines was not known), a short interval between diagnosis and transplant (<18 months) were independent adverse prognostic factors for PFS; advanced-phase disease and the use of URDs were independent adverse prognostic factors for OS.\n This extended series supports that allo-HSCT is able to effectively rescue over one third of the population of patients with advanced-stage MF/SS. High relapse rate is still the major cause of failure and needs to be improved with better strategies before and after transplant. The negative impact of URD is a matter of concern and needs to be further elucidated in future studies.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n130221\nA trial comparing noninvasive ventilation strategies in preterm infants.\n\nKirpalani, H\n\nMillar, D\n\nLemyre, B\n\nYoder, BA\n\nChiu, A\n\nRoberts, RS\n\nNIPPV Study Group\n\nBeiträge in Fachzeitschriften\nISI:000326354500007\n23944299.0\n10.1056/NEJMoa1214533\nNone\nBackgroundTo reduce the risk of bronchopulmonary dysplasia in extremely-low-birth-weight infants, clinicians attempt to minimize the use of endotracheal intubation by the early introduction of less invasive forms of positive airway pressure. MethodsWe randomly assigned 1009 infants with a birth weight of less than 1000 g and a gestational age of less than 30 weeks to one of two forms of noninvasive respiratory support nasal intermittent positive-pressure ventilation (IPPV) or nasal continuous positive airway pressure (CPAP) at the time of the first use of noninvasive respiratory support during the first 28 days of life. The primary outcome was death before 36 weeks of postmenstrual age or survival with bronchopulmonary dysplasia. ResultsOf the 497 infants assigned to nasal IPPV for whom adequate data were available, 191 died or survived with bronchopulmonary dysplasia (38.4%), as compared with 180 of 490 infants assigned to nasal CPAP (36.7%) (adjusted odds ratio, 1.09; 95% confidence interval, 0.83 to 1.43; P=0.56). The frequencies of air leaks and necrotizing enterocolitis, the duration of respiratory support, and the time to full feedings did not differ significantly between treatment groups. ConclusionsAmong extremely-low-birth-weight infants, the rate of survival to 36 weeks of postmenstrual age without bronchopulmonary dysplasia did not differ significantly after noninvasive respiratory support with nasal IPPV as compared with nasal CPAP. (Funded by the Canadian Institutes of Health Research; NIPPV ClinicalTrials.gov number, NCT00433212; Controlled-Trials.com number, ISRCTN15233270.) In a randomized trial involving extremely-low-birth-weight infants eligible for noninvasive ventilation, the survival rate without bronchopulmonary dysplasia after nasal intermittent positive-pressure ventilation was similar to the rate after nasal continuous positive airway pressure. In extremely-low-birth-weight infants, bronchopulmonary dysplasia remains a leading cause of early death, 1) a strong predictor of later neurologic impairment, 2) and a major reason for resource use(3) and rehospitalization during the first year of life.(4) Improvements in survival rates among such infants have led to rates of bronchopulmonary dysplasia of up to 60% at the lowest gestational ages.(1), 5), 6) Tracheal intubation and mechanical ventilation are associated with ventilator-induced lung injury and airway inflammation, leading to bronchopulmonary dysplasia.(7), 8) Prolonged duration of intubation and mechanical ventilation in extremely-low-birth-weight infants is associated with an increased risk of death or survival with neurologic ...\n\nPichler, Gerhard\n\nReiterer, Friedrich\n\nUrlesberger, Berndt\n\n\n"
},
{
"text": "\n131095\nWork-related upper limb musculoskeletal disorders in paediatric laparoscopic surgery. A multicenter survey.\n\nEsposito, C\n\nEl Ghoneimi, A\n\nYamataka, A\n\nRothenberg, S\n\nBailez, M\n\nFerro, M\n\nGamba, P\n\nCastagnetti, M\n\nMattioli, G\n\nDelagausie, P\n\nAntoniou, D\n\nMontupet, P\n\nMarte, A\n\nSaxena, A\n\nBertozzi, M\n\nPhilippe, P\n\nVarlet, F\n\nLardy, H\n\nCaldamone, A\n\nSettimi, A\n\nPelizzo, G\n\nBecmeur, F\n\nEscolino, M\n\nDe Pascale, T\n\nNajmaldin, A\n\nSchier, F\n\nBeiträge in Fachzeitschriften\nISI:000323413000020\n23932617.0\n10.1016/j.jpedsurg.2013.01.054\nNone\nBackground: Surgeons are at risk for developing work-related musculoskeletal symptoms (WMS). The present study aims to examine the physical factors and their association with WMS among pediatric laparoscopic surgeons. Methods: A questionnaire consisting of 21 questions was created and mailed to 25 pediatric laparoscopic surgeons (LG). 23/25 surgeons (92%) completed the survey. The questionnaire was analyzed and then split into 2 groups. Group 1 (LG1) included surgeons with greater laparoscopic experience, and group 2 (LG2) included surgeons with less important laparoscopic experience. In addition, we constructed and sent to the same surgeons a similar questionnaire focused on WMS after an open procedure (OG) with the aim to compare results of LG with OG. Results: The prevalence rate of WMS with shoulder symptoms was 78.2% in surgeons that performed laparoscopy for more than 10 years, with 60.8% also reporting other pain. In 66.6% this pain is evident only after a long-lasting procedure. Forty-four percent of these surgeons require painkillers at least twice a week. Fifty percent of these surgeons also suffer at home. Fifty-five and one half percent of surgeons indicate that this pain is related to their laparoscopic activity. Forty-three and a half percent think that laparoscopy is beneficial only for the patient but has a bad ergonomic effect for surgeons. Sixty-five and two-tenths percent think that robotic surgery can be helpful to improve ergonomics. Comparing the groups, WMS occur more frequently in LG (78.2%) than in OG (56.5%), but this difference was not statistically significant (chi(2) = 0.05). In addition, WMS occur more frequently in LG1 (84.6%) than in LG2 (70%), but this difference was not statistically significant (chi(2) = 0.05). Conclusions: These results confirmed a strong association between WMS and the number of laparoscopic procedures performed. Skilled laparoscopic surgeons have more pain than less skilled laparoscopic surgeons. WMS in the same group of surgeons are more frequent after laparoscopy than after open procedures. The majority of surgeons refer to shoulder symptoms. (C) 2013 Elsevier Inc. All rights reserved.\n\n\n"
},
{
"text": "\n156138\nHistological parameters and alcohol abstinence determine long-term prognosis in patients with alcoholic liver disease.\n\nLackner, C\n\nSpindelboeck, W\n\nHaybaeck, J\n\nDouschan, P\n\nRainer, F\n\nTerracciano, L\n\nHaas, J\n\nBerghold, A\n\nBataller, R\n\nStauber, RE\n\nBeiträge in Fachzeitschriften\nISI:000395218200020\n27894795.0\n10.1016/j.jhep.2016.11.011\nNone\nFew data exist on predictors of long-term prognosis in patients with alcoholic liver disease (ALD). Most studies have only assessed short-term prognosis in patients with advanced ALD. We aimed to assess the prognostic impact of clinical, biochemical and histological parameters on long-term prognosis in patients with early/compensated and decompensated ALD.\n Consecutive patients (n=192) with biopsy-proven liver disease due to alcohol abuse were analyzed retrospectively. Prognostic factors were evaluated in patients with early/compensated ALD (n=60) and in patients with decompensated ALD (clinical decompensation and/or bilirubin >3mg/dl at entry) (n=132). Factors that predict long-term survival were identified using Cox regression models.\n Liver-related mortality at 5years was 13% in early/compensated and 43% in decompensated ALD. In early/compensated ALD patients, long-term prognosis was determined by fibrosis stage, but not by clinical or biochemical variables. Severe fibrosis (F3/4) was present in 52% and had a major impact on 10-year mortality (F3/4: 45% vs. F0-2: 0%, p<0.001). In contrast, in decompensated patients, a combination of clinical features (sex), biochemical markers of liver failure (bilirubin, international normalized ratio [INR]), and histological features (pericellular fibrosis) predicted long-term survival. During follow-up, abstinence from alcohol was an important predictor of survival in both early/compensated and decompensated ALD.\n Fibrosis stage is the main predictor of long-term survival in patients with early/compensated ALD, while clinical, biochemical and histological parameters predict survival in patients with decompensated disease. Promoting abstinence may improve survival in patients with both early and advanced ALD.\n In this study, we evaluated long-term outcome in 192 patients with alcoholic liver disease who underwent liver biopsy: 60 patients with early disease (no symptoms) and 132 patients with advanced disease (jaundice, complications of cirrhosis). Importantly, half of the patients with 'early' disease already had severe fibrosis or cirrhosis on liver histology and dismal outcome (45% mortality at 10years). Abstinence from alcohol improved the prognosis in both early and advanced stages of the disease.\n Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.\n\nBerghold, Andrea\n\nDouschan, Philipp\n\nHaas, Josef\n\nHaybäck, Johannes\n\nLackner, Karoline\n\nRainer, Florian\n\nSpindelböck, Walter Johann\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n156524\nTRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation.\n\nKirschmer, N\n\nBandleon, S\n\nvon Ehrlich-Treuenstätt, V\n\nHartmann, S\n\nSchaaf, A\n\nLamprecht, AK\n\nMiranda-Laferte, E\n\nLangsenlehner, T\n\nRitter, O\n\nEder, P\n\nBeiträge in Fachzeitschriften\nISI:000392842600058\n27992507.0\n10.1371/journal.pone.0168446\nPMC5167390\nThe Transient Receptor Potential Channel Subunit 4 (TRPC4) has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. Gαq protein-coupled receptor (GPCR) stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT) activation. Functional properties of TRPC4 are also based on the expression of the TRPC4 splice variants TRPC4α and TRPC4β. Aim of the present study was to analyze cytosolic Ca2+ signals, signaling, hypertrophy and vitality of cardiomyocytes in dependence on the expression level of either TRPC4α or TRPC4β. The analysis of Ca2+ transients in neonatal rat cardiomyocytes (NRCs) showed that TRPC4α and TRPC4β affected Ca2+ cycling in beating cardiomyocytes with both splice variants inducing an elevation of the Ca2+ transient amplitude at baseline and TRPC4β increasing the Ca2+ peak during angiotensin II (Ang II) stimulation. NRCs infected with TRPC4β (Ad-C4β) also responded with a sustained Ca2+ influx when treated with Ang II under non-pacing conditions. Consistent with the Ca2+ data, NRCs infected with TRPC4α (Ad-C4α) showed an elevated calcineurin/NFAT activity and a baseline hypertrophic phenotype but did not further develop hypertrophy during chronic Ang II/phenylephrine stimulation. Down-regulation of endogenous TRPC4α reversed these effects, resulting in less hypertrophy of NRCs at baseline but a markedly increased hypertrophic enlargement after chronic agonist stimulation. Ad-C4β NRCs did not exhibit baseline calcineurin/NFAT activity or hypertrophy but responded with an increased calcineurin/NFAT activity after GPCR stimulation. However, this effect was not translated into an increased propensity towards hypertrophy but rather less hypertrophy during GPCR stimulation. Further analyses revealed that, although hypertrophy was preserved in Ad-C4α NRCs and even attenuated in Ad-C4β NRCs, cardiomyocytes had an increased apoptosis rate and thus were less viable after chronic GPCR stimulation. These findings suggest that TRPC4α and TRPC4β differentially affect Ca2+ signals, calcineurin/NFAT signaling and hypertrophy but similarly impair cardiomyocyte viability during GPCR stimulation.\n\nLangsenlehner, Tanja\n\n\n"
},
{
"text": "\n159716\nCancer Stem Cell Gene Variants in CD44 Predict Outcome in Stage II and Stage III Colon Cancer Patients.\n\nStotz, M\n\nHerzog, SA\n\nPichler, M\n\nSmolle, M\n\nRiedl, J\n\nRossmann, C\n\nBezan, A\n\nStöger, H\n\nRenner, W\n\nBerghold, A\n\nGerger, A\n\nBeiträge in Fachzeitschriften\nISI:000402167700063\n28373475.0\n10.21873/anticanres.11545\nNone\nGrowing evidence suggests that human cancers are stem cell diseases and recent data support the existence of cancer stem cells (CSCs) in a variety of malignancies, including colon cancer. These CSCs were shown to be capable of initiating tumor development and progression. Several studies have suggested CD133, CD26 and CD44 as markers of tumor-initiating cells of colon cancer. The purpose of the present study was to assess the impact of single-nucleotide polymorphisms (SNPs) in stem cell-related genes on clinical outcome in a large cohort of colon cancer patients with clinical stage II and III.\n Data from 599 consecutive patients with colon cancer stage II and III, treated between 1995 and 2011 at a single centre, were retrospectively evaluated. Genomic DNA was extracted from paraffin-embedded normal tissue distant from the tumor to obtain germline DNA. Allelic distribution of polymorphisms was tested for deviation from Hardy-Weinberg equilibrium using χ2-test. The association of polymorphisms with time to recurrence (TTR) and overall survival (OS) was analyzed using Kaplan-Meier curves and compared by the log-rank test. Case-wise deletion for missing polymorphisms was used in univariable and multivariable analyses.\n CD44 rs187115 showed a statistically significant association with TTR; patients carrying at least one G allele had a significant reduced risk of recurrence compared to patients with the homozygous A/A variant (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.48-0.94, p=0.019). CD44 rs13347 showed a statistically significant association with OS. Patients carrying at least one T allele in rs13347 had a significantly reduced risk of death compared to patients with the homozygous C/C variant (HR=0.61, 95% CI=0.41-0.92, p=0.019). None of the other investigated polymorphisms (CD44 rs187116, CD44 rs7116432, CD44 rs353639, DPP4 rs2268889, DPP4 rs3788979, DPP4 rs7608798 and CD133 rs2240688) were associated with either TTR or OS.\n Germline variants rs13347 and rs187115 in the stem cell gene CD44 are prognostically relevant in stage II and III colon cancer patients.\n Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.\n\nBerghold, Andrea\n\nGerger, Armin\n\nHerzog, Sereina Annik\n\nPichler, Martin\n\nRenner, Wilfried\n\nRiedl, Jakob\n\nSmolle, Maria Anna\n\nStoeger, Herbert\n\nTerbuch, Angelika\n\n\n"
},
{
"text": "\n170917\nThe Use of Central Pathology Review With Digital Slide Scanning in Advanced-stage Mycosis Fungoides and Sézary Syndrome: A Multi-institutional and International Pathology Study.\n\nGru, AA\n\nKim, J\n\nPulitzer, M\n\nGuitart, J\n\nBattistella, M\n\nWood, GS\n\nCerroni, L\n\nKempf, W\n\nWillemze, R\n\nPawade, J\n\nQuerfeld, C\n\nSchaffer, A\n\nPincus, L\n\nTetzlaff, M\n\nDuvic, M\n\nScarisbrick, J\n\nPorcu, P\n\nMangold, AR\n\nDiCaudo, DJ\n\nShinohara, M\n\nHong, EK\n\nHorton, B\n\nKim, YH\n\nBeiträge in Fachzeitschriften\nISI:000432228900004\n29543675.0\n10.1097/PAS.0000000000001041\nNone\nThis pathology PILOT study aims to define the role and feasibility of centralized pathology review in a cohort of 75 patients from different centers in the United States and Europe using digital slide scanning. The pathologic material from 75 patients who had been diagnosed with mycosis fungoides/Sézary syndrome and were clinically staged as IIb or above was retrieved from 11 participating centers. Each pathology reviewer was provided with the pathologic diagnosis (by the referring pathologist), and the following list of histopathologic criteria (presence or absence) from the initial report: epidermotropism, folliculotropism (FT), large cell transformation, syringotropism, and granulomas. Patients with advance stage were selected for this study as this is a population where there is significant variability in the diagnosis of pathologic prognostic and predictive biomarkers. The slides were digitally scanned with an Aperio scanner and consensus review of cases occurred when major or minor discrepancies between the referral diagnosis and central pathology review occurred. Among the 75 cases, 70 (93.3%) had a final consensus diagnosis between the 3 central review pathologists. The overall agreement between the consensus review and the referring pathologist was 60%. The overall agreement was also higher between the reviewers and consensus review, compared with the referring pathologist and consensus. 65.3% of cases had some type of discrepancy (major or minor) between the outside and consensus review. Major discrepancies were seen in 34 of 73 cases (46.6%; 73 cases indicated a yes or no response). Minor discrepancies were seen in 32 of 75 (42.7%) of cases. Most of the major discrepancies were accounted by a difference in interpretation in the presence or absence of large cell transformation or FT. Most minor discrepancies were explained by a different interpretation in the expression of CD30. We found digital slide scanning to be a beneficial, reliable, and practical for a methodical approach to perform central pathology review in the context of a large clinical prospective study.\n\nCerroni, Lorenzo\n\n\n"
},
{
"text": "\n182746\nExpanding the Molecular Spectrum of Secretory Carcinoma of Salivary Glands With a Novel VIM-RET Fusion.\n\nSkálová, A\n\nBanečkova, M\n\nThompson, LDR\n\nPtáková, N\n\nStevens, TM\n\nBrcic, L\n\nHyrcza, M\n\nMichal, M\n\nSimpson, RHW\n\nSantana, T\n\nMichal, M\n\nVaněček, T\n\nLeivo, I\n\nBeiträge in Fachzeitschriften\nISI:000576512100001\n32675658.0\n10.1097/PAS.0000000000001535\nNone\nSecretory carcinoma (SC), originally described as mammary analogue SC, is a predominantly low-grade salivary gland neoplasm characterized by a recurrent t(12;15)(p13;q25) translocation, resulting in ETV6-NTRK3 gene fusion. Recently, alternative ETV6-RET, ETV6-MAML3, and ETV6-MET fusions have been found in a subset of SCs lacking the classic ETV6-NTRK3 fusion transcript, but still harboring ETV6 gene rearrangements.\n Forty-nine cases of SC revealing typical histomorphology and immunoprofile were analyzed by next-generation sequencing using the FusionPlex Solid Tumor kit (ArcherDX). All 49 cases of SC were also tested for ETV6, RET, and NTRK3 break by fluorescence in situ hybridization and for the common ETV6-NTRK3 fusions using reverse transcription polymerase chain reaction.\n Of the 49 cases studied, 37 (76%) occurred in the parotid gland, 7 (14%) in the submandibular gland, 2 (4%) in the minor salivary glands, and 1 (2%) each in the nasal mucosa, facial skin, and thyroid gland. SCs were diagnosed more frequently in males (27/49 cases; 55%). Patients' age at diagnosis varied from 15 to 80 years, with a mean age of 49.9 years. By molecular analysis, 40 cases (82%) presented the classic ETV6-NTRK3 fusion, whereas 9 cases (18%) revealed an alternate fusion. Of the 9 cases negative for the ETV6-NTRK3 fusion, 8 cases presented with ETV6-RET fusion. In the 1 remaining case in the parotid gland, next-generation sequencing analysis identified a novel VIM-RET fusion transcript. In addition, the analysis indicated that 1 recurrent high-grade case in the submandibular gland was positive for both ETV6-NTRK3 and MYB-SMR3B fusion transcripts.\n A novel finding in our study was the discovery of a VIM-RET fusion in 1 patient with SC of the parotid gland who could possibly benefit from RET-targeted therapy. In addition, 1 recurrent high-grade case was shown to harbor 2 different fusions, namely, ETV6-NTRK3 and MYB-SMR3B. The expanded molecular spectrum provides a novel insight into SC oncogenesis and carries important implications for molecular diagnostics, as this is the first SC-associated translocation with a non-ETV6 5' fusion partner. This finding further expands the definition of SC while carrying implications for selecting the appropriate targeted therapy.\n\nBrcic, Luka\n\n\n"
},
{
"text": "\n3109\nLipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells.\n\nPussinen, PJ\n\nLindner, H\n\nGlatter, O\n\nReicher, H\n\nKostner, GM\n\nWintersperger, A\n\nMalle, E\n\nSattler, W\n\nBeiträge in Fachzeitschriften\nISI:000087531100005\n10832094.0\n10.1016/S1388-1981(00)00035-4\nNone\nalpha-Tocopheryl succinate (alpha-TS) is a potent inhibitor of tumor cell proliferation. The goal of the present study was to investigate whether and to what extent alpha-TS associates with plasma lipoproteins and if alpha-TS-enriched lipoproteins inhibit breast cancer cell growth in a manner comparable to the free drug. In vitro enrichment of human plasma revealed that alpha-TS readily associated with the main lipoprotein classes, findings confirmed in vivo in mice. At the highest alpha-TS concentrations, lipoproteins carrying 50000 (VLDL), 5000 (LDL) and 700 (HDL) alpha-TS molecules per lipoprotein particle were generated. alpha-TS enrichment generated lipoprotein particles with slightly decreased density and increased particle radius. To study whether the level of LDL-receptor (LDL-R) expression affects alpha-TS uptake from apoB/E containing lipoprotein particles human breast cancer cells with low (MCF-7) and normal (HBL-100) LDL-R expression were used. The uptake of free, VLDL- and (apoE-free) HDL(3)-associated alpha-TS was nearly identical for both cell lines. In contrast, uptake of LDL-associated alpha-TS by HBL-100 cells (normal LDL-R expression) was about twice as high as compared to MCF-7 cells (low LDL-R expression). VLDL and LDL-associated alpha-TS inhibited proliferation most effectively at the highest concentration of alpha-TS used (100% inhibition of MCF-7 growth with 20 microg/ml of lipoprotein-associated alpha-TS). However, also alpha-TS-free VLDL and LDL inhibited HBL-100 cell proliferation up to 55%. In both cell lines, alpha-TS-enriched HDL(3) inhibited cell growth by 40-60%. Incubation of both cell lines in the presence of free or lipoprotein-associated alpha-TS resulted in DNA fragmentation indicative of apoptosis. Collectively, the present findings demonstrate that: (1) alpha-TS readily associates with lipoproteins in vitro and in vivo; (2) the lipoprotein-enrichment efficacy was dependent on the particle size and/or the triglyceride content of the lipoprotein; (3) uptake of LDL-associated alpha-TS was apparently dependent on the level of LDL-R expression; and (4) lipoproteins were efficient alpha-TS carriers inducing reduced cell proliferation rates and apoptosis in human breast cancer cells as observed for the free drug.\n\nHinteregger, Helga\n\nKostner, Gerhard\n\nMalle, Ernst\n\nSattler, Wolfgang\n\nWintersperger, Andrea\n\n\n"
},
{
"text": "\n119269\nPotentially inappropriate medication in geriatric patients: the Austrian consensus panel list.\n\nMann, E\n\nBöhmdorfer, B\n\nFrühwald, T\n\nRoller-Wirnsberger, RE\n\nDovjak, P\n\nDückelmann-Hofer, C\n\nFischer, P\n\nRabady, S\n\nIglseder, B\n\nBeiträge in Fachzeitschriften\nISI:000302374700005\n22134410.0\n10.1007/s00508-011-0061-5\nNone\nThe practice of inappropriate medication and drug prescription is a major risk factor for adverse drug reactions in geriatric patients and increases the individual, as well as overall, rates of hospital admissions, resulting in increased health care expenditures. A consensus-based list of drugs, generally to be avoided in geriatric patients, is a practical tool to possibly improve the quality of prescribing.\n The aim was to develop a consensus-based list of potentially inappropriate medications (PIM) for geriatric patients in Austria. Local market characteristics and documented prescribing regimens were considered in detail.\n A two-round Delphi process involving eight experts in the field of geriatric medicine was undertaken to create a list of potentially inappropriate medications. Using a 5-point Likert scale (from strong agreement to strong disagreement), mean ratings from the experts were evaluated for each drug selected in the first round. The participants were first asked to comment on the potential inappropriateness of a preliminary list of drugs, and to propose alternate substances missing in the previous questionnaire for a second rating process. All drugs whose upper limit of the 95% CI was less than 3.0 were classified as potentially inappropriate. Drugs with a 95% CI enclosing 3.0 entered a second rating by the experts, in addition to other substances suggested during the first questionnaire. Drugs in the second rating were evaluated in comparable fashion to the first one. The final list was synthesized from the results in both rounds.\n Out of a preliminary list of 102 drugs, 61 drugs (59.2%) were classified as potentially inappropriate for geriatric persons in the first Delphi- round. In the second rating, six drugs that were reevaluated, and six drugs proposed additionally, were rated as potentially inappropriate. The final list contains 73 drugs to be avoided in older patients because of an unfavorable benefit/risk profile and/or unproven effectiveness. The list also contains suggestions for therapeutic alternatives and information about pharmacological and pharmacokinetic characteristics of all drugs judged as potentially inappropriate.\n The current Austrian list of potentially inappropriate medications may be a helpful tool for clinicians to increase the quality of prescribing in older patients. Like all explicit lists previously published, its validity needs to be proven in validation studies.\n\nRoller-Wirnsberger, Regina\n\n\n"
}
]
}