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"text": "\n171683\nExpert-Level Diagnosis of Nonpigmented Skin Cancer by Combined Convolutional Neural Networks.\n\nTschandl, P\n\nRosendahl, C\n\nAkay, BN\n\nArgenziano, G\n\nBlum, A\n\nBraun, RP\n\nCabo, H\n\nGourhant, JY\n\nKreusch, J\n\nLallas, A\n\nLapins, J\n\nMarghoob, A\n\nMenzies, S\n\nNeuber, NM\n\nPaoli, J\n\nRabinovitz, HS\n\nRinner, C\n\nScope, A\n\nSoyer, HP\n\nSinz, C\n\nThomas, L\n\nZalaudek, I\n\nKittler, H\n\nBeiträge in Fachzeitschriften\nISI:000455574400008\n30484822.0\n10.1001/jamadermatol.2018.4378\nPMC6439580\nConvolutional neural networks (CNNs) achieve expert-level accuracy in the diagnosis of pigmented melanocytic lesions. However, the most common types of skin cancer are nonpigmented and nonmelanocytic, and are more difficult to diagnose.\n To compare the accuracy of a CNN-based classifier with that of physicians with different levels of experience.\n A CNN-based classification model was trained on 7895 dermoscopic and 5829 close-up images of lesions excised at a primary skin cancer clinic between January 1, 2008, and July 13, 2017, for a combined evaluation of both imaging methods. The combined CNN (cCNN) was tested on a set of 2072 unknown cases and compared with results from 95 human raters who were medical personnel, including 62 board-certified dermatologists, with different experience in dermoscopy.\n The proportions of correct specific diagnoses and the accuracy to differentiate between benign and malignant lesions measured as an area under the receiver operating characteristic curve served as main outcome measures.\n Among 95 human raters (51.6% female; mean age, 43.4 years; 95% CI, 41.0-45.7 years), the participants were divided into 3 groups (according to years of experience with dermoscopy): beginner raters (<3 years), intermediate raters (3-10 years), or expert raters (>10 years). The area under the receiver operating characteristic curve of the trained cCNN was higher than human ratings (0.742; 95% CI, 0.729-0.755 vs 0.695; 95% CI, 0.676-0.713; P < .001). The specificity was fixed at the mean level of human raters (51.3%), and therefore the sensitivity of the cCNN (80.5%; 95% CI, 79.0%-82.1%) was higher than that of human raters (77.6%; 95% CI, 74.7%-80.5%). The cCNN achieved a higher percentage of correct specific diagnoses compared with human raters (37.6%; 95% CI, 36.6%-38.4% vs 33.5%; 95% CI, 31.5%-35.6%; P = .001) but not compared with experts (37.3%; 95% CI, 35.7%-38.8% vs 40.0%; 95% CI, 37.0%-43.0%; P = .18).\n Neural networks are able to classify dermoscopic and close-up images of nonpigmented lesions as accurately as human experts in an experimental setting.\n\nZalaudek, Iris\n\n\n"
},
{
"text": "\n174992\nAntithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation.\n\nLopes, RD\n\nHeizer, G\n\nAronson, R\n\nVora, AN\n\nMassaro, T\n\nMehran, R\n\nGoodman, SG\n\nWindecker, S\n\nDarius, H\n\nLi, J\n\nAverkov, O\n\nBahit, MC\n\nBerwanger, O\n\nBudaj, A\n\nHijazi, Z\n\nParkhomenko, A\n\nSinnaeve, P\n\nStorey, RF\n\nThiele, H\n\nVinereanu, D\n\nGranger, CB\n\nAlexander, JH\n\nAUGUSTUS Investigators\n\nBeiträge in Fachzeitschriften\nISI:000465144100012\n30883055.0\n10.1056/NEJMoa1817083\nNone\nAppropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear.\n In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events.\n Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group.\n In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).\n Copyright © 2019 Massachusetts Medical Society.\n\nScherr, Daniel\n\n\n"
},
{
"text": "\n181109\nDorsal minimally invasive plate osteosynthesis of the distal tibia with regard to adjacent anatomical characteristics.\n\nHohenberger, GM\n\nSchwarz, AM\n\nGrechenig, C\n\nSchwarz, U\n\nFeigl, GC\n\nBakota, B\n\nBeiträge in Fachzeitschriften\nNone\n32067765.0\n10.1016/j.injury.2020.02.047\nNone\nThe aim of this study was to perform MIPO of the distal tibia from a dorsomedial and dorsolateral approach and to evaluate their feasibility and risk of injury to adjacent anatomical structures.\n A total of 18 extremities from 9 adult human cadavers was included in the study. In each cadaver, one lower leg underwent application of a 12-hole 3.5 LCP metaphyseal plate from the medial and the further one from the lateral approach. For the medial approach, a 4 cm skin incision was performed at the tibial border of the Achilles tendon, starting from 1 cm proximal to its insertion point at the calcaneal tuberosity. Entrance was gained between the medial border of the flexor hallucis longus tendon and the medial neurovascular bundle. Regarding the lateral approach, the skin was incised over a length of about 4 cm at the lateral border of the Achilles tendon, approximately 1 cm proximal to its insertion point. Entrance was gained between the Achilles tendon and the peroneus brevis muscle. The plates were inserted in direct bone contact in a proximal direction and the proximal and distal ends were fixed. During dissection, the proximal and distal holes beneath the crossing points of the neurovascular bundle and the plate were noted. The distal and proximal intersection points of the neurovascular bundle and the plate were measured with reference to the distal border of the plate.\n Concerning the medial approach, the neurovascular bundle was on median located between the 6th and 11th plate holes starting from distal. The bundle intersected the plate distally at a mean height of 65.8 mm and proximally at 156.8 mm on average. For the lateral approach, the neurovascular bundle was situated between the 6th and the 12th plate hole from distal. It crossed the plate distally at a mean of 61.0 mm and proximal at a mean height of 153.9 mm. In none of the cases, lacerations of the neurovascular bundle were observed.\n In conclusion, MIPO from the dorsomedial and dorsolateral approach are both safe procedures as indicated by our study.\n Copyright © 2020 Elsevier Ltd. All rights reserved.\n\nHohenberger, Gloria\n\nSchwarz, Angelika\n\n\n"
},
{
"text": "\n4360\nAnti-inflammatory effects of aspirin and sodium salicylate.\n\nAmann, R\n\nPeskar, BA\n\nBeiträge in Fachzeitschriften\nISI:000176916100001\n12106797.0\n10.1016%2FS0014-2999%2802%2901828-9\nNone\nAspirin (acetylsalicylic acid) is one of the most widely used drugs worldwide. It acetylates cyclooxygenases thereby irreversibly blocking the conversion of arachidonic acid to prostanoids. Biotransformation of aspirin yields salicylate, a compound that possesses similar anti-inflammatory potency as aspirin but lacks aspirin's inhibitory effect on the activity of isolated cyclooxygenase. This article is aimed at providing an overview about the often conflicting results concerning the mechanisms of action of aspirin and sodium salicylate. At present, there is no common agreement about the extent to which salicylate contributes to aspirin's anti-inflammatory properties, as well as there is still no final conclusion reached about the mechanisms of action of sodium salicylate. Several possible sites of action of salicylate have been suggested: It has been shown that in intact cells-but not in purified enzyme preparations-, sodium salicylate inhibits prostanoid biosynthesis. This effect seems to be prevented in the presence of high concentrations of arachidonic acid, which has been shown to interfere with inhibition by salicylate of cyclooxygenase-2-mediated prostanoid formation in vitro. Other possible sites of action that are not directly related to cyclooxygenase inhibition have been suggested based on observations made in vitro using high concentrations of aspirin and sodium salicylate. These effects target intracellular signaling mechanisms such as kinases, including the mitogen activated protein-kinases (MAPK) cascade. With the exception of reported salicylate-induced activation of p38 MAPK, observed effects are usually inhibitory. This may be one reason for the observation that, downstream to kinases, inhibitory effects of salicylates have been observed on several nuclear transcription factors, such as nuclear transcription factor kappa B (NF-kB) or activator protein 1 (AP-1). Several reports have also shown interference by salicylates with the expression of cyclooxygenase-2, which, depending on experimental models, can be observed as inhibitory but also stimulatory effects. Antioxidant properties of salicylates, adenosine release induced by sodium salicylate and aspirin-triggered lipoxin formation are additional mechanisms that may contribute to anti-inflammatory properties of aspirin and/or sodium salicylate. An additional focus of this review is the discussion of interactions between aspirin, sodium salicylate and other non-steroidal anti-inflammatory drugs (NSAIDs), which are of particular relevance in the gastro-intestinal and cardiovascular systems.\n\nPeskar, Bernhard\n\n\n"
},
{
"text": "\n4941\nPassive biaxial mechanical response of aged human iliac arteries.\n\nSchulze-Bauer, CA\n\nMörth, C\n\nHolzapfel, GA\n\nBeiträge in Fachzeitschriften\nISI:000184176500012\n12929245.0\n10.1115/1.1574331\nNone\nInflation and extension tests of arteries are essential for the understanding of arterial wall mechanics. Data for such tests of human arteries are rare. At autopsy we harvested 10 non-diseased external iliac arteries of aged subjects (52-87 yrs). Structural homogeneity was ensured by means of ultrasound imaging, and anamneses of patients were recorded. We measured the axial in situ stretches, load-free geometries and opening angles. Passive biaxial mechanical responses of preconditioned cylindrical specimens were studied in 37 degrees C calcium-free Tyrode solution under quasistatic loading conditions. Specimens were subjected to pressure cycles varying from 0 to 33.3 kPa (250 mmHg) at nine fixed axial loads, varying from 0 to 9.90N. For the description of the load-deformation behavior we employed five "two-dimensional" orthotropic strain-energy functions frequently used in arterial wall mechanics. The associated constitutive models were compared in regard to their ability of representing the experimental data. Histology showed that the arteries were of the muscular type. In contrast to animal arteries they exhibited intimal layers of considerable thickness. The average ratio of wall thickness to outer diameter was 7.7, which is much less than observed for common animal arteries. We found a clear correlation between age and the axial in situ stretch lambda is (r = -0.72, P = 0.03), and between age and distensibility of specimens, i.e. aged specimens are less distensible. Axial in situ stretches were clearly smaller (1.07 +/- 0.09, mean +/- SD) than in animal arteries. For one specimen lambda is was even smaller than 1.0, i.e. the vessel elongated axially upon excision. The nonlinear and anisotropic load-deformation behavior showed small hystereses. For the majority of specimens we observed axial stretches smaller than 1.3 and circumferential stretches smaller than 1.1 for the investigated loading range. Data from in situ inflation tests showed a significant increase of the axial stretch with intraluminal pressure. Thus, for this type of artery the axial in situ stretch of a non-pressurized vessel is not representative of the axial in vivo stretch. None of the constitutive models were able to represent the deformation behavior of the entire loading range. For the physiological loading range, however, some of the models achieved good agreement with the experimental data.\n\n\n"
},
{
"text": "\n5295\nPersisting fetal microchimerism does not interfere with forensic Y-chromosome typing.\n\nKlintschar, M\n\nSchwaiger, P\n\nRegauer, S\n\nMannweiler, S\n\nKleiber, M\n\nBeiträge in Fachzeitschriften\nISI:000189225200007\n15040908.0\n10.1016/j.forsciint.2003.10.011\nNone\nForensic Y-chromosome typing applies Y-chromosomal polymorphisms to the analysis of male/female mixed stains such as vaginal swabs in rape cases. The sensitivity of this approach exceeds that of cytological techniques combined with autosomal DNA typing. Y-chromosome typing is based on the assumption that Y-chromosomal DNA found in tissue or secretions of women must originate from a male individual, usually the perpetrator. Nevertheless, it was shown recently that fetal cells can migrate into the female body during pregnancy and can persist for decades ("persisting fetal microchimerism"). The body of a woman after a pregnancy with a male embryo can thus display a small fraction of fetal cells with Y-chromosomes. Using high sensitivity PCR protocols (reamplification with nested primers and up to 60 PCR cycles) fetal cells were previously identified in a number of maternal tissues including skin, blood, muscle and solid organs. It is, however, not clear at present, whether these cells can occur in vaginal secretions, and whether they are capable of producing false positive results in forensic Y-chromosome typing. To evaluate these questions, 66 blood samples of women with at least one son and nine vaginal swabs of women without sexual intercourse in the last 2 weeks were amplified for a stretch of the SRY gene. Eight thyroid gland tissues with already established male fetal microchimerism were used as positive control samples. Blood samples of 10 young girls without history of pregnancy were used as negative controls. Using a PCR with 10 ng of extracted DNA and 30 PCR cycles ("routine sensitivity assay") none of the samples yielded positive results. However, in a PCR with 200 ng of extracted DNA and 45 PCR cycles ("high sensibility assay"), 14% of the blood samples of mothers and 33% of the vaginal swabs amplified for SRY. Our results thus show that increasing the sensitivity of the PCR method and the amount of template DNA produce positive results while protocols used for routine Y-chromosomal typing with small amounts of DNA (approximately 10 ng of DNA) and with a limited number of PCR cycles (approximately 30) can clearly eliminate this peril.\n\nMannweiler, Sebastian\n\nRegauer, Sigrid\n\n\n"
},
{
"text": "\n89003\nBile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor.\n\nPineda Torra, I\n\nClaudel, T\n\nDuval, C\n\nKosykh, V\n\nFruchart, JC\n\nStaels, B\n\nBeiträge in Fachzeitschriften\nISI:000180699000010\n12554753.0\n10.1210/me.2002-0120\nNone\nPeroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor that controls lipid and glucose metabolism and exerts antiinflammatory activities. PPARalpha is also reported to influence bile acid formation and bile composition. Farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor that mediates the effects of bile acids on gene expression and plays a major role in bile acid and possibly also in lipid metabolism. Thus, both PPARalpha and FXR appear to act on common metabolic pathways. To determine the existence of a molecular cross-talk between these two nuclear receptors, the regulation of PPARalpha expression by bile acids was investigated. Incubation of human hepatoma HepG2 cells with the natural FXR ligand chenodeoxycholic acid (CDCA) as well as with the nonsteroidal FXR agonist GW4064 resulted in a significant induction of PPARalpha mRNA levels. In addition, hPPARalpha gene expression was up-regulated by taurocholic acid in human primary hepatocytes. Cotransfection of FXR/retinoid X receptor in the presence of CDCA led to up to a 3-fold induction of human PPARalpha promoter activity in HepG2 cells. Mutation analysis identified a FXR response element in the human PPARalpha promoter (alpha-FXR response element (alphaFXRE)] that mediates bile acid regulation of this promoter. FXR bound the alphaFXRE site as demonstrated by gel shift analysis, and CDCA specifically increased the activity of a heterologous promoter driven by four copies of the alphaFXRE. In contrast, neither the murine PPARalpha promoter, in which the alphaFXRE is not conserved, nor a mouse alphaFXRE-driven heterologous reporter, were responsive to CDCA treatment. Moreover, PPARalpha expression was not regulated in taurocholic acid-fed mice. Finally, induction of hPPARalpha mRNA levels by CDCA resulted in an enhanced induction of the expression of the PPARalpha target gene carnitine palmitoyltransferase I by PPARalpha ligands. In concert, these results demonstrate that bile acids stimulate PPARalpha expression in a species-specific manner via a FXRE located within the human PPARalpha promoter. These results provide molecular evidence for a cross-talk between the FXR and PPARalpha pathways in humans.\n\n\n"
},
{
"text": "\n91033\nImpact of lymph node dissection on cancer specific survival in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.\n\nRoscigno, M\n\nShariat, SF\n\nMargulis, V\n\nKarakiewicz, P\n\nRemzi, M\n\nKikuchi, E\n\nLangner, C\n\nLotan, Y\n\nWeizer, A\n\nBensalah, K\n\nRaman, JD\n\nBolenz, C\n\nGuo, CC\n\nWood, CG\n\nZigeuner, R\n\nWheat, J\n\nKabbani, W\n\nKoppie, TM\n\nNg, CK\n\nSuardi, N\n\nBertini, R\n\nFernandez, MI\n\nMikami, S\n\nIsida, M\n\nMichel, MS\n\nMontorsi, F\n\nBeiträge in Fachzeitschriften\nISI:000266020500025\n19371878.0\n10.1016/j.juro.2009.02.021\nNone\nPURPOSE: We examined the impact of lymphadenectomy on the clinical outcomes of patients with upper tract urothelial cancer treated with radical nephroureterectomy. MATERIALS AND METHODS: Data were collected on 1, 30 consecutive patients with pT1-4 upper tract urothelial cancer treated with radical nephroureterectomy at 13 centers worldwide. Patients were grouped according to nodal status (pN0 vs pNx vs pN+). The choice to perform lymphadenectomy was determined by the treating surgeon. All pathology slides were reevaluated by dedicated genitourinary pathologists. Univariable and multivariable Cox regression models measured the association of nodal status (pN0 vs pNx vs pN+) with cancer specific survival. RESULTS: Overall 412 patients (36.5%) had pN0 disease, 578 had pNx disease (51.1%) and 140 had pN+ disease (12.4%). The 5-year cancer specific survival estimate was lower in patients with pN+ compared to those with pNx disease (35% vs 69%, p <0.001), which in turn was lower than that in those with pN0 disease (69% vs 77%, p = 0.024). In the subgroup of patients with pT1 disease (345) cancer specific survival rates were not different in those with pN0 and pNx. In pT2-4 cases (813) cancer specific survival estimates were lowest in pN+, intermediate in pNx and highest in pN0 (33% vs 58% vs 70%, p = 0.017). When adjusted for the effects of standard clinicopathological features pN+ was an independent predictor of cancer specific survival (p <0.001). pNx was significantly associated with worse prognosis than pN0 in pT2-4 upper tract urothelial cancer only. CONCLUSIONS: Nodal status is a significant predictor of cancer specific survival in upper tract urothelial cancer. pNx is significantly associated with a worse prognosis than pN0 in pT2-4 tumors. Patients expected to have pT2-4 disease should undergo lymphadenectomy to improve staging and thereby help guide decision making regarding adjuvant chemotherapy.\n\nLangner, Cord\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n107648\nDown-regulation of lung Kruppel-like factor in the nitrofen-induced hypoplastic lung.\n\nLukošiūtė, A\n\nDoi, T\n\nDingemann, J\n\nRuttenstock, EM\n\nPuri, P\n\nBeiträge in Fachzeitschriften\nISI:000287446200010\n21053160.0\n10.1055/s-0030-1262800\nNone\nIntroduction: Pulmonary hypoplasia is a primary cause of high morbidity and mortality in neonates with Congenital Diaphragmatic Hernia (CDH). However, the precise pathogenesis of PH associated with CDH is still not clearly understood. It has been recently reported that lung Kruppel-like factor (LKLF), a member of the Kruppel-like factor family of transcription factors, is predominantly expressed in lungs and plays an important role in lung morphogenesis and functional maturation. It has been reported that homozygous deletion of LKLF gene in mice results in reduced lung morphogenesis. It is further reported that chimeric mice derived from LKLF-/- embryonic stem cells exhibit delayed lung development especially in the later gestational stages. We therefore designed this study to test the hypothesis that the LKLF gene is down-regulated during later stages of lung development in nitrofen-induced hypoplastic lungs. Material and Methods: Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, D18, and D21 and divided into 3 groups: control, nitrofen without CDH(CDH(-)) and nitrofen with CDH(CDH(+)) (n = 24 for each group). Real-time RT-PCR analysis was performed to investigate pulmonary gene expression levels of LKLF. Differences between the 3 groups at each time point were tested statistically and significance was accepted at p < 0.05. Immunohistochemistry was also performed to evaluate LKLF protein expression and distribution. Results: The relative mRNA expression levels of LKLF on D18 and D21 were significantly decreased (p < 0.01) in CDH(-) and CDH(+) groups compared to controls. The gene expression levels of LKLF on D15 did not differ significantly between the nitrofen group and controls. Immunohistochemical study showed strong LKLF immunoreactivity on D18 and D21 in nitrofen-induced hypoplastic lung compared to controls, whereas no difference was seen on D15. Conclusions: Our results provide evidence for the first time that LKLF is down-regulated in the later stages of lung development in nitrofen-induced hypoplastic lungs. These data suggest that the down-regulation of LKLF during this critical period of lung morphogenesis may impair lung development and maturation, resulting in pulmonary hypoplasia in the nitrofen CDH model.\n\n\n"
},
{
"text": "\n132085\nPerception of disease and doctor-patient relationship experienced by patients with psoriasis: a questionnaire-based study.\n\nLinder, D\n\nDall'olio, E\n\nGisondi, P\n\nBerardesca, E\n\nGennaro, ED\n\nPennella, AR\n\nGiannetti, A\n\nPeserico, A\n\nGirolomoni, G\n\nBeiträge in Fachzeitschriften\nISI:000269331100006\n19658445.0\n10.2165/11311190-000000000-00000\nNone\nMany studies have addressed the impact of psoriasis on quality of life, but few studies have investigated patient perception of the disease or the patient-physician relationship. As with most chronic diseases, improvement in the patient-physician relationship may be important in the proper management of patients with psoriasis. To assess how psoriasis and its treatments are subjectively experienced by patients as well as patient expectations with regard to the patient-physician relationship. A discussion agenda for 'focus group meetings' was organized by a group of sociologists, psychologists, educators, researchers, and clinicians active in the field of psychodermatology. Four meetings were held in Northern and Central Italy and participants included one moderator and either eight dermatologists or eight patients. Discussions were based on a predefined agenda and included: (i) the psychological representation of psoriasis; (ii) the hetero- and self-perception of the patient; (iii) the patient-physician relationship; and (iv) the development of an educational intervention for dermatologists in order to improve the patient-physician relationship. A questionnaire, based on the information gathered at the focus groups, was administered to 323 patients with moderate to severe chronic plaque psoriasis from 17 dermatology clinics throughout Italy. Three hundred patients completed the questionnaire. Psoriasis elicited anger, annoyance at the inconvenience of the disease, and irritation in approximately 50% of the patients, whilst 38% of patients were unable to describe their emotional state. Aspects of life that were limited by psoriasis included clothing (57%), social interactions (43%), and personal hygiene (31%). The disease was often seen by patients as incomprehensible, incurable, and uncontrollable. More than half of the patients stressed their need to be listened to by the treating physician, and their wish that the physician should use simple language and should improve their psychological skills and interpersonal communication techniques. Dermatologists need to convey to patients with psoriasis the feeling of 'understanding the disease, of hope about its curability, and the 'perception of control.' These elements should be taken into account when treating patients and whenever educational interventions are planned.\n\nLinder, Michael Dennis\n\n\n"
},
{
"text": "\n139953\nClinical signs in young patients with stroke related to FAST: results of the sifap1 study.\n\nKaps, M\n\nGrittner, U\n\nJungehülsing, G\n\nTatlisumak, T\n\nKessler, C\n\nSchmidt, R\n\nJukka, P\n\nNorrving, B\n\nRolfs, A\n\nTanislav, C\n\nsifap1 Investigators\n\nBeiträge in Fachzeitschriften\nISI:000345762300008\n25380809.0\n10.1136/bmjopen-2014-005276\nPMC4225229\nThe present study aimed to evaluate the frequency of warning signs in younger patients with stroke with a special regard to the 'FAST' scheme, a public stroke recognition instrument (face, arm, speech, timely).\n Primary stroke care in participating centres of a multinational European prospective cross-sectional study (Stroke in Young Fabry Patients; sifap1). Forty-seven centres from 15 European countries participate in sifap1.\n 5023 acute patients with stroke (aged 18-55 years) patients (96.5% Caucasians) were enrolled in the study between April 2007 and January 2010.\n sifap1 was originally designed to investigate the relation of juvenile stroke and Fabry disease. A secondary aim of sifap1 was to investigate stroke patterns in this specific group of patients. The present investigation is a secondary analysis addressing stroke presenting symptoms with a special regard to signs included in the FAST scheme.\n 4535 patients with transient ischaemic attack (TIA; n=1071), ischaemic stroke (n=3396) or other (n=68) were considered in the presented analysis. FAST symptoms could be traced in 76.5% of all cases. 35% of those with at least one FAST symptom had all three symptoms. At least one FAST symptom could be recognised in 69.1% of 18-24 years-old patients, in 74% of those aged 25-34 years, in 75.4% of those aged 35-44 years, and 77.8% in 45-55 years-old patients. With increasing stroke severity signs included in the FAST scheme were more prevalent (National Institute of Health Stroke Scale, NIHSS<5: 69%, NIHSS 6-15: 98.9%, NIHSS>15: 100%). Clustering clinical signs according to FAST lower percentages of strokes in the posterior circulation (65.2%) and in patients with TIA (62.3%) were identified.\n FAST may be applied as a useful and rapid tool to identify stroke symptoms in young individuals aged 18-55 years. Especially in patients eligible for thrombolysis FAST might address the majority of individuals.\n The study was registered in http://www.clinicaltrials.gov (No. NCT00414583).\n Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n165814\nPredicting the Risk to Develop Preeclampsia in the First Trimester Combining Promoter Variant -98A/C of LGALS13 (Placental Protein 13), Black Ethnicity, Previous Preeclampsia, Obesity, and Maternal Age.\n\nMadar-Shapiro, L\n\nKarady, I\n\nTrahtenherts, A\n\nSyngelaki, A\n\nAkolekar, R\n\nPoon, L\n\nCohen, R\n\nSharabi-Nov, A\n\nHuppertz, B\n\nSammar, M\n\nJuhasz, K\n\nThan, NG\n\nPapp, Z\n\nRomero, R\n\nNicolaides, KH\n\nMeiri, H\n\nBeiträge in Fachzeitschriften\nISI:000433980000002\n28728156.0\n10.1159/000477933\nPMC5882584\nLGALS13 (placental protein 13 [PP13]) promoter DNA polymorphisms was evaluated in predicting preeclampsia (PE), given PP13's effects on hypotension, angiogenesis, and immune tolerance.\n First-trimester plasma samples (49 term and 18 intermediate) of PE cases matched with 196 controls were collected from King's College Hospital, London, repository. Cell-free DNA was extracted and the LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs was determined in BeWo trophoblast-like cells with luciferase assays. Adjusted odds ratio (OR) was calculated for the A/A genotype combined with maternal risk factors.\n The A/A, A/C, and C/C genotypes in the -98 promoter position were in Hardy-Weinberg equilibrium in the control but not in the PE group (p < 0.036). The dominant A/A genotype had higher frequency in the PE group (p < 0.001). The A/C and C/C genotypes protected from PE (p < 0.032). The ORs to develop term and all PE, calculated for the A/A genotype, previous PE, body mass index (BMI) >35, black ethnicity, and maternal age >40 were 15.6 and 11.0, respectively (p < 0.001). In luciferase assays, the "-98A" promoter variant had lower expression than the "-98C" variant in non-differentiated (-13%, p = 0.04) and differentiated (-26%, p < 0.001) BeWo cells. Forskolin-induced differentiation led to a larger expression increase in the "-98C" variant than in the "-98A" variant (4.55-fold vs. 3.85-fold, p < 0.001).\n Lower LGALS13 (PP13) expression with the "A" nucleotide in the -98 promoter region position (compared to "C") and high OR calculated for the A/A genotype in the -98A/C promoter region position, history of previous PE, BMI >35, advanced maternal age >40, and black ethnicity could serve to aid in PE prediction in the first trimester.\n © 2017 S. Karger AG, Basel.\n\nHuppertz, Berthold\n\n\n"
},
{
"text": "\n169935\nMuscle and tendon morphology alterations in children and adolescents with mild forms of spastic cerebral palsy.\n\nKruse, A\n\nSchranz, C\n\nTilp, M\n\nSvehlik, M\n\nBeiträge in Fachzeitschriften\nISI:000431830700001\n29743109.0\n10.1186/s12887-018-1129-4\nPMC5941654\nEarly detection of changes at the muscular level before a contracture develops is important to gain knowledge about the development of deformities in individuals with spasticity. However, little information is available about muscle morphology in children with spastic diplegic cerebral palsy (CP) without contracture or equinus gait. Therefore, the aim of this study was to compare the gastrocnemius medialis (GM) and Achilles tendon architecture of children and adolescents with spastic CP without contracture or equinus gait to that of typically developing (TD) children.\n Two-dimensional ultrasonography was used to assess the morphological properties of the GM muscle and Achilles tendon in 10 children with spastic diplegic CP (Gross Motor Function Classification System level I-II) and 12 TD children (mean age 12.0 (2.8) and 11.3 (2.5) years, respectively). The children with CP were not restricted in the performance of daily tasks, and therefore had a high functional capacity. Mean muscle and tendon parameters were statistically compared (independent t-tests or Mann-Whitney U-tests).\n When normalized to lower leg length, muscle-tendon unit length and GM muscle belly length were found to be significantly shorter (p < 0.05, effect size (ES) = 1.00 and 0.98, respectively) in the children with spastic CP. Furthermore, there was a tendency for increased Achilles tendon length when expressed as a percentage of muscle-tendon unit length (p = 0.08, ES = - 0.80) in the individuals with CP. This group also showed shorter muscle fascicles (3.4 cm vs. 4.4 cm, p < 0.01, ES = 1.12) and increased fascicle pennation angle (21.9° vs. 18.1°, p < 0.01, ES = - 1.36, respectively). However, muscle thickness and Achilles tendon cross-sectional area did not differ between groups. Resting ankle joint angle was significantly more plantar flexed (- 26.2° vs. - 20.8°, p < 0.05, ES = 1.06) in the children with CP.\n Morphological alterations of the plantar flexor muscle-tendon unit are also present in children and adolescents with mild forms of spastic CP. These alterations may contribute to functional deficits such as muscle weakness, and therefore have to be considered in the clinical decision-making process, as well as in the selection of therapeutic interventions.\n\n\n"
},
{
"text": "\n170875\nTreatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats.\n\nEverson, F\n\nGenis, A\n\nOgundipe, T\n\nDe Boever, P\n\nGoswami, N\n\nLochner, A\n\nBlackhurst, D\n\nStrijdom, H\n\nBeiträge in Fachzeitschriften\nISI:000452212400105\n30517206.0\n10.1371/journal.pone.0208537\nPMC6281242\nHIV-infection, certain antiretroviral drug classes, especially protease inhibitors (PI), and obesity are associated with increased ischaemic heart disease (IHD) risk. However, the effect of PI-free fixed dose combination (FDC) antiretroviral therapy (ART) on hearts exposed to ischaemia-reperfusion injury (I/R) is unknown, particularly in obesity. This is becoming relevant as World Health Organisation guidelines recommend a FDC ART containing (non-) nucleoside reverse transcriptase inhibitors (tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) as first-line HIV treatment. Additionally, obesity rates are rising in HIV-infected populations, not only in ART-experienced individuals, but also at the time of ART initiation, which may further increase the risk of IHD. Therefore, we investigated the effects of PI-free FDC ART in myocardial I/R-exposed hearts from obese rats. Obesity was induced in male wistar rats via a 16-week high calorie diet. At week 10, treatment with a FDC ART drug containing TDF/FTC/EFV was initiated. Biometric and metabolic parameters, as well as myocardial functional recovery and infract size (IS), and myocardial signalling proteins following I/R were assessed after 16 weeks. Obese rats presented with increased body and intraperitoneal fat mass, elevated triglyceride and TBARS levels, whilst the hearts responded to I/R with impaired functional performance and increased IS. The FDC ART treatment did not alter biometric and metabolic parameters in obese rats. In a novel finding, ART protected obese hearts against I/R as shown by improved functional performance and smaller IS vs. untreated obese hearts. Cardioprotection was underscored by increased myocardial phosphorylated endothelial nitric oxide synthase (eNOS) and reduced AMP-kinase levels. In conclusion, these results demonstrate for the first time, that 6-weeks treatment of obese rats with a FDC ART drug specifically containing TDF/FTC/EFV conferred cardioprotection against I/R. The FDC ART-induced cardioprotection was seemingly unrelated to metabolic changes, but rather due to direct cardiac mechanisms including the up-regulation of myocardial eNOS.\n\nGoswami, Nandu\n\n\n"
},
{
"text": "\n178239\nA Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.\n\nDangas, GD\n\nTijssen, JGP\n\nWöhrle, J\n\nSøndergaard, L\n\nGilard, M\n\nMöllmann, H\n\nMakkar, RR\n\nHerrmann, HC\n\nGiustino, G\n\nBaldus, S\n\nDe Backer, O\n\nGuimarães, AHC\n\nGullestad, L\n\nKini, A\n\nvon Lewinski, D\n\nMack, M\n\nMoreno, R\n\nSchäfer, U\n\nSeeger, J\n\nTchétché, D\n\nThomitzek, K\n\nValgimigli, M\n\nVranckx, P\n\nWelsh, RC\n\nWildgoose, P\n\nVolkl, AA\n\nZazula, A\n\nvan Amsterdam, RGM\n\nMehran, R\n\nWindecker, S\n\nGALILEO Investigators\n\nBeiträge in Fachzeitschriften\nISI:000506581500010\n31733180.0\n10.1056/NEJMoa1911425\nNone\nWhether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear.\n We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns.\n After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53).\n In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).\n Copyright © 2019 Massachusetts Medical Society.\n\nBugger, Heiko Matthias\n\nvon Lewinski, Dirk\n\n\n"
},
{
"text": "\n178296\nDetailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.\n\nFrid, P\n\nDrake, M\n\nGiese, AK\n\nWasselius, J\n\nSchirmer, MD\n\nDonahue, KL\n\nCloonan, L\n\nIrie, R\n\nBouts, MJRJ\n\nMcIntosh, EC\n\nMocking, SJT\n\nDalca, AV\n\nSridharan, R\n\nXu, H\n\nGiralt-Steinhauer, E\n\nHolmegaard, L\n\nJood, K\n\nRoquer, J\n\nCole, JW\n\nMcArdle, PF\n\nBroderick, JP\n\nJimenez-Conde, J\n\nJern, C\n\nKissela, BM\n\nKleindorfer, DO\n\nLemmens, R\n\nMeschia, JF\n\nRundek, T\n\nSacco, RL\n\nSchmidt, R\n\nSharma, P\n\nSlowik, A\n\nThijs, V\n\nWoo, D\n\nWorrall, BB\n\nKittner, SJ\n\nMitchell, BD\n\nPetersson, J\n\nRosand, J\n\nGolland, P\n\nWu, O\n\nRost, NS\n\nLindgren, A\n\nStroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), and the MRI-Genetics Interface Exploration (MRI-GENIE) Study\n\nBeiträge in Fachzeitschriften\nISI:000495426200001\n31709475.0\n10.1007/s00415-019-09613-5\nPMC7035231\nPosterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS.\n Out of 3, 01 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2, 81 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression.\n PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions.\n Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n186710\nSelective denervation of the corrugator supercilii muscle for the treatment of idiopatic trigeminal neuralgia purely paroxysmal distributed in the supraorbital and suprathrochlear dermatomes.\n\nGualdi, A\n\nCambiaso-Daniel, J\n\nGatti, J\n\nPeled, ZM\n\nHagan, R\n\nBertossi, D\n\nWurzer, P\n\nKamolz, LP\n\nScherer, S\n\nPietramaggiori, G\n\nBeiträge in Fachzeitschriften\nISI:000625890900001\n33663369.0\n10.1186/s10194-021-01218-6\nPMC7931360\nIdiopatic trigeminal neuralgia purely paroxysmal (ITNp) distributed in the supraorbital and suprathrochlear dermatomes (SSd), refractory to conventional treatments have been linked to the hyperactivity of the corrugator supercilii muscle (CSM). In these patients, the inactivation of the CSM via botulinum toxin type A (BTA) injections has been proven to be safe and effective in reducing migraine burden. The main limitation of BTA is the need of repetitive injections and relative high costs. Based on the study of the motor innervation of the CSM, we describe here an alternative approach to improve these type of migraines, based on a minimally invasive denervation of the CSM.\n Motor innervation and feasibility of selective CSM denervation was first studied on fresh frozen cadavers. Once the technique was safely established, 15 patients were enrolled. To be considered eligible, patients had to meet the following criteria: positive response to BTA treatment, migraine disability assessment score > 24, > 15 migraine days/month, no occipital/temporal trigger points and plausible reasons to discontinue BTA treatment. Pre- and post- operative migraine headache index (MHI) were compared, and complications were classified following the Clavien-Dindo classification (CDC).\n Fifteen patients (9 females and 6 males) underwent the described surgical procedure. The mean age was 41 ± 10 years. Migraine headache episodes decreased from 24 ± 4 day/month to 2 ± 2 (p < 0.001) The MHI decreased from 208 ± 35 to 10 ± 11 (p < 0.001). One patient (7%) had a grade I complication according to the CDC. No patient needed a second operative procedure.\n Our findings suggest that the selective CSM denervation represents a safe and minimally invasive approach to improve ITNp distributed in the SSd associated with CSM hyperactivation.\n The data collection was conducted as a retrospective quality assessment study and all procedures were performed in accordance with the ethical standards of the national research committee and the 1964 Helsinki Declaration and its later amendments.\n\nCambiaso Daniel, Janos\n\nKamolz, Lars-Peter\n\nWurzer, Paul\n\n\n"
},
{
"text": "\n4207\nProlonged endurance challenge at moderate altitude: effect on serum eosinophil cationic protein, eosinophil dynamics, and lung function.\n\nDomej, W\n\nSchwaberger, G\n\nTilz, GP\n\nFöldes-Papp, Z\n\nDemel, U\n\nLang, J\n\nvon Duvillard, SP\n\nBeiträge in Fachzeitschriften\nISI:000175226400019\n11948040.0\n10.1378%2Fchest.121.4.1111\nNone\nBACKGROUND: Eosinophils contain granule proteins such as eosinophil cationic protein (ECP) that have proinflammatory effects on airways. ECP may be released on activation of eosinophils into the plasma and is widely used as a marker of bronchial hyperreactivity and allergic inflammation. Environmental factors as well as intense physical exertion may influence eosinophil-related bronchial hyperreactivity. STUDY OBJECTIVES: To investigate the effect of endurance exercise at moderate altitude on levels of circulating eosinophils, serum ECP, serum osmolality (sOS), and dynamic pulmonary function parameters in healthy mountaineers. SETTING: Alpine field study performed in the Alps of Upper Styria in Austria. Type of exercise: Ascent of a mountain at maximal speed. PARTICIPANTS: Thirty healthy male volunteers from a troop of military mountaineers. RESULTS: Mean ECP concentration increased by 66% at the summit checkpoint (H2) and remained at 63% above baseline (base checkpoint [H0]) after descent (H4), while the blood eosinophil count decreased concomitantly from 250/microL at H0 (preexercise) to 118/microL (53%) at H2 and to 22/microL (81%) at H4. The total serum ECP concentration adjusted to sOS correlated negatively with blood eosinophil count (r = - 0.37; p < 0.0001) and PaO(2) (r = - 0.34; p < 0.001), but positively with the peak expiratory flow (PEF) [r = 0.45; p < 0.0001]. Although sOS correlated with serum ECP at H2 (r = 0.47; p = 0.02) and at 12 h after the start of the experiment (H12) [r = 0.57; p = 0.003], the relationship between total ECP and sOS (r = 0.19; p = 0.034) was less pronounced. FEV(1) in percentage of FVC (%FEV(1)/FVC) [the Tiffenau test], forced expiratory flow rate at 25% of vital capacity, and PEF were significantly higher at H2 than at H0 and H4. %FEV(1)/FVC decreased to 88% (p < 0.01) and 83% (p < 0.001) predicted at H12 and 24 h after start of the experiment, respectively. CONCLUSION: Results provide strong evidence for nonspecific activation of blood eosinophils during prolonged intense aerobic exercise at moderate altitude, modifying both eosinophil dynamics and regulation of ECP release in healthy subjects.\n\nDemel, Ulrike\n\nDomej, Wolfgang\n\nSchwaberger, Guenther\n\nTilz, Gernot\n\n\n"
},
{
"text": "\n7732\nCapsaicin and nociception in the rat and mouse. Possible role of substance P.\n\nGamse, R\n\nBeiträge in Fachzeitschriften\nISI:A1982PG67300001\n6182473.0\n10.1007/BF00510129\nNone\nNewborn or adult rats and mice were treated with capsaicin. The effect of systemic or intrathecal treatment on thermonociception, chemonociception, content and release of immunoreactive substance P (I-SP) was investigated. Treatment of two day old rats caused a small, but life-long elevation of the hot plate or tail withdrawal latency. Treatment of adult rats led to a large increase in the reaction time on the hot plate for 4--10 days but the tail withdrawal latency was only slightly elevated for not more than 1--2 days. Mice treated on the 2nd day of life had normal reaction times on the hot plate and a small and inconsistent prolongation of the tail withdrawal latency. In contrast, mice treated on day 7, 10 or as adults had greatly prolonged latencies in both tests for at least 3 months. The changes in latencies were not affected by naloxone or methysergide. Responses to noxious chemical stimuli were moderately inhibited in mice treated on the 2nd day of life, but almost abolished in mice treated on day 7, 10 or as adults. Neonatal capsaicin treatment of rats resulted in a depletion of I-SP in spinal cord and sciatic nerve for 20 months. Capsaicin-evoked release of I-SP from rat spinal cord was reduced by 93% after neonatal treatment, but only by 69% 2 weeks after adult treatment. Treatment of mice on day 2 caused a similar decrease of the I-SP content in spinal cord and of the capsaicin-evoked I-SP release (88%) as treatment on day 4 or 7 although behavioral changes were different. After treatment of adult mice release of I-SP was reduced by 93%. Capsaicin administered intrathecally to rats or mice depleted I-SP in the spinal cord but not in the sciatic nerve. The animals were almost insensitive to noxious heat (tail withdrawal test) and to local application of mustard oil or capsaicin to the hindpaw. Chemosensitivity of the eye, however, remained unchanged. The experiments indicate that systemic or intrathecal capsaicin treatment of rats or mice affects thermo- and chemonociception but species differences were found. It appears, furthermore, that changes in substance P alone cannot explain all the observed behavioral effects after capsaicin treatment.\n\n\n"
},
{
"text": "\n89222\nIbandronate prevents bone loss and reduces vertebral fracture risk in male cardiac transplant patients: a randomized double-blind, placebo-controlled trial.\n\nFahrleitner-Pammer, A\n\nPiswanger-Soelkner, JC\n\nPieber, TR\n\nObermayer-Pietsch, BM\n\nPilz, S\n\nDimai, HP\n\nPrenner, G\n\nTscheliessnigg, KH\n\nHauge, E\n\nPortugaller, RH\n\nDobnig, H\n\nBeiträge in Fachzeitschriften\nISI:000267234400023\n19257824.0\n10.1359/jbmr.090216\nNone\nBone loss and fractures are common complications after cardiac transplantation (CTP). The aim of this study was to investigate whether intravenous ibandronate is an effective preventive option. Thirty-five male cardiac transplant recipients received either ibandronate (IBN) 2 mg intravenously every 3 mo or matching placebo (CTR) in addition to 500 mg calcium carbonate and 400 IE vitamin D(3). Sera were collected at CTP and every 3 mo thereafter. At baseline and 6 and 12 mo, standardized spinal X-rays and BMD measurements were taken. Bone biopsies were taken at CTP and after 6 mo from six patients. In the IBN group, 13% of the patients sustained a new morphometric vertebral fracture compared with 53% in the CTR group (absolute risk reduction [ARR], 40%; relative risk reduction [RRR], 75%; p = 0.04). BMD remained unchanged with IBN treatment but in the CTR group decreased at the lumbar spine by 25% and at the femoral neck by 23% (both p < 0.0001) over the 1-yr period. Serum bone resorption markers carboxy-terminal telopeptide region of type I collagen (sCTX) and TRACP 5b were significantly increased in the CTR group and decreased in the IBN group at all time points compared with baseline. In contrast, both osteocalcin and bone-specific alkaline phosphatase levels showed, after a similar decrease over the first 3 mo in both groups, a marked rise in the CTR subjects and steadily declining levels in the IBN patients throughout the remainder of the study period. Three paired biopsies were available from each group. Despite the small sample size, a difference in the relative change of eroded surface (68% in the CTR versus -23% in the IBN group, p < 0.05) could be shown. Intravenous IBN reduced fractures, preserved bone mass, and prevented uncoupling of bone formation and resorption after CTP. The favorable effects on bone turnover were also supported by histomorphometric findings.\n\nDimai, Hans\n\nFahrleitner-Pammer, Astrid\n\nObermayer-Pietsch, Barbara\n\nPieber, Thomas\n\nPilz, Stefan\n\nPiswanger-Solkner, Claudia\n\nPortugaller, Rupert\n\nPrenner, Günther\n\n\n"
}
]
}