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"text": "\n102378\nAzathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial.\n\nReinisch, W\n\nAngelberger, S\n\nPetritsch, W\n\nShonova, O\n\nLukas, M\n\nBar-Meir, S\n\nTeml, A\n\nSchaeffeler, E\n\nSchwab, M\n\nDilger, K\n\nGreinwald, R\n\nMueller, R\n\nStange, EF\n\nHerrlinger, KR\n\nInternational AZT-2 Study Group\n\nBeiträge in Fachzeitschriften\nISI:000278387700012\n20551460.0\n10.1136/gut.2009.194159\nNone\nThe aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn's disease (CD) with moderate or severe endoscopic recurrence.\n This was a 1 year, double-blind, double-dummy, randomised study which took place in 21 gastroenterology centres in Austria, the Czech Republic, Germany and Israel. The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6-24 months without subsequent clinical recurrence and with a Crohn's disease activity index (CDAI) score <200, but with moderate or severe endoscopic recurrence. The study drugs were azathioprine 2.0-2.5 mg/kg/day or mesalazine 4 g/day over 1 year. The primary end point was therapeutic failure during 1 year, defined as a CDAI score > or = 200 and an increase of > or = 60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction.\n Treatment failure occurred in 22.0% (9/41) of azathioprine-treated patients and 10.8% (4/37) of mesalazine-treated patients, a difference of 11.1% (95% CI -5.0% to 27.3%, p=0.19). Clinical recurrence was significantly less frequent with azathioprine versus mesalazine (0/41 (0%) vs 4/37 (10.8%), p=0.031), whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients (9/41 (22.0%) vs 0%, p=0.002). The proportion of patients showing > or = 1 point reduction in Rutgeerts score between baseline and month 12 was 63.3% (19/30) and 34.4% (11/32) in the azathioprine and mesalazine groups, respectively (p=0.023).\n In this population of patients with postoperative CD at high risk of clinical recurrence, superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure.\n\nJahnel, Jörg\n\nPetritsch, Wolfgang\n\n\n"
},
{
"text": "\n120844\nCytokines and the risk of preterm delivery in twin pregnancies.\n\nRode, L\n\nKlein, K\n\nLarsen, H\n\nHolmskov, A\n\nAndreasen, KR\n\nUldbjerg, N\n\nRamb, J\n\nBødker, B\n\nSkibsted, L\n\nSperling, L\n\nHinterberger, S\n\nKrebs, L\n\nZingenberg, H\n\nWeiss, EC\n\nStrobl, I\n\nLaursen, L\n\nChristensen, JT\n\nSkogstrand, K\n\nHougaard, DM\n\nKrampl-Bettelheim, E\n\nRosthøj, S\n\nVogel, I\n\nTabor, A\n\nBeiträge in Fachzeitschriften\nISI:000305764500012\n22914392.0\n10.1097/AOG.0b013e31825bc3cd\nNone\nTo estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment.\n This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay. Cytokine levels in spontaneous preterm delivery at 34-37 weeks of gestation and spontaneous preterm delivery before 34 weeks of gestation were compared with delivery at 37 weeks of gestation or more for placebo-treated women. The association between interleukin (IL)-8 and risk of spontaneous preterm delivery before 34 weeks of gestation was estimated further, including comparison according to treatment. Statistical analyses included Kruskal-Wallis test, Mann-Whitney U test, linear regression, and Cox regression analysis.\n We found a statistically significant association between IL-8 and spontaneous preterm delivery. At 23-33 weeks of gestation, the median IL-8 level was 52 pg/mL (interquartile range 39-71, range 19-1, 61) for term deliveries compared with 65 pg/mL (interquartile range 43-88, range 14-584) for spontaneous preterm delivery at 34-37 weeks of gestation and 75 pg/mL (interquartile range 57-102, range 22-1, 15) for spontaneous preterm delivery before 34 weeks of gestation (P<.001). Risk of spontaneous preterm delivery was associated with a large weekly increase in IL-8 (hazard ratio 2.0, 95% confidence interval [CI] 1.2-3.3). There was no effect of progesterone treatment on IL-8 levels. Levels of IL-8 at 18-24 weeks of gestation were associated with a cervix less than 30 mm (odds ratio 1.8, 95% CI 1.2-2.7).\n Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels.\n\nWeiss, Eva-Christine\n\n\n"
},
{
"text": "\n136116\nBrain activity changes in cognitive networks in relapsing-remitting multiple sclerosis - insights from a longitudinal FMRI study.\n\nLoitfelder, M\n\nFazekas, F\n\nKoschutnig, K\n\nFuchs, S\n\nPetrovic, K\n\nRopele, S\n\nPichler, A\n\nJehna, M\n\nLangkammer, C\n\nSchmidt, R\n\nNeuper, C\n\nEnzinger, C\n\nBeiträge in Fachzeitschriften\nISI:000334339000044\n24718105.0\n10.1371/journal.pone.0093715\nPMC3981758\nExtrapolations from previous cross-sectional fMRI studies suggest cerebral functional changes with progression of Multiple Sclerosis (MS), but longitudinal studies are scarce. We assessed brain activation changes over time in MS patients using a cognitive fMRI paradigm and examined correlations with clinical and cognitive status and brain morphology.\n 13 MS patients and 15 healthy controls (HC) underwent MRI including fMRI (go/no-go task), neurological and neuropsychological exams at baseline (BL) and follow-up (FU; minimum 12, median 20 months). We assessed estimates of and changes in fMRI activation, total brain and subcortical grey matter volumes, cortical thickness, and T2-lesion load. Bland-Altman (BA) plots served to assess fMRI signal variability.\n Cognitive and disability levels remained largely stable in the patients. With the fMRI task, both at BL and FU, patients compared to HC showed increased activation in the insular cortex, precuneus, cerebellum, posterior cingulate cortex, and occipital cortex. At BL, patients vs. HC also had lower caudate nucleus, thalamus and putamen volumes. Over time, patients (but not HC) demonstrated fMRI activity increments in the left inferior parietal lobule. These correlated with worse single-digit-modality test (SDMT) performance. BA-plots attested to reproducibility of the fMRI task. In the patients, the right caudate nucleus decreased in volume which again correlated with worsening SDMT performance.\n Given preserved cognitive performance, the increased activation at BL in the patients may be viewed as largely adaptive. In contrast, the negative correlation with SDMT performance suggests increasing parietal activation over time to be maladaptive. Several areas with purported relevance for cognition showed decreased volumes at BL and right caudate nucleus volume decline correlated with decreasing SDMT performance. This highlights the dynamics of functional changes and the strategic importance of specific brain areas for cognitive processes in MS.\n\nEnzinger, Christian\n\nFazekas, Franz\n\nFuchs, Siegrid\n\nJehna, Margit\n\nKoini, Marisa\n\nLangkammer, Christian\n\nPichler, Alexander\n\nRopele, Stefan\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n155022\nLiraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders: A pilot, open-label study.\n\nMansur, RB\n\nAhmed, J\n\nCha, DS\n\nWoldeyohannes, HO\n\nSubramaniapillai, M\n\nLovshin, J\n\nLee, JG\n\nLee, JH\n\nBrietzke, E\n\nReininghaus, EZ\n\nSim, K\n\nVinberg, M\n\nRasgon, N\n\nHajek, T\n\nMcIntyre, RS\n\nBeiträge in Fachzeitschriften\nISI:000389088600017\n27721184.0\n10.1016/j.jad.2016.09.056\nNone\nThere is a paucity of treatments that are capable of reliably and robustly improving cognitive function in adults with mood disorders. Glucagon-like peptide-1 is synthesized centrally and its receptors are abundantly expressed in neural circuits subserving cognitive function. We aimed to determine the effects of liraglutide, a GLP-1 receptor (GLP-1R) agonist, on objective measures of cognition in adults with a depressive or bipolar disorder.\n In this 4-week, pilot, open-label, domain-based study (e.g. cognition), we recruited 19 individuals with major depressive disorder (MDD) or bipolar disorder (BD) and an impairment in executive function, defined as a below-average performance in the Trail Making Test-B (TMTB). Liraglutide 1.8mg/day was added as an adjunct to existing pharmacotherapy.\n Participants had significant increases from baseline to week 4 in the TMTB standard score (age and education corrected) (Cohen's d=0.64, p=0.009) and in a composite Z-score comprising multiple cognitive tests (i.e. Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop test) (Cohen's d=0.77, p<0.001). Neither changes in mood rating scales nor metabolic parameters were associated with changes in cognitive performance (all p>0.05); however baseline insulin resistance (IR) and body mass index (BMI) moderated the changes in the composite Z-score (p=0.021 and p=0.046, respectively), indicating larger responses in individuals with higher IR and BMI at baseline. There was a significant increase in lipase (p<0.001), but individual values were above the upper limit of normality.\n Small sample size, open-label design, lack of a placebo group.\n Liraglutide was safe and well tolerated by a sample of non-diabetic individuals with mood disorders and had beneficial effects on objective measures of cognitive function. Larger studies with controlled trial designs are necessary to confirm and expand the results described herein.\n Copyright © 2016 Elsevier B.V. All rights reserved.\n\nReininghaus, Eva\n\n\n"
},
{
"text": "\n162171\nPrognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome.\n\nHennes, EM\n\nBaumann, M\n\nSchanda, K\n\nAnlar, B\n\nBajer-Kornek, B\n\nBlaschek, A\n\nBrantner-Inthaler, S\n\nDiepold, K\n\nEisenkölbl, A\n\nGotwald, T\n\nKuchukhidze, G\n\nGruber-Sedlmayr, U\n\nHäusler, M\n\nHöftberger, R\n\nKarenfort, M\n\nKlein, A\n\nKoch, J\n\nKraus, V\n\nLechner, C\n\nLeiz, S\n\nLeypoldt, F\n\nMader, S\n\nMarquard, K\n\nPoggenburg, I\n\nPohl, D\n\nPritsch, M\n\nRaucherzauner, M\n\nSchimmel, M\n\nThiels, C\n\nTibussek, D\n\nVieker, S\n\nZeches, C\n\nBerger, T\n\nReindl, M\n\nRostásy, K\n\nBIOMARKER Study Group\n\nBeiträge in Fachzeitschriften\nISI:000408411900013\n28768844.0\n10.1212/WNL.0000000000004312\nNone\nTo assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS).\n Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study.\n Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab titers were associated with younger age (p = 0.0001), diagnosis of ADEM (p = 0.005), increased CSF cell counts (p = 0.011), and negative OCB (p = 0.012). At 24-month follow-up, 96 children had no further relapses. Thirty-five children developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy-nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were associated with high MOG-ab titers (p = 0.0003) and older age at onset (p = 0.024). MS was predicted by MS-like MRI (p < 0.0001) and OCB (p = 0.007). An MOG-ab cutoff titer ≥1:1, 80 predicted a non-MS course with a sensitivity of 47% and a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and a specificity of 86%.\n Our results show that the presence of MOG-abs strongly depends on the age at disease onset and that high MOG-ab titers were associated with a recurrent non-MS disease course.\n © 2017 American Academy of Neurology.\n\n\n"
},
{
"text": "\n169792\nP2X<sub>7</sub> Deficiency Blocks Lesional Inflammasome Activity and Ameliorates Atherosclerosis in Mice.\n\nStachon, P\n\nHeidenreich, A\n\nMerz, J\n\nHilgendorf, I\n\nWolf, D\n\nWillecke, F\n\nvon Garlen, S\n\nAlbrecht, P\n\nHärdtner, C\n\nEhrat, N\n\nHoppe, N\n\nReinöhl, J\n\nvon Zur Mühlen, C\n\nBode, C\n\nIdzko, M\n\nZirlik, A\n\nBeiträge in Fachzeitschriften\nISI:000403566200015\n28377486.0\n10.1161/CIRCULATIONAHA.117.027400\nNone\nExtracellular adenosine triphosphate (ATP) binds as a danger signal to purinergic receptor P2X7 and promotes inflammasome assembly and interleukin-1β expression. We hypothesized a functional role of the signal axis ATP-P2X7 in inflammasome activation and the chronic inflammation driving atherosclerosis.\n P2X7-competent and P2X7-deficient macrophages were isolated and stimulated with lipopolysaccharide, ATP, or both. To assess whether P2X7 may have a role in atherosclerosis, P2X7 expression was analyzed in aortic arches from low density lipoprotein receptor-/- mice consuming a high-cholesterol or chow diet. P2X7+/+ and P2X7-/- low density lipoprotein receptor-/- mice were fed a high-cholesterol diet to investigate the functional role of P2X7 knockout in atherosclerosis. Human plaques were derived from carotid endarterectomy and stained against P2X7.\n Lipopolysaccharide or ATP stimulation alone did not activate caspase 1 in isolated macrophages. However, priming with lipopolysaccharide, followed by stimulation with ATP, led to an activation of caspase 1 and interleukin-1β in P2X7-competent macrophages. In contrast, P2X7-deficient macrophages showed no activation of caspase 1 after sequential stimulation while still expressing a basal amount of interleukin-1β. P2X7 receptor was higher expressed in murine atherosclerotic lesions, particularly by lesional macrophages. After 16 weeks of a high-cholesterol diet, P2X7-deficient mice showed smaller atherosclerotic lesions than P2X7-competent mice (0.162 cm2±0.023 [n=9], P2X7-/- low density lipoprotein receptor-/- : 0.084 cm2±0.01 [n=11], P=0.004) with a reduced amount of lesional macrophages. In accord with our in vitro findings, lesional caspase 1 activity was abolished in P2X7-/- mice. In addition, intravital microscopy revealed reduced leukocyte rolling and adhesion in P2X7-deficient mice. Last, we observe increased P2X7 expression in human atherosclerotic lesions, suggesting that our findings in mice are relevant for human disease.\n P2X7 deficiency resolved plaque inflammation by inhibition of lesional inflammasome activation and reduced experimental atherosclerosis. Therefore, P2X7 represents an interesting potential new target to combat atherosclerosis.\n © 2017 American Heart Association, Inc.\n\nZirlik, Andreas\n\n\n"
},
{
"text": "\n176388\nPerioperative chemotherapy versus neoadjuvant chemoradiation for patients with adenocarcinoma of the distal esophagus in Austria: a retrospective analysis.\n\nKoch, OO\n\nWeitzendorfer, M\n\nVarga, M\n\nTschoner, A\n\nPartl, R\n\nPerathoner, A\n\nGehwolf, P\n\nKapp, KS\n\nFügger, R\n\nÖfner, D\n\nEmmanuel, K\n\nBeiträge in Fachzeitschriften\nISI:000483392800001\n31426805.0\n10.1186/s12957-019-1693-6\nPMC6701048\nThe aim of this study was to compare the outcome of patients with adenocarcinoma of the distal esophagus (AEG type I) treated with neoadjuvant chemoradiation or perioperative chemotherapy.\n Eligible patients from four Austrian centers were selected to conduct a retrospective analysis. All patients treated between January 2007 and October 2017 with chemotherapy according to EOX-protocol (Epirubicin, Oxaliplatin, Xeloda) or chemoradiation according to CROSS-protocol (carboplatin/paclitaxel + RTX 41.4 Gy), before esophagectomy were included. Primary outcomes disease-free survival (DFS) and overall survival (OS) as well as secondary outcomes downstaging of T- or N-stage and achievement of pathological complete response pCR (ypT0N0M0) were analyzed. Data of 119 patients were included.\n Complete data was available in 104 patients, 53 patients in the chemoradiation group and 51 patients in the chemotherapy group. The mean number of lymph nodes removed was significantly higher in the EOX group (EOX 29 ± 15.5 vs. CROSS 22 ± 8.8; p < 0.05). Median follow-up in the CROSS group was 17 months (CI 95% 8.8-25.2) and in the EOX group 37 months (CI 95% 26.5-47.5). In the chemotherapy group, the OS rate after half a year, - 1, and 3 years was 92%, 75%, and 51%. After chemoradiation, overall survival after half a year was 85 %, after 1 year 66%, and after 3 years 17%. In the EOX group DFS after ½, - 1, and 3 years was 90%, 73%, and 45%, in the chemoradiation group after half a year 81%, after 1 year 55% and after 3 years 15%. Pathological complete response (pCR) was achieved in 23% of patients after CROSS and in 10% after EOX (p < 0.000).\n There seem to be clear advantages for chemoradiation, concerning the major response of the primary tumor, whereas a tendency in favor for chemotherapy is seen in regards to systemic tumor control. Furthermore, the type of neoadjuvant treatment has a significant influence on the number of lymph nodes resected.\n\nPartl, Richard\n\n\n"
},
{
"text": "\n180171\nChest CT in patients after lung transplantation: A retrospective analysis to evaluate impact on image quality and radiation dose using spectral filtration tin-filtered imaging.\n\nWressnegger, A\n\nProsch, H\n\nMoser, B\n\nKlepetko, W\n\nJaksch, P\n\nLambers, C\n\nHoetzenecker, K\n\nSchestak, C\n\nDe Bettignies, A\n\nBeer, L\n\nApfaltrer, G\n\nRingl, H\n\nApfaltrer, P\n\nBeiträge in Fachzeitschriften\nISI:000534621500049\n32023294.0\n10.1371/journal.pone.0228376\nPMC7001933\nThe purpose of this study was to investigate the impact of a 150kV spectral filtration chest imaging protocol (Sn150kVp) combined with advanced modeled iterative reconstruction (ADMIRE) on radiation dose and image quality in patients after lung-transplantation.\n This study included 102 patients who had unenhanced chest-CT examinations available on both, a second-generation dual-source CT (DSCT) using standard protocol (100kVp, filtered-back-projection) and, on a third-generation DSCT using Sn150kVp protocol with ADMIRE. Signal-to-noise-ratio (SNR) was measured in 6 standardized regions. A 5-point Likert scale was used to evaluate subjective image quality. Radiation metrics were compared.\n The mean time interval between the two acquisitions was 1.1±0.7 years. Mean-volume-CT-dose-index, dose-length-product and effective dose were significantly lower for Sn150kVp protocol (2.1±0.5mGy;72.6±16.9mGy*cm;1.3±0.3mSv) compared to 100kVp protocol (6.2±1.8mGy;203.6±55.6mGy*cm;3.7±1.0mSv) (p<0.001), equaling a 65% dose reduction. All studies were considered of diagnostic quality. SNR measured in lung tissue, air inside trachea, vertebral body and air outside the body was significantly higher in 100kVp protocol compared to Sn150kVp protocol (12.5±2.7vs.9.6±1.5;17.4±3.6vs.11.8±1.8;0.7±0.3vs.0.4±0.2;25.2±6.9vs.14.9±3.3;p<0.001). SNR measured in muscle tissue was significantly higher in Sn150kVp protocol (3.2±0.9vs.2.6±1.0;p<0.001). For SNR measured in descending aorta there was a trend towards higher values for Sn150kVp protocol (2.8±0.6 vs. 2.7±0.9;p = 0.3). Overall SNR was significantly higher in 100kVp protocol (5.0±4.0vs.4.0±4.0;p<0.001). On subjective analysis both protocols achieved a median Likert rating of 1 (25th-75th-percentile:1-1;p = 0.122). Interobserver agreement was good (intraclass correlation coefficient = 0.73).\n Combined use of 150kVp tin-filtered chest CT protocol with ADMIRE allows for significant dose reduction while maintaining highly diagnostic image quality in the follow up after lung transplantation when compared to a standard chest CT protocol using filtered back projection.\n\nApfaltrer, Georg\n\nApfaltrer, Paul\n\n\n"
},
{
"text": "\n181409\nTrial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis.\n\nStänder, S\n\nYosipovitch, G\n\nLegat, FJ\n\nLacour, JP\n\nPaul, C\n\nNarbutt, J\n\nBieber, T\n\nMisery, L\n\nWollenberg, A\n\nReich, A\n\nAhmad, F\n\nPiketty, C\n\nBeiträge in Fachzeitschriften\nISI:000517119800006\n32074418.0\n10.1056/NEJMoa1908316\nNone\nPrurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis.\n We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18.\n A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms.\n Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).\n Copyright © 2020 Massachusetts Medical Society.\n\nLegat, Franz\n\n\n"
},
{
"text": "\n184688\nPrevalence of resistance-associated substitutions and retreatment of patients failing a glecaprevir/pibrentasvir regimen.\n\nde Salazar, A\n\nDietz, J\n\ndi Maio, VC\n\nVermehren, J\n\nPaolucci, S\n\nMüllhaupt, B\n\nCoppola, N\n\nCabezas, J\n\nStauber, RE\n\nPuoti, M\n\nArenas Ruiz Tapiador, JI\n\nGraf, C\n\nAragri, M\n\nJimenez, M\n\nCallegaro, A\n\nPascasio Acevedo, JM\n\nMacias Rodriguez, MA\n\nRosales Zabal, JM\n\nMicheli, V\n\nGarcia Del Toro, M\n\nTéllez, F\n\nGarcía, F\n\nSarrazin, C\n\nCeccherini-Silberstein, F\n\nCeccherini-Silberstein, F\n\nBeiträge in Fachzeitschriften\nISI:000593065400035\n32772078.0\n10.1093/jac/dkaa304\nNone\nTo investigate resistance-associated substitutions (RASs) as well as retreatment efficacies in a large cohort of European patients with failure of glecaprevir/pibrentasvir.\n Patients were identified from three European Resistance Reference centres in Spain, Italy and Germany. Sequencing of NS3, NS5A and NS5B was conducted and substitutions associated with resistance to direct antiviral agents were analysed. Clinical and virological parameters were documented retrospectively and retreatment efficacies were evaluated.\n We evaluated 90 glecaprevir/pibrentasvir failures [3a (n = 36), 1a (n = 23), 2a/2c (n = 20), 1b (n = 10) and 4d (n = 1)]. Ten patients were cirrhotic, two had previous exposure to PEG-interferon and seven were coinfected with HIV; 80 had been treated for 8 weeks. Overall, 31 patients (34.4%) failed glecaprevir/pibrentasvir without any NS3 or NS5A RASs, 62.4% (53/85) showed RASs in NS5A, 15.6% (13/83) in NS3 and 10% (9/90) in both NS5A and NS3. Infection with HCV genotypes 1a and 3a was associated with a higher prevalence of NS5A RASs. Patients harbouring two (n = 34) or more (n = 8) RASs in NS5A were frequent. Retreatment was initiated in 56 patients, almost all (n = 52) with sofosbuvir/velpatasvir/voxilaprevir. The overall sustained virological response rate was 97.8% in patients with end-of-follow-up data available.\n One-third of patients failed glecaprevir/pibrentasvir without resistance. RASs in NS5A were more prevalent than in NS3 and were frequently observed as dual and triple combination patterns, with a high impact on NS5A inhibitor activity, particularly in genotypes 1a and 3a. Retreatment of glecaprevir/pibrentasvir failures with sofosbuvir/velpatasvir/voxilaprevir achieved viral suppression across all genotypes.\n © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n187647\nAntithrombotic treatment management in low stroke risk patients undergoing cardioversion of atrial fibrillation <48 h duration: results of an EHRA survey.\n\nMigliore, F\n\nProvidencia, R\n\nFarkowski, MM\n\nDan, GA\n\nDaniel, S\n\nPotpara, TS\n\nJubele, K\n\nChun, JKR\n\nde Asmundis, C\n\nZorzi, A\n\nBoveda, S\n\nBeiträge in Fachzeitschriften\nNone\n33990842.0\n10.1093/europace/euab106\nNone\nData supporting the safety of cardioversion (CV) of atrial fibrillation (AF) without anticoagulation in patients with AF duration <48 h are scarce. Observational studies suggest that the risk of stroke in these patients is very low when the definite duration of the AF episode is of <48 h and the clinical risk profile as estimated through the CHA2DS2VASc score is low (a score of 0 for men and 1 for women). As the recent 2020 European Society of Cardiology (ESC) guidelines indication for this clinical scenario is based mainly on consensus, we sent out a survey to assess the current clinical practice on anticoagulation prior to and post-CV in patients with AF <24-48 h duration and low stroke risk across centres in Europe. Of the 136 respondents, half were affiliated to university hospitals (68/136; 50%). Non-university hospitals (50/136; 36%) and private hospitals (2/136; 1.4%) accounted over a third of respondents. The main findings of our survey were (i) heterogeneity in the anticoagulation management both before and post-CV in low stroke-risk patients with AF <48 h, (ii) higher utilization of periprocedural low-molecular-weight heparin than of non-vitamin K antagonist oral anticoagulant, (iii) higher utilization of pre-CV transoesophageal echocardiography for electrical CV than for pharmacological CV regardless of the duration of AF, (iv) high adherence to a 4-week post-CV oral anticoagulant (OAC) therapy, mainly for electrical CV, and finally, (v) perceived higher acceptance of lack of post-CV OAC therapy in patients with <24 h than 24-48 h episode duration. The results obtained in this survey highlight the need for more research providing definitive clarification on the safety of CV without anticoagulation in patients with short duration AF.\n Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.\n\nScherr, Daniel\n\n\n"
},
{
"text": "\n910\nLack of effect of a selective vasopressin V1A receptor antagonist SR 49,059, on potentiation by vasopressin of adrenoceptor-mediated pressor responses in the rat mesenteric arterial bed.\n\nHeinemann, A\n\nHorina, G\n\nStauber, RE\n\nPertl, C\n\nHolzer, P\n\nPeskar, BA\n\nBeiträge in Fachzeitschriften\nISI:000077085800002\n9863637.0\n10.1038/sj.bjp.0702167\nPMC1565683\nThe vasopressin receptor subtype involved in the enhancement by vasopressin of adrenoceptor-mediated vasoconstriction was investigated in rat isolated perfused mesenteric arteries. [Arg8]vasopressin (1-10 nM) dose-dependently increased the perfusion pressure and enhanced the pressor response to the adrenoceptor agonist methoxamine (40 nmol) or electrical stimulation of periarterial nerves (16 Hz), at the concentration of 10 nM of [Arg8]vasopressin up to 4 and 3 fold, respectively. During prolonged exposure (45 min) the direct vasoconstrictor effect of [Arg8]vasopressin (10 nM) rapidly declined whereas the potentiation of methoxamine-induced vasoconstriction was maintained. The selective vasopressin V1A receptor antagonist SR 49, 59 (1-3 nM) and the non-selective V1A/B and oxytocin receptor antagonist [deamino-Pen1, yr(Me)2, rg8]vasopressin (15-45 nM) inhibited the direct vasoconstrictor action of [Arg8]vasopressin but had no effect on the enhancement of the pressor response to methoxamine or electrical stimulation. The V1B receptor agonist [deamino-Cys1, eta-(3-pyridyl)-D-Ala2, rg8]vasopressin (100-1000 nM) and the V2 receptor agonist [deamino-Cys1, -Arg8]vasopressin (1-10 nM) were devoid of any pressor activity and did not potentiate methoxamine-evoked vasoconstriction. In contrast, [1-triglycyl, ys8]vasopressin (100 - 1000 nM) potentiated the methoxamine responses without per se inducing vasoconstriction. In arteries precontracted with methoxamine (7.5 microM) pressor responses to [Arg8]vasopressin (3-10 nM) were not inhibited by a dose of SR 49, 59 (3 nM) which abolished the peptide's vasoconstrictor effect under control conditions. These data show that the direct vasoconstrictor effect of [Arg8]vasopressin is mediated by V1A receptors while the enhancement of adrenoceptor-mediated pressor responses is insensitive to V1A, V1B, and oxytocin receptor antagonists and is not mimicked by selective agonists of V1B and V2 receptors. In conclusion, an unusual interaction of vasopressin with V1A receptors, or even the existence of a novel receptor subtype, has to be considered.\n\nHeinemann, Akos\n\nHolzer, Peter\n\nPeskar, Bernhard\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n1724\nNovel system for real-time ex vivo lactate monitoring in human whole blood.\n\nGfrerer, RJ\n\nBrunner, GA\n\nTrajanoski, Z\n\nSchaupp, L\n\nSendlhofer, G\n\nSkrabal, F\n\nJobst, G\n\nMoser, I\n\nUrban, G\n\nPieber, TR\n\nWach, P\n\nBeiträge in Fachzeitschriften\nISI:000077555700005\n9883561.0\n10.1016/S0956-5663(98)00090-6\nNone\nThe objective of the study was to evaluate the performance of an amperometric enzyme based lactate sensor and to investigate the possibility of replacing a double lumen catheter based blood withdrawal system with a heparin coated single lumen system. The inner lumen of a double lumen catheter which was placed in a peripheral vein was perfused with heparin solution. The outer lumen was used to collect heparinized blood samples at a defined flow rate. The single lumen system was attached to a heparinized catheter which was also placed in a peripheral vein. The undiluted blood samples were collected at a specified flow rate. A sensor flow chamber incorporating an amperometric thin-film lactate microbiosensor was placed in the sampling line for real-time lactate monitoring. Plasma lactate concentrations were measured during frequently performed hyperlactatemia bicycle ergometer experiments in six healthy volunteers (age 25.8 +/- 2.8 years, BMI 22.7 +/- 1 kg/m2). Additionally, plasma lactate was measured in real-time using the lactate sensors. The first three experiments were performed with a double lumen based catheter system whereas the following three experiments were performed with a heparin coated catheter system. The correlation coefficients of sensor readings and laboratory analyzer results in all six experiments were between 0.93 and 0.99, respectively (P < 0.001). The miniaturized lactate sensors showed a linear range up to 25 mmol/l lactate concentration and 95% response times < 30 s in undiluted serum. During the experiments maximum lactate concentrations of 14 mmol/l were achieved. Improvements of system performance using heparin coated catheter systems could be shown. The overall SD of the sensor readings compared to laboratory results using three double lumen catheter based systems was 0.91 mmol/l whereas the SD using three heparin coated systems was 0.65 mmol/l. In summary, real-time monitoring of lactate in human whole blood is feasible with such a device and can be improved by using heparin coated catheter systems.\n\nBrunner, Gernot\n\nPieber, Thomas\n\nSendlhofer, Gerald\n\n\n"
},
{
"text": "\n4826\nMitral annuloplasty in patients with ischemic versus dilated cardiomyopathy.\n\nSzalay, ZA\n\nCivelek, A\n\nHohe, S\n\nBrunner-LaRocca, HP\n\nKlövekorn, WP\n\nKnez, I\n\nVogt, PR\n\nBauer, EP\n\nBeiträge in Fachzeitschriften\nISI:000182636600022\n12694777.0\n10.1016/S1010-7940(02)00864-3\nNone\nMitral regurgitation is a frequent finding in patients with end-stage cardiomyopathy predicting poor survival. Conventional treatment consists medical treatment or cardiac transplantation. However, despite severely decreased left ventricular function, mitral annuloplasty may improve survival and reduce the need for allografts.\n From January 1996 to July 2002, 121 patients with severe end-stage dilated (DCM) or ischemic cardiomyopathy (ICM), mitral regurgitation > or =2, and left ventricular ejection fraction < or =30% underwent mitral valve annuloplasty using a flexible posterior ring. DCM was diagnosed in 30 patients (25%), whereas ICM was found in 91 patients (75%). Concomitant tricuspid valve repair was performed in 14 (46.6%) patients in the DCM, and in 11 (12%) in the ICM group (P=0.0001), coronary artery bypass grafting in three (10%) in the DCM, and in 78 patients (86%) in the ICM group (P<0.00001). The mean follow-up time was 567+/-74 days in the DCM and 793+/-63 days in the ICM group (ns).\n Early mortality was 6.6% (8/121), and was equal for both groups. Improvement in NYHA class (DCM 3.3+0.1-1.8+/-0.16; ICM from 3.2+0.04 to 1.7+/-0.07) were equal between groups after 1 year. Seventeen (15%) late deaths occurred during the follow-up period. There was no difference in the 2-year actuarial survival between groups (DCM/ICM 0.93/0.85). Risk factors for mitral reconstruction failure, defined as regurgitation > or =2 after 1 year, were preoperative NYHA IV in the DCM group (P=0.03), a preoperative posterior infarction (P=0.025), decreased left ventricular function (P=0.043), larger ring size (P=0.026) and preoperative renal failure (P=0.05) in the ICM group. Risk factors for death were larger ring size (P=0.02) and an increased LVEDD (P=0.027) in the DCM group and the postoperative use of IABP (P=0.002), renal failure (P=0.001), and a larger preoperative LVESD (P=0.035) in the ICM group.\n Mitral reconstruction with a posterior annuloplasty using a flexible ring is effective in patients with severely depressed left ventricle function and has an acceptable operative mortality. Mid-term results are superior to medical treatment alone and comparable to cardiac transplantation.\n\nKnez, Igor\n\n\n"
},
{
"text": "\n106590\nVariants at APOE influence risk of deep and lobar intracerebral hemorrhage.\n\nBiffi, A\n\nSonni, A\n\nAnderson, CD\n\nKissela, B\n\nJagiella, JM\n\nSchmidt, H\n\nJimenez-Conde, J\n\nHansen, BM\n\nFernandez-Cadenas, I\n\nCortellini, L\n\nAyres, A\n\nSchwab, K\n\nJuchniewicz, K\n\nUrbanik, A\n\nRost, NS\n\nViswanathan, A\n\nSeifert-Held, T\n\nStoegerer, EM\n\nTomás, M\n\nRabionet, R\n\nEstivill, X\n\nBrown, DL\n\nSilliman, SL\n\nSelim, M\n\nWorrall, BB\n\nMeschia, JF\n\nMontaner, J\n\nLindgren, A\n\nRoquer, J\n\nSchmidt, R\n\nGreenberg, SM\n\nSlowik, A\n\nBroderick, JP\n\nWoo, D\n\nRosand, J\n\non behalf of the International Stroke Genetics Consortium\n\nBeiträge in Fachzeitschriften\nISI:000285953500021\n21061402.0\n10.1002/ana.22134\nPMC3058266\nObjective: Prior studies investigating the association between APOE alleles epsilon 2/epsilon 4 and risk of intracerebral hemorrhage (ICH) have been inconsistent and limited to small sample sizes, and did not account for confounding by population stratification or determine which genetic risk model was best applied. Methods: We performed a large-scale genetic association study of 2189 ICH cases and 4041 controls from 7 cohorts, which were analyzed using additive models for epsilon 2 and epsilon 4. Results were subsequently meta-analyzed using a random effects model. A proportion of the individuals (322 cases, 357 controls) had available genome-wide data to adjust for population stratification. Results: Alleles epsilon 2 and epsilon 4 were associated with lobar ICH at genome-wide significance levels (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.50-2.23, p = 6.6 x 10(-10); and OR = 2.20, 95%CI = 1.85-2.63, p = 2.4 x 10(-11), respectively). Restriction of analysis to definite/probable cerebral amyloid angiopathy ICH uncovered a stronger effect. Allele epsilon 4 was also associated with increased risk for deep ICH (OR = 1.21, 95% CI = 1.08-1.36, p = 2.6 x 10(-4)). Risk prediction evaluation identified the additive model as best for describing the effect of APOE genotypes. Interpretation: APOE epsilon 2 and epsilon 4 are independent risk factors for lobar ICH, consistent with their known associations with amyloid biology. In addition, we present preliminary findings on a novel association between APOE epsilon 4 and deep ICH. Finally, we demonstrate that an additive model for these APOE variants is superior to other forms of genetic risk modeling previously applied. ANN NEUROL 2010;68:934-943\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\nSeifert-Held, Thomas\n\nStögerer-Oberschmid, Eva Maria\n\n\n"
},
{
"text": "\n138425\nElevated levels of interleukin 17A and kynurenine in candidemic patients, compared with levels in noncandidemic patients in the intensive care unit and those in healthy controls.\n\nKrause, R\n\nZollner-Schwetz, I\n\nSalzer, HJ\n\nValentin, T\n\nRabensteiner, J\n\nPrüller, F\n\nRaggam, R\n\nMeinitzer, A\n\nPrattes, J\n\nRinner, B\n\nStrohmaier, H\n\nQuehenberger, F\n\nStrunk, D\n\nHeidrich, K\n\nBuzina, W\n\nHoenigl, M\n\nBeiträge in Fachzeitschriften\nISI:000350221500014\n25149761.0\n10.1093/infdis/jiu468\nNone\nThe interplay between Candida species and pattern recognition receptors, interleukins, kynurenine, and T cells has been studied in murine and ex vivo human studies, but data are lacking from patients with invasive fungal infections. Interleukin 17A (IL-17A) is considered an important component in host defense against Candida infections and is modulated by Candida-induced impairment of tryptophan-kynurenine metabolism.\n Dectin-1, Toll-like receptor 2, and Toll-like receptor 4 expression; regulatory T cell (Treg) percentages; and interleukin 6, interleukin 10, IL-17A, interleukin 22, interleukin 23, interferon γ, kynurenine, and tryptophan levels were determined in candidemic patients and compared to levels in noncandidemic patients who are in the intensive care unit (ICU) and receiving antibiotic therapy and those in healthy controls, both with and without Candida colonization.\n Candidemic patients had significantly higher IL-17A and kynurenine levels, compared with noncandidemic patients, including Candida-colonized ICU patients and healthy controls. Within candidemic patients, time-dependent elevation of IL-17A and kynurenine levels was detected. IL-17A areas under the curve for differentiation between patients with early candidemia and those without candidemia (ICU patients, including Candida-colonized patients, and healthy controls) were between 0.94 (95% confidence interval [CI], .89-.99) and 0.99 (95% CI, .99-1).\n Candidemic patients had significantly higher IL-17A and kynurenine levels, compared with noncandidemic patients. The statistically significant association between IL-17A and kynurenine levels and candidemia suggests their potential as biomarkers for anticipation of invasive candidiasis.\n NCT00786903.\n © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.\n\nBuzina, Walter\n\nHönigl, Martin\n\nKrause, Robert\n\nMeinitzer, Andreas\n\nPrattes, Jürgen\n\nPrüller, Florian\n\nQuehenberger, Franz\n\nRabensteiner, Jasmin\n\nRaggam, Reinhard Bernd\n\nRinner, Beate\n\nStrohmaier, Heimo\n\nValentin, Thomas\n\nZollner-Schwetz, Ines\n\n\n"
},
{
"text": "\n146693\nP276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in vitro and in vivo in mantle cell lymphoma cell lines.\n\nShirsath, NP\n\nManohar, SM\n\nJoshi, KS\n\nBeiträge in Fachzeitschriften\nISI:000315499600001\n23075291.0\n10.1186/1476-4598-11-77\nPMC3558400\nMantle cell lymphoma (MCL) is a well-defined aggressive lymphoid neoplasm characterized by proliferation of mature B-lymphocytes that have a remarkable tendency to disseminate. This tumor is considered as one of the most aggressive lymphoid neoplasms with poor responses to conventional chemotherapy and relatively short survival. Since cyclin D1 and cell cycle control appears as a natural target, small-molecule inhibitors of cyclin-dependent kinases (Cdks) and cyclins may play important role in the therapy of this disorder. We explored P276-00, a novel selective potent Cdk4-D1, Cdk1-B and Cdk9-T1 inhibitor discovered by us against MCL and elucidated its potential mechanism of action.\n The cytotoxic effect of P276-00 in three human MCL cell lines was evaluated in vitro. The effect of P276-00 on the regulation of cell cycle, apoptosis and transcription was assessed, which are implied in the pathogenesis of MCL. Flow cytometry, western blot, immunoflourescence and siRNA studies were performed. The in vivo efficacy and effect on survival of P276-00 was evaluated in a Jeko-1 xenograft model developed in SCID mice. PK/PD analysis of tumors were performed using LC-MS and western blot analysis.\n P276-00 showed a potent cytotoxic effect against MCL cell lines. Mechanistic studies confirmed down regulation of cell cycle regulatory proteins with apoptosis. P276-00 causes time and dose dependent increase in the sub G1 population as early as from 24 h. Reverse transcription PCR studies provide evidence that P276-00 treatment down regulated transcription of antiapoptotic protein Mcl-1 which is a potential pathogenic protein for MCL. Most importantly, in vivo studies have revealed significant efficacy as a single agent with increased survival period compared to vehicle treated. Further, preliminary combination studies of P276-00 with doxorubicin and bortezomib showed in vitro synergism.\n Our studies thus provide evidence and rational that P276-00 alone or in combination is a potential therapeutic molecule to improve patients' outcome in mantle cell lymphoma.\n\n\n"
},
{
"text": "\n151284\nA 3-dimensional finite-element analysis investigating the biomechanical behavior of the mandible and plate osteosynthesis in cases of fractures of the condylar process.\n\nWagner, A\n\nKrach, W\n\nSchicho, K\n\nUndt, G\n\nPloder, O\n\nEwers, R\n\nBeiträge in Fachzeitschriften\nISI:000179885600009\n12464890.0\n10.1067/moe.2002.126451\nNone\nThe condylar region is one of the most frequent sites for mandibular fractures, with direct application of miniplates being the most commonly used open-fixation technique today. Yet, anatomic and biomechanical limitations continue to make this application technically challenging with a considerable complication rate. We sought to analyze such incongruencies with respect to the complex biomechanical behavior of the mandible.\n Individual human mandible geometry, the specific bone density distribution, and the position and orientation of the masticatory muscles were evaluated by performing computed tomography scans and a sequential dissection of the cadaver mandible. Three-dimensional finite-element analysis was performed for different fracture sites, osteosynthesis plates, and loading conditions.\n Osteosynthesis of fractures of the condylar neck with 1 or 2 miniplates of a diameter of 2.35 x 1.00 mm was found to be an insufficient fixation method. This also applies for plates (3.60 x 1.54 mm), according to Pape et al, 8) when used in singular fashion (high condylar neck fractures excepted). In cases of singular occlusal contacts in the molar region (particularly at the contralateral side of the fracture), the highest stress values inside the mandible and osteosynthetic devices could be observed. With even the static yield limit of titanium being exceeded in such cases, consecutive rapid failure of the miniplates becomes most likely when loading of the condylar region caused by bite forces cannot be prevented.\n We strongly recommend the use, whenever possible, of 2 plates in the manner described by Pape et al(8) for osteosynthesis of fractures of the condylar neck in combination with bicortically placed screws. The stiffness of a singular osteosynthesis plate made of titanium in a diametrical dimension of approximately 5.0 x 1.75 mm was found to be equivalent to the physiological bone stiffness in the investigated fracture sites. The actual stiffness of such a fixation plate is approximately 3 times higher than the stiffness of devices commonly in use.\n\n\n"
},
{
"text": "\n152395\nResults from the Tack Optimized Balloon Angioplasty (TOBA) study demonstrate the benefits of minimal metal implants for dissection repair after angioplasty.\n\nBosiers, M\n\nScheinert, D\n\nHendriks, JM\n\nWissgott, C\n\nPeeters, P\n\nZeller, T\n\nBrodmann, M\n\nStaffa, R\n\nTOBA investigators\n\nBeiträge in Fachzeitschriften\nISI:000378562900016\n27139789.0\n10.1016/j.jvs.2016.02.043\nNone\nThe mechanism of angioplasty is disruption of atherosclerotic plaque, which often results in dissections. Dissection after percutaneous transluminal angioplasty (PTA) remains a significant clinical problem and untreated may cause acute occlusion or later restenosis. Stents are used to manage dissections, which is often followed by in-stent restenosis and occasionally stent fracture. Tack (Intact Vascular, Wayne, Pa) implants have minimal metal and low radial force and are specifically designed for dissection repair. This study evaluated Tack implants for treatment of dissections resulting from standard balloon PTA for femoral-popliteal arterial disease. Twelve-month outcomes after Tack treatment of post-PTA dissections are described.\n This prospective, single-arm study evaluated patients with ischemia (Rutherford clinical category 2-4) caused by lesions of the superficial femoral and popliteal arteries. Patients were treated with standard balloon angioplasty, and post-PTA dissections were treated with Tacks. The primary end points were core laboratory-adjudicated device technical success, defined as the ability of the Tack implants to resolve post-PTA dissection, and device safety, defined as the absence of new-onset major adverse events. Patients were followed up to 12 months after implantation.\n Tacks were used in 130 patients with post-PTA dissections (74.0% ≥ grade C). Technical success was achieved in 128 (98.5%) patients with no major adverse events at 30 days. The 12-month patency was 76.4%, and freedom from target lesion revascularization was 89.5%. Significant improvement from baseline was observed in Rutherford clinical category (82.8% with grade ≤1) and ankle-brachial index (0.68 ± 0.18 to 0.94 ± 0.15; P < .0001).\n Tack implant treatment of post-PTA dissection was safe, produced reasonable patency, and resulted in low rates of target lesion revascularization. Tack treatment represents a new, minimal metal paradigm for dissection repair that can safely improve the clinical results associated with PTA.\n Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.\n\nBrodmann, Marianne\n\nEller, Philipp\n\nPilger, Ernst\n\n\n"
},
{
"text": "\n161345\nFactors associated with high 24-month persistence with denosumab: results of a real-world, non-interventional study of women with postmenopausal osteoporosis in Germany, Austria, Greece, and Belgium.\n\nFahrleitner-Pammer, A\n\nPapaioannou, N\n\nGielen, E\n\nFeudjo Tepie, M\n\nToffis, C\n\nFrieling, I\n\nGeusens, P\n\nMakras, P\n\nBoschitsch, E\n\nCallens, J\n\nAnastasilakis, AD\n\nNiedhart, C\n\nResch, H\n\nKalouche-Khalil, L\n\nHadji, P\n\nBeiträge in Fachzeitschriften\nISI:000404328300001\n28643265.0\n10.1007/s11657-017-0351-2\nPMC5486684\nPersistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium found that persistence with denosumab remains consistently high after 24 months in patients at high risk of fracture.\n Continued persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of clinical practice evaluated medication-taking behavior of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium and factors influencing persistence.\n Subcutaneous denosumab (60 mg every 6 months) was assigned according to prescribing information and local guidelines before and independently of enrollment; outcomes were recorded during routine practice for up to 24 months. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection and adherence as administration of subsequent injections within 6 months ± 4 weeks of the previous injection. Medication coverage ratio (MCR) was calculated as the proportion of time a patient was covered by denosumab. Associations between pre-specified baseline covariates and 24-month persistence were assessed using multivariable logistic regression.\n The 24-month analyses included 1479 women (mean age 66.3-72.5 years) from 140 sites; persistence with denosumab was 75.1-86.0%, adherence 62.9-70.1%, and mean MCR 87.4-92.4%. No covariate had a significant effect on persistence across all four countries. For three countries, a recent fall decreased persistence; patients were generally older with chronic medical conditions. In some countries, other covariates (e.g., older age, comorbidity, immobility, and prescribing reasons) decreased persistence. Adverse drug reactions were reported in 2.3-6.9% patients.\n Twenty-four-month persistence with denosumab is consistently high among postmenopausal women in Europe and may be influenced by patient characteristics. Further studies are needed to identify determinants of low persistence.\n\nFahrleitner-Pammer, Astrid\n\n\n"
}
]
}