HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 127182,
"next": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=124260",
"previous": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=124220",
"results": [
{
"text": "\n182835\nQuality of Life and Limitations in Daily Life of Stable COPD Outpatients in a Real-World Setting in Austria - Results from the CLARA Project.\n\nHorner, A\n\nBurghuber, OC\n\nHartl, S\n\nStudnicka, M\n\nMerkle, M\n\nOlschewski, H\n\nKaiser, B\n\nWallner, EM\n\nLamprecht, B\n\nBeiträge in Fachzeitschriften\nISI:000547519500001\nNone\n10.2147/COPD.S252033\nNone\nBackground: COPD patients suffer from respiratory symptoms and limitations in daily life. We aimed to characterize the impact of disease on overall health, daily life, and perceived well-being in COPD outpatients. Methods: We conducted a national, cross-sectional study among pulmonologists and general practitioners (GPs). The St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) was used. Inclusion criteria were a physician's diagnosis of COPD and age >= 40 years. Subjects with a history of lung surgery, lung cancer or COPD exacerbation within the last four weeks were excluded. Results: Sixty-seven pulmonologists and 6 GPs enrolled 1175 COPD patients. Two hundred forty-eight of those did not fulfill GOLD criteria for COPD (FEV1/FVC <0.7) and 77 were excluded due to missing data. Finally, 850 patients (62.8% men; mean age 66.2 +/- 0.3 (SE) years; mean FEV1%pred. 51.5 +/- 0.6 (SE)) were analyzed. Last year, 55.4% reported at least one exacerbation, and 12.7% were hospitalized for COPD exacerbation. Mean SGRQ-C total score was 43.1 +/- 0.83 (SE) and mean component scores for symptoms, activity and impacts were 55.6, 55.4 and 30.5, respectively. Half of the patients (50.3%) reported not being able to do any sports and 78.7% stated that their respiratory symptoms did not allow them doing anything they would like to do. In patients with less severe COPD (FEV(1)pred >= 50% and non-frequent exacerbations), global health status was overrated, ie, estimated as better by the physician than by the patient, while it was underrated in more severe COPD. Conclusion: In Austria, the burden of disease in COPD outpatients tends to be underestimated in patients with milder airway obstruction and less exacerbations and overestimated in patients with more severe airway obstruction and frequent exacerbations. Our finding suggests that validated assessment of global health status might decrease these differences of perception.\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n186782\nPrognostic value of perfusion defect volume at dual energy CTA in patients with pulmonary embolism: correlation with CTA obstruction scores, CT parameters of right ventricular dysfunction and adverse clinical outcome.\n\nApfaltrer, P\n\nBachmann, V\n\nMeyer, M\n\nHenzler, T\n\nBarraza, JM\n\nGruettner, J\n\nWalter, T\n\nSchoepf, UJ\n\nSchoenberg, SO\n\nFink, C\n\nBeiträge in Fachzeitschriften\nNone\n22495202.0\n10.1016/j.ejrad.2012.02.008\nNone\nTo investigate the prognostic value of perfusion defect volume (PDvol) at dual-energy-CT-angiography (DE-CTA) in patients with acute pulmonary embolism (PE) by correlating PDvol with CTA-obstruction-scores (OS), CT parameters of right-ventricular-dysfunction (RVD), and adverse-clinical-outcome.\n DE-CTA of 60 patients (mean age: 65±14.4 years) with PE were analyzed. Iodine maps were generated, and normalized PDvol--defined as volume of perfusion defects/total lung volume--was quantified. Furthermore, established prognostic parameters (Qanadli and Mastora-OS, and CT parameters of RVD) were obtained. CT parameters of RVD--namely the right ventricle/left ventricle (RV/LV) diameter ratio measured on transverse sections (RV/LVtrans), four-chamber views (RV/LV4ch), and RV/LV volume ratios (RV/LVvol)--were assessed. PDvol was correlated with OS, CT parameters of RVD and adverse clinical outcome (defined as the need for intensive care treatment or death).\n 10 of 60 patients with PE experienced adverse clinical outcome. Patients with adverse clinical outcome showed significantly higher PDvol (35±11% vs. 23±10%, p=0.002), RV/LV ratios (RV/LV4ch 1.46±0.32 vs. 1.18±0.26, p=0.005; RV/LVvol 2.25±1.33 vs. 1.19±0.56, p=0.002) and higher Mastora global scores (52 vs. 13, p=0.02) compared to those without adverse clinical outcome. A weak correlation was observed between PDvol and the Mastora global score (r=0.5; p=0.0003), as well as between PDvol and RV/LV4Ch (r=0.432, p=0.0006). No correlation was found between PDvol and the Qanadli score or the remainder of the RVD-CT parameters.\n The extent of perfusion defects as assessed by DE-CTA correlates with adverse clinical outcome in patients with PE. Therefore, volumetric quantification of perfusion defects at DE-CTA allows the identification of low-risk patients who do not require intensified monitoring and treatment.\n Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.\n\nApfaltrer, Paul\n\n\n"
},
{
"text": "\n1281\nImmunotherapy of metastatic malignant melanoma by a vaccine consisting of autologous interleukin 2-transfected cancer cells: outcome of a phase I study.\n\nSchreiber, S\n\nKämpgen, E\n\nWagner, E\n\nPirkhammer, D\n\nTrcka, J\n\nKorschan, H\n\nLindemann, A\n\nDorffner, R\n\nKittler, H\n\nKasteliz, F\n\nKüpcü, Z\n\nSinski, A\n\nZatloukal, K\n\nBuschle, M\n\nSchmidt, W\n\nBirnstiel, M\n\nKempe, RE\n\nVoigt, T\n\nWeber, HA\n\nPehamberger, H\n\nMertelsmann, R\n\nBröcker, EB\n\nWolff, K\n\nStingl, G\n\nBeiträge in Fachzeitschriften\nISI:000079844900013\n10223732.0\n10.1089/10430349950018382\nNone\nWe performed a phase I trial to evaluate the safety and tolerability of repeated skin injections of IL-2-transfected autologous melanoma cells into patients with advanced disease. Cell suspensions, propagated from excised metastases, were IL-2 gene transfected by adenovirus-enhanced transferrinfection and X-irradiated prior to injection. Vaccine production was successful in 54% of the patients. Fifteen patients (37%) received two to eight skin vaccinations of either 3 x 10(6) (intradermal) or 1 x 10(7) (half intradermal, half subcutaneous) transfected melanoma cells per vaccination (secreting 140-17, 60 biological response modifier program units of IL-2/10(6) cells/24 hr). Analyses of safety and efficacy were carried out in 15 and 14 patients, respectively. Overall, the vaccine was well tolerated. All patients displayed modest local reactions (erythema, induration, and pruritus) and some experienced flu-like symptoms. Apart from newly appearing (4 of 14) and increasing (5 of 14) anti-adenovirus and newly detectable anti-nuclear antibody titers (1 of 15), recipients developed de novo or exhibited increased melanoma cell-specific delayed-type hypersensitivity (DTH) reactions (8 of 15) and vitiligo (3 of 15) and showed signs of tumor regression (3 of 15). This supports the idea of a vaccine-induced or -amplified anti-cancer immune response. None of the patients exhibited complete or partial regressions, but five of them experienced periods of disease stabilization. Three of these individuals received more than the four planned vaccinations and their mean survival time was 15.7 +/- 3.5 months as compared to 7.8 +/- 4.6 months for the entire patient cohort. These data indicate that IL-2-producing, autologous cancer cells can be safely administered to stage IV melanoma patients and could conceivably be of benefit to patients with less advanced disease.\n\nZatloukal, Kurt\n\n\n"
},
{
"text": "\n5075\nSignificant increase in breast conservation in 16 years of trials conducted by the Austrian Breast & Colorectal Cancer Study Group.\n\nJakesz, R\n\nSamonigg, H\n\nGnant, M\n\nKubista, E\n\nDepisch, D\n\nKolb, R\n\nMlineritsch, B\n\nMischinger, HJ\n\nMenzel, RC\n\nSteindorfer, P\n\nKwasny, W\n\nTausch, C\n\nStierer, M\n\nTaucher, S\n\nSeifert, M\n\nHausmaninger, H\n\nAustrian Breast &\n\nColorectal Cancer Study Group\n\nBeiträge in Fachzeitschriften\nISI:000185834400018\n12677153.0\n10.1097/01.SLA.0000059990.43981.4E\nPMC1514470\nObjective To confirm evidence that breast-conserving treatment (BCT) does not impair the prognosis in breast cancer patients as compared to mastectomy and to argue that it be regarded as the treatment of choice in stage I and II disease.Summary Background Data Scientifically, survival rates in breast cancer have been shown to be stage-dependent, but independent of the extent of surgical breast tissue removal, as long as the resection margins are free of tumor infiltration.Methods Between 1984 and 1997, six different trials conducted by the Austrian Breast & Colorectal Cancer Study Group accrued a total of 4, 59 women with hormone-responsive disease. The authors selected and compared three patient groups (n = 3, 16) according to pathologic stage, age, and the surgical procedure applied.Results Over this interval, the BCT rate in the premenopausal node-positive subgroup experienced a highly significant increase from 27.2% to 73.2% overall. In the group of postmenopausal node-negative patients, the BCT rate grew significantly by 37.3% to 77.3% in total. With an overall BCT rate growing from 22.5% to 56.8% in postmenopausal node-positive women, those presenting with T1 tumors saw a significant increase from 35.1% to 65.9%. Mortality and local recurrence rates proved stable or even decreased considerably over time and in all subgroups.Conclusions The presented outcome of BCT rates, significantly improved over this 16-year period and in no way counterbalanced by higher local recurrence or death rates, reflects an excellent example of surgical quality control. BCT can safely be regarded as the standard of therapy for T1 and increasingly for T2 disease. Especially in multi-institutional adjuvant breast cancer trials, the highest priority should be given to breast-conserving procedures.\n\nHofmann, Guenter\n\nKronberger, Leo\n\nMischinger, Hans-Joerg\n\nSamonigg, Hellmut\n\n\n"
},
{
"text": "\n26422\nProposal for revision of the TNM classification system for renal cell carcinoma.\n\nFicarra, V\n\nGuillè, F\n\nSchips, L\n\nde la Taille, A\n\nPrayer Galetti, T\n\nTostain, J\n\nCindolo, L\n\nNovara, G\n\nZigeuner, R\n\nBratti, E\n\nLi, G\n\nAltieri, V\n\nAbbou, CC\n\nZanolla, L\n\nArtibani, W\n\nPatard, JJ\n\nBeiträge in Fachzeitschriften\nISI:000233103000010\n16208703.0\n10.1002/cncr.21465\nNone\nBACKGROUND. The current study defined an optimal tumor size breakpoint to stratify localized renal cell carcinoma (RCC) into groups with significantly different cancer-related outcomes and proposed a revision of the TNM classification system. METHODS. The authors analyzed the data from 1138 patients who had undergone partial or radical nephrectomy for localized RCC at 7 European urologic centers. The optimal pathologic size breakpoint was calculated using the martingale residuals from a Cox proportional hazards regression model. RESULTS. The mean follow-up time was 87 months. The scatterplot of tumor size versus expected risk of death per patient suggested that an interval of 5-6 cm was appropriate. A total of 720 (63.3%) and 418 (36.7%) patients had tumors measuring <= 5.5-cm and tumors measuring > 5.5-cm, respectively. Significant cancer-specific survival differences between the two groups of patients were reported in the series by all the centers participating in the study. On univariate analysis, the other variables found to be associated with cancer-specific survival were the patient's age, symptomatic tumor presentation, and the Fuhrman nuclear grade. On multivariate analysis, the pathologic stage of the primary tumor defined according to the 5.5-cm breakpoint was found to be an independent predictor of cancer-specific survival, as well as age, mode of presentation, and nuclear grade. According to the multivariate analysis, the authors clustered patients into 3 groups with statistically significant outcome differences: 1) patients with <= 5.5-cm incidentally detected RCC; 2) patients with <= 5.5-cm symptomatic RCC) and 3) patients with > 5.5-cm RCC. This cancer-related outcome stratification was valid regardless of the patient's age. CONCLUSIONS. The 5.5-cm breakpoint was found to be the optimal tumor size breakpoint with which to stratify patients with organ-confined RCC. The study supported the upgrade of the TNM classification system according to this breakpoint. (c) 2005 American Cancer Society.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n62689\nCarbamazepine for prevention of oxaliplatin-related neurotoxicity in patients with advanced colorectal cancer: final results of a randomised, controlled, multicenter phase II study.\n\nvon Delius, S\n\nEckel, F\n\nWagenpfeil, S\n\nMayr, M\n\nStock, K\n\nKullmann, F\n\nObermeier, F\n\nErdmann, J\n\nSchmelz, R\n\nQuasthoff, S\n\nAdelsberger, H\n\nBredenkamp, R\n\nSchmid, RM\n\nLersch, C\n\nBeiträge in Fachzeitschriften\nISI:000243046100011\n16983507.0\n10.1007/s10637-006-9010-y\nNone\nBACKGROUND: Oxaliplatin-induced neurotoxicity is a growing, relevant clinical problem. In this study we evaluated the efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer. METHODS: Chemotherapeutic treatment consisted of oxaliplatin 85 mg/m(2) given biweekly and weekly folinic acid 500 mg/m(2) followed by a 24-h infusion of 5-FU 2000 mg/m(2) (FUFOX). One cycle consisted of six consecutive weeks of treatment followed by two weeks of rest (=Treatment B). For Treatment A carbamazepine was added in a dosage for targeted plasma levels of 4-6 mg/L.Neurotoxicity was regularly assessed using a specific scale. Moreover, an evaluation of chronic sensory symptoms and a neurologic examination including tests for vibrational sense, strength and deep tendon reflexes were added creating a peripheral neuropathy (PNP) score. Results: The prospectively defined adequate number of patients needed to provide power for the primary outcome could not be achieved. 19 patients were assigned to Treatment A and 17 to Treatment B. At baseline, the distribution of all clinicopathologic variables was comparable between the two groups. Overall response rates were 16% and 24% and overall survival 15.1 months and 17.4 months for Treatment A and Treatment B, respectively. Between Treatment A and Treatment B there were no major differences when considering worst neurotoxicity during the study period (p=0.46). Grade 3/4 neurotoxicity occured in 4 patients with Treatment A vs. 6 patients with Treatment B. There were no major differences between both groups in each category of the PNP score. CONCLUSIONS: Based on the small number of patients and low statistical power of our study definite conclusions regarding efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer cannot be drawn.\n\nQuasthoff, Stefan\n\n\n"
},
{
"text": "\n106927\nDynamic versus fixed equinus deformity in children with cerebral palsy: how does the triceps surae muscle work?\n\nSvehlík, M\n\nZwick, EB\n\nSteinwender, G\n\nKraus, T\n\nLinhart, WE\n\nBeiträge in Fachzeitschriften\nISI:000285738900012\n21112432.0\n10.1016/j.apmr.2010.09.005\nNone\nSvehlik M, Zwick EB, Steinwender G, Kraus T, Linhart WE. Dynamic versus fixed equinus deformity in children with cerebral palsy: how does the triceps surae muscle work? Arch Phys Med Rehabil 2010;91:1897-1903. Objectives: To detect outcome measures that could help differentiate between dynamic and fixed equinus (FEQ) deformities in children with cerebral palsy, and secondary, to describe the function of the gastrocnemius and soleus (SOL) muscles when either dynamic triceps surae tightness or FEQ contracture is present. Design: A group-comparison study. Setting: Gait analysis laboratory. Participants: Children (N=23; 31 limbs) with cerebral palsy; 12 limbs showed a fixed contracture (FEQ group) and 19 limbs showed dynamic tightness of the triceps muscle (dynamic equinus group). Healthy children (N=12) without a neurologic or orthopedic disorder served as the control group. Interventions: Not applicable. Main Outcome Measures: Time-distance, kinematic and kinetic gait variables, muscle-tendon length, and velocity parameters. Results: Maximal ankle dorsiflexion angles were decreased in both equinus groups compared with the control group. Ankle range of motion, maximal power generation of the plantar flexors, and its timing during the gait cycle were different among groups. The ankle slope parameter showed substantial differences among groups. Muscle-tendon length parameters for the SOL and the medial (MGAC) and lateral gastrocnemius muscles were abnormal in both equinus groups compared with the control group. Maximal muscle lengths of the MGAC and SOL were longer in the dynamic equinus than FEQ group. Peak lengthening velocity of the triceps surae muscle was significantly slower for all triceps surae muscles in the FEQ group than in the dynamic equinus group and occurred in the early swing phase. Conclusions: The presented results indicate that peak lengthening velocity of the triceps surae muscle might be one of the discriminating factors between FEQ and dynamic equinus deformity in children with cerebral palsy. This could help clinical decision making for treatment of an equinus gait pattern.\n\nKraus, Tanja\n\nLinhart, Wolfgang\n\n\n"
},
{
"text": "\n111945\nPenile Carcinogenesis in a Low-Incidence Area: A Clinicopathologic and Molecular Analysis of 115 Invasive Carcinomas With Special Emphasis on Chronic Inflammatory Skin Diseases\n\nMannweiler, S\n\nSygulla, S\n\nBeham-Schmid, C\n\nRazmara, Y\n\nPummer, K\n\nRegauer, S\n\nBeiträge in Fachzeitschriften\nISI:000291676200007\n21681144.0\n10.1097/PAS.0b013e3182147e59\nNone\nBackground: Human papillomavirus (HPV) infections account worldwide for 50% of penile cancers. The role of lichen sclerosus and lichen planus in penile carcinogenesis needs further investigation. Materials and Methods: Archival formalin-fixed high-grade penile intraepithelial neoplasias, differentiated penile intraepithelial neoplasias, and invasive carcinomas from a single pathology institution in a low-incidence area for penile cancer were analyzed for 28 HPV low-risk and HPV high-risk genotypes, p16(INK4a) overexpression, presence of peritumoral lichen sclerosus, lichen planus, precursor lesions, and monoclonal rearrangement of the T-cell receptor gamma locus. Results: A total of 29 penile intraepithelial neoplasias (100%) and 69 of 115 (60%) invasive cancers contained HPV high-risk genotypes with a single HPV high-risk genotype (80% HPV16, 6% HPV33, 2% HPV45 and HPV18, 1% HPV73). Multiple HPV high-risk genotypes were identified in 4% with and in 5% without HPV16/18. p16(INK4a) overexpression correlated in all but 1 case of HPV high-risk 45 cancer. No p16(INK4a) overexpression and HPV genotype was found in 6 differentiated penile intraepithelial neoplasias and 46 of 115 (40%) invasive cancers, 30% of which were pT2/pT3 cancers. For 35 cancers, peritumoral tissue was available for analysis. Advanced lichen sclerosus was identified in 26, lichen planus in 9, and differentiated penile intraepithelial neoplasia in 18 carcinomas. Dense T-cell-dominant lymphocytic infiltrates were identified in 22 of 46 carcinomas and in 3 of 6 differentiated penile intraepithelial neoplasias, with 6 of 13 analyzed carcinomas/penile intraepithelial neoplasias showing a monoclonal rearrangement of the T-cell receptor gamma locus. Conclusions: The prevalence of HPV high-risk in penile cancers from a low-incidence area was slightly higher than the global distribution. HPV-negative carcinomas were associated with advanced lichen sclerosus and lichen planus, differentiated penile intraepithelial neoplasia, and accumulation of T lymphocytes with monoclonal rearrangement of the T-cell receptor gamma locus.\n\nBeham-Schmid, Christine\n\nMannweiler, Sebastian\n\nPummer, Karl\n\nRegauer, Sigrid\n\nSygulla, Stephan\n\n\n"
},
{
"text": "\n126329\nHeterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome.\n\nGordon, CT\n\nVuillot, A\n\nMarlin, S\n\nGerkes, E\n\nHenderson, A\n\nAlKindy, A\n\nHolder-Espinasse, M\n\nPark, SS\n\nOmarjee, A\n\nSanchis-Borja, M\n\nBdira, EB\n\nOufadem, M\n\nSikkema-Raddatz, B\n\nStewart, A\n\nPalmer, R\n\nMcGowan, R\n\nPetit, F\n\nDelobel, B\n\nSpeicher, MR\n\nAurora, P\n\nKilner, D\n\nPellerin, P\n\nSimon, M\n\nBonnefont, JP\n\nTobias, ES\n\nGarcía-Miñaúr, S\n\nBitner-Glindzicz, M\n\nLindholm, P\n\nMeijer, BA\n\nAbadie, V\n\nDenoyelle, F\n\nVazquez, MP\n\nRotky-Fast, C\n\nCouloigner, V\n\nPierrot, S\n\nManach, Y\n\nBreton, S\n\nHendriks, YM\n\nMunnich, A\n\nJakobsen, L\n\nKroisel, P\n\nLin, A\n\nKaban, LB\n\nBasel-Vanagaite, L\n\nWilson, L\n\nCunningham, ML\n\nLyonnet, S\n\nAmiel, J\n\nBeiträge in Fachzeitschriften\nISI:000314877600007\n23315542.0\n10.1136/jmedgenet-2012-101331\nNone\nAuriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, β 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development.\n We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients.\n These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.\n\nKroisel, Peter\n\nSpeicher, Michael\n\n\n"
},
{
"text": "\n127963\nEfficacy and safety of oral chelators in treatment of patients with Wilson disease.\n\nWeiss, KH\n\nThurik, F\n\nGotthardt, DN\n\nSchäfer, M\n\nTeufel, U\n\nWiegand, F\n\nMerle, U\n\nFerenci-Foerster, D\n\nMaieron, A\n\nStauber, R\n\nZoller, H\n\nSchmidt, HH\n\nReuner, U\n\nHefter, H\n\nTrocello, JM\n\nHouwen, RH\n\nFerenci, P\n\nStremmel, W\n\nEUROWILSON Consortium\n\nBeiträge in Fachzeitschriften\nISI:000322707100028\n23542331.0\n10.1016/j.cgh.2013.03.012\nNone\nBACKGROUND & AIMS: Wilson disease is a genetic copper storage disorder that causes hepatic and neurologic symptoms. Chelating agents (D-penicillamine, trientine) are used as first-line therapies for symptomatic patients, but there are few data from large cohorts. We assessed the safety of D-penicillamine and trientine therapy and outcomes of patients with Wilson disease. METHODS: We performed a retrospective analysis of data on 380 patients with Wilson disease from tertiary care centers in Germany and Austria, and 25 additional patients from the EUROWILSON registry. Chelator-based treatment regimens were analyzed for their effect on neurologic and hepatic symptoms and for adverse events that led to discontinuation of therapy (Kaplan-Meier estimation; data were collected for a mean of 13.3 y after therapy began). RESULTS: Changes in medication were common, resulting in analysis of 471 chelator monotherapies (326 patients receiving D-penicillamine and 141 receiving trientine). Nine of 326 patients treated with D-penicillamine and 3 of 141 patients given trientine underwent liver transplantation. Adverse events leading to discontinuation of treatment were more frequent among those receiving D-penicillamine than trientine (P = .039). Forty-eight months after therapy, hepatic deterioration was reported in only 4 of 333 patients treated initially with a chelating agent. Hepatic improvements were observed in more than 90%, and neurologic improvements were observed in more than 55%, of therapy-naive patients, and values did not differ significantly between treatments. However, neurologic deterioration was observed less frequently in patients given D-penicillamine first (6 of 295) than those given trientine first (4 of 38; P = .018). CONCLUSIONS: Chelating agents are effective therapies for most patients with Wilson disease; D-penicillamine and trientine produce comparable outcomes, although D-penicillamine had a higher rate of adverse events. Few patients receiving chelation therapy had neurologic deterioration, which occurred more frequently in patients who received trientine.\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n132661\nProtective effect of the poly(ADP-ribose) polymerase inhibitor PJ34 on mitochondrial depolarization-mediated cell death in hepatocellular carcinoma cells involves attenuation of c-Jun N-terminal kinase-2 and protein kinase B/Akt activation.\n\nRadnai, B\n\nAntus, C\n\nRacz, B\n\nEngelmann, P\n\nPriber, JK\n\nTucsek, Z\n\nVeres, B\n\nTuri, Z\n\nLorand, T\n\nSumegi, B\n\nGallyas, F\n\nBeiträge in Fachzeitschriften\nISI:000310464400001\n22583868.0\n10.1186/1476-4598-11-34\nPMC3481453\nBackground: 2, -Dimethoxyphenyl-E-4-arylidene-3-isochromanone (IK11) was previously described to induce apoptotic death of A431 tumor cells. In this report, we investigated the molecular action of IK11 in the HepG2 human hepatocellular carcinoma cell line to increase our knowledge of the role of poly (ADP-ribose) polymerase (PARP), protein kinase B/Akt and mitogen activated protein kinase (MAPK) activation in the survival and death of tumor cells and to highlight the possible role of PARP-inhibitors in co-treatments with different cytotoxic agents in cancer therapy. Results: We found that sublethal concentrations of IK11 prevented proliferation, migration and entry of the cells into their G2 phase. At higher concentrations, IK11 induced reactive oxygen species (ROS) production, mitochondrial membrane depolarization, activation of c-Jun N-terminal kinase 2 (JNK2), and substantial loss of HepG2 cells. ROS production appeared marginal in mediating the cytotoxicity of IK11 since N-acetyl cysteine was unable to prevent it. However, the PARP inhibitor PJ34, although not a ROS scavenger, strongly inhibited both IK11-induced ROS production and cell death. JNK2 activation seemed to be a major mediator of the effect of IK11 since inhibition of JNK resulted in a substantial cytoprotection while inhibitors of the other kinases failed to do so. Inhibition of Akt slightly diminished the effect of IK11, while the JNK and Akt inhibitor and ROS scavenger trans-resveratrol completely protected against it. Conclusions: These results indicate significant involvement of PARP, a marginal role of ROS and a pro-apoptotic role of Akt in this system, and raise attention to a novel mechanism that should be considered when cancer therapy is augmented with PARP-inhibition, namely the cytoprotection by inhibition of JNK2.\n\n\n"
},
{
"text": "\n148761\nDifferentially circulating miRNAs after recent osteoporotic fractures can influence osteogenic differentiation.\n\nWeilner, S\n\nSkalicky, S\n\nSalzer, B\n\nKeider, V\n\nWagner, M\n\nHildner, F\n\nGabriel, C\n\nDovjak, P\n\nPietschmann, P\n\nGrillari-Voglauer, R\n\nGrillari, J\n\nHackl, M\n\nBeiträge in Fachzeitschriften\nISI:000359509700007\n26026730.0\n10.1016/j.bone.2015.05.027\nNone\nOsteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level and are known to take part in the control of bone formation and bone resorption. In addition, it is known that miRNAs are secreted by many cell types and can transfer "messages" to recipient cells. Thus, circulating miRNAs might not only be useful as surrogate biomarkers for the diagnosis or prognosis of pathological conditions, but could be actively modulating tissue physiology. Therefore, the aim of this study was to test whether circulating miRNAs that exhibit changes in recent osteoporotic fracture patients could be causally related to bone metabolism. In the first step we performed an explorative analysis of 175 miRNAs in serum samples obtained from 7 female patients with recent osteoporotic fractures at the femoral neck, and 7 age-matched female controls. Unsupervised cluster analysis revealed a high discriminatory power of the top 10 circulating miRNAs for patients with recent osteoporotic fractures. In total 6 miRNAs, miR-10a-5p, miR-10b-5p, miR-133b, miR-22-3p, miR-328-3p, and let-7g-5p exhibited significantly different serum levels in response to fracture (adjusted p-value<0.05). These miRNAs were subsequently analyzed in a validation cohort of 23 patients (11 control, 12 fracture), which confirmed significant regulation for miR-22-3p, miR-328-3p, and let-7g-5p. A set of these and of other miRNAs known to change in the context of osteoporotic fractures were subsequently tested for their effects on osteogenic differentiation of human mesenchymal stem cells (MSCs) in vitro. The results show that 5 out of 7 tested miRNAs can modulate osteogenic differentiation of MSCs in vitro. Overall, these data suggest that levels of specific circulating miRNAs change in the context of recent osteoporotic fractures and that such perturbations of "normal" levels might affect bone metabolism or bone healing processes. \n Copyright © 2015. Published by Elsevier Inc.\n\n\n"
},
{
"text": "\n152335\nNovel meta-analysis-derived type 2 diabetes risk loci do not determine prediabetic phenotypes.\n\nStaiger, H\n\nMachicao, F\n\nKantartzis, K\n\nSchäfer, SA\n\nKirchhoff, K\n\nGuthoff, M\n\nSilbernagel, G\n\nStefan, N\n\nFritsche, A\n\nHäring, HU\n\nBeiträge in Fachzeitschriften\nISI:000264420900042\n18714373.0\n10.1371/journal.pone.0003019\nPMC2500187\nGenome-wide association (GWA) studies identified a series of novel type 2 diabetes risk loci. Most of them were subsequently demonstrated to affect insulin secretion of pancreatic beta-cells. Very recently, a meta-analysis of GWA data revealed nine additional risk loci with still undefined roles in the pathogenesis of type 2 diabetes. Using our thoroughly phenotyped cohort of subjects at an increased risk for type 2 diabetes, we assessed the association of the nine latest genetic variants with the predominant prediabetes traits, i.e., obesity, impaired insulin secretion, and insulin resistance.\n One thousand five hundred and seventy-eight metabolically characterized non-diabetic German subjects were genotyped for the reported candidate single nucleotide polymorphisms (SNPs) JAZF1 rs864745, CDC123/CAMK1D rs12779790, TSPAN8/LGR5 rs7961581, THADA rs7578597, ADAMTS9 rs4607103, NOTCH2 rs10923931, DCD rs1153188, VEGFA rs9472138, and BCL11A rs10490072. Insulin sensitivity was derived from fasting glucose and insulin concentrations, oral glucose tolerance test (OGTT), and hyperinsulinemic-euglycemic clamp. Insulin secretion was estimated from OGTT data. After appropriate adjustment for confounding variables and Bonferroni correction for multiple comparisons (corrected alpha-level: p = 0.0014), none of the SNPs was reliably associated with adiposity, insulin sensitivity, or insulin secretion (all p > or = 0.0117, dominant inheritance model). The risk alleles of ADAMTS9 SNP rs4607103 and VEGFA SNP rs9472138 tended to associate with more than one measure of insulin sensitivity and insulin secretion, respectively, but did not reach formal statistical significance. The study was sufficiently powered (1-beta = 0.8) to detect effect sizes of 0.19 < or = d < or = 0.25 (alpha = 0.0014) and 0.13 < or = d < or = 0.16 (alpha = 0.05).\n In contrast to the first series of GWA-derived type 2 diabetes candidate SNPs, we could not detect reliable associations of the novel risk loci with prediabetic phenotypes. Possible weak effects of ADAMTS9 SNP rs4607103 and VEGFA SNP rs9472138 on insulin sensitivity and insulin secretion, respectively, await further confirmation by larger studies.\n\nSilbernagel, Günther\n\n\n"
},
{
"text": "\n152970\nRandomized double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 2 diabetes: IMAGINE 4.\n\nBlevins, T\n\nPieber, TR\n\nColón Vega, G\n\nZhang, S\n\nBastyr, EJ\n\nChang, AM\n\nIMAGINE 4 Investigators\n\nBeiträge in Fachzeitschriften\nISI:000386023700004\n27234693.0\n10.1111/dom.12696\nPMC5096023\nTo evaluate the efficacy and safety of basal insulin peglispro (BIL) with those of insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (T2D).\n In this phase III, multicentre, double-blind, 26-week study, we randomized patients with T2D [glycated haemoglobin (HbA1c) ≥7 and <12%, on ≥1 insulin injections daily) to BIL (n = 691) or glargine (n = 678), in combination with lispro.\n At week 26, the primary objective of non-inferiority of BIL versus glargine for HbA1c reduction was achieved (least squares mean difference -0.21%; 95% confidence interval -0.31 to -0.11%), with statistical superiority of BIL with multiplicity adjustment (p < 0.001). HbA1c at baseline was 8.4% versus 8.5% for BIL versus glargine and at 26 weeks it was 6.8% versus 7.0%. At 26 weeks, more patients reached HbA1c <7% with BIL than with glargine (63.3% vs 53.3%; p < 0.001), the nocturnal hypoglycaemia rate (≤3.9 mmol/l) was lower with BIL (0.51 vs 0.92 events/30 days; p < 0.001), but the daytime hypoglycaemia rate was higher with BIL (5.47 vs 4.53 events/30 days; p < 0.001). The total hypoglycaemia relative rate was 1.10 (p = 0.053). At 26 weeks, patients in the BIL group had lower fasting serum glucose levels, higher basal insulin dosing, with no statistically significant difference in prandial or total insulin dosing, reduced glucose variability and less weight gain (1.3 kg vs 2.2 kg) compared with the glargine group. The BIL group had higher mean triglyceride and aminotransferase levels.\n In patients with T2D, BIL with insulin lispro provided greater improvement in glycaemic control with less nocturnal hypoglycaemia, lower glucose variability and less weight gain compared with glargine. The daytime hypoglycaemia rate and mean triglyceride and aminotransferase levels were higher with BIL.\n © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n155003\nKeratin 23 is a stress-inducible marker of mouse and human ductular reaction in liver disease.\n\nGuldiken, N\n\nKobazi Ensari, G\n\nLahiri, P\n\nCouchy, G\n\nPreisinger, C\n\nLiedtke, C\n\nZimmermann, HW\n\nZiol, M\n\nBoor, P\n\nZucman-Rossi, J\n\nTrautwein, C\n\nStrnad, P\n\nBeiträge in Fachzeitschriften\nISI:000382214000015\n27151178.0\n10.1016/j.jhep.2016.04.024\nNone\nKeratins (K) constitute the epithelial intermediate filaments. Among them, K7/K19 are widely used markers of the regenerative liver response termed ductular reaction (DR) that consists of activated biliary epithelial cells (BECs) and hepatic progenitor cells (HPCs) and correlates with liver disease severity. In the present study we aimed to characterize K23 in the liver.\n We analyzed the expression and localization of K23 in the digestive system under basal conditions as well as in various human and mouse liver diseases/stress models. Cell culture studies were used to study factors regulating K23 expression.\n In untreated mice, K23 was restricted to biliary epithelia. It was (together with K7/K19) markedly upregulated in three different DR/cholestatic injury models, i.e., multidrug resistance protein 2 (Mdr2) knockouts, animals treated with 3, -diethoxycarbonyl-1, -dihydrocollidine or subjected to bile duct ligation. K23 levels correlated with the DR marker Fn14 and immunofluorescence staining showed a distinct co-localization with K7/K19. In chronic human liver disease, K23 expression increased in patients with a more prominent inflammation/fibrosis. A dramatic upregulation (>200times) was observed in patients with acute liver failure (ALF) and end-stage primary biliary cholangitis (PBC). Patients with alcoholic liver cirrhosis displayed increased K23 serum levels. In primary hepatocytes as well as hepatobiliary cell lines, treatment with TNF-related weak inducer of apoptosis (TWEAK), and the type I acute phase inducer interleukin (IL)-1β but not the type II inducer IL-6 elevated K23 expression.\n K23 represents a specific, stress-inducible DR marker, whose levels correlate with liver disease severity. K23 may represent a useful non-invasive DR marker.\n Ductular reaction represents a basic response to liver injury and correlates with liver disease severity. Our study identifies K23 as a novel ductular reaction marker in mice and humans.\n Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.\n\n\n"
},
{
"text": "\n155679\nMaternal obesity modulates intracellular lipid turnover in the human term placenta.\n\nHirschmugl, B\n\nDesoye, G\n\nCatalano, P\n\nKlymiuk, I\n\nScharnagl, H\n\nPayr, S\n\nKitzinger, E\n\nSchliefsteiner, C\n\nLang, U\n\nWadsack, C\n\nHauguel-de Mouzon, S\n\nBeiträge in Fachzeitschriften\nISI:000394143700015\n27780978.0\n10.1038/ijo.2016.188\nPMC5309341\nObesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development.\n We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women.\n Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays.\n Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04-1.24 mg g-1, P<0.05) vs lean (0.84, CI 0.72-1.02 mg g-1) women. Among target genes examined, six showed positive correlation (P<0.05) with maternal pre-pregnancy BMI, namely ATGL (PNPLA2), FATP1 (SLC27A1), FATP3 (SLC27A3), PLIN2, PPARG and CGI-58 (ABHD5). CGI-58 protein abundance was twofold higher (P<0.001) in placentas of obese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, P<0.001 and R=0.64, P<0.001, respectively). CGI-58 and PLIN2 were primarily located in the syncytiotrophoblast and, were upregulated (1.38- and 500-fold, respectively) upon oleic acid and insulin treatment of cultured trophoblast cells.\n Pre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG hydrolysis, contributes to the turnover of intracellular lipids in placenta of obese women, and is tightly regulated by metabolic factors of the mother.\n\nDesoye, Gernot\n\nHirschmugl, Birgit\n\nKlymiuk, Ingeborg\n\nScharnagl, Hubert\n\nSchliefsteiner, Carolin\n\nWadsack, Christian\n\n\n"
},
{
"text": "\n166864\nElevated Cardiac Troponin T in Patients With Skeletal Myopathies.\n\nSchmid, J\n\nLiesinger, L\n\nBirner-Gruenberger, R\n\nStojakovic, T\n\nScharnagl, H\n\nDieplinger, B\n\nAsslaber, M\n\nRadl, R\n\nBeer, M\n\nPolacin, M\n\nMair, J\n\nSzolar, D\n\nBerghold, A\n\nQuasthoff, S\n\nBinder, JS\n\nRainer, PP\n\nBeiträge in Fachzeitschriften\nISI:000428995100007\n29622161.0\n10.1016/j.jacc.2018.01.070\nNone\nCardiac troponins are often elevated in patients with skeletal muscle disease who have no evidence of cardiac disease.\n The goal of this study was to characterize cardiac troponin concentrations in patients with myopathies and derive insights regarding the source of elevated troponin T measurements.\n Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) concentrations were determined by using high sensitivity assays in 74 patients with hereditary and acquired skeletal myopathies. Patients underwent comprehensive cardiac evaluation, including 12-lead electrocardiogram, 24-h electrocardiogram, cardiac magnetic resonance imaging, and coronary artery computed tomography. cTnT and cTnI protein expression was determined in skeletal muscle samples of 9 patients and in control tissues derived from autopsy using antibodies that are used in commercial assays. Relevant Western blot bands were subjected to liquid chromatography tandem mass spectrometry for protein identification.\n Levels of cTnT (median: 24 ng/l; interquartile range: 11 to 54 ng/l) were elevated (>14 ng/l) in 68.9% of patients; cTnI was elevated (>26 ng/l) in 4.1% of patients. Serum cTnT levels significantly correlated with creatine kinase and myoglobin (r = 0.679 and 0.786, respectively; both p < 0.001). Based on cTnT serial testing, 30.1% would have fulfilled current rule-in criteria for myocardial infarction. Noncoronary cardiac disease was present in 23%. Using cTnT antibodies, positive bands were found in both diseased and healthy skeletal muscle at molecular weights approximately 5 kDa below cTnT. Liquid chromatography tandem mass spectrometry identified the presence of skeletal troponin T isoforms in these bands.\n Measured cTnT concentrations were chronically elevated in the majority of patients with skeletal myopathies, whereas cTnI elevation was rare. Our data indicate that cross-reaction of the cTnT immunoassay with skeletal muscle troponin isoforms was the likely cause.\n Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.\n\nAsslaber, Martin\n\nBerghold, Andrea\n\nBinder, Josepha Stephanie\n\nBirner-Grünberger, Ruth\n\nLiesinger, Laura\n\nQuasthoff, Stefan\n\nRadl, Roman\n\nRainer, Peter\n\nScharnagl, Hubert\n\nSchmid, Johannes\n\n\n"
},
{
"text": "\n168650\nPraxis der Teledermatologie.\n\nAugustin, M\n\nWimmer, J\n\nBiedermann, T\n\nBlaga, R\n\nDierks, C\n\nDjamei, V\n\nElmer, A\n\nElsner, P\n\nEnk, A\n\nGass, S\n\nHenningsen, M\n\nHofman-Wellenhof, R\n\nvon Kiedrowski, R\n\nKunz, HD\n\nLiebram, C\n\nNavarini, A\n\nOtten, M\n\nReusch, M\n\nSchüller, C\n\nZink, A\n\nStrömer, K\n\nBeiträge in Fachzeitschriften\nISI:000438344300002\n29998512.0\n10.1111/ddg.13512\nNone\nTeledermatologische Anwendungen werden im deutschen Versorgungssystem in den nächsten Jahren erheblich an Bedeutung gewinnen. Das vorliegende Empfehlungspapier wurde als Expertenkonsens auf der Basis einer qualifizierten Literaturrecherche und eines strukturierten Entscheidungsprozesses der Autorengruppe entwickelt. ZIELSETZUNG: a) die IST-Analyse zum Einsatz der Telemedizin in der Dermatologie, b) die Bewertung der Evidenz ihres Nutzens und ihrer Sicherheit und, c) die Entwicklung von Verfahrensstandards für die ärztliche Praxis in den deutschsprachigen Ländern. Auf der Basis dieser Erkenntnisse soll durch einen Expertenkonsens eine Handlungsorientierung für den Einsatz der Teledermatologie gegeben werden.\n Dreistufiges Vorgehen: 1) Systematische Literaturrecherche in den internationalen medizinischen Onlinedatenbanken Pubmed und Embase, 2) Weitere, teils manuelle Recherchen, 3) Expertenkonsens mit einem systematischen Entscheidungsverfahren mit 21 Teilnehmern.\n In der strukturierten Literaturrecherche fanden sich 204 wissenschaftliche Originalarbeiten, in denen Anwendungen der Telemedizin bei Hautkrankheiten thematisiert wurden. Diese wurden systematisch aufgearbeitet, analysiert und bewertet. In der zweiten Stufe wurden in einer Handsuche zusätzliche relevante Schriften identifiziert und ebenfalls ausgewertet. Das Expertengremium entwickelte dann auf der Basis der externen Evidenz sowie der internen Diskussion Handlungsempfehlungen für die Praxis. Schlussfolgerung der wissenschaftlichen Studienlage ist, dass die telemedizinische Unterstützung der dermatologischen Behandlung und Prävention bei Einsatz leistungsfähiger Systeme, Kenntnis ihrer Anwendung sowie Beachtung der Indikationen und Kontrainidikationen einen erheblichen Mehrnutzen darstellt.\n Die Teledermatologie hat in den deutschsprachigen Ländern wie auch weltweit einen zunehmenden Stellenwert und bietet aufgrund des hohen Innovationsgrades eine Vorreiter- und Vorbildfunktion für weitere telemedizinische Anwendungen anderer Fachrichtungen. Eine qualitätsgesicherte teledermatologische Behandlung ist in den deutschsprachigen Ländern praktikabel und kann zu einem relevanten Mehrnutzen in der Versorgung führen. Ihr Einsatz ist immer dann in Erwägung zu ziehen, wenn relevante Zusatznutzen für die Patienten ohne relevante Nachteile für sie und für die Versorgenden zu erwarten sind. Für die teledermatologische Behandlung wurden mit dem vorliegenden Konsensuspapier praxisrelevante Maßgaben festgelegt. Etwaige situationsabhängige Limitationen in der Versorgung sind stets zu beachten.\n © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.\n\nHofmann-Wellenhof, Rainer\n\n\n"
},
{
"text": "\n168782\nCharacteristics of reversible and nonreversible COPD and asthma and COPD overlap syndrome patients: an analysis of salbutamol Easyhaler data.\n\nMüller, V\n\nGálffy, G\n\nOrosz, M\n\nKováts, Z\n\nOdler, B\n\nSelroos, O\n\nTamási, L\n\nBeiträge in Fachzeitschriften\nISI:000368058800001\n26834466.0\n10.2147/COPD.S92331\nPMC4716721\nThe choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result. On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics. In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70% in chronic obstructive pulmonary disease [COPD]; <80% in asthma) were included (n=121, age: 57.8±17.3 years). Bronchodilator reversibility (American Thoracic Society/European Respiratory Society criteria) was tested in patients with COPD (n=63) and asthma and COPD overlap syndrome (ACOS; n=12). Forty-six asthmatics served as controls. Reversibility was tested with 400 µg salbutamol dry powder inhaler (Buventol Easyhaler, Orion Pharma Ltd, Espoo, Finland). Demographic data and patients' perceptions of Easyhaler compared with β2-agonist pressurized metered dose inhalers (pMDIs) were analyzed. American Thoracic Society/European Respiratory Society guideline defined reversibility was found in 21 out of 63 COPD patients and in two out of 12 ACOS patients. Airway obstruction was more severe in COPD patients as compared with controls (mean FEV1 and FEV1% predicted both P<0.0001). Average response to salbutamol was significantly lower in COPD patients compared with asthma controls (P<0.0001). Reversibility was equally often found in smokers as in never-smokers (33% vs 34%). Nonreversible COPD patients had higher mean weight, body mass index, and FEV1/FVC compared with reversible COPD patients. Most patients preferred Easyhaler and defined its use as simpler and more effective than use of a pMDI. Never-smokers and patients with asthma experienced Easy-haler somewhat easier to use than smokers and patients with COPD. In conclusion, a substantial part of patients with COPD or ACOS showed reversibility to salbutamol dry powder inhaler. Nonreversible patients with COPD were characterized by higher weight and body mass index, and a higher FEV1/FVC ratio. Most patients preferred Easyhaler compared with a pMDI.\n\nOdler, Balazs\n\n\n"
},
{
"text": "\n168844\nOral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema.\n\nAygören-Pürsün, E\n\nBygum, A\n\nGrivcheva-Panovska, V\n\nMagerl, M\n\nGraff, J\n\nSteiner, UC\n\nFain, O\n\nHuissoon, A\n\nKinaciyan, T\n\nFarkas, H\n\nLleonart, R\n\nLonghurst, HJ\n\nRae, W\n\nTriggiani, M\n\nAberer, W\n\nCancian, M\n\nZanichelli, A\n\nSmith, WB\n\nBaeza, ML\n\nDu-Thanh, A\n\nGompels, M\n\nGonzalez-Quevedo, T\n\nGreve, J\n\nGuilarte, M\n\nKatelaris, C\n\nDobo, S\n\nCornpropst, M\n\nClemons, D\n\nFang, L\n\nCollis, P\n\nSheridan, W\n\nMaurer, M\n\nCicardi, M\n\nBeiträge in Fachzeitschriften\nISI:000439757700008\n30044938.0\n10.1056/NEJMoa1716995\nNone\nHereditary angioedema is a life-threatening illness caused by mutations in the gene encoding C1 inhibitor (also called C1 esterase inhibitor) that lead to overactivation of the kallikrein-bradykinin cascade. BCX7353 is a potent oral small-molecule inhibitor of plasma kallikrein with a pharmacokinetic and pharmacodynamic profile that may help prevent angioedema attacks.\n In this international, three-part, dose-ranging, placebo-controlled trial, we evaluated four doses of BCX7353 (62.5 mg, 125 mg, 250 mg, and 350 mg once daily) for the prevention of angioedema attacks over a 28-day period. Patients with type I or II hereditary angioedema with a history of at least two angioedema attacks per month were randomly assigned to BCX7353 or placebo. The primary efficacy end point was the number of confirmed angioedema attacks. Key secondary end points included angioedema attacks according to anatomical location and quality of life.\n A total of 77 patients underwent randomization, 75 received BCX7353 or placebo, and 72 completed the trial. The rate of confirmed angioedema attacks was significantly lower among patients who received BCX7353 at daily doses of 125 mg or more than among those who received placebo, with a 73.8% difference at 125 mg (P<0.001). Significant benefits with respect to quality-of-life scores were observed in the 125-mg and 250-mg dose groups (P<0.05). Gastrointestinal adverse events, predominantly of grade 1, were the most commonly reported adverse events, particularly in the two highest BCX7353 dose groups.\n Once-daily oral administration of BCX7353 at a dose of 125 mg or more resulted in a significantly lower rate of attacks of hereditary angioedema than placebo. Mild gastrointestinal symptoms were the principal side effect. (Funded by BioCryst Pharmaceuticals; APeX-1 ClinicalTrials.gov number, NCT02870972 .).\n\nAberer, Werner\n\n\n"
}
]
}