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"text": "\n165596\nEffects of Teriparatide Compared with Risedronate on the Risk of Fractures in Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial.\n\nGeusens, P\n\nMarin, F\n\nKendler, DL\n\nRusso, LA\n\nZerbini, CA\n\nMinisola, S\n\nBody, JJ\n\nLespessailles, E\n\nGreenspan, SL\n\nBagur, A\n\nStepan, JJ\n\nLakatos, P\n\nCasado, E\n\nMoericke, R\n\nLópez-Romero, P\n\nFahrleitner-Pammer, A\n\nBeiträge in Fachzeitschriften\nISI:000432006800004\n29329484.0\n10.1002/jbmr.3384\nNone\nThe 2-year, randomized, double-blind, active-controlled fracture endpoint VERO study included postmenopausal women with established osteoporosis, who had at least 2 moderate or 1 severe baseline vertebral fractures (VFx), and bone mineral density (BMD) T-score ≤-1.5. Patients were treated with either s.c. daily teriparatide 20 μg or oral weekly risedronate 35 mg. As previously reported, the risk of new VFx and clinical fractures (a composite of clinical VFx and nonvertebral fragility fractures [NVFFx]) was statistically significantly reduced with teriparatide compared with risedronate. Here we present the prospectively planned subgroup analyses of fracture data across subgroups, which were predefined by the following baseline characteristics: age, number and severity of prevalent VFx, prevalent nonvertebral fractures (NVFx), glucocorticoid use, prior osteoporosis drugs, recent bisphosphonate use, clinical VFx in the year before study entry, and baseline BMD. Heterogeneity of the treatment effect on the primary endpoint (new VFx), and the four key secondary endpoints (including clinical fractures and NVFFx) were investigated by logistic and Cox proportional hazards regression models. A total of 1360 women were randomized and treated (680 per group). Mean age was 72.1 years, mean (SD) number of prevalent VFx was 2.7 (2.1), 55.4% had a BMD T-score <-2.5, 36.5% had a recent clinical VFx, 28.3% had a prior major NVFx, 43.2% were osteoporosis drug-naïve, 39.3% were recent bisphosphonate users, and 9.3% were taking glucocorticoids at a prednisone-equivalent dose of >5 mg/d. For most fracture endpoints, the risk reduction of teriparatide versus risedronate did not significantly differ in any of the subgroups analyzed (treatment-by-subgroup interaction p > 0.1), with most subgroups mirroring results from the total study population. In conclusion, in postmenopausal women with severe osteoporosis, the antifracture efficacy of teriparatide compared with risedronate was consistent in a wide range of patient settings, including treatment-naïve and previously treated patients. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.\n © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.\n\nFahrleitner-Pammer, Astrid\n\n\n"
},
{
"text": "\n186991\nA hospital-wide evaluation of delirium prevalence and outcomes in acute care patients - a cohort study.\n\nSchubert, M\n\nSchürch, R\n\nBoettger, S\n\nGarcia Nuñez, D\n\nSchwarz, U\n\nBettex, D\n\nJenewein, J\n\nBogdanovic, J\n\nStaehli, ML\n\nSpirig, R\n\nRudiger, A\n\nBeiträge in Fachzeitschriften\nISI:000438825700006\n30005646.0\n10.1186/s12913-018-3345-x\nPMC6045819\nDelirium is a well-known complication in cardiac surgery and intensive care unit (ICU) patients. However, in many other settings its prevalence and clinical consequences are understudied. The aims of this study were: (1) To assess delirium prevalence in a large, diverse cohort of acute care patients classified as either at risk or not at risk for delirium; (2) To compare these two groups according to defined indicators; and (3) To compare delirious with non-delirious patients regarding hospital mortality, ICU and hospital length of stay, nursing hours and cost per case.\n This cohort study was performed in a Swiss university hospital following implementation of a delirium management guideline. After excluding patients aged < 18 years or with a length of stay (LOS) < 1 day, 29'278 patients hospitalized in the study hospital in 2014 were included. Delirium period prevalence was calculated based on a Delirium Observation Scale (DOS) score ≥ 3 and / or Intensive Care Delirium Screening Checklist (ICDSC) scores ≥4.\n Of 10'906 patients admitted, DOS / ICDSC scores indicated delirium in 28.4%. Delirium was most prevalent (36.2-40.5%) in cardiac surgery, neurosurgery, trauma, radiotherapy and neurology patients. It was also common in geriatrics, internal medicine, visceral surgery, reconstructive plastic surgery and cranio-maxillo-facial surgery patients (prevalence 21.6-28.6%). In the unadjusted and adjusted models, delirious patients had a significantly higher risk of inpatient mortality, stayed significantly longer in the ICU and hospital, needed significantly more nursing hours and generated significantly higher costs per case. For the seven most common ICD-10 diagnoses, each diagnostic group's delirious patients had worse outcomes compared to those with no delirium.\n The results indicate a high number of patients at risk for delirium, with high delirium prevalence across all patient groups. Delirious patients showed significantly worse clinical outcomes and generated higher costs. Subgroup analyses highlighted striking variations in delirium period-prevalence across patient groups. Due to the high prevalence of delirium in patients treated in care centers for radiotherapy, visceral surgery, reconstructive plastic surgery, cranio-maxillofacial surgery and oral surgery, it is recommended to expand the current focus of delirium management to these patient groups.\n\nJenewein, Josef\n\n\n"
},
{
"text": "\n37\n5-Fluorouracil and Folinic Acid with or Without Alpha-2C Interferon in the Treatment of Metastatic Colorectal-Cancer - Preliminary-Results of a Multicenter Prospective Randomized Phase-III Trial\n\nMoser, R\n\nHausmaninger, H\n\nLudwig, H\n\nFridrik, M\n\nSchmidt, H\n\nMlineritsch, B\n\nPecherstorfer, M\n\nMichlmayr, G\n\nKopf, C\n\nSamonigg, H\n\nBeiträge in Fachzeitschriften\nISI:A1995RC51600004\nNone\nNone\nNone\nBackground: For treatment of advanced colorectal cancer sufficient data exist confirming the efficacy of biochemical modulation of 5-fluorouracil (5FU) by folinic acid (FA). Several randomized clinical trials demonstrated a higher objective tumor response for 5FU/FA in comparison with 5FU alone. Thus the 5FU/FA regimen is recommended as treatment of first choice in metastatic colorectal cancer. Based on recent data showing that alpha-2c interferon (IFN) modulates and thereby enhances the cytotoxic effects of 5FU, the present trial was conducted to evaluate the concomitant use of IFN with 5FU/FA with regard to efficacy and toxicity. Patients and Methods: 218 patients with measurable, progressive metastatic colorectal cancer, previously untreated for advanced disease, were enrolled in this trial. They were randomly assigned to receive either treatment with FA 100 mg/m(2) as an i.v. infusion over 15 min immediately followed by 5FU 500 mg/m(2) as an i, v. infusion over 30 min for 4 days and later on once weekly for 7 weeks (arm A) or with FA and 5FU in the same schedule plus IFN 7 million units s. c. 3 times per week (arm B). Results: So far 186 patients are evaluable for assessment of response, in group A 95 and in group B 91 patients. Overall response rate is 25 % for the 5FU/FA arm and 38% for the IFN arm (p=0.067). Median time to disease progression is 150 days vs 200 days (p=0.18), median survival is 13 vs 10 months (p=0.07). Toxicity was mild, mainly restricted to WHO grades I and II, but was reported more often for the IFN arm, especially concerning loss of appetite, fever, flu-like syndrome, fatigue and diarrhea. Major toxicity grades III and IV was rare, there was no treatment-related death. Conclusions: Results of this interim analysis show no statistically significant difference between the two treatment modalities with regard to response rate and survival. It will be of interest whether an observed trend for improved survival (p=0.07) and less toxicity for the 5FU/FA group will be confirmed by a longer follow-up period.\n\nSamonigg, Hellmut\n\nSchaberl-Moser, Renate\n\n\n"
},
{
"text": "\n4548\nIs first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.\n\nHeidemann, E\n\nStoeger, H\n\nSouchon, R\n\nHirschmann, WD\n\nBodenstein, H\n\nOberhoff, C\n\nFischer, JT\n\nSchulze, M\n\nClemens, M\n\nAndreesen, R\n\nMahlke, M\n\nKönig, M\n\nScharl, A\n\nFehnle, K\n\nKaufmann, M\n\nBeiträge in Fachzeitschriften\nISI:000179453600004\n12419743.0\n10.1096/annonc/mdf306\nNone\nBACKGROUND: To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS: A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status. RESULTS: After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment. CONCLUSIONS: No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.\n\nStoeger, Herbert\n\n\n"
},
{
"text": "\n6223\nCervical spine injuries in stable lower cervical spine with spinal stenosis].\n\nSchweighofer, F\n\nStockenhuber, N\n\nBratschitsch, G\n\nRaith, J\n\nBeiträge in Fachzeitschriften\nISI:000174351300014\n11968545.0\n10.1007/s001130100324\nNone\nThe aim of the study was to investigate the neurological outcome of spinal cord injuries in the traumatized cervical spine with a stenosis of the spinal medullary canal. From 1992 to 1999 we treated 145 spinal cord injuries and/or injuries with an unstable cervical spine, 138 were treated operatively, in 7 patients we found an injury of the spinal cord with a stable cervical spine and a stenosis of the spinal medullary canal. The radiological diagnostics consisted of anterioposterior X-rays of the cervical spine, an X-ray view of the dens axis and a stress roentgenogramm in extension and flection. An MRI was performed within the first 12 hours after the accident. The stenosis of the spinal medullary canal was evaluated by the quotient of the mid-sagittal diameter of the spinal medullary canal as well as the vertebral body (Torg-quotient) and ranged from 0.5 to 0.8. Pathological changed values were found in 4 patients within 2 segments and in 3 patients within 3 segments. In the T2-turbospin echo sequence hyperintense lesions of the spinal cord, accordingly to an edema were found in 6 patients. The neurological evaluation was performed according to the "Standard Neurological Classification of Spinal Cord Injuries". Treatment of these 7 patients was performed conservatively, consisting of NSAR as well as Methyl-Prednisolon according to the pattern of NASCIS-II and III. The follow-up was performed after 12 to 18 months. We evaluated the X-rays in anterioposterior and lateral view, stress roentgenogramms and neurological status. Radiological findings showed stable conditions of the cervical spine with block vertebras and increased osteophytes. The neurological outcome was evaluated according to the "Motor-Score" and showed an improvement from 8 to 63 points within 13 months in one case. In 6 cases, the average "Motor-Score" of 78 increased to 100 points within 2 to 5 months after injury. Most defunctionalization symptoms were found in the upper extremities. Disturbances in fine motor movement were unable to be examined with the "Motor-Score". We can conclude that spinal cord injuries in stable cervical spines with stenosis of the spinal medullary canal can be treated conservatively with a good outcome. A regression of the neurological deficiency can be expected within 2 to 5 months, but even after one year, deficiency regression is possible.\n\nBratschitsch, Gerhard\n\n\n"
},
{
"text": "\n12593\nFrequency and significance of lumbar and inferior mesenteric artery perfusion after endovascular repair of abdominal aortic aneurysms.\n\nFritz, GA\n\nDeutschmann, HA\n\nSchoellnast, H\n\nStessel, U\n\nSorantin, E\n\nPortugaller, HR\n\nQuehenberger, F\n\nHausegger, KA\n\nBeiträge in Fachzeitschriften\nISI:000226315200010\n15615556.0\n10.1583/04-1248MR.1\nNone\nTo evaluate the frequency and influence of perfused side branches (lumbar arteries [LA] and inferior mesenteric artery trunks) on development of type II endoleaks (EL-II) and on volume changes of abdominal aortic aneurysms (AAA) after endovascular repair.\n Of 114 patients undergoing EVR of AAA, 89 patients (83 men; mean age 72+/-7.5 years, range 51-88) with >6 months' follow-up and no type I endoleaks were retrospectively analyzed to determine any relationships between retrograde perfusion, endoleaks, and sac volume. Data were derived from computed tomographic angiographic (CTA) scans taken before and after intervention, at discharge, and at 1, 3, 6, and semi-annually thereafter in follow-up. Two groups were identified and compared based on their status at 6 months post EVR: without perfused side branches (group 1) and with perfused collaterals (group 2); group 2 was further divided according to the absence (2a) or presence (2b) of endoleak.\n Median follow-up was 24 months (range 6-36). Based on a total of 582 CTAs analyzed, 17 (19%) patients developed type II endoleaks (EL-II) during follow-up. There was a significant difference in the number of perfused LAs prior to EVR between groups 1 (n=44) and the 45 patients with postprocedural patent collateral arteries in group 2 (p<0.05); there was no significant difference between groups 2a and 2b (p=0.88) relative to the number of pre-existing patent collaterals. The number of pLAs preoperatively and the rate of type II endoleak were significantly correlated (p<0.05). No type II endoleak was seen in patients without perfused side branches (p=0.01). No significant differences in mean volumes were found between groups 1 and 2a (no EL-II), but significant differences between groups 1 and 2b were seen in later follow-up.\n A larger number of patent LAs before EVR was associated with a significantly higher rate of type II endoleak. Patent collateral vessels were common after aneurysm repair, but the frequency decreased during follow-up. Persistent side branch perfusion was associated with increased type II endoleak after endovascular AAA repair. Significant differences in volume changes in later follow-up were seen between patients with or without type II endoleak.\n\nDeutschmann, Hannes\n\nHausegger, Klaus\n\nPortugaller, Rupert\n\nQuehenberger, Franz\n\nSchoellnast, Helmut\n\nSorantin, Erich\n\n\n"
},
{
"text": "\n137969\nAn international multicenter study on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing.\n\nSimen, BB\n\nBraverman, MS\n\nAbbate, I\n\nAerssens, J\n\nBidet, Y\n\nBouchez, O\n\nGabriel, C\n\nIzopet, J\n\nKessler, HH\n\nStelzl, E\n\nDi Giallonardo, F\n\nSchlapbach, R\n\nRadonic, A\n\nParedes, R\n\nRecordon-Pinson, P\n\nSakwa, J\n\nSt John, EP\n\nSchmitz-Agheguian, GG\n\nMetzner, KJ\n\nDäumer, MP\n\n454 HIV Alphastudy Group\n\nBeiträge in Fachzeitschriften\nISI:000337649100006\n24731928.0\n10.1016/j.jviromet.2014.04.007\nNone\nThe detection of mutant spectra within the viral quasispecies is critical for therapeutic management of HIV-1 infections. Routine clinical application of ultrasensitive genotyping requires reproducibility and concordance within and between laboratories. The goal of the study was to evaluate a new protocol on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing (454-UDS) in an international multicenter study. Sixteen blinded HIV-1 subtype B samples were provided for 454-UDS as both RNA and cDNA with viral titers of 88, 00-573, 00 HIV-1 RNA copies/ml. Eight overlapping amplicons spanning protease (PR) codons 10-99 and reverse transcriptase (RT) codons 1-251 were generated using molecular barcoded primers. 454-UDS was performed using the 454 Life Sciences/Roche GS FLX platform. PR and RT sequences were analyzed using 454 Life Sciences Amplicon Variant Analyzer (AVA) software. Quantified variation data were analyzed for intra-laboratory reproducibility and inter-laboratory concordance. Routine population sequencing was performed using the ViroSeq HIV-1 genotyping system. Eleven laboratories and the reference laboratory 454 Life Sciences sequenced the HIV-1 sample set. Data presented are derived from seven laboratories and the reference laboratory since severe study protocol execution errors occurred in four laboratories leading to exclusion. The median sequencing depth across all sites was 1364 reads per position (IQR=809-2065). 100% of the ViroSeq-reported mutations were also detected by 454-UDS. Minority HIV-1 drug resistance mutations, defined as HIV-1 drug resistance mutations identified at frequencies of 1-25%, were only detected by 454-UDS. Analysis of 10 preselected majority and minority mutations were consistently found across sites. The analysis of drug-resistance mutations detected between 1 and 10% demonstrated high intra- and inter-laboratory consistency in frequency estimates for both RNA and prepared cDNA samples, indicating robustness of the method. HIV-1 drug resistance testing using 454 ultra-deep pyrosequencing results in an accurate and highly reproducible, albeit complex, approach to the analysis of HIV-1 mutant spectra, even at frequencies well below those detected by routine population sequencing.\n Copyright © 2014 Elsevier B.V. All rights reserved.\n\nKessler, Harald\n\nStelzl, Evelyn\n\n\n"
},
{
"text": "\n152230\nIdentification of genetic loci associated with Helicobacter pylori serologic status.\n\nMayerle, J\n\nden Hoed, CM\n\nSchurmann, C\n\nStolk, L\n\nHomuth, G\n\nPeters, MJ\n\nCapelle, LG\n\nZimmermann, K\n\nRivadeneira, F\n\nGruska, S\n\nVölzke, H\n\nde Vries, AC\n\nVölker, U\n\nTeumer, A\n\nvan Meurs, JB\n\nSteinmetz, I\n\nNauck, M\n\nErnst, F\n\nWeiss, FU\n\nHofman, A\n\nZenker, M\n\nKroemer, HK\n\nProkisch, H\n\nUitterlinden, AG\n\nLerch, MM\n\nKuipers, EJ\n\nKuipers, E\n\nBeiträge in Fachzeitschriften\nISI:000318481900026\n23652523.0\n10.1001/jama.2013.4350\nNone\nHelicobacter pylori is a major cause of gastritis and gastroduodenal ulcer disease and can cause cancer. H. pylori prevalence is as high as 90% in some developing countries but 10% of a given population is never colonized, regardless of exposure. Genetic factors are hypothesized to confer H. pylori susceptibility.\n To identify genetic loci associated with H. pylori seroprevalence in 2 independent population-based cohorts and to determine their putative pathophysiological role by whole-blood RNA gene expression profiling.\n Two independent genome-wide association studies (GWASs) and a subsequent meta-analysis were conducted for anti-H. pylori IgG serology in the Study of Health in Pomerania (SHIP) (recruitment, 1997-2001 [n = 3830]) as well as the Rotterdam Study (RS-I) (recruitment, 1990-1993) and RS-II (recruitment, 2000-2001 [n = 7108]) populations. Whole-blood RNA gene expression profiles were analyzed in RS-III (recruitment, 2006-2008 [n = 762]) and SHIP-TREND (recruitment, 2008-2012 [n = 991]), and fecal H. pylori antigen in SHIP-TREND (n = 961).\n H. pylori seroprevalence.\n Of 10, 38 participants, 6160 (56.3%) were seropositive for H. pylori. GWASs identified the toll-like receptor (TLR) locus (4p14; top-ranked single-nucleotide polymorphism (SNP), rs10004195; P = 1.4 × 10(-18); odds ratio, 0.70 [95% CI, 0.65 to 0.76]) and the FCGR2A locus (1q23.3; top-ranked SNP, rs368433; P = 2.1 × 10(-8); odds ratio, 0.73 [95% CI, 0.65 to 0.81]) as associated with H. pylori seroprevalence. Among the 3 TLR genes at 4p14, only TLR1 was differentially expressed per copy number of the minor rs10004195-A allele (β = -0.23 [95% CI, -0.34 to -0.11]; P = 2.1 × 10(-4)). Individuals with high fecal H. pylori antigen titers (optical density >1) also exhibited the highest 25% of TLR1 expression levels (P = .01 by χ2 test). Furthermore, TLR1 exhibited an Asn248Ser substitution in the extracellular domain strongly linked to the rs10004195 SNP.\n GWAS meta-analysis identified an association between TLR1 and H. pylori seroprevalence, a finding that requires replication in nonwhite populations. If confirmed, genetic variations in TLR1 may help explain some of the observed variation in individual risk for H. pylori infection.\n\nSteinmetz, Ivo\n\n\n"
},
{
"text": "\n167185\nTherapeutic Targeting of Tumor-Associated Macrophages in Pancreatic Neuroendocrine Tumors.\n\nKrug, S\n\nAbbassi, R\n\nGriesmann, H\n\nSipos, B\n\nWiese, D\n\nRexin, P\n\nBlank, A\n\nPerren, A\n\nHaybaeck, J\n\nHüttelmaier, S\n\nRinke, A\n\nGress, TM\n\nMichl, P\n\nBeiträge in Fachzeitschriften\nISI:000443392100026\n29696624.0\n10.1002/ijc.31562\nNone\nPancreatic neuroendocrine tumors (PNETs) represent a heterogeneous group of neuroendocrine neoplasms with varying biological behaviour and response to treatment. Although targeted therapies have been shown to improve the survival for patients at advanced stage, resistance to current therapies frequently occurs during the course of therapy. Previous reports indicate that the infiltration of tumor-associated macrophages (TAMs) in PNETs might correlate with tumor progression and metastasis formation. We aimed to evaluate the prognostic and functional impact of TAMs in human PNETs in vitro and in vivo and to investigate the effect of therapeutic targeting TAMs in a genetic PNET mouse model. TAM expression pattern was assessed immunohistochemically in human PNET tissue sections and a tissue-micro-array of PNET tumors with different functionality, stage and grading. The effect of liposomal clodronate on TAM cell viability was analysed in myeloid cell lines and isolated murine bone macrophages (mBMM). In vivo, RIP1Tag2 mice developing insulinomas were treated with liposomal clodronate or PBS-Liposomes. Tumor progression, angiogenesis and immune cell infiltration were assessed by immunohistochemistry. In human insulinomas TAM density was correlated with invasiveness and malignant behaviour. Moreover, TAM infiltration in liver metastases was significantly increased compared to primary tumors. In vitro, liposomal clodronate selectively inhibited the viability of myeloid cells and murine bone macrophages, leaving PNET tumor cell lines largely unaffected. In vivo, repeated application of liposomal clodronate to RIP1Tag2 mice significantly diminished the malignant transformation of insulinomas, which was accompanied by a reduced infiltration of F4/80 positive TAM cells and simultaneously by a decreased microvessel density, suggesting a pronounced effect of clodronate-induced myeloid depletion on tumor angiogenesis. Concomitant treatment with the antiangiogenic TKI sunitinib, however, did not show any synergistic effects with liposomal clodronate. TAMs are crucial for malignant transformation in human PNET in particular in insulinomas and correlate with metastatic behaviour. Pharmacological targeting of TAMs via liposomal clodronate disrupts tumor progression in the RIP1Tag2 neuroendocrine tumor model and was associated with reduced tumor angiogenesis Based on these results, using liposomal clodronate to target proangiogenic myeloid cells could be employed as novel therapeutic avenue in highly angiogenic tumors such as PNET. This article is protected by copyright. All rights reserved.\n © 2018 UICC.\n\nHaybäck, Johannes\n\n\n"
},
{
"text": "\n171532\nThe relevance of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentration for postoperative infections and postoperative organ dysfunctions in cardiac surgery patients: The eVIDenCe study.\n\nNey, J\n\nHeyland, DK\n\nAmrein, K\n\nMarx, G\n\nGrottke, O\n\nChoudrakis, M\n\nAutschbach, T\n\nHill, A\n\nMeybohm, P\n\nBenstoem, C\n\nGoetzenich, A\n\nFitzner, C\n\nStoppe, C\n\nBeiträge in Fachzeitschriften\nISI:000501650600034\n30583965.0\n10.1016/j.clnu.2018.11.033\nNone\nRecent studies indicate that vitamin D deficiency is associated with increased morbidity and mortality in critically ill patients. Knowledge about the functional role and clinical relevance of vitamin D for patients undergoing cardiac surgery is sparse. Therefore, we investigated the clinical significance of vitamin D levels on outcome of cardiac surgery patients.\n 92 patients undergoing elective cardiac surgery with cardiopulmonary arrest were included in this prospective observational pilot study. 25-hydroxyvitamin D (25OHD) and 1, 5-dihydroxyvitamin D (1, 5(OH)2D) levels were measured prior to surgery, immediately postoperatively as well as 6, 12 and 24 h after surgery. We assessed postoperative organ dysfunctions, infections and death until hospital discharge.\n The serum concentration of 1, 5(OH)2D significantly decreased intraoperatively by 29.3% (p < 0.001) and was significantly lower at any postoperative time point compared to baseline values, whereas 25OHD levels did not show significant changes during the observation period. Coronary artery bypass graft (CABG) patients had significant higher baseline 1, 5(OH)2D values than patients with valve surgery (39.7 ± 13.9 ng/l vs. 30.1 ± 14.1 ng/l, p = 0.010) or CABG + valve surgery (39.7 ± 13.9 ng/l vs. 32.6 ± 11.8 ng/l, p = 0.044). Our data showed a significant odds ratio to develop postoperative organ dysfunction (OR 0.95; p = 0.009) and PCT levels ≥5 μg/l (OR 0.94; p = 0.046) for every ng/l increment in 1, 5(OH)2D, when performing multivariable analysis and after adjusting for preoperative illness and demographics. In addition, multivariable-adjusted statistical analyses revealed that patients stayed significantly shorter on ICU (-0.21 h; p = 0.001) and in hospital (-2.6 days; p = 0.009) for every ng/l increment in 1, 5(OH)2D.\n Our data highlight important evidence about the clinical significance of 1, 5(OH)2D levels in cardiac surgery patients. Higher levels were associated with significantly less postoperative organ dysfunctions, elevated PCT levels, death and prolonged hospital stay. 1, 5(OH)2D levels decreased significantly intra- and postoperatively, while serum levels of 25OHD did not.\n clinicaltrials.gov (NCT02488876), registered May 1, 2015.\n Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.\n\nAmrein, Karin\n\n\n"
},
{
"text": "\n179224\nSafety of Paclitaxel-Coated Balloon Angioplasty for Femoropopliteal Peripheral Artery Disease.\n\nOuriel, K\n\nAdelman, MA\n\nRosenfield, K\n\nScheinert, D\n\nBrodmann, M\n\nPeña, C\n\nGeraghty, P\n\nLee, A\n\nWhite, R\n\nClair, DG\n\nBeiträge in Fachzeitschriften\nISI:000502833000014\n31575518.0\n10.1016/j.jcin.2019.08.025\nNone\nThe aim of this study was to assess safety outcomes of femoropopliteal drug-coated balloon (DCB) angioplasty using patient-level data from the Lutonix clinical program.\n A recent systematic review and meta-analysis of heterogenous trials and summary-level data identified increased long-term mortality in patients treated with paclitaxel-coated balloons and stents.\n We evaluated DCB angioplasty (n = 1, 93) and uncoated balloon angioplasty (percutaneous transluminal angioplasty [PTA]) (n = 250) outcomes in LEVANT 1 (The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis), LEVANT 2 (Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries), and the LEVANT Japan Clinical Trial. Hazard ratios (HRs) were calculated with Cox proportional hazards modeling.\n There were no significant differences in mortality rates between DCB angioplasty and PTA. The 5-year HR was 1.01 (95% confidence interval [CI]: 0.68 to 1.52) in the aggregated LEVANT trials. The 2-year HR after DCB angioplasty was 0.99 (95% CI: 0.25 to 3.95) in LEVANT 1, 1.40 (95% CI: 0.62 to 3.14) in LEVANT 2, and 0.32 (95% CI: 0.05 to 1.92) in the LEVANT Japan Clinical Trial. The 5-year HR was 1.60 (95% CI: 0.94 to 2.72) in LEVANT 2. Adverse events and causes of death were balanced, without clustering between DCB angioplasty and PTA. Patients who underwent paclitaxel or nonpaclitaxel reinterventions had higher survival rates than those who did not undergo reinterventions. Baseline covariates predicting mortality included, among others, age (HR: 1.03 per year; p < 0.0001), prior treatment of target lesion (HR: 1.67; p = 0.022), arrhythmia (HR: 1.65; p = 0.031), and diabetes (HR: 1.18; p = 0.047), without differences between the 2 arms. No dose-response relationship was identified when adjusted for key predictors of mortality.\n Analyses of patient-level data identified no mortality differences between DCB angioplasty and PTA. Furthermore, the lack of dose-response relationships or clustering of causes of death argues against a causal relationship between paclitaxel and mortality. (LEVANT 1, The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis [LEVANT 1], NCT00930813; Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries [LEVANT 2], NCT01412541; LEVANT 2 Continued Access Registry, NCT01628159; LEVANT Japan Clinical Trial, NCT01816412).\n Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.\n\nBrodmann, Marianne\n\n\n"
},
{
"text": "\n183981\nLION-PAW (lymphadenectomy in ovarian neoplasm) sexual function assessment: a prospective sub-study of the LION trial.\n\nHasenburg, A\n\nSehouli, J\n\nLampe, B\n\nReuss, A\n\nSchmalfeld, B\n\nBelau, AK\n\nBossart, M\n\nMahner, S\n\nHillemanns, P\n\nPetry, U\n\ndu Bois, A\n\nHerwig, U\n\nHilpert, F\n\nGropp-Meier, M\n\nHanf, V\n\nGreimel, E\n\nWagner, U\n\nHarter, P\n\nBeiträge in Fachzeitschriften\nISI:000576755300013\n32938723.0\n10.1136/ijgc-2020-001551\nNone\nThere is limited information about the impact of radical surgery including pelvic and para-aortic lymphadenectomy and subsequent platinum-based chemotherapy on sexuality in patients with advanced ovarian cancer.\n To evaluate the impact of radical surgery including pelvic and para-aortic lymphadenectomy and subsequent platinum-based chemotherapy on sexuality in patients with advanced ovarian cancer as a sub-protocol of the prospectively randomized LION trial.\n The Sexual Activity Questionnaire was applied to assess sexual function according to its sub-scales activity, pleasure, and discomfort. The 'orgasm' sub-scale from the Female Sexual Function Index was also added. The questionnaire was administered in combination with the EORTC QLQ-C30 questionnaire at baseline prior surgery, after 6, 12, and 24 months. The primary endpoint was changes in sexual function.\n Overall, 495 patients received the questionnaires. 254 (51%) responded at baseline. Of these, 55 (22%) patients were sexually active, 182 (72%) were sexually inactive, and for 17 (7%) patients' data were not available. There was a total of 55/495 (11%) patients at 6 months, 139 (28%) patients at 12 months, and 81 (16%) patients at 24 months. Median age was 60.5 years (range 21.4-75.8). At baseline, sexually active responders were significantly younger (median age 51.5 years, than sexually inactive responders (median age 61.8 years) and tended to have a better performance status. Discomfort evaluated as dryness of the vagina and pain during sexual intercourse was significantly worse at 12 months than at baseline (p<0.001); however, the surgical variable, lymphadenectomy, did not have any impact on this. The orgasm sub-scale showed diverging results with a deterioration from baseline to 12 months in the lymphadenectomy group compared with the no-lymphadenectomy group (p=0.02).\n The majority of patients were sexually inactive; however, in those who were sexually active, pain during intercourse was worse at 12 months. In addition, the orgasm sub-scale demonstrated worse results in patients who underwent complete lymphadenectomy. The study suggests that surgery in the retroperitoneal space may influence sexual function.\n © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.\n\nGreimel, Elfriede Renate\n\n\n"
},
{
"text": "\n184920\nAllograft for Anterior Cruciate Ligament Reconstruction (ACLR): A Systematic Review and Meta-Analysis of Long-Term Comparative Effectiveness and Safety. Results of a Health Technology Assessment.\n\nGoetz, G\n\nde Villiers, C\n\nSadoghi, P\n\nGeiger-Gritsch, S\n\nBeiträge in Fachzeitschriften\nNone\n33376999.0\n10.1016/j.asmr.2020.07.003\nPMC7754611\nTo evaluate whether allograft anterior cruciate ligament reconstruction (ACLR) is superior or inferior to autograft ACLR or conservative management in terms of effectiveness and safety.\n A systematic review of the evidence for allograft ACLR was conducted. Randomized controlled trials with a minimum mean follow-up time of 5 years were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the EUnetHTA-Core-Model were used as reporting standards. A meta-analysis was conducted for selected crucial outcomes using a random-effects model. The strength of the available evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.\n Six randomized trials were included comparing allograft with autograft. Patients were on average between 28 and 32.8 years of age (allograft group) and 28.9 and 31.7 years of age (autograft group). Based on the crucial outcomes, the meta-analyses showed no statistically significant differences in Lysholm score, Tegner score, and Cincinnati Knee Score between groups. A small statistical difference favoring autografts was found across studies in the subjective International Knee Documentation Committee score (-2.25; 95% confidence interval -3.02 to -1.47; I2 = 0%; range of all scores: 73.7-90). Two of six studies reported on graft failure, with a statistically significant difference to the detriment of using allografts (13/49 [26.5%] vs 4/48 [8.3%] in one study, 13/43 [30.2%] vs 3/40 [7.5%] in the other study).\n Although no substantial difference in patient-reported function, activity level, and symptoms was demonstrated, evidence from the included studies showed a greater risk for graft failure or revision that may make allograft a less safe treatment modality in ACLR. The strength of available evidence is low based on the crucial outcomes due to the lack of high-quality research and the present increased risk of bias in primary studies. Priority should be shifted toward reflecting on whether there is a subpopulation for whom allograft ACLR may still be advantageous in theory (e.g., less-active older patients) and further conduct RCTs in this population.\n Level II, systematic review of Level II evidence studies.\n © 2020 by the Arthroscopy Association of North America. Published by Elsevier Inc.\n\nSadoghi, Patrick\n\n\n"
},
{
"text": "\n187239\nPredicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium.\n\nGillessen, S\n\nSauvé, N\n\nCollette, L\n\nDaugaard, G\n\nde Wit, R\n\nAlbany, C\n\nTryakin, A\n\nFizazi, K\n\nStahl, O\n\nGietema, JA\n\nDe Giorgi, U\n\nCafferty, FH\n\nHansen, AR\n\nTandstad, T\n\nHuddart, RA\n\nNecchi, A\n\nSweeney, CJ\n\nGarcia-Del-Muro, X\n\nHeng, DYC\n\nLorch, A\n\nChovanec, M\n\nWinquist, E\n\nGrimison, P\n\nFeldman, DR\n\nTerbuch, A\n\nHentrich, M\n\nBokemeyer, C\n\nNegaard, H\n\nFankhauser, C\n\nShamash, J\n\nVaughn, DJ\n\nSternberg, CN\n\nHeidenreich, A\n\nBeyer, J\n\nInternational Germ Cell Cancer Classification Update Consortium\n\nBeiträge in Fachzeitschriften\nISI:000655611500006\n33822655.0\n10.1200/JCO.20.03296\nNone\nThe classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990.\n Data on 9, 28 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3, 43 patients with complete information on potentially relevant variables. The results were validated in an independent data set.\n Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update).\n The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.\n\nTerbuch, Angelika\n\n\n"
},
{
"text": "\n119253\nGenotype-phenotype analysis in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency.\n\nKrone, N\n\nReisch, N\n\nIdkowiak, J\n\nDhir, V\n\nIvison, HE\n\nHughes, BA\n\nRose, IT\n\nO'Neil, DM\n\nVijzelaar, R\n\nSmith, MJ\n\nMacDonald, F\n\nCole, TR\n\nAdolphs, N\n\nBarton, JS\n\nBlair, EM\n\nBraddock, SR\n\nCollins, F\n\nCragun, DL\n\nDattani, MT\n\nDay, R\n\nDougan, S\n\nFeist, M\n\nGottschalk, ME\n\nGregory, JW\n\nHaim, M\n\nHarrison, R\n\nOlney, AH\n\nHauffa, BP\n\nHindmarsh, PC\n\nHopkin, RJ\n\nJira, PE\n\nKempers, M\n\nKerstens, MN\n\nKhalifa, MM\n\nKöhler, B\n\nMaiter, D\n\nNielsen, S\n\nO'Riordan, SM\n\nRoth, CL\n\nShane, KP\n\nSilink, M\n\nStikkelbroeck, NM\n\nSweeney, E\n\nSzarras-Czapnik, M\n\nWaterson, JR\n\nWilliamson, L\n\nHartmann, MF\n\nTaylor, NF\n\nWudy, SA\n\nMalunowicz, EM\n\nShackleton, CH\n\nArlt, W\n\nBeiträge in Fachzeitschriften\nISI:000301226800015\n22162478.0\n10.1210/jc.2011-0640\nPMC3380101\nCONTEXT: P450 oxidoreductase deficiency (PORD) is a unique congenital adrenal hyperplasia variant that manifests with glucocorticoid deficiency, disordered sex development (DSD), and skeletal malformations. No comprehensive data on genotype-phenotype correlations in Caucasian patients are available. OBJECTIVE: The objective of the study was to establish genotype-phenotype correlations in a large PORD cohort. DESIGN: The design of the study was the clinical, biochemical, and genetic assessment including multiplex ligation-dependent probe amplification (MLPA) in 30 PORD patients from 11 countries. RESULTS: We identified 23 P450 oxidoreductase (POR) mutations (14 novel) including an exonic deletion and a partial duplication detected by MLPA. Only 22% of unrelated patients carried homozygous POR mutations. p.A287P was the most common mutation (43% of unrelated alleles); no other hot spot was identified. Urinary steroid profiling showed characteristic PORD metabolomes with variable impairment of 17á-hydroxylase and 21-hydroxylase. Short cosyntropin testing revealed adrenal insufficiency in 89%. DSD was present in 15 of 18 46, X and seven of 12 46, Y individuals. Homozygosity for p.A287P was invariably associated with 46, X DSD but normal genitalia in 46, Y individuals. The majority of patients with mild to moderate skeletal malformations, assessed by a novel scoring system, were compound heterozygous for missense mutations, whereas nearly all patients with severe malformations carried a major loss-of-function defect on one of the affected alleles. CONCLUSIONS: We report clinical, biochemical, and genetic findings in a large PORD cohort and show that MLPA is a useful addition to POR mutation analysis. Homozygosity for the most frequent mutation in Caucasians, p.A287P, allows for prediction of genital phenotype and moderate malformations. Adrenal insufficiency is frequent, easily overlooked, but readily detected by cosyntropin testing.\n\n\n"
},
{
"text": "\n138098\nEvaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis.\n\nStickel, F\n\nBuch, S\n\nZoller, H\n\nHultcrantz, R\n\nGallati, S\n\nÖsterreicher, C\n\nFinkenstedt, A\n\nStadlmayr, A\n\nAigner, E\n\nSahinbegovic, E\n\nSarrazin, C\n\nSchafmayer, C\n\nBraun, F\n\nErhart, W\n\nNothnagel, M\n\nLerch, MM\n\nMayerle, J\n\nVölzke, H\n\nSchaller, A\n\nKratzer, W\n\nBoehm, BO\n\nSipos, B\n\nD'Amato, M\n\nTorkvist, L\n\nStal, P\n\nArlt, A\n\nFranke, A\n\nBecker, T\n\nKrawczak, M\n\nZwerina, J\n\nBerg, T\n\nHinrichsen, H\n\nKrones, E\n\nDejaco, C\n\nStrasser, M\n\nDatz, C\n\nHampe, J\n\nBeiträge in Fachzeitschriften\nISI:000338630300023\n24556216.0\n10.1093/hmg/ddu076\nNone\nGenome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10(-5)) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10(-5), ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation.\n © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.\n\nDejaco, Christian\n\nTatscher, Elisabeth\n\n\n"
},
{
"text": "\n166118\nClinical outcome, biochemical and therapeutic follow-up in 14 Austrian patients with Long-Chain 3-Hydroxy Acyl CoA Dehydrogenase Deficiency (LCHADD).\n\nKarall, D\n\nBrunner-Krainz, M\n\nKogelnig, K\n\nKonstantopoulou, V\n\nMaier, EM\n\nMöslinger, D\n\nPlecko, B\n\nSperl, W\n\nVolkmar, B\n\nScholl-Bürgi, S\n\nBeiträge in Fachzeitschriften\nISI:000369837900001\n25888220.0\n10.1186/s13023-015-0236-7\nPMC4407779\nLCHADD is a long-fatty acid oxidation disorder with immediate symptoms and long-term complications. We evaluated data on clinical status, biochemical parameters, therapeutic regimens and outcome of Austrian LCHADD patients.\n Clinical and outcome data including history, diagnosis, short- and long-term manifestations, growth, psychomotor development, hospitalizations, therapy of 14 Austrian patients with LCHADD were evaluated. Biochemically, we evaluated creatine kinase (CK) and acyl carnitine profiles.\n All LCHADD patients are homozygous for the common mutation. Three are siblings. Diagnosis was first established biochemically. Nine/14 (64%) were prematures, with IRDS occurring in six. In nine (64%), diagnosis was established through newborn screening, the remaining five (36%) were diagnosed clinically. Four pregnancies were complicated by HELLP syndrome, one by preeclampsia. In two, intrauterine growth retardation and placental insufficiency were reported. Five were diagnosed with hepatopathy at some point, seven with cardiomyopathy and eight with retinopathy, clinically relevant only in one patient. Polyneuropathy is only present in one. Three patients have a PEG, one is regularly fed via NG-tube. Growth is normal in all, as well as psychomotor development, except for two extremely premature girls. In 11 patients, 165 episodes with elevated creatine kinase concentrations were observed with 6-31 (median 14) per patient; three have shown no elevated CK concentrations. Median total carnitine on therapy was 19 μmol/l (range 11-61). For 14 patients, there have been 181 hospitalizations (median 9 per patient), comprising 1337 in-patient-days. All centres adhere to treatment with a fat-defined diet; patients have between 15% and 40% of their energy intake from fat (median 29%), out of which between 20% and 80% are medium-chain triglycerides (MCT) (median 62%). Four patients have been treated with heptanoate (C7).\n Our data show LCHADD outcome can be favourable. Growth and psychomotor development is normal, except in two prematures. Frequency of CK measurements decreases with age, correlating with a decreasing number of hospitalizations. About 50% develop complications affecting different organ systems. There is no relevant difference between the patients treated in the respective centers. Concluding from single case reports, anaplerotic therapy with heptanoate should be further evaluated.\n\nBrunner-Krainz, Michaela\n\nPlecko, Barbara\n\n\n"
},
{
"text": "\n167129\nClinical use of cold atmospheric pressure argon plasma in chronic leg ulcers: A pilot study.\n\nUlrich, C\n\nKluschke, F\n\nPatzelt, A\n\nVandersee, S\n\nCzaika, VA\n\nRichter, H\n\nBob, A\n\nHutten, Jv\n\nPainsi, C\n\nHüge, R\n\nKramer, A\n\nAssadian, O\n\nLademann, J\n\nLange-Asschenfeldt, B\n\nBeiträge in Fachzeitschriften\nISI:000355762400002\n25970756.0\n10.12968/jowc.2015.24.5.196\nNone\nIn the age of multiresistant microbes and the increasing lack of efficient antibiotics, conventional antiseptics play a critical role in the prevention and therapy of wound infections. Recent studies have demonstrated the antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot, study we investigate the overall suitability of one of the first APP sources for wound treatment focusing on its potential antimicrobial effects.\n The wound closure rate and the bacterial colonisation of the wounds were investigated. Patients suffering from chronic leg ulcers were treated in a clinical controlled monocentric trial with either APP or octenidine (OCT). In patients who presented with more than one ulceration in different locations, one was treated with APP and the other one with OCT. Each group was treated three times a week over a period of two weeks. The antimicrobial efficacy was evaluated immediately after and following two weeks of treatment.\n Wounds treated with OCT showed a significantly higher microbial reduction (64%) compared to wounds treated with APP (47%) immediately after the treatment. Over two weeks of antiseptic treatment the bacterial density was reduced within the OCT group (-35%) compared to a slight increase in bacterial density in the APP-treated group (+12%). Clinically, there were no signs of delayed wound healing observed in either group and both treatments were well tolerated.\n The immediate antimicrobial effects of the APP prototype source were almost comparable to OCT without any signs of cytotoxicity. This pilot study is limited by current configurations of the plasma source, where the narrow plasma beam made it difficult to cover larger wound surface areas and in order to avoid untreated areas of the wound bed, smaller wounds were assigned to the APP-treatment group. This limits the significance of AAP-related effects on the wound healing dynamics, as smaller wounds tend to heal faster than larger wounds. However, clinical wound healing studies on a larger scale now seem justifiable. A more advanced plasma source prototype allowing the treatment of larger wounds will address APP's influence on healing dynamics, synergetic treatment with current antiseptics and effects on multiresistant bacteria.\n\nPainsi, Clemens\n\n\n"
},
{
"text": "\n180018\nIn vivo investigation of the tissue response to commercial Teflon insulin infusion sets in large swine for 14 days: the effect of angle of insertion on tissue histology and insulin spread within the subcutaneous tissue.\n\nEisler, G\n\nKastner, JR\n\nTorjman, MC\n\nKhalf, A\n\nDiaz, D\n\nDinesen, AR\n\nLoeum, C\n\nThakur, ML\n\nStrasma, P\n\nJoseph, JI\n\nBeiträge in Fachzeitschriften\nISI:000506187100074\n31875136.0\n10.1136/bmjdrc-2019-000881\nPMC6904176\nThis study investigated the effects of the inflammatory tissue response (ITR) to an insulin infusion set (IIS) on insulin bolus spread over wear time, as well as the effect of cannula insertion angle on the ITR, bolus shape, and pump tubing pressure.\n Angled or straight IISs were inserted every other day for 14 days into the subcutaneous tissue of 11 swine and insulin was delivered continuously. Prior to euthanasia, a 70 µL bolus of insulin/X-ray contrast agent was infused while recording a pressure profile (peak tubing pressure, pmax; area under the pressure curve, AUC), followed by the excision of the tissue-catheter specimen. Bolus surface area (SA) and volume (V) were assessed via micro-CT. Tissue was stained to analyze total area of inflammation (TAI) and inflammatory layer thickness (ILT) surrounding the cannula.\n A bolus delivered through an angled IIS had a larger mean SA than a bolus delivered through a straight cannula (314.0±84.2 mm2 vs 229.0±99.7 mm2, p<0.001) and a larger volume (198.7±66.9 mm3 vs 145.0±65.9 mm3, p=0.001). Both decreased significantly over wear time, independent of angle. There was a significant difference in TAI (angled, 9.1±4.0 mm2 vs straight, 14.3±8.6 mm2, p<0.001) and ILT (angled, 0.7±0.4 vs straight, 1.2±0.7 mm, p<0.001). pmax (p=0.005) and AUC (p=0.014) were lower using angled IIS. As ILT increased, pmax increased, while SA and V decreased.\n The progression of the ITR directly affected bolus shape and tubing pressure. Although straight insertion is clinically preferred, our data suggest that an angled IIS elicits lower grades of ITR and delivers a bolus with lower tubing pressure and greater SA and V. The subcutaneous environment plays a crucial role in IIS longevity, and the insertion angle needs to be considered in future IIS designs and clinical trials.\n © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\n\n"
},
{
"text": "\n184205\nGenome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.\n\nKarlsson Linnér, R\n\nBiroli, P\n\nKong, E\n\nMeddens, SFW\n\nWedow, R\n\nFontana, MA\n\nLebreton, M\n\nTino, SP\n\nAbdellaoui, A\n\nHammerschlag, AR\n\nNivard, MG\n\nOkbay, A\n\nRietveld, CA\n\nTimshel, PN\n\nTrzaskowski, M\n\nVlaming, R\n\nZünd, CL\n\nBao, Y\n\nBuzdugan, L\n\nCaplin, AH\n\nChen, CY\n\nEibich, P\n\nFontanillas, P\n\nGonzalez, JR\n\nJoshi, PK\n\nKarhunen, V\n\nKleinman, A\n\nLevin, RZ\n\nLill, CM\n\nMeddens, GA\n\nMuntané, G\n\nSanchez-Roige, S\n\nRooij, FJV\n\nTaskesen, E\n\nWu, Y\n\nZhang, F\n\n23and Me Research Team\n\neQTLgen Consortium\n\nInternational Cannabis Consortium\n\nSocial Science Genetic Association Consortium\n\nAuton, A\n\nBoardman, JD\n\nClark, DW\n\nConlin, A\n\nDolan, CC\n\nFischbacher, U\n\nGroenen, PJF\n\nHarris, KM\n\nHasler, G\n\nHofman, A\n\nIkram, MA\n\nJain, S\n\nKarlsson, R\n\nKessler, RC\n\nKooyman, M\n\nMacKillop, J\n\nMännikkö, M\n\nMorcillo-Suarez, C\n\nMcQueen, MB\n\nSchmidt, KM\n\nSmart, MC\n\nSutter, M\n\nThurik, AR\n\nUitterlinden, AG\n\nWhite, J\n\nWit, H\n\nYang, J\n\nBertram, L\n\nBoomsma, DI\n\nEsko, T\n\nFehr, E\n\nHinds, DA\n\nJohannesson, M\n\nKumari, M\n\nLaibson, D\n\nMagnusson, PKE\n\nMeyer, MN\n\nNavarro, A\n\nPalmer, AA\n\nPers, TH\n\nPosthuma, D\n\nSchunk, D\n\nStein, MB\n\nSvento, R\n\nTiemeier, H\n\nTimmers, PRHJ\n\nTurley, P\n\nUrsano, RJ\n\nWagner, GG\n\nWilson, JF\n\nGratten, J\n\nLee, JJ\n\nCesarini, D\n\nBenjamin, DJ\n\nKoellinger, PD\n\nBeauchamp, JP\n\nBeiträge in Fachzeitschriften\nISI:000457314300011\n30643258.0\n10.1038/s41588-018-0309-3\nPMC6713272\nHumans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.\n\nHofer, Edith\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
}
]
}