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"text": "\n173694\nThe role of tissue remodeling in mechanics and pathogenesis of abdominal aortic aneurysms.\n\nNiestrawska, JA\n\nRegitnig, P\n\nViertler, C\n\nCohnert, TU\n\nBabu, AR\n\nHolzapfel, GA\n\nBeiträge in Fachzeitschriften\nISI:000463688900013\n30735809.0\n10.1016/j.actbio.2019.01.070\nNone\nArterial walls can be regarded as composite materials consisting of collagen fibers embedded in an elastic matrix and smooth muscle cells. Remodeling of the structural proteins has been shown to play a significant role in the mechanical behavior of walls during pathogenesis of abdominal aortic aneurysms (AAA). In this study, we systematically studied the change in the microstructure, histology and mechanics to link them to AAA disease progression. We performed biaxial extension tests, second-harmonic generation imaging and histology on 15 samples from the anterior part of AAA walls harvested during open aneurysm surgery. Structural data were gained by fitting to a bivariate von Mises distribution and yielded the mean fiber direction and in- and out-of-plane fiber dispersions of collagen. Mechanical and structural data were fitted to a recently proposed material model. Additionally, the mechanical data were used to derive collagen recruitment points in the obtained stress-stretch curves. We derived 14 parameters from histology such as smooth muscle cell-, elastin-, and abluminal adipocyte content. In total, 22 parameters were obtained and statistically evaluated. Based on the collagen recruitment points we were able to define three different stages of disease progression. Significant differences in elastin content, collagen orientation and adipocyte contents were discovered. Nerves entrapped inside AAA walls pointed towards a significant deposition of newly formed collagen abluminally, which we propose as neo-adventitia formation. We were able to discriminate two types of remodeled walls with a high collagen content - potentially safe and possibly vulnerable walls with a high adipocyte content inside the wall and significant amounts of inflammation. The study yielded a hypothesis for disease progression, derived from the systematic comparison of mechanical, microstructural and histological changes in AAAs. STATEMENT OF SIGNIFICANCE: Remodeling of the structural proteins plays an important role in the mechanical behavior of walls during pathogenesis of abdominal aortic aneurysms (AAA). We analyzed changes in the microstructure, histology and biomechanics of 15 samples from the anterior part of AAA walls and, for the first time, linked the results to three different stages of disease progression. We identified significant differences in elastin content, collagen orientation, adipocyte contents, and also a deposition of newly formed collagen forming a neoadventitia. We could discriminate two types of remodeled walls: (i) potentially safe and (ii) possibly vulnerable associated with inflammation and a high amount of adipocytes.\n Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.\n\nCohnert, Tina Ulrike\n\nNiestrawska, Justyna Anna\n\nRegitnig, Peter\n\nViertler, Christian\n\n\n"
},
{
"text": "\n182853\nCryoconite Hole Location in East-Antarctic Untersee Oasis Shapes Physical and Biological Diversity.\n\nWeisleitner, K\n\nPerras, AK\n\nUnterberger, SH\n\nMoissl-Eichinger, C\n\nAndersen, DT\n\nSattler, B\n\nBeiträge in Fachzeitschriften\nISI:000543830100001\n32582104.0\n10.3389/fmicb.2020.01165\nPMC7284004\nAntarctic cryoconite holes (CHs) are mostly perennially ice-lidded and sediment-filled depressions that constitute important features on glaciers and ice sheets. Once being hydrologically connected, these microbially dominated mini-ecosystems provide nutrients and biota for downstream environments. For example, the East Antarctic Anuchin Glacier gradually melts into the adjacent perennially ice-covered Lake Untersee, and CH biota from this glacier contribute up to one third of the community composition in benthic microbial mats within the lake. However, biogeochemical features of these CHs and associated spatial patterns across the glacier are still unknown. Here we hypothesized about the CH minerogenic composition between the different sources such as the medial moraine and other zones. Further, we intended to investigate if the depth of the CH mirrors the CH community composition, organic matter (OM) content and would support productivity. In this study we show that both microbial communities and biogeochemical parameters in CHs were significantly different between the zones medial moraine and the glacier terminus. Variations in microbial community composition are the result of factors such as depth, diameter, organic matter, total carbon, particle size, and mineral diversity. More than 90% of all ribosomal sequence variants (RSV) reads were classified as Proteobacteria, Cyanobacteria, Bacteroidetes, Actinobacteria, and Acidobacteria. Archaea were detected in 85% of all samples and exclusively belonged to the classes Halobacteria, Methanomicrobia, and Thermoplasmata. The most abundant genus was Halorubrum (Halobacteria) and was identified in nine RSVs. The core microbiome for bacteria comprised 30 RSVs that were affiliated with Cyanobacteria, Bacteroidetes, Actinobacteria, and Proteobacteria. The archaeal fraction of the core microbiome consisted of three RSVs belonging to unknown genera of Methanomicrobiales and Thermoplasmatales and the genus Rice_Cluster_I (Methanocellales). Further, mean bacterial carbon production in cryoconite was exceptionally low and similar rates have not been reported elsewhere. However, bacterial carbon production insignificantly trended toward higher rates in shallow CHs and did not seem to be supported by accumulation of OM and nutrients, respectively, in deeper holes. OM fractions were significantly different between shallower CHs along the medial moraine and deeper CHs at the glacier terminus. Overall, our findings suggest that wind-blown material originating south and southeast of the Anuchin Glacier and deposits from a nunatak are assumed to be local inoculation sources. High sequence similarities between samples from the Untersee Oasis and other Antarctic sites further indicate long-range atmospheric transport mechanisms that complement local inoculation sources.\n Copyright © 2020 Weisleitner, Perras, Unterberger, Moissl-Eichinger, Andersen and Sattler.\n\nMoissl-Eichinger, Christine\n\n\n"
},
{
"text": "\n2527\nThe effect of positive end-expiratory pressure during partial liquid ventilation in acute lung injury in piglets.\n\nZobel, G\n\nRödl, S\n\nUrlesberger, B\n\nDacar, D\n\nTrafojer, U\n\nTrantina, A\n\nBeiträge in Fachzeitschriften\nISI:000082736300036\n10507621.0\n10.1097%2F00003246-199909000-00036\nNone\nOBJECTIVES: To investigate the effects of positive end-expiratory pressure (PEEP) application during partial liquid ventilation (PLV) on gas exchange, lung mechanics, and hemodynamics in acute lung injury. DESIGN: Prospective, randomized, experimental study. SETTING: University research laboratory. SUBJECTS: Six piglets weighing 7 to 12 kg. INTERVENTIONS: After induction of anesthesia, tracheostomy, and controlled mechanical ventilation, animals were instrumented with two central venous catheters, a pulmonary artery catheter and two arterial catheters, and an ultrasonic flow probe around the pulmonary artery. Acute lung injury was induced by the infusion of oleic acid (0.08 mL/kg) and repeated lung lavage procedures with 0.9% sodium chloride (20 mL/kg). The protocol consisted of four different PEEP levels (0, 5, 10, and 15 cm H2O) randomly applied during PLV. The oxygenated and warmed perfluorocarbon liquid (30 mL/kg) was instilled into the trachea over 5 mins without changing the ventilator settings. MEASUREMENTS AND MAIN RESULTS: Airway pressures, tidal volumes, dynamic and static pulmonary compliance, mean and expiratory airway resistances, and arterial blood gases were measured. In addition, dynamic pressure/volume loops were recorded. Hemodynamic monitoring included right atrial, mean pulmonary artery, pulmonary capillary wedge, and mean systemic arterial pressures and continuous flow recording at the pulmonary artery. The infusion of oleic acid combined with two to five lung lavage procedures induced a significant reduction in PaO2/FI(O2) from 485 +/- 28 torr (64 +/- 3.6 kPa) to 68 +/- 3.2 torr (9.0 +/- 0.4 kPa) (p < .01) and in static pulmonary compliance from 1.3 +/- 0.06 to 0.67 +/- 0.04 mL/cm H2O/kg (p < .01). During PLV, PaO2/FI(O2) increased significantly from 68 +/- 3.2 torr (8.9 +/- 0.4 kPa) to >200 torr (>26 kPa) (p < .01). The highest PaO2 values were observed during PLV with PEEP of 15 cm H2O. Deadspace ventilation was lower during PLV when PEEP levels of 10 to 15 cm H2O were applied. There were no differences in hemodynamic data during PLV with PEEP levels up to 10 cm H2O. However, PEEP levels of 15 cm H2O resulted in a significant decrease in cardiac output. Dynamic pressure/volume loops showed early inspiratory pressure spikes during PLV with PEEP levels of 0 and 5 cm H2O. CONCLUSIONS: Partial liquid ventilation is a useful technique to improve oxygenation in severe acute lung injury. The application of PEEP during PLV further improves oxygenation and lung mechanics. PEEP levels of 10 cm H2O seem to be optimal to improve oxygenation and lung mechanics.\n\nRoedl, Siegfried\n\nUrlesberger, Berndt\n\nYates, Ameli\n\n\n"
},
{
"text": "\n155774\nTreatment of Children and Adolescents With Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters.\n\nvon Bueren, AO\n\nKortmann, RD\n\nvon Hoff, K\n\nFriedrich, C\n\nMynarek, M\n\nMüller, K\n\nGoschzik, T\n\nZur Mühlen, A\n\nGerber, N\n\nWarmuth-Metz, M\n\nSoerensen, N\n\nDeinlein, F\n\nBenesch, M\n\nZwiener, I\n\nKwiecien, R\n\nFaldum, A\n\nBode, U\n\nFleischhack, G\n\nHovestadt, V\n\nKool, M\n\nJones, D\n\nNorthcott, P\n\nKuehl, J\n\nPfister, S\n\nPietsch, T\n\nRutkowski, S\n\nBeiträge in Fachzeitschriften\nISI:000388929900015\n27863192.0\n10.1200/JCO.2016.67.2428\nNone\nPurpose To assess an intensified treatment in the context of clinical and biologic risk factors in metastatic medulloblastoma. Patients and Methods Patients (4 to 21 years old, diagnosed between 2001 and 2007) received induction chemotherapy, dose-escalated hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy. Subgroup status and other biologic parameters were assessed. Results In 123 eligible patients (median age, 8.2 years old; median follow-up, 5.38 years), 5-year event-free survival (EFS) and overall survival (OS) were 62% (95% CI, 52 to 72) and 74% (95% CI, 66 to 82), respectively. OS was superior compared with the precedent HIT '91 trial. The 5-year EFS and OS were both 89% (95% CI, 67 to 100) for desmoplastic/nodular (n = 11), 61% (95% CI, 51 to 71) and 75% (95% CI, 65 to 85) for classic (n = 107), and 20% (95% CI, 0 to 55) and 40% (95% CI, 0 to 83) for large-cell/anaplastic (n = 5) medulloblastoma ( P < .001 for EFS; P = .001 for OS). Histology (hazard ratio, 0.19 for desmoplastic/nodular and 45.97 for large-cell/anaplastic medulloblastoma) and nonresponse to the first chemotherapy cycle (hazard ratio, 1.97) were independent risk factors (EFS). Among 81 (66%) patients with tumor material, 5-year EFS and OS differed between low-risk (wingless [WNT], n = 4; both 100%), high-risk ( MYCC/ MYCN amplification; n = 5, both 20%), and intermediate-risk patients (neither; n = 72, 63% and 73%, respectively). Survival rates were different between molecular subgroups (WNT, n = 4; sonic hedgehog [SHH; n = 4]; group 4 [n = 41]; group 3 with [n = 3] or without [n = 17] MYCC/MYCN amplification; P < .001). All cases showed p53 immuno-negativity. There was no association between patients with nonresponding tumors to induction chemotherapy and WNT ( P = .143) or MYCC/MYCN status ( P = .075), histologic subtype ( P = .814), or molecular subtype ( P = .383), as assessed by Fisher's exact test. Conclusion This regimen was feasible and conferred overall favorable survival. Our data confirm the relevance of subgroup status and biologic parameters (WNT/ MYCC/ MYCN status) in a homogeneous prospective trial population, and show that metastatic group 3 patients do not uniformly have poor outcomes. Biologic subgroup, MYCC/ MYCN status, response to induction chemotherapy, and histologic subtype may serve for improved treatment stratification.\n\nBenesch, Martin\n\n\n"
},
{
"text": "\n160336\nModification of low-density lipoprotein during radiolabeling with 99mTc using three labeling methods.\n\nSobal, G\n\nResch, U\n\nTatzber, F\n\nSinzinger, H\n\nBeiträge in Fachzeitschriften\nISI:000243827200010\n17043631.0\nNone\nNone\nThe mechanisms of native low-density lipoprotein (LDL) uptake by monocytes and macrophages via the specific cholesterol down-regulated LDL-receptor differs form the mechanism responsible for the unregulated scavenging of the modified, for example, oxidized LDL, by the atherosclerotic plaques and foam cells. For this reason, we investigated if the 99mTc-labeled LDL stands for the native or modified molecule. The influence of the LDL sampling methods, isolation, preparation and radiolabeling of lipoproteins on structure modification and the subsequent imaging behavior has as yet not been addressed in detail.\n Herein we present data on the effects of 99mTc labeling on some oxidation relevant parameters of LDL, such as the lag-time, thiobarbituric acid reactive substances (TBARS), relative electrophoretic mobility (REM), baseline dienes (BD), lipid peroxides (POX), free amino-groups (NH2-groups) and free sulphydryl-groups (SH-groups). Three methods of 99mTc labeling were compared: dithionite method (1), borohydride method (2) and ascorbic acid method (3). Data for oxidation parameters are expressed as a percent of freshly isolated native LDL (% native LDL) or as a percent of LDL treated with the labeling buffers and reagents, but in absence of the radioisotope (% control LDL).\n The levels of BD were most influenced by methods 2 and 3, and remained almost unchanged when the method 1 was used. The lag-time of 99mTc-LDL produced by method 2 doubled but it was decreased by 23% when the method 3 was employed. No change in the lag-time compared to the native LDL was observed with the method 1. The TBARS levels were 3-5 fold higher than in native LDL when methods 1 and 2 were used, but 33% lower in products made by the method 3. The number of thiol groups increased 3 fold in method 1, was only slightly elevated in method 3, but reduced in method 2 compared to native LDL. NH2-groups were increased with all three labeling procedures, but this increase was not considered significant. REM was altered only in products obtained by methods 1 (1.5x increase) and by method 2 (1.25x increase). No fragmentation of Apo B using sodium dodecyl sulfate polyacrylamide gel (SDS-PAGE) electrophoresis was observed by 99mTc-LDL produced in any of the\n The increase of lipid peroxide generation was observed only when the method 2 was used.\n Of the three tested methods, we found all of them to render LDL oxidatively modified to some extent. Therefore, it appears that the native-LDL imaging with 99mTc-labeled LDL is impossible. Only the ascorbic acid method 3 appears to offer some protection and exerts antioxidant effects.\n\nTatzber, Franz\n\n\n"
},
{
"text": "\n165195\nInternational validation of the European Organisation for Research and Treatment of Cancer QLQ-BRECON23 quality-of-life questionnaire for women undergoing breast reconstruction.\n\nWinters, ZE\n\nAfzal, M\n\nRutherford, C\n\nHolzner, B\n\nRumpold, G\n\nda Costa Vieira, RA\n\nHartup, S\n\nFlitcroft, K\n\nBjelic-Radisic, V\n\nOberguggenberger, A\n\nPanouilleres, M\n\nMani, M\n\nCatanuto, G\n\nDouek, M\n\nKokan, J\n\nSinai, P\n\nKing, MT\n\nEuropean Organisation for Research and Treatment of Cancer Quality of Life Group\n\nBeiträge in Fachzeitschriften\nISI:000424159800007\n29116657.0\n10.1002/bjs.10656\nNone\nThe aim was to carry out phase 4 international field-testing of the European Organisation for Research and Treatment of Cancer (EORTC) breast reconstruction (BRECON) module. The primary objective was finalization of its scale structure. Secondary objectives were evaluation of its reliability, validity, responsiveness, acceptability and interpretability in patients with breast cancer undergoing mastectomy and reconstruction.\n The EORTC module development guidelines were followed. Patients were recruited from 28 centres in seven countries. A prospective cohort completed the QLQ-BRECON15 before mastectomy and the QLQ-BRECON24 at 4-8 months after reconstruction. The cross-sectional cohort completed the QLQ-BRECON24 at 1-5 years after reconstruction, and repeated this 2-8 weeks later (test-retest reliability). All participants completed debriefing questionnaires.\n A total of 438 patients were recruited, 234 in the prospective cohort and 204 in the cross-sectional cohort. A total of 414 reconstructions were immediate, with a comparable number of implants (176) and donor-site flaps (166). Control groups comprised patients who underwent two-stage implant procedures (72, 75 per cent) or delayed reconstruction (24, 25 per cent). Psychometric scale validity was supported by moderate to high item-own scale and item-total correlations (over 0·5). Questionnaire validity was confirmed by good scale-to-sample targeting, and computable scale scores exceeding 50 per cent, except nipple cosmesis (over 40 per cent). In known-group comparisons, QLQ-BRECON24 scales and items differentiated between patient groups defined by clinical criteria, such as type and timing of reconstruction, postmastectomy radiotherapy and surgical complications, with moderate effect sizes. Prospectively, sexuality and surgical side-effects scales showed significant responsiveness over time (P < 0·001). Scale reliability was supported by high Cronbach's α coefficients (over 0·7) and test-retest (intraclass correlation more than 0·8). One item (finding a well fitting bra) was excluded based on high floor/ceiling effects, poor test-retest and weak correlations in factor analysis (below 0·3), thus generating the QLQ-BRECON23 questionnaire.\n The QLQ-BRECON23 is an internationally validated tool to be used alongside the EORTC QLQ-C30 (cancer) and QLQ-BR23 (breast cancer) questionnaires for evaluating quality of life and satisfaction after breast reconstruction.\n © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.\n\nBjelic-Radisic, Vesna\n\n\n"
},
{
"text": "\n3145\nItraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B.\n\nHarousseau, JL\n\nDekker, AW\n\nStamatoullas-Bastard, A\n\nFassas, A\n\nLinkesch, W\n\nGouveia, J\n\nDe Bock, R\n\nRovira, M\n\nSeifert, WF\n\nJoosen, H\n\nPeeters, M\n\nDe Beule, K\n\nBeiträge in Fachzeitschriften\nISI:000087961400021\n10858349.0\n10.1128%2FAAC.44.7.1887-1893.2000\nPMC89980\nSystemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.\n\n\n"
},
{
"text": "\n113278\nQuality of postoperative pain therapy in Austria: national survey of all departments of anesthesiology.\n\nKinstner, C\n\nLikar, R\n\nSandner-Kiesling, A\n\nHutschala, D\n\nPipam, W\n\nGustorff, B\n\nBeiträge in Fachzeitschriften\nISI:000295085900005\n21915703.0\n10.1007/s00101-011-1911-2\nNone\nBACKGROUND: Despite increasingly sophisticated concepts of perioperative pain therapy, such as increased use of combined regional anesthesia techniques, the renaissance of ketamine and dipyrone or the use of oral opioids, no significant improvement has been achieved in postoperative pain therapy since 1995. About 300, 00 of the approximately 700, 00 patients undergoing major surgery each year in Austria experience moderate to severe postoperative pain. The aim of this study was therefore to assess the nationwide status of perioperative acute pain management in postoperative recovery rooms and surgical wards in order to identify potential areas for improvement. METHODS: In 2006 the directors of all Austrian anesthesiology departments (n=125, 100%) were contacted and asked to give detailed information on the status of acute pain management of each individual hospital in Austria using a standardized questionnaire. Data of each individual department were derived from quality control and self-assessment of each department. No patients were questioned. The return rate was 96% (n=120) due to intensive personal contact in cases of missing data. RESULTS: In this nationwide survey 120 anesthesiology departments participated together accounting for a total of 757, 95 operations per year. Of the patients 63.6% were informed preoperatively on the available regimens of acute pain management. In 81% of patients perioperative pain therapy consisted of a multimodal therapeutic approach, 58.6% of the departments used international guidelines and 39.7% worked with international guidelines adapted to local requirements. In 88% of patients a detailed prescription for postoperative pain therapy was available when transferred to the surgical ward. Surgical wards were equipped with routine pain therapy protocols in 28% another 20% of wards had special pain therapy protocols for individual operations. In 22% of cases pain assessment was repeated 3-4 times per day and in 33.9% postoperative pain was assessed only once twice per day. Pain assessments were recorded in the patient charts in 60.7% of cases. If changes to the pain therapy regimen were required anesthesiologists were involved in only 14.3% of cases. In addition an acute pain service was available only in 39.2% of Austrian anesthesiology departments. CONCLUSIONS: Although the multimodal approach to acute pain therapy is widely used and standardized therapeutic regimens are well established in the majority of anesthesiology and surgical wards, there still remains room for improvement. Pain assessment is generally barely adequate and written documentation of pain assessment is missing almost completely. In addition, almost two thirds of hospitals in Austria are still lacking an acute pain service.\n\nSandner-Kiesling, Andreas\n\n\n"
},
{
"text": "\n152121\nContinuous free-flap monitoring with tissue-oxygen measurements: experiences of the last years].\n\nKamolz, LP\n\nSchrögendorfer, KF\n\nGiovanoli, P\n\nKoller, R\n\nFrey, M\n\nBeiträge in Fachzeitschriften\nNone\n12203156.0\n10.1055/s-2002-33695\nNone\nEarly recognition of flap failure is the prerequisite for flap salvage. Many methods are used to monitor free-flaps. The time interval for re-establishing vascular patency is the deciding factor for a successful revision. Prompt revision surgery and a quick and sufficient correction of the microvascular anastomosis are necessary to reestablish flap viability. The aim of this study was to evaluate the real impact of this probe as a continuous, precise and clinically relevant monitoring system in free-flap surgery. One of our main objectives was to create guidelines and "normal" ranges of p ti O 2 -values for the uncomplicated use of the Licox Probe in free-flap surgery for the first time. The Licox Catheter pO 2 Mikro-Probe instrument is used for continuous determination of oxygen partial pressure (pO 2 ) in body fluids and tissue (p ti O 2 ). Over a period of more than three years, 70 free tissue-transplantations to the head and neck, trunk, and upper and lower extremities were monitored by use of the implantable Licox Catheter Probe System. In all patients, a decrease of the p ti O 2 -levels was noted during the first minutes, until a more or less stable level was reached. At the time of weaning off, the p ti O 2 values decreased once again. After approximately 30 minutes, an almost stable but reduced p ti O 2 -level was reestablished (34, +/- 10, mm Hg). During the next days, we observed a more or less constant but reduced level. These values from the second day on were lower than the mean values of the first day. The mean value for all flaps was 23, +/- 6, mm Hg. Nevertheless, in all cases (10 of 70 flaps) where the p ti O 2 -level decreased more than 10 mm Hg within a half hour period, the flap showed vascular problems on re-exploration. Another clinically relevant value that was observed in all flaps with vascular problems was a drop of the p ti O 2 -value, below 10 mm Hg. In the cases of arterial thrombosis (2 of 10 flaps), a rapid decrease was noted. In the cases of venous complications (8 of 10 flaps), a more or less slow decrease of the p ti O 2 -value was observed. These observations may serve as precise indicators for vascular complications and flap failure. Based on our observations and data, it seems that the Licox-Probe is a sensitive and accurate monitoring system for a variety of free flaps.\n\nKamolz, Lars-Peter\n\n\n"
},
{
"text": "\n161556\nMonitoring and evaluation of disaster response efforts undertaken by local health departments: a rapid realist review.\n\nGossip, K\n\nGouda, H\n\nLee, YY\n\nFirth, S\n\nBermejo, R\n\nZeck, W\n\nJimenez Soto, E\n\nBeiträge in Fachzeitschriften\nISI:000405237100002\n28662654.0\n10.1186/s12913-017-2396-8\nPMC5492906\nLocal health departments are often at the forefront of a disaster response, attending to the immediate trauma inflicted by the disaster and also the long term health consequences. As the frequency and severity of disasters are projected to rise, monitoring and evaluation (M&E) efforts are critical to help local health departments consolidate past experiences and improve future response efforts. Local health departments often conduct M&E work post disaster, however, many of these efforts fail to improve response procedures.\n We undertook a rapid realist review (RRR) to examine why M&E efforts undertaken by local health departments do not always result in improved disaster response efforts. We aimed to complement existing frameworks by focusing on the most basic and pragmatic steps of a M&E cycle targeted towards continuous system improvements. For these purposes, we developed a theoretical framework that draws on the quality improvement literature to 'frame' the steps in the M&E cycle. This framework encompassed a M&E cycle involving three stages (i.e., document and assess, disseminate and implement) that must be sequentially completed to learn from past experiences and improve future disaster response efforts. We used this framework to guide our examination of the literature and to identify any context-mechanism-outcome (CMO) configurations which describe how M&E may be constrained or enabled at each stage of the M&E cycle.\n This RRR found a number of explanatory CMO configurations that provide valuable insights into some of the considerations that should be made when using M&E to improve future disaster response efforts. Firstly, to support the accurate documentation and assessment of a disaster response, local health departments should consider how they can: establish a culture of learning within health departments; use embedded training methods; or facilitate external partnerships. Secondly, to enhance the widespread dissemination of lessons learned and facilitate inter-agency learning, evaluation reports should use standardised formats and terminology. Lastly, to increase commitment to improvement processes, local health department leaders should possess positive leadership attributes and encourage shared decision making.\n This study is among the first to conduct a synthesis of the CMO configurations which facilitate or hinder M&E efforts aimed at improving future disaster responses. It makes a significant contribution to the disaster literature and provides an evidence base that can be used to provide pragmatic guidance for improving M&E efforts of local health departments.\n PROSPERO 2015: CRD42015023526 .\n\n\n"
},
{
"text": "\n179756\nFirst case studies of successful ABO-incompatible living-related liver transplantation in infants in Germany.\n\nSchukfeh, N\n\nLenz, V\n\nMetzelder, ML\n\nPaul, A\n\nMathe, Z\n\nKathemann, S\n\nHoyer, PF\n\nDohna-Schwake, C\n\nGerner, P\n\nBeiträge in Fachzeitschriften\nISI:000348524500017\n25555094.0\n10.1055/s-0034-1387936\nNone\nA series study mainly from Asia suggests that ABO-incompatible (ABOi) living-related liver transplantation (LRLT) for pediatric recipients is associated with excellent short- and long-term graft and patient survival. Until now, ABOi LRLT has been rarely performed in Europe. The aim of this study was to analyze the safety and early results of an ABOi LRLT in a German high-volume pediatric liver transplant center.\n Six consecutive pediatric patients (four males and two females) were included in this prospective study from January, 2010 to January, 2013 with a median age of 13 months (range, 6-30 months) receiving ABOi LRLT and were matched with six patients receiving ABO-compatible LRLT in the same period. In the ABOi group, titers of IgG and IgM isoagglutinins against the donor's blood group were determined at day 14 before the transplantation and from day 1 to 14 after the transplantation, and then twice a week for another 8 weeks. The titer results were determined as the reciprocal number of the highest serum dilution that caused macroscopical reaction.\n The patients receiving ABOi and those receiving ABO-compatible LRLT were comparable regarding the recipient's preoperative pediatric end-stage liver disease (PELD), age, gender, and technical aspects of transplantation. The median follow-up was 2.6 years (range, 1-4.5 years). At the time of operation, the mean body weight was 7.7 kg (range, 5.7-16 kg) in ABO-compatible LRLT recipients and 8.8 kg (range, 5.5-18 kg) in ABOi LRLT recipients. In each group, the median PELD score was 28 (range, 28-35), respectively. All recipients received tacrolimus plus mycophenolate mofetil-based standard immunosuppression and four ABOi transplanted patients received intravenous immunoglobulins at days 1, 3, and 5 after liver transplantation. Patient and graft survival in this group was 83%. One female patient died within 24 hours due to fulminant gram-negative sepsis. Another patient developed acute cellular rejection at the 8th postoperative day, which responded to steroid treatment. No further complications occurred. In the ABO-compatible group, patient survival was 100% and graft survival was 83%; one patient in this group received retransplantation after 4 days. During follow-up, two patients of the ABOi group had maximum alloantibody titers of four against the donor's blood group; all other patients had titers below four.\n ABOi LRLT seems to be safe without an escalation of immunosuppression and should be considered as an additional option to timely facilitate the transplantation.\n Georg Thieme Verlag KG Stuttgart · New York.\n\n\n"
},
{
"text": "\n183257\nNonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort.\n\nMynarek, M\n\nvon Hoff, K\n\nPietsch, T\n\nOttensmeier, H\n\nWarmuth-Metz, M\n\nBison, B\n\nPfister, S\n\nKorshunov, A\n\nSharma, T\n\nJaeger, N\n\nRyzhova, M\n\nZheludkova, O\n\nGolanov, A\n\nRushing, EJ\n\nHasselblatt, M\n\nKoch, A\n\nSchüller, U\n\nvon Deimling, A\n\nSahm, F\n\nSill, M\n\nRiemenschneider, MJ\n\nDohmen, H\n\nMonoranu, CM\n\nSommer, C\n\nStaszewski, O\n\nMawrin, C\n\nSchittenhelm, J\n\nBrück, W\n\nFilipski, K\n\nHartmann, C\n\nMeinhardt, M\n\nPietschmann, K\n\nHaberler, C\n\nSlavc, I\n\nGerber, NU\n\nGrotzer, M\n\nBenesch, M\n\nSchlegel, PG\n\nDeinlein, F\n\nvon Bueren, AO\n\nFriedrich, C\n\nJuhnke, BO\n\nObrecht, D\n\nFleischhack, G\n\nKwiecien, R\n\nFaldum, A\n\nKortmann, RD\n\nKool, M\n\nRutkowski, S\n\nBeiträge in Fachzeitschriften\nISI:000559978400005\n32330099.0\n10.1200/JCO.19.03057\nNone\nThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.\n From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.\n Five years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).\n Systemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma.\n\nBenesch, Martin\n\n\n"
},
{
"text": "\n120625\nPlanar embryos have poor prognosis in terms of blastocyst formation and implantation.\n\nEbner, T\n\nMaurer, M\n\nShebl, O\n\nMoser, M\n\nMayer, RB\n\nDuba, HC\n\nTews, G\n\nBeiträge in Fachzeitschriften\nISI:000309603100007\n22796233.0\n10.1016/j.rbmo.2012.05.007\nNone\nNormally, day-2 embryos show a crosswise arrangement of four cells with three blastomeres lying side by side. Cleavage anomalies include embryos that are characterized by a particular planar constellation of four blastomeres with presumed incomplete cleavage. Since little is known on the developmental fate of such conceptuses, within a 10-month period all consecutive patients were screened for day-2 planar embryos. A total of 64/2070 embryos with suboptimal blastomere configuration were detected (3.1%). In conventional IVF, planar embryos were significantly less frequent (0.7%) as compared with intracytoplasmic sperm injection (2.8%; P<0.05) and cases of testicular sperm extraction (5.4%; P<0.01). Interestingly, embryos with a cleavage anomaly showed better morphology both on day 2 (P<0.005) and day 3 (P<0.001). In contrast, blastocyst formation (P<0.001) and blastocyst quality (P=NS) was higher in tetrahedral embryos. There was a significant increase in implantation rate if tetrahedral embryos could be transferred compared with when planar embryos had to be transferred (P<0.01). It may be postulated that, in planar embryos, the mitotic spindle might have been affected, e.g. sperm centrosome composition or function, which in turn might have led to the observed cleavage anomaly. Normally, day-2 embryos show a crosswise arrangement of four cells with three blastomeres lying side by side. Cleavage anomalies include more planar embryos that are characterized by a particular flat constellation of four blastomeres with presumed premature cleavage (like a tetrafoliate clover). Since little is known on the developmental fate of such embryos within a 10-month study period, all consecutive patients were screened for the presence of day-2 planar embryos (study group). A total of 64 (out of 2070) embryos with abnormal blastomere configuration were detected (3.1%). Interestingly, in conventional IVF (0.7%), the presence of planar embryos was significantly less frequent as compared with intracytoplasmic sperm injection (2.8%; P<0.05) and cases of testicular biopsy (5.4%; P<0.01). Embryos from the study group showed better morphology both on day 2 (P<0.005) and day 3 (P<0.001). In contrast, blastocyst formation (survival to day 5 of preimplantation development) was higher in the normally cleaved control group (P<0.001) and so was blastocyst quality; however, the latter parameter did not reach level of significance. This was also reflected in a significantly higher implantation rate in the control group (P<0.01). Based on present data, it may be postulated that, in planar embryos, the mitotic spindle (which involves the sperm centrosome) might have been affected, which in turn might have led to an incomplete cleavage.\n\nEbner, Thomas\n\n\n"
},
{
"text": "\n135824\nMeta-analysis of Genome-wide Association Studies Identifies 1q22 as a Susceptibility Locus for Intracerebral Hemorrhage.\n\nWoo, D\n\nFalcone, GJ\n\nDevan, WJ\n\nBrown, WM\n\nBiffi, A\n\nHoward, TD\n\nAnderson, CD\n\nBrouwers, HB\n\nValant, V\n\nBattey, TW\n\nRadmanesh, F\n\nRaffeld, MR\n\nBaedorf-Kassis, S\n\nDeka, R\n\nWoo, JG\n\nMartin, LJ\n\nHaverbusch, M\n\nMoomaw, CJ\n\nSun, G\n\nBroderick, JP\n\nFlaherty, ML\n\nMartini, SR\n\nKleindorfer, DO\n\nKissela, B\n\nComeau, ME\n\nJagiella, JM\n\nSchmidt, H\n\nFreudenberger, P\n\nPichler, A\n\nEnzinger, C\n\nHansen, BM\n\nNorrving, B\n\nJimenez-Conde, J\n\nGiralt-Steinhauer, E\n\nElosua, R\n\nCuadrado-Godia, E\n\nSoriano, C\n\nRoquer, J\n\nKraft, P\n\nAyres, AM\n\nSchwab, K\n\nMcCauley, JL\n\nPera, J\n\nUrbanik, A\n\nRost, NS\n\nGoldstein, JN\n\nViswanathan, A\n\nStögerer, EM\n\nTirschwell, DL\n\nSelim, M\n\nBrown, DL\n\nSilliman, SL\n\nWorrall, BB\n\nMeschia, JF\n\nKidwell, CS\n\nMontaner, J\n\nFernandez-Cadenas, I\n\nDelgado, P\n\nMalik, R\n\nDichgans, M\n\nGreenberg, SM\n\nRothwell, PM\n\nLindgren, A\n\nSlowik, A\n\nSchmidt, R\n\nLangefeld, CD\n\nRosand, J\n\nInternational Stroke Genetics Consortium\n\nBeiträge in Fachzeitschriften\nISI:000333765300003\n24656865.0\n10.1016/j.ajhg.2014.02.012\nPMC3980413\nIntracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1, 45 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1, 81 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1, 81 individuals (484 lobar and 1, 94 nonlobar cases) and a control cohort of 2, 61 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.\n\nEnzinger, Christian\n\nPichler, Alexander\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\nStögerer-Oberschmid, Eva Maria\n\n\n"
},
{
"text": "\n163369\nCHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: a SUNFRAIL report.\n\nBousquet, J\n\nOnorato, GL\n\nBachert, C\n\nBarbolini, M\n\nBedbrook, A\n\nBjermer, L\n\nde Sousa, JC\n\nChavannes, NH\n\nCruz, AA\n\nDe Manuel Keenoy, E\n\nDevillier, P\n\nFonseca, J\n\nHun, S\n\nKostka, T\n\nHellings, PW\n\nIllario, M\n\nIvancevich, JC\n\nLarenas-Linnemann, D\n\nMillot-Keurinck, J\n\nRyan, D\n\nSamolinski, B\n\nSheikh, A\n\nYorgancioglu, A\n\nAgache, I\n\nArnavielhe, S\n\nBewick, M\n\nAnnesi-Maesano, I\n\nAnto, JM\n\nBergmann, KC\n\nBindslev-Jensen, C\n\nBosnic-Anticevich, S\n\nBouchard, J\n\nCaimmi, DP\n\nCamargos, P\n\nCanonica, GW\n\nCardona, V\n\nCarriazo, AM\n\nCingi, C\n\nColgan, E\n\nCustovic, A\n\nDahl, R\n\nDemoly, P\n\nDe Vries, G\n\nFokkens, WJ\n\nFontaine, JF\n\nGemicioğlu, B\n\nGuldemond, N\n\nGutter, Z\n\nHaahtela, T\n\nHellqvist-Dahl, B\n\nJares, E\n\nJoos, G\n\nJust, J\n\nKhaltaev, N\n\nKeil, T\n\nKlimek, L\n\nKowalski, ML\n\nKull, I\n\nKuna, P\n\nKvedariene, V\n\nLaune, D\n\nLouis, R\n\nMagnan, A\n\nMalva, J\n\nMathieu-Dupas, E\n\nMelén, E\n\nMenditto, E\n\nMorais-Almeida, M\n\nMösges, R\n\nMullol, J\n\nMurray, R\n\nNeffen, H\n\nO'Hehir, R\n\nPalkonen, S\n\nPapadopoulos, NG\n\nPassalacqua, G\n\nPépin, JL\n\nPortejoie, F\n\nPrice, D\n\nPugin, B\n\nRaciborski, F\n\nSimons, FER\n\nSova, M\n\nSpranger, O\n\nStellato, C\n\nTodo Bom, A\n\nTomazic, PV\n\nTriggiani, M\n\nValero, A\n\nValovirta, E\n\nVandenPlas, O\n\nValiulis, A\n\nvan Eerd, M\n\nVentura, MT\n\nWickman, M\n\nYoung, I\n\nZuberbier, T\n\nZurkuhlen, A\n\nSenn, A\n\nBeiträge in Fachzeitschriften\nISI:000413588100001\n29075437.0\n10.1186/s13601-017-0173-8\nPMC5654064\nA Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.\n\nTomazic, Peter Valentin\n\n\n"
},
{
"text": "\n177424\nWhen and why was the phrenicoabdominal branch of the left phrenic nerve placed into the esophageal hiatus in German textbooks of anatomy? An anatomical study on 400 specimens reevaluating its course through the diaphragm.\n\nPretterklieber, B\n\nHader, M\n\nHammer, N\n\nPryymachuk, G\n\nPröls, F\n\nVielmuth, F\n\nBarnerßoi, M\n\nCotofana, S\n\nCustozzo, A\n\nWeyers, I\n\nWedel, T\n\nArnold, P\n\nRahner, C\n\nMüller-Gerbl, M\n\nPretterklieber, ML\n\nBeiträge in Fachzeitschriften\nISI:000539110300023\n31513915.0\n10.1016/j.aanat.2019.151415\nNone\nThe phrenicoabdominal branch of the left phrenic nerve passes between muscle fiber bundles within the costal part of the diaphragm near the pericardium. In most German textbooks of anatomy, however, its passage is described to be found in the esophageal hiatus. The aim of this study was to reevaluate its topography relative to the diaphragm in a multicentric study and to identify the initiation of this description.\n In this multicentric study, the most dorsomedial branch of the left phrenic nerve was identified as the phrenicoabdominal branch in 400 embalmed anatomic specimens of Caucasian origin. The distance between its passage and the apex of the pericardium, the left border of the esophageal hiatus, and the inner aspect of the left sixth rib was measured on the cranial aspect of the diaphragm. Textbooks on human anatomy published in German language between 1700 and 2018 were reviewed for their description of the passage of the left phrenicoabdominal branch through the diaphragm.\n The first statement on the passage of the left phrenicoabdominal branch through the esophageal hiatus was given in 1791 by Sömmering. Since then, in German textbooks of anatomy, a duality in the description of the passage of the left phrenicoabdominal branch persists. In none of the individuals examined in this study, the left phrenicoabdominal branch passed through the esophageal hiatus. In 99.5% of all cases, it pierced the costal part of the diaphragm dorsal to or at the same level as the apex of the pericardium. The mean distances (standard deviations) were 3.4 (±1.5) cm to the apex of the pericardium, 5.8 (±2.2) cm to the esophageal hiatus, and 5.5 (±1.6) cm to the inner aspect of the left sixth rib.\n The findings on the position of the left phrenicoabdominal branch relative to the diaphragm help to improve topographical knowledge and prevent inadvertent nerve injury during surgical interventions on or near the diaphragm. Further to this, these results may form a substantial basis to adopt the correct description of the passage of the left phrenicoabdominal branch to anatomical textbook knowledge.\n Copyright © 2019 Elsevier GmbH. All rights reserved.\n\nHammer, Niels\n\nPretterklieber, Bettina\n\nPretterklieber, Michael\n\n\n"
},
{
"text": "\n168671\nBai Hu Tang, Si Ni Tang, and Xue Bi Tang amplify pro-inflammatory activities and reduce apoptosis in endothelial cells in a cell culture model of sepsis.\n\nBrislinger, D\n\nDaxböck, C\n\nRoßmanith, E\n\nStückler, M\n\nLang, I\n\nFalkenhagen, D\n\nBeiträge in Fachzeitschriften\nISI:000442060400029\n30036577.0\n10.1016/j.jep.2018.07.021\nNone\nSepsis is a systemic inflammatory response of the body to a severe infection or massive tissue injury. Despite intensive research, sepsis continues to have a high mortality rate and successful treatment options are strongly needed. Bai Hu Tang (BHT), Si Ni Tang (SNT), and Xue Bi Tang (XBT) are ancient traditional Chinese formulas derived from Chinese herbs that are used to treat Sepsis, but their mechanisms of activity are largely unknown.\n We aimed to examine dose-dependent effects of BHT, SNT, and XBT in a cell culture model of Sepsis, with special focus on endothelial cell apoptosis and the expression of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)6, IL8, the surface adhesion molecule intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1).\n We stimulated THP1 monocytic cells with lipopolysaccharide (LPS, Escherichia coli (E. coli)) for 4 h and used the resulting culture medium to stimulate human umbilical vein endothelial cells (HUVECs). HUVECs were also simultaneously treated with hydrophilic concentrates of BHT, SNT or XBT. We evaluated the mRNA and protein expression levels of IL6, IL8, MCP-1, ICAM-1, and ELAM-1 and the activity of caspase 3/7, a marker of cell apoptosis, after stimulation and treatment. In addition, we stimulated cannulated veins from human umbilical cords for 24 h and treated them with BHT, SNT or XBT. Immunohistochemistry visualized expression of ICAM-1 and ELAM-1.\n The mRNA and protein levels of IL6, IL8, ICAM-1, and ELAM-1 were higher in stimulated HUVECs than in controls. Treating stimulated HUVECs with BHT, SNT or XBT induced an additional increase in IL6 (13- to 132-fold) and IL8 (17- to 32-fold) mRNA levels but did not influence their protein levels. In addition, BHT induced an additional increase in ICAM-1 mRNA (9-fold) expression, whereas XBT increased the mRNA and protein levels of ELAM-1 by 42-fold and 10-fold, respectively. Finally, caspase 3/7 levels, and therefore apoptosis, were up to 100% lower in cells treated with BHT than in the stimulated control (P < 0.001).\n The results of this study indicate that BHT, SNT, and XBT interfere in inflammatory pathways during septic processes by reducing the apoptotic effects of LPS and modifying the endothelial expression of pro-inflammatory cytokines and surface adhesion molecules.\n Copyright © 2018 Elsevier B.V. All rights reserved.\n\nBrislinger, Dagmar\n\nDaxboeck, Christine\n\nLang-Olip, Ingrid\n\n\n"
},
{
"text": "\n183971\nLow-dose antibiotic prophylaxis has no significant impact on the stability of the intestinal microbiome in children with urogenital tract malformations under 1 year of age.\n\nStrasser, C\n\nSpindelboeck, W\n\nKashofer, K\n\nOswald, J\n\nHaid, B\n\nBeiträge in Fachzeitschriften\nISI:000574920700023\n32665196.0\n10.1016/j.jpurol.2020.05.165\nNone\nAccumulating data point at potentially lasting effects of early childhood therapeutic antibiotic exposure on the intestinal microbial. Little is known on the impact of low-dose longterm antibiotic prophylaxis on the developing intestinal microbiota in children during their first year of life.\n To investigate compositional changes of the intestinal microbiota by next generation sequencing based microbiome analysis and bacterial metabolites in longitudinally collected fecal samples.\n Twelve patients were analyzed in this prospective, longitudinal pilot study during a period of 70 days (sampling on days 0, , 4, 0, 0). Only transvaginally and term born babies, breastfed with no prior antibiotic exposure with urogenital malformation (vesicoureteral reflux and/or upper urinary tract dilatation) were included into the study. Seven patients received antibiotic longterm prophylaxis with a second-generation cephalosporin and five did not. Sequencing of bacterial 16 S rRNA allowed for an analysis of the microbiome composition. The Principal coordinate analysis was performed for the evaluation of compositional profile. Furthermore, quantitative measurement of short chain fatty acids served as a proxy for the metabolic activity of the individual microbiome over the study time.\n Analysis of observed species, Shannon Index and weighted Unifrac distances between timepoints revealed neither significant difference comparing the prophylaxis group versus the control group over the study period, nor significant changes within the groups over time. Principal coordinate analysis (PCoA) was performed for the evaluation of compositional profile. Also, no differences regarding the fecal SCFA content were found between the two groups (>0.05 at each tested point, Mann-Whitney Test).\n Although there were interindividual compositional differences of the microbiome (cluster of bacterial composition) at the beginning of the observation, we did not observe significant longitudinal changes regarding both bacterial diversity and SCFAs in neither group. Over the study period, the patient's microbiome remained stable and resilient to the antibiotic exposure in terms of bacterial abundance and metabolism. Limitations to the study are the low number of patients included and the use of one single antibiotic (cefaclor).\n This is the first pilot study to demonstrate that long term low-dose antibiotic administration in children under one year of age does neither seem to influence the composition of the intestinal microbiota nor the quantities of bacterial fermentation products compared to untreated controls.\n Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.\n\nKashofer, Karl\n\nSpindelböck, Walter Johann\n\n\n"
},
{
"text": "\n982\nEscherichia coli endotoxin inhibits agonist-mediated cytosolic Ca2+ mobilization and nitric oxide biosynthesis in cultured endothelial cells.\n\nGraier, WF\n\nMyers, PR\n\nRubin, LJ\n\nAdams, HR\n\nParker, JL\n\nBeiträge in Fachzeitschriften\nISI:A1994PH62900007\n7923612.0\n10.1161/01.RES.75.4.659\nNone\nAltered release of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) has been proposed as a final common pathway underlying the abnormal vasodilator responses to gram-negative lipopolysaccharide (endotoxin). However, mechanisms responsible for lipopolysaccharide-induced changes in EDRF/NO release from endothelial cells have not been clarified. We evaluated direct effects of Escherichia coli endotoxin on agonist-stimulated cytosolic Ca2+ mobilization and NO biosynthesis in cultured bovine and porcine aortic endothelial cells (ECs). Two methods were used to assay for NO: (1) analysis of NO-induced endothelial levels of cGMP as a biological indicator of NO generation and (2) direct quantitative measurement of NO release (chemiluminescence method). Cytosolic free Ca2+ ([Ca2+]i) was evaluated using fura 2 fluorescence methodology (340/380-nm ratio excitation and 500-nm emission). Incubation of ECs with endotoxin (0.5 microgram/mL, 1 hour plus 1-hour wash) significantly inhibited bradykinin (100 nmol/L)- and ADP (10 mumol/L)-mediated increases in endothelial cell cGMP to 37% and 22% of control responses, respectively. In contrast, endotoxin failed to inhibit the increase in cGMP produced by the non-receptor-dependent Ca2+ ionophore A23187 (1 mumol/L) or sodium nitroprusside (1 mmol/L). Similarly, incubation with endotoxin inhibited ADP-stimulated increases in NO release and EDRF bioactivity to 55% and 56% of control values, respectively, but did not affect A23187-stimulated increases in NO release or EDRF bioactivity. Endotoxin produced significant decreases in both transient and sustained [Ca2+]i responses of ECs to bradykinin and ADP. For example, the initial rapid increase in bovine EC [Ca2+]i in response to bradykinin was reduced to 31% of the initial increases in control cells, and the secondary plateau phase was reduced to only 3% of respective control responses. Concentration-response relation to endotoxin (10(-3)) to 10(0) micrograms/mL) indicated high correlation and similar IC50 values (0.025 and 0.021 micrograms/mL, respectively) for inhibitory effects on cGMP and [Ca2+]i. Endotoxin had no effect on inositol trisphosphate formation ([3H]myo-inositol incorporation) and intracellular Ca2+ release ([Ca2+]i responses in Ca(2+)-free medium) induced by bradykinin. However, agonist-stimulated Mn2+ quenching (index of Ca2+ influx) was significantly attenuated by endotoxin treatment. These studies demonstrate that endotoxin directly decreases agonist (bradykinin and ADP)-mediated biosynthesis and release of EDRF/NO from ECs. These effects can be explained by altered [Ca2+]i mobilization mechanisms, which in turn produce subsequent decreases in activity of the Ca(2+)-calmodulin-dependent constitutive isoform of NO synthase and, ultimately, impairment of agonist-mediated NO release and endothelium-dependent vasodilation.\n\nGraier, Wolfgang\n\n\n"
},
{
"text": "\n175265\nEffects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial.\n\nRESTART Collaboration\n\nBeiträge in Fachzeitschriften\nISI:000473263600032\n31128924.0\n10.1016/S0140-6736(19)30840-2\nPMC6617509\nAntiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events.\n The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627).\n Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92).\n These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention.\n British Heart Foundation.\n Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.\n\nGattringer, Thomas\n\n\n"
}
]
}