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        {
            "text": "\n185233\nEuropean Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update.\n\nRouprêt, M\n\nBabjuk, M\n\nBurger, M\n\nCapoun, O\n\nCohen, D\n\nCompérat, EM\n\nCowan, NC\n\nDominguez-Escrig, JL\n\nGontero, P\n\nHugh Mostafid, A\n\nPalou, J\n\nPeyronnet, B\n\nSeisen, T\n\nSoukup, V\n\nSylvester, RJ\n\nRhijn, BWGV\n\nZigeuner, R\n\nShariat, SF\n\nBeiträge in Fachzeitschriften\nISI:000599925300030\n32593530.0\n10.1016/j.eururo.2020.05.042\nNone\nThe European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice.\n                To provide an overview of the EAU guidelines on UTUC as an aid to clinicians.\n                The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract carcinoma, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, adjuvant treatment, instillation, recurrence, risk factors, and survival. References were weighted by a panel of experts.\n                Owing to the rarity of UTUC, there are insufficient data to provide strong recommendations. The 2017 tumour, node, metastasis (TNM) classification is recommended. Recommendations are given for diagnosis and risk stratification as well as for radical and conservative treatment, and prognostic factors are discussed. A single postoperative dose of intravesical mitomycin after nephroureterectomy reduces the risk of bladder tumour recurrence. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk tumour and two functional kidneys. After radical nephroureterectomy, cisplatin-based chemotherapy is indicated in locally advanced UTUC.\n                These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours.\n                Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, an appropriate diagnosis is most important. A number of known risk factors exist.\n                Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nZigeuner, Richard\n\n\n"
        },
        {
            "text": "\n185939\nMicrobiome dynamics during the HI-SEAS IV mission, and implications for future crewed missions beyond Earth.\n\nMahnert, A\n\nVerseux, C\n\nSchwendner, P\n\nKoskinen, K\n\nKumpitsch, C\n\nBlohs, M\n\nWink, L\n\nBrunner, D\n\nGoessler, T\n\nBilli, D\n\nMoissl-Eichinger, C\n\nBeiträge in Fachzeitschriften\nISI:000613072700001\n33487169.0\n10.1186/s40168-020-00959-x\nPMC7831191\nBACKGROUND: Human health is closely interconnected with its microbiome. Resilient microbiomes in, on, and around the human body will be key for safe and successful long-term space travel. However, longitudinal dynamics of microbiomes inside confined built environments are still poorly understood. Herein, we used the Hawaii Space Exploration Analog and Simulation IV (HI-SEAS IV) mission, a 1 year-long isolation study, to investigate microbial transfer between crew and habitat, in order to understand adverse developments which may occur in a future outpost on the Moon or Mars. RESULTS: Longitudinal 16S rRNA gene profiles, as well as quantitative observations, revealed significant differences in microbial diversity, abundance, and composition between samples of the built environment and its crew. The microbiome composition and diversity associated with abiotic surfaces was found to be rather stable, whereas the microbial skin profiles of individual crew members were highly dynamic, resulting in an increased microbiome diversity at the end of the isolation period. The skin microbiome dynamics were especially pronounced by a regular transfer of the indicator species Methanobrevibacter between crew members within the first 200 days. Quantitative information was used to track the propagation of antimicrobial resistance in the habitat. Together with functional and phenotypic predictions, quantitative and qualitative data supported the observation of a delayed longitudinal microbial homogenization between crew and habitat surfaces which was mainly caused by a malfunctioning sanitary facility. CONCLUSIONS: This study highlights main routes of microbial transfer, interaction of the crew, and origins of microbial dynamics in an isolated environment. We identify key targets of microbial monitoring, and emphasize the need for defined baselines of microbiome diversity and abundance on surfaces and crew skin. Targeted manipulation to counteract adverse developments of the microbiome could be a highly important strategy to ensure safety during future space endeavors. Video abstract.\n\nBlohs, Marcus\n\nKoskinen Mora, Kaisa\n\nKumpitsch, Christina Sarah\n\nMahnert, Alexander\n\nMoissl-Eichinger, Christine\n\nWink, Lisa\n\n\n"
        },
        {
            "text": "\n500\nCMV antigenemia (the lower matrix protein PP65), a marker for the guidance of antiviral therapy in cytomegalovirus disease after orthotopic heart transplantation.\n\nIberer, F\n\nTscheliessnigg, KH\n\nHalwachs, G\n\nAuer, T\n\nWasler, A\n\nPetutschnigg, B\n\nMüller, H\n\nFreigassner, M\n\nAllmayr, T\n\nHipmair, G\n\nBeiträge in Fachzeitschriften\nISI:A1995TJ51700005\n8560893.0\nNone\nNone\nDuring CMV viremia, the CMV specific lower matrix protein CMV pp65 can be detected in the nucleus of polymorphonuclear cells. A relationship has been found between the number of CMV pp65 positive cells, the clinical course and the effect of antiviral treatment on CMV disease. From 1990, heart recipients (triple drug therapy) were screened for CMV pp65 (antigenemia, according to the method described by The et al.), anti-CMV-IgM and -IgG. Tests were repeated at least every 4 weeks. Group 1 consisted of 23 patients who had been transplanted at least one year before the introduction of CMV testing as described. Between 1990 and 1992 26 patients were followed up during the first year after transplantation and represent group 2. In group 1, 1184 antigenemia assays were performed and 13 tested positive. In group 2 (1195 tests, 261 positive results), 20 out of the 26 recipients tested positive for CMV pp65. Without preceding evidence of a positive CMV pp65, no rise of IgM or IgG antibodies was observed. The time until the first antigenemia (time from detection until a subsequent test remains negative); 13 were found in group 1, 84 in group 2. In group 2, 46 episodes of antigenemia (mean duration 24.5 +/- 27.1 days) consisted of more than 1 consecutive positive result of the antigenemia assay (4.8 +/- 4.1). During these episodes the white blood cell count was 3460 +/- 1790/mm3. After the episodes, the mean leucocyte count was 6320 +/- 1870/mm3. The detection of CMV antigenemia indicated the initiation of antiviral treatment (hyperimmune globulin and ganciclovir). Therapy was stopped again when the antigenemia assay tested negative again. Antigenemia disappeared in all patients after initiation of antiviral treatment, CMV disease was not observed. CMV antigenemia mainly cumulates within the first year after heart transplantation. Antigenemia directed antiviral therapy does not prevent infection or repeated antigenemia but prevents CMV disease after heart transplantation.\n\nAuer-Schönbach, Thomas\n\nMüller, Helmut\n\nPetutschnigg, Berthold\n\n\n"
        },
        {
            "text": "\n64058\nEffect of electrostatic charge, flow, delay and multiple actuations on the in vitro delivery of salbutamol from different small volume spacers for infants.\n\nWildhaber, JH\n\nDevadason, SG\n\nEber, E\n\nHayden, MJ\n\nEverard, ML\n\nSummers, QA\n\nLeSouëf, PN\n\nBeiträge in Fachzeitschriften\nISI:A1996VQ12300007\n8977597.0\n10.1136/thx.51.10.985\nPMC472645\nBACKGROUND: A study was undertaken to determine the influences of electrostatic charge, flow, delay, and multiple actuations on the in vitro delivery of salbutamol generated by a pressurised metered dose inhaler (pMDI) from small volume spacers used in infants. METHODS: Ten actuations from a salbutamol pMDI were drawn at different flow rates after either single or multiple actuations, with or without delay, through either static or reduced static spacers. An ionic detergent was used to reduce the charge of plastic spacers (Babyhaler, Babyspacer, Aerochamber, Nebuhaler). Electrostatic charge was measured using an electrometer. A multistage liquid impinger was used to determine the particle size distribution of the output of the pMDI through the spacers. RESULTS: Electrostatic charge on the surface of plastic spacers had the greatest influence on delivery, causing a decrease in drug delivery. Reducing charge by coating the surface with ionic detergent resulted in an increase of 46.5-71.1% (p < 0.001) in small (< 6.8 microns) particle delivery from small volume plastic spacers. Lower flow, delay, and multiple actuations resulted in decreased delivery from static spacers. Lower flow resulted in a decrease of 15% in small (< 9.6 microns) particle delivery. Delay and multiple actuations resulted in a decrease of 40.7% and 76.0%, respectively, in small (< 6.8 microns) particle delivery. The influences of lower flow, delay, and multiple actuations were greatly reduced or even eliminated by reducing charge. However, multiple actuations still resulted in a significant decreased delivery (p < 0.05). The reduced static Nebuhaler had a higher delivery than all small volume spacers. CONCLUSIONS: Electrostatic charge has a major influence on the delivery of salbutamol from small volume spacers. Using a metal spacer or ionic detergent coating of plastic spacers resulted in no or reduced charge and hence in improved delivery. Lower flow, delay, and multiple actuations played a major part only in static spacers.\n\nEber, Ernst\n\n\n"
        },
        {
            "text": "\n64785\nHistamine induces K+, Ca2+, and Cl- currents in human vascular endothelial cells. Role of ionic currents in stimulation of nitric oxide biosynthesis.\n\nGroschner, K\n\nGraier, WF\n\nKukovetz, WR\n\nBeiträge in Fachzeitschriften\nISI:A1994NZ34900013\n8033342.0\n10.1161/01.RES.75.2.304\nNone\nThe nature of the membrane currents mediating agonist-induced Ca2+ entry and enhanced nitric oxide (NO) production in endothelial cells is still unclear. Using both perforated-patch and conventional whole-cell clamp technique, we have studied the membrane response associated with histamine stimulation of human vascular endothelial cells. In perforated-patch experiments, the initial histamine (10 mumol/L)-induced current reversed close to the K+ equilibrium potential and was blocked by tetrabutylammonium ions (TBA, 10 mmol/L). In addition, a TBA-insensitive current that developed slowly in the presence of histamine was recorded. This delayed histamine-induced current reversed close to neutral potential and was inhibited by SK&F 96365 (25 mumol/L), a putative blocker of receptor-operated Ca2+ channels. Similar histamine effects were observed in conventional whole-cell experiments using pipette solutions with low Ca(2+)-buffering capacity. Strong buffering of intracellular free Ca2+ suppressed the initial, but not the delayed, current response. The delayed component of histamine-induced current was substantially inhibited by the Cl- channel blocker N-phenylanthranilic acid (NPA, 100 mumol/L), and an eightfold change in the Cl- gradient shifted the reversal potential of this current by 30 mV. In Cl(-)-free solutions, histamine induced an SK&F 96365-sensitive NPA-resistant current, which, according to reversal potential measurements in 20 mmol/L extracellular Ca2+, corresponded to a cation conductance with 13- to 25-fold selectivity for Ca2+ over K+. Both SK&F 96365 and TBA strongly suppressed histamine-induced rises in intracellular free Ca2+ and cellular cGMP levels, whereas NPA did not. Our results provide the first demonstration that three distinct ionic conductances contribute to the histamine-induced membrane response of endothelial cells. It is suggested that histamine induces a Cl- conductance that is apparently not involved in Ca2+ homeostasis and regulation of NO biosynthesis, while, in parallel, joint activation of a rapidly induced K+ permeability and a slowly developing cation permeability mediate Ca2+ entry and stimulation of endothelial NO production.\n\nGraier, Wolfgang\n\nGroschner, Klaus\n\n\n"
        },
        {
            "text": "\n82615\nMicrocystic/reticular schwannoma: a distinct variant with predilection for visceral locations.\n\nLiegl, B\n\nBennett, MW\n\nFletcher, CDM\n\nBeiträge in Fachzeitschriften\nISI:000257298000017\n18520439.0\n10.1097/PAS.0b013e318160cfda\nNone\nSchwannomas are benign, generally nonrecurring tumors most frequently arising in the subcutaneous tissue of adults with no sex predilection. Herein we report 10 cases of a distinctive morphologic variant of schwannoma with predominantly microcystic-reticular morphology and characterize the clinicopathologic spectrum. The age at presentation ranged from 11 to 93 years (median age 63 y). The tumor size ranged from 0.4 to 23 cm (median size 4.3 cm). Five tumors arose in the gastrointestinal tract, most often in the submucosa. Two cases arose in subcutaneous tissue and 1 case each in the upper respiratory tract, the adrenal gland, and deep soft tissue. None of the patients had features of neurofibromatosis type 1 or type 2 (NF1, NF2). Histologically 8 tumors were circumscribed but unencapsulated and 2 cases located in the subcutaneous fat were circumscribed and encapsulated. At visceral locations, focally pushing margins and microscopic foci of infiltration into surrounding parenchyma were seen. All cases showed a striking microcystic and reticular lesional growth pattern with anastomosing and intersecting strands of spindle cells with eosinophilic cytoplasm distributed around islands of myxoid or collagenous/hyalinized stroma. The nuclei were round, oval, and tapered and showed inconspicuous nucleoli. Three cases had smaller areas resembling conventional schwannoma. Mitotic activity did not exceed more than 3 mitoses/50 high-power fields (HPF) (median 1/30 HPF). Pleomorphism and necrosis were absent. All tumors showed strong nuclear and cytoplasmic positivity for S-100 and variably strong glial fibrillary acidic protein staining. A surrounding tumor capsule was highlighted with epithelial membrane antigen in 2 out of 10 cases. Smooth muscle actin, Desmin, Pan-CK, AE/AE3, Cam5.2, and p-63 were negative in all cases evaluated. Neurofilament protein highlighted axons in one out of 7 cases investigated. CD117 showed weak focal positivity in 1 out of 4 cases. Follow-up data were available in 7 cases (median duration 15 mo). None has recurred to date. Microcystic schwannoma represents a distinctive morphologic variant of schwannoma with predilection for visceral locations. Recognition of this distinct entity is essential to avoid confusion with malignant tumors, especially in the gastrointestinal and upper respiratory tracts.\n\nLiegl-Atzwanger, Bernadette\n\n\n"
        },
        {
            "text": "\n83301\nPredictive value of seven preoperative prognostic scoring systems for spinal metastases.\n\nLeithner, A\n\nRadl, R\n\nGruber, G\n\nHochegger, M\n\nLeithner, K\n\nWelkerling, H\n\nRehak, P\n\nWindhager, R\n\nBeiträge in Fachzeitschriften\nISI:000260950800012\n18787846.0\n10.1007/s00586-008-0763-1\nPMC2583181\nPredicting prognosis is the key factor in selecting the proper treatment modality for patients with spinal metastases. Therefore, various assessment systems have been designed in order to provide a basis for deciding the course of treatment. Such systems have been proposed by Tokuhashi, Sioutos, Tomita, Van der Linden, and Bauer. The scores differ greatly in the kind of parameters assessed. The aim of this study was to evaluate the prognostic value of each score. Eight parameters were assessed for 69 patients (37 male, 32 female): location, general condition, number of extraspinal bone metastases, number of spinal metastases, visceral metastases, primary tumour, severity of spinal cord palsy, and pathological fracture. Scores according to Tokuhashi (original and revised), Sioutos, Tomita, Van der Linden, and Bauer were assessed as well as a modified Bauer score without scoring for pathologic fracture. Nineteen patients were still alive as of September 2006 with a minimum follow-up of 12 months. All other patients died after a mean period of 17 months after operation. The mean overall survival period was only 3 months for lung cancer, followed by prostate (7 months), kidney (23 months), breast (35 months), and multiple myeloma (51 months). At univariate survival analysis, primary tumour and visceral metastases were significant parameters, while Karnofsky score was only significant in the group including myeloma patients. In multivariate analysis of all seven parameters assessed, primary tumour and visceral metastases were the only significant parameters. Of all seven scoring systems, the original Bauer score and a Bauer score without scoring for pathologic fracture had the best association with survival (P < 0.001). The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases. However, decision for or against surgery should never be based alone on a prognostic score but should take symptoms like pain or neurological compromise into account.\n\nLeithner, Andreas\n\nLeithner, Katharina\n\nRadl, Roman\n\n\n"
        },
        {
            "text": "\n85813\nMyeloperoxidase as serum marker for detection of CMV infections and rejections in patients after liver or heart transplantation.\n\nZelzer, S\n\nStiegler, P\n\nKapitan, M\n\nSchaffellner, S\n\nSchweiger, M\n\nStettin, M\n\nStojakovic, T\n\nTruschnig-Wilders, M\n\nTscheliessnigg, KH\n\nKhoschsorur, G\n\nBeiträge in Fachzeitschriften\nISI:000262898100003\n18930821.0\n10.1016/j.trim.2008.09.014\nNone\nRejection episodes and infections are common problems after organ transplantations (TX). Rejection can be diagnosed in liver-transplant (LTX) patients when liver-specific enzymes in the serum are elevated. As endomyocardial biopsy (EMB) is the gold standard for detecting heart transplant (HTX) rejection, serum parameters would permit more selective use of this invasive procedure. Cytomegalovirus (CMV) infections can have serious consequences for TX patients and so should be diagnosed and treated timely. At present, there are no suitable diagnostic methods other than CMV antigen pp65 and CMV polymerase chain reaction (PCR). Our study aimed to test the sensitivity of myeloperoxidase (MPO), an enzyme of neutrophilic granulocytes, as a new serum parameter in addition to established serum parameters and EMB for diagnosis of infection and rejection episodes after LTX and HTX. MPO in plasma from 246 blood samples (103 used for statistical analysis) from 27 patients (18 LTX and 9 HTX) was determined using ELISA; C-reactive protein (CRP), gamma-glutamyl-transpeptidase (GGT), white blood count and CMV pp65 antigen were monitored routinely. EMBs were performed at defined intervals after HTX. Results were analyzed with descriptive statistics, T-test, Wilcoxon test and Cox regression analysis, whereby a p<0.05 was viewed as significant. MPO values in TX patients with an infection (7 LTX, 2 HTX) were significantly higher than in TX patients without complications (control group) (253.9 microg/l vs. 116.6 microg/l, p=0.0194). In TX patients with rejections (6 LTX, 6 HTX), there is also a significant increase in comparison to controls (429.7 microg/l vs. 116.6 microg/l, p=0.0001). Data from individual TX patients, however, indicate that MPO levels rise distinctly earlier with infection (CMV) than with rejection, enabling earlier detection of the complication and initiation of suitable treatment. Our findings suggest that a larger and prospective study should be designed to evaluate the usefulness of MPO levels in assessing organ transplant recipients.\n\nSchaffellner, Silvia\n\nStiegler, Philipp\n\nZelzer, Sieglinde\n\n\n"
        },
        {
            "text": "\n131555\nComparative biomechanical and radiological characterization of osseointegration of a biodegradable magnesium alloy pin and a copolymeric control for osteosynthesis.\n\nLindtner, RA\n\nCastellani, C\n\nTangl, S\n\nZanoni, G\n\nHausbrandt, P\n\nTschegg, EK\n\nStanzl-Tschegg, SE\n\nWeinberg, AM\n\nBeiträge in Fachzeitschriften\nISI:000328234500021\n24001403.0\n10.1016/j.jmbbm.2013.08.008\nNone\nMagnesium alloys offer great advantages as degradable implant material for pediatric fracture fixation and hold the potential to overcome certain critical shortcomings inherent to currently used degradable (co)polymers. Besides good biocompatibility and appropriate degradation kinetics, sufficient implant anchorage in host bone is critical to prevent implant failure. Bone-implant anchorage of biodegradable magnesium alloys, however, has not yet been related and compared to that of copolymers, their degradable counterparts currently in clinical use. The aim of this study, therefore, was to comparatively assess bone-implant interface strength and the amount of peri-implant bone of a biodegradable magnesium alloy pin (Mg-Y-Nd-HRE) and a self-reinforced copolymeric control (85/15 poly(l-lactic-co-glycolic acid)). To this purpose, push-out testing, microfocus computed tomography (μCT), histological and scanning electron microscopic examination was performed after 4, 12 and 24 weeks of transcortical implantation in 72 rats. Biomechanical testing revealed significantly higher ultimate shear strength for the magnesium alloy pins than for the copolymeric controls at all 3 timepoints (P≤0.001 for all comparisons). As evaluated by μCT, the amount of bone present near the interface and in a wider radius (up to 0.5mm) around it was higher in the magnesium alloy implants at 4 weeks, without significant differences at 12 and 24 weeks. Histological examination confirmed direct bone-to-implant contact for both implant types. In vivo degradation of implants did not induce any noticeable local or systemic inflammation. This data suggests that the investigated degradable magnesium alloy rod exhibits markedly superior bone-implant interface strength and a greater amount of peri-implant bone than a self-reinforced copolymeric control currently in use; thus it fulfills a crucial prerequisite for its successful clinical deployment as an alternative degradable orthopedic implant material. Further studies, however, are warranted to evaluate the long-term degradation behavior and biocompatibility of the investigated degradable magnesium-based alloy.\n                © 2013 Elsevier Ltd. All rights reserved.\n\nCastellani, Christoph\n\nWeinberg, Annelie-Martina\n\n\n"
        },
        {
            "text": "\n152475\nFirst pass dual input volume CT-perfusion of lung lesions: The influence of the CT- value range settings on the perfusion values of benign and malignant entities.\n\nBohlsen, D\n\nTalakic, E\n\nFritz, GA\n\nQuehenberger, F\n\nTillich, M\n\nSchoellnast, H\n\nBeiträge in Fachzeitschriften\nISI:000375944400010\n27161059.0\n10.1016/j.ejrad.2016.03.013\nNone\nTo assess the influence of the lower threshold for segmentation of the volume of interest on the perfusion values in first-pass dual input volume CT-perfusion of lung lesions.\n                Dual input maximum slope volume CT-perfusion was performed in 48 patients (mean age±standard deviation [SD], 68±10years; range, 46-87 years) who underwent subsequent CT-guided biopsy to evaluate a lung lesion. Using commercial perfusion software, a lower and upper threshold was set for determination of the CT-value range, which again determined the volume of interest for perfusion calculation. The pulmonary arterial flow (PAF), bronchial arterial flow (BAF), and perfusion index (PI; PAF/(PAF+BAF)) were calculated at following pre contrast CT value range settings: -80 to 150HU (setting 1), -200 to 150HU (setting 2), -300 to 150HU (setting 3), and -500 to 150HU (setting 4). Perfusion parameters were compared between benign (n, 15) and malignant (n, 33) lesions for each setting. Intraobserver- and interobserver reliability were calculated for setting 4.\n                Median PAF was significantly higher in malignant lesions than in benign lesions for all settings (53-96 versus 29-62mL/min/100mL, P<0.05). There was no significant difference in BAF between malignant and benign lesions. Median PAF of all lesions was significantly influenced by the CT value range setting (P<0.05), whereas the values increased from setting 1 to 4. Intraobserver analysis as well as interobserver analysis of PAF at setting 4 showed excellent reliability (Cronbach's alpha 0.98 and 0.95, respectively, P<0.01).\n                PAF derived from first-pass dual-input maximum slope volume CT perfusion is statistically significantly higher in malignant than in benign lesion, whereas the measurements are influenced by the lower threshold of the CT value range setting. This has to be considered when using cutoff values provided in the literature for differentiation between benign and malignant lung lesions.\n                Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.\n\nQuehenberger, Franz\n\nSchoellnast, Helmut\n\nTalakic, Emina\n\n\n"
        },
        {
            "text": "\n158126\nPreceding and subsequent high- and low-trauma fracture patterns-a 13-year epidemiological study in females and males in Austria.\n\nMuschitz, C\n\nKocijan, R\n\nBaierl, A\n\nDormann, R\n\nFeichtinger, X\n\nHaschka, J\n\nSzivak, M\n\nMuschitz, GK\n\nSchanda, J\n\nPietschmann, P\n\nResch, H\n\nDimai, HP\n\nBeiträge in Fachzeitschriften\nISI:000399443600011\n28138718.0\n10.1007/s00198-017-3925-3\nNone\nThis study investigated the implication of a preceding high-trauma fracture on subsequent high- and low-trauma fractures at different skeletal sites in postmenopausal women and similarly aged men at an age range of 54 to 70 years. A preceding high-trauma fracture increases the risk of future low-trauma non-vertebral fractures including hip.\n                Little is known about the impact of the skeletal fracture site in conjunction with the severity of a past fracture (high- or low-trauma preceding fracture) and its effect on future fracture risk.\n                Patients with de novo high- and low-trauma fractures admitted to seven large trauma centers across Austria between 2000 and 2012 were stratified into sex and different age groups. Kaplan-Meier estimates, Cox proportional hazards regression models (HR), and likelihood calculations estimated effects of age, sex, and the anatomic region on the probability of a subsequent fracture in the same patient.\n                Included in the study were 433, 99 female and male patients at an age range of 0 to 100 years with 575, 72 de novo high- and low-trauma fractures. In the age range of 54-70 years, subsequent fractures were observed in 16% of females and 12.1% of males. A preceding high-trauma fracture was associated with 12.9% of subsequent fractures, thereof 6.5% of high- and 6.4% of low-trauma in origin, usually at the hip, humerus, or pelvis. The highest effect sizes were observed for femur, humerus, and thorax fractures with hazard ratios (HR) of 1.26, 1.18, and 1.14. After splitting into high-trauma preceding and subsequent low-trauma fractures, the femoral neck (HR = 1.59), the female sex (HR = 2.02), and age (HR = 1.03) were discriminators for increased future fracture risk.\n                Preceding high-trauma fractures increase the risk of future low-trauma non-vertebral fractures including hip. For each patient with a fracture, regardless of the severity of the trauma, osteoporosis should be taken into clinical consideration.\n\nDimai, Hans\n\n\n"
        },
        {
            "text": "\n168553\nUtility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease.\n\nBedossa, P\n\nFLIP Pathology Consortium\n\nBeiträge in Fachzeitschriften\nISI:000339497600016\n24753132.0\n10.1002/hep.27173\nNone\nBiopsy is still the gold standard for the diagnosis of nonalcoholic steatohepatitis but the definition may vary among pathologists, a drawback especially in evaluation of biopsies for clinical trials. We previously developed a scoring system (steatosis, activity, fibrosis [SAF]) allowing the use of an algorithm (fatty liver inhibition of progression [FLIP]) for the classification of liver injury in morbid obesity. The aim of this study was to determine whether the use of the SAF score and FLIP algorithm can decrease interobserver variations among pathologists. In a first session, pathologists categorized 40 liver biopsies of patients with nonalcoholic fatty liver disease (NAFLD) according to their own experience. In a second reading session, each pathologist reclassified the same slides by using the FLIP algorithm and SAF score, blinded to their first evaluation. The experiment was repeated with two different groups of pathologists at varying levels of training in liver pathology. The percentage of biopsy interpretation concordant with reference evaluation increased from 77% to 97% in Group 1 and from 42% to 75% in Group 2 after the use of the SAF score and FLIP algorithm. The strength of concordance in classification increased in Group 1 from moderate (κ = 0.54) to substantial (κ = 0.66) and from fair (κ = 0.35) to substantial (κ = 0.61) in Group 2 with application of the algorithm. With regard to the SAF score, concordance was substantial in Group 1 for steatosis (κ = 0.61), activity (κ = 0.75), and almost perfect for fibrosis (κ = 0.83 after pooling 1a, 1b, and 1c together into a single score F1). Similar trends were observed in Group 2 (κ = 0.54 for S, κ = 0.68 for A, and κ = 0.72 for F).\n                The FLIP algorithm based on the SAF score should decrease interobserver variations among pathologists and are likely to be implemented in pathology practice.\n                © 2014 by the American Association for the Study of Liver Diseases.\n\nLackner, Karoline\n\n\n"
        },
        {
            "text": "\n172277\nUse case driven evaluation of open databases for pediatric cancer research.\n\nJeanquartier, F\n\nJean-Quartier, C\n\nHolzinger, A\n\nBeiträge in Fachzeitschriften\nISI:000455751000001\n30675185.0\n10.1186/s13040-018-0190-8\nPMC6334395\nA plethora of Web resources are available offering information on clinical, pre-clinical, genomic and theoretical aspects of cancer, including not only the comprehensive cancer projects as ICGC and TCGA, but also less-known and more specialized projects on pediatric diseases such as PCGP. However, in case of data on childhood cancer there is very little information openly available. Several web-based resources and tools offer general biomedical data which are not purpose-built, for neither pediatric nor cancer analysis. Additionally, many Web resources on cancer focus on incidence data and statistical social characteristics as well as self-regulating communities.\n                We summarize those resources which are open and are considered to support scientific fundamental research, while we address our comparison to 11 identified pediatric cancer-specific resources (5 tools, 6 databases). The evaluation consists of 5 use cases on the example of brain tumor research and covers user-defined search scenarios as well as data mining tasks, also examining interactive visual analysis features.\n                Web resources differ in terms of information quantity and presentation. Pedican lists an abundance of entries with few selection features. PeCan and PedcBioPortal include visual analysis tools while the latter integrates published and new consortia-based data. UCSC Xena Browser offers an in-depth analysis of genomic data. ICGC data portal provides various features for data analysis and an option to submit own data. Its focus lies on adult Pan-Cancer projects. Pediatric Pan-Cancer datasets are being integrated into PeCan and PedcBioPortal. Comparing information on prominent mutations within glioma discloses well-known, unknown, possible, as well as inapplicable biomarkers. This summary further emphasizes the varying data allocation. Tested tools show advantages and disadvantages, depending on the respective use case scenario, providing inhomogeneous data quantity and information specifics.\n                Web resources on specific pediatric cancers are less abundant and less-known compared to those offering adult cancer research data. Meanwhile, current efforts of ongoing pediatric data collection and Pan-Cancer projects indicate future opportunities for childhood cancer research, that is greatly needed for both fundamental as well as clinical research.\n\nHolzinger, Andreas\n\n\n"
        },
        {
            "text": "\n172905\nSafety and risks of vegetarian and vegan nutrition during pregnancy, lactation and the first years of life. Statement by the Nutrition Committee of the Austrian Society of Pediatric and Adolescent Medicine on the safety and risks of various forms of vegetarian and vegan nutrition of the mother during pregnancy and lactation and in infants and toddlers\n\nPlank, R\n\nBeiträge in Fachzeitschriften\nISI:000456608700002\nNone\n10.1007/s00112-018-0554-7\nNone\nA well-balanced ovo-lacto vegetarian diet can be a good alternative to the omnivorous lifestyle, also for pregnant and lactating women as well as infants and toddlers, and can provide adequate nutrients for mother and child. The more restrictive the vegetarianism becomes, the higher is the risk of nutrient deficiencies. In a vegan diet the most critical nutrient with risk for deficiency is vitamin B12. There is a risk of severe, irreversible vitamin B12 deficiency especially in breastfed infants in case of inadequate supplementation of women. There is no international consensus on vitamin B12 supplementation in vegan diets. Therefore, the Committee of Nutrition of the Austrian Society for Pediatrics and Adolescent Medicine is currently unable to recommend a vegan diet during pregnancy, lactation and the first years of life. Other potentially critical nutrients include protein, omega-3 fatty acids, vitamin D and minerals such as calcium, iron, zinc and iodine. Due to the growing interest in vegetarian diets, one is frequently confronted with parents desiring to start their children on a vegetarian or vegan diet. With this position paper the Committee of Nutrition of the Austrian Society for Pediatrics and Adolescent Medicine wants to provide an overview of the critical nutrients that have to be taken into account in vegetarian diets of mother and child. The key objective is to bear potential deficiencies in mind and allow an implementation of vegetarian diets in a way that is as safe and knowledgeable as possible. In case of a vegan diet, medical and dietary support is essential.\n\nHauer, Almuthe\n\n\n"
        },
        {
            "text": "\n179696\nEfficacy and safety of linezolid in liver transplant patients.\n\nRadunz, S\n\nJuntermanns, B\n\nKaiser, GM\n\nTreckmann, J\n\nMathe, Z\n\nPaul, A\n\nSaner, FH\n\nBeiträge in Fachzeitschriften\nISI:000293658000004\n21355969.0\n10.1111/j.1399-3062.2011.00617.x\nNone\nBacterial infections are the main cause of death within the first year after liver transplantation, and the increased incidence of multidrug-resistant gram-positive pathogens has created a major challenge in the treatment of these patients. Linezolid, the first US Food & Drug Administration-approved oxazolidinone, offers a valuable novel treatment option for serious gram-positive infections. Linezolid is relatively non-toxic but prolonged treatment with linezolid was associated with thrombocytopenia. Here we report on the experience of linezolid treatment in adult liver transplant patients, who are at an increased risk for thrombocytopenia because of hypersplenism. From November 2003 until December 2009, we evaluated the clinical course of 46 liver transplant patients (27 male/19 female) in our surgical intensive care unit. For proven or probable gram-positive infection, all patients received linezolid 600 mg intravenously every 12 h. On clinical improvement, treatment was changed to oral linezolid 600 mg twice daily. Treatment duration was 11 ± 7 days. Treatment indications were pneumonia (n = 8), blood stream infection (n = 30), and surgical site/abdominal infection (n = 3). Clinical cure was achieved in 43 out of 46 patients. During the course of treatment, no cases of severe thrombocytopenia occurred and a statistically significant platelet count increase was seen from day 1 (110 ± 73/nL) to day 7 (165 ± 116/nL) and day 14 (180 ± 140/nL). We did not observe any further adverse events, especially no severe neurological complications (e.g., serotonin syndrome) or signs of lactate acidosis. Two patients died from uncontrolled vancomycin-resistant Enterococcus faecium sepsis with septic shock and one due to uncontrolled methicillin-resistant Staphylococcus aureus pneumonia. These deaths were considered to be unrelated to linezolid treatment, and linezolid was regarded as the optimal treatment choice in these patients. A subgroup analysis of patients treated for >14 days revealed no statistically significant differences when compared with patients on shorter treatment. In particular, no cases of thrombocytopenia occurred during longer treatment. In conclusion, linezolid is a safe and effective treatment for adult liver transplant patients with gram-positive infections.\n                © 2011 John Wiley & Sons A/S.\n\n\n"
        },
        {
            "text": "\n181151\nAlterations and test-retest reliability of functional connectivity network measures in cerebral small vessel disease.\n\nGesierich, B\n\nTuladhar, AM\n\nTer Telgte, A\n\nWiegertjes, K\n\nKonieczny, MJ\n\nFinsterwalder, S\n\nHübner, M\n\nPirpamer, L\n\nKoini, M\n\nAbdulkadir, A\n\nFranzmeier, N\n\nNorris, DG\n\nMarques, JP\n\nZu Eulenburg, P\n\nEwers, M\n\nSchmidt, R\n\nde Leeuw, FE\n\nDuering, M\n\nBeiträge in Fachzeitschriften\nISI:000540009000006\n32087047.0\n10.1002/hbm.24967\nPMC7294060\nWhile structural network analysis consolidated the hypothesis of cerebral small vessel disease (SVD) being a disconnection syndrome, little is known about functional changes on the level of brain networks. In patients with genetically defined SVD (CADASIL, n = 41) and sporadic SVD (n = 46), we independently tested the hypothesis that functional networks change with SVD burden and mediate the effect of disease burden on cognitive performance, in particular slowing of processing speed. We further determined test-retest reliability of functional network measures in sporadic SVD patients participating in a high-frequency (monthly) serial imaging study (RUN DMC-InTENse, median: 8 MRIs per participant). Functional networks for the whole brain and major subsystems (i.e., default mode network, DMN; fronto-parietal task control network, FPCN; visual network, VN; hand somatosensory-motor network, HSMN) were constructed based on resting-state multi-band functional MRI. In CADASIL, global efficiency (a graph metric capturing network integration) of the DMN was lower in patients with high disease burden (standardized beta = -.44; p [corrected] = .035) and mediated the negative effect of disease burden on processing speed (indirect path: std. beta = -.20, p = .047; direct path: std. beta = -.19, p = .25; total effect: std. beta = -.39, p = .02). The corresponding analyses in sporadic SVD showed no effect. Intraclass correlations in the high-frequency serial MRI dataset of the sporadic SVD patients revealed poor test-retest reliability and analysis of individual variability suggested an influence of age, but not disease burden, on global efficiency. In conclusion, our results suggest that changes in functional connectivity networks mediate the effect of SVD-related brain damage on cognitive deficits. However, limited reliability of functional network measures, possibly due to age-related comorbidities, impedes the analysis in elderly SVD patients.\n                © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.\n\nKoini, Marisa\n\nPirpamer, Lukas\n\nSchmidt, Reinhold\n\n\n"
        },
        {
            "text": "\n184255\nPrimary tumor and metastasis-sectioning the different steps of the metastatic cascade.\n\nPopper, H\n\nBeiträge in Fachzeitschriften\nISI:000582799700059\nNone\n10.21037/tlcr-20-175\nNone\nPatients with lung cancer in the majority die of metastases. Treatment options include surgery, chemo- and radiotherapy, targeted therapy by tyrosine kinase inhibitors (TKIs), and immuno-oncologic treatment. Despite the success with these treatment options, cure of lung cancer is achieved in only a very small proportion of patients. In most patients' recurrence and metastasis will occur, and finally kill the patient. Metastasis is a multistep procedure. It requires a change in adhesion of tumor cells for detachment from their neighboring cells. The next step is migration either as single cells [epithelial-mesenchymal transition (EMT)], or as cell clusters (hybrid-EMT or bulk migration). A combination of genetic changes is required to facilitate migration. Then tumor cells have to orient themselves along matrix proteins, detect oxygen concentrations, prevent attacks by immune cells, and induce a tumor-friendly switch of stroma cells (macrophages, myofibroblasts, etc.). Having entered the blood stream tumor cells need to adapt to shear stress, avoid being trapped by coagulation, but also use coagulation in small veins for adherence to endothelia, and express homing molecules for extravasation. Within a metastatic site, tumor cells need a well-prepared niche to establish a metastatic focus. Tumor cells again have to establish a vascular net for maintaining nutrition and oxygen supply, communicate with stroma cells, grow out and set further metastases. In this review the different steps will be discussed with a focus on pulmonary carcinomas. The vast amount of research manuscripts published so far are not easy to analyze: in most reports' single steps of the metastatic cascade are interpreted as evidence for the whole process; for example, migration is interpreted as evidence for metastasis. In lung cancer most often latency periods are shorter, in between 1-5 years. In other cases, despite widespread migration occurs, tumor cells die within the circulation and do not reach a metastatic site. Therefore, migration is a requisite, but does not necessarily predict metastasis. The intention of this review is to point to these different aspects and hopefully provoke research directed into a more functional analysis of the metastatic process.\n\nPopper, Helmuth\n\n\n"
        },
        {
            "text": "\n184538\nMyeloperoxidase-Derived 2-Chlorohexadecanal Is Generated in Mouse Heart during Endotoxemia and Induces Modification of Distinct Cardiomyocyte Protein Subsets In Vitro.\n\nPrasch, J\n\nBernhart, E\n\nReicher, H\n\nKollroser, M\n\nRechberger, GN\n\nKoyani, CN\n\nTrummer, C\n\nRech, L\n\nRainer, PP\n\nHammer, A\n\nMalle, E\n\nSattler, W\n\nBeiträge in Fachzeitschriften\nISI:000597518500001\n33287422.0\n10.3390/ijms21239235\nPMC7730634\nSepsis is a major cause of mortality in critically ill patients and associated with cardiac dysfunction, a complication linked to immunological and metabolic aberrations. Cardiac neutrophil infiltration and subsequent release of myeloperoxidase (MPO) leads to the formation of the oxidant hypochlorous acid (HOCl) that is able to chemically modify plasmalogens (ether-phospholipids) abundantly present in the heart. This reaction gives rise to the formation of reactive lipid species including aldehydes and chlorinated fatty acids. During the present study, we tested whether endotoxemia increases MPO-dependent lipid oxidation/modification in the mouse heart. In hearts of lipopolysaccharide-injected mice, we observed significantly higher infiltration of MPO-positive cells, increased fatty acid content, and formation of 2-chlorohexadecanal (2-ClHDA), an MPO-derived plasmalogen modification product. Using murine HL-1 cardiomyocytes as in vitro model, we show that exogenously added HOCl attacks the cellular plasmalogen pool and gives rise to the formation of 2-ClHDA. Addition of 2-ClHDA to HL-1 cardiomyocytes resulted in conversion to 2-chlorohexadecanoic acid and 2-chlorohexadecanol, indicating fatty aldehyde dehydrogenase-mediated redox metabolism. However, a recovery of only 40% indicated the formation of non-extractable (protein) adducts. To identify protein targets, we used a clickable alkynyl analog, 2-chlorohexadec-15-yn-1-al (2-ClHDyA). After Huisgen 1, -dipolar cycloaddition of 5-tetramethylrhodamine azide (N3-TAMRA) and two dimensional-gel electrophoresis (2D-GE), we were able to identify 51 proteins that form adducts with 2-ClHDyA. Gene ontology enrichment analyses revealed an overrepresentation of heat shock and chaperone, energy metabolism, and cytoskeletal proteins as major targets. Our observations in a murine endotoxemia model demonstrate formation of HOCl-modified lipids in the heart, while pathway analysis in vitro revealed that the chlorinated aldehyde targets specific protein subsets, which are central to cardiac function.\n\nBernhart, Eva Maria\n\nHammer, Astrid\n\nHinteregger, Helga\n\nKollroser, Manfred\n\nMalle, Ernst\n\nPrasch, Jürgen\n\nRainer, Peter\n\nRech, Cara Lavinia Shirin\n\nSattler, Wolfgang\n\nTrummer, Christopher\n\n\n"
        },
        {
            "text": "\n186649\nHospital admissions of acute cerebrovascular diseases during and after the first wave of the COVID-19 pandemic: a state-wide experience from Austria.\n\nGattringer, T\n\nFandler-Höfler, S\n\nKneihsl, M\n\nHofer, E\n\nKöle, W\n\nSchmidt, R\n\nTscheliessnigg, KH\n\nFrank, AM\n\nEnzinger, C\n\nBeiträge in Fachzeitschriften\nISI:000622676100002\n33641003.0\n10.1007/s00415-021-10488-8\nPMC7914046\nWe investigated hospital admission rates for the entire spectrum of acute cerebrovascular diseases and of recanalization treatments for ischaemic stroke (IS) in the Austrian federal state of Styria during and also after the first coronavirus disease 2019 (COVID-19) wave. We retrospectively identified all patients with transient ischaemic attack (TIA), IS and non-traumatic intracranial haemorrhage (ICH; including intracerebral, subdural and subarachnoid bleeding types) admitted to one of the 11 public hospitals in Styria (covering > 95% of inhospital cerebrovascular events in this region). Information was extracted from the electronic medical documentation network connecting all public Styrian hospitals. We analysed two periods of interest: (1) three peak months of the first COVID-19 wave (March-May 2020), and (2) three recovery months thereafter (June-August 2020), compared to respective periods 4 years prior (2016-2019) using Poisson regression. In the three peak months of the first COVID-19 wave, there was an overall decline in hospital admissions for acute cerebrovascular diseases (RR = 0.83, 95% CI 0.78-0.89, p < 0.001), which was significant for TIA (RR = 0.61, 95% CI 0.52-0.72, p < 0.001) and ICH (0.78, 95% CI 0.67-0.91, p = 0.02), but not for IS (RR = 0.93, 95% CI 0.85-1, p = 0.08). Thrombolysis and thrombectomy numbers were not different compared to respective months 4 years prior. In the recovery period after the first COVID-19 wave, TIA (RR = 0.82, 95% CI 0.71-0.96, p = 0.011) and ICH (RR = 0.86, 95% CI 0.74-0.99, p = 0.045) hospitalizations remained lower, while the frequency of IS and recanalization treatments was unchanged. In this state-wide analysis covering all types of acute cerebrovascular diseases, hospital admissions for TIA and ICH were reduced during and also after the first wave of the COVID-19 pandemic, but hospitalizations and recanalization treatments for IS were not affected in these two periods.\n\nEnzinger, Christian\n\nFandler-Höfler, Simon\n\nGattringer, Thomas\n\nHofer, Edith\n\nKneihsl, Markus\n\nKöle, Wolfgang\n\nSchmidt, Reinhold\n\n\n"
        },
        {
            "text": "\n187779\nIntact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias.\n\nThijssen, R\n\nDiepstraten, ST\n\nMoujalled, D\n\nChew, E\n\nFlensburg, C\n\nShi, MX\n\nDengler, MA\n\nLitalien, V\n\nMacRaild, S\n\nChen, M\n\nAnstee, NS\n\nReljić, B\n\nGabriel, SS\n\nDjajawi, TM\n\nRiffkin, CD\n\nAubrey, BJ\n\nChang, C\n\nTai, L\n\nXu, Z\n\nMorley, T\n\nPomilio, G\n\nBruedigam, C\n\nKallies, A\n\nStroud, DA\n\nBajel, A\n\nKluck, RM\n\nLane, SW\n\nSchoumacher, M\n\nBanquet, S\n\nMajewski, IJ\n\nStrasser, A\n\nRoberts, AW\n\nHuang, DCS\n\nBrown, FC\n\nKelly, GL\n\nWei, AH\n\nBeiträge in Fachzeitschriften\nNone\n33824975.0\n10.1182/blood.2020010167\nPMC8138548\nSelective targeting of BCL-2 with the BH3-mimetic venetoclax has been a transformative treatment for patients with various leukemias. TP-53 controls apoptosis upstream of where BCL-2 and its prosurvival relatives, such as MCL-1, act. Therefore, targeting these prosurvival proteins could trigger apoptosis across diverse blood cancers, irrespective of TP53 mutation status. Indeed, targeting BCL-2 has produced clinically relevant responses in blood cancers with aberrant TP-53. However, in our study, TP53-mutated or -deficient myeloid and lymphoid leukemias outcompeted isogenic controls with intact TP-53, unless sufficient concentrations of BH3-mimetics targeting BCL-2 or MCL-1 were applied. Strikingly, tumor cells with TP-53 dysfunction escaped and thrived over time if inhibition of BCL-2 or MCL-1 was sublethal, in part because of an increased threshold for BAX/BAK activation in these cells. Our study revealed the key role of TP-53 in shaping long-term responses to BH3-mimetic drugs and reconciled the disparate pattern of initial clinical response to venetoclax, followed by subsequent treatment failure among patients with TP53-mutant chronic lymphocytic leukemia or acute myeloid leukemia. In contrast to BH3-mimetics targeting just BCL-2 or MCL-1 at doses that are individually sublethal, a combined BH3-mimetic approach targeting both prosurvival proteins enhanced lethality and durably suppressed the leukemia burden, regardless of TP53 mutation status. Our findings highlight the importance of using sufficiently lethal treatment strategies to maximize outcomes of patients with TP53-mutant disease. In addition, our findings caution against use of sublethal BH3-mimetic drug regimens that may enhance the risk of disease progression driven by emergent TP53-mutant clones.\n                © 2021 by The American Society of Hematology.\n\nDengler, Michael Andreas\n\n\n"
        }
    ]
}