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"text": "\n67126\nFactors influencing the complication rate of subduroperitoneal shunt placement for the treatment of subdural hematomas in infants.\n\nKurschel, S\n\nPuget, S\n\nBourgeois, M\n\nZerah, M\n\nOfner, P\n\nRenier, D\n\nBeiträge in Fachzeitschriften\nISI:000244952700002\n17465380.0\n10.3171/ped.2007.106.3.172\nNone\nOBJECT: In this study the authors' goal was to identify the complication rate of subduroperitoneal (SDP) shunts for the treatment of subdural hematomas (SDHs) in infants and to determine the influences on and predictive factors for these complications. METHODS: The authors present a case series spanning the years 1994 to 2003 and include a statistical analysis of 161 children 2 years of age or younger with SDH who were treated using a unilateral valveless SDP shunt. The patient history, characteristics, and treatment methods including prior therapies, neuroimaging findings, and clinical outcomes were measures of evaluation. Thirty-six children (22.4%) suffered complications related to SDP shunts: obstruction in 27 (16.8%), infections in eight (5%), disconnection in four (2.5%), migration in three (1.9%), wound complications (leakage and skin ulceration) in two (1.2%), and symptomatic subdural rebleeding in one (0.6%) necessitating bur hole evacuation. Seventeen children (10.6%) underwent placement of a second SDP shunt because of ipsilateral or contralateral persistent fluid collections, or premature shunt removal. With the exception of 12 patients (7.4%), shunt removal was performed systematically and resulted in the following minor complications in 30 children (18.6%): an adherent proximal catheter in 16 (9.9%), transient symptoms of intracranial hypertension in six (3.7%), subcutaneous cerebrospinal fluid accumulation in four (2.5%), local infections in three (1.9%), and hydrocephalus requiring placement of a ventriculoperitoneal shunt in one (0.6%). Status epilepticus at presentation and neuroimaging findings such as areas of hyperdensity on computed tomography (CT) scans representing fresh blood in the subdural fluid collections before shunt insertion and at follow up were predictors of shunt-related complications. Correlations were also discovered for the following CT findings: ischemic lesions before shunt treatment, cerebral atrophy and ventricular dilation during the last follow up, and residual medium to large collections before shunt removal. Children who attained a good outcome were less affected by shunt-related complications, unlike those who presented with focal deficits and/or visual impairment. CONCLUSIONS: Subduroperitoneal shunt placement for the treatment of SDH in infants is--despite the complication rate--an effective and often inevitable treatment option, especially for most large and symptomatic SDHs; a certain number of complications could be reduced with careful and precise surgical techniques. Close observation for detection of risks is mandatory, and seizure control is essential to prevent further brain injury that may result in large subdural fluid collections that are difficult to treat.\n\nKurschel, Senta\n\nOfner-Kopeinig, Petra\n\n\n"
},
{
"text": "\n141047\nCerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial.\n\nHyttel-Sorensen, S\n\nPellicer, A\n\nAlderliesten, T\n\nAustin, T\n\nvan Bel, F\n\nBenders, M\n\nClaris, O\n\nDempsey, E\n\nFranz, AR\n\nFumagalli, M\n\nGluud, C\n\nGrevstad, B\n\nHagmann, C\n\nLemmers, P\n\nvan Oeveren, W\n\nPichler, G\n\nPlomgaard, AM\n\nRiera, J\n\nSanchez, L\n\nWinkel, P\n\nWolf, M\n\nGreisen, G\n\nBeiträge in Fachzeitschriften\nISI:000348129900002\n25569128.0\n10.1136/bmj.g7635\nPMC4283997\nTo determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry.\n Phase II randomised, single blinded, parallel clinical trial.\n Eight tertiary neonatal intensive care units in eight European countries.\n 166 extremely preterm infants born before 28 weeks of gestation: 86 were randomised to cerebral NIRS monitoring and 80 to blinded NIRS monitoring. The only exclusion criterion was a decision not to provide life support.\n Monitoring of cerebral oxygenation using NIRS in combination with a dedicated treatment guideline during the first 72 hours of life (experimental) compared with blinded NIRS oxygenation monitoring with standard care (control).\n The primary outcome measure was the time spent outside the target range of 55-85% for cerebral oxygenation multiplied by the mean absolute deviation, expressed in %hours (burden of hypoxia and hyperoxia). One hour with an oxygenation of 50% gives 5%hours of hypoxia. Secondary outcomes were all cause mortality at term equivalent age and a brain injury score assessed by cerebral ultrasonography.\n Allocation sequence 1:1 with block sizes 4 and 6 in random order concealed for the investigators. The allocation was stratified for gestational age (<26 weeks or ≥ 26 weeks).\n Cerebral oxygenation measurements were blinded in the control group. All outcome assessors were blinded to group allocation.\n The 86 infants randomised to the NIRS group had a median burden of hypoxia and hyperoxia of 36.1%hours (interquartile range 9.2-79.5%hours) compared with 81.3 (38.5-181.3) %hours in the control group, a reduction of 58% (95% confidence interval 35% to 73%, P<0.001). In the experimental group the median burden of hypoxia was 16.6 (interquartile range 5.4-68.1) %hours, compared with 53.6 (17.4-171.3) %hours in the control group (P=0.0012). The median burden of hyperoxia was similar between the groups: 1.2 (interquartile range 0.3-9.6) %hours in the experimental group compared with 1.1 (0.1-23.4) %hours in the control group (P=0.98). We found no statistically significant differences between the two groups at term corrected age. No severe adverse reactions were associated with the device.\n Cerebral oxygenation was stabilised in extremely preterm infants using a dedicated treatment guideline in combination with cerebral NIRS monitoring.Trial registration ClinicalTrial.gov NCT01590316.\n © Hyttel-Sorensen et al 2015.\n\nPichler, Gerhard\n\n\n"
},
{
"text": "\n142861\nHirschsprung's disease associated with Down syndrome: a meta-analysis of incidence, functional outcomes and mortality.\n\nFriedmacher, F\n\nPuri, P\n\nBeiträge in Fachzeitschriften\nISI:000323542000011\n23943251.0\n10.1007/s00383-013-3361-1\nNone\nDown syndrome (DS) is the most frequent chromosomal abnormality associated with Hirschsprung's disease (HD). It has often been suggested that this association results in poorer outcomes with regard to postoperative complications, continence and mortality. On the other hand, the results after surgical treatment of HD in patients with DS are reportedly similar to those in cases with HD alone. The objective of this study was to determine the incidence of DS in cohorts with HD, and to compare pre-/postoperative complications, functional outcome and mortality between cohorts with and without coexisting DS.\n A systematic literature-based search for relevant cohorts was conducted using multiple online databases. The number of DS cases in HD cohorts was recorded and data on pre-/postoperative complications, functional outcome and mortality were extracted. Pooled odds ratios with 95% confidence intervals were calculated using meta-analysis methodology.\n Sixty-one articles met defined inclusion criteria, comprising data from 16, 97 patients with HD. The overall incidence of DS among them was 7.32%. Vice versa, the incidence of HD in 29, 18 patients with DS was 2.62%. There were no significant differences regarding the male-to-female ratio between cohorts with and without coexisting DS (4:1 vs. 3:1 respectively; P = 0.5376). The rate of additional comorbidities was significantly higher in HD associated with DS (P < 0.0001). Recto-sigmoid HD was in both cohorts the most common type of HD (P = 0.8231). Long-segment HD was significantly more frequent in HD with coexisting DS (P = 0.0267), while total colonic aganglionosis occurred significantly more often in HD without DS (P = 0.0003). There were no significant differences in preoperative constipation/obstruction (P = 0.5967), but the rate of preoperative enterocolitis was significantly higher in HD associated with DS (P = 0.0486). Postoperative complications such as recurrent enterocolitis (P = 0.0112) and soiling (P = 0.0002) were significantly more frequent in HD with coexisting DS. Although not statistically significant, fecal incontinence (P = 0.1014) and persistent constipation (P = 0.1670) occurred more often after surgical treatment of HD with DS. The mortality rate was significantly higher in HD associated with DS (P < 0.0001).\n The association of HD with DS is well-recognized with an incidence of 7.32%. A large number of patients with DS continue to have persistent bowel dysfunction after surgical treatment of HD. Our data provide strong evidence that the coexistence of HD and DS is associated with higher rates of pre-/postoperative enterocolitis, poorer functional outcomes and increased mortality.\n\n\n"
},
{
"text": "\n154961\nGenetic variants in CETP increase risk of intracerebral hemorrhage.\n\nAnderson, CD\n\nFalcone, GJ\n\nPhuah, CL\n\nRadmanesh, F\n\nBrouwers, HB\n\nBattey, TW\n\nBiffi, A\n\nPeloso, GM\n\nLiu, DJ\n\nAyres, AM\n\nGoldstein, JN\n\nViswanathan, A\n\nGreenberg, SM\n\nSelim, M\n\nMeschia, JF\n\nBrown, DL\n\nWorrall, BB\n\nSilliman, SL\n\nTirschwell, DL\n\nFlaherty, ML\n\nKraft, P\n\nJagiella, JM\n\nSchmidt, H\n\nHansen, BM\n\nJimenez-Conde, J\n\nGiralt-Steinhauer, E\n\nElosua, R\n\nCuadrado-Godia, E\n\nSoriano, C\n\nvan Nieuwenhuizen, KM\n\nKlijn, CJ\n\nRannikmae, K\n\nSamarasekera, N\n\nAl-Shahi Salman, R\n\nSudlow, CL\n\nDeary, IJ\n\nMorotti, A\n\nPezzini, A\n\nPera, J\n\nUrbanik, A\n\nPichler, A\n\nEnzinger, C\n\nNorrving, B\n\nMontaner, J\n\nFernandez-Cadenas, I\n\nDelgado, P\n\nRoquer, J\n\nLindgren, A\n\nSlowik, A\n\nSchmidt, R\n\nKidwell, CS\n\nKittner, SJ\n\nWaddy, SP\n\nLangefeld, CD\n\nAbecasis, G\n\nWiller, CJ\n\nKathiresan, S\n\nWoo, D\n\nRosand, J\n\nGlobal Lipids Genetics Consortium and International Stroke Genetics Consortium\n\nBeiträge in Fachzeitschriften\nISI:000388570800010\n27717122.0\n10.1002/ana.24780\nPMC5115931\nIn observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH.\n We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1, 49 ICH cases and 1, 38 controls from 3 studies, followed by replication in 1, 25 cases and 1, 45 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk.\n Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10-4 ) with no heterogeneity across studies (I2 = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10-6 ).\n Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.\n © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.\n\nEnzinger, Christian\n\nPichler, Alexander\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n157966\nTopical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial.\n\nSchwameis, M\n\nKündig, T\n\nHuber, G\n\nvon Bidder, L\n\nMeinel, L\n\nWeisser, R\n\nAberer, E\n\nHärter, G\n\nWeinke, T\n\nJelinek, T\n\nFätkenheuer, G\n\nWollina, U\n\nBurchard, GD\n\nAschoff, R\n\nNischik, R\n\nSattler, G\n\nPopp, G\n\nLotte, W\n\nWiechert, D\n\nEder, G\n\nMaus, O\n\nStaubach-Renz, P\n\nGräfe, A\n\nGeigenberger, V\n\nNaudts, I\n\nSebastian, M\n\nReider, N\n\nWeber, R\n\nHeckmann, M\n\nReisinger, EC\n\nKlein, G\n\nWantzen, J\n\nJilma, B\n\nBeiträge in Fachzeitschriften\nISI:000394732600041\n28007428.0\n10.1016/S1473-3099(16)30529-1\nNone\nLyme borreliosis develops in 1-5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings.\n In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39.\n Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42-2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0·87), and most adverse events were mild.\n Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks.\n Ixodes AG.\n Copyright © 2017 Elsevier Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n185167\nComposite Measures of Physical Fitness to Discriminate Between Healthy Aging and Heart Failure: The COmPLETE Study.\n\nWagner, J\n\nKnaier, R\n\nKönigstein, K\n\nKlenk, C\n\nCarrard, J\n\nLichtenstein, E\n\nScharnagl, H\n\nMärz, W\n\nHanssen, H\n\nHinrichs, T\n\nSchmidt-Trucksäss, A\n\nArbeev, K\n\nBeiträge in Fachzeitschriften\nISI:000603007100001\n33384610.0\n10.3389/fphys.2020.596240\nPMC7770139\nAging and changing age demographics represent critical problems of our time. Physiological functions decline with age, often ending in a systemic process that contributes to numerous impairments and age-related diseases including heart failure (HF). We aimed to analyze whether differences in composite measures of physiological function [health distance (HD)], specifically physical fitness, between healthy individuals and patients with HF, can be observed.\n The COmPLETE Project is a cross-sectional study of 526 healthy participants aged 20-91 years and 79 patients with stable HF. Fifty-nine biomarkers characterizing fitness (cardiovascular endurance, muscle strength, and neuromuscular coordination) and general health were assessed. We computed HDs as the Mahalanobis distance for vectors of biomarkers (all and domain-specific subsets) that quantified deviations of individuals' biomarker profiles from "optimums" in the "reference population" (healthy participants aged <40 years). We fitted linear regressions with HD outcomes and disease status (HF/Healthy) and relevant covariates as predictors and logistic regressions for the disease outcome and sex, age, and age2 as covariates in the base model and the same covariates plus combinations of one or two HDs.\n Nine out of 10 calculated HDs showed evidence for group differences between Healthy and HF (p ≤ 0.002) and most models presented a negative estimate of the interaction term age by group (p < 0.05 for eight HDs). The predictive performance of the base model for HF cases significantly increased by adding HD General health or HD Fitness [areas under the receiver operating characteristic (ROC) curve (AUCs) 0.63, 0.89, and 0.84, respectively]. HD Cardiovascular endurance alone reached an AUC of 0.88. Further, there is evidence that the combination of HDs Cardiovascular endurance and General health shows superior predictive power compared to single HDs.\n HD composed of physical fitness biomarkers differed between healthy individuals and patients with HF, and differences between groups diminished with increasing age. HDs can successfully predict HF cases, and HD Cardiovascular endurance can significantly increase the predictive power beyond classic clinical biomarkers. Applications of HD could strengthen a comprehensive assessment of physical fitness and may present an optimal target for interventions to slow the decline of physical fitness with aging and, therefore, to increase health span.\n Copyright © 2020 Wagner, Knaier, Königstein, Klenk, Carrard, Lichtenstein, Scharnagl, März, Hanssen, Hinrichs, Schmidt-Trucksäss and Arbeev.\n\nMärz, Winfried\n\nScharnagl, Hubert\n\n\n"
},
{
"text": "\n151517\nGenome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).\n\nIyengar, SK\n\nSedor, JR\n\nFreedman, BI\n\nKao, WH\n\nKretzler, M\n\nKeller, BJ\n\nAbboud, HE\n\nAdler, SG\n\nBest, LG\n\nBowden, DW\n\nBurlock, A\n\nChen, YD\n\nCole, SA\n\nComeau, ME\n\nCurtis, JM\n\nDivers, J\n\nDrechsler, C\n\nDuggirala, R\n\nElston, RC\n\nGuo, X\n\nHuang, H\n\nHoffmann, MM\n\nHoward, BV\n\nIpp, E\n\nKimmel, PL\n\nKlag, MJ\n\nKnowler, WC\n\nKohn, OF\n\nLeak, TS\n\nLeehey, DJ\n\nLi, M\n\nMalhotra, A\n\nMärz, W\n\nNair, V\n\nNelson, RG\n\nNicholas, SB\n\nO'Brien, SJ\n\nPahl, MV\n\nParekh, RS\n\nPezzolesi, MG\n\nRasooly, RS\n\nRotimi, CN\n\nRotter, JI\n\nSchelling, JR\n\nSeldin, MF\n\nShah, VO\n\nSmiles, AM\n\nSmith, MW\n\nTaylor, KD\n\nThameem, F\n\nThornley-Brown, DP\n\nTruitt, BJ\n\nWanner, C\n\nWeil, EJ\n\nWinkler, CA\n\nZager, PG\n\nIgo, RP\n\nHanson, RL\n\nLangefeld, CD\n\nFamily Investigation of Nephropathy and Diabetes (FIND)\n\nBeiträge in Fachzeitschriften\nISI:000360823100004\n26305897.0\n10.1371/journal.pgen.1005352\nPMC4549309\nDiabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6, 97 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7, 39 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n187335\nPembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer.\n\nGandhi, L\n\nRodríguez-Abreu, D\n\nGadgeel, S\n\nEsteban, E\n\nFelip, E\n\nDe Angelis, F\n\nDomine, M\n\nClingan, P\n\nHochmair, MJ\n\nPowell, SF\n\nCheng, SY\n\nBischoff, HG\n\nPeled, N\n\nGrossi, F\n\nJennens, RR\n\nReck, M\n\nHui, R\n\nGaron, EB\n\nBoyer, M\n\nRubio-Viqueira, B\n\nNovello, S\n\nKurata, T\n\nGray, JE\n\nVida, J\n\nWei, Z\n\nYang, J\n\nRaftopoulos, H\n\nPietanza, MC\n\nGarassino, MC\n\nKEYNOTE-189 Investigators\n\nBeiträge in Fachzeitschriften\nNone\n29658856.0\n10.1056/NEJMoa1801005\nNone\nFirst-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial.\n In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression. The primary end points were overall survival and progression-free survival, as assessed by blinded, independent central radiologic review.\n After a median follow-up of 10.5 months, the estimated rate of overall survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in the pembrolizumab-combination group versus 49.4% (95% CI, 42.1 to 56.2) in the placebo-combination group (hazard ratio for death, 0.49; 95% CI, 0.38 to 0.64; P<0.001). Improvement in overall survival was seen across all PD-L1 categories that were evaluated. Median progression-free survival was 8.8 months (95% CI, 7.6 to 9.2) in the pembrolizumab-combination group and 4.9 months (95% CI, 4.7 to 5.5) in the placebo-combination group (hazard ratio for disease progression or death, 0.52; 95% CI, 0.43 to 0.64; P<0.001). Adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group.\n In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck; KEYNOTE-189 ClinicalTrials.gov number, NCT02578680 .).\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n832\nEffect of postural changes on the reliability of volume estimations from bioimpedance spectroscopy data.\n\nScharfetter, H\n\nMonif, M\n\nLászló, Z\n\nLambauer, T\n\nHutten, H\n\nHinghofer-Szalkay, H\n\nBeiträge in Fachzeitschriften\nISI:A1997WP69600012\n9083273.0\n10.1038/ki.1997.150\nNone\nBioimpedance spectroscopy (BIS) has been suggested for the assessment of fluid shifts between intracellular (ICV) and extracellular volume (ECV) during dialysis. The electrical tissue parameters are estimated by fitting a Cole-Cole model to the impedance data. Those parameters are used for the calculation of ICV and ECV with a fluid distribution model (FDM). We investigated whether postural changes cause artifacts in the volume data measured with a commercial BIS system. This is of importance at the beginning of dialysis, when the patient lies down for treatment. Volume estimations were performed during tilt table experiments with 11 healthy volunteers. Impedance spectra (5 to 500 kHz) were recorded for the total body as well as for body segments (leg and arm) during three phases: (1) 30 minutes resting in a supine position after standing; (2) 30 minutes 70 degrees head up tilt; and (3) a 30-minute resting period in a supine position. ECV and ICV were estimated with a commercially utilized FDM which is based on Hanai's mixture theory. A monoexponential function was fitted to the data for extracting the time constants and the extrapolated steady state values of the volume changes. The ECV and ICV data changed significantly during all three periods, that is, a steady state could not be reached within 30 minutes. During phase 1 the ECV decreased by 1.8 +/- 0.7%, in the tilt phase it increased by 3.8 +/- 1.1%, and in phase 3 it decreased again by 2.9 +/- 1%. The ICV increased by 3.6 +/- 2.4% during phase 1 and decreased by 6.8 +/- 5.1% during tilting; in phase 3 it increased by 4.6 +/- 1.7%. The time constants were 36.4 +/- 12.7 minutes (ECV) and 10.8 +/- 5.4 minutes (ICV) during phase 3. Segmental measurements revealed that the legs contribute significantly to the measured volume changes. The absolute volume changes in ICV and ECV differed significantly in all phases, and the same was found for the time constants during phases 1 and 3. From this discrepancy it is concluded that the measured volume changes are artifacts that are caused by extracellular fluid redistribution. Furthermore, it appears unlikely that the measured fluid shifts actually occur between ECV and ICV in the absence of osmotic changes in the body fluids. The validity of the method for a reliable assessment of volume changes during dialysis appears questionable, as dialysis-induced volume changes lie in the same range as the orthostatically-induced spurious volume changes.\n\nHinghofer-Szalkay, Helmut\n\n\n"
},
{
"text": "\n17988\nAnalysis of the prognostic impact of tumor embolization before definitive radiotherapy for cervical carcinoma.\n\nKapp, KS\n\nPoschauko, J\n\nTauss, J\n\nBerghold, A\n\nOechs, A\n\nLahousen, M\n\nPetru, E\n\nWinter, R\n\nKapp, DS\n\nBeiträge in Fachzeitschriften\nISI:000230767300020\n16029799.0\n10.1016/j.ijrobp.2004.12.037\nNone\nTo assess whether embolization compromises the radiocurability of primary cervical cancer.\n Two hundred fifty-four patients with primary cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] stages IB: 47; II: 91; IIIB: 102; IV: 14) were treated with external beam irradiation and Ir-192 high-dose-rate brachytherapy over a period of 15 years. Of these, 24 patients (9.4%) (FIGO stages IB: 1; II: 8; IIIB: 12; IV: 3) had had bilateral embolization of the internal iliac arteries before referral. The median age of the entire cohort was 66 years (range, 34-85 years). Tumor size was >5 cm and paraortic nodes were enlarged (> or =1 cm) on pretreatment CAT scan in 39.4% and 9.1% of patients, respectively. All patients with hemoglobin levels (hb-l) < or =11 g/dL (28.3%) received packed red cell transfusions (PRCT) before and/or during radiotherapy in an attempt to maintain levels >11 g/dL throughout treatment. Cross-table tests were used to compare the distribution of FIGO stage, tumor size, lymph node status, and pretreatment and treatment hb-l of embolized and nonembolized patients. The impact of embolization, along with the above-listed tumor characteristics, on disease-specific survival (DSS), pelvic control (PC), and distant metastases-free survival (MFS) was determined by univariate and multivariate analyses.\n Embolized patients presented at a statistically significant younger median age (55 vs. 67 years; p = 0.003), with larger tumors (66.7% vs. 36.5%; p = 0.007), and lower pretreatment hb-l (75% vs. 23.5%; p < 0.001) than nonembolized patients. There was no significant difference in stage distribution or lymph node status, and although embolized patients responded better to PRCT (50% vs. 29.6%), this difference was not statistically significant. Univariate analysis showed a trend toward decreased DSS (p = 0.09) and PC (p = 0.07) for embolized patients but no effect on MFS, whereas all other variables tested were significantly correlated with DSS, PC, and MFS (all p < 0.001). In the multivariate model, tumor embolization, FIGO stage, and pretreatment hb-l ceased to impact significantly on outcome. Tumor size remained the most powerful independent predictor for all endpoints tested, followed by treatment hb-l. Paraortic node status was significantly correlated with DSS and MFS.\n Although a trend toward poorer DSS and PC was observed in embolized patients, no impact on radiocurability could be demonstrated in multivariate analysis after controlling for the major tumor characteristics and treatment hb-l.\n\nBerghold, Andrea\n\nPetru, Edgar\n\n\n"
},
{
"text": "\n113483\nPhotodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo.\n\nDirschka, T\n\nRadny, P\n\nDominicus, R\n\nMensing, H\n\nBrüning, H\n\nJenne, L\n\nKarl, L\n\nSebastian, M\n\nOster-Schmidt, C\n\nKlövekorn, W\n\nReinhold, U\n\nTanner, M\n\nGröne, D\n\nDeichmann, M\n\nSimon, M\n\nHübinger, F\n\nHofbauer, G\n\nKrähn-Senftleben, G\n\nBorrosch, F\n\nReich, K\n\nBerking, C\n\nWolf, P\n\nLehmann, P\n\nMoers-Carpi, M\n\nHönigsmann, H\n\nWernicke-Panten, K\n\nHelwig, C\n\nFoguet, M\n\nSchmitz, B\n\nLübbert, H\n\nSzeimies, RM\n\nAK-CT002 Study Group\n\nBeiträge in Fachzeitschriften\nISI:000300695900050\n21910711.0\n10.1111/j.1365-2133.2011.10613.x\nNone\nBACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) or its methylester [methyl-5-aminolaevulinate (MAL) or 5-amino-4-oxopentanoate] was recently ranked as first-line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF-200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration. OBJECTIVES: To evaluate the efficacy and safety of PDT of AKs with BF-200 ALA in comparison with a registered MAL cream and with placebo. METHODS: The study was performed as a randomized, multicentre, observer-blind, placebo-controlled, interindividual trial with BF-200 ALA, a registered MAL cream and placebo in a ratio of 3:3:1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3months after treatment, PDT was repeated. Results: PDT with BF-200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P<0·0001) and lesion complete clearance rate (90·4% vs. 37·1%) at 3months after the last PDT. Moreover, superiority was demonstrated over the MAL cream regarding the primary endpoint patient complete clearance (78·2% vs. 64·2%; P<0·05). Significant differences in the patient and lesion complete clearance rates and severity of treatment-related adverse events were observed for the narrow- and broad-spectrum light sources. CONCLUSIONS: BF-200 ALA is a very effective, well-tolerated new formulation for AK treatment with PDT and is superior to a registered MAL medication. Efficacies and adverse events vary greatly with the different light sources used. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.\n\nWolf, Peter\n\n\n"
},
{
"text": "\n149766\nThe Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Studies: Design and Baseline Characteristics: ProgStar Report No. 1.\n\nStrauss, RW\n\nHo, A\n\nMuñoz, B\n\nCideciyan, AV\n\nSahel, JA\n\nSunness, JS\n\nBirch, DG\n\nBernstein, PS\n\nMichaelides, M\n\nTraboulsi, EI\n\nZrenner, E\n\nSadda, S\n\nErvin, AM\n\nWest, S\n\nScholl, HP\n\nProgression of Stargardt Disease Study Group\n\nBeiträge in Fachzeitschriften\nISI:000372718300026\n26786511.0\n10.1016/j.ophtha.2015.12.009\nNone\nTo describe the design and baseline characteristics of patients enrolled into 2 natural history studies of Stargardt disease (STGD1).\n Multicenter retrospective and prospective cohort studies.\n Three hundred sixty-five unique patients aged 6 years and older at baseline harboring disease-causing variants in the ABCA4 gene and with specified ocular lesions were enrolled from 9 centers in the United States and Europe.\n In the retrospective study, patients contributed medical record data from at least 2 and up to 4 visits for at least 1 examination modality: fundus autofluorescence (FAF), spectral-domain (SD) optical coherence tomography (SD OCT), and/or microperimetry (MP). The total observational period was at least 2 years and up to 5 years between single visits. Demographic and visual acuity (VA) data also were obtained. In the prospective study, eligible patients were examined at baseline using a standard protocol, with 6-month follow-up visits planned for a 2-year period for serial Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected VA, SD OCT, FAF, and MP.\n Design and rationale of a multicenter study to determine the progression of STGD1 in 2 large retrospective and prospective international cohorts. Detailed baseline characteristics of both cohorts are presented, including demographics, and structural and functional retinal metrics.\n Into the retrospective study, 251 patients (458 eyes) were enrolled; mean follow-up ± standard deviation was 3.9±1.6 years. At baseline, 36% had no or mild VA loss, and 47% of the study eyes had areas of definitely decreased autofluorescence (DDAF) with an average lesion area of 2.5±2.9 mm(2) (range, 0.02-16.03 mm(2)). Two hundred fifty-nine patients (489 eyes) were enrolled in the prospective study. At baseline, 20% had no or mild VA loss, and 64% had areas of DDAF with an average lesion area of 4.0±4.4 mm(2) (range, 0.03-24.24 mm(2)). The mean retinal sensitivity with MP was 10.8±5.0 dB.\n The ProgStar cohorts have baseline characteristics that encompass a wide range of disease severity and are expected to provide valuable data on progression based on serial quantitative measurements derived from multiple methods, which will be critical to the design of planned clinical trials.\n Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.\n\nStrauß, Rupert\n\n\n"
},
{
"text": "\n159816\nPressure Ulcer Prevalence and Care in Indonesian Hospitals: A Multicenter, Cross-sectional Evaluation Using an Extended Donabedian Model.\n\nAmir, Y\n\nTan, FE\n\nHalfens, R\n\nLohrmann, C\n\nSchols, J\n\nBeiträge in Fachzeitschriften\nISI:000397247900001\n28267680.0\nNone\nNone\nAlthough the number of studies on pressure ulcer (PU) occurrence continues to grow, research regarding the quality of PU care and its effect on outcomes is limited. Using an extended Donabedian model, a 1-day, multicenter, cross-sectional evaluation of the quality of PU care was conducted in a convenience sample of Indonesian hospitals among patients ≥18 years of age in the medical, surgical, and intensive care units. Structure (ie, hospital attributes), process (recommended PU preventive measures), and outcome indicators (nosocomial PU prevalence excluding nonblanchable erythema), along with patient characteristics (age, gender, ethnicity, admission days, diseases [per ICD-10], recent surgery, PU categorization [4 categories according to National Pressure Ulcer Advisory Panel-European Pressure Ulcer Advisory Panel guidelines], PU history, care dependency, and Braden score) were examined. Patient data were collected by 2 nurses -1 from the patient's unit and 1 from another unit - using the Landelijke Prevalentiemeting Zorgproblemen-International questionnaire, a paper-and-pencil survey translated into Indonesian. Heads of wards and nursing units completed the questionnaires at institutional and ward levels, respectively. The data were analyzed using descriptive and bivariate analyses, and multilevel logistic regression modeling was applied according to the generalized estimating equation approach. Among the 4 participating hospitals, 66 care units, 36 pairs of nurses, and 1132 adult patients (mean age 48.7 ± 17.4 years, 40.9% women) were involved. Ninety-one (91) patients developed 1 or more PUs; the nosocomial PU prevalence (excluding nonblanchable erythema, category I) was 3.6%. The most frequently used PU preventive measures were patient education (329, 29.1%), repositioning (269, 23.8%), and skin moisturizing (266, 23.5%). The factors most associated with nosocomial PU rate excluding category I were the inclusion of PU care in patient care files (P = .001), repositioning (P = .002), skin moisturizing (P = .009), age (P = .013), admission days (P = .001), care dependency scores (P = .047), immobility (P = .001), sensory perception limitation (P = .001), moist skin (P = .032, OR 13.74), and friction and shear problem (P = .001). The prevalence of nosocomial PUs in this study was comparable to previous research in the Netherlands and rather low, even though limited structural indicators and suboptimal preventive measures were noted. Also, outdated preventive measures such as massage, donuts, and water-filled gloves were still used. The quality of PU care in these hospitals may be improved by addressing the absence of structural factors, including protocols/guidelines. Future research is needed for guideline implementation programs in Indonesian hospitals.\n\nLohrmann, Christa\n\n\n"
},
{
"text": "\n184519\nQS ENDO Real - A Study by the German Endometriosis Research Foundation (SEF) on the Reality of Care for Patients with Endometriosis in Germany, Austria and Switzerland.\n\nZeppernick, F\n\nZeppernick, M\n\nJanschek, E\n\nWölfler, M\n\nBornemann, S\n\nHoltmann, L\n\nOehmke, F\n\nBrandes, I\n\nScheible, CM\n\nSalehin, D\n\nPethick, SV\n\nBoosz, AS\n\nKrämer, B\n\nSillem, M\n\nBühler, K\n\nKeckstein, J\n\nSchweppe, KW\n\nMeinhold-Heerlein, I\n\nQS Endo Working Group of the Endometriosis Research Foundation (SEF)\n\nBeiträge in Fachzeitschriften\nISI:000518008600019\n32109970.0\n10.1055/a-1068-9260\nPMC7035138\nEndometriosis affects a significant number of young premenopausal women. Quite apart from the medical challenges, endometriosis is a relevant burden for healthcare and social security systems. Standardized quality indicators for the treatment of endometriosis have not previously been systematically verified. The three-stage study QS ENDO was initiated to record and improve the reality and quality of care. One of its aims is to create quality indicators for the diagnosis and treatment of endometriosis. For the first stage of QS ENDO Real, letters were sent to all 1014 gynecological departments in the German-speaking area of Europe (the DACH region) which included a questionnaire as a means of surveying the current state of care. A total of 296 (29.2%) of the centers which received the questionnaire participated in the survey. The subsequent evaluation of the completed questionnaires showed that the majority of patients with endometriosis (around 60%, based on estimates from the data) are not treated in hospitals which have been certified by the SEF. The guidelines recommend the use of specific classification systems (rASRM, ENZIAN) but, depending on the level of care offered by the hospital, only around 44.4 to 66.4% of departments used the rASRM score and only 27% of hospitals used the ENZIAN classification system to describe deep-infiltrating endometriosis. When taking patients' medical history, some centers (6.6 - 17.9%) considered questions about leading symptoms such as dyschezia, dysuria and dyspareunia to be unimportant. QS ENDO Real has made it possible, for the first time, to get an overview of the reality of care provided to patients with endometriosis in the German-speaking areas of Europe. The findings indicate that several of the measures recommended in international guidelines as the gold standard of care are only used to treat some of the patients. In this respect, more efforts will be needed to provide more advanced training. The approach used for treatment must be guideline-based, also in not-certified centers, to improve the quality of care in the treatment of patients with endometriosis.\n\nWölfler, Monika Martina\n\n\n"
},
{
"text": "\n185296\nCardiopulmonary Resuscitation of Asystolic Newborn Lambs Prior to Umbilical Cord Clamping; the Timing of Cord Clamping Matters!\n\nPolglase, GR\n\nSchmölzer, GM\n\nRoberts, CT\n\nBlank, DA\n\nBadurdeen, S\n\nCrossley, KJ\n\nMiller, SL\n\nStojanovska, V\n\nGalinsky, R\n\nKluckow, M\n\nGill, AW\n\nHooper, SB\n\nBeiträge in Fachzeitschriften\nNone\n32848852.0\n10.3389/fphys.2020.00902\nPMC7406709\nBackground: Current guidelines recommend immediate umbilical cord clamping (UCC) for newborns requiring chest compressions (CCs). Physiological-based cord clamping (PBCC), defined as delaying UCC until after lung aeration, has advantages over immediate UCC in mildly asphyxiated newborns, but its efficacy in asystolic newborns requiring CC is unknown. The aim of this study was to compare the cardiovascular response to CCs given prior to or after UCC in asystolic near-term lambs. Methods: Umbilical, carotid, pulmonary, and femoral arterial flows and pressures as well as systemic and cerebral oxygenation were measured in near-term sheep fetuses [139 ± 2 (SD) days gestation]. Fetal asphyxia was induced until asystole ensued, whereupon lambs received ventilation and CC before (PBCC; n = 16) or after (n = 12) UCC. Epinephrine was administered 1 min after ventilation onset and in 3-min intervals thereafter. The PBCC group was further separated into UCC at either 1 min (PBCC1, n = 8) or 10 min (PBCC10, n = 8) after return of spontaneous circulation (ROSC). Lambs were maintained for a further 30 min after ROSC. Results: The duration of CCs received and number of epinephrine doses required to obtain ROSC were similar between groups. After ROSC, we found no physiological benefits if UCC was delayed for 1 min compared to immediate cord clamping (ICC). However, if UCC was delayed for 10 min after ROSC, we found significant reductions in post-asphyxial rebound hypertension, cerebral blood flow, and cerebral oxygenation. The prevention of the post-asphyxial rebound hypertension in the PBCC10 group occurred due to the contribution of the placental circulation to a low peripheral resistance. As a result, left and right ventricular outputs continued to perfuse the placenta and were evidenced by reduced mean pulmonary blood flow, persistence of right-to-left shunting across the ductus arteriosus, and persistence of umbilical arterial and venous blood flows. Conclusion: It is possible to obtain ROSC after CC while the umbilical cord remains intact. There were no adverse effects of PBCC compared to ICC; however, the physiological changes observed after ROSC in the ICC and early PBCC groups may result in additional cerebral injury. Prolonging UCC after ROSC may provide significant physiological benefits that may reduce the risk of harm to the cerebral circulation.\n Copyright © 2020 Polglase, Schmölzer, Roberts, Blank, Badurdeen, Crossley, Miller, Stojanovska, Galinsky, Kluckow, Gill and Hooper.\n\n\n"
},
{
"text": "\n1327\nInduced mutant mice expressing lipoprotein lipase exclusively in muscle have subnormal triglycerides yet reduced high density lipoprotein cholesterol levels in plasma.\n\nLevak-Frank, S\n\nWeinstock, PH\n\nHayek, T\n\nVerdery, R\n\nHofmann, W\n\nRamakrishnan, R\n\nSattler, W\n\nBreslow, JL\n\nZechner, R\n\nBeiträge in Fachzeitschriften\nISI:A1997XH44600072\n9202040.0\n10.1074%2Fjbc.272.27.17182\nNone\nTo determine the contribution of muscle lipoprotein lipase (LPL) to lipoprotein metabolism, induced mutant mice were generated that express human LPL exclusively in muscle. By cross-breeding heterozygous LPL knockout mice with transgenic mice expressing human LPL only in muscle, animals were obtained that express human LPL primarily in skeletal muscle on either the null (L0-MCK) or normal (L2-MCK) LPL backgrounds, and these were compared with control littermates (L2). Fed and fasted post-heparin plasma (PHP) LPL activities were increased 1.4- and 2.3-fold, respectively, in L2-MCK mice and were normal in L0-MCK mice compared with controls. The specific enzyme activities of human LPL in mouse plasma was comparable to human LPL in human PHP. Skeletal muscle LPL activity was increased in both L2-MCK and L0-MCK mice in the fed (6.6-fold) and fasted (4.2-fold in L2-MCK; and 3.4-fold in L0-MCK) states. Adipose tissue LPL mRNA and activity were not detectable in L0-MCK mice. Growth and body mass composition were similar among all groups. In the fasted and fed state, L2-MCK mice had 31% and 53% reductions, respectively, in plasma triglycerides (TG), compatible with increased PHP LPL activity. Unexpectedly, both in the fasted and fed state the L0-MCK mice also had reduced TG (22%), despite normal PHP LPL activities. Very low density lipoprotein (VLDL) turnover studies revealed that the decreased TG were due to increased particle fractional catabolic rate in both L2-MCK and L0-MCK mice. Despite reduced TG, both L2-MCK and L0-MCK mice showed reduced high density lipoprotein (HDL) cholesterol levels (16% and 19%, respectively). HDL turnover studies indicated increased HDL cholesteryl ester fractional catabolic rate in the L2-MCK and L0-MCK compared with control mice. In summary, these studies suggest that muscle LPL is particularly potent with regard to VLDL metabolism and is sufficient to compensate for the lack of LPL in other tissues with regard to lipolyzing VLDL particles. With regard to HDL, muscle LPL expression does not result in normal levels due to enhanced breakdown either by mediating accelerated HDL clearance or by failing to establish normal HDL particles that are then cleared more quickly than normal. These studies provide new insights on the tissue-specific effects of LPL on lipoprotein metabolism.\n\nLevak, Sanja\n\nSattler, Wolfgang\n\n\n"
},
{
"text": "\n167109\nArgon preconditioning enhances postischaemic cardiac functional recovery following cardioplegic arrest and global cold ischaemia.\n\nKiss, A\n\nShu, H\n\nHamza, O\n\nSanter, D\n\nTretter, EV\n\nYao, S\n\nMarkstaller, K\n\nHallström, S\n\nPodesser, BK\n\nKlein, KU\n\nBeiträge in Fachzeitschriften\nISI:000443565900020\n29547976.0\n10.1093/ejcts/ezy104\nNone\nPrevious studies demonstrated that preconditioning with argon gas provided a marked reduction in inflammation and apoptosis and increased myocardial contractility in the setting of acute myocardial ischaemia-reperfusion (IR). There is substantial evidence that myocardial IR injury following cardioplegic arrest is associated with the enhancement of apoptosis and inflammation, which is considered to play a role in cardiac functional impairment. Therefore, the present study was designed to clarify whether preconditioning with argon gas enhances recovery of cardiac function following cardioplegic arrest.\n Sprague-Dawley rats were anaesthetized and ventilated and allocated to (i) the control group (control IR, n = 10) and (ii) the in vivo group (argon IR), which received 3 cycles of argon (50% argon, 21% oxygen and 29% nitrogen, n = 10) administered for 5 min interspersed with 5 min of a gas mixture (79% nitrogen and 21% oxygen). The hearts were excised and then evaluated in an erythrocyte-perfused isolated working heart system. Cold ischaemia (4°C) for 60 min was induced by histidine-tryptophan-ketoglutarate cardioplegia, followed by 40 min of reperfusion. Cardiac functional parameters were assessed. In left ventricular tissue samples, the expressions of extracellular-regulated kinase (ERK1/2), AKT serine/threonine kinase (Akt), jun N-terminal kinase (JNK), endothelial nitric oxide synthase (eNOS) and HMGB1: high-mobility group box 1 (HMGB1) protein were assessed by western blot, and high-energy phosphates were evaluated by high-performance liquid chromatography.\n At the end of reperfusion, the rats preconditioned with argon showed significantly enhanced recovery of cardiac output (101 ± 6% vs 87 ± 11%; P < 0.01), stroke volume (94 ± 4% vs 80 ± 11%; P = 0.001), external heart work (100 ± 6% vs 81 ± 13%; P < 0.001) and coronary flow (90 ± 13% vs 125 ± 21%; P < 0.01) compared with the control IR group. These results were accompanied by a significant increase in the levels of myocardial phosphocreatine (23.71 ± 2.07 µmol/g protein vs the control IR group, 13.50 ± 4.75; P = 0.001) and maintained adenosine triphosphate levels (13.62 ±1.89 µmol/g protein vs control IR group adenosine triphosphate: 10.08 ± 1.94 µmol/g; P = 0.017). Additionally, preconditioning with argon markedly reduced the activation of JNK (0.11 ± 0.01 vs 0.25 ± 0.03; P = 0.005) and the expression of HMGB1 protein (0.52 ± 0.04 vs 1.5 ± 0.10; P < 0.001) following reperfusion.\n Preconditioning with argon enhanced cardiac functional recovery in rat hearts arrested with histidine-tryptophan-ketoglutarate cardioplegia, thereby representing a potential novel cardioprotective approach in cardiac surgery.\n\nHallström, Seth\n\n\n"
},
{
"text": "\n3141\nPrevalence and characterization of renal tubular acidosis in patients with osteopenia and osteoporosis and in non-porotic controls.\n\nWeger, W\n\nKotanko, P\n\nWeger, M\n\nDeutschmann, H\n\nSkrabal, F\n\nBeiträge in Fachzeitschriften\nISI:000087943300011\n10862634.0\n10.1093%2Fndt%2F15.7.975\nNone\nBACKGROUND: Chronic metabolic acidosis may increase alkali mobilization from the bone and thus promote the development of osteoporosis. The objective of the current study was to compare urinary acidification in patients with reduced bone mineral content with that in control subjects with normal bone density. METHODS: Forty-six subjects (41 females, 5 males) with osteopenia or osteoporosis were studied. In none of the subjects were overt metabolic acidosis, derangement of potassium homeostasis, or renal insufficiency present. Distal tubular acidification was studied by means of oral ammonium chloride loading test (0.1 g/kg body weight) and the oral frusemide test (40 mg). In addition the frusemide test was performed in 20 healthy age- and sex-matched controls (17 females, 3 males). RESULTS: In all control subjects a urinary pH <5. 5 was observed following the ingestion of 40 mg frusemide. In contrast, in patients with reduced bone mineral density incomplete renal tubular acidosis type I (RTA I) was diagnosed in 10 of 46 subjects (22%) by oral ammonium chloride loading test. Disorders possibly related to RTA I were detected in eight of these 10 patients. Thirty-six patients had a normal urinary pH response following oral ammonium chloride loading. Oral frusemide, 40 mg, failed to lower urinary pH <5.5 in sixteen patients (35%), these included 10 subjects with incomplete RTA I, and six subjects with a normal oral ammonium chloride loading test. An abnormal frusemide test was found in 35% of patients with reduced bone mass and in none of the normal controls (chi(2)=7.39; P<0.01). With the ammonium chloride test as the gold standard for diagnosis of distal RTA, the frusemide test showed a sensitivity of 1.0 (95% CI, 0.69-1.0) and a specificity of 0.89 (95% CI, 0.78-0.96) for the diagnosis of distal RTA. Patients with incomplete RTA I were younger than those without incomplete RTA I (42+/-16 vs 54+/-14 years; P=0.025; mean+/-SD). Basal serum bicarbonate concentrations and capillary pH did not differ between the groups. CONCLUSION: Incomplete RTA I may be prevalent in a significant proportion of patients suffering from osteopenia or osteoporosis. The outcome of the frusemide test suggests either a defect of the H(+)ATPase in the cortical collecting tubule (CCT) or a defective Na(+) reabsorption in the CCT. Prospective studies are needed to further elucidate the impact of incomplete RTA I on the development of reduced bone mineral content.\n\nDeutschmann, Hannes\n\nWeger, Martin\n\nWeger, Wolfgang\n\n\n"
},
{
"text": "\n35969\nRadiofrequency tissue volume reduction of the soft palate and UPPP in the treatment of snoring.\n\nHofmann, T\n\nSchwantzer, G\n\nReckenzaun, E\n\nKoch, H\n\nWolf, G\n\nBeiträge in Fachzeitschriften\nISI:000234934500016\n16362264.0\n10.1007/s00405-005-0959-5\nNone\nThe purpose of this study was to evaluate the efficiency of radiofrequency tissue volume reduction (RFTVR) and uvulopalatopharyngoplasty (UPPP) in the treatment of snoring in a prospective clinical trial of 79 patients consecutively undergoing surgery for snoring. Seventy-nine patients with primary snoring or mild OSAS (obstructive sleep apnea syndrome) were enrolled in this clinical trial (66 males and 13 females). According to the anatomical findings (the size of the tonsils and uvula), the patients underwent UPPP/TE of the RFTVR of the soft palate. Forty-seven patients had UPPP/TE (age 45.81+/-12.11 years; median AHI: 8; range 1-29). Thirty-two patients were treated with RFTVR of the soft palate (age 48.10+/-10.92; median AHI: 5.0; range 0-26). The average number of treatments was 2.2. All patients underwent preoperative polysomnography to exclude severe OSAS. Pre- and postoperative snoring scores were evaluated from the patients with bed partners. Postoperative follow-up data were collected at a median of 4 months after treatment; 85.1% of the UPPP group and 53.1% of the RFTVR group underwent postoperative polysomnography. Subjective snoring scores of all study participants were evaluated. Preoperatively, there was no statistically significant difference of subjective symptoms, age and BMI between the two groups. The snoring scores improved statistically significantly in both groups (P <0.001 in the UPPP group; P =0.001 in the RFTVR group). After UPPP/TE snoring improved in 37 patients (78.7%), and 29 (61.7%) thereof were free of bothersome snoring; no change was found in 9 patients (19.2%), and 1 (2.1%) worsened. In the RFTVR group, snoring improved in 15 (46.9%), and 9 (28.1%) thereof were free of bothersome snoring; no change was found in 13 patients (50%), and 1 worsened (3.1%). Preoperative AHI was statistically higher (P =0.016) and mean minimal oxygen saturation significantly lower (P =0.002) in the UPPP group. In the UPPP group AHI and HI showed statistically significant improvement postoperatively (P =0.025 and P =0.034, respectively). After RFTVR, no statistically significant change of AHI, HI or oxygen saturation was found. Besides limited mucosal erosions (15%) after RFTVR and foreign body sensations (<10%) after UPPP/TE, no side effects were observed. The success rate of RFTVR of the soft palate is lower compared to the more invasive technique of UPPP. Due to its minimally invasive character, RFTVR is suitable as first-step treatment for snoring, but patients should be counseled about possible success rates and different treatment options.\n\nHofmann, Thiemo\n\nKoch, Horst\n\nSchwantzer, Gerold\n\nWolf, Gerald\n\n\n"
},
{
"text": "\n164115\nCo-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in adult and pediatric burn patients.\n\nHundeshagen, G\n\nHerndon, DN\n\nCapek, KD\n\nBranski, LK\n\nVoigt, CD\n\nKillion, EA\n\nCambiaso-Daniel, J\n\nSljivich, M\n\nDe Crescenzo, A\n\nMlcak, RP\n\nKinsky, MP\n\nFinnerty, CC\n\nNorbury, WB\n\nBeiträge in Fachzeitschriften\nISI:000418662100001\n29262848.0\n10.1186/s13054-017-1899-3\nPMC5738705\nBurn patients are prone to infections which often necessitate broad antibiotic coverage. Vancomycin is a common antibiotic after burn injury and is administered alone (V), or in combination with imipenem-cilastin (V/IC) or piperacillin-tazobactam (V/PT). Sparse reports indicate that the combination V/PT is associated with increased renal dysfunction. The purpose of this study was to evaluate the short-term impact of the three antibiotic administration types on renal dysfunction.\n All pediatric and adult patients admitted to our centers between 2004 and 2016 with a burn injury were included in this retrospective review if they met the criteria of exposition to either V, V/IC, or V/PT for at least 48 h, had normal baseline creatinine, and no pre-existing renal dysfunction. Creatinine was monitored for 7 days after initial exposure; the absolute and relative increase was calculated, and patient renal outcomes were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria depending on creatinine increases and estimated creatinine clearance. Secondary endpoints (demographic and clinical data, incidences of septicemia, and renal replacement therapy) were analyzed. Antibiotic doses were modeled in logistic and linear multivariable regression models to predict categorical KDIGO events and relative creatinine increase.\n Out of 1449 patients who were screened, 718 met the inclusion criteria, 246 were adults, and 472 were children. Between the study cohorts V, V/IC, and V/PT, patient characteristics at admission were comparable. V/PT administration was associated with a statistically higher serum creatinine, and lower creatinine clearance compared to patients receiving V alone or V/IC in adults and children after burn injury. The incidence of KDIGO stages 1, 2, and 3 was higher after V/PT treatment. In children, the incidence of KDIGO stage 3 following administration of V/PT was greater than after V/IC. In adults, the incidence of renal replacement therapy was higher after V/PT compared with V or V/IC. Multivariate modeling demonstrated that V/PT is an independent predictor of renal dysfunction.\n Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in pediatric and adult burn patients when compared to vancomycin alone or vancomycin plus imipenem-cilastin. The mechanism of this increased nephrotoxicity remains elusive and warrants further scientific evaluation.\n\nBranski, Ludwik\n\nCambiaso Daniel, Janos\n\n\n"
}
]
}