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"text": "\n172258\nLarge-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.\n\nDay, F\n\nKaraderi, T\n\nJones, MR\n\nMeun, C\n\nHe, C\n\nDrong, A\n\nKraft, P\n\nLin, N\n\nHuang, H\n\nBroer, L\n\nMagi, R\n\nSaxena, R\n\nLaisk, T\n\nUrbanek, M\n\nHayes, MG\n\nThorleifsson, G\n\nFernandez-Tajes, J\n\nMahajan, A\n\nMullin, BH\n\nStuckey, BGA\n\nSpector, TD\n\nWilson, SG\n\nGoodarzi, MO\n\nDavis, L\n\nObermayer-Pietsch, B\n\nUitterlinden, AG\n\nAnttila, V\n\nNeale, BM\n\nJarvelin, MR\n\nFauser, B\n\nKowalska, I\n\nVisser, JA\n\nAndersen, M\n\nOng, K\n\nStener-Victorin, E\n\nEhrmann, D\n\nLegro, RS\n\nSalumets, A\n\nMcCarthy, MI\n\nMorin-Papunen, L\n\nThorsteinsdottir, U\n\nStefansson, K\n\n23andMe Research Team\n\nStyrkarsdottir, U\n\nPerry, JRB\n\nDunaif, A\n\nLaven, J\n\nFranks, S\n\nLindgren, CM\n\nWelt, CK\n\nBeiträge in Fachzeitschriften\nISI:000455099000014\n30566500.0\n10.1371/journal.pgen.1007813\nPMC6300389\nPolycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10, 74 PCOS cases and 103, 64 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health.\n\nObermayer-Pietsch, Barbara\n\n\n"
},
{
"text": "\n177232\nRelative Body Weight and Standardised Brightness-Mode Ultrasound Measurement of Subcutaneous Fat in Athletes: An International Multicentre Reliability Study, Under the Auspices of the IOC Medical Commission.\n\nMüller, W\n\nFürhapter-Rieger, A\n\nAhammer, H\n\nLohman, TG\n\nMeyer, NL\n\nSardinha, LB\n\nStewart, AD\n\nMaughan, RJ\n\nSundgot-Borgen, J\n\nMüller, T\n\nHarris, M\n\nKirihennedige, N\n\nMagalhaes, JP\n\nMelo, X\n\nPirstinger, W\n\nReguant-Closa, A\n\nRisoul-Salas, V\n\nAckland, TR\n\nBeiträge in Fachzeitschriften\nISI:000518609300001\n31571156.0\n10.1007/s40279-019-01192-9\nPMC7018793\nFat is a metabolic fuel, but excess body fat is ballast mass, and therefore, many elite athletes reduce body fat to dangerously low levels. Uncompressed subcutaneous adipose tissue (SAT) thickness measured by brightness-mode ultrasound (US) provides an estimate of body fat content.\n The accuracy for determining tissue borders is about 0.1-0.2 mm and reliability (experienced measurers) was within ± 1.4 mm (95% limit of agreement, LOA). We present here inter- and intra-measurer scores of three experienced US measurers from each of the centres C1 and C2, and of three novice measurers from each of the centres C3-C5. Each of the five centres measured 16 competitive adult athletes of national or international level, except for one centre where the number was 12. The following sports were included: artistic gymnastics, judo, pentathlon, power lifting, rowing, kayak, soccer, tennis, rugby, basketball, field hockey, water polo, volleyball, American football, triathlon, swimming, cycling, long-distance running, mid-distance running, hurdles, cross-country skiing, snowboarding, and ice hockey. SAT contour was detected semi-automatically: typically, 100 thicknesses of SAT at a given site (i.e., in a given image), with and without fibrous structures, were measured.\n At SAT thickness sums DI (of eight standardised sites) between 6.0 and 70.0 mm, the LOA of experienced measurers was 1.2 mm, and the intra-class correlation coefficient ICC was 0.998; novice measurers: 3.1 mm and 0.988. Intra-measurer differences were similar. The median DI value of all 39 female participants was 51 mm (11% fibrous structures) compared to 17 mm (18%) in the 37 male participants.\n DI measurement accuracy and precision enables detection of fat mass changes of approximately 0.2 kg. Such reliability has not been reached with any other method. Although females' median body mass index and mass index were lower than those of males, females' median DI was three times higher, and their percentage of fibrous structures was lower. The standardised US method provides a highly accurate and reliable tool for measuring SAT and thus changes in body fat, but training of measurers is important.\n\nAhammer, Helmut\n\nFürhapter-Rieger, Alfred\n\nMüller, Wolfram\n\n\n"
},
{
"text": "\n183958\nKidney function and other factors and their association with falls : The screening for CKD among older people across Europe (SCOPE) study.\n\nBritting, S\n\nArtzi-Medvedik, R\n\nFabbietti, P\n\nTap, L\n\nMattace-Raso, F\n\nCorsonello, A\n\nLattanzio, F\n\nÄrnlöv, J\n\nCarlsson, AC\n\nRoller-Wirnsberger, R\n\nWirnsberger, G\n\nKostka, T\n\nGuligowska, A\n\nFormiga, F\n\nMoreno-Gonzalez, R\n\nGil, P\n\nMartinez, SL\n\nKob, R\n\nMelzer, I\n\nFreiberger, E\n\nSCOPE investigators\n\nBeiträge in Fachzeitschriften\nISI:000576901000002\n33008307.0\n10.1186/s12877-020-01698-2\nPMC7531089\nReduced kidney function has become a major public health concern, especially among older people, as Chronic Kidney Disease (CKD) is associated with increased risk of end stage renal disease and mortality. Falls are a serious negative health outcome in older persons with one third of people aged 65 years experiencing a fall per year and increasing fall rates with increasing age. The impact of CKD on falls in older community-dwelling persons is not well investigated. Additionally, lower urinary tract symptoms (LUTS) may also increase the risk of falls. Therefore, our aim was to investigate the impact of CKD and LUTS on falls as well as on injurious falls.\n The SCOPE study is an observational, multinational, multicenter, prospective cohort study involving community-dwelling older persons aged 75 years and more recruited from August 2016 to March 2018 in seven European countries. The main outcomes of the present study were any falls and any injurious falls during the 12 months before enrolment. The cross-sectional association of estimated glomerular filtration rate (eGFR) and LUTS with study outcomes was investigated by logistic regression analysis adjusted for baseline characteristics of enrolled subjects.\n Our series consisted of 2256 SCOPE participants (median age = 79.5 years, 55.7% female). Of them, 746 participants experienced a fall and 484 reported an injurious fall in the 12 months prior to baseline assessment. CKD was not significantly associated with falls (OR = 0.95, 95%CI = 0.79-1.14 for eGFR< 60; OR = 1.02, 95%CI = 0.81-1.28 for eGFR< 45; OR = 1.08, 95%CI = 0.74-1.57 for eGFR< 30) or injurious falls (OR = 0.91, 95%CI = 0.67-1.24 for eGFR< 60; OR = 0.93, 95%CI = 0.63-1.37 for eGFR< 45; OR = 1.19, 95%CI = 0.62-2.29 for eGFR< 30). LUTS were found significantly associated with both falls (OR = 1.56, 95%CI = 1.29-1.89) and injurious falls (OR = 1.58, 95%CI = 1.14-2.19), and such associations were confirmed in all multivariable models.\n Cross-sectional data suggest that CKD may not be associated with history of falls or injurious falls, whereas LUTS is significantly associated with the outcomes.\n This study was registered on 25th February 2016 at clinicaltrials.gov ( NCT02691546 ).\n\nRoller-Wirnsberger, Regina\n\nWirnsberger, Gerhard\n\n\n"
},
{
"text": "\n136643\n[New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk : Statement of the D•A•CH Society for Prevention of Cardiovascular Diseases, the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society for Cardiology].\n\nKlose, G\n\nBeil, FU\n\nDieplinger, H\n\nvon Eckardstein, A\n\nFöger, B\n\nGouni-Berthold, I\n\nKoenig, W\n\nKostner, GM\n\nLandmesser, U\n\nLaufs, U\n\nLeistikow, F\n\nMärz, W\n\nMerkel, M\n\nMüller-Wieland, D\n\nNoll, G\n\nParhofer, KG\n\nPaulweber, B\n\nRiesen, W\n\nSchaefer, JR\n\nSteinhagen-Thiessen, E\n\nSteinmetz, A\n\nToplak, H\n\nWanner, C\n\nWindler, E\n\nBeiträge in Fachzeitschriften\nISI:000335450500011\n24770979.0\n10.1007/s00108-014-3492-z\nNone\nGuidelines for the reduction of cholesterol to prevent atherosclerotic vascular events were recently released by the American Heart Association and the American College of Cardiology. The authors claim to refer entirely to evidence from randomized controlled trials, thereby confining their guidelines to statins as the primary therapeutic option. The guidelines derived from these trials do not specify treatment goals, but refer to the percentage of cholesterol reduction by statin medication with low, moderate, and high intensity. However, these targets are just as little tested in randomized trials as are the cholesterol goals derived from clinical experience. The same applies to the guidelines of the four patient groups which are defined by vascular risk. No major statin trial has included patients on the basis of their global risk; thus the allocation criteria are also arbitrarily chosen. These would actually lead to a significant increase in the number of patients to be treated with high or maximum dosages of statins. Also, adhering to dosage regulations instead of cholesterol goals contradicts the principles of individualized patient care. The option of the new risk score to calculate lifetime risk up to the age of 80 years in addition to the 10-year risk can be appreciated. Unfortunately it is not considered in the therapeutic recommendations provided, despite evidence from population and genetic studies showing that even a moderate lifetime reduction of low-density lipoprotein (LDL) cholesterol or non-HDL cholesterol has a much stronger effect than an aggressive treatment at an advanced age. In respect to secondary prevention, the new American guidelines broadly match the European guidelines. Thus, the involved societies from Germany, Austria and Switzerland recommend continuing according to established standards, such as the EAS/ESC guidelines.\n\nKostner, Gerhard\n\nMärz, Winfried\n\nToplak, Hermann\n\n\n"
},
{
"text": "\n145159\nComparison of postoperative volume therapy in heart surgery patients].\n\nBrock, H\n\nRapf, B\n\nNecek, S\n\nGabriel, C\n\nPeterlik, C\n\nPölz, W\n\nSchimetta, W\n\nBergmann, H\n\nBeiträge in Fachzeitschriften\nISI:A1995RL63100005\n7661335.0\n10.1007/s001010050181\nNone\nPatients who have undergone cardiac surgery with use of extracorporeal circulation frequently reveal marked hypovolaemia in spite of a highly positive fluid balance. This is thought to be due to transient microvascular damage and extravascular fluid shift. Further volume replacement to achieve haemodynamic stability in the postoperative period may cause fluid overload and congestive heart failure. The present study was designed to investigate whether this fluid overload could be avoided by using a hypertonic-hyperoncotic solution (group I: HHL, 10% hydroxyethylstarch 200/0.5 in 7.2% saline) instead of two different standard colloid solutions (group II: HA, 5% albumin; group III: HES, 6% hydroxyethylstarch in 0.9% saline).\n Twenty-one patients meeting our criteria for hypovolaemia immediately after cardiac surgery were randomly assigned to three groups. Patients in group I received HHL in increments of 150 ml, while patients in group II and group III were given HA and HES respectively in increments of 500 ml until hypovolemia was corrected. Haemodynamic assessment was done using a pulmonary artery thermodilution catheter. Intra- and extravascular volumes, including extravascular lung water (EVLW), intrathoracic blood volume (ITBV), and total blood volume (TBV) were measured by the double indicator technique using lung water software (COLD-System, Pulsion, Munich, Germany).\n Correction of hypovolaemia-related haemodynamic parameters and restoration of normal TBV were achieved by 236 +/- 80 ml of HHL (group I), 857 +/- 244 ml of HA (group II) and 1000 +/- 0 ml of HES (group III) respectively. TBV increased significantly in each group, compared to baseline values. EVLW did not change significantly in any group. We found that the volume-augmenting effect of HHL per millilitre infused solution was more than four times that of HA and HES, primarily as a result of increasing plasma osmolality due to an increase of plasma sodium levels. This pronounced effect on intravascular volume of HHL lasted for only 2 h following infusion, however, and did not lead to any unwanted side effects. In the period between 2 and 20 h after primary volume replacement, further fluid therapy with colloids and crystalloids, guided by clinical signs of hypovolaemia, was necessary in each group of patients. The overall fluid requirements for the first 20 h after operation did not differ among the three resuscitation regimens.\n We found that HHL is a safe and effective solution for acute correction of hypovolaemia after cardiac surgery. The advantages of a smaller initial volume load by HHL cannot be maintained for longer than 2 h.\n\n\n"
},
{
"text": "\n159776\nWork productivity in rhinitis using cell phones: The MASK pilot study.\n\nBousquet, J\n\nBewick, M\n\nArnavielhe, S\n\nMathieu-Dupas, E\n\nMurray, R\n\nBedbrook, A\n\nCaimmi, DP\n\nVandenplas, O\n\nHellings, PW\n\nBachert, C\n\nAnto, JM\n\nBergmann, KC\n\nBindslev-Jensen, C\n\nBosnic-Anticevich, S\n\nBouchard, J\n\nCanonica, GW\n\nChavannes, NH\n\nCruz, AA\n\nDahl, R\n\nDemoly, P\n\nDe Vries, G\n\nDevillier, P\n\nFink-Wagner, A\n\nFokkens, WJ\n\nFonseca, J\n\nGuldemond, NA\n\nHaahtela, T\n\nHellqvist-Dahl, B\n\nJust, J\n\nKeil, T\n\nKlimek, L\n\nKowalski, ML\n\nKuna, P\n\nKvedariene, V\n\nLaune, D\n\nLarenas-Linnemann, D\n\nMullol, J\n\nPereira, AM\n\nCarreiro-Martins, P\n\nMelén, E\n\nMorais-Almeida, M\n\nNogueira-Silva, L\n\nO'Hehir, RE\n\nPapadopoulos, NG\n\nPassalacqua, G\n\nPortejoie, F\n\nPrice, D\n\nRyan, D\n\nSamolinski, B\n\nSheikh, A\n\nSimons, FER\n\nSpranger, O\n\nTodo Bom, A\n\nTomazic, PV\n\nTriggiani, M\n\nValero, A\n\nValovirta, E\n\nValiulis, A\n\nvan Eerd, M\n\nWickman, M\n\nYoung, I\n\nZuberbier, T\n\nBeiträge in Fachzeitschriften\nISI:000412545200004\n28387952.0\n10.1111/all.13177\nNone\nAllergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.\n © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.\n\nTomazic, Peter Valentin\n\n\n"
},
{
"text": "\n167640\nMay Measurement Month 2017: an analysis of blood pressure screening results worldwide.\n\nBeaney, T\n\nSchutte, AE\n\nTomaszewski, M\n\nAriti, C\n\nBurrell, LM\n\nCastillo, RR\n\nCharchar, FJ\n\nDamasceno, A\n\nKruger, R\n\nLackland, DT\n\nNilsson, PM\n\nPrabhakaran, D\n\nRamirez, AJ\n\nSchlaich, MP\n\nWang, J\n\nWeber, MA\n\nPoulter, NR\n\nMMM Investigators\n\nBeiträge in Fachzeitschriften\nISI:000435591400021\n29778399.0\n10.1016/S2214-109X(18)30259-6\nNone\nIncreased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screening programmes.\n This cross-sectional survey included volunteer adults (≥18 years) who ideally had not had their blood pressures measured in the past year. Each participant had their blood pressure measured three times and received a a questionnaire about demographic, lifestyle, and environmental factors. The primary objective was to raise awareness of blood pressure, measured by number of countries involved, number of people screened, and number of people who have untreated or inadequately treated hypertension (defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, or on the basis of receiving antihypertensive medication). Multiple imputation was used to estimate the mean of the second and third blood pressure readings if these were not recorded. Measures of association were analysed using linear mixed models.\n Data were collected from 1 201 570 individuals in 80 countries. After imputation, of the 1 128 635 individuals for whom a mean of the second and third readings was available, 393 924 (34·9%) individuals had hypertension. 153 905 (17·3%) of 888 616 individuals who were not receiving antihypertensive treatment were hypertensive, and 105 456 (46·3%) of the 227 721 individuals receiving treatment did not have controlled blood pressure. Significant differences in adjusted blood pressures and hypertension prevalence were apparent between regions. Adjusted blood pressure was higher in association with antihypertensive medication, diabetes, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm than on the left arm, and blood pressure was highest on Saturdays.\n Inexpensive global screening of blood pressure is achievable using volunteers and convenience sampling. Pending the set-up of systematic surveillance systems worldwide, MMM will be repeated annually to raise awareness of blood pressure.\n International Society of Hypertension, Centers for Disease Control and Prevention, Servier Pharmaceutical Co.\n Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.\n\nPerl, Sabine\n\n\n"
},
{
"text": "\n167821\nEffects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials.\n\nSwart, KM\n\nLips, P\n\nBrouwer, IA\n\nJorde, R\n\nHeymans, MW\n\nGrimnes, G\n\nGrübler, MR\n\nGaksch, M\n\nTomaschitz, A\n\nPilz, S\n\nEiriksdottir, G\n\nGudnason, V\n\nWamberg, L\n\nRejnmark, L\n\nSempos, CT\n\nDurazo-Arvizu, RA\n\nDowling, KG\n\nHull, G\n\nŠkrabáková, Z\n\nKiely, M\n\nCashman, KD\n\nvan Schoor, NM\n\nBeiträge in Fachzeitschriften\nISI:000435459400022\n29868916.0\n10.1093/ajcn/nqy078\nPMC6248392\nEvidence from randomized controlled trials (RCTs) for the causal role of vitamin D on noncommunicable disease outcomes is inconclusive.\n The aim of this study was to investigate whether there are beneficial or harmful effects of cholecalciferol (vitamin D3) supplementation according to subgroups of remeasured serum 25-hydroxyvitamin D [25(OH)D] on cardiovascular and glucometabolic surrogate markers with the use of individual participant data (IPD) meta-analysis of RCTs.\n Twelve RCTs (16 wk to 1 y of follow-up) were included. For standardization, 25(OH)D concentrations for all participants (n = 2994) at baseline and postintervention were re-measured in bio-banked serum samples with the use of a certified liquid chromatography-tandem mass spectrometry method traceable to a reference measurement procedure. IPD meta-analyses were performed according to subgroups of remeasured 25(OH)D. Main outcomes were blood pressure and glycated hemoglobin (HbA1c). Secondary outcomes were LDL, HDL, and total cholesterol and triglycerides; parathyroid hormone (PTH); fasting glucose, insulin, and C-peptide; and 2-h glucose. In secondary analyses, other potential effect modifiers were studied.\n Remeasurement of 25(OH)D resulted in a lower mean 25(OH)D concentration in 10 of 12 RCTs. Vitamin D supplementation had no effect on the main outcomes of blood pressure and HbA1c. Supplementation resulted in 10-20% lower PTH concentrations, irrespective of the 25(OH)D subgroups. The subgroup analyses according to achieved 25(OH)D concentrations showed a significant decrease in LDL-cholesterol concentrations after vitamin D supplementation in 25(OH)D subgroups with <75, <100, and <125 nmol of -0.10 mmol/L (95% CI: -0.20, -0.00 mmol/L), -0.10 mmol/L (95% CI: -0.18, -0.02 mmol/L), and -0.07 mmol/L (95% CI: -0.14, -0.00 mmol/L), respectively. Patient features that modified the treatment effect could not be identified.\n For the main outcomes of blood pressure and HbA1c, the data support no benefit for vitamin D supplementation. For the secondary outcomes, in addition to its effect on PTH, we observed indications for a beneficial effect of vitamin D supplementation only on LDL cholesterol, which warrants further investigation. This trial was registered at www.clinicaltrials.gov as NCT02551835.\n\nPilz, Stefan\n\n\n"
},
{
"text": "\n170584\nDrug-coated balloons for small coronary artery disease (BASKET-SMALL 2): an open-label randomised non-inferiority trial.\n\nJeger, RV\n\nFarah, A\n\nOhlow, MA\n\nMangner, N\n\nMöbius-Winkler, S\n\nLeibundgut, G\n\nWeilenmann, D\n\nWöhrle, J\n\nRichter, S\n\nSchreiber, M\n\nMahfoud, F\n\nLinke, A\n\nStephan, FP\n\nMueller, C\n\nRickenbacher, P\n\nCoslovsky, M\n\nGilgen, N\n\nOsswald, S\n\nKaiser, C\n\nScheller, B\n\nBASKET-SMALL 2 Investigators\n\nBeiträge in Fachzeitschriften\nISI:000444130000030\n30170854.0\n10.1016/S0140-6736(18)31719-7\nNone\nDrug-coated balloons (DCB) are a novel therapeutic strategy for small native coronary artery disease. However, their safety and efficacy is poorly defined in comparison with drug-eluting stents (DES).\n BASKET-SMALL 2 was a multicentre, open-label, randomised non-inferiority trial. 758 patients with de-novo lesions (<3 mm in diameter) in coronary vessels and an indication for percutaneous coronary intervention were randomly allocated (1:1) to receive angioplasty with DCB versus implantation of a second-generation DES after successful predilatation via an interactive internet-based response system. Dual antiplatelet therapy was given according to current guidelines. The primary objective was to show non-inferiority of DCB versus DES regarding major adverse cardiac events (MACE; ie, cardiac death, non-fatal myocardial infarction, and target-vessel revascularisation) after 12 months. The non-inferiority margin was an absolute difference of 4% in MACE. This trial is registered with ClinicalTrials.gov, number NCT01574534.\n Between April 10, 2012, and February 1, 2017, 382 patients were randomly assigned to the DCB group and 376 to DES group. Non-inferiority of DCB versus DES was shown because the 95% CI of the absolute difference in MACE in the per-protocol population was below the predefined margin (-3·83 to 3·93%, p=0·0217). After 12 months, the proportions of MACE were similar in both groups of the full-analysis population (MACE was 7·5% for the DCB group vs 7·3% for the DES group; hazard ratio [HR] 0·97 [95% CI 0·58-1·64], p=0·9180). There were five (1·3%) cardiac-related deaths in the DES group and 12 (3·1%) in the DCB group (full analysis population). Probable or definite stent thrombosis (three [0·8%] in the DCB group vs four [1·1%] in the DES group; HR 0·73 [0·16-3·26]) and major bleeding (four [1·1%] in the DCB group vs nine [2·4%] in the DES group; HR 0·45 [0·14-1·46]) were the most common adverse events.\n In small native coronary artery disease, DCB was non-inferior to DES regarding MACE up to 12 months, with similar event rates for both treatment groups.\n Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Basel Cardiovascular Research Foundation, and B Braun Medical AG.\n Copyright © 2018 Elsevier Ltd. All rights reserved.\n\nSchmidt, Albrecht\n\nvon Lewinski, Dirk\n\n\n"
},
{
"text": "\n176060\nSurgical Treatment of Localized-Type Tenosynovial Giant Cell Tumors of Large Joints: A Study Based on a Multicenter-Pooled Database of 31 International Sarcoma Centers.\n\nMastboom, MJL\n\nStaals, EL\n\nVerspoor, FGM\n\nRueten-Budde, AJ\n\nStacchiotti, S\n\nPalmerini, E\n\nSchaap, GR\n\nJutte, PC\n\nAston, W\n\nLeithner, A\n\nDammerer, D\n\nTakeuchi, A\n\nThio, Q\n\nNiu, X\n\nWunder, JS\n\nvan de Sande, MAJ\n\nBeiträge in Fachzeitschriften\nISI:000480804800016\n31318811.0\n10.2106/JBJS.18.01147\nNone\nLocalized-type tenosynovial giant cell tumor (TGCT) is a rare, neoplastic disease with only limited data supporting treatment protocols. We describe treatment protocols and evaluate their oncological outcome, complications, and functional results in a large multicenter cohort of patients. A secondary study aim was to identify factors associated with local recurrence after surgical treatment.\n Patients with histologically proven localized TGCT of a large joint were included if they had been treated between 1990 and 2017 in 1 of 31 tertiary sarcoma centers. Of 941 patients with localized TGCT, 62% were female. The median age at initial treatment was 39 years, and the median duration of follow-up was 34 months. Sixty-seven percent of the tumors affected the knee, and the primary treatment at the tertiary center was 1-stage open resection in 73% of the patients. Proposed factors for predicting a first local recurrence after treatment in the tertiary center were tested in a univariate analysis, and those that demonstrated significance were subsequently included in a multivariate analysis.\n The localized TGCT recurred in 12% of all cases, with local-recurrence-free rates at 3, 5, and 10 years of 88%, 83%, and 79%, respectively. The strongest factor for predicting recurrent disease was a prior recurrence (p < 0.001). Surgical treatment decreased pain and swelling in 71% and 85% of the patients, respectively, and such treatment was associated with complications in 4% of the patients. Univariate and multivariate analyses of the patients who had not undergone therapy previously yielded positive associations between local recurrence and a tumor size of ≥5 cm versus <5 cm (hazard ratio [HR] = 2.50; 95% confidence interval [CI] = 1.32 to 4.74; p = 0.005). Arthroscopy (versus open surgery) was significantly associated with tumor recurrence in the univariate analysis (p = 0.04) but not in the multivariate analysis (p = 0.056).\n Factors associated with recurrence after resection of localized-type TGCT were larger tumor size and initial treatment with arthroscopy. Relatively low complication rates and good functional outcomes warrant an open approach with complete resection when possible to reduce recurrence rates in high-risk patients.\n Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.\n\nLeithner, Andreas\n\n\n"
},
{
"text": "\n178341\nRadiation Exposure of Patient and Operating Room Personnel by Fluoroscopy and Navigation during Spinal Surgery.\n\nBratschitsch, G\n\nLeitner, L\n\nStücklschweiger, G\n\nGuss, H\n\nSadoghi, P\n\nPuchwein, P\n\nLeithner, A\n\nRadl, R\n\nBeiträge in Fachzeitschriften\nISI:000499137900001\n31776364.0\n10.1038/s41598-019-53472-z\nPMC6881318\nIntraoperative radiography imaging is essential for accurate spinal implant placement. Hazards caused by ionizing radiation raised concern on personnel's work life long exposure in the operating room (OR). To particularize a cumulative risk estimation of radiation of personnel and patient, depending on used methods (C-arm fluoroscopy, O-arm navigation) and patient characteristics during spinal surgery, detailed investigation of radiation exposure in a clinical setting is required. Lumbosacral dorsal spinal fusion was performed in 37 patients (19 navigated, 18 fluoroscopy) during this prospective study. Radiation exposure was measured on several body regions with thermoluminescent dosimeters on patient and OR personnel (surgeon, assistant, sterile nurse, radiology technologist). Comparison between patient characteristics and radiation exposure was included. The highest patients values were measured in the surgery field and gonads area during navigation (43.2 ± 19.4 mSv; fluoroscopy: 27.7 ± 31.3 mSv; p = 0.02), followed by the thoracic region during fluoroscopy (7.7 ± 14.8 mSv; navigation: 1.1 ± 1.0 mSv; p = 0.06), other measured regions can be considered marginal in comparison. Amongst OR personnel exposure of the surgeon was significant higher during fluoroscopy (right hand: 566 ± 560 µSv and thoracic region: 275 ± 147 µSv; followed by thyroid and forehead) compared to navigation (right finger: 49 ± 19 µSv; similar levels for all regions; p < 0.001 in all regions). When compared to the surgeon, other OR personnel had significantly lower radiation doses on all body regions using fluoroscopy, and similar dose during navigation. The highest eye's lens region value was measured during fluoroscopy for the patient (185 ± 165 µSv; navigation: 205 ± 60 µSv; p = 0.57) and the surgeon (164 ± 74 µSv; navigation: 92 ± 41 µSv; p < 0.001). There was a significant correlation between patient BMI and radiation exposure to the surgery field during fluoroscopy. To our knowledge, these data present the first real life, detailed comparison of radiation exposure on OR personnel and patients between clinical use of navigation and fluoroscopy. Although patient's radiation dose is approximately 3-fold during navigation compared to the fluoroscopy, we found that a spinal surgeon could perform up to 10-fold number of surgeries (10.000 versus 883) until maximum permissible annual effective radiation dose would be reached. Especially for a spinal surgeon, who is mainly exposed amongst OR personnel, radiation prevention and protection must remain a main issue.\n\nBratschitsch, Gerhard\n\nLeithner, Andreas\n\nLeitner, Lukas\n\nPuchwein, Paul\n\nRadl, Roman\n\nSadoghi, Patrick\n\n\n"
},
{
"text": "\n182836\nVitamin D - Deglycosylated Vitamin D Binding Protein Dimer: Positive Synergistic Effects on Recognition, Activation, Phagocytosis and Oxidative Stress on Macrophages.\n\nGreilberger, J\n\nHerwig, R\n\nBeiträge in Fachzeitschriften\nISI:000545455000024\n32013346.0\n10.7754/Clin.Lab.2019.191121\nNone\nWe have recently shown positive effects in the quality of life in autism and amyloid lateral sclerosis patients using a newly developed 25-OH vitamin D deglycosylated vitamin D binding protein complex (VitD~dgVDBP) by reducing oxidative stress. The question arises whether this reduction of oxidative stress was due to a synergistic effect of the dimer in the recognition and activation of phagocytosis on macrophages combined with a lower oxidative burst compared to the VitD free proteins, namely vitamin D binding protein (VDBP: Gc Protein) and deglycosylated dgVDBP (GcMAF).\n VDBP sandwich ELISA of equal protein concentration of VDBP, dgVDBP, and VitD~dgVDBP (1 µg/ mL by BCA protein technique) was used to identify immune affinity to polyclonal antibodies raised against human VDBP. The 25(OH) vitamin D levels of VDBP, dgVDBP and VitD~dgVDBP were estimated by a competitive immune assay using a monoclonal antibody. Macrophage phagocytosis and oxidative burst in absence or presence of 400 pg/mL VDBP, 400 pg/mL dgVDBP, and 400 pg/mL VitD~dgVDBP was measured.\n The recognition of the antibody against VDBP protein was significantly more than 4-fold higher for VitD~dgVDBP (769.2 +/- 35.1%) compared to dgVDBP (186.5 +/- 16.8 %; p < 0.01) and 7-fold higher to VDBP (100 +/- 11.4 %; p < 0.001). 25(OH) vitamin D levels of VDBP (20.7 nmol/mg; p < 0.001) and dgVDBP (28.8 +/- 3.9 nmol/mL; p < 0.001) was significantly lower than of VitD~dgVDBP (324.0 +/- 12.8 nmol/mL). The calculated VitD/ protein ratio showed significantly higher results in favor of VitD~dgVDBP (1.01 +/- 0.12) compared to dgVDBP (0.06 +/- 0.03; p < 0.001) and VDBP (0.05 +/- 0.01; p < 0.001). The estimation of macrophage phagocytosis rate of VitD~dgVDBP (5, 64.3 +/- 742.2 cps) was significantly higher compared to dgVDBP (2, 89.6 +/- 102.7 cps; p < 0.01) and VDBP (1, 34.3 +/- 135.9 cps) whereas the production of macrophage superoxide anion radicals showed significantly higher levels of dgVDBP (255.3 +/- 14.5 cps) in comparison to VDBP (148.6 +/- 24.7 cps, p < 0.01) and VitD~dgVDBP (142.3 +/- 20.0 cps; p < 0.001). Linear regression between VDBP antibody affinity and macrophage phagocytosis of VDBP, dgVDBP and VitD~dgVDBP resulted in a correlation coefficient of r = 0.95 in favor of VitD~dgVDBP.\n VitD~dgVDBP (Il-42) showed higher macrophage activation and lower oxidative burst than VitD free dgVDBP (GcMaf) and VDBP (Gc) which may result from a synergistic effect by presenting protein bound Vitamin D better to macrophages.\n\nGreilberger, Joachim\n\n\n"
},
{
"text": "\n142841\nCurrent practice in diagnosis and treatment of acute graft-versus-host disease: results from a survey among German-Austrian-Swiss hematopoietic stem cell transplant centers.\n\nWolff, D\n\nAyuk, F\n\nElmaagacli, A\n\nBertz, H\n\nLawitschka, A\n\nSchleuning, M\n\nMeyer, RG\n\nGerbitz, A\n\nHilgendorf, I\n\nHildebrandt, GC\n\nEdinger, M\n\nKlein, S\n\nHalter, J\n\nMousset, S\n\nHoller, E\n\nGreinix, HT\n\nBeiträge in Fachzeitschriften\nISI:000318132500014\n23376495.0\n10.1016/j.bbmt.2013.01.018\nNone\nTo assess current clinical practice in diagnosis and treatment of acute graft-versus-host disease (aGVHD), we performed a survey among German, Austrian, and Swiss allogeneic hematopoietic stem cell transplantation (allo-HSCT) centers. Thirty-four of 72 contacted centers (47%) completed both the diagnostic and therapeutic sections of the survey, representing 65% of allo-HSCT activity within the participating countries in 2011. Three pediatric centers answered as requested only the diagnostic part of the survey. In the presence of diarrhea and decreased oral intake after engraftment, only 4 centers (12%) do not perform any endoscopy before the start of immunosuppressive treatment. In case of a skin rash with the differential diagnosis of drug reaction, only 12 centers (35%) perform a skin biopsy up front, whereas 19 do so after failure of systemic steroids. In the presence of rapidly increasing cholestasis occurring without any other signs of aGVHD, 11 centers (32%) perform a liver biopsy up front and 14 only after failure of steroid treatment, whereas 9 centers do not perform a liver biopsy at all. Twenty centers (59%) use a percutaneous approach, 12 a transvenous approach, and 1 mini-laparoscopy for liver biopsies. First-line treatment of cutaneous aGVHD stage 1 consists of topical treatment alone in 17 of 31 responding centers (61%), whereas isolated cutaneous aGVHD stage III is treated with systemic steroids (prednisolone below 0.5 mg/kg/day n = 2, 0.5 to 1.0 mg/kg/day n = 10, above 1.0 to 2.5 mg/kg/day n = 19) without or with topical agents (steroids n = 10; calcineurin inhibitors n = 3). In gastrointestinal manifestations of aGVHD, 9 centers (29%) add topical to systemic steroids, and 3 consider topical steroids as the only treatment for mild gastrointestinal and cutaneous aGVHD. The choice of agent for second-line treatment as well as the sequence of administration are extremely heterogeneous, most likely due to a lack of convincing data published. Most frequently used are mycophenolate mofetil (n = 14) and extracorporeal photopheresis (n = 10). Our survey also demonstrates that clinicians chose salvage therapies for steroid-refractory aGVHD based on their centers' own clinical experience.\n Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n187715\nGenome-wide analysis identifies novel susceptibility loci for myocardial infarction\n\nHartiala, JA\n\nHan, Y\n\nJia, Q\n\nHilser, JR\n\nHuang, P\n\nGukasyan, J\n\nSchwartzman, WS\n\nCai, ZH\n\nBiswas, S\n\nTregouet, DA\n\nSmith, NL\n\nSeldin, M\n\nPan, C\n\nMehrabian, M\n\nLusis, AJ\n\nBazeley, P\n\nSun, YV\n\nLiu, C\n\nQuyyumi, AA\n\nScholz, M\n\nThiery, J\n\nDelgado, GE\n\nKleber, ME\n\nMarz, W\n\nHowe, LJ\n\nAsselbergs, FW\n\nvan Vugt, M\n\nVlachojannis, GJ\n\nPatel, RS\n\nLyytikainen, LP\n\nKahonen, M\n\nLehtimaki, T\n\nNieminen, TVM\n\nKuukasjarvi, P\n\nLaurikka, JO\n\nChang, XL\n\nHeng, CK\n\nJiang, R\n\nKraus, WE\n\nHauser, ER\n\nFerguson, JF\n\nReilly, MP\n\nIto, K\n\nKoyama, S\n\nKamatani, Y\n\nKomuro, I\n\nJapan, B\n\nStolze, LK\n\nRomanoski, CE\n\nKhan, MD\n\nTurner, AW\n\nMiller, CL\n\nAherrahrou, R\n\nCivelek, M\n\nMa, LJ\n\nBjorkegren, JLM\n\nKumar, SR\n\nTang, WHW\n\nHazen, SL\n\nAllayee, H\n\nBeiträge in Fachzeitschriften\nISI:000646254000010\n33532862.0\n10.1093/eurheartj/ehaa1040\nNone\nAims While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation Methods and results We carried out a genome-wide association study for MI in the UK Biobank (n similar to 472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n similar to 167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n similar to 165 000) and 16 independent angiography-based cohorts (n similar to 27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1 beta (vs. vehicle), and associated with smooth muscle cell migration in vitro Conclusions A large-scale analysis comprising similar to 831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n165433\nProspective study of telomere length and LINE-1 methylation in peripheral blood cells: the role of B vitamins supplementation.\n\nPusceddu, I\n\nHerrmann, M\n\nKirsch, SH\n\nWerner, C\n\nHübner, U\n\nBodis, M\n\nLaufs, U\n\nWagenpfeil, S\n\nGeisel, J\n\nHerrmann, W\n\nBeiträge in Fachzeitschriften\nISI:000380125600006\n26293976.0\n10.1007/s00394-015-1003-1\nNone\nDeficiencies of folate, vitamins B12 and D are common age-related conditions. Vitamin B12 and folate are necessary for DNA methylation. Telomeres appear to be regulated by DNA methylation. Here, we study the effect of B vitamins supplementation on telomere length and global DNA methylation in a prospective study.\n In total, 60 elderly subjects were supplemented for 1 year with either vitamin B12, B6, folate, vitamin D and calcium (group A n = 31) or only vitamin D and calcium (group B n = 29). LINE-1 methylation, relative telomere length (T/S), vitamin B12, folate, homocysteine (tHcy) , 5-methyltetrahydrofolate (5-methylTHF), S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), cystathionine and vitamin D were quantified before and after supplementation.\n At baseline, tHcy was high, vitamin D was low, and T/S did not differ between groups A and B. Vitamin supplementation increased LINE-1 methylation in group A at site 317 but reduced LINE-1 methylation in group B at site 327. There was no correlation between T/S and LINE-1 methylation at baseline. Multiple backward regression analysis revealed baseline tHcy and 5-methylTHF are significant predictors of T/S. After supplementation in group B but not in group A, LINE-1 methylation correlated inversely with T/S, and LINE-1 methylation variation was an independent predictor of T/S variation. B vitamins decreased tHcy significantly in group A. Multiple backward regression analysis showed 5-methylTHF in group A and tHcy in group B were significant predictors for LINE-1 methylation. At baseline, the lower LINE-1 methylation observed in subjects with 5-methylTHF >10 nmol/l was in agreement with a reduced methyl group transfer due to a lower SAM formation. In group B, an increase in telomere length was correlated with lower LINE-1 methylation. Subjects with hyperhomocysteinemia >12 µmol/L had compared to those with normal tHcy a reduced LINE-1 methylation accompanied by a higher SAM and SAH (that inhibits demethylation of SAM) as well as lower 5-methylTHF. Additionally, subjects with tHcy > 12 µmol/L had longer telomeres when compared with subjects having tHcy < 12 µmol/L.\n The results suggest a possible effect of B vitamins for telomere biology in blood cells. Suboptimal B vitamins status and hyperhomocysteinemia are associated with altered DNA methylation and telomere length. These data have to be confirmed in future studies.\n\nHerrmann, Markus\n\n\n"
},
{
"text": "\n168847\nVisual Acuity Change Over 24 Months and Its Association With Foveal Phenotype and Genotype in Individuals With Stargardt Disease: ProgStar Study Report No. 10.\n\nKong, X\n\nFujinami, K\n\nStrauss, RW\n\nMunoz, B\n\nWest, SK\n\nCideciyan, AV\n\nMichaelides, M\n\nAhmed, M\n\nErvin, AM\n\nSchönbach, E\n\nCheetham, JK\n\nScholl, HPN\n\nProgStar Study Group\n\nBeiträge in Fachzeitschriften\nISI:000441186300018\n29902293.0\n10.1001/jamaophthalmol.2018.2198\nPMC6142940\nLimited data from prospective studies are available to understand the natural history of ABCA4-related Stargardt disease (STGD1). Such data are important for determining appropriate outcome measures for future STGD1 trials.\n To estimate the rate of loss of best-corrected visual acuity (BCVA) during 2 years and to estimate the associations of BCVA loss with foveal phenotype and genotype in patients with STGD1.\n This multicenter prospective cohort study included 259 participants (489 study eyes) with molecularly confirmed STGD1 who were 6 years or older. The participants were enrolled at 9 centers in the United States and Europe and were followed up every 6 months for 2 years.\n Baseline BCVA and presence and type of foveal lesion (determined via fundus autofluorescence images) and genotype (classified into 4 groups based on the number and pathogenicity of ABCA4 mutations).\n Rate of BCVA change per year.\n The mean (SD) age was 33 (15) years. Of 259 the participants, 141 (54%) were female, and 222 (85%) were white. The overall rate of BCVA loss was 0.55 (95% CI, 0.20-0.90) letters per year during the 2 years. Eyes with baseline BCVA worse than 20/200 showed an improvement of 0.65 (95% CI, 0.1-1.2) letters per year. At baseline, the mean BCVA for eyes without foveal lesion was 20/32, and their BCVA change rate over time was 0.1 (95% CI, -1.2 to 1.35) letters per year (P = .89). Eyes with a foveal lesion but having BCVA of 20/70 or better at baseline lost BCVA at a rate of 3 (95% CI, 1.5-4.4) letters per year (P < .001). Genotype was neither associated with baseline BCVA nor with the rate of BCVA change during the follow-up.\n A clinically small BCVA loss was observed during 2 years, and the change rate varied depending on baseline BCVA. Eyes without lesion in the fovea had better BCVA at baseline and showed minimal change of BCVA throughout 2 years. Eyes with no or modest acuity impairment but with a foveal lesion at baseline had the fastest loss rate. For trials of STGD1 with 2 years of duration, it may be difficult to show efficacy using BCVA as an end point owing to its slow rate of change over this time.\n\nStrauß, Rupert\n\n\n"
},
{
"text": "\n177361\nPatient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer.\n\nLorusso, D\n\nHilpert, F\n\nGonzález Martin, A\n\nRau, J\n\nOttevanger, P\n\nGreimel, E\n\nLück, HJ\n\nSelle, F\n\nColombo, N\n\nKroep, JR\n\nMirza, MR\n\nBerger, R\n\nPardo, B\n\nGrischke, EM\n\nBerton-Rigaud, D\n\nMartinez-Garcia, J\n\nVergote, I\n\nRedondo, A\n\nCardona, A\n\nBastière-Truchot, L\n\ndu Bois, A\n\nKurzeder, C\n\nPENELOPE trial investigators\n\nBeiträge in Fachzeitschriften\nISI:000486848200011\n31420414.0\n10.1136/ijgc-2019-000370\nNone\nThe PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes.\n Eligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression.\n At database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms.\n Consistent with the primary results, adding pertuzumab to chemotherapy for low tumor HER3 mRNA-expressing platinum-resistant ovarian cancer did not improve overall survival, but showed trends in some cohorts. Except for increased diarrhea symptoms, pertuzumab had no impact on patient-reported outcomes. ClinicalTrials.gov: ClinicalTrials.gov: NCT01684878.\n © IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.\n\nGreimel, Elfriede Renate\n\n\n"
},
{
"text": "\n11788\nHemofiltration in acute kidney failure. Experiences of a surgical intensive care station\n\nList, WF\n\nKulier, A\n\nKiesling, A\n\nSemu, J\n\nBeiträge in Fachzeitschriften\nISI:A1990EF64300017\n2278375.0\nNone\nNone\nUntil recently acute renal failure (ARF) in critically ill patients has been known to have a very poor prognosis, particularly when associated with multiple organ failure (MOF). Mortality rates for ARF in combination with at least two other failing organ systems have ranged over 90%. Despite the use of intermittent hemodialysis no better outcome was possible until continuous arteriovenous hemofiltration (CAVH) was introduced by Kramer in 1977. From several extracorporeal clearance methods we chose to evaluate the pump-driven intermittent venovenous hemofiltration (HF) system in the ICU and its effect on mortality in MOF. PATIENTS and METHODS. Over a period of 39 months we evaluated 63 patients, 58 of them with MOF undergoing altogether 532 sessions of HF. The reason for the development of ARF was prerenal in 47% (circulatory shock, hypovolemia), renal in 43% (septic) and other problems in 10% (ARDS, cardiac failure). After special optimizing therapy for patients with ARF (10), HF was required for treatment as defined by a serum creatinine greater than 3 mg/dl (BUN greater than 150 mg/dl), oliguria of less than 30 ml/h or a creatinine clearance of less than 20 ml/min. Vascular access was obtained by a double lumen venous cannula inserted into the subclavian vein. HF was performed by a machine equipped with 3 roller pumps and an electronic fluid equilibration system using a hollow fiber filter running for 6-8 h. The average flow of ultrafiltrate was 74 ml/min. RESULTS. The average decrease per hemofiltration of creatinine levels was 1.97 +/- 0.77 mg/dl, of BUN 73.5 +/- 28.3 mg/dl. Moreover, we noticed decreasing platelet counts, fibrinogen and osmolarity levels, as well as a slight increase in pH values. Mortality was 37%. DISCUSSION. When comparing HF with other clearance methods such as hemodialysis there are some remarkable advantages: easier handling of the fluid and electrolyte balance; the possibility of total i.v. alimentation in septic, hypercatabolic patients, safe and precise administration of antibiotics, glycosides and sedatives because of their highly predictable and steady elimination rates throughout HF; last but not least, the removal of renal and vasoactive toxins. There was practically no impairment of the cardiovascular system during HF. Our experiences in the ICU show that HF has been successfully used with decreasing mortality. This kind of treatment improved the fate of the critically ill patient with ARF alone or combined with MOF to the extent that the patient's prognosis was excellent if the main surgical problems could be solved.\n\nSandner-Kiesling, Andreas\n\n\n"
},
{
"text": "\n22640\nX-PERT: weight reduction with orlistat in obese subjects receiving a mildly or moderately reduced-energy diet: early response to treatment predicts weight maintenance.\n\nToplak, H\n\nZiegler, O\n\nKeller, U\n\nHamann, A\n\nGodin, C\n\nWittert, G\n\nZanella, MT\n\nZuniga-Guajardo, S\n\nVan Gaal, L\n\nBeiträge in Fachzeitschriften\nISI:000232390600008\n16219013.0\n10.1111/j.1463-1326.2005.00483.x\nNone\nAIM: To determine the effect of two different levels of energy deficit on weight loss in obese patients treated with orlistat. METHODS: Patients (n=430) were randomized in a 1-year, multicentre, open-label, parallel group study conducted at 23 hospital centres and university medical departments worldwide. Obese outpatients (body mass index 30--43 kg/m(2)) aged 18--70 years with a body weight of >or=90 kg and a waist circumference of >or=88 cm (women) or >or=102 cm (men) were treated with orlistat 120 mg three times daily plus a diet that provided an energy deficit of either 500 or 1, 00 kcal/day for 1 year. Orlistat treatment was discontinued in patients who did not achieve >or=5% weight loss after assessment at 3 and 6 months. The primary outcome measure was change in body weight from baseline at week 52. RESULTS: Reported mean difference in energy intake between the two groups (500-1, 00 kcal/day deficit) at weeks 24 and 52 was actually 111 and 95 kcal/day respectively. Of the 430 patients involved in the study, 295 achieved >or=5% weight loss at both 3 and 6 months. In this population, at week 52, weight loss from baseline was similar for patients randomized to either the 500 or the 1, 00 kcal/day deficit diet (-11.4 kg vs. -11.8 kg, respectively; p=0.778). After 12 months of treatment with orlistat, 84% (n=118/141) and 85% (n=131/154) of patients in the 500 and 1, 00 kcal/day deficit groups, respectively, achieved >or=5% weight loss, and 50% (n=70/141) and 53% (n=82/154) of patients, respectively, achieved >or=10% weight loss. Patients in both the diet treatment groups showed similar significant improvements in blood pressure, lipid levels and waist circumference at week 52. CONCLUSIONS: Treatment with orlistat was associated with a clinically beneficial weight loss, irrespective of the prescribed dietary energy restriction (-500 or -1000 kcal/day). Patients who achieved >or=5% weight loss at 3 months achieved long-term, clinically beneficial weight loss with orlistat plus either diet. Therefore, identifying patients who lose at least 5% weight after 3 months and who maintain this weight loss up to 6 months is a valuable treatment algorithm to select patients who will benefit most from orlistat treatment in combination with diet.\n\nToplak, Hermann\n\n\n"
},
{
"text": "\n65950\nRationale and design of a trial improving outcome of type 2 diabetics on hemodialysis. Die Deutsche Diabetes Dialyse Studie Investigators.\n\nWanner, C\n\nKrane, V\n\nRuf, G\n\nMärz, W\n\nRitz, E\n\nBeiträge in Fachzeitschriften\nISI:000081081800059\n10412782.0\n10.1046/j.1523-1755.1999.07158.x\nNone\nBACKGROUND: Non-insulin-dependent diabetes mellitus dialysis patients have the highest cardiovascular mortality known in any group of patients. Mixed dyslipidemia with moderately elevated low-density lipoprotein (LDL) cholesterol and high levels of triglyceride-rich lipoproteins is common in this condition. It is not known, however, whether patients with type 2 diabetes on dialysis with this form of dyslipidemia derive benefit from lipid-lowering therapy. Recently, drugs have become available that potently lower triglyceride-rich, apoB-containing lipoproteins and thus permit testing of this issue. This is the first trial to address specifically the issue of whether the excessive cardiovascular mortality of patients with type 2 diabetes on dialysis can be lowered by statins. METHODS: The Die Deutsche Diabetes Dialyse Studie is a prospective randomized placebo-controlled trial that tests the hypothesis that atorvastatin, a hydroxymethyl-glutaryl coenzyme A reductase inhibitor, decreases the rate of cardiovascular mortality and of nonfatal myocardial infarction in patients with type 2 diabetes who have been on hemodialysis treatment for no more than two years. The primary endpoint, cardiovascular mortality, includes fatal myocardial infarction, sudden death, death during coronary intervention, death from heart failure, and other coronary causes. Secondary endpoints comprise overall mortality, nonfatal cardiovascular events, fatal and nonfatal cerebrovascular disease, and the mean percentage change in lipid profile from baseline. The trial enrolls 1200 men and women on hemodialysis for less than two years and with type 2 diabetes at 150 centers throughout Germany. Inclusion criteria are age of 18 to 80 years, low-density cholesterol of 80 to 190 mg/dl (2.1 to 4.9 mmol/liter), and triglyceride levels of less than 1000 mg/dl (11.4 mmol/liter). Patients are randomized to cither inactive (placebo) or active (atorvastatin, 20 mg/day) drug therapy. The average duration of follow-up is more than 2.5 years. To protect against a lower than expected rate of events, the trial will be continued until a predetermined fixed number of endpoints occurs in the entire cohort so that the predefined power of the trial will be guaranteed. CONCLUSIONS: This trial was designed to demonstrate that lipid lowering with atorvastatin will improve life expectancy and quality of life in type 2 diabetics on hemodialysis. The resolution of this question is important because the genesis of vascular lesions in this condition is multifactorial and the precise role of dyslipidemia has not been defined.\n\nMärz, Winfried\n\n\n"
}
]
}