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"text": "\n156069\nResults of renal transplantation using kidneys harvested from living donors at the University of Heidelberg\n\nMehrabi, A\n\nWiesel, M\n\nZeier, M\n\nKashfi, A\n\nSchemmer, P\n\nKraus, T\n\nBuchler, MW\n\nSchmidt, J\n\nBeiträge in Fachzeitschriften\nISI:000223205100010\n15240850.0\n10.1093/ndt/gfh1042\nNone\nAlthough a majority of patients undergoing renal transplantation currently receive a cadaver kidney, living donors continue to be an important source of transplanted kidneys. Recipients of living donor kidneys demonstrate improved graft survival. To expand the pool of suitable organ donors an organ procurement programme of living donors has been developed over the past 35 years. We have reviewed our living donor nephrectomy experience over this period to analyse the donor and recipient peri- and postoperative morbidity and mortality rate.\n We reviewed the operative complications and the long-term outcome of 219 living donated kidney transplantations before and after introduction of cyclosporine A. Donor and graft complications as well as recipient complications and survival rate were investigated. Additionally, the findings of 16 laparoscopically operated living donors were compared to a group of 20 patients who underwent a conventional surgery.\n The overall recipient 3 and 5 year survival rates in the cyclosporine A era were 95 and 94%, respectively. Prior to the introduction of cyclosporine A, the overall recipient survival rates at 3 and 5 years were 84 and 84%, respectively. The overall graft survival rates were 92 and 85% for the cyclosporine A era compared to 68 and 60% before introduction of cyclosporine A, at 3 and 5 years, respectively. The patient and graft survival rate in the cyclosporine group were significantly higher than in the pre-cyclosporine group (log-rank: P = 0.0107 and P = 0.0003, respectively). Donor complications included pain at the incision site (35%), mild hypertension (27%), proteinuria (19%), urinary tract infections (11%), pneumothorax (5%), blood transfusion (3.5%) and wound infection (3%), with no mortalities. Our results showed a longer duration of operation, and longer warm ischaemia and cold ischaemia times in laparoscopically operated living donors than those that were seen in the conventional approach. There was no statistically significant difference in complications between both techniques. However, the hospitalization days and usage of analgesic medication in laparoscopy donors were lower than in the conventional approach.\n Similar to previous studies the results of the present analysis confirm an increase in patient and graft survival rates in the cyclosporine era compared to before its usage. Living donor nephrectomy, done through a conventional or laparoscopic approach, remains a valuable source of kidneys for transplantation with low complication rates.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n157361\nGenome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.\n\nvan Rooij, FJ\n\nQayyum, R\n\nSmith, AV\n\nZhou, Y\n\nTrompet, S\n\nTanaka, T\n\nKeller, MF\n\nChang, LC\n\nSchmidt, H\n\nYang, ML\n\nChen, MH\n\nHayes, J\n\nJohnson, AD\n\nYanek, LR\n\nMueller, C\n\nLange, L\n\nFloyd, JS\n\nGhanbari, M\n\nZonderman, AB\n\nJukema, JW\n\nHofman, A\n\nvan Duijn, CM\n\nDesch, KC\n\nSaba, Y\n\nOzel, AB\n\nSnively, BM\n\nWu, JY\n\nSchmidt, R\n\nFornage, M\n\nKlein, RJ\n\nFox, CS\n\nMatsuda, K\n\nKamatani, N\n\nWild, PS\n\nStott, DJ\n\nFord, I\n\nSlagboom, PE\n\nYang, J\n\nChu, AY\n\nLambert, AJ\n\nUitterlinden, AG\n\nFranco, OH\n\nHofer, E\n\nGinsburg, D\n\nHu, B\n\nKeating, B\n\nSchick, UM\n\nBrody, JA\n\nLi, JZ\n\nChen, Z\n\nZeller, T\n\nGuralnik, JM\n\nChasman, DI\n\nPeters, LL\n\nKubo, M\n\nBecker, DM\n\nLi, J\n\nEiriksdottir, G\n\nRotter, JI\n\nLevy, D\n\nGrossmann, V\n\nPatel, KV\n\nChen, CH\n\nBioBank Japan Project\n\nRidker, PM\n\nTang, H\n\nLauner, LJ\n\nRice, KM\n\nLi-Gao, R\n\nFerrucci, L\n\nEvans, MK\n\nChoudhuri, A\n\nTrompouki, E\n\nAbraham, BJ\n\nYang, S\n\nTakahashi, A\n\nKamatani, Y\n\nKooperberg, C\n\nHarris, TB\n\nJee, SH\n\nCoresh, J\n\nTsai, FJ\n\nLongo, DL\n\nChen, YT\n\nFelix, JF\n\nYang, Q\n\nPsaty, BM\n\nBoerwinkle, E\n\nBecker, LC\n\nMook-Kanamori, DO\n\nWilson, JG\n\nGudnason, V\n\nO'Donnell, CJ\n\nDehghan, A\n\nCupples, LA\n\nNalls, MA\n\nMorris, AP\n\nOkada, Y\n\nReiner, AP\n\nZon, LI\n\nGanesh, SK\n\nBeiträge in Fachzeitschriften\nISI:000391910500005\n28017375.0\n10.1016/j.ajhg.2016.11.016\nPMC5223059\nGenome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71, 38 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.\n Copyright © 2017 American Society of Human Genetics. All rights reserved.\n\nHofer, Edith\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n169637\nRelationship between Clinic and Ambulatory Blood-Pressure Measurements and Mortality\n\nZweiker, R\n\nBeiträge in Fachzeitschriften\nISI:000445149200006\nNone\nNone\nNone\nBackground: Evidence for the influence of ambulatory blood pressure on prognosis derives mainly from populationbased studies and a few relatively small clinical investigations. This study examined the associations of blood pressure measured in the clinic (clinic blood pressure) and 24-hour ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of patients in primary care. Methods: We analyzed data from a registry-based, multicenter, national cohort that included 63, 10 adults recruited from 2004 through 2014 in Spain. Clinic and 24-hour ambulatory blood-pressure data were examined in the following categories: sustained hypertension (elevated clinic and elevated 24-hour ambulatory blood pressure) "white-coat" hypertension (elevated clinic and normal 24-hour ambulatory blood pressure), masked hypertension (normal clinic and elevated 24-hour ambulatory blood pressure), and normotension (normal clinic and normal 24-hour ambulatory blood pressure). Analyses were conducted with Cox regression models, adjusted for clinic and 24-hour ambulatory blood pressures and for confounders. Results: During a median follow-up of 4.7 years, 3808 patients died from any cause, and 1295 of these patients died from cardiovascular causes. In a model that included both 24-hour and clinic measurements, 24-hour systolic pressure was more strongly associated with all-cause mortality (hazard ratio, 1.58 per 1-SD increase in pressure; 95% confidence interval [CI], 1.56 to 1.60, after adjustment for clinic blood pressure) than the clinic systolic pressure (hazard ratio, 1.02; 95% CI, 1.00 to 1.04, after adjustment for 24-hour blood pressure). Corresponding hazard ratios per 1-SD increase in pressure were 1.55 (95% CI, 1.53 to 1.57, after adjustment for clinic and daytime blood pressures) for nighttime ambulatory systolic pressure and 1.54 (95% CI, 1.52 to 1.56, -after adjustment for clinic and night-time blood pressures) for daytime ambulatory systolic pressure. These relationships were consistent across subgroups of age, sex, and status with respect to obesity, diabetes, cardiovascular disease, and antihypertensive treatment. Masked hypertension was more strongly associated with all-cause mortality (hazard ratio, 2.83; 95% CI, 2.12 to 3.79) than sustained hypertension (hazard ratio, 1.80; 95% CI, 1.41 to 2.31) or white-coat hypertension (hazard ratio, 1.79; 95% CI, 1.38 to 2.32). Results for cardiovascular mortality were similar to those for all-cause mortality. Conclusions: Ambulatory blood-pressure measurements were a stronger predictor of all-cause and cardiovascular mortality than clinic blood-pressure measurements. White-coat hypertension was not benign, and masked hypertension was associated with a greater risk of death than sustained hypertension. (Funded by the Spanish Society of Hypertension and others.)\n\nZweiker, Robert\n\n\n"
},
{
"text": "\n177612\nA review on multiplatform evaluations of semi-automatic open-source based image segmentation for cranio-maxillofacial surgery.\n\nWallner, J\n\nSchwaiger, M\n\nHochegger, K\n\nGsaxner, C\n\nZemann, W\n\nEgger, J\n\nBeiträge in Fachzeitschriften\nISI:000498061900005\n31610359.0\n10.1016/j.cmpb.2019.105102\nNone\nComputer-assisted technologies, such as image-based segmentation, play an important role in the diagnosis and treatment support in cranio-maxillofacial surgery. However, although many segmentation software packages exist, their clinical in-house use is often challenging due to constrained technical, human or financial resources. Especially technological solutions or systematic evaluations of open-source based segmentation approaches are lacking. The aim of this contribution is to assess and review the segmentation quality and the potential clinical use of multiple commonly available and license-free segmentation methods on different medical platforms.\n In this contribution, the quality and accuracy of open-source segmentation methods was assessed on different platforms using patient-specific clinical CT-data and reviewed with the literature. The image-based segmentation algorithms GrowCut, Robust Statistics Segmenter, Region Growing 3D, Otsu & Picking, Canny Segmentation and Geodesic Segmenter were investigated in the mandible on the platforms 3D Slicer, MITK and MeVisLab. Comparisons were made between the segmentation algorithms and the ground truth segmentations of the same anatomy performed by two clinical experts (n = 20). Assessment parameters were the Dice Score Coefficient (DSC), the Hausdorff Distance (HD), and Pearsons correlation coefficient (r).\n The segmentation accuracy was highest with the GrowCut (DSC 85.6%, HD 33.5 voxel) and the Canny (DSC 82.1%, HD 8.5 voxel) algorithm. Statistical differences between the assessment parameters were not significant (p < 0.05) and correlation coefficients were close to the value one (r > 0.94) for any of the comparison made between the segmentation methods and the ground truth schemes. Functionally stable and time-saving segmentations were observed.\n High quality image-based semi-automatic segmentation was provided by the GrowCut and the Canny segmentation method. In the cranio-maxillofacial complex, these segmentation methods provide algorithmic alternatives for image-based segmentation in the clinical practice for e.g. surgical planning or visualization of treatment results and offer advantages through their open-source availability. This is the first systematic multi-platform comparison that evaluates multiple license-free, open-source segmentation methods based on clinical data for the improvement of algorithms and a potential clinical use in patient-individualized medicine. The results presented are reproducible by others and can be used for clinical and research purposes.\n Copyright © 2019 Elsevier B.V. All rights reserved.\n\nEgger, Jan\n\nSchwaiger, Michael\n\nWallner, Jürgen\n\nZemann, Wolfgang\n\n\n"
},
{
"text": "\n63601\nAutonomic regulation of circulation and cardiac contractility during a 14-month space flight.\n\nBaevsky, RM\n\nMoser, M\n\nNikulina, GA\n\nPolyakov, VV\n\nFuntova, II\n\nChernikova, AG\n\nBeiträge in Fachzeitschriften\nISI:000075549800015\n11541600.0\n10.1016/S0094-5765(98)00114-3\nNone\nThe space flight of physician cosmonaut V.V. Polyakov, the longest to date (438 days), has yielded new data about human adaptation to long-term weightlessness. Autonomic regulation of circulation and cardiac contractility were evaluated in three experiments entitled Pulstrans, Night, and Holter. In the Pulstrans experiment electrocardiographic (ECG), ballistocardiographic (BCG), seismocardiographic (SCG), and some other parameters were recorded. In the Night experiment, only the ballistocardiogram was recorded, but a special feature of this experiment is that the BCG records were obtained with a contactless method. This method has several advantages, the most important of which are the possibility of studying slow-wave variations in physiologic parameters (ultradian rhythms) on the basis of recordings made under standard conditions over a prolonged period. The Holter experiment (24-hour electrocardiographic monitoring) used a portable cardiorecorder (Spacelab, USA). The obtained electrocardiographic data were used to analyze heart rate variability. In the first 6 months of the 14-month flight, the dynamics of cardiovascular parameters in V.V. Polyakov was virtually the same as in the other cosmonauts. The data obtained after the first 6 months of Polyakov's sojourn in space are unique and mention should be made of at least three important aspects: (1) activation of a new, additional adaptive mechanism in the 8th-9th months of flight, as is evidenced by alterations in the periodicity and power of superslow wave oscillations (ultradian rhythms) reflecting the activity of the subcortical cardiovascular centers and of the higher levels of autonomic regulation; (2) growth of cardiac contractility accompanied by a decrease in heart rate during the last few months of flight; (3) a considerable increase in the daily average values of absolute power of heart rate's variability MF component, which reflects the activity of the vasomotor center. Specific mechanisms of adaptation to weightless conditions appear to be associated with activation of higher autonomic centers. The hypothesis that central levels of circulation regulation are activated in a long-term space flight was investigated by analyzing of ultradian rhythms in nighttime. The data, received during the flight of V. V. Polyakov, show, that the process of human adaptation to long influence of weightlessness consists of a number of consecutive stages, during which the activation of more and more high levels of control system of physiological functions occurs.\n\nMoser, Maximilian\n\n\n"
},
{
"text": "\n164461\nQuality of life for up to 18 months after low-energy hip, vertebral, and distal forearm fractures-results from the ICUROS.\n\nSvedbom, A\n\nBorgstöm, F\n\nHernlund, E\n\nStröm, O\n\nAlekna, V\n\nBianchi, ML\n\nClark, P\n\nCuriel, MD\n\nDimai, HP\n\nJürisson, M\n\nKallikorm, R\n\nLember, M\n\nLesnyak, O\n\nMcCloskey, E\n\nSanders, KM\n\nSilverman, S\n\nSolodovnikov, A\n\nTamulaitiene, M\n\nThomas, T\n\nToroptsova, N\n\nUusküla, A\n\nTosteson, ANA\n\nJönsson, B\n\nKanis, JA\n\nBeiträge in Fachzeitschriften\nISI:000426646900004\n29230511.0\n10.1007/s00198-017-4317-4\nNone\nThis study used data from the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) to estimate the quality of life (QoL) impact of fracture. Hip, vertebral, and distal forearm fractures incur substantial QoL losses. Hip and vertebral fracture results in markedly impaired QoL for at least 18 months.\n The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) is a multinational observational study that aims to describe costs and quality of life (QoL) consequences of osteoporotic fractures. To date, 11 countries have participated in the study: Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, the UK, and the USA. The objective of this paper is to describe the QoL impact of hip, vertebral, and distal forearm fracture.\n Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall) and at 4, 12, and 18 months after fracture. Quality of life was measured as health state utility values (HSUVs) derived from the EQ-5D-3L. Complete case analysis was conducted as the base case with available case and multiple imputation performed as sensitivity analyses. Multivariate analysis was performed to explore predictors of QoL impact of fracture.\n Among 5456 patients enrolled using convenience sampling, 3021 patients were eligible for the base case analysis (1415 hip, 1047 distal forearm, and 559 vertebral fractures). The mean (SD) difference between HSUV before and after fracture for hip, vertebral, and distal forearm fracture was estimated at 0.89 (0.40), 0.67 (0.45), and 0.48 (0.34), respectively (p < 0.001 for all fracture types). Eighteen months after fracture, mean HSUVs were lower than before the fracture in patients with hip fracture (0.66 vs. 0.77 p < 0.001) and vertebral fracture (0.70 vs. 0.83 p < 0.001). Hospitalization and higher recalled pre-fracture QoL were associated with increased QoL impact for all fracture types.\n Hip, vertebral, and distal forearm fractures incur substantial loss in QoL and for patients with hip or vertebral fracture, QoL is markedly impaired for at least 18 months.\n\nDimai, Hans\n\n\n"
},
{
"text": "\n171998\nNovel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study.\n\nLackner, S\n\nMörkl, S\n\nMüller, W\n\nFürhapter-Rieger, A\n\nOberascher, A\n\nLehofer, M\n\nBieberger, C\n\nWonisch, W\n\nAmouzadeh-Ghadikolai, O\n\nMoser, M\n\nMangge, H\n\nZelzer, S\n\nHolasek, SJ\n\nBeiträge in Fachzeitschriften\nISI:000501650600055\n30670293.0\n10.1016/j.clnu.2018.12.031\nNone\nAnorexia nervosa (AN) is a severe psychosomatic disease that seriously affects nutritional status. Therapeutic approaches primarily aim for rapid weight restoration by high caloric diets and activity restriction. This often promotes abdominal body fat gain, which potentially negatively influences the patient's compliance and increases the risk of relapse. This study focused on the evaluation of body weight and subcutaneous adipose tissue (SAT) in AN patients by novel approaches.\n The SAT of AN patients (n = 18, body mass index (BMI) 15.3 ± 1.3 kg/m2) was determined by a highly accurate and reliable ultrasound method. The sum of SAT thicknesses of eight sites (DINCL) was calculated. Individual metabolic profiles were analyzed. The mass index (MI), which considers body proportions, was used in addition to BMI. Additional to the standard laboratory diagnostics, dermal carotenoids measured by resonance Raman spectroscopy, leptin, and oxidative stress indicators were determined.\n The mean MI was 15.7 ± 1.4 kg/m2. The DINCL considerably differed between individuals with the same BMI. Half of the patients (Group 1) had low DINCL: 1.3-28.4 mm, and Group 2 showed values up to 58.2 mm (corresponding to approximately 6 kg SAT mass). The two group means differed by more than 300% (P < 0.001). Accordingly, leptin levels significantly differed (P < 0.001). Mean SAT thicknesses were significantly higher in Group 2 at all eight sites. The groups also significantly differed in two oxidative stress parameters: total antioxidative capacity, malondialdehyde-modified low density lipoprotein immunoglobulin M (MDA-LDL IgM), and in the carotenoid level.\n Half of the patients had sufficiently high fat mass, despite very low BMI. Consequently, their muscle (and other organ) masses must have been extremely low. Diagnostic criteria and treatment protocols for AN should consider each patient's body composition. In addition to dietary treatments, muscle training at low energy turnover rates may be essential for avoiding unnecessary body fat gain, better treatment results, and long-term recovery.\n Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.\n\nFürhapter-Rieger, Alfred\n\nHolasek, Sandra Johanna\n\nLackner, Sonja\n\nMangge, Harald\n\nMörkl, Sabrina\n\nMoser, Maximilian\n\nMüller, Wolfram\n\nWonisch, Willibald\n\nZelzer, Sieglinde\n\n\n"
},
{
"text": "\n182742\nWhole-genome sequencing of a sporadic primary immunodeficiency cohort.\n\nThaventhiran, JED\n\nLango Allen, H\n\nBurren, OS\n\nRae, W\n\nGreene, D\n\nStaples, E\n\nZhang, Z\n\nFarmery, JHR\n\nSimeoni, I\n\nRivers, E\n\nMaimaris, J\n\nPenkett, CJ\n\nStephens, J\n\nDeevi, SVV\n\nSanchis-Juan, A\n\nGleadall, NS\n\nThomas, MJ\n\nSargur, RB\n\nGordins, P\n\nBaxendale, HE\n\nBrown, M\n\nTuijnenburg, P\n\nWorth, A\n\nHanson, S\n\nLinger, RJ\n\nBuckland, MS\n\nRayner-Matthews, PJ\n\nGilmour, KC\n\nSamarghitean, C\n\nSeneviratne, SL\n\nSansom, DM\n\nLynch, AG\n\nMegy, K\n\nEllinghaus, E\n\nEllinghaus, D\n\nJorgensen, SF\n\nKarlsen, TH\n\nStirrups, KE\n\nCutler, AJ\n\nKumararatne, DS\n\nChandra, A\n\nEdgar, JDM\n\nHerwadkar, A\n\nCooper, N\n\nGrigoriadou, S\n\nHuissoon, AP\n\nGoddard, S\n\nJolles, S\n\nSchuetz, C\n\nBoschann, F\n\nPrimary Immunodeficiency Consortium for the NIHR Bioresource\n\nLyons, PA\n\nHurles, ME\n\nSavic, S\n\nBurns, SO\n\nKuijpers, TW\n\nTurro, E\n\nOuwehand, WH\n\nThrasher, AJ\n\nSmith, KGC\n\nBeiträge in Fachzeitschriften\nNone\n32499645.0\n10.1038/s41586-020-2265-1\nPMC7334047\nPrimary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies1-3. Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1, 18 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of-and interplay between-novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans.\n\nKovacs, Gabor\n\nOlschewski, Andrea\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n184230\nOptimized drug-coated balloon angioplasty of the superficial femoral and proximal popliteal arteries using the Tack Endovascular System: TOBA III 12-month results.\n\nBrodmann, M\n\nWissgott, C\n\nBrechtel, K\n\nNikol, S\n\nZeller, T\n\nLichtenberg, M\n\nBlessing, E\n\nGray, W\n\nTOBA III Investigators\n\nBeiträge in Fachzeitschriften\nISI:000580652000018\n32414527.0\n10.1016/j.jvs.2020.01.078\nNone\nThe Tack Endovascular System (Intact Vascular, Wayne, Pa) combines low-metallic content with focal delivery to seal areas of dissection associated with balloon angioplasty. The device system is designed to treat vascular dissections in the superficial femoral and proximal popliteal arteries. Tack implants exert low radial force and are associated with minimal metal burden, which reduces the mechanical stress on the arterial wall in treating dissections after balloon angioplasty. This study investigated the safety and effectiveness of the Tack Endovascular System in patients with dissections after drug-coated balloon (DCB) angioplasty.\n The Tack Optimized Balloon Angioplasty III (TOBA III) study is a prospective, multicenter, single-arm study in which patients who underwent percutaneous transluminal angioplasty with the Medtronic IN.PACT Admiral DCB (Medtronic, Dublin, Ireland) and experienced dissection after angioplasty were treated with Tack implants. The primary end points were freedom from major adverse events at 30 days and primary patency at 12 months.\n A total of 201 patients were enrolled in the trial, 169 with standard-length lesions (≥20 mm and ≤150 mm) and 32 with long-length lesions (>150 mm and ≤250 mm). Safety and effectiveness results were favorable compared with historical benchmarks at 12 months in the standard-lesion cohort. Notably, patients in the standard-lesion cohort experienced 95.0% primary patency, 97.5% freedom from clinically driven target lesion revascularization, 100% freedom from amputation, and 100% survival at 12 months (P < .0001). Primary patency in long-lesion patients was 89.3%, freedom from clinically driven target lesion revascularization was 96.8%, and freedom from amputation was 100% at 12 months. Device success was achieved in 95.8% (182/190) and 97.7% (43/44) of devices deployed into standard-lesion and long-lesion patients, respectively. Procedural success was 99.4% (168/169) and 100% (44/44) in the standard-lesion and long-lesion cohorts, respectively, with only one bailout stent placed in the entire population.\n The Tack Endovascular System is a safe and effective treatment option for patients with dissections after angioplasty in the superficial femoral and proximal popliteal arteries, with high patency, low rates of secondary intervention, and low incidence of bailout stenting when it is used in combination with DCB.\n Copyright © 2020. Published by Elsevier Inc.\n\nBrodmann, Marianne\n\n\n"
},
{
"text": "\n185301\nAssessment of Healthcare Provider Workload in Neonatal Resuscitation.\n\nZehnder, EC\n\nLaw, BHY\n\nSchmölzer, GM\n\nBeiträge in Fachzeitschriften\nNone\n33415089.0\n10.3389/fped.2020.598475\nPMC7784715\nObjective: Human errors or protocol deviations during neonatal resuscitation are common. Excess workload has been proposed as a contributor to human error during medical tasks. We aim to characterize healthcare providers' perceived workload during neonatal resuscitation. Design: Perceived workload was measured using a multi-dimensional retrospective National Aeronautics and Space Administration Task Load Index (NASA TLX) survey. The NASA TLX collects data on mental, physical, and temporal demand, performance, effort, and frustration. Each section is rated independently by participants on a scale of 0-20 (0 being lowest and 20 being highest). The Raw-TLX score is a composite score of all dimensions and presented on a scale of 0-100. Healthcare providers complete a paper and pencil survey after attending delivery room resuscitations within 3 months. Setting: Level three neonatal intensive care unit at the Royal Alexandra Hospital, Edmonton, AB, Canada. Participants: All neonatal healthcare providers who attended deliveries. Exposure: Participation in the delivery room care of newborns. Measurement: Raw TLX scores as a measure of overall workload and scores for each dimension of workload. Main Results: During the study period, ~880 neonatal resuscitation events occurred, and a total of 204 surveys were completed. Healthcare providers completed one survey for 179 deliveries, two surveys for 20 deliveries, and three surveys for 5 deliveries. The mean (standard deviation) gestational age was 35 (5) weeks, and the median (interquartile range) birth weight was 2, 90 (1, 30-3, 40) g. Interventions at delivery were (i) stimulation 149 (73%), suction 130 (64%), continuous positive airway pressure 120 (59%), positive pressure ventilation 105 (52%), intubation 33 (16%), chest compression 10 (5%), and epinephrine 4 (2%). The overall median (interquartile range) Raw-TLX was 34 (18-49). The scores varied by dimension with mental demand 10 (5-14), physical demand 4 (1-6), temporal demand 8 (3-14), performance 4 (2-6), effort 8 (4-13), and frustration 4 (1-10). Raw-TLX scores were higher when healthcare providers performed any intervention compared to no intervention [35 (22-49) vs. 8 (6-18), p = 0.0011]; intubation and no intubation was [55 (46-62) vs. 30 (17-46), p = 0.0001], and between performing chest compression vs. no chest compression [55 (49-64) vs. 33 (18-47), p = 0.001]. Conclusion: Perceived workload of neonatal healthcare providers increases during higher acuity deliveries. Healthcare providers' workload during neonatal resuscitation can be measured using NASATLX and was inversely associated with 5-min Apgar score. Future studies assessing healthcare providers' perceived workload during neonatal resuscitation in different settings are warranted.\n Copyright © 2020 Zehnder, Law and Schmölzer.\n\n\n"
},
{
"text": "\n185778\nScreening policies, preventive measures and in-hospital infection of COVID-19 in global surgical practices.\n\nBellato, V\n\nKonishi, T\n\nPellino, G\n\nAn, Y\n\nPiciocchi, A\n\nSensi, B\n\nSiragusa, L\n\nKhanna, K\n\nPirozzi, BM\n\nFranceschilli, M\n\nCampanelli, M\n\nEfetov, S\n\nSica, GS\n\nS-COVID Collaborative Group\n\nBeiträge in Fachzeitschriften\nNone\n33110590.0\n10.7189/jogh.10.020507\nPMC7567431\nIn a surgical setting, COVID-19 patients may trigger in-hospital outbreaks and have worse postoperative outcomes. Despite these risks, there have been no consistent statements on surgical guidelines regarding the perioperative screening or management of COVID-19 patients, and we do not have objective global data that describe the current conditions surrounding this issue. This study aimed to clarify the current global surgical practice including COVID-19 screening, preventive measures and in-hospital infection under the COVID-19 pandemic, and to clarify the international gaps on infection control policies among countries worldwide.\n During April 2-8, 2020, a cross-sectional online survey on surgical practice was distributed to surgeons worldwide through international surgical societies, social media and personal contacts. Main outcome and measures included preventive measures and screening policies of COVID-19 in surgical practice and centers' experiences of in-hospital COVID-19 infection. Data were analyzed by country's cumulative deaths number by April 8, 2020 (high risk, >5000; intermediate risk, 100-5000; low risk, <100).\n A total of 936 centers in 71 countries responded to the survey (high risk, 330 centers; intermediate risk, 242 centers; low risk, 364 centers). In the majority (71.9%) of the centers, local guidelines recommended preoperative testing based on symptoms or suspicious radiologic findings. Universal testing for every surgical patient was recommended in only 18.4% of the centers. In-hospital COVID-19 infection was reported from 31.5% of the centers, with higher rates in higher risk countries (high risk, 53.6%; intermediate risk, 26.4%; low risk, 14.8%; P < 0.001). Of the 295 centers that experienced in-hospital COVID-19 infection, 122 (41.4%) failed to trace it and 58 (19.7%) reported the infection originating from asymptomatic patients/staff members. Higher risk countries adopted more preventive measures including universal testing, routine testing of hospital staff and use of dedicated personal protective equipment in operation theatres, but there were remarkable discrepancies across the countries.\n This large international survey captured the global surgical practice under the COVID-19 pandemic and highlighted the insufficient preoperative screening of COVID-19 in the current surgical practice. More intensive screening programs will be necessary particularly in severely affected countries/institutions.\n Registered in ClinicalTrials.gov: NCT04344197.\n Copyright © 2020 by the Journal of Global Health. All rights reserved.\n\nLemmerer, Martina\n\n\n"
},
{
"text": "\n937\nElevated plasma levels of soluble tumor necrosis factor receptor (sTNFRp60) reflect severity of acute pancreatitis.\n\nKaufmann, P\n\nTilz, GP\n\nLueger, A\n\nDemel, U\n\nBeiträge in Fachzeitschriften\nISI:A1997XW38500007\n9310801.0\n10.1007%2Fs001340050420\nNone\nOBJECTIVE: To investigate the role of activated leukocytes in acute pancreatitis, we measured soluble receptors of tumour necrosis factor alpha (sTNFR, p60 subtype) in plasma and evaluated the association of sTNFR with the clinical severity of the disease. DESIGN: Prospective, descriptive study. SETTING: A medical intensive care unit (ICU) in a university hospital. PATIENTS: 25 consecutive ICU admissions of adult patients with acute pancreatitis. MEASUREMENTS AND RESULTS: The clinical severity of the disease was assessed using weights for the worst 17 physiological abnormalities of the Acute Physiology and Chronic Health Evaluation III score over a 24-h period after admission. According to the sum of these weights (giving the Acute Physiology Score, APS) patients were divided into a group with mild pancreatitis (APS < 25) and into a group with severe pancreatitis (APS > or = 25). Soluble TNFR was determined in plasma using an enzyme-linked immunoadsorbent assay. In patients with clinically severe pancreatitis, plasma sTNFR concentrations of 8.8 (16) ng/ ml (median, interquartile range) were significantly higher when compared to patients with mild disease [2.7 (1.5) ng/ml; p < 0.0001]. The sensitivity and specificity of sTNFR plasma concentrations (cutoff point at 5 ng/ml) for the prediction of severe pancreatitis were 90 and 100%, respectively. A highly positive correlation between sTNFR and deviations of physiological parameters from normal (APS score) was demonstrated (r = 0.81). The development of multiple organ failure (MOF) and death was associated with significantly higher sTNFR levels when compared to patients without MOF and survivors [16.4 (17) vs 3.2 (2) ng/ml, p = 0.0014 and 16.0 (18) vs 3.3 (4) ng/ml, p = 0.016, respectively]. For evidence of necrotizing pancreatitis, plasma C-reactive protein concentrations were measured and a significant exponential regression was found with sTNFR (r = 0.77, p < 0.0001). Patients developing pancreatic necrosis, as demonstrated by contrast-enhanced computed tomography, had significantly higher sTNFR concentrations when compared to patients with edematous pancreatitis [9.1 (17) vs 3.2 (2) ng/ml, p = 0.0018). CONCLUSION: The p60 subtype of soluble TNFR is elevated in the plasma of patients with clinically severe acute pancreatitis. This elevation is positively correlated to abnormalities in physiological parameters, development of MOF, and mortality. The association with pancreatic necrosis suggests that, by mediating the effects of TNF, TNFRp60 reflects inflammatory tissue damage leading to severe systemic complications.\n\nDemel, Ulrike\n\nLueger, Andreas\n\nTilz, Gernot\n\n\n"
},
{
"text": "\n4176\nSupracondylar humerus fracture in childhood--an efficacy study. Results of a multicenter study by the Pediatric Traumatology Section of the German Society of Trauma Surgery--II: Costs and effectiveness of the treatment\n\nvon Laer, L\n\nGünter, SM\n\nKnopf, S\n\nWeinberg, AM\n\nBeiträge in Fachzeitschriften\nISI:000174860500005\n11995216.0\nNone\nNone\nThe following are the results and conclusions of a retrospective research study done on 886 patients with supracondylar fractures of the humerus. The study evaluates how effective the treatment procedures of the fractures are. The patients' fractures were categorized into four groups. It made it easier to differentiate between dislocated and undislocated fractures (see part I Weinberg A et al.). The following parameters were established to evaluate the treatment procedures and to create relevancy to the final outcome depending on the degree of difficulty of the fractures: Length of hospitalization, amount of repositioning procedures (including if an open or closed procedure was needed), amount of post repositioning procedures and the recommended change of therapy, method of retention and fixation, necessary metal removal, amount of check ups needed. The amount of x-ray exams could not be established due to insufficient documentation. The study showed a rather random pattern regarding length of hospitalization and the amount of check ups especially among type I and II patients. Open versus closed repositioning procedures did not seem to be advantageous. The implanted wires did not prevent infections. It just increased the treatment procedure by another hospitalization and anesthesia to remove the implanted wires. Physical therapy was not necessary and was only prescribed in cases of prolonged immobilization. The results of this study generated consequences regarding treatment procedures and developed a more efficient treatment protocol: Type I and II (dislocated and undislocated fractures in one plane) will be treated conservatively on an out-patient basis. Type I in a cast. Type II in a blount or plaster cast with flexed angle between 100 degrees and 130 degrees. Type III an IV (dislocated and undislocated fractures in two or three planes) will be treated if possible with a closed repositioning procedure. Otherwise a close repositioning procedure will be necessary and followed with some kind of KD-osteosynthese to capture the fracture. The patient will be hospitalized for a short period. The blount procedure will not be sufficient for this type of fracture. Therapy and procedure will be translated put in a perspective research study.\n\nWeinberg, Annelie-Martina\n\n\n"
},
{
"text": "\n80772\nThe impact of photon dose calculation algorithms on expected dose distributions in lungs under different respiratory phases.\n\nFogliata, A\n\nNicolini, G\n\nVanetti, E\n\nClivio, A\n\nWinkler, P\n\nCozzi, L\n\nBeiträge in Fachzeitschriften\nISI:000255120100012\n18421117.0\n10.1088/0031-9155/53/9/011\nNone\nA planning study was carried out on a cohort of CT datasets from breast patients scanned during different respiratory phases. The aim of the study was to investigate the influence of different air filling in lungs on the calculation accuracy of photon dose algorithms and to identify potential patterns of failure with clinical implications. Selected respiratory phases were free breathing (FB), representative of typical end expiration, and deep inspiration breath hold (DIBH), a typical condition for clinical treatment with respiratory gating. Algorithms investigated were the pencil beam (PBC), the anisotropic analytical algorithm (AAA) and the collapsed cone (CC) from the Varian Eclipse or Philips Pinnacle planning system. Reference benchmark calculations were performed with the Voxel Monte Carlo (VMC++). An analysis was performed in terms of physical quantities inspecting either dose-volume or dose-mass histograms and in terms of an extension to three dimensions of the gamma index of Low. Results were stratified according to a breathing phase and algorithm. Collectives acquired in FB or DIBH showed well-separated average lung density distributions with mean densities of 0.27 +/- 0.04 and 0.16 +/- 0.02 g cm(-3), respectively, and average peak densities of 0.17 +/- 0.03 and 0.09 +/- 0.02 g cm(-3). Analysis of volume-dose or mass-dose histograms proved the expected deviations on PBC results due to the missing lateral transport of electrons with underestimations in the low dose region and overestimations in the high dose region. From the gamma analysis, it resulted that PBC is systematically defective compared to VMC++ over the entire range of lung densities and dose levels with severe violations in both respiratory phases. The fraction of lung voxels with gamma > 1 for PBC reached 25% in DIBH and about 15% in FB. CC and AAA performed, in contrast, similarly and with fractions of lung voxels with gamma > 1 in average inferior to 2% in FB and 4-5% (AAA) or 6-8% (CC) in DIBH. In summary, PBC proved to be severely defective in calculations involving lungs and particularly for cases where specific respiratory phases (e.g. DIBH) are assumed for treatment. In contrast, CC and AAA manifested a high degree of consistency against the Monte Carlo method and provided stable results over the entire range of clinically relevant densities.\n\nWinkler, Peter\n\n\n"
},
{
"text": "\n91269\nThe vascular anatomy of the tensor fasciae latae perforator flap.\n\nHubmer, MG\n\nSchwaiger, N\n\nWindisch, G\n\nFeigl, G\n\nKoch, H\n\nHaas, FM\n\nJustich, I\n\nScharnagl, E\n\nBeiträge in Fachzeitschriften\nISI:000267895000024\n19568071.0\n10.1097/PRS.0b013e3181ab114c\nNone\nBACKGROUND: The purpose of this study was to differentiate between musculocutaneous and septocutaneous perforators of the tensor fasciae latae perforator flap; to evaluate their number, size, and location; and to provide landmarks to facilitate flap dissection. An additional injection study estimated the skin area of the flap. METHODS: The anatomical study was performed on 23 fixed and injected cadavers. The perforators of the tensor fasciae latae were identified and classified as septocutaneous or musculocutaneous. Diameter, location, and numbers were measured and the perforators were dissected up to their origin. The injection study was performed on 10 fresh cadavers. On one side, the ascending branch of the lateral circumflex femoral artery was injected with methylene blue; on the other side, the septocutaneous perforators were injected selectively. The size, location, and borders of the stained skin were measured. RESULTS: Forty-five thighs were included in this study. All perforators emerged from the ascending branch of the lateral circumflex artery. The average number of musculocutaneous perforators was 2.3 (range, 0 to 5), the distance from the anterior superior iliac spine was 10.9 cm (range, 4.5 to 16.1 cm), and the diameter was 0.9 mm (range, 0.2 to 2 mm). Four specimens had no musculocutaneous perforator. The average number of septocutaneous perforators was 1.8 (range, 1 to 3), the distance from the anterior superior iliac spine was 10.9 cm (range, 6.2 to 15.7 cm), and the diameter was 1.5 mm (range, 0.5 to 3 mm). Seventy-six percent of the septocutaneous perforators emerged between 8 and 12 cm from the anterior superior iliac spine. The possible pedicle length of a flap based on these vessels is 8.1 cm (range, 6.5 to 10 cm). In the injection study, the average skin area stained with methylene blue was 19.4 x 13.4 cm (range, 10 to 24 cm x 7 to 17 cm) in the ascending branch group. In the perforator group, the average skin area was 19.2 x 13.7 cm (range, 15 to 22 cm x 12 to 16 cm). CONCLUSIONS: The authors could show that the number of septocutaneous perforators for the tensor fasciae latae flap is more constant and that their diameter is greater than that of musculocutaneous perforators. The location of these perforators on a line extending from the ilium to the greater trochanter facilitates planning and dissection of a flap.\n\nHubmer, Martin\n\nJustich, Ivo\n\nKoch, Horst\n\n\n"
},
{
"text": "\n130280\nDo young patients with renal cell carcinoma feature a distinct outcome after surgery? A comparative analysis of patient age based on the multinational CORONA database.\n\nAziz, A\n\nMay, M\n\nZigeuner, R\n\nPichler, M\n\nChromecki, T\n\nCindolo, L\n\nSchips, L\n\nDe Cobelli, O\n\nRocco, B\n\nDe Nunzio, C\n\nTubaro, A\n\nComan, I\n\nTruss, M\n\nDalpiaz, O\n\nHoschke, B\n\nGilfrich, C\n\nFeciche, B\n\nFenske, F\n\nSountoulides, P\n\nFigenshau, RS\n\nMadison, K\n\nSánchez-Chapado, M\n\nDel Carmen Santiago Martin, M\n\nWieland, WF\n\nSalzano, L\n\nLotrecchiano, G\n\nWaidelich, R\n\nStief, C\n\nBrookman-May, S\n\nMembers of the CORONA Project and the Young Academic Urologists Renal Cancer Group\n\nBeiträge in Fachzeitschriften\nISI:000329832800009\n23973516.0\n10.1016/j.juro.2013.08.021\nNone\nWe analyzed the distinct clinicopathological features and prognosis of patients with renal cell carcinoma age 40 years or less compared to a reference group of patients 60 to 70 years old.\n Overall 2, 72 patients retrieved from a multicenter international database comprised of 6, 34 patients with surgically treated renal cell carcinoma were included in this retrospective study. Clinical and histopathological features of 297 patients 40 years old or younger (4.8%) were compared to those of 2, 75 patients (36.5%) 60 to 70 years old, who served as the reference group. Median followup was 59 months. The impact of young age and further parameters on disease specific mortality and all cause mortality was evaluated by multivariate Cox proportional hazards regression analyses.\n Young patients more frequently underwent nephron sparing surgery (27% vs 20%, p = 0.008) and regional lymph node dissection compared to older patients (38% vs 32%, p = 0.025). Organ confined tumor stage (81% vs 70%, p <0.001), smaller tumor diameter (4.5 vs 4.7 cm, p = 0.014) and chromophobe subtype (10% vs 4%, p <0.001) were significantly more frequent in young patients. On multivariate analysis older patients had a higher disease specific (HR 2.21, p <0.001) and all cause mortality (HR 3.05, p <0.001). The c indices for the Cox models were 0.87 and 0.78, respectively. However, integration of the variable age group did not significantly increase the predictive accuracy of the disease specific and all cause mortality models.\n Young patients with renal cell carcinoma (40 years old or younger) have significantly different frequencies of clinical and histopathological features, and a significantly lower all cause and disease specific mortality compared to patients 60 to 70 years old.\n Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.\n\nDalpiaz, Orietta\n\nPichler, Martin\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n133715\nNovel genetic markers associate with atrial fibrillation risk in Europeans and Japanese.\n\nLubitz, SA\n\nLunetta, KL\n\nLin, H\n\nArking, DE\n\nTrompet, S\n\nLi, G\n\nKrijthe, BP\n\nChasman, DI\n\nBarnard, J\n\nKleber, ME\n\nDörr, M\n\nOzaki, K\n\nSmith, AV\n\nMüller-Nurasyid, M\n\nWalter, S\n\nAgarwal, SK\n\nBis, JC\n\nBrody, JA\n\nChen, LY\n\nEverett, BM\n\nFord, I\n\nFranco, OH\n\nHarris, TB\n\nHofman, A\n\nKääb, S\n\nMahida, S\n\nKathiresan, S\n\nKubo, M\n\nLauner, LJ\n\nMacfarlane, PW\n\nMagnani, JW\n\nMcKnight, B\n\nMcManus, DD\n\nPeters, A\n\nPsaty, BM\n\nRose, LM\n\nRotter, JI\n\nSilbernagel, G\n\nSmith, JD\n\nSotoodehnia, N\n\nStott, DJ\n\nTaylor, KD\n\nTomaschitz, A\n\nTsunoda, T\n\nUitterlinden, AG\n\nVan Wagoner, DR\n\nVölker, U\n\nVölzke, H\n\nMurabito, JM\n\nSinner, MF\n\nGudnason, V\n\nFelix, SB\n\nMärz, W\n\nChung, M\n\nAlbert, CM\n\nStricker, BH\n\nTanaka, T\n\nHeckbert, SR\n\nJukema, JW\n\nAlonso, A\n\nBenjamin, EJ\n\nEllinor, PT\n\nBeiträge in Fachzeitschriften\nISI:000333256100014\n24486271.0\n10.1016/j.jacc.2013.12.015\nPMC4009240\nThis study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk.\n AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored.\n We performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64, 83 individuals of European ancestry (3, 69 incident and 3, 02 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11, 09 individuals of Japanese ancestry (7, 16 prevalent AF cases).\n We observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements.\n The chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity.\n Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.\n\nMärz, Winfried\n\nSilbernagel, Günther\n\n\n"
},
{
"text": "\n142145\nCommon variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease.\n\nRannikmäe, K\n\nDavies, G\n\nThomson, PA\n\nBevan, S\n\nDevan, WJ\n\nFalcone, GJ\n\nTraylor, M\n\nAnderson, CD\n\nBattey, TW\n\nRadmanesh, F\n\nDeka, R\n\nWoo, JG\n\nMartin, LJ\n\nJimenez-Conde, J\n\nSelim, M\n\nBrown, DL\n\nSilliman, SL\n\nKidwell, CS\n\nMontaner, J\n\nLangefeld, CD\n\nSlowik, A\n\nHansen, BM\n\nLindgren, AG\n\nMeschia, JF\n\nFornage, M\n\nBis, JC\n\nDebette, S\n\nIkram, MA\n\nLongstreth, WT\n\nSchmidt, R\n\nZhang, CR\n\nYang, Q\n\nSharma, P\n\nKittner, SJ\n\nMitchell, BD\n\nHolliday, EG\n\nLevi, CR\n\nAttia, J\n\nRothwell, PM\n\nPoole, DL\n\nBoncoraglio, GB\n\nPsaty, BM\n\nMalik, R\n\nRost, N\n\nWorrall, BB\n\nDichgans, M\n\nVan Agtmael, T\n\nWoo, D\n\nMarkus, HS\n\nSeshadri, S\n\nRosand, J\n\nSudlow, CL\n\nMETASTROKE Consortium\n\nCHARGE WMH Group\n\nISGC ICH GWAS Study Collaboration\n\nWMH in Ischemic Stroke GWAS Study Collaboration\n\nInternational Stroke Genetics Consortium\n\nBeiträge in Fachzeitschriften\nISI:000350576700015\n25653287.0\n10.1212/WNL.0000000000001309\nPMC4351667\nWe hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease.\n We conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1, 70 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1, 45 cases, 1, 85 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12, 89 cases, 62, 04 controls); and white matter hyperintensities (2, 33 individuals with ischemic stroke and 9, 61 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs (p < 0.000084).\n Three intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14-1.46, p = 0.00003; r(2) > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes.\n Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry.\n © 2015 American Academy of Neurology.\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n151328\nVitamin D deficiency in Europe: pandemic?\n\nCashman, KD\n\nDowling, KG\n\nŠkrabáková, Z\n\nGonzalez-Gross, M\n\nValtueña, J\n\nDe Henauw, S\n\nMoreno, L\n\nDamsgaard, CT\n\nMichaelsen, KF\n\nMølgaard, C\n\nJorde, R\n\nGrimnes, G\n\nMoschonis, G\n\nMavrogianni, C\n\nManios, Y\n\nThamm, M\n\nMensink, GB\n\nRabenberg, M\n\nBusch, MA\n\nCox, L\n\nMeadows, S\n\nGoldberg, G\n\nPrentice, A\n\nDekker, JM\n\nNijpels, G\n\nPilz, S\n\nSwart, KM\n\nvan Schoor, NM\n\nLips, P\n\nEiriksdottir, G\n\nGudnason, V\n\nCotch, MF\n\nKoskinen, S\n\nLamberg-Allardt, C\n\nDurazo-Arvizu, RA\n\nSempos, CT\n\nKiely, M\n\nBeiträge in Fachzeitschriften\nISI:000373426400012\n26864360.0\n10.3945/ajcn.115.120873\nPMC5527850\nVitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys.\n This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe.\n The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography-tandem mass spectrometry on biobanked sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n= 55, 44). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data.\n An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55, 44 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October-March) and summer (April-November) periods, respectively. According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations.\n Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency in the majority of the European population.\n © 2016 American Society for Nutrition.\n\nPilz, Stefan\n\n\n"
},
{
"text": "\n151409\nCausal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study.\n\nKeenan, T\n\nZhao, W\n\nRasheed, A\n\nHo, WK\n\nMalik, R\n\nFelix, JF\n\nYoung, R\n\nShah, N\n\nSamuel, M\n\nSheikh, N\n\nMucksavage, ML\n\nShah, O\n\nLi, J\n\nMorley, M\n\nLaser, A\n\nMallick, NH\n\nZaman, KS\n\nIshaq, M\n\nRasheed, SZ\n\nMemon, FU\n\nAhmed, F\n\nHanif, B\n\nLakhani, MS\n\nFahim, M\n\nIshaq, M\n\nShardha, NK\n\nAhmed, N\n\nMahmood, K\n\nIqbal, W\n\nAkhtar, S\n\nRaheel, R\n\nO'Donnell, CJ\n\nHengstenberg, C\n\nMärz, W\n\nKathiresan, S\n\nSamani, N\n\nGoel, A\n\nHopewell, JC\n\nChambers, J\n\nCheng, YC\n\nSharma, P\n\nYang, Q\n\nRosand, J\n\nBoncoraglio, GB\n\nKazmi, SU\n\nHakonarson, H\n\nKöttgen, A\n\nKalogeropoulos, A\n\nFrossard, P\n\nKamal, A\n\nDichgans, M\n\nCappola, T\n\nReilly, MP\n\nDanesh, J\n\nRader, DJ\n\nVoight, BF\n\nSaleheen, D\n\nBeiträge in Fachzeitschriften\nISI:000368615600009\n26821629.0\n10.1016/j.jacc.2015.10.086\nPMC5503188\nAlthough epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain.\n Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF).\n This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26, 88/83, 64), CHD (54, 01/68, 75), ischemic stroke (14, 79/67, 12), and HF (4, 26/18, 00). As a positive control, this study also investigated our genetic instrument in 3, 51 gout cases and 68, 50 controls.\n Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations.\n Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions.\n Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.\n\nMärz, Winfried\n\n\n"
}
]
}