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        {
            "text": "\n141363\nCommon genetic variants influence human subcortical brain structures.\n\nHibar, DP\n\nStein, JL\n\nRenteria, ME\n\nArias-Vasquez, A\n\nDesrivières, S\n\nJahanshad, N\n\nToro, R\n\nWittfeld, K\n\nAbramovic, L\n\nAndersson, M\n\nAribisala, BS\n\nArmstrong, NJ\n\nBernard, M\n\nBohlken, MM\n\nBoks, MP\n\nBralten, J\n\nBrown, AA\n\nChakravarty, MM\n\nChen, Q\n\nChing, CR\n\nCuellar-Partida, G\n\nden Braber, A\n\nGiddaluru, S\n\nGoldman, AL\n\nGrimm, O\n\nGuadalupe, T\n\nHass, J\n\nWoldehawariat, G\n\nHolmes, AJ\n\nHoogman, M\n\nJanowitz, D\n\nJia, T\n\nKim, S\n\nKlein, M\n\nKraemer, B\n\nLee, PH\n\nOlde Loohuis, LM\n\nLuciano, M\n\nMacare, C\n\nMather, KA\n\nMattheisen, M\n\nMilaneschi, Y\n\nNho, K\n\nPapmeyer, M\n\nRamasamy, A\n\nRisacher, SL\n\nRoiz-Santiañez, R\n\nRose, EJ\n\nSalami, A\n\nSämann, PG\n\nSchmaal, L\n\nSchork, AJ\n\nShin, J\n\nStrike, LT\n\nTeumer, A\n\nvan Donkelaar, MM\n\nvan Eijk, KR\n\nWalters, RK\n\nWestlye, LT\n\nWhelan, CD\n\nWinkler, AM\n\nZwiers, MP\n\nAlhusaini, S\n\nAthanasiu, L\n\nEhrlich, S\n\nHakobjan, MM\n\nHartberg, CB\n\nHaukvik, UK\n\nHeister, AJ\n\nHoehn, D\n\nKasperaviciute, D\n\nLiewald, DC\n\nLopez, LM\n\nMakkinje, RR\n\nMatarin, M\n\nNaber, MA\n\nMcKay, DR\n\nNeedham, M\n\nNugent, AC\n\nPütz, B\n\nRoyle, NA\n\nShen, L\n\nSprooten, E\n\nTrabzuni, D\n\nvan der Marel, SS\n\nvan Hulzen, KJ\n\nWalton, E\n\nWolf, C\n\nAlmasy, L\n\nAmes, D\n\nArepalli, S\n\nAssareh, AA\n\nBastin, ME\n\nBrodaty, H\n\nBulayeva, KB\n\nCarless, MA\n\nCichon, S\n\nCorvin, A\n\nCurran, JE\n\nCzisch, M\n\nde Zubicaray, GI\n\nDillman, A\n\nDuggirala, R\n\nDyer, TD\n\nErk, S\n\nFedko, IO\n\nFerrucci, L\n\nForoud, TM\n\nFox, PT\n\nFukunaga, M\n\nGibbs, JR\n\nGöring, HH\n\nGreen, RC\n\nGuelfi, S\n\nHansell, NK\n\nHartman, CA\n\nHegenscheid, K\n\nHeinz, A\n\nHernandez, DG\n\nHeslenfeld, DJ\n\nHoekstra, PJ\n\nHolsboer, F\n\nHomuth, G\n\nHottenga, JJ\n\nIkeda, M\n\nJack, CR\n\nJenkinson, M\n\nJohnson, R\n\nKanai, R\n\nKeil, M\n\nKent, JW\n\nKochunov, P\n\nKwok, JB\n\nLawrie, SM\n\nLiu, X\n\nLongo, DL\n\nMcMahon, KL\n\nMeisenzahl, E\n\nMelle, I\n\nMohnke, S\n\nMontgomery, GW\n\nMostert, JC\n\nMühleisen, TW\n\nNalls, MA\n\nNichols, TE\n\nNilsson, LG\n\nNöthen, MM\n\nOhi, K\n\nOlvera, RL\n\nPerez-Iglesias, R\n\nPike, GB\n\nPotkin, SG\n\nReinvang, I\n\nReppermund, S\n\nRietschel, M\n\nRomanczuk-Seiferth, N\n\nRosen, GD\n\nRujescu, D\n\nSchnell, K\n\nSchofield, PR\n\nSmith, C\n\nSteen, VM\n\nSussmann, JE\n\nThalamuthu, A\n\nToga, AW\n\nTraynor, BJ\n\nTroncoso, J\n\nTurner, JA\n\nValdés Hernández, MC\n\nvan 't Ent, D\n\nvan der Brug, M\n\nvan der Wee, NJ\n\nvan Tol, MJ\n\nVeltman, DJ\n\nWassink, TH\n\nWestman, E\n\nZielke, RH\n\nZonderman, AB\n\nAshbrook, DG\n\nHager, R\n\nLu, L\n\nMcMahon, FJ\n\nMorris, DW\n\nWilliams, RW\n\nBrunner, HG\n\nBuckner, RL\n\nBuitelaar, JK\n\nCahn, W\n\nCalhoun, VD\n\nCavalleri, GL\n\nCrespo-Facorro, B\n\nDale, AM\n\nDavies, GE\n\nDelanty, N\n\nDepondt, C\n\nDjurovic, S\n\nDrevets, WC\n\nEspeseth, T\n\nGollub, RL\n\nHo, BC\n\nHoffmann, W\n\nHosten, N\n\nKahn, RS\n\nLe Hellard, S\n\nMeyer-Lindenberg, A\n\nMüller-Myhsok, B\n\nNauck, M\n\nNyberg, L\n\nPandolfo, M\n\nPenninx, BW\n\nRoffman, JL\n\nSisodiya, SM\n\nSmoller, JW\n\nvan Bokhoven, H\n\nvan Haren, NE\n\nVölzke, H\n\nWalter, H\n\nWeiner, MW\n\nWen, W\n\nWhite, T\n\nAgartz, I\n\nAndreassen, OA\n\nBlangero, J\n\nBoomsma, DI\n\nBrouwer, RM\n\nCannon, DM\n\nCookson, MR\n\nde Geus, EJ\n\nDeary, IJ\n\nDonohoe, G\n\nFernández, G\n\nFisher, SE\n\nFrancks, C\n\nGlahn, DC\n\nGrabe, HJ\n\nGruber, O\n\nHardy, J\n\nHashimoto, R\n\nHulshoff Pol, HE\n\nJönsson, EG\n\nKloszewska, I\n\nLovestone, S\n\nMattay, VS\n\nMecocci, P\n\nMcDonald, C\n\nMcIntosh, AM\n\nOphoff, RA\n\nPaus, T\n\nPausova, Z\n\nRyten, M\n\nSachdev, PS\n\nSaykin, AJ\n\nSimmons, A\n\nSingleton, A\n\nSoininen, H\n\nWardlaw, JM\n\nWeale, ME\n\nWeinberger, DR\n\nAdams, HH\n\nLauner, LJ\n\nSeiler, S\n\nSchmidt, R\n\nChauhan, G\n\nSatizabal, CL\n\nBecker, JT\n\nYanek, L\n\nvan der Lee, SJ\n\nEbling, M\n\nFischl, B\n\nLongstreth, WT\n\nGreve, D\n\nSchmidt, H\n\nNyquist, P\n\nVinke, LN\n\nvan Duijn, CM\n\nXue, L\n\nMazoyer, B\n\nBis ...\n\nBeiträge in Fachzeitschriften\nISI:000352454600040\n25607358.0\n10.1038/nature14101\nPMC4393366\nThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30, 17 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
        },
        {
            "text": "\n187896\nThe trans-ancestral genomic architecture of glycemic traits\n\nChen, J\n\nSpracklen, CN\n\nMarenne, G\n\nVarshney, A\n\nCorbin, LJ\n\nLuan, JA\n\nWillems, SM\n\nWu, Y\n\nZhang, XS\n\nHorikoshi, M\n\nBoutin, TS\n\nMagi, R\n\nWaage, J\n\nLi-Gao, RF\n\nChan, KHK\n\nYao, J\n\nAnasanti, MD\n\nChu, AY\n\nClaringbould, A\n\nHeikkinen, J\n\nHong, J\n\nHottenga, JJ\n\nHuo, SF\n\nKaakinen, MA\n\nLouie, T\n\nMarz, W\n\nMoreno-Macias, H\n\nNdungu, A\n\nNelson, SC\n\nNolte, IM\n\nNorth, KE\n\nRaulerson, CK\n\nRay, D\n\nRohde, R\n\nRybin, D\n\nSchurmann, C\n\nSim, XL\n\nSoutham, L\n\nStewart, ID\n\nWang, CA\n\nWang, YJ\n\nWu, PT\n\nZhang, WH\n\nAhluwalia, TS\n\nAppel, EVR\n\nBielak, LF\n\nBrody, JA\n\nBurtt, NP\n\nCabrera, CP\n\nCade, BE\n\nChai, JF\n\nChai, XR\n\nChang, LC\n\nChen, CH\n\nChen, BH\n\nChitrala, KN\n\nChiu, YF\n\nde Haan, HG\n\nDelgado, GE\n\nDemirkan, A\n\nDuan, Q\n\nEngmann, J\n\nFatumo, SA\n\nGayan, J\n\nGiulianini, F\n\nGong, JH\n\nGustafsson, S\n\nHai, Y\n\nHartwig, FP\n\nHe, J\n\nHeianza, Y\n\nHuang, T\n\nHuerta-Chagoya, A\n\nHwang, MY\n\nJensen, RA\n\nKawaguchi, T\n\nKentistou, KA\n\nKim, YJ\n\nKleber, ME\n\nKooner, IK\n\nLai, SQ\n\nLange, LA\n\nLangefeld, CD\n\nLauzon, M\n\nLi, M\n\nLigthart, S\n\nLiu, J\n\nLoh, M\n\nLong, JR\n\nLyssenko, V\n\nMangino, M\n\nMarzi, C\n\nMontasser, ME\n\nNag, A\n\nNakatochi, M\n\nNoce, D\n\nNoordam, R\n\nPistis, G\n\nPreuss, M\n\nRaffield, L\n\nRasmussen-Torvik, LJ\n\nRich, SS\n\nRobertson, NR\n\nRueedi, R\n\nRyan, K\n\nSanna, S\n\nSaxena, R\n\nSchraut, KE\n\nSennblad, B\n\nSetoh, K\n\nSmith, AV\n\nSparso, T\n\nStrawbridge, RJ\n\nTakeuchi, F\n\nTan, JY\n\nTrompet, S\n\nvan den Akker, E\n\nvan der Most, PJ\n\nVerweij, N\n\nVogel, M\n\nWang, HM\n\nWang, CL\n\nWang, N\n\nWarren, HR\n\nWen, WQ\n\nWilsgaard, T\n\nWong, A\n\nWood, AR\n\nXie, T\n\nZafarmand, MH\n\nZhao, JH\n\nZhao, W\n\nAmin, N\n\nArzumanyan, Z\n\nAstrup, A\n\nBakker, SJL\n\nBaldassarre, D\n\nBeekman, M\n\nBergman, RN\n\nBertoni, A\n\nBluher, M\n\nBonnycastle, LL\n\nBornstein, SR\n\nBowden, DW\n\nCai, QY\n\nCampbell, A\n\nCampbell, H\n\nChang, YC\n\nde Geus, EJC\n\nDehghan, A\n\nDu, SF\n\nEiriksdottir, G\n\nFarmaki, AE\n\nFranberg, M\n\nFuchsberger, C\n\nGao, YT\n\nGjesing, AP\n\nGoel, A\n\nHan, S\n\nHartman, CA\n\nHerder, C\n\nHicks, AA\n\nHsieh, CH\n\nHsueh, WA\n\nIchihara, S\n\nIgase, M\n\nIkram, MA\n\nJohnson, WC\n\nJorgensen, ME\n\nJoshi, PK\n\nKalyani, RR\n\nKandeel, FR\n\nKatsuya, T\n\nKhor, CC\n\nKiess, W\n\nKolcic, I\n\nKuulasmaa, T\n\nKuusisto, J\n\nLall, K\n\nLam, K\n\nLawlor, DA\n\nLee, NR\n\nLemaitre, RN\n\nLi, HL\n\nLin, SY\n\nLindstrom, J\n\nLinneberg, A\n\nLiu, JJ\n\nLorenzo, C\n\nMatsubara, T\n\nMatsuda, F\n\nMingrone, G\n\nMooijaart, S\n\nMoon, S\n\nNabika, T\n\nNadkarni, GN\n\nNadler, JL\n\nNelis, M\n\nNeville, MJ\n\nNorris, JM\n\nOhyagi, Y\n\nPeters, A\n\nPeyser, PA\n\nPolasek, O\n\nQi, QB\n\nRaven, D\n\nReilly, DF\n\nReiner, A\n\nRivideneira, F\n\nRoll, K\n\nRudan, I\n\nSabanayagam, C\n\nSandow, K\n\nSattar, N\n\nSchurmann, A\n\nShi, JX\n\nStringham, HM\n\nTaylor, KD\n\nTeslovich, TM\n\nThuesen, B\n\nTimmers, PRHJ\n\nTremoli, E\n\nTsai, MY\n\nUitterlinden, A\n\nvan Dam, RM\n\nvan Heemst, D\n\nVlieg, AV\n\nvan Vliet-Ostaptchouk, JV\n\nVangipurapu, J\n\nVestergaard, H\n\nWang, T\n\nvan Dijk, KW\n\nZemunik, T\n\nAbecasis, GR\n\nAdair, LS\n\nAguilar-Salinas, CA\n\nAlarcon-Riquelme, ME\n\nAn, P\n\nAviles-Santa, L\n\nBecker, DM\n\nBeilin, LJ\n\nBergmann, S\n\nBisgaard, H\n\nBlack, C\n\nBoehnke, M\n\nBoerwinkle, E\n\nBohm, BO\n\nBonnelykke, K\n\nBoomsma, DI\n\nBottinger, EP\n\nBuchanan, TA\n\nCanouil, M\n\nCaulfield, MJ\n\nChambers, JC\n\nChasman, DI\n\nChen, YDI\n\nCheng, CY\n\nCollins, FS\n\nCorrea, A\n\nCucca, F\n\nde Silva, HJ\n\nDedoussis, G\n\nElmstahl, S\n\nEvans, MK\n\nFerrannini, E\n\nFerrucci, L\n\nFlorez, JC\n\nFranks, PW\n\nFrayling, TM\n\nFroguel, P\n\nGigante, B\n\nGoodarzi, MO\n\nGordon-Larsen, P\n\nGrallert, H\n\nGrarup, N\n\nGrimsgaard, S\n\nGroop, L\n\nGudnason, V\n\nGuo, XQ\n\nHamsten, A\n\nHansen, T\n\nHayward, C\n\nHeckbert, SR\n\nHorta, BL\n\nHuang, W\n\nIngelsson, E\n\nJames, PS\n\nJarvelin, MR\n\nJonas, JB\n\nJukema, JW\n\nKaleeb\n\nBeiträge in Fachzeitschriften\nISI:000656384400001\n34059833.0\n10.1038/s41588-021-00852-9\nNone\nGlycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281, 16 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281, 16 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.\n\nMärz, Winfried\n\n\n"
        },
        {
            "text": "\n146817\nMACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation.\n\nBousquet, J\n\nSchunemann, HJ\n\nFonseca, J\n\nSamolinski, B\n\nBachert, C\n\nCanonica, GW\n\nCasale, T\n\nCruz, AA\n\nDemoly, P\n\nHellings, P\n\nValiulis, A\n\nWickman, M\n\nZuberbier, T\n\nBosnic-Anticevitch, S\n\nBedbrook, A\n\nBergmann, KC\n\nCaimmi, D\n\nDahl, R\n\nFokkens, WJ\n\nGrisle, I\n\nLodrup Carlsen, K\n\nMullol, J\n\nMuraro, A\n\nPalkonen, S\n\nPapadopoulos, N\n\nPassalacqua, G\n\nRyan, D\n\nValovirta, E\n\nYorgancioglu, A\n\nAberer, W\n\nAgache, I\n\nAdachi, M\n\nAkdis, CA\n\nAkdis, M\n\nAnnesi-Maesano, I\n\nAnsotegui, IJ\n\nAnto, JM\n\nArnavielhe, S\n\nArshad, H\n\nBaiardini, I\n\nBaigenzhin, AK\n\nBarbara, C\n\nBateman, ED\n\nBeghé, B\n\nBel, EH\n\nBen Kheder, A\n\nBennoor, KS\n\nBenson, M\n\nBewick, M\n\nBieber, T\n\nBindslev-Jensen, C\n\nBjermer, L\n\nBlain, H\n\nBoner, AL\n\nBoulet, LP\n\nBonini, M\n\nBonini, S\n\nBosse, I\n\nBourret, R\n\nBousquet, PJ\n\nBraido, F\n\nBriggs, AH\n\nBrightling, CE\n\nBrozek, J\n\nBuhl, R\n\nBurney, PG\n\nBush, A\n\nCaballero-Fonseca, F\n\nCalderon, MA\n\nCamargos, PA\n\nCamuzat, T\n\nCarlsen, KH\n\nCarr, W\n\nCepeda Sarabia, AM\n\nChavannes, NH\n\nChatzi, L\n\nChen, YZ\n\nChiron, R\n\nChkhartishvili, E\n\nChuchalin, AG\n\nCiprandi, G\n\nCirule, I\n\nCorreia de Sousa, J\n\nCox, L\n\nCrooks, G\n\nCosta, DJ\n\nCustovic, A\n\nDahlen, SE\n\nDarsow, U\n\nDe Carlo, G\n\nDe Blay, F\n\nDedeu, T\n\nDeleanu, D\n\nDenburg, JA\n\nDevillier, P\n\nDidier, A\n\nDinh-Xuan, AT\n\nDokic, D\n\nDouagui, H\n\nDray, G\n\nDubakiene, R\n\nDurham, SR\n\nDykewicz, MS\n\nEl-Gamal, Y\n\nEmuzyte, R\n\nFink Wagner, A\n\nFletcher, M\n\nFiocchi, A\n\nForastiere, F\n\nGamkrelidze, A\n\nGemicioğlu, B\n\nGereda, JE\n\nGonzález Diaz, S\n\nGotua, M\n\nGrouse, L\n\nGuzmán, MA\n\nHaahtela, T\n\nHellquist-Dahl, B\n\nHeinrich, J\n\nHorak, F\n\nHourihane, JO\n\nHowarth, P\n\nHumbert, M\n\nHyland, ME\n\nIvancevich, JC\n\nJares, EJ\n\nJohnston, SL\n\nJoos, G\n\nJonquet, O\n\nJung, KS\n\nJust, J\n\nKaidashev, I\n\nKalayci, O\n\nKalyoncu, AF\n\nKeil, T\n\nKeith, PK\n\nKhaltaev, N\n\nKlimek, L\n\nKoffi N'Goran, B\n\nKolek, V\n\nKoppelman, GH\n\nKowalski, ML\n\nKull, I\n\nKuna, P\n\nKvedariene, V\n\nLambrecht, B\n\nLau, S\n\nLarenas-Linnemann, D\n\nLaune, D\n\nLe, LT\n\nLieberman, P\n\nLipworth, B\n\nLi, J\n\nLouis, R\n\nMagard, Y\n\nMagnan, A\n\nMahboub, B\n\nMajer, I\n\nMakela, MJ\n\nManning, P\n\nDe Manuel Keenoy, E\n\nMarshall, GD\n\nMasjedi, MR\n\nMaurer, M\n\nMavale-Manuel, S\n\nMelén, E\n\nMelo-Gomes, E\n\nMeltzer, EO\n\nMerk, H\n\nMiculinic, N\n\nMihaltan, F\n\nMilenkovic, B\n\nMohammad, Y\n\nMolimard, M\n\nMomas, I\n\nMontilla-Santana, A\n\nMorais-Almeida, M\n\nMösges, R\n\nNamazova-Baranova, L\n\nNaclerio, R\n\nNeou, A\n\nNeffen, H\n\nNekam, K\n\nNiggemann, B\n\nNyembue, TD\n\nO'Hehir, RE\n\nOhta, K\n\nOkamoto, Y\n\nOkubo, K\n\nOuedraogo, S\n\nPaggiaro, P\n\nPali-Schöll, I\n\nPalmer, S\n\nPanzner, P\n\nPapi, A\n\nPark, HS\n\nPavord, I\n\nPawankar, R\n\nPfaar, O\n\nPicard, R\n\nPigearias, B\n\nPin, I\n\nPlavec, D\n\nPohl, W\n\nPopov, TA\n\nPortejoie, F\n\nPostma, D\n\nPotter, P\n\nPrice, D\n\nRabe, KF\n\nRaciborski, F\n\nRadier Pontal, F\n\nRepka-Ramirez, S\n\nRobalo-Cordeiro, C\n\nRolland, C\n\nRosado-Pinto, J\n\nReitamo, S\n\nRodenas, F\n\nRoman Rodriguez, M\n\nRomano, A\n\nRosario, N\n\nRosenwasser, L\n\nRottem, M\n\nSanchez-Borges, M\n\nScadding, GK\n\nSerrano, E\n\nSchmid-Grendelmeier, P\n\nSheikh, A\n\nSimons, FE\n\nSisul, JC\n\nSkrindo, I\n\nSmit, HA\n\nSolé, D\n\nSooronbaev, T\n\nSpranger, O\n\nStelmach, R\n\nStrandberg, T\n\nSunyer, J\n\nThijs, C\n\nTodo-Bom, A\n\nTriggiani, M\n\nValenta, R\n\nValero, AL\n\nvan Hage, M\n\nVandenplas, O\n\nVezzani, G\n\nVichyanond, P\n\nViegi, G\n\nWagenmann, M\n\nWalker, S\n\nWang, DY\n\nWahn, U\n\nWilliams, DM\n\nWright, J\n\nYawn, BP\n\nYiallouros, PK\n\nYusuf, OM\n\nZar, HJ\n\nZernotti, ME\n\nZhang, L\n\nZhong, N\n\nZidarn, M\n\nMercier, J\n\nBeiträge in Fachzeitschriften\nISI:000363329400003\n26148220.0\n10.1111/all.12686\nNone\nSeveral unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards. \n                © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.\n\nAberer, Werner\n\n\n"
        },
        {
            "text": "\n161315\nRare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.\n\nSims, R\n\nvan der Lee, SJ\n\nNaj, AC\n\nBellenguez, C\n\nBadarinarayan, N\n\nJakobsdottir, J\n\nKunkle, BW\n\nBoland, A\n\nRaybould, R\n\nBis, JC\n\nMartin, ER\n\nGrenier-Boley, B\n\nHeilmann-Heimbach, S\n\nChouraki, V\n\nKuzma, AB\n\nSleegers, K\n\nVronskaya, M\n\nRuiz, A\n\nGraham, RR\n\nOlaso, R\n\nHoffmann, P\n\nGrove, ML\n\nVardarajan, BN\n\nHiltunen, M\n\nNöthen, MM\n\nWhite, CC\n\nHamilton-Nelson, KL\n\nEpelbaum, J\n\nMaier, W\n\nChoi, SH\n\nBeecham, GW\n\nDulary, C\n\nHerms, S\n\nSmith, AV\n\nFunk, CC\n\nDerbois, C\n\nForstner, AJ\n\nAhmad, S\n\nLi, H\n\nBacq, D\n\nHarold, D\n\nSatizabal, CL\n\nValladares, O\n\nSquassina, A\n\nThomas, R\n\nBrody, JA\n\nQu, L\n\nSánchez-Juan, P\n\nMorgan, T\n\nWolters, FJ\n\nZhao, Y\n\nGarcia, FS\n\nDenning, N\n\nFornage, M\n\nMalamon, J\n\nNaranjo, MCD\n\nMajounie, E\n\nMosley, TH\n\nDombroski, B\n\nWallon, D\n\nLupton, MK\n\nDupuis, J\n\nWhitehead, P\n\nFratiglioni, L\n\nMedway, C\n\nJian, X\n\nMukherjee, S\n\nKeller, L\n\nBrown, K\n\nLin, H\n\nCantwell, LB\n\nPanza, F\n\nMcGuinness, B\n\nMoreno-Grau, S\n\nBurgess, JD\n\nSolfrizzi, V\n\nProitsi, P\n\nAdams, HH\n\nAllen, M\n\nSeripa, D\n\nPastor, P\n\nCupples, LA\n\nPrice, ND\n\nHannequin, D\n\nFrank-García, A\n\nLevy, D\n\nChakrabarty, P\n\nCaffarra, P\n\nGiegling, I\n\nBeiser, AS\n\nGiedraitis, V\n\nHampel, H\n\nGarcia, ME\n\nWang, X\n\nLannfelt, L\n\nMecocci, P\n\nEiriksdottir, G\n\nCrane, PK\n\nPasquier, F\n\nBoccardi, V\n\nHenández, I\n\nBarber, RC\n\nScherer, M\n\nTarraga, L\n\nAdams, PM\n\nLeber, M\n\nChen, Y\n\nAlbert, MS\n\nRiedel-Heller, S\n\nEmilsson, V\n\nBeekly, D\n\nBraae, A\n\nSchmidt, R\n\nBlacker, D\n\nMasullo, C\n\nSchmidt, H\n\nDoody, RS\n\nSpalletta, G\n\nLongstreth, WT\n\nFairchild, TJ\n\nBossù, P\n\nLopez, OL\n\nFrosch, MP\n\nSacchinelli, E\n\nGhetti, B\n\nYang, Q\n\nHuebinger, RM\n\nJessen, F\n\nLi, S\n\nKamboh, MI\n\nMorris, J\n\nSotolongo-Grau, O\n\nKatz, MJ\n\nCorcoran, C\n\nDunstan, M\n\nBraddel, A\n\nThomas, C\n\nMeggy, A\n\nMarshall, R\n\nGerrish, A\n\nChapman, J\n\nAguilar, M\n\nTaylor, S\n\nHill, M\n\nFairén, MD\n\nHodges, A\n\nVellas, B\n\nSoininen, H\n\nKloszewska, I\n\nDaniilidou, M\n\nUphill, J\n\nPatel, Y\n\nHughes, JT\n\nLord, J\n\nTurton, J\n\nHartmann, AM\n\nCecchetti, R\n\nFenoglio, C\n\nSerpente, M\n\nArcaro, M\n\nCaltagirone, C\n\nOrfei, MD\n\nCiaramella, A\n\nPichler, S\n\nMayhaus, M\n\nGu, W\n\nLleó, A\n\nFortea, J\n\nBlesa, R\n\nBarber, IS\n\nBrookes, K\n\nCupidi, C\n\nMaletta, RG\n\nCarrell, D\n\nSorbi, S\n\nMoebus, S\n\nUrbano, M\n\nPilotto, A\n\nKornhuber, J\n\nBosco, P\n\nTodd, S\n\nCraig, D\n\nJohnston, J\n\nGill, M\n\nLawlor, B\n\nLynch, A\n\nFox, NC\n\nHardy, J\n\nARUK Consortium\n\nAlbin, RL\n\nApostolova, LG\n\nArnold, SE\n\nAsthana, S\n\nAtwood, CS\n\nBaldwin, CT\n\nBarnes, LL\n\nBarral, S\n\nBeach, TG\n\nBecker, JT\n\nBigio, EH\n\nBird, TD\n\nBoeve, BF\n\nBowen, JD\n\nBoxer, A\n\nBurke, JR\n\nBurns, JM\n\nBuxbaum, JD\n\nCairns, NJ\n\nCao, C\n\nCarlson, CS\n\nCarlsson, CM\n\nCarney, RM\n\nCarrasquillo, MM\n\nCarroll, SL\n\nDiaz, CC\n\nChui, HC\n\nClark, DG\n\nCribbs, DH\n\nCrocco, EA\n\nDeCarli, C\n\nDick, M\n\nDuara, R\n\nEvans, DA\n\nFaber, KM\n\nFallon, KB\n\nFardo, DW\n\nFarlow, MR\n\nFerris, S\n\nForoud, TM\n\nGalasko, DR\n\nGearing, M\n\nGeschwind, DH\n\nGilbert, JR\n\nGraff-Radford, NR\n\nGreen, RC\n\nGrowdon, JH\n\nHamilton, RL\n\nHarrell, LE\n\nHonig, LS\n\nHuentelman, MJ\n\nHulette, CM\n\nHyman, BT\n\nJarvik, GP\n\nAbner, E\n\nJin, LW\n\nJun, G\n\nKarydas, A\n\nKaye, JA\n\nKim, R\n\nKowall, NW\n\nKramer, JH\n\nLaFerla, FM\n\nLah, JJ\n\nLeverenz, JB\n\nLevey, AI\n\nLi, G\n\nLieberman, AP\n\nLunetta, KL\n\nLyketsos, CG\n\nMarson, DC\n\nMartiniuk, F\n\nMash, DC\n\nMasliah, E\n\nMcCormick, WC\n\nMcCurry, SM\n\nMcDavid, AN\n\nMcKee, AC\n\nMesulam, M\n\nMiller, BL\n\nMiller, CA\n\nMiller, JW\n\nMorris, JC\n\nMurrell, JR\n\nMyers, AJ\n\nO'Bryant, S\n\nOlichney, JM\n\nPankratz, VS\n\nParisi, JE\n\nPaulson, HL\n\nPerry, W\n\nPeskind, E\n\nPierce, A\n\nPoon, WW\n\nPotter, H\n\nQuinn, JF\n\nRaj, A\n\nRaskind, M\n\nReisberg, B\n\nReitz, C\n\nRingman, JM\n\nRobe ...\n\nBeiträge in Fachzeitschriften\nISI:000408672000016\n28714976.0\n10.1038/ng.3916\nPMC5669039\nWe identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85, 33 subjects. In stage 1, we genotyped 34, 74 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35, 62 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14, 97 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
        },
        {
            "text": "\n124614\nDiagnosis and therapy of bee and wasp venom allergy.\n\nPrzybilla, B\n\nRueff, F\n\nWalker, A\n\nRawer, HC\n\nAberer, W\n\nBauer, CP\n\nBerdel, D\n\nBiedermann, T\n\nBrockow, K\n\nForster, J\n\nFuchs, T\n\nHamelmann, E\n\nJakob, T\n\nJarisch, R\n\nMerk, HF\n\nMuller, U\n\nOtt, H\n\nSitter, W\n\nUrbanek, R\n\nWedi, B\n\n\n\nBeiträge in Fachzeitschriften\nISI:000311766500004\nNone\n10.5414/ALX01447\nNone\nDiagnosis and therapy of bee and wasp venom allergy Allergic reactions caused by stings of honey bees (Apis mellifera) or social wasps (particularly Vespula vulgaris, V germanica) nearly always present as large local reactions (in up to 25% of the population) or as systemic reactions with symptoms of immediate type allergy (anaphylaxis; in up to 3.5% of the population). Systemic sting reactions are induced by IgE antibodies interacting with venom components. Other clinical presentations of allergic reactions (ANDquot;unusual sting reactionsANDquot;) and toxic reactions after numerous stings are very rare. Particularly severe anaphylactic reactions may be fatal or result in disability. Acute reactions are managed by symptomatic treatment. Patients with allergic reactions profit from long-term treatment comprising education to avoid further stings, and from training to be prepared for self-management including the use of emergency medication in case of further stings. Adrenaline for self-administration is part of the emergency kit in those patients presenting with systemic immediate type reactions. Specific immunotherapy (SIT) is the main treatment option to prevent subsequent systemic reactions. Diagnostics in patients with systemic immediate type reactions are based on history, skin tests, and assessment of specific IgE antibodies to whole venom. Sometimes, these tests may not yield a venom sensitization which corresponds with the patientANDapos;s history. In such cases, it is recommended to determine concentrations of specific serum IgE antibodies to relevant single venom allergens (currently Api m 1 and Ves v 5 are available) and to perform cellular tests, if appropriate. The results of diagnostic procedures, however, are sensitive to a variety of interferences. Therefore, ANDquot;false-negativeANDquot; or ANDquot;false-positiveANDquot; reactions may occur in any system. Patients with an elevated serum concentration of baseline tryptase (95th percentile 11.4 mu g/l) and/or with mastocytosis frequently suffer from very severe anaphylactic sting reactions. To recognize these risks, baseline serum tryptase concentration should be determined and the skin should be inspected for the presence of cutaneous mastocytosis. SIT with bee or wasp venom is mandatory for patients who have experienced sting reactions with respiratory or cardiovascular symptoms. For patients with mild systemic sting reactions limited to the skin and with individual risk factors, SIT is also urgently recommended. Beyond that, SIT is advisable to all adult patients with systemic immediate type sting reactions independently of the severity grade. Only for children with systemic immediate type reactions confined to the skin data are available showing that SIT is not mandatory. There are numerous protocols for dose increase during the initial phase of venom SIT: The maintenance dose may be reached within one day (ultrarush), alter 3 5 days (rush) or within weeks or months (conventional SIT). The frequency of adverse effects is related to the speed of dose increase. The standard maintenance dose is 100 mu g. Bee venom SIT is less effective than wasp venom SIT. Therefore, high-risk patients suffering from bee venom-allergy may receive an increased maintenance dose of 200 mu g right from the start; this strategy may be also indicated in selected high-risk patients with wasp venom allergy. Systemic anaphylactic reactions and subjective complaints are the most important adverse effects of venom SIT, occurring particularly during the incremental phase. Mostly, these reactions are mild.\nRarely, there are repeated anaphylactic reactions which substantially hamper treatment or even necessitate its termination. In such cases, co-treatment and/or pre-treatment with the anti-IgE antibody omalizumab appears to be the best option currently available to achieve tolerance of SIT; it has to be considered, however, that using omalizumab for this indication would be an off-label use. Also, these patients are treated with an increased maintenance dose (ANDgt;= 200 mu g). There are no laboratory tests to determine the efficacy of SIT. A sting challenge test using a living insect should be performed about 6 18 months alter the maintenance dose has been reached to identify treatment failure. If necessary, this interval may be shortened in high-risk patients. Sting challenge tests need to be performed with utmost caution providing emergency room conditions. If a patient continues to develop a systemic reaction despite SIT, administration of an increased maintenance dose nearly always provides protection (usually 200 mu g are sufficient). In most patients, SIT can be stopped after 3 5 years, if SIT and a re-sting were tolerated without systemic reactions. If there is no tolerance or if a patient presents with individual risks, a decision has to be made as to whether SIT should be continued or not. This decision largely depends on the patientANDapos;s individual risk profile, and usually prolonged treatment is necessary. Life-long SIT is indicated for some patients, e.g. for those with mastocytosis or in case of a prior sting reaction requiring cardiopulmonary resuscitation.\n\nAberer, Werner\n\n\n"
        },
        {
            "text": "\n138324\nLaryngeal mask airway versus endotracheal tube for percutaneous dilatational tracheostomy in critically ill adult patients.\n\nStrametz, R\n\nPachler, C\n\nKramer, JF\n\nByhahn, C\n\nSiebenhofer, A\n\nWeberschock, T\n\nBeiträge in Fachzeitschriften\nISI:000338309000022\n24979320.0\n10.1002/14651858.CD009901.pub2\nNone\nPercutaneous dilatational tracheostomy (PDT) is one of the most common bedside surgical procedures performed in critically ill adult patients on intensive care units (ICUs) who require long-term ventilation. PDT is generally associated with relevant life-threatening complications (e.g. cuff rupture leading to possible hypoxia or aspiration, puncture of the oesophagus, accidental extubation, mediastinitis, pneumothorax, emphysema). The patient's airway can be secured with an endotracheal tube (ETT) or a laryngeal mask airway (LMA).\n                To assess the safety and effectiveness of ETT versus LMA in critically ill adult patients undergoing PDT on the ICU.This review addresses the following research questions.1. Is an LMA more effective than an ETT in terms of procedure-related or all-cause mortality?2. Is an LMA safer than an ETT in terms of procedure-related life-threatening complications during a PDT procedure?3. Does use of an LMA influence the conditions for performing a tracheostomy (e.g. duration of procedure)?\n                We searched the Cochrane Database of Systematic Reviews (CDSR); the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 6 (part ofThe Cochrane Library); MEDLINE (from 1984 to 27 June 2013) and EMBASE (from 1984 to 27 June 2013). We searched for reports of ongoing trials in the metaRegister of Controlled Trials (mRCT). We handsearched for relevant studies in conference proceedings of the International Symposium on Intensive Care and Emergency Medicine (ISICEM), the Annual Congress of the European Society of Intensive Care Medicine (ESICM), the Annual Congress of the Society of Critical Care Medicine (SCCM), the American Thoracic Society (ATS) and the Annual Meeting of the American College of Chest Physicians (ACCP). We contacted study authors and experts concerning unpublished data and ongoing trials. We searched for further relevant studies in the reference lists of all included trials and of relevant systematic reviews identified in theCDSR.\n                We included randomized controlled trials (RCTs) that compared use of endotracheal tubes versus laryngeal mask airways in critically ill adult patients undergoing PDT on the ICU. We imposed no restrictions with regard to language, timing or technique of PDT performed.\n                Two review authors independently assessed the eligibility and methodological quality of each study and carried out data extraction. We resolved disagreements by discussion. Our primary outcomes were all-cause mortality, procedure-related mortality and tally of participants with one or more serious adverse events. When available, we reported on our secondary outcomes, which included duration of the procedure, failure of the procedure requiring conversion to any other procedure, time to extubation after tracheostomy, length of ICU stay after tracheostomy, length of hospital stay after tracheostomy and any other serious adverse events. When possible, we combined homogeneous studies for meta-analysis. We used the risk of bias tool of The Cochrane Collaboration to assess the internal validity of all included studies in six different domains.\n                We included in this review eight RCTs involving 467 participants. The included trials exclusively assessed critically ill participants (e.g. with head injury, neurological disease, multi-trauma, sepsis, acute respiratory failure (ARF) and/or chronic obstructive pulmonary disease (COPD)). Internal validity was considerably low in studies with a high or unclear risk of bias. The main reason for this was low methodological quality or missing data, even after study authors were contacted. Study size was generally small, with a minimum of 40 and a maximum of 73 participants. Only one study (40 participants) reported on overall mortality, showing no clear evidence of a difference between treatment groups (risk ratio (RR) 1.5, 95% confidence interval (CI) 0.28 to 8.04, Fisher test P value 1.0, low-quality evidence). Four studies (231 participants) reported that no procedure-related deaths occurred with any intervention. Seven studies reported the numbers of participants with adverse events, showing no clear evidence of benefit of either LMA or ETT during PDT (RR 0.73, 95% CI 0.35 to 1.52, P value 0.41, low-quality evidence). The tally of participants in included studies with adverse events ranged from 0% to 33% in the LMA group and from 0% to 50% in the ETT group. However, the duration of the procedure was significantly shorter in the LMA group (mean difference (MD) -1.46 minutes, 95% CI -1.92 to -1.01 minutes, 324 participants, P value ≤ 0.00001, low-quality evidence). No clear evidence of a difference between ETT and LMA groups was found for all other outcomes. Only one study provided follow-up data for late complications related to the intervention, showing no clear evidence of benefit for any treatment group.\n                Evidence on the safety of LMA for PDT is too limited to allow conclusions to be drawn on its efficacy or safety compared with ETT. Although the LMA procedure is shorter because of optimal visual conditions, its effect on especially late complications has not been investigated sufficiently. Studies focusing on late complications and relevant patient-related outcomes are necessary for definitive conclusions on safety issues related to this procedure.\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
        },
        {
            "text": "\n156766\nARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle.\n\nBousquet, J\n\nHellings, PW\n\nAgache, I\n\nBedbrook, A\n\nBachert, C\n\nBergmann, KC\n\nBewick, M\n\nBindslev-Jensen, C\n\nBosnic-Anticevitch, S\n\nBucca, C\n\nCaimmi, DP\n\nCamargos, PA\n\nCanonica, GW\n\nCasale, T\n\nChavannes, NH\n\nCruz, AA\n\nDe Carlo, G\n\nDahl, R\n\nDemoly, P\n\nDevillier, P\n\nFonseca, J\n\nFokkens, WJ\n\nGuldemond, NA\n\nHaahtela, T\n\nIllario, M\n\nJust, J\n\nKeil, T\n\nKlimek, L\n\nKuna, P\n\nLarenas-Linnemann, D\n\nMorais-Almeida, M\n\nMullol, J\n\nMurray, R\n\nNaclerio, R\n\nO'Hehir, RE\n\nPapadopoulos, NG\n\nPawankar, R\n\nPotter, P\n\nRyan, D\n\nSamolinski, B\n\nSchunemann, HJ\n\nSheikh, A\n\nSimons, FE\n\nStellato, C\n\nTodo-Bom, A\n\nTomazic, PV\n\nValiulis, A\n\nValovirta, E\n\nVentura, MT\n\nWickman, M\n\nYoung, I\n\nYorgancioglu, A\n\nZuberbier, T\n\nAberer, W\n\nAkdis, CA\n\nAkdis, M\n\nAnnesi-Maesano, I\n\nAnkri, J\n\nAnsotegui, IJ\n\nAnto, JM\n\nArnavielhe, S\n\nAsarnoj, A\n\nArshad, H\n\nAvolio, F\n\nBaiardini, I\n\nBarbara, C\n\nBarbagallo, M\n\nBateman, ED\n\nBeghé, B\n\nBel, EH\n\nBennoor, KS\n\nBenson, M\n\nBiałoszewski, AZ\n\nBieber, T\n\nBjermer, L\n\nBlain, H\n\nBlasi, F\n\nBoner, AL\n\nBonini, M\n\nBonini, S\n\nBosse, I\n\nBouchard, J\n\nBoulet, LP\n\nBourret, R\n\nBousquet, PJ\n\nBraido, F\n\nBriggs, AH\n\nBrightling, CE\n\nBrozek, J\n\nBuhl, R\n\nBunu, C\n\nBurte, E\n\nBush, A\n\nCaballero-Fonseca, F\n\nCalderon, MA\n\nCamuzat, T\n\nCardona, V\n\nCarreiro-Martins, P\n\nCarriazo, AM\n\nCarlsen, KH\n\nCarr, W\n\nCepeda Sarabia, AM\n\nCesari, M\n\nChatzi, L\n\nChiron, R\n\nChivato, T\n\nChkhartishvili, E\n\nChuchalin, AG\n\nChung, KF\n\nCiprandi, G\n\nde Sousa, JC\n\nCox, L\n\nCrooks, G\n\nCustovic, A\n\nDahlen, SE\n\nDarsow, U\n\nDedeu, T\n\nDeleanu, D\n\nDenburg, JA\n\nDe Vries, G\n\nDidier, A\n\nDinh-Xuan, AT\n\nDokic, D\n\nDouagui, H\n\nDray, G\n\nDubakiene, R\n\nDurham, SR\n\nDu Toit, G\n\nDykewicz, MS\n\nEklund, P\n\nEl-Gamal, Y\n\nEllers, E\n\nEmuzyte, R\n\nFarrell, J\n\nFink Wagner, A\n\nFiocchi, A\n\nFletcher, M\n\nForastiere, F\n\nGaga, M\n\nGamkrelidze, A\n\nGemicioğlu, B\n\nGereda, JE\n\nvan Wick, RG\n\nGonzález Diaz, S\n\nGrisle, I\n\nGrouse, L\n\nGutter, Z\n\nGuzmán, MA\n\nHellquist-Dahl, B\n\nHeinrich, J\n\nHorak, F\n\nHourihane, JO\n\nHumbert, M\n\nHyland, M\n\nIaccarino, G\n\nJares, EJ\n\nJeandel, C\n\nJohnston, SL\n\nJoos, G\n\nJonquet, O\n\nJung, KS\n\nJutel, M\n\nKaidashev, I\n\nKhaitov, M\n\nKalayci, O\n\nKalyoncu, AF\n\nKardas, P\n\nKeith, PK\n\nKerkhof, M\n\nKerstjens, HA\n\nKhaltaev, N\n\nKogevinas, M\n\nKolek, V\n\nKoppelman, GH\n\nKowalski, ML\n\nKuitunen, M\n\nKull, I\n\nKvedariene, V\n\nLambrecht, B\n\nLau, S\n\nLaune, D\n\nLe, LT\n\nLieberman, P\n\nLipworth, B\n\nLi, J\n\nLodrup Carlsen, KC\n\nLouis, R\n\nLupinek, C\n\nMacNee, W\n\nMagar, Y\n\nMagnan, A\n\nMahboub, B\n\nMaier, D\n\nMajer, I\n\nMalva, J\n\nManning, P\n\nDe Manuel Keenoy, E\n\nMarshall, GD\n\nMasjedi, MR\n\nMathieu-Dupas, E\n\nMaurer, M\n\nMavale-Manuel, S\n\nMelén, E\n\nMelo-Gomes, E\n\nMeltzer, EO\n\nMercier, J\n\nMerk, H\n\nMiculinic, N\n\nMihaltan, F\n\nMilenkovic, B\n\nMillot-Keurinck, J\n\nMohammad, Y\n\nMomas, I\n\nMösges, R\n\nMuraro, A\n\nNamazova-Baranova, L\n\nNadif, R\n\nNeffen, H\n\nNekam, K\n\nNieto, A\n\nNiggemann, B\n\nNogueira-Silva, L\n\nNogues, M\n\nNyembue, TD\n\nOhta, K\n\nOkamoto, Y\n\nOkubo, K\n\nOlive-Elias, M\n\nOuedraogo, S\n\nPaggiaro, P\n\nPali-Schöll, I\n\nPalkonen, S\n\nPanzner, P\n\nPapi, A\n\nPark, HS\n\nPassalacqua, G\n\nPedersen, S\n\nPereira, AM\n\nPfaar, O\n\nPicard, R\n\nPigearias, B\n\nPin, I\n\nPlavec, D\n\nPohl, W\n\nPopov, TA\n\nPortejoie, F\n\nPostma, D\n\nPoulsen, LK\n\nPrice, D\n\nRabe, KF\n\nRaciborski, F\n\nRoberts, G\n\nRobalo-Cordeiro, C\n\nRodenas, F\n\nRodriguez-Mañas, L\n\nRolland, C\n\nRoman Rodriguez, M\n\nRomano, A\n\nRosado-Pinto, J\n\nRosario, N\n\nRottem, M\n\nSanchez-Borges, M\n\nSastre-Dominguez, J\n\nScadding, GK\n\nScichilone, N\n\nSchmid-Grendelmeier, P\n\nSerrano, E\n\nShields, M\n\nSiroux, V\n\nSisul, JC\n\nSkrindo, I\n\nSmit, HA\n\nSolé, D\n\nSooronbaev, T\n\nSpranger, ...\n\nBeiträge in Fachzeitschriften\nISI:000396071500001\n28050247.0\n10.1186/s13601-016-0137-4\nPMC5203711\nThe Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.\n\nAberer, Werner\n\nTomazic, Peter Valentin\n\n\n"
        },
        {
            "text": "\n156419\nScaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).\n\nBousquet, J\n\nFarrell, J\n\nCrooks, G\n\nHellings, P\n\nBel, EH\n\nBewick, M\n\nChavannes, NH\n\nde Sousa, JC\n\nCruz, AA\n\nHaahtela, T\n\nJoos, G\n\nKhaltaev, N\n\nMalva, J\n\nMuraro, A\n\nNogues, M\n\nPalkonen, S\n\nPedersen, S\n\nRobalo-Cordeiro, C\n\nSamolinski, B\n\nStrandberg, T\n\nValiulis, A\n\nYorgancioglu, A\n\nZuberbier, T\n\nBedbrook, A\n\nAberer, W\n\nAdachi, M\n\nAgusti, A\n\nAkdis, CA\n\nAkdis, M\n\nAnkri, J\n\nAlonso, A\n\nAnnesi-Maesano, I\n\nAnsotegui, IJ\n\nAnto, JM\n\nArnavielhe, S\n\nArshad, H\n\nBai, C\n\nBaiardini, I\n\nBachert, C\n\nBaigenzhin, AK\n\nBarbara, C\n\nBateman, ED\n\nBeghé, B\n\nKheder, AB\n\nBennoor, KS\n\nBenson, M\n\nBergmann, KC\n\nBieber, T\n\nBindslev-Jensen, C\n\nBjermer, L\n\nBlain, H\n\nBlasi, F\n\nBoner, AL\n\nBonini, M\n\nBonini, S\n\nBosnic-Anticevitch, S\n\nBoulet, LP\n\nBourret, R\n\nBousquet, PJ\n\nBraido, F\n\nBriggs, AH\n\nBrightling, CE\n\nBrozek, J\n\nBuhl, R\n\nBurney, PG\n\nBush, A\n\nCaballero-Fonseca, F\n\nCaimmi, D\n\nCalderon, MA\n\nCalverley, PM\n\nCamargos, PA\n\nCanonica, GW\n\nCamuzat, T\n\nCarlsen, KH\n\nCarr, W\n\nCarriazo, A\n\nCasale, T\n\nCepeda Sarabia, AM\n\nChatzi, L\n\nChen, YZ\n\nChiron, R\n\nChkhartishvili, E\n\nChuchalin, AG\n\nChung, KF\n\nCiprandi, G\n\nCirule, I\n\nCox, L\n\nCosta, DJ\n\nCustovic, A\n\nDahl, R\n\nDahlen, SE\n\nDarsow, U\n\nDe Carlo, G\n\nDe Blay, F\n\nDedeu, T\n\nDeleanu, D\n\nDe Manuel Keenoy, E\n\nDemoly, P\n\nDenburg, JA\n\nDevillier, P\n\nDidier, A\n\nDinh-Xuan, AT\n\nDjukanovic, R\n\nDokic, D\n\nDouagui, H\n\nDray, G\n\nDubakiene, R\n\nDurham, SR\n\nDykewicz, MS\n\nEl-Gamal, Y\n\nEmuzyte, R\n\nFabbri, LM\n\nFletcher, M\n\nFiocchi, A\n\nFink Wagner, A\n\nFonseca, J\n\nFokkens, WJ\n\nForastiere, F\n\nFrith, P\n\nGaga, M\n\nGamkrelidze, A\n\nGarces, J\n\nGarcia-Aymerich, J\n\nGemicioğlu, B\n\nGereda, JE\n\nGonzález Diaz, S\n\nGotua, M\n\nGrisle, I\n\nGrouse, L\n\nGutter, Z\n\nGuzmán, MA\n\nHeaney, LG\n\nHellquist-Dahl, B\n\nHenderson, D\n\nHendry, A\n\nHeinrich, J\n\nHeve, D\n\nHorak, F\n\nHourihane, JO\n\nHowarth, P\n\nHumbert, M\n\nHyland, ME\n\nIllario, M\n\nIvancevich, JC\n\nJardim, JR\n\nJares, EJ\n\nJeandel, C\n\nJenkins, C\n\nJohnston, SL\n\nJonquet, O\n\nJulge, K\n\nJung, KS\n\nJust, J\n\nKaidashev, I\n\nKaitov, MR\n\nKalayci, O\n\nKalyoncu, AF\n\nKeil, T\n\nKeith, PK\n\nKlimek, L\n\nKoffi N'Goran, B\n\nKolek, V\n\nKoppelman, GH\n\nKowalski, ML\n\nKull, I\n\nKuna, P\n\nKvedariene, V\n\nLambrecht, B\n\nLau, S\n\nLarenas-Linnemann, D\n\nLaune, D\n\nLe, LT\n\nLieberman, P\n\nLipworth, B\n\nLi, J\n\nLodrup Carlsen, K\n\nLouis, R\n\nMacNee, W\n\nMagard, Y\n\nMagnan, A\n\nMahboub, B\n\nMair, A\n\nMajer, I\n\nMakela, MJ\n\nManning, P\n\nMara, S\n\nMarshall, GD\n\nMasjedi, MR\n\nMatignon, P\n\nMaurer, M\n\nMavale-Manuel, S\n\nMelén, E\n\nMelo-Gomes, E\n\nMeltzer, EO\n\nMenzies-Gow, A\n\nMerk, H\n\nMichel, JP\n\nMiculinic, N\n\nMihaltan, F\n\nMilenkovic, B\n\nMohammad, GM\n\nMolimard, M\n\nMomas, I\n\nMontilla-Santana, A\n\nMorais-Almeida, M\n\nMorgan, M\n\nMösges, R\n\nMullol, J\n\nNafti, S\n\nNamazova-Baranova, L\n\nNaclerio, R\n\nNeou, A\n\nNeffen, H\n\nNekam, K\n\nNiggemann, B\n\nNinot, G\n\nNyembue, TD\n\nO'Hehir, RE\n\nOhta, K\n\nOkamoto, Y\n\nOkubo, K\n\nOuedraogo, S\n\nPaggiaro, P\n\nPali-Schöll, I\n\nPanzner, P\n\nPapadopoulos, N\n\nPapi, A\n\nPark, HS\n\nPassalacqua, G\n\nPavord, I\n\nPawankar, R\n\nPengelly, R\n\nPfaar, O\n\nPicard, R\n\nPigearias, B\n\nPin, I\n\nPlavec, D\n\nPoethig, D\n\nPohl, W\n\nPopov, TA\n\nPortejoie, F\n\nPotter, P\n\nPostma, D\n\nPrice, D\n\nRabe, KF\n\nRaciborski, F\n\nRadier Pontal, F\n\nRepka-Ramirez, S\n\nReitamo, S\n\nRennard, S\n\nRodenas, F\n\nRoberts, J\n\nRoca, J\n\nRodriguez Mañas, L\n\nRolland, C\n\nRoman Rodriguez, M\n\nRomano, A\n\nRosado-Pinto, J\n\nRosario, N\n\nRosenwasser, L\n\nRottem, M\n\nRyan, D\n\nSanchez-Borges, M\n\nScadding, GK\n\nSchunemann, HJ\n\nSerrano, E\n\nSchmid-Grendelmeier, P\n\nSchulz, H\n\nSheikh, A\n\nShields, M\n\nSiafakas, N\n\nSibille, Y\n\nSimilowski, T\n\nSimons, FE\n\nSisul, JC\n\nSkrindo, I\n\nSmit, HA ...\n\nBeiträge in Fachzeitschriften\nISI:000390119300001\n27478588.0\n10.1186/s13601-016-0116-9\nPMC4966705\nAction Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.\n\nAberer, Werner\n\n\n"
        },
        {
            "text": "\n170225\nGenome Analyses of &gt;200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.\n\nLigthart, S\n\nVaez, A\n\nVõsa, U\n\nStathopoulou, MG\n\nde Vries, PS\n\nPrins, BP\n\nVan der Most, PJ\n\nTanaka, T\n\nNaderi, E\n\nRose, LM\n\nWu, Y\n\nKarlsson, R\n\nBarbalic, M\n\nLin, H\n\nPool, R\n\nZhu, G\n\nMacé, A\n\nSidore, C\n\nTrompet, S\n\nMangino, M\n\nSabater-Lleal, M\n\nKemp, JP\n\nAbbasi, A\n\nKacprowski, T\n\nVerweij, N\n\nSmith, AV\n\nHuang, T\n\nMarzi, C\n\nFeitosa, MF\n\nLohman, KK\n\nKleber, ME\n\nMilaneschi, Y\n\nMueller, C\n\nHuq, M\n\nVlachopoulou, E\n\nLyytikäinen, LP\n\nOldmeadow, C\n\nDeelen, J\n\nPerola, M\n\nZhao, JH\n\nFeenstra, B\n\nLifeLines Cohort Study\n\nAmini, M\n\nCHARGE Inflammation Working Group\n\nLahti, J\n\nSchraut, KE\n\nFornage, M\n\nSuktitipat, B\n\nChen, WM\n\nLi, X\n\nNutile, T\n\nMalerba, G\n\nLuan, J\n\nBak, T\n\nSchork, N\n\nDel Greco M, F\n\nThiering, E\n\nMahajan, A\n\nMarioni, RE\n\nMihailov, E\n\nEriksson, J\n\nOzel, AB\n\nZhang, W\n\nNethander, M\n\nCheng, YC\n\nAslibekyan, S\n\nAng, W\n\nGandin, I\n\nYengo, L\n\nPortas, L\n\nKooperberg, C\n\nHofer, E\n\nRajan, KB\n\nSchurmann, C\n\nden Hollander, W\n\nAhluwalia, TS\n\nZhao, J\n\nDraisma, HHM\n\nFord, I\n\nTimpson, N\n\nTeumer, A\n\nHuang, H\n\nWahl, S\n\nLiu, Y\n\nHuang, J\n\nUh, HW\n\nGeller, F\n\nJoshi, PK\n\nYanek, LR\n\nTrabetti, E\n\nLehne, B\n\nVozzi, D\n\nVerbanck, M\n\nBiino, G\n\nSaba, Y\n\nMeulenbelt, I\n\nO'Connell, JR\n\nLaakso, M\n\nGiulianini, F\n\nMagnusson, PKE\n\nBallantyne, CM\n\nHottenga, JJ\n\nMontgomery, GW\n\nRivadineira, F\n\nRueedi, R\n\nSteri, M\n\nHerzig, KH\n\nStott, DJ\n\nMenni, C\n\nFrånberg, M\n\nSt Pourcain, B\n\nFelix, SB\n\nPers, TH\n\nBakker, SJL\n\nKraft, P\n\nPeters, A\n\nVaidya, D\n\nDelgado, G\n\nSmit, JH\n\nGroßmann, V\n\nSinisalo, J\n\nSeppälä, I\n\nWilliams, SR\n\nHolliday, EG\n\nMoed, M\n\nLangenberg, C\n\nRäikkönen, K\n\nDing, J\n\nCampbell, H\n\nSale, MM\n\nChen, YI\n\nJames, AL\n\nRuggiero, D\n\nSoranzo, N\n\nHartman, CA\n\nSmith, EN\n\nBerenson, GS\n\nFuchsberger, C\n\nHernandez, D\n\nTiesler, CMT\n\nGiedraitis, V\n\nLiewald, D\n\nFischer, K\n\nMellström, D\n\nLarsson, A\n\nWang, Y\n\nScott, WR\n\nLorentzon, M\n\nBeilby, J\n\nRyan, KA\n\nPennell, CE\n\nVuckovic, D\n\nBalkau, B\n\nConcas, MP\n\nSchmidt, R\n\nMendes de Leon, CF\n\nBottinger, EP\n\nKloppenburg, M\n\nPaternoster, L\n\nBoehnke, M\n\nMusk, AW\n\nWillemsen, G\n\nEvans, DM\n\nMadden, PAF\n\nKähönen, M\n\nKutalik, Z\n\nZoledziewska, M\n\nKarhunen, V\n\nKritchevsky, SB\n\nSattar, N\n\nLachance, G\n\nClarke, R\n\nHarris, TB\n\nRaitakari, OT\n\nAttia, JR\n\nvan Heemst, D\n\nKajantie, E\n\nSorice, R\n\nGambaro, G\n\nScott, RA\n\nHicks, AA\n\nFerrucci, L\n\nStandl, M\n\nLindgren, CM\n\nStarr, JM\n\nKarlsson, M\n\nLind, L\n\nLi, JZ\n\nChambers, JC\n\nMori, TA\n\nde Geus, EJCN\n\nHeath, AC\n\nMartin, NG\n\nAuvinen, J\n\nBuckley, BM\n\nde Craen, AJM\n\nWaldenberger, M\n\nStrauch, K\n\nMeitinger, T\n\nScott, RJ\n\nMcEvoy, M\n\nBeekman, M\n\nBombieri, C\n\nRidker, PM\n\nMohlke, KL\n\nPedersen, NL\n\nMorrison, AC\n\nBoomsma, DI\n\nWhitfield, JB\n\nStrachan, DP\n\nHofman, A\n\nVollenweider, P\n\nCucca, F\n\nJarvelin, MR\n\nJukema, JW\n\nSpector, TD\n\nHamsten, A\n\nZeller, T\n\nUitterlinden, AG\n\nNauck, M\n\nGudnason, V\n\nQi, L\n\nGrallert, H\n\nBorecki, IB\n\nRotter, JI\n\nMärz, W\n\nWild, PS\n\nLokki, ML\n\nBoyle, M\n\nSalomaa, V\n\nMelbye, M\n\nEriksson, JG\n\nWilson, JF\n\nPenninx, BWJH\n\nBecker, DM\n\nWorrall, BB\n\nGibson, G\n\nKrauss, RM\n\nCiullo, M\n\nZaza, G\n\nWareham, NJ\n\nOldehinkel, AJ\n\nPalmer, LJ\n\nMurray, SS\n\nPramstaller, PP\n\nBandinelli, S\n\nHeinrich, J\n\nIngelsson, E\n\nDeary, IJ\n\nMägi, R\n\nVandenput, L\n\nvan der Harst, P\n\nDesch, KC\n\nKooner, JS\n\nOhlsson, C\n\nHayward, C\n\nLehtimäki, T\n\nShuldiner, AR\n\nArnett, DK\n\nBeilin, LJ\n\nRobino, A\n\nFroguel, P\n\nPirastu, M\n\nJess, T\n\nKoenig, W\n\nLoos, RJF\n\nEvans, DA\n\nSchmidt, H\n\nSmith, GD\n\nSlagboom, PE\n\nEiriksdottir, G\n\nMorris, AP\n\nPsaty, BM\n\nTracy, RP\n\nNolte, IM\n\nBoerwinkle, E\n\nVisvikis-Siest, S\n\nReiner, AP\n\nGross, M\n\nBis, JC\n\nFranke, L\n\nFranco, OH\n\nBenjamin, EJ\n\nChasm\n\nBeiträge in Fachzeitschriften\nISI:000448942100006\n30388399.0\n10.1016/j.ajhg.2018.09.009\nPMC6218410\nC-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204, 02 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.\n                Copyright © 2018 American Society of Human Genetics. All rights reserved.\n\nHofer, Edith\n\nMärz, Winfried\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
        },
        {
            "text": "\n187108\nGlobal Impact of COVID-19 on Stroke Care and Intravenous Thrombolysis.\n\nNogueira, RG\n\nQureshi, MM\n\nAbdalkader, M\n\nMartins, SO\n\nYamagami, H\n\nQiu, Z\n\nMansour, OY\n\nSathya, A\n\nCzlonkowska, A\n\nTsivgoulis, G\n\nAguiar de Sousa, D\n\nDemeestere, J\n\nMikulik, R\n\nVanacker, P\n\nSiegler, JE\n\nKõrv, J\n\nBiller, J\n\nLiang, CW\n\nSangha, NS\n\nZha, AM\n\nCzap, AL\n\nHolmstedt, CA\n\nTuran, TN\n\nNtaios, G\n\nMalhotra, K\n\nTayal, A\n\nLoochtan, A\n\nRanta, A\n\nMistry, EA\n\nAlexandrov, AW\n\nHuang, DY\n\nYaghi, S\n\nRaz, E\n\nSheth, SA\n\nMohammaden, MH\n\nFrankel, M\n\nBila Lamou, EG\n\nAref, HM\n\nElbassiouny, A\n\nHassan, F\n\nMenecie, T\n\nMustafa, W\n\nShokri, HM\n\nRoushdy, T\n\nSarfo, FS\n\nAlabi, TO\n\nArabambi, B\n\nNwazor, EO\n\nSunmonu, TA\n\nWahab, K\n\nYaria, J\n\nMohammed, HH\n\nAdebayo, PB\n\nRiahi, AD\n\nBen Sassi, S\n\nGwaunza, L\n\nNgwende, GW\n\nSahakyan, D\n\nRahman, A\n\nAi, Z\n\nBai, F\n\nDuan, Z\n\nHao, Y\n\nHuang, W\n\nLi, G\n\nLi, W\n\nLiu, G\n\nLuo, J\n\nShang, X\n\nSui, Y\n\nTian, L\n\nWen, H\n\nWu, B\n\nYan, Y\n\nYuan, Z\n\nZhang, H\n\nZhang, J\n\nZhao, W\n\nZi, W\n\nLeung, TW\n\nChugh, C\n\nHuded, V\n\nMenon, B\n\nPandian, JD\n\nSylaja, PN\n\nUsman, FS\n\nFarhoudi, M\n\nHokmabadi, ES\n\nHorev, A\n\nReznik, A\n\nHoffmann, RS\n\nOhara, N\n\nSakai, N\n\nWatanabe, D\n\nYamamoto, R\n\nDoijiri, R\n\nTokuda, N\n\nYamada, T\n\nTerasaki, T\n\nYazawa, Y\n\nUwatoko, T\n\nDembo, T\n\nShimizu, H\n\nSugiura, Y\n\nMiyashita, F\n\nFukuda, H\n\nMiyake, K\n\nShimbo, J\n\nSugimura, Y\n\nYagita, Y\n\nTakenobu, Y\n\nMatsumaru, Y\n\nYamada, S\n\nKono, R\n\nKanamaru, T\n\nYamazaki, H\n\nSakaguchi, M\n\nTodo, K\n\nYamamoto, N\n\nSonoda, K\n\nYoshida, T\n\nHashimoto, H\n\nNakahara, I\n\nKondybayeva, A\n\nFaizullina, K\n\nKamenova, S\n\nZhanuzakov, M\n\nBaek, JH\n\nHwang, Y\n\nLee, JS\n\nLee, SB\n\nMoon, J\n\nPark, H\n\nSeo, JH\n\nSeo, KD\n\nSohn, SI\n\nYoung, CJ\n\nAhdab, R\n\nWan Zaidi, WA\n\nAziz, ZA\n\nBasri, HB\n\nChung, LW\n\nIbrahim, AB\n\nIbrahim, KA\n\nLooi, I\n\nTan, WY\n\nYahya, NW\n\nGroppa, S\n\nLeahu, P\n\nAl Hashmi, AM\n\nImam, YZ\n\nAkhtar, N\n\nPineda-Franks, MC\n\nCo, CO\n\nKandyba, D\n\nAlhazzani, A\n\nAl-Jehani, H\n\nTham, CH\n\nMamauag, MJ\n\nVenketasubramanian, N\n\nChen, CH\n\nTang, SC\n\nChurojana, A\n\nAkil, E\n\nAykaç, O\n\nOzdemir, AO\n\nGiray, S\n\nHussain, SI\n\nJohn, S\n\nLe Vu, H\n\nTran, AD\n\nNguyen, HH\n\nPham, TN\n\nNguyen, TH\n\nNguyen, TQ\n\nGattringer, T\n\nEnzinger, C\n\nKiller-Oberpfalzer, M\n\nBellante, F\n\nDe Blauwe, S\n\nVanhooren, G\n\nDe Raedt, S\n\nDusart, A\n\nLemmens, R\n\nLigot, N\n\nRutgers, MP\n\nYperzeele, L\n\nAlexiev, F\n\nSakelarova, T\n\nBedeković, MR\n\nBudincevic, H\n\nCindrić, I\n\nHucika, Z\n\nOzretic, D\n\nSaric, MS\n\nPfeifer, F\n\nKarpowic, I\n\nCernik, D\n\nSramek, M\n\nSkoda, M\n\nHlavacova, H\n\nKlecka, L\n\nKoutny, M\n\nVaclavik, D\n\nSkoda, O\n\nFiksa, J\n\nHanelova, K\n\nNevsimalova, M\n\nRezek, R\n\nProchazka, P\n\nKrejstova, G\n\nNeumann, J\n\nVachova, M\n\nBrzezanski, H\n\nHlinovsky, D\n\nTenora, D\n\nJura, R\n\nJurák, L\n\nNovak, J\n\nNovak, A\n\nTopinka, Z\n\nFibrich, P\n\nSobolova, H\n\nVolny, O\n\nChristensen, HK\n\nDrenck, N\n\nIversen, HK\n\nSimonsen, CZ\n\nTruelsen, TC\n\nWienecke, T\n\nVibo, R\n\nGross-Paju, K\n\nToomsoo, T\n\nAntsov, K\n\nCaparros, F\n\nCordonnier, C\n\nDan, M\n\nFaucheux, JM\n\nMechtouff, L\n\nEker, O\n\nLesaine, E\n\nOndze, B\n\nPeres, R\n\nPico, F\n\nPiotin, M\n\nPop, R\n\nRouanet, F\n\nGubeladze, T\n\nKhinikadze, M\n\nLobjanidze, N\n\nTsikaridze, A\n\nNagel, S\n\nRingleb, PA\n\nRosenkranz, M\n\nSchmidt, H\n\nSedghi, A\n\nSiepmann, T\n\nSzabo, K\n\nThomalla, G\n\nPalaiodimou, L\n\nSagris, D\n\nKargiotis, O\n\nKlivenyi, P\n\nSzapary, L\n\nTarkanyi, G\n\nAdami, A\n\nBandini, F\n\nCalabresi, P\n\nFrisullo, G\n\nRenieri, L\n\nSangalli, D\n\nPirson, AV\n\nUyttenboogaart, M\n\nvan den Wijngaard, I\n\nKristoffersen, ES\n\nBrola, W\n\nFudala, M\n\nHoroch-Lyszczarek, E\n\nKarlinski, M\n\nKazmierski, R\n\nKram, P\n\nRogoziewicz, M\n\nKaczorowski, R\n\nLuchowski, P\n\nSienkiewicz-Jarosz, H\n\nSobolewski, P\n\nFryze, W\n\nWisniewska, A\n\nWiszniewska, M\n\nFerreira, P\n\nF ...\n\nBeiträge in Fachzeitschriften\nNone\n33766997.0\n10.1212/WNL.0000000000011885\nNone\nThe objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods.\n                We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases.\n                There were 91, 73 stroke admissions in the 4 months immediately before compared to 80, 94 admissions during the pandemic months, representing an 11.5% (95%CI, -11.7 to - 11.3, p<0.0001) decline. There were 13, 34 IVT therapies in the 4 months preceding compared to 11, 70 procedures during the pandemic, representing a 13.2% (95%CI, -13.8 to -12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1, 37 to 1, 78, or an 11.9% decrease (95%CI, -13.7 to -10.3, p=0.001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119, 67 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1, 22/52, 26) of all stroke admissions.\n                The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.\n                © 2021 American Academy of Neurology.\n\nEnzinger, Christian\n\nGattringer, Thomas\n\n\n"
        },
        {
            "text": "\n151534\nStrategies for improving outcome of assisted reproduction in women with polycystic ovary syndrome: systematic review and meta-analysis.\n\nKollmann, M\n\nMartins, WP\n\nLima, ML\n\nCraciunas, L\n\nNastri, CO\n\nRichardson, A\n\nRaine-Fenning, N\n\nBeiträge in Fachzeitschriften\nISI:000390815100004\n26924636.0\n10.1002/uog.15898\nNone\nTo identify, appraise and summarize the current evidence regarding the efficacy of strategies aimed at improving assisted reproductive techniques in women with polycystic ovary syndrome (PCOS).\n                A comprehensive literature search of the standard medical databases was performed. The last electronic search was run in July 2015. The primary outcome measures were live birth/ongoing pregnancy and ovarian hyperstimulation syndrome (OHSS). The secondary outcome measures were clinical pregnancy and miscarriage.\n                We screened 1021 records and completely assessed 173, finally including 66 studies in the quantitative analysis. Many different interventions were assessed, however the overall quality of the studies was low. We observed moderate-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (relative risk (RR), 0.95 (95% CI, 0.84-1.08)), or clinical pregnancy (RR, 1.02 (95% CI, 0.91-1.15)) when comparing antagonist and agonist protocols for ovarian stimulation. Additionally, we found low-quality evidence that metformin improves live birth/ongoing pregnancy (RR, 1.28 (95% CI, 1.01-1.63)) and clinical pregnancy rates (RR, 1.26 (95% CI, 1.04-1.53)) when compared with placebo or no intervention. We further found low-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (RR, 1.03 (95% CI, 0.80-1.34)) and clinical pregnancy rates (RR, 0.99 (95% CI, 0.81-1.22)) when comparing human menopausal gonadotropin for inducing ovulation and artificial preparation with estradiol valerate for endometrial preparation for frozen embryo transfer (FET). Low-quality evidence suggests that mannitol compared with no intervention (RR, 0.54 (95% CI, 0.39-0.77)) and antagonist protocols compared with agonist protocols (RR, 0.63 (95% CI, 0.49-0.80)) reduce rates of OHSS.\n                There is low- to moderate-quality evidence suggesting that antagonist protocols are preferable to agonist ones, because they reduce the incidence of OHSS without interfering with clinical pregnancy and live birth for women with PCOS. Additionally there is low-quality evidence pointing to a benefit of metformin supplementation on clinical pregnancy and live birth; and that ovulation induction and administration of estradiol seem to be equally effective for endometrial preparation before FET for women with PCOS. For all other interventions, the evidence is of very low quality, not allowing any meaningful conclusions to be drawn. Estrategias para mejorar el resultado de la reproducción asistida en mujeres con síndrome de ovario poliquístico: revisión sistemática y metaanálisis RESUMEN OBJETIVOS: Identificar, evaluar y resumir la evidencia actual sobre la eficacia de las estrategias para mejorar las técnicas de reproducción asistida en mujeres con síndrome de ovario poliquístico (SOP). MÉTODOS: Se realizó una búsqueda exhaustiva de literatura en las bases de datos médicas estándar. La última búsqueda electrónica se realizó en julio de 2015. Las medidas de resultado primarias fueron los nacimientos vivos/embarazos en curso y el síndrome de hiperestimulación ovárica (SHO). Las medidas de resultado secundarias fueron el embarazo confirmado ecográficamente y el aborto.\n                Se cribaron 1021 registros, de los que se evaluaron por completo 173, para finalmente incluir 66 estudios en el análisis cuantitativo. Aunque se evaluaron muchas intervenciones diferentes, en general la calidad de los estudios fue baja. Se observó evidencia de calidad moderada de que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (riesgo relativo (RR): 0, 5 (IC 95%, 0, 4-1, 8)), o de embarazos confirmados ecográficamente (RR: 1, 2 (IC 95%, 0, 1-1, 5)), cuando se comparan los protocolos de antagonistas y agonistas para la estimulación ovárica. Además, se encontró evidencia de baja calidad en que la metformina mejora las tasas de nacimientos vivos/embarazos en curso (RR: 1, 8 (IC 95%, 1, 1-1, 3)) y de embarazos confirmados ecográficamente (RR: 1, 6 (IC 95%, 1, 4-1, 3)) en comparación con un placebo o la no intervención. Se encontró también evidencia de baja calidad en que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (RR: 1, 3 (IC 95%, 0, 0-1, 4)) y las tasas de embarazos confirmados ecográficamente (RR: 0, 9 (IC 95%, 0.81-1, 2)) al comparar la gonadotropina menopáusica humana para la inducción de la ovulación y la preparación artificial con el valerato de estradiol para preparar el endometrio para la transferencia de embriones congelados (TEC). La baja calidad de la evidencia sugiere que el manitol, en comparación con la no intervención (RR: 0, 4 (IC 95%, 0, 9-0, 7)), y los protocolos de antagonistas, en comparación con los protocolos de agonistas (RR: 0, 3 (IC 95%, 0, 9-0, 0)), reducen las tasas de SHO. CONCLUSIÓN: Hay evidencia de calidad baja a moderada que sugiere que los protocolos de antagonistas son preferibles a los de agonistas, ya que reducen la tasa de SHO sin interferir con el embarazo confirmado ecográficamente y los nacimientos vivos en las mujeres con SOP. Además, existe evidencia de baja calidad que indica un beneficio del uso de metformina como aporte suplementario en embarazos confirmados ecográficamente y en nacimientos vivos; y que la inducción de la ovulación y la administración de estradiol parecen ser igualmente eficaces para la preparación del endometrio antes de la TEC en mujeres con SOP. Para el resto de procedimientos, la evidencia es de muy baja calidad, y por ello no permite extraer conclusiones importantes.\n                Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.\n\nKollmann, Martina\n\n\n"
        },
        {
            "text": "\n146237\nDirectional dominance on stature and cognition in diverse human populations.\n\nJoshi, PK\n\nEsko, T\n\nMattsson, H\n\nEklund, N\n\nGandin, I\n\nNutile, T\n\nJackson, AU\n\nSchurmann, C\n\nSmith, AV\n\nZhang, W\n\nOkada, Y\n\nStančáková, A\n\nFaul, JD\n\nZhao, W\n\nBartz, TM\n\nConcas, MP\n\nFranceschini, N\n\nEnroth, S\n\nVitart, V\n\nTrompet, S\n\nGuo, X\n\nChasman, DI\n\nO'Connel, JR\n\nCorre, T\n\nNongmaithem, SS\n\nChen, Y\n\nMangino, M\n\nRuggiero, D\n\nTraglia, M\n\nFarmaki, AE\n\nKacprowski, T\n\nBjonnes, A\n\nvan der Spek, A\n\nWu, Y\n\nGiri, AK\n\nYanek, LR\n\nWang, L\n\nHofer, E\n\nRietveld, CA\n\nMcLeod, O\n\nCornelis, MC\n\nPattaro, C\n\nVerweij, N\n\nBaumbach, C\n\nAbdellaoui, A\n\nWarren, HR\n\nVuckovic, D\n\nMei, H\n\nBouchard, C\n\nPerry, JRB\n\nCappellani, S\n\nMirza, SS\n\nBenton, MC\n\nBroeckel, U\n\nMedland, SE\n\nLind, PA\n\nMalerba, G\n\nDrong, A\n\nYengo, L\n\nBielak, LF\n\nZhi, D\n\nvan der Most, PJ\n\nShriner, D\n\nMägi, R\n\nHemani, G\n\nKaraderi, T\n\nWang, Z\n\nLiu, T\n\nDemuth, I\n\nZhao, JH\n\nMeng, W\n\nLataniotis, L\n\nvan der Laan, SW\n\nBradfield, JP\n\nWood, AR\n\nBonnefond, A\n\nAhluwalia, TS\n\nHall, LM\n\nSalvi, E\n\nYazar, S\n\nCarstensen, L\n\nde Haan, HG\n\nAbney, M\n\nAfzal, U\n\nAllison, MA\n\nAmin, N\n\nAsselbergs, FW\n\nBakker, SJL\n\nBarr, RG\n\nBaumeister, SE\n\nBenjamin, DJ\n\nBergmann, S\n\nBoerwinkle, E\n\nBottinger, EP\n\nCampbell, A\n\nChakravarti, A\n\nChan, Y\n\nChanock, SJ\n\nChen, C\n\nChen, YI\n\nCollins, FS\n\nConnell, J\n\nCorrea, A\n\nCupples, LA\n\nSmith, GD\n\nDavies, G\n\nDörr, M\n\nEhret, G\n\nEllis, SB\n\nFeenstra, B\n\nFeitosa, MF\n\nFord, I\n\nFox, CS\n\nFrayling, TM\n\nFriedrich, N\n\nGeller, F\n\nScotland, G\n\nGillham-Nasenya, I\n\nGottesman, O\n\nGraff, M\n\nGrodstein, F\n\nGu, C\n\nHaley, C\n\nHammond, CJ\n\nHarris, SE\n\nHarris, TB\n\nHastie, ND\n\nHeard-Costa, NL\n\nHeikkilä, K\n\nHocking, LJ\n\nHomuth, G\n\nHottenga, JJ\n\nHuang, J\n\nHuffman, JE\n\nHysi, PG\n\nIkram, MA\n\nIngelsson, E\n\nJoensuu, A\n\nJohansson, Å\n\nJousilahti, P\n\nJukema, JW\n\nKähönen, M\n\nKamatani, Y\n\nKanoni, S\n\nKerr, SM\n\nKhan, NM\n\nKoellinger, P\n\nKoistinen, HA\n\nKooner, MK\n\nKubo, M\n\nKuusisto, J\n\nLahti, J\n\nLauner, LJ\n\nLea, RA\n\nLehne, B\n\nLehtimäki, T\n\nLiewald, DCM\n\nLind, L\n\nLoh, M\n\nLokki, ML\n\nLondon, SJ\n\nLoomis, SJ\n\nLoukola, A\n\nLu, Y\n\nLumley, T\n\nLundqvist, A\n\nMännistö, S\n\nMarques-Vidal, P\n\nMasciullo, C\n\nMatchan, A\n\nMathias, RA\n\nMatsuda, K\n\nMeigs, JB\n\nMeisinger, C\n\nMeitinger, T\n\nMenni, C\n\nMentch, FD\n\nMihailov, E\n\nMilani, L\n\nMontasser, ME\n\nMontgomery, GW\n\nMorrison, A\n\nMyers, RH\n\nNadukuru, R\n\nNavarro, P\n\nNelis, M\n\nNieminen, MS\n\nNolte, IM\n\nO'Connor, GT\n\nOgunniyi, A\n\nPadmanabhan, S\n\nPalmas, WR\n\nPankow, JS\n\nPatarcic, I\n\nPavani, F\n\nPeyser, PA\n\nPietilainen, K\n\nPoulter, N\n\nProkopenko, I\n\nRalhan, S\n\nRedmond, P\n\nRich, SS\n\nRissanen, H\n\nRobino, A\n\nRose, LM\n\nRose, R\n\nSala, C\n\nSalako, B\n\nSalomaa, V\n\nSarin, AP\n\nSaxena, R\n\nSchmidt, H\n\nScott, LJ\n\nScott, WR\n\nSennblad, B\n\nSeshadri, S\n\nSever, P\n\nShrestha, S\n\nSmith, BH\n\nSmith, JA\n\nSoranzo, N\n\nSotoodehnia, N\n\nSoutham, L\n\nStanton, AV\n\nStathopoulou, MG\n\nStrauch, K\n\nStrawbridge, RJ\n\nSuderman, MJ\n\nTandon, N\n\nTang, ST\n\nTaylor, KD\n\nTayo, BO\n\nTöglhofer, AM\n\nTomaszewski, M\n\nTšernikova, N\n\nTuomilehto, J\n\nUitterlinden, AG\n\nVaidya, D\n\nvan Hylckama Vlieg, A\n\nvan Setten, J\n\nVasankari, T\n\nVedantam, S\n\nVlachopoulou, E\n\nVozzi, D\n\nVuoksimaa, E\n\nWaldenberger, M\n\nWare, EB\n\nWentworth-Shields, W\n\nWhitfield, JB\n\nWild, S\n\nWillemsen, G\n\nYajnik, CS\n\nYao, J\n\nZaza, G\n\nZhu, X\n\nProject, TBJ\n\nSalem, RM\n\nMelbye, M\n\nBisgaard, H\n\nSamani, NJ\n\nCusi, D\n\nMackey, DA\n\nCooper, RS\n\nFroguel, P\n\nPasterkamp, G\n\nGrant, SFA\n\nHakonarson, H\n\nFerrucci, L\n\nScott, RA\n\nMorris, AD\n\nPalmer, CNA\n\nDedoussis, G\n\nDeloukas, P\n\nBertram, L\n\nLindenberger, U\n\nBerndt, SI\n\nLindgren, CM\n\nTimpson, NJ\n\nTönjes, A\n\nMunroe, PB\n\nSørensen, TIA\n\nRotimi, CN\n\nArnett, DK\n\nOldehinkel, AJ\n\nKardia, ...\n\nBeiträge in Fachzeitschriften\nISI:000358378900036\n26131930.0\n10.1038/nature14618\nPMC4516141\nHomozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354, 24 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.\n\nBirkl-Töglhofer, Anna Maria\n\nHofer, Edith\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
        },
        {
            "text": "\n185025\nUse of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)<sup>A</sup>, Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)<sup>B</sup>, Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)<sup>C</sup>, Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)<sup>D</sup>, Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)<sup>E</sup>, Österreichische Gesellschaft für Pneumologie (ÖGP)<sup>F</sup> in co-operation with the German, Austrian, and Swiss ARIA groups<sup>G</sup>, and the European Academy of Allergy and Clinical Immunology (EAACI)<sup>H</sup>.\n\nKlimek, L\n\nPfaar, O\n\nWorm, M\n\nEiwegger, T\n\nHagemann, J\n\nOllert, M\n\nUntersmayr, E\n\nHoffmann-Sommergruber, K\n\nVultaggio, A\n\nAgache, I\n\nBavbek, S\n\nBossios, A\n\nCasper, I\n\nChan, S\n\nChatzipetrou, A\n\nVogelberg, C\n\nFirinu, D\n\nKauppi, P\n\nKolios, A\n\nKothari, A\n\nMatucci, A\n\nPalomares, O\n\nSzépfalusi, Z\n\nPohl, W\n\nHötzenecker, W\n\nRosenkranz, AR\n\nBergmann, KC\n\nBieber, T\n\nBuhl, R\n\nButers, J\n\nDarsow, U\n\nKeil, T\n\nKleine-Tebbe, J\n\nLau, S\n\nMaurer, M\n\nMerk, H\n\nMösges, R\n\nSaloga, J\n\nStaubach, P\n\nJappe, U\n\nRabe, KF\n\nRabe, U\n\nVogelmeier, C\n\nBiedermann, T\n\nJung, K\n\nSchlenter, W\n\nRing, J\n\nChaker, A\n\nWehrmann, W\n\nBecker, S\n\nFreudelsperger, L\n\nMülleneisen, N\n\nNemat, K\n\nCzech, W\n\nWrede, H\n\nBrehler, R\n\nFuchs, T\n\nTomazic, PV\n\nAberer, W\n\nFink-Wagner, AH\n\nHorak, F\n\nWöhrl, S\n\nNiederberger-Leppin, V\n\nPali-Schöll, I\n\nPohl, W\n\nRoller-Wirnsberger, R\n\nSpranger, O\n\nValenta, R\n\nAkdis, M\n\nMatricardi, PM\n\nSpertini, F\n\nKhaltaev, N\n\nMichel, JP\n\nNicod, L\n\nSchmid-Grendelmeier, P\n\nIdzko, M\n\nHamelmann, E\n\nJakob, T\n\nWerfel, T\n\nWagenmann, M\n\nTaube, C\n\nJensen-Jarolim, E\n\nKorn, S\n\nHentges, F\n\nSchwarze, J\n\nO Mahony, L\n\nKnol, EF\n\nDel Giacco, S\n\nChivato Pérez, T\n\nBousquet, J\n\nBedbrook, A\n\nZuberbier, T\n\nAkdis, C\n\nJutel, M\n\nBeiträge in Fachzeitschriften\nNone\n32915172.0\n10.5414/ALX02166E\nPMC7480069\nSince the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.\n                A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.\n                In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.\n                The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.\n                © Dustri-Verlag Dr. K. Feistle.\n\nAberer, Werner\n\nRoller-Wirnsberger, Regina\n\nRosenkranz, Alexander\n\nTomazic, Peter Valentin\n\n\n"
        },
        {
            "text": "\n136109\nIntensive glucose control versus conventional glucose control for type 1 diabetes mellitus.\n\nFullerton, B\n\nJeitler, K\n\nSeitz, M\n\nHorvath, K\n\nBerghold, A\n\nSiebenhofer, A\n\nBeiträge in Fachzeitschriften\nISI:000332082900022\n24526393.0\n10.1002/14651858.CD009122.pub2\nNone\nClinical guidelines differ regarding their recommended blood glucose targets for patients with type 1 diabetes and recent studies on patients with type 2 diabetes suggest that aiming at very low targets can increase the risk of mortality.\n                To assess the effects of intensive versus conventional glycaemic targets in patients with type 1 diabetes in terms of long-term complications and determine whether very low, near normoglycaemic values are of additional benefit.\n                A systematic literature search was performed in the databases The Cochrane Library, MEDLINE and EMBASE. The date of the last search was December 2012 for all databases.\n                We included all randomised controlled trials (RCTs) that had defined different glycaemic targets in the treatment arms, studied patients with type 1 diabetes, and had a follow-up duration of at least one year.\n                Two review authors independently extracted data, assessed studies for risk of bias, with differences resolved by consensus. Overall study quality was evaluated by the 'Grading of Recommendations Assessment, Development, and Evaluation' (GRADE) system. Random-effects models were used for the main analyses and the results are presented as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes.\n                We identified 12 trials that fulfilled the inclusion criteria, including a total of 2230 patients. The patient populations varied widely across studies with one study only including children, one study only including patients after a kidney transplant, one study with newly diagnosed adult patients, and several studies where patients had retinopathy or microalbuminuria at baseline. The mean follow-up duration across studies varied between one and 6.5 years. The majority of the studies were carried out in the 1980s and all trials took place in Europe or North America. Due to the nature of the intervention, none of the studies could be carried out in a blinded fashion so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the studies. Fifty per cent of the studies were judged to have a high risk of bias in at least one other category.Under intensive glucose control, the risk of developing microvascular complications was reduced compared to conventional treatment for a) retinopathy: 23/371 (6.2%) versus 92/397 (23.2%); RR 0.27 (95% CI 0.18 to 0.42); P < 0.00001; 768 participants; 2 trials; high quality evidence; b) nephropathy: 119/732 (16.3%) versus 211/743 (28.4%); RR 0.56 (95% CI 0.46 to 0.68); P < 0.00001; 1475 participants; 3 trials; moderate quality evidence; c) neuropathy: 29/586 (4.9%) versus 86/617 (13.9%); RR 0.35 (95% CI 0.23 to 0.53); P < 0.00001; 1203 participants; 3 trials; high quality evidence. Regarding the progression of these complications after manifestation, the effect was weaker (retinopathy) or possibly not existent (nephropathy: RR 0.79 (95% CI 0.37 to 1.70); P = 0.55; 179 participants with microalbuminuria; 3 trials; very low quality evidence); no adequate data were available regarding the progression of neuropathy. For retinopathy, intensive glucose control reduced the risk of progression in studies with a follow-up duration of at least two years (85/366 (23.2%) versus 154/398 (38.7%); RR 0.61 (95% CI 0.49 to 0.76); P < 0.0001; 764 participants; 2 trials; moderate quality evidence), while we found evidence for an initial worsening of retinopathy after only one year of intensive glucose control (17/49 (34.7%) versus 7/47 (14.9%); RR 2.32 (95% CI 1.16 to 4.63); P = 0.02; 96 participants; 2 trials; low quality evidence).Major macrovascular outcomes (stroke and myocardial infarction) occurred very rarely, and no firm evidence could be established regarding these outcome measures (low quality evidence).We found that intensive glucose control increased the risk for severe hypoglycaemia, however the results were heterogeneous and only the 'Diabetes Complications Clinical Trial' (DCCT) showed a clear increase in severe hypoglycaemic episodes under intensive treatment. A subgroup analysis according to the baseline haemoglobin A1c (HbA1c) of participants in the trials (low quality evidence) suggests that the risk of hypoglycaemia is possibly only increased for patients who started with relatively low HbA1c values (< 9.0%). Several of the included studies also showed a greater weight gain under intensive glucose control, and the risk of ketoacidosis was only increased in studies using insulin pumps in the intensive treatment group (very low quality evidence).Overall, all-cause mortality was very low in all studies (moderate quality evidence) except in one study investigating renal allograft as treatment for end-stage diabetic nephropathy. Health-related quality of life was only reported in the DCCT trial, showing no statistically significant differences between the intervention and comparator groups (moderate quality evidence). In addition, only the DCCT published data on costs, indicating that intensive glucose therapy control was highly cost-effective considering the reduction of potential diabetes complications (moderate quality evidence).\n                Tight blood sugar control reduces the risk of developing microvascular diabetes complications. The evidence of benefit is mainly from studies in younger patients at early stages of the disease. Benefits need to be weighed against risks including severe hypoglycaemia, and patient training is an important aspect in practice. The effects of tight blood sugar control seem to become weaker once complications have been manifested. However, further research is needed on this issue. Furthermore, there is a lack of evidence from RCTs on the effects of tight blood sugar control in older patient populations or patients with macrovascular disease. There is no firm evidence for specific blood glucose targets and treatment goals need to be individualised taking into account age, disease progression, macrovascular risk, as well as the patient's lifestyle and disease management capabilities.\n\nBerghold, Andrea\n\nHorvath, Karl\n\nJeitler, Klaus\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
        },
        {
            "text": "\n833\nEffect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.\n\nBALL, SG\n\nCOWAN, JC\n\nWINTER, C\n\nMACKINTOSH, AF, TAN, LB\n\nCALDICOTT, L\n\nCHANNER, K\n\nHAWLEY SK, WILSON A, DEWS I, KADR H, STANTON J, STATUCH C, STEPHENS JD, BERKIN KE, DAVIES S, RAJ MVJ, CALLAGHAN TS, JOSEPH S, RAO AC, HAMBLETON D, HORNUNG RS, RODRIGUES E, ROBERTS H, WALLER D, WARNER N, PUGH SE, RAMAKRISHNAN N, SEKAR M, BLACKWOOD RA, ROBINSON P, CLARK M, ROBSON RH, PICKENS PT, TILDESLEY G, WHITE RWB, KELLY P, WILSON JI, JONES S, KINGDOM C, PATTERSON DLH, BENTLEY A, GUPTA S, HENDRY WG, DAVIDSON C, GLENNON P, BISHOP A, KLUTH D, MOONEY A, WILKINSON P, ANTHONY TP, GHOSH AK, ROBSON D, MCALEER B, VARMA MPS, LARKIN H, KADDOURA S, KNIGHT C, SUTTON G, CLARK RS, BEEN M, RAMAN A, BROWN AK, FOALE R, SHAHI J, BORLAND C, JAYASURIYA TG, SOMASUNDRAM U, EKDAHL S, HANSEN S, BROQVIST M, DAHLSTROM U, KONGSTAD O, CLINE C, ERHARDT L, WILLENHEIMER R, BERGLUND H, NYQUIST O, NYMAN P, URSING D, JENSEN S, GYLAND F, LINNE R, RAGNARTZ T, WATZ R, FREITAG M, OLSSON L, HALLGREN J, LINDVALL P, BERGIN C, CREAN P, ELGUYLANI N, MCADAMS B, MORAIS D, SHEAHAN R, MCKENNA J, MURRAY D, SULLIVAN P, FENNELL W, KEARNEY P, VAUGHAN C, GALVIN J, SUGRUE D, PEIRCE T, GHAISAS N, HARKIN E, OCALLAGHAN T, MCHUGH P, NISAR S, DALY K, LAVIN F, SHAH P, JUNEJA R, MCGARRY K, JUNEJO S, MACMAHON B, PILLAY NP, LONG D, MAGUIRE C, MULDOON BC, SHIELS P, BANNAN L, CONNELLY E, BARTON J, MCCREERY C, QUIGLEY P, CASSIM S, NAIDOO DP, MYBURGH DP, MARX JD, COMMERFORD PJ, LAWRENSON J, THERON HD, RAJPUT MC, BENNETT JM, SARELI P, ARCE P, RICCITELLI MA, RYBA D, BECK E, DEMARTINI A, BORREGA NG, LAZZARI J, GONZALEZ M, LIPRANDI AS, MARTINEZ JM, SAMPO EA, BORTMAN G, GRANCELLI H, CARBAJALES J, GIROTTI A, MAUTNER B, GABRIELLI O, CAGIDE A, LAPUENTE A, ESPER R, TAKENS LJ, VANDERHEIJDEN MY, KRAGTEN JA, RENKENS R, TANS AC, GROSFELD MJW, KRUYSWIJK HH, DEGROOT A, LIEM KL, OLTHOF H, HAERKENSARENDS HE, HOOGHOUDT TEH, KUYPERS A, NIEMEYER MG, VANMANTGEM JP, AELFERS E, SLEGERS LC, SCHEFFER MG, DOEBE BO, SCHRIJVERS LEJM, VANWELY LR, HERWEIJER AH, DEMYTTENAERE M, PEERENBOOM P, BEKAERT I, SURMONT P, VANDORPE A, BEYS J, CLEMENT D, BENIT E, BEYLOOS M, DURIEUX C, BAYART M, HERSSENS M, CREMERS S, DEKEYSER F, VANWALLEGHEM U, HOPF R, MOLLER A, HAUBER J, HOFGARTNER F, SIGEL HA, GRIESHABER M, NEUBAUER M, RUDOLPH K, SEHNERT W, CARTSBURG R, KLEINE P, HENNECKE TH, KINDLER J, RAMME P, HELLMANN D, HEMMENFUNK DA, FREYTAG F, BECKER HJ, EISENMENGER A, FACH WA, BERNHARDT P, ERNST BKH, JACOB H, MALINOWSKI K, ROTH H, SIMON H, BIAS HJ, BISCHOFF KO, GERNER U, TORNOW P, JENSEN SG, MELLEMGAARD K, AMTOFT A, AXELSEN A, CHRISTENSEN C, HAUNSO S, JORGENSEN P, RASMUSSEN S, STRUNGE P, SVENDSEN TL, MADSEN H, NIELSEN W, EGEDE F, RASMUSSEN J, MARKENVARD J, MOLLERUP H, SIGURD B, KIRCHHOFF M, MCNAIR A, NIELSEN PE, NIELSEN JER, ANDERSEN MP, BUCHER E, ELLIOTT P, SLANY J, GRISOLD M, KLEIN W, ALDOR E, DORNAUS C, KAINZ W, MLCZOCH J, NOBIS H, TRINKS S, POHJOLASINTONEN S, NAUKKARINEN V, SIPILA R, NIKUS K, WINGREN PE, HARKONEN M, JAGERHOLM S, ELORANTA M, ISOJARVI J, SUHONEN O, KOSKELAINEN J, DECIAN F, VOLTA SD, BERTON G, CUCCHINI F, ABELLI I, GAZZOLA U, VILLANI GQ, CENTOFANTE P, MOSELE GM, VINCENZI M, ACCORSI F, DEITOS GA, DELAGARDELLE C, MUNCH U, VOGELIN HP\n\nBeiträge in Fachzeitschriften\nISI:A1993MA02500007\n8104270.0\nNone\nNone\nSurvival after acute myocardial infarction has been enhanced by treatment with thrombolytic agents, aspirin, and beta-adrenoceptor blockade. However there remains a substantial subgroup of patients who manifest clinical evidence of heart failure despite the first two of these treatments, and for whom beta-adrenoceptor antagonists are relatively or absolutely contraindicated. These patients have a greatly increased risk of fatal and non-fatal ischaemic, arrhythmic, and haemodynamic events. In this selected high-risk subset of patients we investigated the effect of therapy with the angiotensin converting enzyme (ACE) inhibitor rampiril, postulating that it would lengthen survival. 2006 patients who had shown clinical evidence of heart failure at any time after an acute myocardial infarction (AMI) were recruited from 144 centres in 14 countries. Patients were randomly allocated to double-blind treatment with either placebo (992 patients) or ramipril (1014 patients) on day 3 to day 10 after AMI (day 1). Patients with severe heart failure resistant to conventional therapy, in whom the attending physician considered the use of an ACE inhibitor to be mandatory, were excluded. Follow-up was continued for a minimum of 6 months and an average of 15 months. On intention-to-treat analysis mortality from all causes was significantly lower for patients randomised to receive ramipril (170 deaths; 17%) than for those randomised to receive placebo (222 deaths; 23%). The observed risk reduction was 27% (95 % Cl 11% to 40%; p = 0.002). Analysis of prespecified secondary outcomes revealed a risk reduction of 19% for the first validated outcome (i.e., first event in an individual patient)--namely, death, severe/resistent heart failure, myocardial infarction, or stroke (95% Cl 5% to 31%; p = 0.008). Oral administration of rampiril to patients with clinical evidence of either transient or ongoing heart failure, initiated between the second and ninth day after myocardial infarction, resulted in a substantial reduction in premature death from all causes. This benefit was apparent as early as 30 days and was consistent across a range of subgroups.\n\n\n"
        },
        {
            "text": "\n149236\nThe Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.\n\nWinkler, TW\n\nJustice, AE\n\nGraff, M\n\nBarata, L\n\nFeitosa, MF\n\nChu, S\n\nCzajkowski, J\n\nEsko, T\n\nFall, T\n\nKilpeläinen, TO\n\nLu, Y\n\nMägi, R\n\nMihailov, E\n\nPers, TH\n\nRüeger, S\n\nTeumer, A\n\nEhret, GB\n\nFerreira, T\n\nHeard-Costa, NL\n\nKarjalainen, J\n\nLagou, V\n\nMahajan, A\n\nNeinast, MD\n\nProkopenko, I\n\nSimino, J\n\nTeslovich, TM\n\nJansen, R\n\nWestra, HJ\n\nWhite, CC\n\nAbsher, D\n\nAhluwalia, TS\n\nAhmad, S\n\nAlbrecht, E\n\nAlves, AC\n\nBragg-Gresham, JL\n\nde Craen, AJ\n\nBis, JC\n\nBonnefond, A\n\nBoucher, G\n\nCadby, G\n\nCheng, YC\n\nChiang, CW\n\nDelgado, G\n\nDemirkan, A\n\nDueker, N\n\nEklund, N\n\nEiriksdottir, G\n\nEriksson, J\n\nFeenstra, B\n\nFischer, K\n\nFrau, F\n\nGalesloot, TE\n\nGeller, F\n\nGoel, A\n\nGorski, M\n\nGrammer, TB\n\nGustafsson, S\n\nHaitjema, S\n\nHottenga, JJ\n\nHuffman, JE\n\nJackson, AU\n\nJacobs, KB\n\nJohansson, Å\n\nKaakinen, M\n\nKleber, ME\n\nLahti, J\n\nMateo Leach, I\n\nLehne, B\n\nLiu, Y\n\nLo, KS\n\nLorentzon, M\n\nLuan, J\n\nMadden, PA\n\nMangino, M\n\nMcKnight, B\n\nMedina-Gomez, C\n\nMonda, KL\n\nMontasser, ME\n\nMüller, G\n\nMüller-Nurasyid, M\n\nNolte, IM\n\nPanoutsopoulou, K\n\nPascoe, L\n\nPaternoster, L\n\nRayner, NW\n\nRenström, F\n\nRizzi, F\n\nRose, LM\n\nRyan, KA\n\nSalo, P\n\nSanna, S\n\nScharnagl, H\n\nShi, J\n\nSmith, AV\n\nSoutham, L\n\nStančáková, A\n\nSteinthorsdottir, V\n\nStrawbridge, RJ\n\nSung, YJ\n\nTachmazidou, I\n\nTanaka, T\n\nThorleifsson, G\n\nTrompet, S\n\nPervjakova, N\n\nTyrer, JP\n\nVandenput, L\n\nvan der Laan, SW\n\nvan der Velde, N\n\nvan Setten, J\n\nvan Vliet-Ostaptchouk, JV\n\nVerweij, N\n\nVlachopoulou, E\n\nWaite, LL\n\nWang, SR\n\nWang, Z\n\nWild, SH\n\nWillenborg, C\n\nWilson, JF\n\nWong, A\n\nYang, J\n\nYengo, L\n\nYerges-Armstrong, LM\n\nYu, L\n\nZhang, W\n\nZhao, JH\n\nAndersson, EA\n\nBakker, SJ\n\nBaldassarre, D\n\nBanasik, K\n\nBarcella, M\n\nBarlassina, C\n\nBellis, C\n\nBenaglio, P\n\nBlangero, J\n\nBlüher, M\n\nBonnet, F\n\nBonnycastle, LL\n\nBoyd, HA\n\nBruinenberg, M\n\nBuchman, AS\n\nCampbell, H\n\nChen, YD\n\nChines, PS\n\nClaudi-Boehm, S\n\nCole, J\n\nCollins, FS\n\nde Geus, EJ\n\nde Groot, LC\n\nDimitriou, M\n\nDuan, J\n\nEnroth, S\n\nEury, E\n\nFarmaki, AE\n\nForouhi, NG\n\nFriedrich, N\n\nGejman, PV\n\nGigante, B\n\nGlorioso, N\n\nGo, AS\n\nGottesman, O\n\nGräßler, J\n\nGrallert, H\n\nGrarup, N\n\nGu, YM\n\nBroer, L\n\nHam, AC\n\nHansen, T\n\nHarris, TB\n\nHartman, CA\n\nHassinen, M\n\nHastie, N\n\nHattersley, AT\n\nHeath, AC\n\nHenders, AK\n\nHernandez, D\n\nHillege, H\n\nHolmen, O\n\nHovingh, KG\n\nHui, J\n\nHusemoen, LL\n\nHutri-Kähönen, N\n\nHysi, PG\n\nIllig, T\n\nDe Jager, PL\n\nJalilzadeh, S\n\nJørgensen, T\n\nJukema, JW\n\nJuonala, M\n\nKanoni, S\n\nKaraleftheri, M\n\nKhaw, KT\n\nKinnunen, L\n\nKittner, SJ\n\nKoenig, W\n\nKolcic, I\n\nKovacs, P\n\nKrarup, NT\n\nKratzer, W\n\nKrüger, J\n\nKuh, D\n\nKumari, M\n\nKyriakou, T\n\nLangenberg, C\n\nLannfelt, L\n\nLanzani, C\n\nLotay, V\n\nLauner, LJ\n\nLeander, K\n\nLindström, J\n\nLinneberg, A\n\nLiu, YP\n\nLobbens, S\n\nLuben, R\n\nLyssenko, V\n\nMännistö, S\n\nMagnusson, PK\n\nMcArdle, WL\n\nMenni, C\n\nMerger, S\n\nMilani, L\n\nMontgomery, GW\n\nMorris, AP\n\nNarisu, N\n\nNelis, M\n\nOng, KK\n\nPalotie, A\n\nPérusse, L\n\nPichler, I\n\nPilia, MG\n\nPouta, A\n\nRheinberger, M\n\nRibel-Madsen, R\n\nRichards, M\n\nRice, KM\n\nRice, TK\n\nRivolta, C\n\nSalomaa, V\n\nSanders, AR\n\nSarzynski, MA\n\nScholtens, S\n\nScott, RA\n\nScott, WR\n\nSebert, S\n\nSengupta, S\n\nSennblad, B\n\nSeufferlein, T\n\nSilveira, A\n\nSlagboom, PE\n\nSmit, JH\n\nSparsø, TH\n\nStirrups, K\n\nStolk, RP\n\nStringham, HM\n\nSwertz, MA\n\nSwift, AJ\n\nSyvänen, AC\n\nTan, ST\n\nThorand, B\n\nTönjes, A\n\nTremblay, A\n\nTsafantakis, E\n\nvan der Most, PJ\n\nVölker, U\n\nVohl, MC\n\nVonk, JM\n\nWaldenberger, M\n\nWalker, RW\n\nWennauer, R\n\nWidén, E\n\nWillemsen, G\n\nWilsgaard, T\n\nWright, AF\n\nZillikens, MC\n\nvan Dijk, SC\n\nvan Schoor, NM\n\nAsselbergs, FW\n\nde Bakker, PI\n\nBeckmann, JS\n\nBeilby, J\n\nBennett, DA\n\nBergma ...\n\nBeiträge in Fachzeitschriften\nISI:000364401600002\n26426971.0\n10.1371/journal.pgen.1005378\nPMC4591371\nGenome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320, 85 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.\n\nScharnagl, Hubert\n\n\n"
        },
        {
            "text": "\n170447\nDVO Guideline 2017 for the Prophylaxis, Diagnosis and Treatment of Osteoporosis in postmenopausal Women and Men Short Version\n\nThomasius, F\n\nBaum, E\n\nBernecker, P\n\nBocker, W\n\nBrabant, T\n\nClarenz, P\n\nDemary, W\n\nDimai, HP\n\nEngelbrecht, M\n\nEngelke, K\n\nFratermann, U\n\nGrieser, T\n\nGulich, M\n\nHadji, P\n\nHenning, J\n\nJehle, PM\n\nKern, PM\n\nKetteler, M\n\nKlatt, G\n\nKraenzlin, M\n\nMaus, U\n\nMeier, C\n\nMoser, U\n\nMuller, D\n\nPeichl, P\n\nPfeifer, M\n\nRintelen, B\n\nRueger, JM\n\nSchober, HC\n\nSchoffel, D\n\nSchwarz, H\n\nSiggelkow, H\n\nSuhm, N\n\nWiese, KG\n\nWortler, K\n\nKurth, AA\n\nBeiträge in Fachzeitschriften\nISI:000449033500006\nNone\n10.1055/s-0038-1673537\nNone\nZusammenfassung Diese DVO Leitlinien, die in erster Linie fur Allgemeinmediziner und Spezialisten fur Knochenerkrankungen bestimmt sind, sollten von allen im klinischen und ambulanten Bereich tatigen medizinischen Fachkraften angewendet werden. Ziel der Leitlinie ist die Verbesserung der Diagnose, Pravention und Behandlung von Osteoporose und der Folgen der Erkrankung auf der Grundlage evidenzbasierter Medizin. Klare Empfehlungen, welche Patienten zu diagnostizieren und behandeln sind (basierend auf Risikofaktoren [einschlie ss lich sekundarer Osteoporose]) sowie Primar-, Sekundar- oder Tertiarpravention werden dargestellt, mit dem Schwerpunkt auf der postmenopausalen Osteoporose und der Osteoporose bei Mannern. Die Identifizierung von Patienten mit einem hohen Risiko fur Frakturen wird hervorgehoben, und spezifische Schwellenwerte fur die Intervention sind definiert (20 % Huftfrakturrisiko innerhalb von 10 Jahren diagnostischer Schwellenwert, 30 % Huftfrakturrisiko innerhalb von 10 Jahren therapeutische Schwelle). Die Diagnose von Osteoporose basiert auf der Anamnese des Patienten, der korperlichen Untersuchung, dem Funktionstest (z. B. Timed Up and Go Test), konventionellen Rontgenaufnahmen der Brust- und Lendenwirbelsaule und der Bestimmung der Knochenmineraldichte (BMD) durch das DXA Verfahren. Die Anamnese ist entscheidend fur die Abschatzung des Frakturrisikos auf der Grundlage von 40 wissenschaftlich uberpruften Risikofaktoren, die das Frakturrisiko mindestens verdoppeln (z. B. Begleiterkrankungen, Huftfrakturen in der Familie, pravalente Frakturen an jedem Ort, Lebensstil, Anwendung von Medikamenten, korperliche Aktivitat und Sturze). Rontgenaufnahmen der Brust- und Lendenwirbelsaule sind wichtig, um pravalente Wirbelkorperfrakturen zu erkennen. Beim Fehlen eines gro ss en Traumas kann jede Fraktur bei Erwachsenen uber dem Alter von 50 Jahren eine Diagnose von Osteoporose nahelegen, mit dem hochsten Risiko fur eine nachfolgende Fraktur innerhalb einer kurzen Zeit nach der ersten Fraktur. BMD-Messungen mit DXA sind wichtig, um das individuelle Frakturrisiko besser abschatzen zu konnen. Eine grundlegende Laboruntersuchung ist obligatorisch, um verschiedene Formen der sekundaren Osteoporose ausschlie ss en zu konnen. Der DVO-Patientenfindungs-Algorithmus basiert auf dem Geschlecht, Alter, Knochenmineraldichte und vorbestehenden Frakturen als wichtigste Informationen. Die Indikation fur eine aktive anti-osteoporotische Therapie kann durch multiple Risikofaktoren modifiziert und verfeinert werden. Dieser Algorithmus wurde seit dem Richtlinien-Update 2006 verwendet und wurde entsprechend der internationalen Literatur zu Risikofaktoren fur Osteoporose und osteoporotische Frakturen aktualisiert und angepasst. Die Behandlung der Osteoporose enthalt viele Therapiepfeiler. Zusammen mit Empfehlungen fur Bewegung, Physiotherapie und Sturzpravention sowie Ernahrung (z. B. Calcium, Vit. D), werden pharmakologische Behandlungen basierend auf evidenzbasierter Medizin empfohlen. Die aktiven Anti-Osteoporose-Medikamente mussen fur die Indikation postmenopausale Osteoporose und mannliche Osteoporose in Deutschland, osterreich und der Schweiz zugelassen sein. Das Management und die Vorbeugung von haufigen oder seltenen Nebenwirkungen aufgrund von Anti-Osteoporose-Behandlungen, die in der klinischen Praxis angewendet werden, werden ebenfalls detailliert behandelt. Summary These guidelines, which are primarily intended for general practitioners and bone disease specialists, should be used by any health-care professionals in a clinical and outpatient setting. Goal of the guideline is to improve diagnosis, prevention and treatment of osteoporosis and the consequences of the disease based on evidence based medicine principals Guidelines for the case finding, based on risk factors (including secondary osteoporosis), as well as primary, secondary, or tertiary prevention are described, focusing on postmenopausal osteoporosis and osteoporosis in men. The identification of subjects at high risk for fractures are highlighted, and specific thresholds for intervention are defined (20 % hip fracture risk within 10 years diagnostic threshold, 30 % hip fracture risk within 10 years therapeutic threshold). The diagnosis of osteoporosis is based on patient medical history, physical examination, functional test (e. g. Timed Up and GO), conventional X-rays of the thoracic and lumbar spine, and bone mineral density (BMD) measurements by DXA. The medical history is essential to estimate the fracture risk based on any of 40 evaluated risk factors, which at least double the fracture risk (e. g. concomitant disorders, a family history of hip fractures, prevalent fractures at any site, lifestyle, use of medications, physical activity, and falls). X-rays of the thoracic and lumbar spine are useful for detecting prevalent vertebral fractures. In the absence of major trauma, any fracture in adults beyond the age of 50 years may suggest a diagnosis of osteoporosis with the highest risk for subsequent fracture within a short time after the first fracture. BMD measurements by DXA are important as they can be used to better estimate the individual fracture risk. A basic Laboratory examination is mandatory to exclude different forms of secondary osteoporosis. The DVO case finding algorithm is based on gender, age, bone mineral density measurements, and prevalent fractures as the main information. The indication for an active antiosteoporotic treatment can be refined by multiple risk factors. This algorithm has been used since the guideline update 2006 and has been modified and adapted according to the international literature on risk factors for osteoporosis and osteoporotic fractures. The treatment of osteoporosis contains multiple modalities. Along with recommendations for exercise, physiotherapy and fall prevention, as well as nutrition (e. g. Calcium, Vit. D), pharmacologic treatments based on evidence based medicine are recommended. The active anti-osteoporotic drugs have to be approved for the indication postmenopausal osteoporosis and male osteoporosis in Germany, Austria, Switzerland. The management and prevention of common or rare side effects due to anti-osteoporotic treatments employed in clinical practice are addressed.\n\nDimai, Hans\n\n\n"
        },
        {
            "text": "\n163024\nImpact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.\n\nWheeler, E\n\nLeong, A\n\nLiu, CT\n\nHivert, MF\n\nStrawbridge, RJ\n\nPodmore, C\n\nLi, M\n\nYao, J\n\nSim, X\n\nHong, J\n\nChu, AY\n\nZhang, W\n\nWang, X\n\nChen, P\n\nMaruthur, NM\n\nPorneala, BC\n\nSharp, SJ\n\nJia, Y\n\nKabagambe, EK\n\nChang, LC\n\nChen, WM\n\nElks, CE\n\nEvans, DS\n\nFan, Q\n\nGiulianini, F\n\nGo, MJ\n\nHottenga, JJ\n\nHu, Y\n\nJackson, AU\n\nKanoni, S\n\nKim, YJ\n\nKleber, ME\n\nLadenvall, C\n\nLecoeur, C\n\nLim, SH\n\nLu, Y\n\nMahajan, A\n\nMarzi, C\n\nNalls, MA\n\nNavarro, P\n\nNolte, IM\n\nRose, LM\n\nRybin, DV\n\nSanna, S\n\nShi, Y\n\nStram, DO\n\nTakeuchi, F\n\nTan, SP\n\nvan der Most, PJ\n\nVan Vliet-Ostaptchouk, JV\n\nWong, A\n\nYengo, L\n\nZhao, W\n\nGoel, A\n\nMartinez Larrad, MT\n\nRadke, D\n\nSalo, P\n\nTanaka, T\n\nvan Iperen, EPA\n\nAbecasis, G\n\nAfaq, S\n\nAlizadeh, BZ\n\nBertoni, AG\n\nBonnefond, A\n\nBöttcher, Y\n\nBottinger, EP\n\nCampbell, H\n\nCarlson, OD\n\nChen, CH\n\nCho, YS\n\nGarvey, WT\n\nGieger, C\n\nGoodarzi, MO\n\nGrallert, H\n\nHamsten, A\n\nHartman, CA\n\nHerder, C\n\nHsiung, CA\n\nHuang, J\n\nIgase, M\n\nIsono, M\n\nKatsuya, T\n\nKhor, CC\n\nKiess, W\n\nKohara, K\n\nKovacs, P\n\nLee, J\n\nLee, WJ\n\nLehne, B\n\nLi, H\n\nLiu, J\n\nLobbens, S\n\nLuan, J\n\nLyssenko, V\n\nMeitinger, T\n\nMiki, T\n\nMiljkovic, I\n\nMoon, S\n\nMulas, A\n\nMüller, G\n\nMüller-Nurasyid, M\n\nNagaraja, R\n\nNauck, M\n\nPankow, JS\n\nPolasek, O\n\nProkopenko, I\n\nRamos, PS\n\nRasmussen-Torvik, L\n\nRathmann, W\n\nRich, SS\n\nRobertson, NR\n\nRoden, M\n\nRoussel, R\n\nRudan, I\n\nScott, RA\n\nScott, WR\n\nSennblad, B\n\nSiscovick, DS\n\nStrauch, K\n\nSun, L\n\nSwertz, M\n\nTajuddin, SM\n\nTaylor, KD\n\nTeo, YY\n\nTham, YC\n\nTönjes, A\n\nWareham, NJ\n\nWillemsen, G\n\nWilsgaard, T\n\nHingorani, AD\n\nEPIC-CVD Consortium\n\nEPIC-InterAct Consortium\n\nLifelines Cohort Study\n\nEgan, J\n\nFerrucci, L\n\nHovingh, GK\n\nJula, A\n\nKivimaki, M\n\nKumari, M\n\nNjølstad, I\n\nPalmer, CNA\n\nSerrano Ríos, M\n\nStumvoll, M\n\nWatkins, H\n\nAung, T\n\nBlüher, M\n\nBoehnke, M\n\nBoomsma, DI\n\nBornstein, SR\n\nChambers, JC\n\nChasman, DI\n\nChen, YI\n\nChen, YT\n\nCheng, CY\n\nCucca, F\n\nde Geus, EJC\n\nDeloukas, P\n\nEvans, MK\n\nFornage, M\n\nFriedlander, Y\n\nFroguel, P\n\nGroop, L\n\nGross, MD\n\nHarris, TB\n\nHayward, C\n\nHeng, CK\n\nIngelsson, E\n\nKato, N\n\nKim, BJ\n\nKoh, WP\n\nKooner, JS\n\nKörner, A\n\nKuh, D\n\nKuusisto, J\n\nLaakso, M\n\nLin, X\n\nLiu, Y\n\nLoos, RJF\n\nMagnusson, PKE\n\nMärz, W\n\nMcCarthy, MI\n\nOldehinkel, AJ\n\nOng, KK\n\nPedersen, NL\n\nPereira, MA\n\nPeters, A\n\nRidker, PM\n\nSabanayagam, C\n\nSale, M\n\nSaleheen, D\n\nSaltevo, J\n\nSchwarz, PE\n\nSheu, WHH\n\nSnieder, H\n\nSpector, TD\n\nTabara, Y\n\nTuomilehto, J\n\nvan Dam, RM\n\nWilson, JG\n\nWilson, JF\n\nWolffenbuttel, BHR\n\nWong, TY\n\nWu, JY\n\nYuan, JM\n\nZonderman, AB\n\nSoranzo, N\n\nGuo, X\n\nRoberts, DJ\n\nFlorez, JC\n\nSladek, R\n\nDupuis, J\n\nMorris, AP\n\nTai, ES\n\nSelvin, E\n\nRotter, JI\n\nLangenberg, C\n\nBarroso, I\n\nMeigs, JB\n\nBeiträge in Fachzeitschriften\nISI:000411970300003\n28898252.0\n10.1371/journal.pmed.1002383\nPMC5595282\nGlycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.\n                Using genome-wide association meta-analyses in up to 159, 40 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33, 41). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.\n                As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.\n\nMärz, Winfried\n\n\n"
        },
        {
            "text": "\n184142\n(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus.\n\nSemlitsch, T\n\nEngler, J\n\nSiebenhofer, A\n\nJeitler, K\n\nBerghold, A\n\nHorvath, K\n\nBeiträge in Fachzeitschriften\nISI:000595647200011\n33166419.0\n10.1002/14651858.CD005613.pub4\nNone\nEvidence that antihyperglycaemic therapy is beneficial for people with type 2 diabetes mellitus is conflicting. While the United Kingdom Prospective Diabetes Study (UKPDS) found tighter glycaemic control to be positive, other studies, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, found the effects of an intensive therapy to lower blood glucose to near normal levels to be more harmful than beneficial. Study results also showed different effects for different antihyperglycaemic drugs, regardless of the achieved blood glucose levels. In consequence, firm conclusions on the effect of interventions on patient-relevant outcomes cannot be drawn from the effect of these interventions on blood glucose concentration alone. In theory, the use of newer insulin analogues may result in fewer macrovascular and microvascular events.\n                To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues (insulin glargine U100 and U300, insulin detemir and insulin degludec) with NPH (neutral protamine Hagedorn) insulin (human isophane insulin) in adults with type 2 diabetes mellitus.\n                For this Cochrane Review update, we searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 5 November 2019, except Embase which was last searched 26 January 2017. We applied no language restrictions.\n                We included randomised controlled trials (RCTs) comparing the effects of treatment with (ultra-)long-acting insulin analogues to NPH in adults with type 2 diabetes mellitus.\n                Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated the overall certainty of the evidence using GRADE. Trials were pooled using random-effects meta-analyses.\n                We identified 24 RCTs. Of these, 16 trials compared insulin glargine to NPH insulin and eight trials compared insulin detemir to NPH insulin. In these trials, 3419 people with type 2 diabetes mellitus were randomised to insulin glargine and 1321 people to insulin detemir. The duration of the included trials ranged from 24 weeks to five years. For studies, comparing insulin glargine to NPH insulin, target values ranged from 4.0 mmol/L to 7.8 mmol/L (72 mg/dL to 140 mg/dL) for fasting blood glucose (FBG), from 4.4 mmol/L to 6.6 mmol/L (80 mg/dL to 120 mg/dL) for nocturnal blood glucose and less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, when applicable. Blood glucose and glycosylated haemoglobin A1c (HbA1c) target values for studies comparing insulin detemir to NPH insulin ranged from 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for FBG, less than 6.7 mmol/L (120 mg/dL) to less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for nocturnal blood glucose and 5.8% to less than 6.4% HbA1c, when applicable. All trials had an unclear or high risk of bias for several risk of bias domains. Overall, insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Changes in HbA1c were comparable for long-acting insulin analogues and NPH insulin. Insulin glargine compared to NPH insulin had a risk ratio (RR) for severe hypoglycaemia of 0.68 (95% confidence interval (CI) 0.46 to 1.01; P = 0.06; absolute risk reduction (ARR) -1.2%, 95% CI -2.0 to 0; 14 trials, 6164 participants; very low-certainty evidence). The RR for serious hypoglycaemia was 0.75 (95% CI 0.52 to 1.09; P = 0.13; ARR -0.7%, 95% CI -1.3 to 0.2; 10 trials, 4685 participants; low-certainty evidence). Treatment with insulin glargine reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Treatment with insulin detemir compared to NPH insulin found an RR for severe hypoglycaemia of 0.45 (95% CI 0.17 to 1.20; P = 0.11; ARR -0.9%, 95% CI -1.4 to 0.4; 5 trials, 1804 participants; very low-certainty evidence). The Peto odds ratio for serious hypoglycaemia was 0.16, 95% CI 0.04 to 0.61; P = 0.007; ARR -0.9%, 95% CI -1.1 to -0.4; 5 trials, 1777 participants; low-certainty evidence). Treatment with detemir also reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Information on patient-relevant outcomes such as death from any cause, diabetes-related complications, health-related quality of life and socioeconomic effects was insufficient or lacking in almost all included trials. For those outcomes for which some data were available, there were no meaningful differences between treatment with glargine or detemir and treatment with NPH. There was no clear difference between insulin-analogues and NPH insulin in terms of weight gain. The incidence of adverse events was comparable for people treated with glargine or detemir, and people treated with NPH. We found no trials comparing ultra-long-acting insulin glargine U300 or insulin degludec with NPH insulin.\n                While the effects on HbA1c were comparable, treatment with insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Treatment with insulin detemir also reduced the incidence of serious hypoglycaemia. However, serious hypoglycaemic events were rare and the absolute risk reducing effect was low. Approximately one in 100 people treated with insulin detemir instead of NPH insulin benefited. In the studies, low blood glucose and HbA1c targets, corresponding to near normal or even non-diabetic blood glucose levels, were set. Therefore, results from the studies are only applicable to people in whom such low blood glucose concentrations are targeted. However, current guidelines recommend less-intensive blood glucose lowering for most people with type 2 diabetes in daily practice (e.g. people with cardiovascular diseases, a long history of type 2 diabetes, who are susceptible to hypoglycaemia or older people). Additionally, low-certainty evidence and trial designs that did not conform with current clinical practice meant it remains unclear if the same effects will be observed in daily clinical practice. Most trials did not report patient-relevant outcomes.\n                Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n\nBerghold, Andrea\n\nHorvath, Karl\n\nJeitler, Klaus\n\nSemlitsch, Thomas\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
        },
        {
            "text": "\n177389\nWhich Factors Are Associated with Local Control and Survival of Patients with Localized Pelvic Ewing's Sarcoma? A Retrospective Analysis of Data from the Euro-EWING99 Trial.\n\nAndreou, D\n\nRanft, A\n\nGosheger, G\n\nTimmermann, B\n\nLadenstein, R\n\nHartmann, W\n\nBauer, S\n\nBaumhoer, D\n\nvan den Berg, H\n\nDijkstra, PDS\n\nDürr, HR\n\nGelderblom, H\n\nHardes, J\n\nHjorth, L\n\nKreyer, J\n\nKruseova, J\n\nLeithner, A\n\nScobioala, S\n\nStreitbürger, A\n\nTunn, PU\n\nWardelmann, E\n\nWindhager, R\n\nJürgens, H\n\nDirksen, U\n\nGPOH-Euro-EWING99 consortium\n\nBeiträge in Fachzeitschriften\nISI:000533562600019\n31580267.0\n10.1097/CORR.0000000000000962\nPMC7438129\nLocal treatment of pelvic Ewing's sarcoma may be challenging, and intergroup studies have focused on improving systemic treatments rather than prospectively evaluating aspects of local tumor control. The Euro-EWING99 trial provided a substantial number of patients with localized pelvic tumors treated with the same chemotherapy protocol. Because local control included surgical resection, radiation therapy, or a combination of both, we wanted to investigate local control and survival with respect to the local modality in this study cohort.\n                (1) Do patients with localized sacral tumors have a lower risk of local recurrence and higher survival compared with patients with localized tumors of the innominate bones? (2) Is the local treatment modality associated with local control and survival in patients with sacral and nonsacral tumors? (3) Which local tumor- and treatment-related factors, such as response to neoadjuvant chemotherapy, institution where the biopsy was performed, and surgical complications, are associated with local recurrence and patient survival in nonsacral tumors? (4) Which factors, such as persistent extraosseous tumor growth after chemotherapy or extent of bony resection, are independently associated with overall survival in patients with bone tumors undergoing surgical treatment?\n                Between 1998 and 2009, 1411 patients with previously untreated, histologically confirmed Ewing's sarcoma were registered in the German Society for Pediatric Oncology and Hematology Ewing's sarcoma database and treated in the Euro-EWING99 trial. In all, 24% (339 of 1411) of these patients presented with a pelvic primary sarcoma, 47% (159 of 339) of which had macroscopic metastases at diagnosis and were excluded from this analysis. The data from the remaining 180 patients were reviewed retrospectively, based on follow-up data as of July 2016. The median (range) follow-up was 54 months (5 to 191) for all patients and 84 months (11 to 191) for surviving patients. The study endpoints were overall survival, local recurrence and event-free survival probability, which were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) with their respective 95% CIs were estimated in a multivariate Cox regression model.\n                Sacral tumors were associated with a reduced probability of local recurrence (12% [95% CI 1 to 22] versus 28% [95% CI 20 to 36] at 5 years, p = 0.032), a higher event-free survival probability (66% [95% CI 51 to 81] versus 50% [95% CI 41 to 58] at 5 years, p = 0.026) and a higher overall survival probability (72% [95% CI 57 to 87] versus 56% [95% CI 47 to 64] at 5 years, p = 0.025) compared with nonsacral tumors. With the numbers available, we found no differences between patients with sacral tumors who underwent definitive radiotherapy and those who underwent combined surgery and radiotherapy in terms of local recurrence (17% [95% CI 0 to 34] versus 0% [95% CI 0 to 20] at 5 years, p = 0.125) and overall survival probability (73% [95% CI 52 to 94] versus 78% [95% CI 56 to 99] at 5 years, p = 0.764). In nonsacral tumors, combined local treatment was associated with a lower local recurrence probability (14% [95% CI 5 to 23] versus 33% [95% CI 19 to 47] at 5 years, p = 0.015) and a higher overall survival probability (72% [95% CI 61 to 83] versus 47% [95% CI 33 to 62] at 5 years, p = 0.024) compared with surgery alone. Even in a subgroup of patients with wide surgical margins and a good histologic response to induction treatment, the combined local treatment was associated with a higher overall survival probability (87% [95% CI 74 to 100] versus 51% [95% CI 33 to 69] at 5 years, p = 0.009), compared with surgery alone.A poor histologic response to induction chemotherapy in nonsacral tumors (39% [95% CI 19 to 59] versus 64% [95% CI 52 to 76] at 5 years, p = 0.014) and the development of surgical complications after tumor resection (35% [95% CI 11 to 59] versus 68% [95% CI 58 to 78] at 5 years, p = 0.004) were associated with a lower overall survival probability in nonsacral tumors, while a tumor biopsy performed at the same institution where the tumor resection was performed was associated with lower local recurrence probability (14% [95% CI 4 to 24] versus 32% [95% CI 16 to 48] at 5 years, p = 0.035), respectively.In patients with bone tumors who underwent surgical treatment, we found that after controlling for tumor localization in the pelvis, tumor volume, and surgical margin status, patients who did not undergo complete (defined as a Type I/II resection for iliac bone tumors, a Type II/III resection for pubic bone and ischium tumors and a Type I/II/III resection for tumors involving the acetabulum, according to the Enneking classification) removal of the affected bone (HR 5.04 [95% CI 2.07 to 12.24]; p < 0.001), patients with a poor histologic response to induction chemotherapy (HR 3.72 [95% CI 1.51 to 9.21]; p = 0.004), and patients who did not receive additional radiotherapy (HR 4.34 [95% CI 1.71 to 11.05]; p = 0.002) had a higher risk of death. The analysis suggested that the same might be the case in patients with a persistent extraosseous tumor extension after induction chemotherapy (HR 4.61 [95% CI 1.03 to 20.67]; p = 0.046), although the wide CIs pointing at a possible sparse-data bias precluded any definitive conclusions.\n                Patients with sacral Ewing's sarcoma appear to have a lower probability for local recurrence and a higher overall survival probability compared with patients with tumors of the innominate bones. Our results seem to support a recent recommendation of the Scandinavian Sarcoma Group to locally treat most sacral Ewing's sarcomas with definitive radiotherapy. Combined surgical resection and radiotherapy appear to be associated with a higher overall survival probability in nonsacral tumors compared with surgery alone, even in patients with a wide resection and a good histologic response to neoadjuvant chemotherapy. Complete removal of the involved bone, as defined above, in patients with nonsacral tumors may be associated with a decreased likelihood of local recurrence and improved overall survival. Persistent extraosseous tumor growth after induction treatment in patients with nonsacral bone tumors undergoing surgical treatment might be an important indicator of poorer overall survival probability, but the possibility of sparse-data bias in our cohort means that this factor should first be validated in future studies.\n                Level III, therapeutic study.\n\nLeithner, Andreas\n\n\n"
        }
    ]
}