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"text": "\n114241\nGenetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease.\n\nSchmidt, H\n\nZeginigg, M\n\nWiltgen, M\n\nFreudenberger, P\n\nPetrovic, K\n\nCavalieri, M\n\nGider, P\n\nEnzinger, C\n\nFornage, M\n\nDebette, S\n\nRotter, JI\n\nIkram, MA\n\nLauner, LJ\n\nSchmidt, R\n\nCHARGE consortium Neurology working group\n\nBeiträge in Fachzeitschriften\nISI:000296976500030\n22006983.0\n10.1093/brain/awr252\nPMC3212720\nCerebral small vessel disease-related brain lesions such as white matter lesions and lacunes are common findings of magnetic resonance imaging in the elderly. These lesions are thought to be major contributors to disability in old age, and risk factors that include age and hypertension have been established. The radiological, histopathologic and clinical phenotypes of age-related cerebral small vessel disease remarkably resemble autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, which is caused by mutations in NOTCH3. We hypothesized that genetic variations in NOTCH3 also play a role in age-related cerebral small vessel disease. We directly sequenced all 33 exons, the promoter and 3'-untranslated region of NOTCH3 in 195 participants with either coalescent white matter lesions or lacunes and compared the results to 82 randomly selected participants with no focal changes on magnetic resonance images in the Austrian Stroke Prevention Study. We detected nine common and 33 rare single nucleotide polymorphisms, of which 20 were novel. All common single nucleotide polymorphisms were genotyped in the entire cohort (n = 888), and four of them, rs1043994, rs10404382, rs10423702 and rs1043997, were associated significantly with both the presence and progression of white matter lesions. The association was confined to hypertensives, a result which we replicated in the Cohorts for Heart and Ageing Research in Genomic Epidemiology Consortium on an independent sample of 4773 stroke-free hypertensive elderly individuals of European descent (P = 0.04). The 33 rare single nucleotide polymorphisms were scattered over the NOTCH3 gene with three being located in the promoter region, 24 in exons (18 non-synonymous), three in introns and three in the 3'-untranslated region. None of the single nucleotide polymorphisms affected a cysteine residue. Sorting Intolerant From Tolerant, PolyPhen2 analyses and protein structure simulation consistently predicted six of the non-synonymous single nucleotide polymorphisms (H170R, P496L, V1183M, L1518M, D1823N and V1952M) to be functional, with four being exclusively or mainly detected in subjects with severe white matter lesions. In four individuals with rare non-synonymous single nucleotide polymorphisms, we noted anterior temporal lobe hyperintensity, hyperintensity in the external capsule, lacunar infarcts or subcortical lacunar lesions. None of the observed abnormalities were specific to cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. This is the first comprehensive study investigating (i) the frequency of NOTCH3 variations in community-dwelling elderly and (ii) their effect on cerebral small vessel disease related magnetic resonance imaging phenotypes. We show that the NOTCH3 gene is highly variable with both common and rare single nucleotide polymorphisms spreading across the gene, and that common variants at the NOTCH3 gene increase the risk of age-related white matter lesions in hypertensives. Additional investigations are required to explore the biological mechanisms underlying the observed association.\n\nCavalieri, Margherita\n\nEnzinger, Christian\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\nWiltgen, Marco\n\n\n"
},
{
"text": "\n185077\nEuropean Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel.\n\nSylvester, RJ\n\nRodríguez, O\n\nHernández, V\n\nTurturica, D\n\nBauerová, L\n\nBruins, HM\n\nBründl, J\n\nvan der Kwast, TH\n\nBrisuda, A\n\nRubio-Briones, J\n\nSeles, M\n\nHentschel, AE\n\nKusuma, VRM\n\nHuebner, N\n\nCotte, J\n\nMertens, LS\n\nVolanis, D\n\nCussenot, O\n\nSubiela Henríquez, JD\n\nde la Peña, E\n\nPisano, F\n\nPešl, M\n\nvan der Heijden, AG\n\nHerdegen, S\n\nZlotta, AR\n\nHacek, J\n\nCalatrava, A\n\nMannweiler, S\n\nBosschieter, J\n\nAshabere, D\n\nHaitel, A\n\nCôté, JF\n\nEl Sheikh, S\n\nLunelli, L\n\nAlgaba, F\n\nAlemany, I\n\nSoria, F\n\nRunneboom, W\n\nBreyer, J\n\nNieuwenhuijzen, JA\n\nLlorente, C\n\nMolinaro, L\n\nHulsbergen-van de Kaa, CA\n\nEvert, M\n\nKiemeney, LALM\n\nN'Dow, J\n\nPlass, K\n\nČapoun, O\n\nSoukup, V\n\nDominguez-Escrig, JL\n\nCohen, D\n\nPalou, J\n\nGontero, P\n\nBurger, M\n\nZigeuner, R\n\nMostafid, AH\n\nShariat, SF\n\nRouprêt, M\n\nCompérat, EM\n\nBabjuk, M\n\nvan Rhijn, BWG\n\nBeiträge in Fachzeitschriften\nISI:000632030700019\n33419683.0\n10.1016/j.eururo.2020.12.033\nNone\nThe European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s.\n To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression.\n Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel.\n Patients underwent TURBT followed by intravesical instillations at the physician's discretion.\n Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves.\n A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review.\n This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary.\n The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule.\n Copyright © 2020 European Association of Urology. All rights reserved.\n\nMannweiler, Sebastian\n\nSeles, Maximilian\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n135597\nDynamic reconstruction of eye closure by muscle transposition or functional muscle transplantation in facial palsy.\n\nFrey, M\n\nGiovanoli, P\n\nTzou, CH\n\nKropf, N\n\nFriedl, S\n\nBeiträge in Fachzeitschriften\nISI:000223693000006\n15468391.0\n10.1097/01.PRS.0000133028.02305.16\nNone\nFor patients with facial palsy, lagophthalmus is often a more serious problem than the inability to smile. Dynamic reconstruction of eye closure by muscle transposition or by free functional muscle transplantation offers a good solution for regaining near-normal eye protection without the need for implants. This is the first quantitative study of three-dimensional preoperative and postoperative lid movements in patients treated for facial paralysis. Between February of 1998 and April of 2002, 44 patients were treated for facial palsy, including reconstruction of eye closure. Temporalis muscle transposition to the eye was used in 34 cases, and a regionally differentiated part of a free gracilis muscle transplant after double cross-face nerve grafting was used in 10 cases. Patients' facial movements were documented by a three-dimensional video analysis system preoperatively and 6, 12, 18, and 24 months postoperatively. For this comparative study, only the data of patients with preoperative and 12-month postoperative measurements were included. In the 27 patients with a final result after temporalis muscle transposition for eye closure, the distance between the upper and lower eyelid points during eye closing (as for sleep) was reduced from 10.33 +/- 2.43 mm (mean +/- SD) preoperatively to 5.84 +/- 4.34 mm postoperatively on the paralyzed side, compared with 0.0 +/- 0.0 mm preoperatively and postoperatively on the contralateral healthy side. In the resting position, preoperative values for the paralyzed side changed from 15.11 +/- 1.92 mm preoperatively to 13.46 +/- 1.94 mm postoperatively, compared with 12.17 +/- 2.02 mm preoperatively and 12.05 +/- 1.95 mm postoperatively on the healthy side. In the nine patients with a final result after surgery using a part of the free gracilis muscle transplant reinnervated by a zygomatic branch of the contralateral healthy side through a cross-face nerve graft, eyelid closure changed from 10.21 +/- 2.72 mm to 1.68 +/- 1.35 mm, compared with 13.70 +/- 1.56 mm to 6.63 +/- 1.51 mm preoperatively. The average closure for the healthy side was from 11.20 +/- 3.11 mm to 0.0 +/- 0.0 mm preoperatively and from 12.70 +/- 1.95 mm to 0.0 +/- 0.0 mm postoperatively. In three cases, the resting tonus of the part of the gracilis muscle transplant around the eye had increased to an extent that muscle weakening became necessary. Temporalis muscle transposition and free functional muscle transplantation for reanimation of the eye and mouth at the same time are reliable methods for reconstructing eye closure, with clinically adequate results. Detailed analysis of the resulting facial movements led to an important improvement of the authors' operative techniques within the last few years. Thus, the number of secondary operative corrections could be significantly reduced. These qualitative and quantitative studies of the reconstructed lid movements by three-dimensional video analysis support the authors' clinical concept of temporalis muscle transposition being the first-choice method in adult patients with facial palsy. In children, free muscle transplantation is preferred for eye closure, so as not to interfere with the growth of the face by transposition of a masticatory muscle. In addition, a higher degree of central plasticity in children might be expected.\n\n\n"
},
{
"text": "\n127798\nEarly results of a European multicentre experience with a new self-anchoring adjustable transobturator system for treatment of stress urinary incontinence in men.\n\nHoda, MR\n\nPrimus, G\n\nFischereder, K\n\nVon Heyden, B\n\nMohammed, N\n\nSchmid, N\n\nMoll, V\n\nHamza, A\n\nKarsch, JJ\n\nBrossner, C\n\nFornara, P\n\nBauer, W\n\n\n\nBeiträge in Fachzeitschriften\nISI:000315030200019\n23186285.0\n10.1111/j.1464-410X.2012.11482.x\nNone\nWhat's known on the subject? and What does the study add? Surgical treatment options for male stress urinary incontinence (SUI) include collagen injection, artificial urinary sphincter, or male sling placement. In recent years, various minimally invasive sling systems have been investigated as treatment options for post-prostatectomy SUI. One of the drawbacks of using male slings is the lack of ability to make postoperative adjustments. To overcome the challenges associated with peri- and postoperative adjustment of male sling systems, the adjustable transobturator male system (ATOMS (R)) was introduced. Our initial European multicentre experience with this device treatment shows a significant improvement in the severity of incontinence and mean pad use as well as quality-of-life scores. Our data suggest that the ability at any time to make adjustments in male sling systems should be considered as a prerequisite when managing men with SUI. Objective To report our experience with a new self-anchoring adjustable transobturator male system (ATOMS (R); AMI, Vienna, Austria) for the treatment of stress urinary incontinence (SUI) in men. Patients and Methods A total of 99 men, in a number of centres, were treated for SUI with the new ATOMS (R) device. The device was implanted in all patients using an outside-in technique by passing the obturator foramen and anchoring the device to the inferior pubic ramus. The titanium port was placed s.c. on the left symphysis region. Adjustments were performed via port access. Postoperative evaluation consisted of physical examination, 24-h pad test, and 24h-pad count. Preoperatively and at 6-month follow-up, patients completed a validated quality-of-life questionnaire. Two-way ANOVA was used to analyse changes over time. Within-group effects for time were tested using post hoc Dunnett's contrasts of baseline values vs subsequent measurements. Results The most common indication was SUI after radical prostatectomy (92.9%). Failure of previous surgeries was present in 34.3% patients and 31.3% patients had undergone secondary radiation. The mean (SD; range) surgery time was 47 (13.8; 29112) min. Temporary urinary retention occurred in two patients (2%) and transient perineal/scrotal dysaesthesia or pain was reported by 68 patients (68.7%) and resolved after 34 weeks of non-opioid analgesics. There were four (4%) cases of wound infection at the site of the titanium port leading to explantation. No urethral or bladder injuries related to the device or erosions occurred. The mean (SD; range) number of adjustments to reach the desired result (dryness, improvement and/or patient satisfaction) was 3.8 (1.3; 16). After a mean (SD; range) follow-up time of 17.8 (1.6; 1233) months, the overall success rate was 92% and the mean pad use decreased from 7.1 to 1.3 pads/24h (P < 0.001). Overall, 63% were considered dry and 29% were improved. Conclusion Treatment of male SUI with this self-anchored adjustable system is safe and effective.\n\n\n"
},
{
"text": "\n2973\nRole of serum amyloid A during metabolism of acute-phase HDL by macrophages.\n\nArtl, A\n\nMarsche, G\n\nLestavel, S\n\nSattler, W\n\nMalle, E\n\nBeiträge in Fachzeitschriften\nISI:000085834100023\n10712402.0\n10.1161/01.ATV.20.3.763\nNone\nThe serum amyloid A (SAA) family of proteins is encoded by multiple genes that display allelic variation and a high degree of homology in mammals. Triggered by inflammation after stimulation of hepatocytes by lymphokine-mediated processes, the concentrations of SAA may increase during the acute-phase reaction to levels 1000-fold greater than those found in the noninflammatory state. In addition to its role as an acute-phase reactant, SAA (104 amino acids, 12 kDa) is considered to be the precursor protein of secondary reactive amyloidosis, in which the N-terminal portion is incorporated into the bulk of amyloid fibrils. However, the association with lipoproteins of the high-density range and subsequent modulation of the metabolic properties of its physiological carrier appear to be the principal role of SAA. Because SAA may displace apolipoprotein A-I, the major protein component of native high density lipoprotein (HDL), during the acute-phase reaction, the present study was aimed at (1) investigating binding properties of native and acute-phase (SAA-enriched) HDL by J774 macrophages, (2) elucidating whether the presence of SAA on HDL particles affects selective uptake of HDL-associated cholesteryl esters, and (3) comparing cellular cholesterol efflux mediated by native and acute-phase HDL. Both the total and the specific binding at 4 degrees C of rabbit acute-phase HDL were approximately 2-fold higher than for native HDL. Nonlinear regression analysis revealed K(d) values of 7.0 x 10(-7) mol/L (native HDL) and 3.1 x 10(-7) mol/L (acute-phase HDL), respectively. The corresponding B(max) values were 203 ng of total lipoprotein per milligram of cell protein (native HDL) and 250 ng of total lipoprotein per milligram of cell protein (acute-phase HDL). At 37 degrees C, holoparticle turnover was slightly enhanced for acute-phase HDL, a fact reflected by 2-fold higher degradation rates. In contrast, the presence of SAA on HDL specifically increased (1. 7-fold) the selective uptake of HDL cholesteryl esters from acute-phase HDL by J774 macrophages, a widely used in vitro model to study foam cell formation and cholesterol efflux properties. Although ligand blotting experiments with solubilized J774 membrane proteins failed to identify the scavenger receptor-BI as a binding protein for both native and acute-phase HDL, 2 binding proteins with molecular masses of 100 and 72 kDa, the latter comigrating with CD55 (also termed decay-accelerating factor), were identified. During cholesterol efflux studies, it became apparent that the ability of acute-phase HDL with regard to cellular cholesterol removal was considerably lower than that for native HDL. This was reflected by a 1.7-fold increase in tau/2 values (22 versus 36 hours; native versus acute-phase HDL). Our observations of increased HDL cholesteryl ester uptake and reduced cellular cholesterol efflux (acute-phase versus native HDL) suggest that displacement of apolipoprotein A-I by SAA results in considerable altered metabolic properties of its main physiological carrier. These changes in the apolipoprotein moieties appear (at least in the in vitro system tested) to transform an originally antiatherogenic into a proatherogenic lipoprotein particle.\n\nMalle, Ernst\n\nMarsche, Gunther\n\nSattler, Wolfgang\n\n\n"
},
{
"text": "\n175589\nAuthor Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.\n\nDavies, G\n\nLam, M\n\nHarris, SE\n\nTrampush, JW\n\nLuciano, M\n\nHill, WD\n\nHagenaars, SP\n\nRitchie, SJ\n\nMarioni, RE\n\nFawns-Ritchie, C\n\nLiewald, DCM\n\nOkely, JA\n\nAhola-Olli, AV\n\nBarnes, CLK\n\nBertram, L\n\nBis, JC\n\nBurdick, KE\n\nChristoforou, A\n\nDeRosse, P\n\nDjurovic, S\n\nEspeseth, T\n\nGiakoumaki, S\n\nGiddaluru, S\n\nGustavson, DE\n\nHayward, C\n\nHofer, E\n\nIkram, MA\n\nKarlsson, R\n\nKnowles, E\n\nLahti, J\n\nLeber, M\n\nLi, S\n\nMather, KA\n\nMelle, I\n\nMorris, D\n\nOldmeadow, C\n\nPalviainen, T\n\nPayton, A\n\nPazoki, R\n\nPetrovic, K\n\nReynolds, CA\n\nSargurupremraj, M\n\nScholz, M\n\nSmith, JA\n\nSmith, AV\n\nTerzikhan, N\n\nThalamuthu, A\n\nTrompet, S\n\nvan der Lee, SJ\n\nWare, EB\n\nWindham, BG\n\nWright, MJ\n\nYang, J\n\nYu, J\n\nAmes, D\n\nAmin, N\n\nAmouyel, P\n\nAndreassen, OA\n\nArmstrong, NJ\n\nAssareh, AA\n\nAttia, JR\n\nAttix, D\n\nAvramopoulos, D\n\nBennett, DA\n\nBöhmer, AC\n\nBoyle, PA\n\nBrodaty, H\n\nCampbell, H\n\nCannon, TD\n\nCirulli, ET\n\nCongdon, E\n\nConley, ED\n\nCorley, J\n\nCox, SR\n\nDale, AM\n\nDehghan, A\n\nDick, D\n\nDickinson, D\n\nEriksson, JG\n\nEvangelou, E\n\nFaul, JD\n\nFord, I\n\nFreimer, NA\n\nGao, H\n\nGiegling, I\n\nGillespie, NA\n\nGordon, SD\n\nGottesman, RF\n\nGriswold, ME\n\nGudnason, V\n\nHarris, TB\n\nHartmann, AM\n\nHatzimanolis, A\n\nHeiss, G\n\nHolliday, EG\n\nJoshi, PK\n\nKähönen, M\n\nKardia, SLR\n\nKarlsson, I\n\nKleineidam, L\n\nKnopman, DS\n\nKochan, NA\n\nKonte, B\n\nKwok, JB\n\nLe Hellard, S\n\nLee, T\n\nLehtimäki, T\n\nLi, SC\n\nLill, CM\n\nLiu, T\n\nKoini, M\n\nLondon, E\n\nLongstreth, WT\n\nLopez, OL\n\nLoukola, A\n\nLuck, T\n\nLundervold, AJ\n\nLundquist, A\n\nLyytikäinen, LP\n\nMartin, NG\n\nMontgomery, GW\n\nMurray, AD\n\nNeed, AC\n\nNoordam, R\n\nNyberg, L\n\nOllier, W\n\nPapenberg, G\n\nPattie, A\n\nPolasek, O\n\nPoldrack, RA\n\nPsaty, BM\n\nReppermund, S\n\nRiedel-Heller, SG\n\nRose, RJ\n\nRotter, JI\n\nRoussos, P\n\nRovio, SP\n\nSaba, Y\n\nSabb, FW\n\nSachdev, PS\n\nSatizabal, CL\n\nSchmid, M\n\nScott, RJ\n\nScult, MA\n\nSimino, J\n\nSlagboom, PE\n\nSmyrnis, N\n\nSoumaré, A\n\nStefanis, NC\n\nStott, DJ\n\nStraub, RE\n\nSundet, K\n\nTaylor, AM\n\nTaylor, KD\n\nTzoulaki, I\n\nTzourio, C\n\nUitterlinden, A\n\nVitart, V\n\nVoineskos, AN\n\nKaprio, J\n\nWagner, M\n\nWagner, H\n\nWeinhold, L\n\nWen, KH\n\nWiden, E\n\nYang, Q\n\nZhao, W\n\nAdams, HHH\n\nArking, DE\n\nBilder, RM\n\nBitsios, P\n\nBoerwinkle, E\n\nChiba-Falek, O\n\nCorvin, A\n\nDe Jager, PL\n\nDebette, S\n\nDonohoe, G\n\nElliott, P\n\nFitzpatrick, AL\n\nGill, M\n\nGlahn, DC\n\nHägg, S\n\nHansell, NK\n\nHariri, AR\n\nIkram, MK\n\nJukema, JW\n\nVuoksimaa, E\n\nKeller, MC\n\nKremen, WS\n\nLauner, L\n\nLindenberger, U\n\nPalotie, A\n\nPedersen, NL\n\nPendleton, N\n\nPorteous, DJ\n\nRäikkönen, K\n\nRaitakari, OT\n\nRamirez, A\n\nReinvang, I\n\nRudan, I\n\nDan Rujescu, I\n\nSchmidt, R\n\nSchmidt, H\n\nSchofield, PW\n\nSchofield, PR\n\nStarr, JM\n\nSteen, VM\n\nTrollor, JN\n\nTurner, ST\n\nVan Duijn, CM\n\nVillringer, A\n\nWeinberger, DR\n\nWeir, DR\n\nWilson, JF\n\nMalhotra, A\n\nMcIntosh, AM\n\nGale, CR\n\nSeshadri, S\n\nMosley, TH\n\nBressler, J\n\nLencz, T\n\nDeary, IJ\n\nBeiträge in Fachzeitschriften\nISI:000466339700001\n31043617.0\n10.1038/s41467-019-10160-w\nPMC6494826\nChristina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.\n\nHofer, Edith\n\nKoini, Marisa\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n177774\nThe role of gut microbiota for the activity of medicinal plants traditionally used in the European Union for gastrointestinal disorders.\n\nThumann, TA\n\nPferschy-Wenzig, EM\n\nMoissl-Eichinger, C\n\nBauer, R\n\nBeiträge in Fachzeitschriften\nISI:000488331300032\n31408679.0\n10.1016/j.jep.2019.112153\nNone\nMany medicinal plants have been traditionally used for the treatment of gastrointestinal disorders. According to the monographs published by the Committee on Herbal Medicinal Products (HMPC) at the European Medicines Agency, currently 44 medicinal plants are recommended in the European Union for the treatment of gastrointestinal disorders based on traditional use. The main indications are functional and chronic gastrointestinal disorders, such as functional dyspepsia and irritable bowel syndrome (IBS), and typical effects of these plants are stimulation of gastric secretion, spasmolytic and carminative effects, soothing effects on the gastrointestinal mucosa, laxative effects, adstringent or antidiarrheal activities, and anti-inflammatory effects. A possible interaction with human gut microbiota has hardly been considered so far, although it is quite likely.\n In this review, we aimed to identify and evaluate published studies which have investigated interactions of these plants with the gut microbiome.\n According to this survey, only a minor portion of the 44 medicinal plants considered in EMA monographs for the treatment of gastrointestinal diseases has been studied so far with regard to potential interactions with gut microbiota. We could identify eight relevant in vitro studies that have been performed with six of these medicinal plants, 17 in vivo studies performed in experimental animals involving seven of the medicinal plants, and three trials in humans performed with two of the plants. The most robust evidence exists for the use of inulin as a prebiotic, and in this context also the prebiotic activity of chicory root has been investigated quite intensively. Flaxseed dietary fibers are also known to be fermented by gut microbiota to short chain fatty acids, leading to prebiotic effects. This could cause a health-beneficial modulation of gut microbiota by flaxseed supplementation. In flaxseed, also other compound classes like lignans and polyunsaturated fatty acids are present, that also have been shown to interact with gut microbiota. Drugs rich in tannins and anthocyanins also interact intensively with gut microbiota, since these compounds reach the colon at high levels in unchanged form. Tannins and anthocyanins are intensively metabolized by certain gut bacteria, leading to the generation of small, bioavailable and potentially bioactive metabolites. Moreover, interaction with these compounds may exert a prebiotic-like effect on gut microbiota. Gut microbial metabolization has also been shown for certain licorice constituents, but their potential effects on gut microbiota still need to be investigated in detail. Only a limited amount of studies investigated the interactions of essential oil- and secoiridoid-containing drugs with human gut microbiota. However, other constituents present in some of these drugs, like curcumin (curcuma), shogaol (ginger), and rosmarinic acid have been shown to be metabolized by human gut microbiota, and preliminary data also indicate potential gut microbiome modulatory effects. To conclude, the interaction with gut microbiota is still not fully investigated for many herbal drugs traditionally used for gastrointestinal disorders, which offers a vast field for future research.\n Copyright © 2019 Elsevier B.V. All rights reserved.\n\nMoissl-Eichinger, Christine\n\n\n"
},
{
"text": "\n183817\nMolecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.\n\nGalluzzi, L\n\nVitale, I\n\nAaronson, SA\n\nAbrams, JM\n\nAdam, D\n\nAgostinis, P\n\nAlnemri, ES\n\nAltucci, L\n\nAmelio, I\n\nAndrews, DW\n\nAnnicchiarico-Petruzzelli, M\n\nAntonov, AV\n\nArama, E\n\nBaehrecke, EH\n\nBarlev, NA\n\nBazan, NG\n\nBernassola, F\n\nBertrand, MJM\n\nBianchi, K\n\nBlagosklonny, MV\n\nBlomgren, K\n\nBorner, C\n\nBoya, P\n\nBrenner, C\n\nCampanella, M\n\nCandi, E\n\nCarmona-Gutierrez, D\n\nCecconi, F\n\nChan, FK\n\nChandel, NS\n\nCheng, EH\n\nChipuk, JE\n\nCidlowski, JA\n\nCiechanover, A\n\nCohen, GM\n\nConrad, M\n\nCubillos-Ruiz, JR\n\nCzabotar, PE\n\nD'Angiolella, V\n\nDawson, TM\n\nDawson, VL\n\nDe Laurenzi, V\n\nDe Maria, R\n\nDebatin, KM\n\nDeBerardinis, RJ\n\nDeshmukh, M\n\nDi Daniele, N\n\nDi Virgilio, F\n\nDixit, VM\n\nDixon, SJ\n\nDuckett, CS\n\nDynlacht, BD\n\nEl-Deiry, WS\n\nElrod, JW\n\nFimia, GM\n\nFulda, S\n\nGarcía-Sáez, AJ\n\nGarg, AD\n\nGarrido, C\n\nGavathiotis, E\n\nGolstein, P\n\nGottlieb, E\n\nGreen, DR\n\nGreene, LA\n\nGronemeyer, H\n\nGross, A\n\nHajnoczky, G\n\nHardwick, JM\n\nHarris, IS\n\nHengartner, MO\n\nHetz, C\n\nIchijo, H\n\nJäättelä, M\n\nJoseph, B\n\nJost, PJ\n\nJuin, PP\n\nKaiser, WJ\n\nKarin, M\n\nKaufmann, T\n\nKepp, O\n\nKimchi, A\n\nKitsis, RN\n\nKlionsky, DJ\n\nKnight, RA\n\nKumar, S\n\nLee, SW\n\nLemasters, JJ\n\nLevine, B\n\nLinkermann, A\n\nLipton, SA\n\nLockshin, RA\n\nLópez-Otín, C\n\nLowe, SW\n\nLuedde, T\n\nLugli, E\n\nMacFarlane, M\n\nMadeo, F\n\nMalewicz, M\n\nMalorni, W\n\nManic, G\n\nMarine, JC\n\nMartin, SJ\n\nMartinou, JC\n\nMedema, JP\n\nMehlen, P\n\nMeier, P\n\nMelino, S\n\nMiao, EA\n\nMolkentin, JD\n\nMoll, UM\n\nMuñoz-Pinedo, C\n\nNagata, S\n\nNuñez, G\n\nOberst, A\n\nOren, M\n\nOverholtzer, M\n\nPagano, M\n\nPanaretakis, T\n\nPasparakis, M\n\nPenninger, JM\n\nPereira, DM\n\nPervaiz, S\n\nPeter, ME\n\nPiacentini, M\n\nPinton, P\n\nPrehn, JHM\n\nPuthalakath, H\n\nRabinovich, GA\n\nRehm, M\n\nRizzuto, R\n\nRodrigues, CMP\n\nRubinsztein, DC\n\nRudel, T\n\nRyan, KM\n\nSayan, E\n\nScorrano, L\n\nShao, F\n\nShi, Y\n\nSilke, J\n\nSimon, HU\n\nSistigu, A\n\nStockwell, BR\n\nStrasser, A\n\nSzabadkai, G\n\nTait, SWG\n\nTang, D\n\nTavernarakis, N\n\nThorburn, A\n\nTsujimoto, Y\n\nTurk, B\n\nVanden Berghe, T\n\nVandenabeele, P\n\nVander Heiden, MG\n\nVillunger, A\n\nVirgin, HW\n\nVousden, KH\n\nVucic, D\n\nWagner, EF\n\nWalczak, H\n\nWallach, D\n\nWang, Y\n\nWells, JA\n\nWood, W\n\nYuan, J\n\nZakeri, Z\n\nZhivotovsky, B\n\nZitvogel, L\n\nMelino, G\n\nKroemer, G\n\nBeiträge in Fachzeitschriften\nISI:000426395800006\n29362479.0\n10.1038/s41418-017-0012-4\nPMC5864239\nOver the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.\n\nJost, Philipp\n\n\n"
},
{
"text": "\n61446\nActions of endothelin and corticotropin releasing factor in the guinea-pig ileum: no evidence for an interaction with capsaicin-sensitive neurons.\n\nLázár, Z\n\nBenkó, R\n\nBölcskei, K\n\nRumbus, Z\n\nWolf, M\n\nHolzer, P\n\nMaggi, CA\n\nBarthó, L\n\nBeiträge in Fachzeitschriften\nISI:000184892900003\n12906840.0\n10.1016/S0143-4179(03)00048-9\nNone\nBoth endothelins and corticotropin releasing factor (CRF) appear in capsaicin-sensitive neurons. We have investigated the effects of human endothelin-1 (ET-1) and CRF in the guinea-pig ileum longitudinal and circular preparations and sought for ways of specific antagonism. With the aid of tachyphylaxis to capsaicin (i.e., rendering capsaicin-sensitive neurons functionally impaired) it was tested if these neurons played a mediating role in the effects of ET-1 or CRF. We also tried to find out whether endogenous endothelin or CRF plays a role in the excitatory and inhibitory effects of capsaicin in the ileum. In preparations at basal tone, both exogenous ET-1 (1-100 nM) and CRF (3-100 nM) caused contraction. These responses were not influenced by capsaicin tachyphylaxis. The contractile effect of ET-1 was not affected by tetrodotoxin (1 microM), atropine (1 microM), methysergide (100 nM), chloropyramine (100 nM) or SR140333 (100 nM) but was significantly inhibited or even abolished by the receptor antagonist BQ123 (3 microM) or BQ788 (3 microM). CRF caused contraction that was fully sensitive to tetrodotoxin (1 microM), tachyphylaxis to CRF or to atropine (1 microM) plus the tachykinin NK1 receptor antagonist SR140333 (200 nM). Atropine alone had a weak inhibitory effect on the contractile action of CRF. Neither the antagonist BQ123 (3 microM) nor CRF tachyphylaxis inhibited the contractile action of capsaicin (2 microM), even in the presence of a mixture of GR82334 (3 microM) and SR142801 (100 nM), for blocking tachykinin NK1 and NK3 receptors, respectively--a treatment that by itself significantly reduced the effect of capsaicin. Exogenous ET-1 (0.3-5 nM), but not CRF (30-100 nM), caused relaxation of the atropine-treated, histamine-precontracted ileum. This effect of ET-1 was significantly inhibited or abolished by BQ123 (10 microM), or BQ788 (3 microM), but was not influenced by capsaicin tachyphylaxis. Likewise, relaxation of the atropine-treated, histamine-precontracted ileum in response to capsaicin was not influenced by the endothelin receptor antagonist BQ788 (3 microM) or BQ788 (3 microM) plus BQ123 (3 microM). Apamin (300 nM) was also without effect on the capsaicin-induced relaxation. In circular muscle strips ET-1 inhibited the indomethacin-induced spontaneous activity. This effect was abolished by BQ123 (3 microM) or BQ788 (3 microM). CRF caused a stimulation of the circular muscle. This stimulatory effect was not influenced by atropine (1 microM) alone, but was inhibited by atropine plus tachykinin NK1 and NK2 receptor antagonists (SR140333 (200 nM) and SR48968 (200 nM)) and also by tetrodotoxin (1 microM). It is concluded that capsaicin-sensitive neurons do not play a role in the effects of exogenous ET-1 or CRF in the guinea-pig ileum. ET-1 can both contract and relax the ileal longitudinal smooth muscle directly, probably via both ETA and ETB receptors. CRF acts by specifically stimulating excitatory (but not inhibitory) neurons of the myenteric plexus. Neither endogenous ET-1 nor CRF seems to play a role in the excitatory or inhibitory effects of capsaicin.\n\nHolzer, Peter\n\n\n"
},
{
"text": "\n146640\nRationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia.\n\nNosè, M\n\nAccordini, S\n\nArtioli, P\n\nBarale, F\n\nBarbui, C\n\nBeneduce, R\n\nBerardi, D\n\nBertolazzi, G\n\nBiancosino, B\n\nBisogno, A\n\nBivi, R\n\nBogetto, F\n\nBoso, M\n\nBozzani, A\n\nBucolo, P\n\nCasale, M\n\nCascone, L\n\nCiammella, L\n\nCicolini, A\n\nCipresso, G\n\nCipriani, A\n\nColombo, P\n\nDal Santo, B\n\nDe Francesco, M\n\nDi Lorenzo, G\n\nDi Munzio, W\n\nDucci, G\n\nErlicher, A\n\nEsposito, E\n\nFerrannini, L\n\nFerrato, F\n\nFerro, A\n\nFragomeno, N\n\nParise, VF\n\nFrova, M\n\nGardellin, F\n\nGarzotto, N\n\nGiambartolomei, A\n\nGiupponi, G\n\nGrassi, L\n\nGrazian, N\n\nGrecu, L\n\nGuerrini, G\n\nLaddomada, F\n\nLazzarin, E\n\nLintas, C\n\nMalchiodi, F\n\nMalvini, L\n\nMarchiaro, L\n\nMarsilio, A\n\nMauri, MC\n\nMautone, A\n\nMenchetti, M\n\nMigliorini, G\n\nMollica, M\n\nMoretti, D\n\nMulè, S\n\nNicholau, S\n\nNosè, F\n\nOcchionero, G\n\nPacilli, AM\n\nPecchioli, S\n\nPercudani, M\n\nPiantato, E\n\nPiazza, C\n\nPontarollo, F\n\nPycha, R\n\nQuartesan, R\n\nRillosi, L\n\nRisso, F\n\nRizzo, R\n\nRocca, P\n\nRoma, S\n\nRossattini, M\n\nRossi, G\n\nRossi, G\n\nSala, A\n\nSantilli, C\n\nSaraò, G\n\nSarnicola, A\n\nSartore, F\n\nScarone, S\n\nSciarma, T\n\nSiracusano, A\n\nStrizzolo, S\n\nTansella, M\n\nTarga, G\n\nTasser, A\n\nTomasi, R\n\nTravaglini, R\n\nVeronese, A\n\nZiero, S\n\nBeiträge in Fachzeitschriften\nISI:000266532800001\n19445659.0\n10.1186/1745-6215-10-31\nPMC2689216\nOne third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.\n The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.\n The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.\n\n\n"
},
{
"text": "\n164869\nGrading of Urothelial Carcinoma and The New "World Health Organisation Classification of Tumours of the Urinary System and Male Genital Organs 2016".\n\nCompérat, EM\n\nBurger, M\n\nGontero, P\n\nMostafid, AH\n\nPalou, J\n\nRouprêt, M\n\nvan Rhijn, BWG\n\nShariat, SF\n\nSylvester, RJ\n\nZigeuner, R\n\nBabjuk, M\n\nBeiträge in Fachzeitschriften\nISI:000486154800025\n29366854.0\n10.1016/j.euf.2018.01.003\nNone\nIn the management of urothelial carcinoma, determination of the pathological grade aims at stratifying tumours into different prognostic groups to allow evaluation of treatment results, and optimise patient management. This article reviews the principles behind different grading systems for urothelial bladder carcinoma discussing their reproducibility and prognostic value.\n This paper aims to show the evolution of the World Health Organisation (WHO) grading system, discussing their reproducibility and prognostic value, and evaluating which classification system best predicts disease recurrence and progression. The most optimal classification system is robust, reproducible, and transparent with comprehensive data on interobserver and intraobserver variability. The WHO published an updated tumour classification in 2016, which presents a step forward, but its performance will need validation in clinical studies.\n Medline and EMBASE were searched using the key terms WHO 1973, WHO/International Society of Urological Pathology 1998, WHO 2004, WHO 2016, histology, reproducibility, and prognostic value, in the time frame 1973 to May 2016. The references list of relevant papers was also consulted, resulting in the selection of 48 papers.\n There are still inherent limitations in all available tumour classification systems. The WHO 1973 presents considerable ambiguity for classification of the G2 tumour group and grading of the G1/2 and G2/3 groups. The 2004 WHO classification introduced the concept of low-grade and high-grade tumours, as well as the papillary urothelial neoplasm of low malignant potential category which is retained in the 2016 classification. Furthermore, while molecular markers are available that have been shown to contribute to a more accurate histological grading of urothelial carcinomas, thereby improving selection of treatment for a given patient, these are not (yet) part of standard clinical practice.\n The prognosis of patients diagnosed with urothelial carcinoma greatly depends on correct histological grading of the tumour. There is still limited data regarding intraobserver and interobserver variability differences between the WHO 1973 and 2004 classification systems. Additionally, reproducibility remains a concern: histological differences between the various types of tumour may be subtle and there is still no consensus amongst pathologists. The recent WHO 2016 classification presents a further improvement on the 2004 classification, but until further data becomes available, the European Association of Urology currently recommends the use of both WHO 1973 and WHO 2004/2016 classifications.\n Bladder cancer, when treated in time, has a good prognosis. However, selection of the most optimal treatment is largely dependent on the information your doctor will receive from the pathologist following evaluation of the tissue resected from the bladder. It is therefore important that the classification system that the pathologist uses to grade the tissue is transparent and clear for both urologists and pathologists. A reliable classification system will ensure that aggressive tumours are not misinterpreted, and less aggressive cancer is not overtreated.\n Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n153127\nGenome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.\n\nHou, L\n\nBergen, SE\n\nAkula, N\n\nSong, J\n\nHultman, CM\n\nLandén, M\n\nAdli, M\n\nAlda, M\n\nArdau, R\n\nArias, B\n\nAubry, JM\n\nBacklund, L\n\nBadner, JA\n\nBarrett, TB\n\nBauer, M\n\nBaune, BT\n\nBellivier, F\n\nBenabarre, A\n\nBengesser, S\n\nBerrettini, WH\n\nBhattacharjee, AK\n\nBiernacka, JM\n\nBirner, A\n\nBloss, CS\n\nBrichant-Petitjean, C\n\nBui, ET\n\nByerley, W\n\nCervantes, P\n\nChillotti, C\n\nCichon, S\n\nColom, F\n\nCoryell, W\n\nCraig, DW\n\nCruceanu, C\n\nCzerski, PM\n\nDavis, T\n\nDayer, A\n\nDegenhardt, F\n\nDel Zompo, M\n\nDePaulo, JR\n\nEdenberg, HJ\n\nÉtain, B\n\nFalkai, P\n\nForoud, T\n\nForstner, AJ\n\nFrisén, L\n\nFrye, MA\n\nFullerton, JM\n\nGard, S\n\nGarnham, JS\n\nGershon, ES\n\nGoes, FS\n\nGreenwood, TA\n\nGrigoroiu-Serbanescu, M\n\nHauser, J\n\nHeilbronner, U\n\nHeilmann-Heimbach, S\n\nHerms, S\n\nHipolito, M\n\nHitturlingappa, S\n\nHoffmann, P\n\nHofmann, A\n\nJamain, S\n\nJiménez, E\n\nKahn, JP\n\nKassem, L\n\nKelsoe, JR\n\nKittel-Schneider, S\n\nKliwicki, S\n\nKoller, DL\n\nKönig, B\n\nLackner, N\n\nLaje, G\n\nLang, M\n\nLavebratt, C\n\nLawson, WB\n\nLeboyer, M\n\nLeckband, SG\n\nLiu, C\n\nMaaser, A\n\nMahon, PB\n\nMaier, W\n\nMaj, M\n\nManchia, M\n\nMartinsson, L\n\nMcCarthy, MJ\n\nMcElroy, SL\n\nMcInnis, MG\n\nMcKinney, R\n\nMitchell, PB\n\nMitjans, M\n\nMondimore, FM\n\nMonteleone, P\n\nMühleisen, TW\n\nNievergelt, CM\n\nNöthen, MM\n\nNovák, T\n\nNurnberger, JI\n\nNwulia, EA\n\nÖsby, U\n\nPfennig, A\n\nPotash, JB\n\nPropping, P\n\nReif, A\n\nReininghaus, E\n\nRice, J\n\nRietschel, M\n\nRouleau, GA\n\nRybakowski, JK\n\nSchalling, M\n\nScheftner, WA\n\nSchofield, PR\n\nSchork, NJ\n\nSchulze, TG\n\nSchumacher, J\n\nSchweizer, BW\n\nSeverino, G\n\nShekhtman, T\n\nShilling, PD\n\nSimhandl, C\n\nSlaney, CM\n\nSmith, EN\n\nSquassina, A\n\nStamm, T\n\nStopkova, P\n\nStreit, F\n\nStrohmaier, J\n\nSzelinger, S\n\nTighe, SK\n\nTortorella, A\n\nTurecki, G\n\nVieta, E\n\nVolkert, J\n\nWitt, SH\n\nWright, A\n\nZandi, PP\n\nZhang, P\n\nZollner, S\n\nMcMahon, FJ\n\nBeiträge in Fachzeitschriften\nISI:000393077300018\n27329760.0\n10.1093/hmg/ddw181\nPMC5179929\nBipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9, 84 bipolar disorder patients and 30, 71 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2, 00 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 × 10 - 9; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 × 10 - 9; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.\n Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nReininghaus, Eva\n\n\n"
},
{
"text": "\n183962\nSUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer.\n\nChiva, L\n\nZanagnolo, V\n\nQuerleu, D\n\nMartin-Calvo, N\n\nArévalo-Serrano, J\n\nCăpîlna, ME\n\nFagotti, A\n\nKucukmetin, A\n\nMom, C\n\nChakalova, G\n\nAliyev, S\n\nMalzoni, M\n\nNarducci, F\n\nArencibia, O\n\nRaspagliesi, F\n\nToptas, T\n\nCibula, D\n\nKaidarova, D\n\nMeydanli, MM\n\nTavares, M\n\nGolub, D\n\nPerrone, AM\n\nPoka, R\n\nTsolakidis, D\n\nVujić, G\n\nJedryka, MA\n\nZusterzeel, PLM\n\nBeltman, JJ\n\nGoffin, F\n\nHaidopoulos, D\n\nHaller, H\n\nJach, R\n\nYezhova, I\n\nBerlev, I\n\nBernardino, M\n\nBharathan, R\n\nLanner, M\n\nMaenpaa, MM\n\nSukhin, V\n\nFeron, JG\n\nFruscio, R\n\nKukk, K\n\nPonce, J\n\nMinguez, JA\n\nVázquez-Vicente, D\n\nCastellanos, T\n\nChacon, E\n\nAlcazar, JL\n\nSUCCOR study Group\n\nBeiträge in Fachzeitschriften\nISI:000572333600001\n32788262.0\n10.1136/ijgc-2020-001506\nNone\nMinimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse.\n We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group.\n Mean age was 48.3 years (range; 23-83) while the mean BMI was 25.7 kg/m2 (range; 15-49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52).\n Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.\n © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.\n\nLanner, Maximilian\n\n\n"
},
{
"text": "\n168039\nDoes Endometriosis Affect Sexual Activity and Satisfaction of the Man Partner? A Comparison of Partners From Women Diagnosed With Endometriosis and Controls.\n\nHämmerli, S\n\nKohl Schwartz, AS\n\nGeraedts, K\n\nImesch, P\n\nRauchfuss, M\n\nWölfler, MM\n\nHaeberlin, F\n\nvon Orelli, S\n\nEberhard, M\n\nImthurn, B\n\nLeeners, B\n\nBeiträge in Fachzeitschriften\nISI:000433423700008\n29706579.0\n10.1016/j.jsxm.2018.03.087\nNone\nEndometriosis-associated pain and dyspareunia influence female sexuality, but little is known about men's experiences in affected couples.\n To investigate how men partners experience sexuality in partnership with women with endometriosis.\n A multi-center case-control study was performed between 2010 and 2015 in Switzerland, Germany, and Austria. 236 Partners of endometriosis patients and 236 partners of age-matched control women without endometriosis with a similar ethnic background were asked to answer selected, relevant questions of the Brief Index of Sexual Functioning and the Global Sexual Functioning questionnaire, as well as some investigator-derived questions.\n We sought to evaluate sexual satisfaction of men partners of endometriosis patients, investigate differences in sexual activities between men partners of women with and without endometriosis, and identify options to improve partnership sexuality in couples affected by endometriosis.\n Many partners of endometriosis patients reported changes in sexuality (75%). A majority of both groups was (very) satisfied with their sexual relationship (73.8% vs 58.1%, P = .002). Nevertheless, more partners of women diagnosed with endometriosis were not satisfied (P = .002) and their sexual problems more strongly interfered with relationship happiness (P = .001) than in partners of control women. Frequencies of sexual intercourse (P < .001) and all other partnered sexual activities (oral sex, petting) were significantly higher in the control group. The wish for an increased frequency of sexual activity (P = .387) and sexual desire (P = .919) did not differ statistically between both groups.\n There is a need to evaluate qualitative factors that influence sexual satisfaction in endometriosis patients.\n This is one of the first studies to investigate male sexuality affected by endometriosis. The meticulous verification of diagnosis and disease stage according to operation reports and histology allows for a high reliability of diagnosis. Our men's response rate of almost 50% is higher compared to other studies. Recruiting men through their woman partner may have caused selection bias. The adjustment to the specific situation in endometriosis by selecting questions from the Brief Index of Sexual Functioning and Global Sexual Functioning and adding investigator-derived questions likely influenced the validity of the questionnaires. Despite the fact that both partners of endometriosis patients and of control women largely reported high sexual satisfaction, there are challenges for some couples that arise in the context of a sexual relationship when one partner has endometriosis. Challenges such as sexuality-related pain or a reduced frequency of sexual activities should be addressed by health care professionals to ameliorate any current difficulties and to prevent the development or aggravation of sexual dysfunction. Hämmerli S, Kohl Schwartz AS, Geraedts K, et al. Does Endometriosis Affect Sexual Activity and Satisfaction of the Man Partner? A Comparison of Partners From Women Diagnosed With Endometriosis and Controls. J Sex Med 2018;15:853-865.\n Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.\n\nWölfler, Monika Martina\n\n\n"
},
{
"text": "\n186260\nPrognostic Value of the WHO1973 and WHO2004/2016 Classification Systems for Grade in Primary Ta/T1 Non-muscle-invasive Bladder Cancer: A Multicenter European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel Study.\n\nvan Rhijn, BWG\n\nHentschel, AE\n\nBründl, J\n\nCompérat, EM\n\nHernández, V\n\nČapoun, O\n\nBruins, HM\n\nCohen, D\n\nRouprêt, M\n\nShariat, SF\n\nMostafid, AH\n\nZigeuner, R\n\nDominguez-Escrig, JL\n\nBurger, M\n\nSoukup, V\n\nGontero, P\n\nPalou, J\n\nvan der Kwast, TH\n\nBabjuk, M\n\nSylvester, RJ\n\nMulti-center EAU Non-Muscle-Invasive Bladder Cancer Guidelines Panel Study Consortium on the WHO1973 WHO 2004 2016 Classification Systems for Grade\n\nBeiträge in Fachzeitschriften\nISI:000640189300007\n33423944.0\n10.1016/j.euo.2020.12.002\nNone\nIn the current European Association of Urology (EAU) non-muscle-invasive bladder cancer (NMIBC) guideline, two classification systems for grade are advocated: WHO1973 and WHO2004/2016.\n To compare the prognostic value of these WHO systems.\n Individual patient data for 5145 primary Ta/T1 NMIBC patients from 17 centers were collected between 1990 and 2019. The median follow-up was 3.9 yr.\n Univariate and multivariable analyses of WHO1973 and WHO2004/2016 stratified by center were performed for time to recurrence, progression (primary endpoint), cystectomy, and duration of survival, taking into account age, concomitant carcinoma in situ, gender, multiplicity, tumor size, initial treatment, and tumor stage. Harrell's concordance (C-index) was used for prognostic accuracy of classification systems.\n The median age was 68 yr; 3292 (64%) patients had Ta tumors. Neither classification system was prognostic for recurrence. For a four-tier combination of both WHO systems, progression at 5-yr follow-up was 1.4% in low-grade (LG)/G1, 3.8% in LG/G2, 7.7% in high grade (HG)/G2, and 18.8% in HG/G3 (log-rank, p < 0.001). In multivariable analyses with WHO1973 and WHO2004/2016 as independent variables, WHO1973 was a significant prognosticator of progression (p < 0.001), whereas WHO2004/2016 was not anymore (p = 0.067). C-indices for WHO1973, WHO2004, and the WHO systems combined for progression were 0.71, 0.67, and 0.73, respectively. Prognostic analyses for cystectomy and survival showed results similar to those for progression.\n In this large prognostic factor study, both classification systems were prognostic for progression but not for recurrence. For progression, the prognostic value of WHO1973 was higher than that of WHO 2004/2016. The four-tier combination (LG/G1, LG/G2, HG/G2, and HG/G3) of both WHO systems proved to be superior, as it divides G2 patients into two subgroups (LG and HG) with different prognoses. Hence, the current EAU-NMIBC guideline recommendation to use both WHO classification systems remains correct.\n At present, two classification systems are used in parallel to grade non-muscle-invasive bladder tumors. Our data on a large number of patients showed that the older classification system (WHO1973) performed better in terms of assessing progression than the more recent (WHO2004/2016) one. Nevertheless, we conclude that the current guideline recommendation for the use of both classification systems remains correct, since this has the advantage of dividing the large group of WHO1973 G2 patients into two subgroups (low and high grade) with different prognoses.\n Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nSeles, Maximilian\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n112095\nAPOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study.\n\nBiffi, A\n\nAnderson, CD\n\nJagiella, JM\n\nSchmidt, H\n\nKissela, B\n\nHansen, BM\n\nJimenez-Conde, J\n\nPires, CR\n\nAyres, AM\n\nSchwab, K\n\nCortellini, L\n\nPera, J\n\nUrbanik, A\n\nRomero, JM\n\nRost, NS\n\nGoldstein, JN\n\nViswanathan, A\n\nPichler, A\n\nEnzinger, C\n\nRabionet, R\n\nNorrving, B\n\nTirschwell, DL\n\nSelim, M\n\nBrown, DL\n\nSilliman, SL\n\nWorrall, BB\n\nMeschia, JF\n\nKidwell, CS\n\nBroderick, JP\n\nGreenberg, SM\n\nRoquer, J\n\nLindgren, A\n\nSlowik, A\n\nSchmidt, R\n\nWoo, D\n\nRosand, J\n\non behalf of the International Stroke Genetics Consortium\n\nBeiträge in Fachzeitschriften\nISI:000293612600012\n21741316.0\n10.1016/S1474-4422(11)70148-X\nPMC3153411\nBackground Carriers of APOE epsilon 2 and epsilon 4 have an increased risk of intracerebral haemorrhage (ICH) in lobar regions, presumably because of the effects of these gene variants on risk of cerebral amyloid angiopathy. We aimed to assess whether these variants also associate with severity of ICH, in terms of haematoma volume at presentation and subsequent outcome. Methods We investigated the association of APOE epsilon 2 and epsilon 4 with ICH volume and outcomes in patients with primary ICH in three phases: a discovery phase of 865 individuals of European ancestry from the Genetics of Cerebral Hemorrhage on Anticoagulation study, and replication phases of 946 Europeans (replication 1) and 214 African-Americans (replication 2) from an additional six studies. We also assessed the association of APOE variants with ICH volume and outcomes in meta-analyses of results from all three phases, and the association of APOE epsilon 4 with mortality in a further meta-analysis including data from previous reports. Admission ICH volume was quantified on CT scan. We assessed functional outcome (modified Rankin scale score 3-6) and mortality at 90 days. We used linear regression to establish the effect of genotype on haematoma volume and logistic regression to assess the effect on outcome from ICH. Findings For patients with lobar ICH, carriers of the APOE epsilon 2 allele had larger ICH volumes than did non-carriers in the discovery phase (p=2. 5x10(-5)), in both replication phases (p=0.008 in Europeans and p=0.016 in African-Americans), and in the meta-analysis (p=3.2x10(-8)). In the meta-analysis, each copy of APOE epsilon 2 increased haematoma size by a mean of 5.3 mL (95% CI 4.7-5.9; p=0.004). Carriers of APOE epsilon 2 had increased mortality (odds ratio [OR] 1.50, 95% CI 1.23-1.82; p=2.45x10(-5)) and poorer functional outcomes (modified Rankin scale score 3-6; 1-52, 1.25-1.85; p=1.74x10(-5)) compared with non-carriers after lobar ICH. APOE epsilon 4 was not associated with lobar ICH volume, functional outcome, or mortality in the discovery phase, replication phases, or meta-analysis of these three phases; in our further meta-analysis of 2194 patients, this variant did not increase risk of mortality (1.08, .86-1.36; p=0.52). APOE allele variants were not associated with deep ICH volume, functional outcome, or mortality. Interpretation Vasculopathic changes associated with the APOE epsilon 2 allele might have a role in the severity and clinical course of lobar ICH. Screening of patients who have ICH to identify the epsilon 2 variant might allow identification of those at increased risk of mortality and poor functional outcomes.\n\nEnzinger, Christian\n\nPichler, Alexander\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n170384\nGroup 1 ITI Consensus Report: The influence of implant length and design and medications on clinical and patient-reported outcomes.\n\nJung, RE\n\nAl-Nawas, B\n\nAraujo, M\n\nAvila-Ortiz, G\n\nBarter, S\n\nBrodala, N\n\nChappuis, V\n\nChen, B\n\nDe Souza, A\n\nAlmeida, RF\n\nFickl, S\n\nFinelle, G\n\nGaneles, J\n\nGholami, H\n\nHammerle, C\n\nJensen, S\n\nJokstad, A\n\nKatsuyama, H\n\nKleinheinz, J\n\nKunavisarut, C\n\nMardas, N\n\nMonje, A\n\nPapaspyridakos, P\n\nPayer, M\n\nSchiegnitz, E\n\nSmeets, R\n\nStefanini, M\n\nTen Bruggenkate, C\n\nVazouras, K\n\nWeber, HP\n\nWeingart, D\n\nWindisch, P\n\nBeiträge in Fachzeitschriften\nISI:000449074000006\n30328189.0\n10.1111/clr.13342\nNone\nThe aim of Working Group 1 was to address the influence of different local (implant length, diameter, and design) and systemic (medications) factors on clinical, radiographic, and patient-reported outcomes in implant dentistry. Focused questions on (a) short posterior dental implants (≤6 mm), (b) narrow diameter implants, (c) implant design (tapered compared to a non-tapered implant design), and (d) medication-related dental implant failures were addressed.\n Four systematic reviews were prepared in advance of the Consensus Conference and were discussed among the participants of Group 1. Consensus statements, clinical recommendations, and recommendations for future research were based on structured group discussions until consensus was reached among the entire expert Group 1. The statements were then presented and accepted following further discussion and modifications as required by the plenary.\n Short implants (≤6 mm) revealed a survival rate ranging from 86.7% to 100%, whereas standard implant survival rate ranged from 95% to 100% with a follow-up from 1 to 5 years. Short implants demonstrated a higher variability and a higher Risk Ratio [RR: 1.24 (95% CI: 0.63, 2.44, p = 0.54)] for failure compared to standard implants. Narrow diameter implants (NDI) have been classified into three categories: Category 1: Implants with a diameter of <2.5 mm ("Mini-implants"); Category 2: Implants with a diameter of 2.5 mm to <3.3 mm; Category 3: Implants with a diameter of 3.3 mm to 3.5 mm. Mean survival rates were 94.7 ± 5%, 97.3 ± 5% and 97.7 ± 2.3% for category 1, 2 and 3. Tapered versus non-tapered implants demonstrated only insignificant differences regarding clinical, radiographic, and patient-reported outcomes. The intake of certain selective serotonin reuptake inhibitors and proton pump inhibitors is associated with a statistically significant increased implant failure rate. The intake of bisphosphonates related to the treatment of osteoporosis was not associated with an increased implant failure rate.\n It is concluded that short implants (≤6 mm) are a valid option in situations of reduced bone height to avoid possible morbidity associated with augmentation procedures; however, they reveal a higher variability and lower predictability in survival rates. Narrow diameter implants with diameters of 2.5 mm and more demonstrated no difference in implant survival rates compared to standard diameter implants. In contrast, it is concluded that narrow diameter implants with diameters of less than 2.5 mm exhibited lower survival rates compared to standard diameter implants. It is further concluded that there are no differences between tapered versus non-tapered dental implants. Certain medications such as selective serotonin reuptake inhibitors and proton pump inhibitors showed an association with a higher implant failure rate.\n © 2018 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.\n\nPayer, Michael\n\n\n"
},
{
"text": "\n2219\nRecombinant human erythropoietin in the anemia associated with multiple myeloma or non-Hodgkin's lymphoma: dose finding and identification of predictors of response.\n\nCazzola, M\n\nMessinger, D\n\nBattistel, V\n\nBron, D\n\nCimino, R\n\nEnller-Ziegler, L\n\nEssers, U\n\nGreil, R\n\nGrossi, A\n\nJäger, G\n\nLeMevel, A\n\nNajman, A\n\nSilingardi, V\n\nSpriano, M\n\nvan Hoof, A\n\nEhmer, B\n\nBeiträge in Fachzeitschriften\nISI:A1995TK47900008\n8541533.0\n10.1182/blood.V86.12.4446.bloodjournal86124446\nNone\nPrevious phase I-II clinical trials have shown that recombinant human erythropoietin (rHuEpo) can ameliorate anemia in a portion of patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Therefore, we performed a randomized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo. A total of 146 patients who had hemoglobin (Hb) levels < or = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial. Patients were randomized to receive 1, 00 U (n = 31), 2, 00 U (n = 29), 5, 00 U (n = 31), or 10, 00 U (n = 26) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy (n = 29). Of the patients, 84 suffered from MM and 62 from low- to intermediate-grade NHL, including chronic lymphocytic leukemia; 116 of 146 (79%) received chemotherapy during the study. The mean baseline Hb level was 9.4 +/- 1.0 g/dL. The median serum Epo level was 32 mU/mL, and endogenous Epo production was found to be defective in 77% of the patients, as judged by a value for the ratio of observed-to-predicted serum Epo levels (O/P ratio) of < or = 0.9. An intention-to-treat analysis was performed to evaluate treatment efficacy. The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 (P = .57), 0.22 (P = .05), 0.43 (P = .01), and 0.58 (P = .0001) g/dL in the 1, 00 U, 2, 00 U, 5, 00 U, and 10, 00 U groups, respectively (P values versus control). The probability of response (delta Hb > or = 2 g/dL) increased steadily and, after 8 weeks, reached 31% (2, 00 U), 61% (5, 00 U), and 62% (10, 00 U), respectively. Regression analysis using Cox's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5, 00 or 10, 00 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo, whereas only one quarter of those with adequate Epo levels did so. Classification and regression tree analysis also showed that doses of 2, 00 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50% of these patients are expected to respond to rHuEpo. Thus, rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production. From a practical point of view, we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels, whereas the choice of the initial dosage should be based on residual marrow function.\n\n\n"
},
{
"text": "\n103572\nVITATOPS, the VITAmins TO prevent stroke trial: rationale and design of a randomised trial of B-vitamin therapy in patients with recent transient ischaemic attack or stroke (NCT00097669) (ISRCTN74743444).\n\nVITATOPS Trial Study Group\n\nHankey, GJ\n\nAlgra, A\n\nChen, C\n\nWong, MC\n\nCheung, R\n\nWong, L\n\nDivjak, I\n\nFerro, J\n\nde Freitas, G\n\nGommans, J\n\nGroppa, S\n\nHill, M\n\nSpence, D\n\nLees, K\n\nLisheng, L\n\nNavarro, J\n\nRanawaka, U\n\nRicci, S\n\nSchmidt, R\n\nSlivka, A\n\nTan, K\n\nTsiskaridze, A\n\nUddin, W\n\nVanhooren, G\n\nXavier, D\n\nArmitage, J\n\nHobbs, M\n\nLe, M\n\nSudlow, C\n\nWheatley, K\n\nYi, Q\n\nBulder, M\n\nEikelboom, JW\n\nHankey, GJ\n\nHo, WK\n\nJamrozik, K\n\nKlijn, K\n\nKoedam, E\n\nLangton, P\n\nNijboer, E\n\nTuch, P\n\nPizzi, J\n\nTang, M\n\nAntenucci, M\n\nChew, Y\n\nChinnery, D\n\nCockayne, C\n\nLoh, K\n\nMcMullin, L\n\nSmith, F\n\nSchmidt, R\n\nChen, C\n\nWong, MC\n\nde Freitas, G\n\nHankey, GJ\n\nLoh, K\n\nSong, S\n\nBeiträge in Fachzeitschriften\nISI:000247202000016\n18705976.0\n10.1111/j.1747-4949.2007.00111.x\nNone\nBACKGROUND: Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischaemic stroke, dementia and depression. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B(12) and vitamin B(6), it is not known whether lowering tHcy, by means of B vitamin therapy, can prevent stroke and other major atherothromboembolic vascular events. AIM: To determine whether the addition of B-vitamin supplements (folic acid 2 mg, B(6) 25 mg, B(12) 500 microg) to best medical and surgical management will reduce the combined incidence of stroke, myocardial infarction (MI) and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. DESIGN: A prospective, international, multicentre, randomised, double blind, placebo-controlled clinical trial. SETTING: One hundred and four medical centres in 20 countries on five continents. SUBJECTS: Eight thousand (6600 recruited as of 5 January, 2006) patients with recent (<7 months) stroke (ischaemic or haemorrhagic) or TIA (brain or eye). RANDOMISATION: Randomisation and data collection are performed by means of a central telephone service or secure internet site. INTERVENTION: One tablet daily of either placebo or B vitamins (folic acid 2 mg, B(6) 25 mg, B(12) 500 mug). PRIMARY OUTCOME: The composite of stroke, MI or death from any vascular cause, whichever occurs first. Outcome and serious adverse events are adjudicated blinded to treatment allocation. SECONDARY OUTCOMES: TIA, unstable angina, revascularisation procedures, dementia, depression. STATISTICAL POWER: With 8000 patients followed up for a median of 2 years and an annual incidence of the primary outcome of 8% among patients assigned placebo, the study will have at least 80% power to detect a relative reduction of 15% in the incidence of the primary outcome among patients assigned B vitamins (to 6.8%/year), applying a two-tailed level of significance of 5%. CONCLUSION: VITATOPS aims to recruit and follow-up 8000 patients between 1998 and 2008, and provide a reliable estimate of the safety and effectiveness of folic acid, vitamin B(12), and vitamin B(6) supplementation in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke throughout the world.\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n171867\nAssociation of Infants Exposed to Prenatal Zika Virus Infection With Their Clinical, Neurologic, and Developmental Status Evaluated via the General Movement Assessment Tool.\n\nEinspieler, C\n\nUtsch, F\n\nBrasil, P\n\nPanvequio Aizawa, CY\n\nPeyton, C\n\nHydee Hasue, R\n\nFrançoso Genovesi, F\n\nDamasceno, L\n\nMoreira, ME\n\nAdachi, K\n\nMarschik, PB\n\nNielsen-Saines, K\n\nGM Zika Working Group\n\nBeiträge in Fachzeitschriften\nISI:000465422700020\n30657537.0\n10.1001/jamanetworkopen.2018.7235\nPMC6431234\nThere is an urgent need to assess neurodevelopment in Zika virus (ZIKV)-exposed infants.\n To perform general movement assessment (GMA) at 9 to 20 weeks' postterm age and to evaluate whether the findings are associated with neurodevelopmental outcomes at age 12 months in infants prenatally exposed to acute maternal illness with rash in Brazil during the ZIKV outbreak and in age-matched controls.\n In this cohort study, infants prenatally exposed to acute maternal illness with rash were recruited at medical institutions in Rio de Janeiro and Belo Horizonte, Brazil, from February 1, 2016, to April 30, 2017, while infants without any exposure to maternal illness originated from the Graz University Audiovisual Research Database for the Interdisciplinary Analysis of Neurodevelopment. Participants were 444 infants, including 76 infants without congenital microcephaly, 35 infants with microcephaly, and 333 neurotypical children matched for sex, gestational age at birth, and age at GMA.\n General movement assessment performed at 9 to 20 weeks' postterm age, with negative predictive value, positive predictive value, sensitivity, and specificity generated, as well as clinical, neurologic, and developmental status (Bayley Scales of Infant and Toddler Development, Third Edition [Bayley-III] scores) at age 12 months. Motor Optimality Scores were generated based on the overall quality of the motor repertoire. Adverse outcomes were defined as a Bayley-III score less than 2 SD in at least 1 domain, a score less than 1 SD in at least 2 domains, and/or atypical neurologic findings.\n A total of 444 infants were enrolled, including 111 children prenatally exposed to a maternal illness with rash and 333 children without any prenatal exposure to maternal illness (57.7% male and mean [SD] age, 14 [2] weeks for both groups); 82.1% (46 of 56) of ZIKV-exposed infants without congenital microcephaly were healthy at age 12 months. Forty-four of 46 infants were correctly identified by GMA at 3 months, with a negative predictive value of 94% (95% CI, 85%-97%). Seven of 10 ZIKV-exposed children without microcephaly with adverse neurodevelopmental outcomes were identified by GMA. The GMA positive predictive value was 78% (95% CI, 46%-94%), sensitivity was 70% (95% CI, 35%-93%), specificity was 96% (95% CI, 85%-99%), and accuracy was 91% (95% CI, 80%-97%). Children with microcephaly had bilateral spastic cerebral palsy; none had normal movements. The Motor Optimality Score differentiated outcomes: the median Motor Optimality Score was 23 (interquartile range [IQR], 21-26) in children with normal development, 12 (IQR, 8-19) in children with adverse outcomes, and 5 (IQR, 5-6) in children with microcephaly, a significant difference (P = .001).\n This study suggests that although a large proportion of ZIKV-exposed infants without microcephaly develop normally, many do not. The GMA should be incorporated into routine infant assessments to enable early entry into targeted treatment programs.\n\nBartl-Pokorny, Katrin Daniela\n\nEinspieler, Christa\n\nKrieber-Tomantschger, Magdalena\n\nMarschik, Dajie\n\nMarschik, Peter\n\nPokorny, Florian\n\nScheuchenegger, Anna Birgitta\n\n\n"
}
]
}