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"text": "\n100078\nNew loci associated with kidney function and chronic kidney disease.\n\nKöttgen, A\n\nPattaro, C\n\nBöger, CA\n\nFuchsberger, C\n\nOlden, M\n\nGlazer, NL\n\nParsa, A\n\nGao, X\n\nYang, Q\n\nSmith, AV\n\nO'Connell, JR\n\nLi, M\n\nSchmidt, H\n\nTanaka, T\n\nIsaacs, A\n\nKetkar, S\n\nHwang, SJ\n\nJohnson, AD\n\nDehghan, A\n\nTeumer, A\n\nParé, G\n\nAtkinson, EJ\n\nZeller, T\n\nLohman, K\n\nCornelis, MC\n\nProbst-Hensch, NM\n\nKronenberg, F\n\nTönjes, A\n\nHayward, C\n\nAspelund, T\n\nEiriksdottir, G\n\nLauner, LJ\n\nHarris, TB\n\nRampersaud, E\n\nMitchell, BD\n\nArking, DE\n\nBoerwinkle, E\n\nStruchalin, M\n\nCavalieri, M\n\nSingleton, A\n\nGiallauria, F\n\nMetter, J\n\nde Boer, IH\n\nHaritunians, T\n\nLumley, T\n\nSiscovick, D\n\nPsaty, BM\n\nZillikens, MC\n\nOostra, BA\n\nFeitosa, M\n\nProvince, M\n\nde Andrade, M\n\nTurner, ST\n\nSchillert, A\n\nZiegler, A\n\nWild, PS\n\nSchnabel, RB\n\nWilde, S\n\nMunzel, TF\n\nLeak, TS\n\nIllig, T\n\nKlopp, N\n\nMeisinger, C\n\nWichmann, HE\n\nKoenig, W\n\nZgaga, L\n\nZemunik, T\n\nKolcic, I\n\nMinelli, C\n\nHu, FB\n\nJohansson, A\n\nIgl, W\n\nZaboli, G\n\nWild, SH\n\nWright, AF\n\nCampbell, H\n\nEllinghaus, D\n\nSchreiber, S\n\nAulchenko, YS\n\nFelix, JF\n\nRivadeneira, F\n\nUitterlinden, AG\n\nHofman, A\n\nImboden, M\n\nNitsch, D\n\nBrandstätter, A\n\nKollerits, B\n\nKedenko, L\n\nMägi, R\n\nStumvoll, M\n\nKovacs, P\n\nBoban, M\n\nCampbell, S\n\nEndlich, K\n\nVölzke, H\n\nKroemer, HK\n\nNauck, M\n\nVölker, U\n\nPolasek, O\n\nVitart, V\n\nBadola, S\n\nParker, AN\n\nRidker, PM\n\nKardia, SL\n\nBlankenberg, S\n\nLiu, Y\n\nCurhan, GC\n\nFranke, A\n\nRochat, T\n\nPaulweber, B\n\nProkopenko, I\n\nWang, W\n\nGudnason, V\n\nShuldiner, AR\n\nCoresh, J\n\nSchmidt, R\n\nFerrucci, L\n\nShlipak, MG\n\nvan Duijn, CM\n\nBorecki, I\n\nKrämer, BK\n\nRudan, I\n\nGyllensten, U\n\nWilson, JF\n\nWitteman, JC\n\nPramstaller, PP\n\nRettig, R\n\nHastie, N\n\nChasman, DI\n\nKao, WH\n\nHeid, IM\n\nFox, CS\n\nBeiträge in Fachzeitschriften\nISI:000277179500006\n20383146.0\n10.1038/ng.568\nPMC2997674\nChronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67, 93 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5, 07 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22, 82 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.\n\nCavalieri, Margherita\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n158520\nA randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients.\n\nRello, J\n\nKrenn, CG\n\nLocker, G\n\nPilger, E\n\nMadl, C\n\nBalica, L\n\nDugernier, T\n\nLaterre, PF\n\nSpapen, H\n\nDepuydt, P\n\nVincent, JL\n\nBogár, L\n\nSzabó, Z\n\nVölgyes, B\n\nMáñez, R\n\nCakar, N\n\nRamazanoglu, A\n\nTopeli, A\n\nMastruzzo, MA\n\nJasovich, A\n\nRemolif, CG\n\nDel Carmen Soria, L\n\nAndresen Hernandez, MA\n\nRuiz Balart, C\n\nKrémer, I\n\nMolnár, Z\n\nvon Sonnenburg, F\n\nLyons, A\n\nJoannidis, M\n\nBurgmann, H\n\nWelte, T\n\nKlingler, A\n\nHochreiter, R\n\nWestritschnig, K\n\nBeiträge in Fachzeitschriften\nISI:000393824200001\n28159015.0\n10.1186/s13054-017-1601-9\nPMC5291979\nCurrently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients.\n We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days.\n Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1-10.6%) was observed in the IC43 groups.\n This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns.\n ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.\n\nPilger, Ernst\n\n\n"
},
{
"text": "\n158677\nCase-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management From the International Task Force on ONJ.\n\nKhan, AA\n\nMorrison, A\n\nKendler, DL\n\nRizzoli, R\n\nHanley, DA\n\nFelsenberg, D\n\nMcCauley, LK\n\nO'Ryan, F\n\nReid, IR\n\nRuggiero, SL\n\nTaguchi, A\n\nTetradis, S\n\nWatts, NB\n\nBrandi, ML\n\nPeters, E\n\nGuise, T\n\nEastell, R\n\nCheung, AM\n\nMorin, SN\n\nMasri, B\n\nCooper, C\n\nMorgan, SL\n\nObermayer-Pietsch, B\n\nLangdahl, BL\n\nDabagh, RA\n\nDavison, KS\n\nSándor, GK\n\nJosse, RG\n\nBhandari, M\n\nEl Rabbany, M\n\nPierroz, DD\n\nSulimani, R\n\nSaunders, DP\n\nBrown, JP\n\nCompston, J\n\nInternational Task Force on Osteonecrosis of the Jaw\n\nBeiträge in Fachzeitschriften\nISI:000395849400004\n27956123.0\n10.1016/j.jocd.2016.09.005\nNone\nOsteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence.\n Copyright © 2017. Published by Elsevier Inc.\n\nObermayer-Pietsch, Barbara\n\n\n"
},
{
"text": "\n162143\nEpidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe.\n\nEgan, AM\n\nVellinga, A\n\nHarreiter, J\n\nSimmons, D\n\nDesoye, G\n\nCorcoy, R\n\nAdelantado, JM\n\nDevlieger, R\n\nVan Assche, A\n\nGaljaard, S\n\nDamm, P\n\nMathiesen, ER\n\nJensen, DM\n\nAndersen, L\n\nLapolla, A\n\nDalfrà, MG\n\nBertolotto, A\n\nMantaj, U\n\nWender-Ozegowska, E\n\nZawiejska, A\n\nHill, D\n\nJelsma, JGM\n\nSnoek, FJ\n\nWorda, C\n\nBancher-Todesca, D\n\nvan Poppel, MNM\n\nKautzky-Willer, A\n\nDunne, FP\n\nDALI Core Investigator group\n\nBeiträge in Fachzeitschriften\nISI:000408770300008\n28702810.0\n10.1007/s00125-017-4353-9\nPMC6448875\nAccurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria.\n Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies.\n The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24-28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35-37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not.\n The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies.\n\nDesoye, Gernot\n\n\n"
},
{
"text": "\n176403\nEffects of Serelaxin in Patients with Acute Heart Failure.\n\nMetra, M\n\nTeerlink, JR\n\nCotter, G\n\nDavison, BA\n\nFelker, GM\n\nFilippatos, G\n\nGreenberg, BH\n\nPang, PS\n\nPonikowski, P\n\nVoors, AA\n\nAdams, KF\n\nAnker, SD\n\nArias-Mendoza, A\n\nAvendaño, P\n\nBacal, F\n\nBöhm, M\n\nBortman, G\n\nCleland, JGF\n\nCohen-Solal, A\n\nCrespo-Leiro, MG\n\nDorobantu, M\n\nEcheverría, LE\n\nFerrari, R\n\nGoland, S\n\nGoncalvesová, E\n\nGoudev, A\n\nKøber, L\n\nLema-Osores, J\n\nLevy, PD\n\nMcDonald, K\n\nManga, P\n\nMerkely, B\n\nMueller, C\n\nPieske, B\n\nSilva-Cardoso, J\n\nŠpinar, J\n\nSquire, I\n\nStępińska, J\n\nVan Mieghem, W\n\nvon Lewinski, D\n\nWikström, G\n\nYilmaz, MB\n\nHagner, N\n\nHolbro, T\n\nHua, TA\n\nSabarwal, SV\n\nSeverin, T\n\nSzecsödy, P\n\nGimpelewicz, C\n\nRELAX-AHF-2 Committees Investigators\n\nBeiträge in Fachzeitschriften\nISI:000483203400007\n31433919.0\n10.1056/NEJMoa1801291\nNone\nSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.\n In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.\n A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.\n In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).\n Copyright © 2019 Massachusetts Medical Society.\n\nvon Lewinski, Dirk\n\n\n"
},
{
"text": "\n181816\nEschar removal by bromelain based enzymatic debridement (Nexobrid®) in burns: European consensus guidelines update.\n\nHirche, C\n\nKreken Almeland, S\n\nDheansa, B\n\nFuchs, P\n\nGoverna, M\n\nHoeksema, H\n\nKorzeniowski, T\n\nLumenta, DB\n\nMarinescu, S\n\nMartinez-Mendez, JR\n\nPlock, JA\n\nSander, F\n\nZiegler, B\n\nKneser, U\n\nBeiträge in Fachzeitschriften\nISI:000538860100005\n32241591.0\n10.1016/j.burns.2020.03.002\nNone\nBromelain-based Enzymatic Debridement has been introduced as an additional concept to the burn surgeon's armamentarium and is best indicated for mid-to deep dermal burns with mixed patterns. Increasing evidence has been published focusing on special regions and settings as well as on limitations of Enzymatic Debridement to improve patient care. To better guide Enzymatic Debridement in view of the increasing experience, there is a need to update the formerly published consensus guidelines with user-orientated recommendations, which were last produced in 2017.\n A multi-professional expert panel of plastic surgeons and burn care specialists from twelve European centers was convened, to assist in developing current recommendations for best practices with use of Enzymatic Debridement. Consensus statements were based on peer-reviewed publications and clinical relevance, and topics for re-evaluation and refinement were derived from the formerly published European guidelines. For consensus agreement, the methodology employed was an agreement algorithm based on a modification of the Willy and Stellar method. For this study on Enzymatic Debridement, consensus was considered when there was at least 80 % agreement to each statement.\n The updated consensus guidelines from 2019 refer to the clinical experience and practice patterns of 1232 summarized patient cases treated by the panelists with ED in Europe (2017: 500 cases), reflecting the impact of the published recommendations. Forty-three statements were formulated, addressing the following topics: indications, pain management and anesthesia, large surface treatment, timing of application for various indications, preparation and application, post-interventional wound management, skin grafting, outcome, scar and revision management, cost-effectiveness, patient´s perspective, logistic aspects and training strategies. The degree of consensus was remarkably high, with consensus in 42 out of 43 statements (97.7%). A classification with regard to timing of application for Enzymatic Debridement was introduced, discriminating immediate/very early (≤12 h), early (12-72 h) or delayed (>72 h) treatment. All further recommendations are addressed in the publication.\n The updated guidelines in this publication represent further refinement of the recommended indication, application and post-interventional management for the use of ED. The published statements contain detailed, user-orientated recommendations aiming to align current and future users and prevent pitfalls, e.g. for the successful implementation of ED in further countries like the USA. The significance of this work is reflected by the magnitude of patient experience behind it, larger than the total number of patients treated in all published ED clinical trials.\n Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.\n\nLumenta, David Benjamin\n\n\n"
},
{
"text": "\n151245\nA comparative analysis of optical and conventional axiography for the analysis of temporomandibular joint movements.\n\nWagner, A\n\nSeemann, R\n\nSchicho, K\n\nEwers, R\n\nPiehslinger, E\n\nBeiträge in Fachzeitschriften\nISI:000186476900013\n14586314.0\n10.1016/S0022391303004827\nNone\nCurrently available systems for pantographic tracing are heavy, bulky, and can interfere with jaw movements.\n This study describes the development and clinical application of optoelectronic axiography designed to overcome system inherent problems of conventional bulky frame-based registration axiography. The purpose of this study is the comparison of the newly developed system and conventional axiography.\n Three-dimensional recordings of condylar pathways were acquired by means of infrared digitizers interfaced to newly developed software. Ten distinct curves in each of 10 subjects were recorded by synchronous optoelectronic axiography (100 tracings) and by conventional axiography (100 tracings). Usually, two 3-dimensional (3D) light weight sensors are provisionally fixed to the facial surface of a maxillary and mandibular incisor by means of a single orthodontic bracket. To allow for direct comparison of all 100 pairs of curves in this study, the 3D sensors of the optoelectronic system were attached to the bulky double face-bow system of the axiograph. The conformity of tracings (protrusion, opening/closing, mediotrusion, and laterotrusion) was evaluated by means of correlation analysis. Resulting axiographic recordings from both systems were evaluated by 3 experts (dentists, experienced in axiographic investigations, who were blind to the source of the data), focusing on standardized qualitative criteria of the recordings (homogeneity/smoothness, pathway-characteristics, excursion, and left/right-symmetry). After testing for normal distribution of the ratio scaled data (length of pathway, horizontal condylar inclination [HCI], Bennett angle) with the Kolmogoroff-Smirnov test (alpha=.01), axiographic curves were quantitatively compared by means of an intraclass correlation coefficient ([ICC] alpha =.01). The Wilcoxon test (alpha=.01) was used to evaluate equivalence of ordinally scaled values (homogeneity of tracings) and Cohen's Kappa was used to compare excursion and left/right symmetry.\n High correspondence between curves recorded by conventional and optoelectronic axiography was observed. The mean differences of lengths between the protrusive, opening/closing, and mediotrusive pathways were 0.0 mm, 0.6 mm, and 0.1 mm, respectively. Pathways and values for HCI were found highly correlated (pathways: 95% CI of ICC 0.9776-0.9908; HCI: 95% CI of ICC 0.8641-0.9597). The 95% CIs for differences of pathways, HCI-value, and Bennett angle were -0.1mm/0.3mm, -3.4 degrees/1.9 degrees, and -2.8 degrees/4.8 degrees, respectively. Pathway characteristics also corresponded well (Cohen's Kappa: 0.73 for symmetric and 0.72 for asymmetric movements), 0.77 for left/right symmetry, whereas other characteristics showed less significant correlation (Cohen's Kappa of excursion: 0.21 for symmetric and 0.09 for asymmetric movements, homogeneity: 0.08 for symmetric and 0.15 for asymmetric movements).\n Within the limitations of this study, optoelectronic axiography proved to be an applicable, promising technique, leading to diagnostic interpretations equivalent (with respect to the CIs) to conventional axiography.\n\n\n"
},
{
"text": "\n170864\nInternal fixation of proximal humerus fractures using the locking proximal humerus plate.\n\nPlecko, M\n\nKraus, A\n\nBeiträge in Fachzeitschriften\nNone\n16007377.0\n10.1007/s00064-005-1120-8\nNone\nStable fixation of unstable proximal humerus fractures until bony consolidation. Early mobilization of the shoulder and early active rehabilitation program to ensure a good functional outcome and a good restoration of the activities of daily living.\n Unstable two-, three- and four-part fractures of the proximal humerus (classified according to the AO classification as: 11-A2, A3, B1, B2, B3, C1, C2, C3). Nonunions of the proximal humerus, especially at the neck. Pathologic fractures of the proximal humerus.\n Comminuted humeral head fractures in old patients, which cannot be reconstructed adequately. Proximal humerus fractures in the immature patient. Local infection after previous surgery.\n Deltopectoral approach. Blunt mobilization of the deltoid muscle. Suture loops through the supraspinatus tendon, the infraspinatus tendon, and the subscapularis tendon close to their bony insertion. Careful indirect reduction of the fracture fragments without further damage to their blood supply. Correct positioning of the LPHP (Locking Proximal Humerus Plate) on the lateral side of the humerus, approximately 5 mm below the tip of the greater tuberosity. Indirect approximation of the subcapital fracture component to the plate, by tightening a standard 3.5-mm cortical bone screw inserted into the first hole distal to the metaphyseal fracture line. Temporary fixation of the plate with 1.8-mm Kirschner wires. Fixed-angle fixation of the plate to the bone, using locking screws. Additional stabilization of the tuberosities to the plate with suture loops.\n Between January 1, 1997 and April 30, 2002, 64 patients with acute fractures of the proximal humerus were treated with fixed-angle plating at the UKH Graz. 36 patients meeting the inclusion criteria (that is primary operative stabilization within 14 days after trauma in a standardized way and minimal follow-up period of 12 months) were assessed 31 months after surgery on average, using the Constant Score and the DASH Score. The mean age of the 22 women and 14 men was 57.5 years (21-78 years). According to the AO classification eight fractures were classified as 11-A3, one fracture as B1, five fractures as B2, three fractures as B3, one fracture as C1, 16 fractures as C2, and two fractures as C3. A mean Constant Score of 62.6 points and an age-related Constant Score of 80.7% on average, as well as a DASH Score of 18.0 points were obtained, constituting a satisfactory result in three quarters of all patients. Complications observed were two humeral head necroses, one partial necrosis after a head-splitting fracture with nevertheless good clinical result, and a deep infection in two cases. Breakage of the plate was seen in one patient with an A3.3 fracture without medial buttress; no further surgery was necessary; the fracture healed after a short period of immobilization.\n\nPlecko, Michael\n\n\n"
},
{
"text": "\n178217\nGlobal Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis.\n\nEkker, M\n\nJacob, M\n\nvan Dongen, M\n\nAarnio, K\n\nAnnamalai, A\n\nArauz, A\n\nArnold, M\n\nBarboza, M\n\nBolognese, M\n\nBrouns, R\n\nChuluun, B\n\nChuluunbaatar, E\n\nDagvajantsan, B\n\nDebette, S\n\nDon, A\n\nEnzinger, C\n\nEkizoglu, E\n\nFandler-Höfler, S\n\nFazekas, F\n\nFromm, A\n\nGattringer, T\n\nGulli, G\n\nHoffmann, M\n\nHora, T\n\nJern, C\n\nJood, K\n\nKamouchi, M\n\nKim, YS\n\nKitazono, T\n\nKittner, S\n\nKleinig, T\n\nKlijn, K\n\nKorv, J\n\nLee, TH\n\nLeys, D\n\nMaaijwee, N\n\nMartinez-Majander, N\n\nMarto, JP\n\nMehndiratta, M\n\nMifsud, V\n\nMontanaro, V\n\nOwolabi, MO\n\nPatel, V\n\nPhillips, M\n\nPiechowski-Iozwiak, B\n\nPikula, A\n\nRuiz-Sandoval, JL\n\nSarnowski, B\n\nSchreuder, F\n\nSwartz, R\n\nTan, KS\n\nTanne, D\n\nTatlisumak, T\n\nThijs, V\n\nTuladhar, A\n\nViana-Baptista, M\n\nVibo, R\n\nWu, T\n\nYesilot, N\n\nWaje-Andreassen, U\n\nPezzini, A\n\nPutaala, J\n\nde Leeuw, FE\n\nBeiträge in Fachzeitschriften\nISI:000512774800183\n31727655.0\n10.1136/bmjopen-2019-031144\nPMC6887075\nWorldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients.\n The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.\n Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.\n © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\nEnzinger, Christian\n\nFandler-Höfler, Simon\n\nFazekas, Franz\n\nGattringer, Thomas\n\n\n"
},
{
"text": "\n1851\nOmega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter trial.\n\nMayser, P\n\nMrowietz, U\n\nArenberger, P\n\nBartak, P\n\nBuchvald, J\n\nChristophers, E\n\nJablonska, S\n\nSalmhofer, W\n\nSchill, WB\n\nKrämer, HJ\n\nSchlotzer, E\n\nMayer, K\n\nSeeger, W\n\nGrimminger, F\n\nBeiträge in Fachzeitschriften\nISI:000072990100002\n9555791.0\n10.1016/S0190-9622(98)70114-8\nNone\nBACKGROUND: Profound changes in the metabolism of eicosanoids with increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Free eicosapentaenoic acid (EPA) may compete with liberated AA and result in an antiinflammatory effect. OBJECTIVE: Our purpose was to assess the efficacy and safety of intravenously administered fish-oil-derived lipid emulsion on chronic plaque-type psoriasis. METHODS: A double-blind, randomized, parallel group study was performed in eight European centers. Eighty-three patients hospitalized for chronic plaque-type psoriasis with a severity score of at least 15 according to the Psoriasis Area and Severity Index (PASI) participated in a 14-day trial. They were randomly allocated to receive daily infusions with either a omega-3 fatty acid-based lipid emulsion (Omegavenous; 200 ml/day with 4.2 gm of both EPA and docosahexaenoic acid (DHA); 43 patients) or a conventional omega-6-lipid emulsion (Lipovenous; EPA+DHA < 0.1 gm/100 ml; 40 patients). The groups were well matched with respect to demographic data and psoriasis-specific medical history. Efficacy of therapy was evaluated by changes in PASI, in an overall assessment of psoriasis by the investigator, and a self-assessment by the patient. In one center neutrophil 4- versus 5-series leukotriene (LT) generation and platelet 2- versus 3- thromboxane generation were investigated and plasma-free fatty acids were determined. RESULTS: The total PASI score decreased by 11.2 +/- 9.8 in the omega-3 group and by 7.5 +/- 8.8 in the omega-6 group (p = 0.048). In addition, the omega-3 group was superior to the omega-6 group with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient. Response (defined as decrease in total PASI of at least 50% between admission and last value) was seen in 16 of 43 patients (37%) receiving the omega-3 emulsion and 9 of 40 patients (23%) receiving omega-6 fatty acid-based lipid emulsion. No serious side effects were observed. Within the first few days of omega-3 lipid administration, but not in the omega-6 supplemented patients, a manifold increase in plasma-free EPA concentration, neutrophil leukotriene B5 and platelet thromboxane B3 generation occurred. CONCLUSION: Intravenous omega-3-fatty acid administration is effective in the treatment of chronic plaque-type psoriasis. This effect may be related to changes in inflammatory eicosanoid generation.\n\nSalmhofer, Wolfgang\n\n\n"
},
{
"text": "\n156825\n16S Based Microbiome Analysis from Healthy Subjects' Skin Swabs Stored for Different Storage Periods Reveal Phylum to Genus Level Changes.\n\nKlymiuk, I\n\nBambach, I\n\nPatra, V\n\nTrajanoski, S\n\nWolf, P\n\nBeiträge in Fachzeitschriften\nISI:000390161000001\n28066342.0\n10.3389/fmicb.2016.02012\nPMC5167739\nMicrobiome research and improvements in high throughput sequencing technologies revolutionize our current scientific viewpoint. The human associated microbiome is a prominent focus of clinical research. Large cohort studies are often required to investigate the human microbiome composition and its changes in a multitude of human diseases. Reproducible analyses of large cohort samples require standardized protocols in study design, sampling, storage, processing, and data analysis. In particular, the effect of sample storage on actual results is critical for reproducibility. So far, the effect of storage conditions on the results of microbial analysis has been examined for only a few human biological materials (e.g., stool samples). There is a lack of data and information on appropriate storage conditions on other human derived samples, such as skin. Here, we analyzed skin swab samples collected from three different body locations (forearm, V of the chest and back) of eight healthy volunteers. The skin swabs were soaked in sterile buffer and total DNA was isolated after freezing at -80°C for 24 h, 90 or 365 days. Hypervariable regions V1-2 were amplified from total DNA and libraries were sequenced on an Illumina MiSeq desktop sequencer in paired end mode. Data were analyzed using Qiime 1.9.1. Summarizing all body locations per time point, we found no significant differences in alpha diversity and multivariate community analysis among the three time points. Considering body locations separately significant differences in the richness of forearm samples were found between d0 vs. d90 and d90 vs. d365. Significant differences in the relative abundance of major skin genera (Propionibacterium, Streptococcus, Bacteroides, Corynebacterium, and Staphylococcus) were detected in our samples in Bacteroides only among all time points in forearm samples and between d0 vs. d90 and d90 vs. d365 in V of the chest and back samples. Accordingly, significant differences were detected in the ratios of the main phyla Actinobacteria, Firmicutes, and Bacteroidetes: Actinobacteria vs. Bacteroidetes at d0 vs. d90 (p-value = 0.0234), at d0 vs. d365 (p-value = 0.0234) and d90 vs. d365 (p-value = 0.0234) in forearm samples and at d90 vs. d365 in V of the chest (p-value = 0.0234) and back samples (p-value = 0.0234). The ratios of Firmicutes vs. Bacteroidetes showed no significant changes in any of the body locations as well as the ratios of Actinobacteria vs. Firmicutes at any time point. Studies with larger sample sizes are required to verify our results and determine long term storage effects with regard to specific biological questions.\n\nKlymiuk, Ingeborg\n\nPatra, Vijaykumar\n\nPerchthaler, Isabella\n\nTrajanoski, Slave\n\nWolf, Peter\n\n\n"
},
{
"text": "\n173979\nTranscatheter Aortic Valve Replacement With Next-Generation Self-Expanding Devices: A Multicenter, Retrospective, Propensity-Matched Comparison of Evolut PRO Versus Acurate neo Transcatheter Heart Valves.\n\nPagnesi, M\n\nKim, WK\n\nConradi, L\n\nBarbanti, M\n\nStefanini, GG\n\nZeus, T\n\nPilgrim, T\n\nSchofer, J\n\nZweiker, D\n\nTesta, L\n\nTaramasso, M\n\nHildick-Smith, D\n\nAbizaid, A\n\nWolf, A\n\nVan Mieghem, NM\n\nSedaghat, A\n\nWöhrle, J\n\nKhogali, S\n\nVan der Heyden, JAS\n\nWebb, JG\n\nEstévez-Loureiro, R\n\nMylotte, D\n\nMacCarthy, P\n\nBrugaletta, S\n\nHamm, CW\n\nBhadra, OD\n\nSchäfer, U\n\nCosta, G\n\nTamburino, C\n\nCannata, F\n\nReimers, B\n\nVeulemans, V\n\nAsami, M\n\nWindecker, S\n\nEitan, A\n\nSchmidt, A\n\nBianchi, G\n\nBedogni, F\n\nSaccocci, M\n\nMaisano, F\n\nAlsanjari, O\n\nSiqueira, D\n\nJensen, CJ\n\nNaber, CK\n\nZiviello, F\n\nSinning, JM\n\nSeeger, J\n\nRottbauer, W\n\nBrouwer, J\n\nAlenezi, A\n\nWood, DA\n\nTzalamouras, V\n\nRegueiro, A\n\nColombo, A\n\nLatib, A\n\nBeiträge in Fachzeitschriften\nISI:000460127700008\n30846081.0\n10.1016/j.jcin.2018.11.036\nNone\nThe aim of this study was to compare transcatheter aortic valve replacement (TAVR) with the Acurate neo (NEO) and Evolut PRO (PRO) devices.\n The NEO and PRO bioprostheses are 2 next-generation self-expanding devices developed for TAVR.\n The NEOPRO (A Multicenter Comparison of Acurate NEO Versus Evolut PRO Transcatheter Heart Valves) registry retrospectively included patients who underwent transfemoral TAVR with either NEO or PRO valves at 24 centers between January 2012 and March 2018. One-to-one propensity score matching resulted in 251 pairs. Pre-discharge and 30-day Valve Academic Research Consortium (VARC)-2 defined outcomes were evaluated. Binary logistic regression was performed to adjust the treatment effect for propensity score quintiles.\n A total of 1, 51 patients (n = 1, 63 NEO; n = 288 PRO) were included. The mean age was 82 years, and the mean Society of Thoracic Surgeons score was 5.1%. After propensity score matching (n = 502), VARC-2 device success (90.6% vs. 91.6%; p = 0.751) and pre-discharge moderate to severe (II+) paravalvular aortic regurgitation (7.3% vs. 5.7%; p = 0.584) were comparable between the NEO and PRO groups. Furthermore, there were no significant differences in any 30-day clinical outcome between matched NEO and PRO pairs, including all-cause mortality (3.2% vs. 1.2%; p = 0.221), stroke (2.4% vs. 2.8%; p = 1.000), new permanent pacemaker implantation (11.0% vs. 12.8%; p = 0.565), and VARC-2 early safety endpoint (10.6% vs. 10.4%; p = 1.000). Logistic regression on the unmatched cohort confirmed a similar risk of VARC-2 device success, paravalvular aortic regurgitation II+, and 30-day clinical outcomes after NEO and PRO implantation.\n In this multicenter registry, transfemoral TAVR with the NEO and PRO bioprostheses was associated with high device success, acceptable rates of paravalvular aortic regurgitation II+, and good 30-day clinical outcomes. After adjusting for potential confounders, short-term outcomes were similar between the devices.\n Copyright © 2019. Published by Elsevier Inc.\n\nSchmidt, Albrecht\n\nZweiker, David\n\n\n"
},
{
"text": "\n124013\nInitial Prostate Biopsy: Development and Internal Validation of a Biopsy-specific Nomogram Based on the Prostate Cancer Antigen 3 Assay.\n\nHansen, J\n\nAuprich, M\n\nAhyai, SA\n\nde la Taille, A\n\nvan Poppel, H\n\nMarberger, M\n\nStenzl, A\n\nMulders, PF\n\nHuland, H\n\nFisch, M\n\nAbbou, CC\n\nSchalken, JA\n\nFradet, Y\n\nMarks, LS\n\nEllis, W\n\nPartin, AW\n\nPummer, K\n\nGraefen, M\n\nHaese, A\n\nWalz, J\n\nBriganti, A\n\nShariat, SF\n\nChun, FK\n\nBeiträge in Fachzeitschriften\nISI:000313572100009\n22854248.0\n10.1016/j.eururo.2012.07.030\nNone\nBackground: Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX). Objective: To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a man's risk of harboring any PCa and high-grade PCa (HGPCa). Design, setting, and participants: Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies. Intervention: IBX (>= 10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement. Outcome measurements and statistical analysis: PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model. Results and limitations: Any PCa and HGPCa were diagnosed in 46% (n = 318) and 20% (n = 137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p < 0.001). The PCA3-based IBX nomograms significantly outperformed the clinical models without PCA3 (all p < 0.001). Accuracy was increased by 4.5-7.1% related to PCA3 inclusion. When applying nomogram-derived PCa probability thresholds <= 30%, only a few patients with HGPCa (<= 2%) will be missed while avoiding up to 55% of unnecessary biopsies. External validation of the PCA3-based IBX-specific nomogram is warranted. Conclusions: The internally validated PCA3-based IBX-specific nomogram outperforms a clinical prediction model without PCA3 for the prediction of any PCa, leading to the avoidance of unnecessary biopsies while missing only a few cases of HGPCa. Our findings support the concepts of a combination of novel markers with established clinical risk factors and the superiority of decision tools that are specific to a clinical scenario. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.\n\nPummer, Karl\n\n\n"
},
{
"text": "\n173295\nPatterns of paediatric end-of-life care: a chart review across different care settings in Switzerland.\n\nZimmermann, K\n\nCignacco, E\n\nEngberg, S\n\nRamelet, AS\n\nvon der Weid, N\n\nEskola, K\n\nBergstraesser, E\n\nPELICAN Consortium\n\nAnsari, M\n\nAebi, C\n\nBaer, R\n\nPopovic, MB\n\nBernet, V\n\nBrazzola, P\n\nBucher, HU\n\nBuder, R\n\nCagnazzo, S\n\nDinten, B\n\nDorsaz, A\n\nElmer, F\n\nEnriquez, R\n\nFahrni-Nater, P\n\nFinkbeiner, G\n\nFrey, B\n\nFrey, U\n\nGreiner, J\n\nHassink, RI\n\nKeller, S\n\nKretschmar, O\n\nKroell, J\n\nLaubscher, B\n\nLeibundgut, K\n\nMalaer, R\n\nMeyer, A\n\nStuessi, C\n\nNelle, M\n\nNeuhaus, T\n\nNiggli, F\n\nPerrenoud, G\n\nPfammatter, JP\n\nPlecko, B\n\nRupf, D\n\nSennhauser, F\n\nStade, C\n\nSteinlin, M\n\nStoffel, L\n\nThomas, K\n\nVonarburg, C\n\nvon Vigier, R\n\nWagner, B\n\nWieland, J\n\nWernz, B\n\nBeiträge in Fachzeitschriften\nISI:000425779300004\n29452600.0\n10.1186/s12887-018-1021-2\nPMC5816353\nPaediatric end-of-life care is challenging and requires a high level of professional expertise. It is important that healthcare teams have a thorough understanding of paediatric subspecialties and related knowledge of disease-specific aspects of paediatric end-of-life care. The aim of this study was to comprehensively describe, explore and compare current practices in paediatric end-of-life care in four distinct diagnostic groups across healthcare settings including all relevant levels of healthcare providers in Switzerland.\n In this nationwide retrospective chart review study, data from paediatric patients who died in the years 2011 or 2012 due to a cardiac, neurological or oncological condition, or during the neonatal period were collected in 13 hospitals, two long-term institutions and 10 community-based healthcare service providers throughout Switzerland.\n Ninety-three (62%) of the 149 reviewed patients died in intensive care units, 78 (84%) of them following withdrawal of life-sustaining treatment. Reliance on invasive medical interventions was prevalent, and the use of medication was high, with a median count of 12 different drugs during the last week of life. Patients experienced an average number of 6.42 symptoms. The prevalence of various types of symptoms differed significantly among the four diagnostic groups. Overall, our study patients stayed in the hospital for a median of six days during their last four weeks of life. Seventy-two patients (48%) stayed at home for at least one day and only half of those received community-based healthcare.\n The study provides a wide-ranging overview of current end-of-life care practices in a real-life setting of different healthcare providers. The inclusion of patients with all major diagnoses leading to disease- and prematurity-related childhood deaths, as well as comparisons across the diagnostic groups, provides additional insight and understanding for healthcare professionals. The provision of specialised palliative and end-of-life care services in Switzerland, including the capacity of community healthcare services, need to be expanded to meet the specific needs of seriously ill children and their families.\n\nPlecko, Barbara\n\n\n"
},
{
"text": "\n4061\nAtypical fibrous histiocytoma of the skin: clinicopathologic analysis of 59 cases with evidence of infrequent metastasis.\n\nKaddu, S\n\nMcMenamin, ME\n\nFletcher, CD\n\nBeiträge in Fachzeitschriften\nISI:000173097600004\n11756767.0\n10.1097%2F00000478-200201000-00004\nNone\nAtypical fibrous histiocytoma is an uncommon, poorly documented variant of cutaneous fibrous histiocytoma. We studied 59 cases of atypical fibrous histiocytoma to better characterize the clinicopathologic spectrum. There were 33 males and 26 females (median age 38 years; range 5-79 years) with solitary lesions arising on lower (25 cases) and upper (17 cases) extremities, trunk (6 cases), head and neck (4 cases), and vulva (1 case); anatomic location was not stated in six cases. Lesions measured 0.4-8 cm in diameter (median 1.5 cm) and clinically were nodules (40 cases), polypoid tumors (18 cases), or a slightly elevated plaque (1 case). Histologically, the lesions were primarily dermal with superficial involvement of the subcutis in one third of the cases. Salient features included a proliferation of pleomorphic, plump, spindle, and/or polyhedral cells with mainly large, hyperchromatic, irregular, or bizarre nuclei, set in a background of classic features of fibrous histiocytoma, including spindle cell areas showing a storiform pattern and entrapped thickened, hyaline collagen bundles, especially at the periphery. Multinucleated giant cells, often with bizarre nuclei and foamy, sometimes hemosiderin-rich, cytoplasm were also variably present. The degree of pleomorphism varied from only focal and minimal (14 cases) or moderate (24 cases) to marked (21 cases). Mitotic activity was observed in 55 lesions, and the number of mitotic figures ranged from 1 to 15 per 10 high power fields. Atypical mitoses were noted in 20 lesions. Furthermore, some cases of atypical fibrous histiocytoma displayed other worrisome features less often observed in ordinary FH, including unusually large size (diameter >2 cm, 8 cases), involvement of the superficial subcutis (19 cases), and geographic necrosis (7 cases). Immunohistochemical studies performed in 42 cases showed only focal smooth muscle actin (10 cases) and CD34 (4 cases) positivity, whereas CD68, S-100 protein, desmin, pan-keratin, and epithelial membrane antigen were negative. Clinical follow-up data available in 21 patients (mean duration of follow-up 50.6 months, median 43 months) revealed local recurrences in three patients (one repeated); two patients developed distant metastases, one of whom died after 96 months. These two cases were not histologically distinct from the group as a whole. We conclude that atypical fibrous histiocytoma has a broader clinicopathologic spectrum than previously realized. Lesions with floridly atypical features represent potential pitfalls for overinterpretation as pleomorphic sarcoma, which would appear to be inappropriate in most cases. Provided that atypical fibrous histiocytoma is treated by complete excision, a benign outcome is to be expected in most cases. However, similar to the cellular and aneurysmal variants of fibrous histiocytoma, atypical fibrous histiocytoma shows a higher tendency to recur locally than ordinary fibrous histiocytoma and may rarely metastasize.\n\nKaddu, Steven\n\n\n"
},
{
"text": "\n168508\nNo Overt Clinical Immunodeficiency Despite Immune Biological Abnormalities in Patients With Constitutional Mismatch Repair Deficiency.\n\nTesch, VK\n\nIJspeert, H\n\nRaicht, A\n\nRueda, D\n\nDominguez-Pinilla, N\n\nAllende, LM\n\nColas, C\n\nRosenbaum, T\n\nIlencikova, D\n\nBaris, HN\n\nNathrath, MHM\n\nSuerink, M\n\nJanuszkiewicz-Lewandowska, D\n\nRagab, I\n\nAzizi, AA\n\nWenzel, SS\n\nZschocke, J\n\nSchwinger, W\n\nKloor, M\n\nBlattmann, C\n\nBrugieres, L\n\nvan der Burg, M\n\nWimmer, K\n\nSeidel, MG\n\nBeiträge in Fachzeitschriften\nISI:000436994400001\n30013564.0\n10.3389/fimmu.2018.01506\nPMC6036136\nImmunoglobulin class-switch recombination (CSR) and somatic hypermutations (SHMs) are prerequisites for antibody and immunoglobulin receptor maturation and adaptive immune diversity. The mismatch repair (MMR) machinery, consisting of homologs of MutSα, MutLα, and MutSβ (MSH2/MSH6, MLH1/PMS2, and MSH2/MSH3, respectively) and other proteins, is involved in CSR, primarily acting as a backup for nonhomologous end-joining repair of activation-induced cytidine deaminase-induced DNA mismatches and, furthermore, in addition to error-prone polymerases, in the repair of SHM-induced DNA breaks. A varying degree of antibody formation defect, from IgA or selective IgG subclass deficiency to common variable immunodeficiency and hyper-IgM syndrome, has been detected in a small number of patients with constitutional mismatch repair deficiency (CMMRD) due to biallelic loss-of-function mutations in one of the MMR genes (PMS2, MSH6, MLH1, or MSH2). To elucidate the clinical relevance of a presumed primary immunodeficiency (PID) in CMMRD, we systematically collected clinical history and laboratory data of a cohort of 15 consecutive, unrelated patients (10 not previously reported) with homozygous/compound heterozygous mutations in PMS2 (n = 8), MSH6 (n = 5), and MLH1 (n = 2), most of whom manifested with typical malignancies during childhood. Detailed descriptions of their genotypes, phenotypes, and family histories are provided. Importantly, none of the patients showed any clinical warning signs of PID (infections, immune dysregulation, inflammation, failure to thrive, etc.). Furthermore, we could not detect uniform or specific patterns of laboratory abnormalities. The concentration of IgM was increased in 3 out of 12, reduced in 3 out of 12, and normal in 6 out of 12 patients, while concentrations of IgG and IgG subclasses, except IgG4, and of IgA, and specific antibody formation were normal in most. Class-switched B memory cells were reduced in 5 out of 12 patients, and in 9 out of 12 also the CD38hiIgM- plasmablasts were reduced. Furthermore, results of next generation sequencing-based analyses of antigen-selected B-cell receptor rearrangements showed a significantly reduced frequency of SHM and an increased number of rearranged immunoglobulin heavy chain (IGH) transcripts that use IGHG3, IGHG1, and IGHA1 subclasses. T cell subsets and receptor repertoires were unaffected. Together, neither clinical nor routine immunological laboratory parameters were consistently suggestive of PID in these CMMRD patients, but previously shown abnormalities in SHM and rearranged heavy chain transcripts were confirmed.\n\nSchwinger, Wolfgang\n\nSeidel, Markus\n\nTesch, Victoria Katharina\n\n\n"
},
{
"text": "\n177429\nA biomechanical comparison between human calvarial bone and a skull simulant considering the role of attached periosteum and dura mater.\n\nOndruschka, B\n\nLee, JHC\n\nScholze, M\n\nZwirner, J\n\nTong, D\n\nWaddell, JN\n\nHammer, N\n\nBeiträge in Fachzeitschriften\nISI:000482517700036\n31203433.0\n10.1007/s00414-019-02102-4\nNone\nCurrent forensic analysis of blunt force trauma relies on the use of cadaveric or animal tissues, posing ethical and reproducibility concerns. Artificial substitutes may help overcome such issues. However, existing substitutes exhibit poor anatomic and mechanical biofidelity, especially in the choice of skull simulant material. Progress has been made in identifying materials that have similar mechanical properties to the human skull bone, with the potential to behave similarly in mechanical loading.\n To compare the biomechanical properties of the human calvarial bone with an epoxy resin-based simulant material. Data collected was also used to analyse the effect of periosteal attachment on the mechanical properties of skull bone compared with that of the counterpart samples.\n Fifty-six human skull bone specimens were prepared from two cadaveric heads. Half of these specimens were removed of periosteum and dura mater as the PR (periosteum removed) group, whereas periosteum was left attached in the PA (periosteum attached) group. Duplicates of the bone specimens were fabricated out of an epoxy resin and paired in corresponding PR and PA groups. The specimens were loaded under three-point bending tests until fracture with image-based deformation detection.\n Comparison of the epoxy resin and skull specimens yielded similarity for both the PR and PA groups, being closer to the PA group (bending modulus resin PR 2665 MPa vs. skull PR 1979 MPa, resin PA 3165 MPa vs. skull PA 3330 MPa; maximum force resin PR 574 N vs. skull PR 728 N, resin PA 580 N vs. skull PA 1034 N; strain at maximum force resin PR 2.7% vs. skull PR 5.1%, resin PA 2.3% vs. skull PA 3.5%, deflection at maximum force resin PR 0.5 mm vs. skull PR 0.8 mm, resin PA 0.5 mm vs. skull PA 1.0 mm). Bending strength was significantly lower in the resin groups (resin PR 43 MPa vs. skull PR 55 MPa, resin PA 44 MPa vs. skull PA 75 MPa). Moreover, the correlations of the mechanical data exhibited closer accordance of the PR group with the epoxy resin compared with the PA group with the epoxy resin.\n The load-deformation properties of the epoxy resin samples assessed in this study fell within a closer range to the skull specimens with PR than with PA. Moreover, the values obtained for the resin fall within the reference range for skull tissues in the literature suggesting that the proposed epoxy resin may provide a usable artificial substitute for PA but does not totally represent the human skull in its complex anatomical structure.\n\nHammer, Niels\n\n\n"
},
{
"text": "\n179138\nMan against machine reloaded: performance of a market-approved convolutional neural network in classifying a broad spectrum of skin lesions in comparison with 96 dermatologists working under less artificial conditions.\n\nHaenssle, HA\n\nFink, C\n\nToberer, F\n\nWinkler, J\n\nStolz, W\n\nDeinlein, T\n\nHofmann-Wellenhof, R\n\nLallas, A\n\nEmmert, S\n\nBuhl, T\n\nZutt, M\n\nBlum, A\n\nAbassi, MS\n\nThomas, L\n\nTromme, I\n\nTschandl, P\n\nEnk, A\n\nRosenberger, A\n\nReader Study Level I and Level II Groups\n\nBeiträge in Fachzeitschriften\nISI:000516712000020\n31912788.0\n10.1016/j.annonc.2019.10.013\nNone\nConvolutional neural networks (CNNs) efficiently differentiate skin lesions by image analysis. Studies comparing a market-approved CNN in a broad range of diagnoses to dermatologists working under less artificial conditions are lacking.\n One hundred cases of pigmented/non-pigmented skin cancers and benign lesions were used for a two-level reader study in 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Additionally, dermoscopic images were classified by a CNN approved for the European market as a medical device (Moleanalyzer Pro, FotoFinder Systems, Bad Birnbach, Germany). Primary endpoints were the sensitivity and specificity of the CNN's dichotomous classification in comparison with the dermatologists' management decisions. Secondary endpoints included the dermatologists' diagnostic decisions, their performance according to their level of experience, and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC).\n The CNN revealed a sensitivity, specificity, and ROC AUC with corresponding 95% confidence intervals (CI) of 95.0% (95% CI 83.5% to 98.6%), 76.7% (95% CI 64.6% to 85.6%), and 0.918 (95% CI 0.866-0.970), respectively. In level I, the dermatologists' management decisions showed a mean sensitivity and specificity of 89.0% (95% CI 87.4% to 90.6%) and 80.7% (95% CI 78.8% to 82.6%). With level II information, the sensitivity significantly improved to 94.1% (95% CI 93.1% to 95.1%; P < 0.001), while the specificity remained unchanged at 80.4% (95% CI 78.4% to 82.4%; P = 0.97). When fixing the CNN's specificity at the mean specificity of the dermatologists' management decision in level II (80.4%), the CNN's sensitivity was almost equal to that of human raters, at 95% (95% CI 83.5% to 98.6%) versus 94.1% (95% CI 93.1% to 95.1%); P = 0.1. In contrast, dermatologists were outperformed by the CNN in their level I management decisions and level I and II diagnostic decisions. More experienced dermatologists frequently surpassed the CNN's performance.\n Under less artificial conditions and in a broader spectrum of diagnoses, the CNN and most dermatologists performed on the same level. Dermatologists are trained to integrate information from a range of sources rendering comparative studies that are solely based on one single case image inadequate.\n Copyright © 2019 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.\n\nDeinlein, Teresa Maria\n\nHofmann-Wellenhof, Rainer\n\n\n"
},
{
"text": "\n179420\nFailure properties and microstructure of healthy and aneurysmatic human thoracic aortas subjected to uniaxial extension with a focus on the media.\n\nSherifova, S\n\nSommer, G\n\nViertler, C\n\nRegitnig, P\n\nCaranasos, T\n\nSmith, MA\n\nGriffith, BE\n\nOgden, RW\n\nHolzapfel, GA\n\nBeiträge in Fachzeitschriften\nISI:000505271200036\n31465883.0\n10.1016/j.actbio.2019.08.038\nPMC6851440\nCurrent clinical practice for aneurysmatic interventions is often based on the maximum diameter of the vessel and/or on the growth rate, although rupture can occur at any diameter and growth rate, leading to fatality. For 27 medial samples obtained from 12 non-aneurysmatic (control) and 9 aneurysmatic human descending thoracic aortas we examined: the mechanical responses up to rupture using uniaxial extension tests of circumferential and longitudinal specimens; the structure of these tissues using second-harmonic imaging and histology, in particular, the content proportions of collagen, elastic fibers and smooth muscle cells in the media. It was found that the mean failure stresses were higher in the circumferential directions (Control-C 1474kPa; Aneurysmatic-C 1446kPa), than in the longitudinal directions (Aneurysmatic-L 735kPa; Control-L 579kPa). This trend was the opposite to that observed for the mean collagen fiber directions measured from the loading axis (Control-L > Aneurysmatic-L > Aneurysmatic-C > Control-C), thus suggesting that the trend in the failure stress can in part be attributed to the collagen architecture. The difference in the mean values of the out-of-plane dispersion in the radial/longitudinal plane between the control and aneurysmatic groups was significant. The difference in the mean values of the mean fiber angle from the circumferential direction was also significantly different between the two groups. Most specimens showed delamination zones near the ruptured region in addition to ruptured collagen and elastic fibers. This study provides a basis for further studies on the microstructure and the uniaxial failure properties of (aneurysmatic) arterial walls towards realistic modeling and prediction of tissue failure. STATEMENT OF SIGNIFICANCE: A data set relating uniaxial failure properties to the microstructure of non-aneurysmatic and aneurysmatic human thoracic aortic medias under uniaxial extension tests is presented for the first time. It was found that the mean failure stresses were higher in the circumferential directions, than in the longitudinal directions. The general trend for the failure stresses was Control-C > Aneurysmatic-C > Aneurysmatic-L > Control-L, which was the opposite of that observed for the mean collagen fiber direction relative to the loading axis (Control-L > Aneurysmatic-L > Aneurysmatic-C > Control-C) suggesting that the trend in the failure stress can in part be attributed to the collagen architecture. This study provides a first step towards more realistic modeling and prediction of tissue failure.\n Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.\n\nRegitnig, Peter\n\nViertler, Christian\n\n\n"
},
{
"text": "\n64357\nTemporal changes in the messenger RNA levels of cellular immediate early genes and neurotransmitter/receptor genes in the rat neostriatum and substantia nigra after acute treatment with eticlopride, a dopamine D2 receptor antagonist.\n\nSirinathsinghji, DJ\n\nSchuligoi, R\n\nHeavens, RP\n\nDixon, A\n\nIversen, SD\n\nHill, RG\n\nBeiträge in Fachzeitschriften\nISI:A1994PJ33100011\n7830888.0\n10.1016/0306-4522(94)90376-X\nNone\nThe cellular immediate early genes are involved in the transcriptional events associated with the dopaminergic regulation of neurotransmitter expression within neurons of the neostriatum. To characterize these events in detail, quantitative in situ hybridization histochemistry was used to assess the temporal effects of acute dopamine receptor blockade with eticlopride, a dopamine D2 receptor antagonist, on the messenger RNA expression of the immediate early genes and neurotransmitters/receptors in the caudate-putamen and ventral tegmental area/substantia nigra pars compacta of the rat. Groups of rats were injected with a single dose of either isotonic saline or eticlopride (0.5 mg/kg i.p.) and killed at various time intervals ranging from 5 min to 24 h and frozen brain sections processed by in situ hybridization histochemistry. Using computerized image analysis, the changes in messenger RNA expression for c-fos, c-jun, jun B, jun D, nerve growth factor I-A and nerve growth factor I-B and for neurotensin, glutamate decarboxylase, proenkephalin, the dopamine D1 receptor and the short and long isoforms of the D2 receptor were examined in the caudate-putamen. In the ventral tegmental area and substantia nigra pars compacta, the messenger RNA expression of the above early response genes and that for neurotensin, tyrosine hydroxylase, cholecystokinin and the D2 receptor isoforms were also examined. In the neostriatum, eticlopride caused a rapid increase in c-fos messenger RNA with significantly increased levels at 10 min (P < 0.01). The levels peaked at 30 min and thereafter declined to control levels. A similar profile was observed for jun B messenger RNA, although levels were still significantly (P < 0.01) elevated at 1 h and declined to basal levels thereafter. No significant changes were observed for c-jun, jun D, nerve growth factor I-A and nerve growth factor I-B messenger RNAs. In the dorsolateral neostriatum, there was an increase in proneurotensin messenger RNA 10 min after eticlopride, this increase becoming significant (P < 0.01) at 60 min. Levels were maximal at 2-6 h and decreased after 12 h to basal levels. There were small increases in proenkephalin messenger RNA, but these were not significant (P < 0.05) until 6 h after the injection. Eticlopride did not have any significant effects on the messenger RNA levels for glutamate decarboxylase, the D1 receptor and the short and long isoforms of the D2 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)\n\nSchuligoi, Rufina\n\n\n"
}
]
}