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"text": "\n144368\nHow to regulate the acute physiological response to "aerobic" high-intensity interval exercise.\n\nTschakert, G\n\nKroepfl, J\n\nMueller, A\n\nMoser, O\n\nGroeschl, W\n\nHofmann, P\n\nBeiträge in Fachzeitschriften\nISI:000350048900005\n25729286.0\nNone\nPMC4306779\nThe acute physiological processes during "aerobic" high-intensity interval exercise (HIIE) and their regulation are inadequately studied. The main goal of this study was to investigate the acute metabolic and cardiorespiratory response to long and short HIIE compared to continuous exercise (CE) as well as its regulation and predictability. Six healthy well-trained sport students (5 males, 1 female; age: 25.7 ± 3.1 years; height: 1.80 ± 0.04 m; weight: 76.7 ± 6.4 kg; VO2max: 4.33 ± 0.7 l·min(-1)) performed a maximal incremental exercise test (IET) and subsequently three different exercise sessions matched for mean load (Pmean) and exercise duration (28 min): 1) long HIIE with submaximal peak workloads (Ppeak = power output at 95 % of maximum heart rate), peak workload durations (tpeak) of 4 min, and recovery durations (trec) of 3 min, 2) short HIIE with Ppeak according to the maximum power output (Pmax) from IET, tpeak of 20 s, and individually calculated trec (26.7 ± 13.4 s), and 3) CE with a target workload (Ptarget) equating to Pmean of HIIE. In short HIIE, mean lactate (Lamean) (5.22 ± 1.41 mmol·l(-1)), peak La (7.14 ± 2.48 mmol·l(-1)), and peak heart rate (HRpeak) (181.00 ± 6.66 b·min(-1)) were significantly lower compared to long HIIE (Lamean: 9.83 ± 2.78 mmol·l(-1); Lapeak: 12.37 ± 4.17 mmol·l(-1), HRpeak: 187.67 ± 5.72 b·min(-1)). No significant differences in any parameters were found between short HIIE and CE despite considerably higher peak workloads in short HIIE. The acute metabolic and peak cardiorespiratory demand during "aerobic" short HIIE was significantly lower compared to long HIIE and regulable via Pmean. Consequently, short HIIE allows a consciously aimed triggering of specific and desired or required acute physiological responses. Key pointsHigh-intensity interval exercise (HIIE) with short peak workload durations (tpeak) induce a lower acute metabolic and peak cardiorespiratory response compared to intervals with long tpeak despite higher peak workload intensities (Ppeak) and identical mean load (Pmean).Short HIIE response is the same as in continuous exercise (CE) matched for Pmean.It is possible to regulate and predict the acute physiological response by means of Pmean for short HIIE but not for long HIIE.The use of fixed percentages of maximal heart rate (HRmax) for exercise intensity prescription yields heterogeneous exercise stimuli across subjects. Therefore, objective individual markers such as the first and the second lactate turn point are recommend prescribing exercise intensity not only for continuous but also for intermittent exercise.\n\n\n"
},
{
"text": "\n154730\nGenome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.\n\nWalford, GA\n\nGustafsson, S\n\nRybin, D\n\nStančáková, A\n\nChen, H\n\nLiu, CT\n\nHong, J\n\nJensen, RA\n\nRice, K\n\nMorris, AP\n\nMägi, R\n\nTönjes, A\n\nProkopenko, I\n\nKleber, ME\n\nDelgado, G\n\nSilbernagel, G\n\nJackson, AU\n\nAppel, EV\n\nGrarup, N\n\nLewis, JP\n\nMontasser, ME\n\nLandenvall, C\n\nStaiger, H\n\nLuan, J\n\nFrayling, TM\n\nWeedon, MN\n\nXie, W\n\nMorcillo, S\n\nMartínez-Larrad, MT\n\nBiggs, ML\n\nChen, YD\n\nCorbaton-Anchuelo, A\n\nFærch, K\n\nGómez-Zumaquero, JM\n\nGoodarzi, MO\n\nKizer, JR\n\nKoistinen, HA\n\nLeong, A\n\nLind, L\n\nLindgren, C\n\nMachicao, F\n\nManning, AK\n\nMartín-Núñez, GM\n\nRojo-Martínez, G\n\nRotter, JI\n\nSiscovick, DS\n\nZmuda, JM\n\nZhang, Z\n\nSerrano-Rios, M\n\nSmith, U\n\nSoriguer, F\n\nHansen, T\n\nJørgensen, TJ\n\nLinnenberg, A\n\nPedersen, O\n\nWalker, M\n\nLangenberg, C\n\nScott, RA\n\nWareham, NJ\n\nFritsche, A\n\nHäring, HU\n\nStefan, N\n\nGroop, L\n\nO'Connell, JR\n\nBoehnke, M\n\nBergman, RN\n\nCollins, FS\n\nMohlke, KL\n\nTuomilehto, J\n\nMärz, W\n\nKovacs, P\n\nStumvoll, M\n\nPsaty, BM\n\nKuusisto, J\n\nLaakso, M\n\nMeigs, JB\n\nDupuis, J\n\nIngelsson, E\n\nFlorez, JC\n\nBeiträge in Fachzeitschriften\nISI:000388372900037\n27416945.0\n10.2337/db16-0199\nPMC5033262\nGenome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16, 53 individuals, and replication was attempted for the 23 most significant novel loci in 13, 54 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.\n © 2016 by the American Diabetes Association.\n\nMärz, Winfried\n\nSilbernagel, Günther\n\n\n"
},
{
"text": "\n164463\nCost-utility analysis of fracture risk assessment using microRNAs compared with standard tools and no monitoring in the Austrian female population.\n\nWalter, E\n\nDellago, H\n\nGrillari, J\n\nDimai, HP\n\nHackl, M\n\nBeiträge in Fachzeitschriften\nISI:000425579300007\n29269173.0\n10.1016/j.bone.2017.12.017\nNone\nOsteoporosis poses an immense burden to the society in terms of morbidity, mortality and financial cost. To reduce this burden, it is essential to accurately assess the individual patient's fracture risk and, where indicated, to initiate appropriate treatment that reduces fracture probability. Current screening and monitoring approaches include utilization of FRAX®, a web-based country-specific fracture risk assessment tool, and bone mineral density measurement by Dual Energy X-ray Absorptiometry (DXA). Recently, microRNAs have been recognized as important regulators of bone physiology and potential biomarkers for fracture risk assessment and monitoring. A fracture risk assessment tool based on microRNAs (osteomiR™ test) is currently being developed. The aim of this study was to estimate the cost-effectiveness of fracture risk screening, monitoring, and resulting treatment decisions for the Austrian female population using the osteomiR™ test compared with DXA, with FRAX®, or with no screening/monitoring.\n A cost-utility-model was developed to simulate long-term consequences of Austrian women from age 50 over lifetime or death with respect to osteoporosis. Markov-modelling techniques were used to calculate health state transitions of fracture incidence according to risk groups (high, intermediate, low). High-risk patients receive medical treatment. Probabilities were derived via systematic-literature-review; direct costs (2015, €) from published sources from the payer's perspective. Results evaluate the incremental cost-effectiveness ratios (ICER) for osteomiR™ against the comparators, gains or losses of fractures, life years (LYs), quality-adjusted life years (QALYs), and direct costs. QALYs, life years (LYs) and costs were discounted (3% p.a).\n Fracture risk assessment and monitoring using the osteomiR™ test reduces fracture incidence compared with no monitoring, DXA alone, or FRAX® alone. In the per-patient analysis, the ICER/QALY of osteomiR™ vs. no-monitoring was 13, 03 €, vs. FRAX® 37, 13 €, and vs. DXA -19, 05 €, indicating that costs can be saved while gaining QALYs. Considering the total cohort over lifetime, the osteomiR™ test can avoid 57, 19 fractures compared with DXA, 31, 85 fractures compared with FRAX® and 133, 94 fractures compared with no monitoring. Sensitivity analysis confirmed the robustness of these findings.\n Fracture risk assessment and monitoring using the osteomiR™ test dominates DXA-strategy and constitutes a cost-effective alternative to FRAX®, and no-monitoring, respectively.\n Copyright © 2017 Elsevier Inc. All rights reserved.\n\nDimai, Hans\n\n\n"
},
{
"text": "\n4789\nEarly fluoxetine treatment of post-stroke depression--a three-month double-blind placebo-controlled study with an open-label long-term follow up.\n\nFruehwald, S\n\nGatterbauer, E\n\nRehak, P\n\nBaumhackl, U\n\nBeiträge in Fachzeitschriften\nISI:000182207900013\n12638027.0\n10.1007/s00415-003-1014-3\nNone\nOBJECTIVE: Poststroke depression is a frequent psychiatric complication after stroke that may have strong negative impact on rehabilitation therapy and functional recovery. This study was conducted to show the efficacy and safety of early treatment with the selective serotonin reuptake inhibitor fluoxetine in post-stroke depressed patients. METHODS: This double-blind, randomized placebo-controlled study was of patients within two weeks after stroke. Moderate to severe depressed patients (determined by Hamilton Depression Scale (HDS) > 15, the Beck Depression Inventory (BDI) and the Clinical Global Impression (CGI) Scale) were randomized to receive either 20 mg/d fluoxetine or placebo for 3 months. Beside the psychiatric assessment, patients were evaluated by use of the Scandinavian Stroke Scale (SSS), the Mini-Mental-State-Examination (MMSE) and the Barthel-Index (BI). An open-label long-term follow up was done 18 months after the initial assessment. RESULTS: 54 depressed patients of an inpatient population of 242 consecutive stroke patients aged 25 to 85 years entered the trial within the first two weeks post-stroke. 50 patients completed the trial per-protocol. The initial severity of depression was comparable in the two groups (mean baseline HDS score 32.8 in the fluoxetine vs. 30.3 in the placebo group), as were neurological symptom severity and demographic parameters. Significant improvement was seen in both groups within 4 weeks of treatment, whereas no advantages of fluoxetine could be observed at this time. This indicates a high degree of spontaneous recovery during early rehabilitation therapy. BDI scores of patients treated with fluoxetine further decreased until the follow-up at 12 weeks, whereas the scores increased again in the placebo group. This depressive relapse of the placebo patients after the end of most rehabilitation efforts was evident at a long-term follow-up 18 months after inclusion, when patients who had been treated with fluoxetine were significantly less depressed. No side effects of fluoxetine treatment were detected. CONCLUSIONS: The advantages of fluoxetine were obvious at the follow-up 18 months after inclusion, but could not be demonstrated within the first three months of controlled treatment. The multitude of therapeutic efforts that take place in the early phase of rehabilitation might have facilitated spontaneous recovery from depression and might have hindered benefits of antidepressant treatment to become obvious. Fluoxetine treatment was well tolerated and safe.\n\n\n"
},
{
"text": "\n88016\nRhabdomyosarcomatous Differentiation in Gastrointestinal Stromal Tumors After Tyrosine Kinase Inhibitor Therapy A Novel Form of Tumor Progression\n\nLiegl, B\n\nHornick, JL\n\nAntonescu, CR\n\nCorless, CL\n\nFletcher, CDM\n\nBeiträge in Fachzeitschriften\nISI:000262920400007\nNone\n10.1097/PAS.0b013e31817ec2e6\nNone\nApproximately 80% of advanced metastatic gastrointestinal stromal tumors (GISTs) respond to treatment with the tyrosine kinase inhibitor (TKI) imatinib mesylate. However, the majority of patients suffer disease progression at a median of 2 years due to drug resistance. In general, progressing GISTs retain their typical morphology. Herein, we report 5 cases of progressing metastatic GIST with heterologous rhabdomyoblastic differentiation after TKI treatment. Histologic, immunohistochemical, and mutational analyses were performed on histologically classic GISTs and components with rhabdomyoblastic differentiation. There were 3 men and 2 women (ranging from 35 to 66y of age). Three tumors were localized at presentation (2 stomach and I small bowel) and 2 presented with metastases. All localized primary tumors were high risk. Two tumors showed spindle cell morphology and 3 were epithelioid, including I with marked pleomorphism. After resection of the 3 localized primary tumors, intra-abdominal (2 patients) and liver (I patient) metastases developed. All patients were treated with imatinib and showed partial clinical responses (4 patient) or stable disease (I patient). Four patients subsequently progressed; 2 patients were treated with sunitinib after progression with minor responses. Four patients underwent Surgical debulking. At last follow-up (range: 20 to 87 mo), 2 patients died of disease, 2 were alive with metastatic disease resistant to TKIs, and I was alive without evidence of disease. In all cases, rhabdomyoblastic differentiation was identified adjacent to areas with classic GIST morphology in at least 1 metastatic site; in 1 case, the primary tumor (after treatment with TKIs) showed heterologous differentiation. The rhabdomyoblastic components showed strong and diffuse positivity for desmin and expressed myogenin, whereas KIT was negative in the rhabdomyoblastic component in all cases. Primary KIT mutations were. detected in both the conventional GIST and rhabdomyoblastic components from all patients: KIT exon 11 mutations in 4 cases and a platelet-derived growth factor receptor alpha gene exon IS deletion in I case. No secondary mutations of the type associated with TKI resistance were identified in the rhabdomyoblastic areas. This is the first report of rhabdomyoblastic differentiation occurring in GISTs that progressed on TKI therapy. It is associated with loss of KIT expression, but retention of the receptor tyrosine kinase mutation of the precursor GIST. The rhabdomyoblastic differentiation can represent a diagnostic pitfall. The molecular mechanisms for this form of TKI-resistant clonal evolution remain to be determined.\n\nLiegl-Atzwanger, Bernadette\n\n\n"
},
{
"text": "\n123999\nChild abuse. Social demographics, patterns, and medical interventions - a retrospective analysis of 59 cases.\n\nLandgraf, M\n\nZahner, L\n\nNickel, P\n\nTill, H\n\nKeller, A\n\nGeyer, C\n\nSchwanitz, N\n\nGausche, R\n\nSchmutzer, G\n\nBrahler, E\n\nKiess, W\n\n\n\nBeiträge in Fachzeitschriften\nISI:000274333600010\nNone\n10.1007/s00112-009-2129-0\nNone\nChild abuse leads to acute and long-term physical and emotional harm to children and adolescents. Medical personnel have a special challenge and responsibility regarding early recognition, protection of the child, and support for the whole family. The aims of this study were to analyse the frequency and types of child abuse as well as the social backgrounds of the affected families and to evaluate the clinical management of the children treated at the Children's Centre at the University of Leipzig. Data were analysed for all 59 patients admitted to the Children's Centre at the University of Leipzig with a confirmed diagnosis of child abuse between January 2001 and June 2007. For the retrospective analysis, a data collection questionnaire with 91 items was developed, containing the main categories of sociodemographics, medical findings, and clinical case management. The data were evaluated using descriptive statistics (Excel and SPSS). The treated inpatients included 36 cases of physical child abuse, 11 of neglect, six of sexual abuse, five of combined physical abuse and neglect, and one of Munchhausen-by-proxy syndrome. The gender distribution was almost equal, but the age varied significantly (2.5 weeks to 15 10/12 years). Seventeen percent of the abused children showed symptoms of a developmental disorder. In 54 of the 59 cases, no routine medical checkups were documented. Seventeen percent of the parents had alcohol and drug problems, and 53% of the mothers and 10% of the fathers were single parents. Seven percent of the fathers and mothers and 5% of the siblings of the abused children were chronically ill. In the 59 children and adolescents, 108 consultations were performed at the Children's Centre. In only 20% was an interdisciplinary case conference documented. Child abuse is a problem of society and health care policy. The study at Leipzig showed that parental drug abuse, chronic disease in the family, and single parentage are social risk factors for child abuse. As a risk factor on the child's side, developmental disorders were identified. Within the distribution of the types of child abuse, child neglect is certainly underrepresented. Data acquisition and documentation concerning the social history, the psychological conspicuity of children and their parents, and the concerted assessments of the professionals involved in patient care must be strongly improved.\n\nTill, Holger\n\n\n"
},
{
"text": "\n159308\nMore than 5000 patients with metastatic melanoma in Europe per year do not have access to recommended first-line innovative treatments.\n\nKandolf Sekulovic, L\n\nPeris, K\n\nHauschild, A\n\nStratigos, A\n\nGrob, JJ\n\nNathan, P\n\nDummer, R\n\nForsea, AM\n\nHoeller, C\n\nGogas, H\n\nDemidov, L\n\nLebbe, C\n\nBlank, C\n\nOlah, J\n\nBastholt, L\n\nHerceg, D\n\nNeyns, B\n\nVieira, R\n\nHansson, J\n\nRutkowski, P\n\nKrajsova, I\n\nBylaite-Bucinskiene, M\n\nZalaudek, I\n\nMaric-Brozic, J\n\nBabovic, N\n\nBanjin, M\n\nPutnik, K\n\nWeinlich, G\n\nTodorovic, V\n\nKirov, K\n\nOcvirk, J\n\nZhukavets, A\n\nKukushkina, M\n\nDe La Cruz Merino, L\n\nYmeri, A\n\nRisteski, M\n\nGarbe, C\n\nBeiträge in Fachzeitschriften\nISI:000399856400040\n28264791.0\n10.1016/j.ejca.2017.01.012\nNone\nDespite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF).\n Web-based online survey was conducted in 30 European countries with questions about the treatment schedules from 1st May 2015 to 1st May 2016: number of metastatic melanoma patients, registration and reimbursement of innovative medicines (updated data, as of 1st October 2016), percentage of patients treated and availability of clinical studies and compassionate-use programmes.\n The recommended BRAF inhibitor (BRAFi) + MEK inhibitor (MEKi) combination was both registered and fully reimbursed in 9/30 (30%) countries, and in 13/30 (43%) (all from Eastern Europe) not reimbursed. First-line immunotherapy with anti-PD1 antibodies was registered and fully reimbursed in 14/30 (47%) countries, while in 13/30 (43%) (all from Eastern Europe) not reimbursed. It was estimated that in Europe 19, 00 patients with metastatic melanoma are treated, and 5238 (27%) do not have access to recommended first-line therapy. Significant correlation was found between human development index (HDI, UNDP report 2015), (r = 0.662; p < 0.001), health expenditure per capita (r = 0.695; p < 0.001) and the Mackenbach score of health policy performance (r = 0.765; p < 0.001) with the percentage of patients treated with innovative medicines and a number of reimbursed medicines.\n Great discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma industry.\n Copyright © 2017 Elsevier Ltd. All rights reserved.\n\nZalaudek, Iris\n\n\n"
},
{
"text": "\n176304\nElderly versus younger patients with hereditary angioedema type I/II: patient characteristics and safety analysis from the Icatibant Outcome Survey.\n\nBygum, A\n\nCaballero, T\n\nGrumach, AS\n\nLonghurst, HJ\n\nBouillet, L\n\nAberer, W\n\nZanichelli, A\n\nBotha, J\n\nAndresen, I\n\nMaurer, M\n\nIOS Study Group\n\nBeiträge in Fachzeitschriften\nISI:000476515800001\n31360439.0\n10.1186/s13601-019-0272-9\nPMC6639901\nHereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by recurrent swelling in subcutaneous or submucosal tissues. Symptoms often begin by age 5-11 years and worsen during puberty, but attacks can occur at any age and recur throughout life. Disease course in elderly patients is rarely reported.\n The Icatibant Outcome Survey (IOS) is an observational study evaluating the safety, tolerability, and efficacy of icatibant. We conducted descriptive analyses in younger (age < 65 years) versus elderly patients (age ≥ 65 years). Here, we report patient characteristics and safety-related findings.\n As of February 2018, 872 patients with C1-INH-HAE type I/II were enrolled, of whom 100 (11.5%) were ≥ 65 years old. Significant differences between elderly versus younger patients, respectively, were noted for median age at symptom onset (17.0 vs 12.0 years), age at diagnosis (41.0 vs 19.4 years), and delay between symptom onset and diagnosis (23.9 vs 4.8 years) (P ≤ 0.0001 for all). Median age at diagnosis was significantly higher in elderly patients regardless of family history (P < 0.0001). Throughout the study, icatibant was used to treat 6798 attacks in 574 patients, with 63 elderly patients reporting 715 (10.5%) of the icatibant-treated attacks. No serious adverse events (SAEs) in elderly patients were judged to be possibly related to icatibant, whereas two younger patients reported three possibly related SAEs. Excluding off-label use and pregnancy (evaluated for regulatory purposes), the percentage of patients with at least one possibly/probably related AE was similar for elderly (2.0%) versus younger patients (2.7%). No deaths linked to icatibant treatment were identified. All related events in elderly patients were attributed to general disorders/administration site conditions, whereas related events in younger patients occurred across various system organ class designations.\n Elderly patients with C1-INH-HAE were significantly older at diagnosis and had greater delay in diagnosis than younger patients. Elderly patients contributed to approximately 10% of the icatibant-treated attacks. Our analysis found similar AE rates (overall and possibly/probably related) in icatibant-treated elderly versus younger patients, despite the fact that elderly patients had significantly more comorbidities and were receiving a greater number of concomitant medications. Our analysis did not identify any new or unexpected safety concerns.\n\nAberer, Werner\n\n\n"
},
{
"text": "\n177925\nQuantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial.\n\nCheng, B\n\nBoutitie, F\n\nNickel, A\n\nWouters, A\n\nCho, TH\n\nEbinger, M\n\nEndres, M\n\nFiebach, JB\n\nFiehler, J\n\nGalinovic, I\n\nPuig, J\n\nThijs, V\n\nLemmens, R\n\nMuir, KW\n\nNighoghossian, N\n\nPedraza, S\n\nSimonsen, CZ\n\nGerloff, C\n\nThomalla, G\n\nBeiträge in Fachzeitschriften\nISI:000504225600044\n31662118.0\n10.1161/STROKEAHA.119.027390\nNone\nBackground and Purpose- Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods- FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results- FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions- In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.\n\nFandler-Höfler, Simon\n\nFazekas, Franz\n\nGattringer, Thomas\n\nPichler, Alexander\n\n\n"
},
{
"text": "\n181339\nValidation of the all-comers design: Results of the TARGET-AC substudy.\n\nToth, GG\n\nLansky, A\n\nBaumbach, A\n\nKelbaek, H\n\nvan Royen, N\n\nHolmvang, L\n\nJanssens, L\n\nBrugaletta, S\n\nBarbato, E\n\nMaillard, L\n\nKiemeneij, F\n\nNailer, CK\n\nPucher, F\n\nLaursen, PN\n\nAmeloot, K\n\nRobles, C\n\nMilkas, A\n\nSevilla, J\n\nJensen, C\n\nWijns, W\n\nBeiträge in Fachzeitschriften\nISI:000512980500018\n31924299.0\n10.1016/j.ahj.2019.10.019\nNone\nResults of clinical trials are often criticized by low inclusion rate and potential sampling bias in patient recruitment. The aim of this validation registry is to evaluate how far an all-comers design in the context of clinical research can ensure the representation of the true all-comers population.\n This validation registry is a prospective international multicentre registry, conducted at 10 out of the total 21 centers, participating in TARGET-AC (registered under NCT02520180). During a predefined four-week period data were recorded prospectively on all PCIs performed in the participating centers, whether or not patients were enrolled in TARGET-AC. Data were collected on patient demographics, angiographic lesion- and procedural characteristics. For patients who were not enrolled in the study, operators were asked to declare the reason for not enrolling the patient, using a single-choice questionnaire.\n A total of 131 patients were enrolled in the TARGET-AC study during the investigated period (ER group), standing as 20% (range 4% and 54%) of all eligible cases per protocol. In the ER group more patients presented with stable angina (61% vs. 43%, respectively; P < .001). Whereas ST-elevation infarction was less common (5% vs. 26%, respectively; P < .001), there was no difference in non-ST elevation acute coronary syndrome (32% vs. 27%, respectively; P = .248). Risk factors and comorbidities did not show any difference between the ER and the non-enrolled (NER) groups, except for greater rate of significant valvular disease in the NER group (12% vs 19%, respectively; P = .037). The NER group presented more thrombotic stenoses than the ER group (20% vs 12%, respectively; P = .040). No difference was found in any other investigated angiographic parameters, like target vessels, bifurcation lesion, severe calcification or chronic total occlusions. Admission during regular working hours and availability of study nurse were associated with markedly higher recruitment rate.\n Results suggest that TARGET AC was outbalanced for stable patients over primary PCIs as compared to real world. However in terms of risk factors and comorbidities the trial managed to represent the collective of real world clinical practice. Fairly representative cases were included at an average inclusion-to-eligible rate of 20%.\n Copyright © 2019 Elsevier Inc. All rights reserved.\n\nToth-Gayor, Gabor\n\n\n"
},
{
"text": "\n153028\nPolymyalgia Rheumatica and Giant Cell Arteritis: A Systematic Review.\n\nButtgereit, F\n\nDejaco, C\n\nMatteson, EL\n\nDasgupta, B\n\nBeiträge in Fachzeitschriften\nISI:000377656900022\n27299619.0\n10.1001/jama.2016.5444\nNone\nPolymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are related inflammatory disorders occurring in persons aged 50 years and older. Diagnostic and therapeutic approaches are heterogeneous in clinical practice.\n To summarize current evidence regarding optimal methods for diagnosing and treating PMR and GCA.\n MEDLINE, EMBASE, and Cochrane databases were searched from their inception dates to March 30, 2016. Screening by 2 authors resulted in 6626 abstracts, of which 50 articles met the inclusion criteria. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool or American College of Cardiology Foundation/American Heart Association methodology.\n Twenty randomized clinical trials for therapy (n = 1016 participants) and 30 imaging studies for diagnosis and/or assessing response to therapy (n = 2080 participants) were included. The diagnosis of PMR is based on clinical features such as new-onset bilateral shoulder pain, including subdeltoid bursitis, muscle or joint stiffness, and functional impairment. Headache and visual disturbances including loss of vision are characteristic of GCA. Constitutional symptoms and elevated inflammatory markers (>90%) are common in both diseases. Ultrasound imaging enables detection of bilateral subdeltoid bursitis in 69% of PMR patients. In GCA, temporal artery biopsy remains the standard for definitive diagnosis. Ultrasound and magnetic resonance imaging (MRI) of large vessels revealing inflammation-induced wall thickening support the diagnosis of GCA (specificity 78%-100% for ultrasound and 73%-97% for MRI). Glucocorticoids remain the primary treatment, but the optimal initial dose and tapering treatment regimens are unknown. According to consensus-based recommendations, initial therapy for PMR is prednisone, 12.5 to 25 mg/day or equivalent, and 40 to 60 mg/day for GCA, followed by individualized tapering regimens in both diseases. Adjunctive methotrexate may reduce cumulative glucocorticoid dosage by 20% to 44% and relapses by 36% to 54% in both PMR and GCA. Use of tocilizumab as additional treatment with prednisone showed a 2- to 4-fold increase in remission rates of GCA in a randomized clinical trial (N = 30).\n Diagnosis of PMR/GCA is made by clinical features and elevated inflammatory markers. In PMR, ultrasound imaging may improve diagnostic accuracy. In GCA, temporal artery biopsy may not be required in patients with typical disease features accompanied by characteristic ultrasound or MRI findings. Consensus-based recommendations suggest glucocorticoids as the most effective therapy for PMR/GCA. Methotrexate may be added to glucocorticoids in patients at risk for relapse and in those with glucocorticoid-related adverse effects or need for prolonged glucocorticoid therapy.\n\nDejaco, Christian\n\n\n"
},
{
"text": "\n156314\nGadolinium accumulation in organs of Sprague-Dawley® rats after implantation of a biodegradable magnesium-gadolinium alloy.\n\nMyrissa, A\n\nBraeuer, S\n\nMartinelli, E\n\nWillumeit-Römer, R\n\nGoessler, W\n\nWeinberg, AM\n\nBeiträge in Fachzeitschriften\nISI:000393247000044\n27845277.0\n10.1016/j.actbio.2016.11.024\nNone\nBiodegradable magnesium implants are under investigation because of their promising properties as medical devices. For enhancing the mechanical properties and the degradation resistance, rare earth elements are often used as alloying elements. In this study Mg10Gd pins were implanted into Sprague-Dawley® rats. The pin volume loss and a possible accumulation of magnesium and gadolinium in the rats' organs and blood were investigated in a long-term study over 36weeks. The results showed that Mg10Gd is a fast disintegrating material. Already 12weeks after implantation the alloy is fragmented to smaller particles, which can be found within the intramedullary cavity and the cortical bones. They disturbed the bone remodeling until the end of the study. The results concerning the elements' distribution in the animals' bodies were even more striking, since an accumulation of gadolinium could be observed in the investigated organs over the whole time span. The most affected tissue was the spleen, with up to 3240μgGd/kg wet mass, followed by the lung, liver and kidney (up to 1040, 685 and 207μgGd/kg). In the brain, muscle and heart, the gadolinium concentrations were much smaller (less than 20μg/kg), but an accumulation could still be detected. Interestingly, blood serum samples showed no accumulation of magnesium and gadolinium. This is the first time that an accumulation of gadolinium in animal organs was observed after the application of a gadolinium-containing degradable magnesium implant. These findings demonstrate the importance of future investigations concerning the distribution of the constituents of new biodegradable materials in the body, to ensure the patients' safety.\n In the last years, biodegradable Mg alloys are under investigation due to their promising properties as orthopaedic devices used for bone fracture stabilization. Gadolinium as Rare Earth Element enhances the mechanical properties of Mg-Gd alloys but its toxicity in humans is still questionable. Up to now, there is no study investigating the elements' metabolism of a REE-containing Magnesium alloy in an animal model. In this study, we examined the gadolinium distribution and accumulation in rat organs during the degradation of Mg10Gd. Our findings showed that Gd is accumulating in the animal organs, especially in spleen, liver and kidney. This study is of crucial benefit regarding a safe application of REE-containing Magnesium alloys in humans.\n Copyright © 2016. Published by Elsevier Ltd.\n\nWeinberg, Annelie-Martina\n\n\n"
},
{
"text": "\n175487\nClinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation.\n\nJosifovska, N\n\nLumi, X\n\nSzatmari-Tóth, M\n\nKristóf, E\n\nRussell, G\n\nNagymihály, R\n\nAnisimova, N\n\nMalyugin, B\n\nKolko, M\n\nIvastinović, D\n\nPetrovski, G\n\nBeiträge in Fachzeitschriften\nISI:000470970000010\n31185026.0\n10.1371/journal.pone.0217548\nPMC6559703\nRetinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment.\n 12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin).\n OCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer-their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo, the SRF doubled their capacity for engulfing dying RPEs.\n Fresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.\n\nIvastinovic, Domagoj\n\n\n"
},
{
"text": "\n177265\n[Are Higher Prices for Larger Femoral Heads in Total Hip Arthroplasty Justified from the Perspective of Health Care Economics? An Analysis of Costs and Effects in Germany].\n\nGrunert, R\n\nSchleifenbaum, S\n\nMöbius, R\n\nSommer, G\n\nZajonz, D\n\nHammer, N\n\nPrietzel, T\n\nBeiträge in Fachzeitschriften\nISI:000396282000014\n27716867.0\n10.1055/s-0042-113003\nNone\nBackground: In total hip arthroplasty (THA), femoral head diameter has not been regarded as a key parameter which should be restored when reconstructing joint biomechanics and geometry. Apart from the controversial discussion on the advantages and disadvantages of using larger diameter heads, their higher cost is another important reason that they have only been used to a limited extent. The goal of this study was to analyse the price structure of prosthetic heads in comparison to other components used in THA. A large group of patients with hip endoprostheses were evaluated with respect to the implanted socket diameter and thus the theoretically attainable head diameter. Materials and Methods: The relative prices of various THA components (cups, inserts, stems and ball heads) distributed by two leading German manufacturers were determined and analysed. Special attention was paid to different sizes and varieties in a series of components. A large patient population treated with THA was evaluated with respect to the implanted cup diameter and therefore the theoretically attainable head diameter. Results: The pricing analysis of the THA components of two manufacturers showed identical prices for cups, inserts and stems in a series. In contrast to this, the prices for prosthetic heads with a diameter of 36-44 mm were 11-50 % higher than for 28 mm heads. Identical prices for larger heads were the exception. The distribution of the head diameter in 2719 THA cases showed significant differences between the actually implanted and the theoretically attainable heads. Conclusion: There are proven advantages in using larger diameter ball heads in THA and the remaining problems can be solved. It is therefore desirable to correct the current pricing practice of charging higher prices for larger components. Instead, identical prices should be charged for all head diameters in a series, as is currently established practice for all other THA components. Thus when reconstructing biomechanics and joint geometry in THA, it should be possible to recover not only leg length, femoral offset and antetorsion of the femoral neck, but also to approximately restore the diameter of the femoral head and thereby optimise the functional outcome.\n Georg Thieme Verlag KG Stuttgart · New York.\n\nHammer, Niels\n\n\n"
},
{
"text": "\n177804\n[Popliteal Artery Entrapment Syndrome: Three Unusual Cases with Different Courses to Diagnosis].\n\nSiegl, G\n\nCohnert, T\n\nBrodmann, M\n\nAschauer, M\n\nOswald, W\n\nTiesenhausen, K\n\nBeiträge in Fachzeitschriften\nISI:000491344700014\n31634975.0\n10.1055/a-1011-4427\nNone\nPopliteal artery entrapment syndrome (PAES) is a pathology characterised by anatomical anomalies of the relative position of the popliteal artery (PA) to the medial head of the gastrocnemius muscle (MHGM), resulting in mechanical compression causing damage to and occlusion of the artery.\n From 2012 to 2018, we operated on 3 male patients aged 17 to 48 years, who presented with PAES in our department. The first and oldest patient had previously undergone femoro-popliteal bypass surgery in 2003 when aged 23, with the underlying diagnosis of "posttraumatic PAOD II b" followed by several reoperations. In 2012, during the preparation of the popliteal fossa for the interposition of the aneurysmatic bypass vein a strong tendinous strand of the MHGM was found intraoperatively to be constricting the vessels. This aberrant part of the MHGM was resected and the vein replaced. The second patient was referred to us in 2014 with the diagnosis "PAOD II b with thrombosed popliteal aneurysm" after having undergone intra-arterial lysis at age 33. Due to the remaining wall adherent thrombi and position of the aneurysm, interposition of the PA with a venous graft was planned. Intraoperatively a tendon was found proximal to the aneurysm, causing significant stenosis of the PA. This structure was resected and the interposition performed as planned. The third patient was a 17 year old adolescent, who presented with plantar and calf claudication in his right leg with paleness and pulselessness. Imaging showed occlusion of the popliteal artery in both legs. After initial intra-arterial lysis, HRMRI of the knee showed the atypical course of the PA undercrossing the MHGM from the medial side. Open surgical treatment was performed by myotomy, leading to refixation of the tendon of the MHGM in its physiological position. All patients received individual medical treatment for prophylaxis of rethrombosis. All three patients declined surgical treatment of the asymptomatic contralaterally diagnosed PAES.\n Popliteal artery entrapment syndrome is rare and usually associated with athletic, largely young male patients with pronounced calf muscles. Delayed diagnosis of PAES leads to severe vascular defects, unnecessary reintervention and prolonged illness as is shown in our first case. Therefore, calf and foot claudication in young patients should always bring to mind the differential diagnosis of popliteal entrapment syndrome.\n Georg Thieme Verlag KG Stuttgart · New York.\n\nAschauer, Manuela\n\nBrodmann, Marianne\n\nCohnert, Tina Ulrike\n\nOswald, Wolfgang Kurt\n\nTiesenhausen, Kurt\n\n\n"
},
{
"text": "\n21974\nCombination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension.\n\nGhofrani, HA\n\nWiedemann, R\n\nRose, F\n\nOlschewski, H\n\nSchermuly, RT\n\nWeissmann, N\n\nSeeger, W\n\nGrimminger, F\n\nBeiträge in Fachzeitschriften\nISI:000174682100003\n11926786.0\n10.7326/0003-4819-136-7-200204020-00008\nNone\nBACKGROUND: Inhalation of the stable prostacyclin analogue iloprost is being studied for treatment of pulmonary hypertension. The selective phosphodiesterase-5 inhibitor sildenafil has been reported to cause pulmonary vasodilatation. OBJECTIVE: To evaluate the safety and effectiveness of oral sildenafil, alone and in combination with inhaled iloprost, for treatment of pulmonary hypertension. DESIGN: Randomized, controlled, open-label trial. SETTING: Intensive care unit. PATIENTS: 30 patients with severe pulmonary arterial hypertension (n = 16), chronic thromboembolic pulmonary hypertension (n = 13), or pulmonary hypertension due to aplasia of the left pulmonary artery (n = 1), all classified as New York Heart Association class III or IV. INTERVENTION: All patients received inhaled nitric oxide and aerosolized iloprost (inhaled dose, 2.8 microg). They were then randomly assigned to receive 12.5 mg of oral sildenafil, 50 mg of sildenafil, 12.5 mg of sildenafil plus inhaled iloprost, or 50 mg of sildenafil plus inhaled iloprost. MEASUREMENTS: Systemic and pulmonary arterial pressure, pulmonary arterial occlusion pressure, cardiac output, central venous pressure, peripheral arterial oxygen saturation, and arterial and mixed venous blood gases were measured during right-heart catheterization by using a Swan-Ganz catheter. RESULTS: In rank order of pulmonary vasodilatory potency (maximum reduction of pulmonary vascular resistance and increase in cardiac index), 50 mg of sildenafil plus iloprost was most effective, followed by 12.5 mg of sildenafil plus iloprost. Iloprost alone and 50 mg of sildenafil were almost equally effective but were less potent than the combination regimens, and the least potent treatments were 12.5 mg of sildenafil and nitric oxide. In patients who received 50 mg of sildenafil plus iloprost, the maximum change in pulmonary vasodilatory potency was -44.2% (95% CI, -49.5% to -38.8%), compared with -14.1% (CI, -19.1% to -9.2%) in response to nitric oxide. With administration of 50 mg of sildenafil plus iloprost, the area under the curve for reduction in pulmonary vasodilatory resistance surpassed that of administration of 50 mg of sildenafil alone and iloprost alone combined, the vasodilatory effect lasted longer than 3 hours, and systemic arterial pressure and arterial oxygenation were maintained. No serious adverse events occurred. CONCLUSION: Although limited by the small sample and lack of long-term observations, the study shows that oral sildenafil is a potent pulmonary vasodilator that acts synergistically with inhaled iloprost to cause strong pulmonary vasodilatation in both severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n151463\nDo we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database.\n\nWolff, I\n\nMay, M\n\nHoschke, B\n\nZigeuner, R\n\nCindolo, L\n\nHutterer, G\n\nSchips, L\n\nDe Cobelli, O\n\nRocco, B\n\nDe Nunzio, C\n\nTubaro, A\n\nComan, I\n\nFeciche, B\n\nTruss, M\n\nDalpiaz, O\n\nFigenshau, RS\n\nMadison, K\n\nSánchez-Chapado, M\n\nSantiago Martin, MD\n\nSalzano, L\n\nLotrecchiano, G\n\nShariat, SF\n\nHohenfellner, M\n\nWaidelich, R\n\nStief, C\n\nMiller, K\n\nPahernik, S\n\nBrookman-May, S\n\nMembers of the CORONA Project and the European Association of Urology (EAU) Young Academic Urologists (YAU) Renal Cancer Group\n\nBeiträge in Fachzeitschriften\nISI:000375366000022\n26899942.0\n10.1016/j.ejso.2016.01.009\nNone\nSince there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients.\n The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index.\n During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%).\n Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5-year-recurrence rate of almost 40%.\n Copyright © 2016 Elsevier Ltd. All rights reserved.\n\nDalpiaz, Orietta\n\nHutterer, Georg\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n163837\nProgression of Stargardt Disease as Determined by Fundus Autofluorescence in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 9).\n\nStrauss, RW\n\nMuñoz, B\n\nHo, A\n\nJha, A\n\nMichaelides, M\n\nCideciyan, AV\n\nAudo, I\n\nBirch, DG\n\nHariri, AH\n\nNittala, MG\n\nSadda, S\n\nWest, S\n\nScholl, HPN\n\nProgStar Study Group\n\nBeiträge in Fachzeitschriften\nISI:000414798100020\n29049437.0\n10.1001/jamaophthalmol.2017.4152\nPMC5710470\nSensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease.\n To describe the yearly progression rate of atrophic lesions in the retrospective Progression of Stargardt Disease study.\n A multicenter retrospective cohort study was conducted at tertiary referral centers in the United States and Europe. A total of 251 patients aged 6 years or older at baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 centers between August 2, 2013, and December 12, 2014; of these patients, 215 had at least 2 gradable fundus autofluorescence images with atrophic lesion(s) present in at least 1 eye.\n Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence were quantified by a reading center. Progression rates were estimated from linear mixed models with time as the independent variable.\n Yearly rate of progression using the growth of atrophic lesions measured by fundus autofluorescence.\n A total of 251 participants (458 study eyes) were enrolled. Images from 386 eyes of 215 participants (126 females and 89 males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9 [13.3] years) showed atrophic lesions present on at least 2 visits and were graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224 eyes (123 female participants and 101 male participants; mean [SD] age, 33.0 [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were included in the estimation of the progression of the area of DDAF. At the first visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2 (2.7) mm2. The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm2. Mean progression of DDAF was 0.51 mm2/y (95% CI, 0.42-0.61 mm2/y), and of total decreased fundus autofluorescence was 0.35 mm2/y (95% CI, 0.28-0.43 mm2/y). Rates of progression depended on the initial size of the lesion.\n In Stargardt disease with DDAF lesions, fundus autofluorescence may serve as a monitoring tool for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.\n\nStrauß, Rupert\n\n\n"
},
{
"text": "\n183059\nThe sacral chordoma margin.\n\nRadaelli, S\n\nFossati, P\n\nStacchiotti, S\n\nAkiyama, T\n\nAsencio, JM\n\nBandiera, S\n\nBoglione, A\n\nBoland, P\n\nBolle, S\n\nBruland, Ø\n\nBrunello, A\n\nBruzzi, P\n\nCampanacci, D\n\nCananzi, F\n\nCapanna, R\n\nCasadei, R\n\nCordoba, A\n\nCourt, C\n\nDei Tos, AP\n\nDeLaney, TF\n\nDe Paoli, A\n\nDe Pas, TM\n\nDesai, A\n\nDi Brina, L\n\nDonati, DM\n\nFabbri, N\n\nFiore, MR\n\nFrezza, A\n\nGambarotti, M\n\nGasbarrini, A\n\nGeorg, P\n\nGrignani, G\n\nHindi, N\n\nHug, EB\n\nJones, R\n\nKawai, A\n\nKrol, AD\n\nLe Grange, F\n\nLuzzati, A\n\nMarquina, G\n\nMartin-Benlloch, JA\n\nMazzocco, K\n\nNavarria, F\n\nNavarria, P\n\nParchi, PD\n\nPatel, S\n\nPennacchioli, E\n\nPetrongari, MG\n\nPicci, P\n\nPollock, R\n\nPorcu, L\n\nQuagliuolo, V\n\nSangalli, C\n\nScheipl, S\n\nScotto, GM\n\nSpalek, M\n\nSteinmeier, T\n\nTimmermann, B\n\nTrama, A\n\nUhl, M\n\nValverde, C\n\nVarga, PP\n\nVerges, R\n\nWeber, DC\n\nZoccali, C\n\nCasali, PG\n\nSommer, J\n\nGronchi, A\n\nBeiträge in Fachzeitschriften\nISI:000552132400004\n32402509.0\n10.1016/j.ejso.2020.04.028\nNone\nAim of the manuscript is to discuss how to improve margins in sacral chordoma.\n Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery.\n A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed.\n En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment.\n Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.\n Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.\n\nScheipl, Susanne\n\n\n"
},
{
"text": "\n3101\nHistamine-induced Ca2+ oscillations in a human endothelial cell line depend on transmembrane ion flux, ryanodine receptors and endoplasmic reticulum Ca2+-ATPase.\n\nPaltauf-Doburzynska, J\n\nFrieden, M\n\nSpitaler, M\n\nGraier, WF\n\nBeiträge in Fachzeitschriften\nISI:000087391200006\n10790152.0\n10.1111%2Fj.1469-7793.2000.00701.x\nPMC2269898\nUsing single cell microfluorometry to monitor changes in bulk Ca2+ concentration ([Ca2+]bulk) and the whole-cell configuration of the patch clamp technique to measure K+ currents (voltage clamp) and membrane potential (current clamp), the mechanisms of histamine-induced Ca2+ oscillations in the umbilical vein endothelial cell-derived cell line EA.hy926 were studied. In single cells, histamine (10 microM) evoked sinusoidal Ca2+ oscillations in low extracellular Ca2+ concentrations ([Ca2+]o = 10-30 microM). In contrast, histamine did not initiate Ca2+ oscillations either in the absence of extracellular Ca2+ (10 microM EGTA) or in the presence of 2.5 mM extracellular Ca2+. Ca2+ oscillations were accompanied by rhythmic activation of Ca2+-activated K+ (KCa) channels and membrane hyperpolarization of 18.1 +/- 3.9 mV. Hence, cell depolarization with 70 mM extracellular K+ or the inhibition of non-selective cation channels (NSCCs) and KCa channels by 10 microM Loe 908 and 10 mM tetrabutylammonium prevented histamine-evoked Ca2+ oscillations. Preventing Na+-Ca2+ exchange (NCX) by 10 microM 2', 4'-dichlorobenzamil, or removal of extracellular Na+, abolished histamine-induced Ca2+ oscillations. Lowering the extracellular Na+ concentration and thus promoting the reversed mode of NCX (3Na+ out and 1Ca2+ in) increased the amplitude and frequency of histamine-induced Ca2+ oscillations by 25 and 13 %, respectively. Hence, in the absence of extracellular Ca2+, 10 microM histamine induced an elevation of intracellular Na+ concentration in certain subplasmalemmal domains. The inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2, -di-tert-butyl-1, 4-benzo-hydroquinone (15 microM) prevented histamine-induced Ca2+ oscillations. In addition, blockage of ryanodine-sensitive Ca2+ release (RsCR) by 25 microM ryanodine blunted Ca2+ oscillations. In endothelial cells that were treated for 16 h with 10 microM nocodazole to collapse the superficial endoplasmic reticulum (sER), no histamine-induced Ca2+ oscillations were found. We conclude that in low [Ca2+]o conditions histamine-induced Ca2+ oscillations depend on transmembrane Na+ loading through NSCCs that leads to Ca2+ entry via NCX. Cation influx is controlled by KCa channel activity that triggers membrane hyperpolarization and, thus, provides the driving force for cation influx. Hence, the Ca2+ entering needs to be sequestrated via SERCA into sER to become released by RsCR to evoke Ca2+ spiking. These data further support our previous work on localized Ca2+ signalling as a key phenomenon in endothelial Ca2+ homeostasis.\n\nGraier, Wolfgang\n\n\n"
}
]
}