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"text": "\n175264\nEffects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial.\n\nAl-Shahi Salman, R\n\nMinks, DP\n\nMitra, D\n\nRodrigues, MA\n\nBhatnagar, P\n\ndu Plessis, JC\n\nJoshi, Y\n\nDennis, MS\n\nMurray, GD\n\nNewby, DE\n\nSandercock, PAG\n\nSprigg, N\n\nStephen, J\n\nSudlow, CLM\n\nWerring, DJ\n\nWhiteley, WN\n\nWardlaw, JM\n\nWhite, PM\n\nRESTART Collaboration\n\nBeiträge in Fachzeitschriften\nISI:000471176500013\n31129065.0\n10.1016/S1474-4422(19)30184-X\nPMC7645733\nFindings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy.\n RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.\n Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08-1·13] vs 0·77 [0·13-4·61]; pinteraction=0·41), cerebral microbleed number 0-1 versus 2-4 versus 5 or more (HR 0·77 [0·13-4·62] vs 0·32 [0·03-3·66] vs 0·33 [0·07-1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004-6·79] vs 0·37 [0·09-1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05).\n Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision.\n British Heart Foundation.\n Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.\n\nGattringer, Thomas\n\n\n"
},
{
"text": "\n185309\nHealth Care Providers' Performance, Mindset, and Attitudes Toward a Neonatal Resuscitation Computer-Based Simulator: Empirical Study.\n\nCutumisu, M\n\nGhoman, SK\n\nLu, C\n\nPatel, SD\n\nGarcia-Hidalgo, C\n\nFray, C\n\nBrown, MRG\n\nGreiner, R\n\nSchmölzer, GM\n\nBeiträge in Fachzeitschriften\nISI:000629136000010\n33346741.0\n10.2196/21855\nPMC7781798\nNeonatal resuscitation involves a complex sequence of actions to establish an infant's cardiorespiratory function at birth. Many of these responses, which identify the best action sequence in each situation, are taught as part of the recurrent Neonatal Resuscitation Program training, but they have a low incidence in practice, which leaves health care providers (HCPs) less prepared to respond appropriately and efficiently when they do occur. Computer-based simulators are increasingly used to complement traditional training in medical education, especially in the COVID-19 pandemic era of mass transition to digital education. However, it is not known how learners' attitudes toward computer-based learning and assessment environments influence their performance.\n This study explores the relation between HCPs' attitudes toward a computer-based simulator and their performance in the computer-based simulator, RETAIN (REsuscitation TrAINing), to uncover the predictors of performance in computer-based simulation environments for neonatal resuscitation.\n Participants were 50 neonatal HCPs (45 females, 4 males, 1 not reported; 16 respiratory therapists, 33 registered nurses and nurse practitioners, and 1 physician) affiliated with a large university hospital. Participants completed a demographic presurvey before playing the game and an attitudinal postsurvey after completing the RETAIN game. Participants' survey responses were collected to measure attitudes toward the computer-based simulator, among other factors. Knowledge on neonatal resuscitation was assessed in each round of the game through increasingly difficult neonatal resuscitation scenarios. This study investigated the moderating role of mindset on the association between the perceived benefits of understanding the terminology used in the computer-based simulator, RETAIN, and their performance on the neonatal resuscitation tasks covered by RETAIN.\n The results revealed that mindset moderated the relation between participants' perceived terminology used in RETAIN and their actual performance in the game (F3, 4=4.56, R2=0.24, adjusted R2=0.19; P=.007; estimate=-1.19, SE=0.38, t44=-3.12, 95% CI -1.96 to -0.42; P=.003). Specifically, participants who perceived the terminology useful also performed better but only when endorsing more of a growth mindset; they also performed worse when endorsing more of a fixed mindset. Most participants reported that they enjoyed playing the game. The more the HCPs agreed that the terminology in the tutorial and in the game was accessible, the better they performed in the game, but only when they reported endorsing a growth mindset exceeding the average mindset of all the participants (F3, 4=6.31, R2=0.30, adjusted R2=0.25; P=.001; estimate=-1.21, SE=0.38, t44=-3.16, 95% CI -1.99 to -0.44; P=.003).\n Mindset moderates the strength of the relationship between HCPs' perception of the role that the terminology employed in a game simulator has on their performance and their actual performance in a computer-based simulator designed for neonatal resuscitation training. Implications of this research include the design and development of interactive learning environments that can support HCPs in performing better on neonatal resuscitation tasks.\n ©Maria Cutumisu, Simran K Ghoman, Chang Lu, Siddhi D Patel, Catalina Garcia-Hidalgo, Caroline Fray, Matthew R G Brown, Russell Greiner, Georg M Schmölzer. Originally published in JMIR Serious Games (http://games.jmir.org), 21.12.2020.\n\n\n"
},
{
"text": "\n53245\nWhom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study.\n\nKaptoge, S\n\nArmbrecht, G\n\nFelsenberg, D\n\nLunt, M\n\nWeber, K\n\nBoonen, S\n\nJajic, I\n\nStepan, JJ\n\nBanzer, D\n\nReisinger, W\n\nJanott, J\n\nKragl, G\n\nScheidt-Nave, C\n\nFelsch, B\n\nMatthis, C\n\nRaspe, HH\n\nLyritis, G\n\nPóor, G\n\nNuti, R\n\nMiazgowski, T\n\nHoszowski, K\n\nArmas, JB\n\nVaz, AL\n\nBenevolenskaya, LI\n\nMasaryk, P\n\nCannata, JB\n\nJohnell, O\n\nReid, DM\n\nBhalla, A\n\nWoolf, AD\n\nTodd, CJ\n\nCooper, C\n\nEastell, R\n\nKanis, JA\n\nO'Neill, TW\n\nSilman, AJ\n\nReeve, J\n\nBeiträge in Fachzeitschriften\nISI:000239300400007\n16821002.0\n10.1007/s00198-005-0067-9\nNone\nIntroduction: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. Methods: Data was analysed from 5, 61 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. Results: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2, 09), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). Conclusion: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n171438\nGlobal, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.\n\nGBD 2016 Dementia Collaborators\n\nBeiträge in Fachzeitschriften\nISI:000453007700024\n30497964.0\n10.1016/S1474-4422(18)30403-4\nPMC6291454\nThe number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists.\n GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugar-sweetened beverages).\n In 2016, the global number of individuals who lived with dementia was 43·8 million (95% uncertainty interval [UI] 37·8-51·0), increased from 20.2 million (17·4-23·5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1·7% (1·0-2·4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27·0 million, 95% UI 23·3-31·4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2·4 million (95% UI 2·1-2·8) deaths. Overall, 28·8 million (95% UI 24·5-34·0) DALYs were attributed to dementia; 6·4 million (95% UI 3·4-10·5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages.\n The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide.\n Bill & Melinda Gates Foundation.\n Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n151610\nAcute Physiological Responses to Short- and Long-Stage High-Intensity Interval Exercise in Cardiac Rehabilitation: A Pilot Study.\n\nTschakert, G\n\nKroepfl, JM\n\nMueller, A\n\nHarpf, H\n\nHarpf, L\n\nTraninger, H\n\nWallner-Liebmann, S\n\nStojakovic, T\n\nScharnagl, H\n\nMeinitzer, A\n\nPichlhoefer, P\n\nHofmann, P\n\nBeiträge in Fachzeitschriften\nISI:000371070700011\n26957930.0\nNone\nPMC4763850\nDespite described benefits of aerobic high-intensity interval exercise (HIIE), the acute responses during different HIIE modes and associated health risks have only been sparsely discovered in heart disease patients. Therefore, the aim of this study was to investigate the acute responses for physiological parameters, cardiovascular and inflammatory biomarkers, and catecholamines yielded by two different aerobic HIIE protocols compared to continuous exercise (CE) in phase III cardiac rehabilitation. Eight cardiac patients (7 with coronary heart disease, 1 with myocarditis; 7 males, 1 female; age: 63.0 ± 9.4 years; height: 1.74 ± 0.05 m; weight: 83.6 ± 8.7 kg), all but one treated with ß-blocking agents, performed a maximal symptom-limited incremental exercise test (IET) and three different exercise tests matched for mean load (Pmean) and total duration: 1) short HIIE with a peak workload duration (tpeak) of 20 s and a peak workload (Ppeak) equal to the maximum power output (Pmax) from IET; 2) long HIIE with a tpeak of 4 min, Ppeak was corresponding to the power output at 85 % of maximal heart rate (HRmax) from IET; 3) CE with a target workload equal to Pmean of both HIIE modes. Acute metabolic and peak cardiorespiratory responses were significantly higher during long HIIE compared to short HIIE and CE (p < 0.05) except HRpeak which tended to be higher in long HIIE than in short HIIE (p = 0.08). Between short HIIE and CE, no significant difference was found for any parameter. Acute responses of cardiovascular and inflammatory biomarkers and catecholamines didn't show any significant difference between tests (p > 0.05). All health-related variables remained in a normal range in any test except NT-proBNP, which was already elevated at baseline. Despite a high Ppeak particularly in short HIIE, both HIIE modes were as safe and as well tolerated as moderate CE in cardiac patients by using our methodological approach. 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 and identical mean load. No significant difference for any physiological parameter was found between short HIIE and CE.Between short HIIE, long HIIE, and CE, no significant difference was found in the increase (or decrease, respectively, of health related markers such as cardiovascular biomarkers, catecholamines, or inflammatory parameters during exercise.During all exercise modes, all risk markers remained in a normal range except for NT-proBNP which was, however, already elevated at baseline.Short HIIE, long HIIE, and CE were safely performed by patients with CHD or myocarditis in cardiac rehabilitation by using our methodological approach to exercise prescription. This approach included the prescription of exercise intensities with respect to LTP1, LTP2, and Pmax as well as a conscious setting of Pmean at a moderate level (80 % of PLTP2). Importantly, all exercise modes were matched for Pmean and exercise duration in order to enable a comparison of the three protocols.\n\nHolasek, Sandra Johanna\n\nMeinitzer, Andreas\n\nScharnagl, Hubert\n\n\n"
},
{
"text": "\n187572\nEndocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C.\n\nPelletier, F\n\nPerrier, S\n\nCayami, FK\n\nMirchi, A\n\nSaikali, S\n\nTran, LT\n\nUlrick, N\n\nGuerrero, K\n\nRampakakis, E\n\nvan Spaendonk, RML\n\nNaidu, S\n\nPohl, D\n\nGibson, WT\n\nDemos, M\n\nGoizet, C\n\nTejera-Martin, I\n\nPotic, A\n\nFogel, BL\n\nBrais, B\n\nSylvain, M\n\nSébire, G\n\nLourenço, CM\n\nBonkowsky, JL\n\nCatsman-Berrevoets, C\n\nPinto, PS\n\nTirupathi, S\n\nStrømme, P\n\nde Grauw, T\n\nGieruszczak-Bialek, D\n\nKrägeloh-Mann, I\n\nMierzewska, H\n\nPhilippi, H\n\nRankin, J\n\nAtik, T\n\nBanwell, B\n\nBenko, WS\n\nBlaschek, A\n\nBley, A\n\nBoltshauser, E\n\nBratkovic, D\n\nBrozova, K\n\nCimas, I\n\nClough, C\n\nCorenblum, B\n\nDinopoulos, A\n\nDolan, G\n\nFaletra, F\n\nFernandez, R\n\nFletcher, J\n\nGarcia Garcia, ME\n\nGasparini, P\n\nGburek-Augustat, J\n\nGonzalez Moron, D\n\nHamati, A\n\nHarting, I\n\nHertzberg, C\n\nHill, A\n\nHobson, GM\n\nInnes, AM\n\nKauffman, M\n\nKirwin, SM\n\nKluger, G\n\nKolditz, P\n\nKotzaeridou, U\n\nLa Piana, R\n\nListon, E\n\nMcClintock, W\n\nMcEntagart, M\n\nMcKenzie, F\n\nMelançon, S\n\nMisbahuddin, A\n\nSuri, M\n\nMonton, FI\n\nMoutton, S\n\nMurphy, RPJ\n\nNickel, M\n\nOnay, H\n\nOrcesi, S\n\nÖzkınay, F\n\nPatzer, S\n\nPedro, H\n\nPekic, S\n\nPineda Marfa, M\n\nPizzino, A\n\nPlecko, B\n\nPoll-The, BT\n\nPopovic, V\n\nRating, D\n\nRioux, MF\n\nRodriguez Espinosa, N\n\nRonan, A\n\nOstergaard, JR\n\nRossignol, E\n\nSanchez-Carpintero, R\n\nSchossig, A\n\nSenbil, N\n\nSønderberg Roos, LK\n\nStevens, CA\n\nSynofzik, M\n\nSztriha, L\n\nTibussek, D\n\nTimmann, D\n\nTonduti, D\n\nvan de Warrenburg, BP\n\nVázquez-López, M\n\nVenkateswaran, S\n\nWasling, P\n\nWassmer, E\n\nWebster, RI\n\nWiegand, G\n\nYoon, G\n\nRotteveel, J\n\nSchiffmann, R\n\nvan der Knaap, MS\n\nVanderver, A\n\nMartos-Moreno, GÁ\n\nPolychronakos, C\n\nWolf, NI\n\nBernard, G\n\nBeiträge in Fachzeitschriften\nISI:000637325300048\n33005949.0\n10.1210/clinem/dgaa700\nPMC7823228\n4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date.\n To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy.\n An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated.\n This was a multicenter retrospective study using information collected from 3 predominant centers.\n A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included.\n Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts.\n The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients.\n Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.\n © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.\n\nPlecko, Barbara\n\n\n"
},
{
"text": "\n136439\nInfluence of probiotic and conventional yoghurt on the status of vitamins B1, B2 and B6 in young healthy women.\n\nFabian, E\n\nMajchrzak, D\n\nDieminger, B\n\nMeyer, E\n\nElmadfa, I\n\nBeiträge in Fachzeitschriften\nISI:000255290500006\n18230968.0\n10.1159/000114408\nNone\nBackground: In vitro studies indicate that yoghurt bacteria are able to generate several water-soluble vitamins and therefore yoghurt could be a good source of these micronutrients. However, whether lactobacilli or other viable bacteria release the synthesized vitamins or utilize vitamins from their surroundings is a matter of debate. This study was carried out to investigate whether probiotic and traditional yoghurt bacteria are able to influence the status of different B vitamins (B 1, B 2, B 6) in young healthy women. Methods: In this investigation, female volunteers consumed 100 g/day of probiotic (n = 17) or conventional yoghurt (n = 16) for 2 weeks (T1-T2) and 200 g/day for another 2 weeks (T2-T3). A washout phase lasting 2 weeks followed. Plasma and urine concentrations of thiamine (vitamin B 1), riboflavin (B 2) and pyridoxine (B 6) were analyzed using HPLC. The functional parameters, i. e. the erythrocyte transketolase (alpha-ETK) expressed as TPP (thiamine pyrophosphate) effect, erythrocyte glutathione reductase (alpha-EGR) and glutamic oxaloacetic transaminase (alpha-EGOT) were determined photometrically. Results: The plasma levels of vitamin B 1 increased significantly in both the probiotic (p < 0.001) and the control group (p < 0.01) when consuming 200 g yoghurt/day (T2-T3) and decreased to the baseline levels after the wash-out phase (T3-T4). Urinary excretion of thiamine and the TPP effect did not significantly change in either the probiotic or the control group during the period of daily yoghurt consumption (T1-T3). The plasma concentration of flavin adenine dinucleotide (FAD) decreased significantly (p < 0.001) after consuming 100 g yoghurt/day (T1-T2) while plasma concentrations of flavin mononucleotide (FMN) (probiotic: p < 0.01, control: p < 0.001) and free riboflavin increased significantly (probiotic: p < 0.01, control: p < 0.001). Afterwards, the levels of these parameters remained unchanged to the end of the study in both tested groups. The urinary excretion of riboflavin and alpha-EGR remained unaffected throughout the study in both the probiotic and the control group. The average status of vitamin B 6, evaluated by its plasma level, urinary excretion and alpha-EGOT was unaffected by daily intake of 100 g (T1-T2) and 200 g yoghurt (T2-T3), respectively, for 4 weeks (T1-T3). Conclusion: The results of the present study indicate that daily consumption of 200 g of both, probiotic and conventional yoghurt for 2 weeks can contribute to the total intake of vitamin B 1 and B 2 reflected by increased levels of plasma thiamine and free riboflavin in healthy women. The diminished plasma FAD and increased FMN concentrations, observed during the period of daily yoghurt consumption in both groups, may be the result of enhanced immune function and an oxidant/antioxidant imbalance, caused by the daily intake of lactic acid bacteria. Since the long term status parameters of all three investigated vitamins (B-1, B-2, B-6) remained unaffected during the investigation the changes in plasma concentrations seem more likely the result of regular yoghurt consumption as a fermented dairy product, rather than of the specific intake of probiotic bacteria. Copyright (C) 2008 S. Karger AG, Basel.\n\n\n"
},
{
"text": "\n167307\nProgression of regional grey matter atrophy in multiple sclerosis.\n\nEshaghi, A\n\nMarinescu, RV\n\nYoung, AL\n\nFirth, NC\n\nPrados, F\n\nJorge Cardoso, M\n\nTur, C\n\nDe Angelis, F\n\nCawley, N\n\nBrownlee, WJ\n\nDe Stefano, N\n\nLaura Stromillo, M\n\nBattaglini, M\n\nRuggieri, S\n\nGasperini, C\n\nFilippi, M\n\nRocca, MA\n\nRovira, A\n\nSastre-Garriga, J\n\nGeurts, JJG\n\nVrenken, H\n\nWottschel, V\n\nLeurs, CE\n\nUitdehaag, B\n\nPirpamer, L\n\nEnzinger, C\n\nOurselin, S\n\nGandini Wheeler-Kingshott, CA\n\nChard, D\n\nThompson, AJ\n\nBarkhof, F\n\nAlexander, DC\n\nCiccarelli, O\n\nBeiträge in Fachzeitschriften\nISI:000434113500018\n29741648.0\n10.1093/brain/awy088\nPMC5995197\nSee Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis.\n\nEnzinger, Christian\n\nPirpamer, Lukas\n\n\n"
},
{
"text": "\n88060\nEffects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study.\n\nDiener, HC\n\nSacco, RL\n\nYusuf, S\n\nCotton, D\n\nOunpuu, S\n\nLawton, WA\n\nPalesch, Y\n\nMartin, RH\n\nAlbers, GW\n\nBath, P\n\nBornstein, N\n\nChan, BP\n\nChen, ST\n\nCunha, L\n\nDahlöf, B\n\nDe Keyser, J\n\nDonnan, GA\n\nEstol, C\n\nGorelick, P\n\nGu, V\n\nHermansson, K\n\nHilbrich, L\n\nKaste, M\n\nLu, C\n\nMachnig, T\n\nPais, P\n\nRoberts, R\n\nSkvortsova, V\n\nTeal, P\n\nToni, D\n\nVanderMaelen, C\n\nVoigt, T\n\nWeber, M\n\nYoon, BW\n\nPrevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) study group\n\nBeiträge in Fachzeitschriften\nISI:000259725700011\n18757238.0\n10.1016/S1474-4422(08)70198-4\nPMC2772657\nBACKGROUND: The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. METHODS: Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062. FINDINGS: 20, 32 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups. INTERPRETATION: Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.\n\nHorner, Susanna\n\n\n"
},
{
"text": "\n4881\nIncidence and detection of fungi and eosinophilic granulocytes in chronic rhinosinusitis\n\nBraun, H\n\nStammberger, H\n\nBuzina, W\n\nFreudenschuss, K\n\nLackner, A\n\nBeham, A\n\nBeiträge in Fachzeitschriften\nISI:000183193100005\n12800078.0\n10.1055/s-2003-39777\nNone\nBACKGROUND: Chronic Rhinosinusitis (CRS) is the most common chronic disease in the United States. Though for Europe no data are available, we have to assume that the situation is similar. Although the disease is defined very well by clinical symptoms, up to date the etiology and pathogenesis of chronic rhinosinusitis are unknown. CRS is considered to be multifactorial, with thickening of the mucosa and formation of polyps as an end stage of the disease. Treatment of choice includes corticosteroids and/or endoscopic or microscopic surgery. Antibiotics only help, if there is an acute bacterial exacerbation of the disease. They are not able to cure chronic rhinosinusitis per se. In 1999 Mayo Clinic researchers published data concerning the incidence of so-called "allergic" fungal sinusitis (AFS) in their patients suffering from chronic rhinosinusitis, demonstrating the majority of patients investigated presenting those criteria. Our own initial data from 2000 confirmed their findings. MATERIAL AND METHODS: In an open prospective study fungal cultures were obtained from nasal mucus of 238 consecutive patients suffering from CRS. As control group acted 23 members of our staff, who did not show any evidence for CRS. In addition, in 37 CRS patients surgical specimens (mucus and tissue) were investigated histologically for evidence of eosinophilic granulocytes and fungal elements. RESULTS: Using new techniques for fungal detection in culture and histology as proposed by Mayo Clinic researchers, positive detection of fungal cultures of the mucus of our CRS patients developed from 7 % in the past up to 87 % at present. 91.3 % of our control group yielded a positive result in fungal culture. Histologically, eosinophilic clusters were evident in 94.6 % and fungal elements were detected in 75.5 % within the mucus of 37 surgical CRS patients. Overall, 89.2 % of our surgical patients thus fulfilled the criteria of so-called AFS. Compared to our findings in the past, our latest results show an increase of 80 % in detection of fungal elements in our CRS patients. In all we were able to identify 654 positive fungal cultures in 238 CRS patients and 23 healthy controls respectively. 88 different genera grew, with 2.4 different species per patient and 3.1 different species per healthy control, on average. CONCLUSION: Utilizing new techniques of fungal culturing out of the mucus of CRS patients and healthy controls, the number of positive fungal cultures increased dramatically from 7 % to 87 % in our patients and 91.3 % in healthy controls respectively. To obtain these results it is crucial to perform special techniques of mucus sampling and pretreatment for culturing as well as for histological investigations. Our results show, that with suitable techniques fungi can be identified in almost everybody's nose, CRS patient or healthy. When inhaled, those airborne fungi are only "in transit" through the nose. Positive fungal cultures from nasal secretion therefore have to be considered normal findings. The reason for this delayed recognition has to be attributed to our inadequate methods in the past. In contrast to healthy controls, clusters of eosinophils and fungal elements are present simultaneously within the mucus of CRS patients and appear to be a marker of the disease.\n\nBraun, Hannes\n\nBuzina, Walter\n\n\n"
},
{
"text": "\n139126\nEffect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial.\n\nAmrein, K\n\nSchnedl, C\n\nHoll, A\n\nRiedl, R\n\nChristopher, KB\n\nPachler, C\n\nUrbanic Purkart, T\n\nWaltensdorfer, A\n\nMünch, A\n\nWarnkross, H\n\nStojakovic, T\n\nBisping, E\n\nToller, W\n\nSmolle, KH\n\nBerghold, A\n\nPieber, TR\n\nDobnig, H\n\nBeiträge in Fachzeitschriften\nISI:000342983200016\n25268295.0\n10.1001/jama.2014.13204\nNone\nLow vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal.\n To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs.\n A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243).\n Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540, 00 IU followed by monthly maintenance doses of 90, 00 IU for 5 months.\n The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis.\n A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12).\n Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study.\n clinicaltrials.gov Identifier: NCT01130181.\n\nAmrein, Karin\n\nBerghold, Andrea\n\nBisping, Egbert Hubertus\n\nMünch, Andreas\n\nPieber, Thomas\n\nRiedl, Regina\n\nToller, Wolfgang\n\nUrbanic Purkart, Tadeja\n\nWaltensdorfer, Andreas\n\n\n"
},
{
"text": "\n178113\nEuropean Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update.\n\nBabjuk, M\n\nBurger, M\n\nCompérat, EM\n\nGontero, P\n\nMostafid, AH\n\nPalou, J\n\nvan Rhijn, BWG\n\nRouprêt, M\n\nShariat, SF\n\nSylvester, R\n\nZigeuner, R\n\nCapoun, O\n\nCohen, D\n\nEscrig, JLD\n\nHernández, V\n\nPeyronnet, B\n\nSeisen, T\n\nSoukup, V\n\nBeiträge in Fachzeitschriften\nISI:000490122200035\n31443960.0\n10.1016/j.eururo.2019.08.016\nNone\nThis overview presents the updated European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS).\n To provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation and recommendations.\n A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines has been performed annually since the last published version in 2017. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned.\n Tumours staged as Ta, T1, and/or CIS are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of the tissue obtained by transurethral resection (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system. Stratification of patients into low-, intermediate-, and high-risk groups is pivotal to the recommendation of adjuvant treatment. In patients with tumours presumed to be at a low risk and in those presumed to be at an intermediate risk with a low previous recurrence rate and an expected EORTC recurrence score of <5, one immediate chemotherapy instillation is recommended. Patients with intermediate-risk tumours should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at the highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-unresponsive tumours. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/.\n These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice.\n The European Association of Urology Non-muscle-invasive Bladder Cancer (NMIBC) Panel has released an updated version of their guidelines, which contains information on classification, risk factors, diagnosis, prognostic factors, and treatment of NMIBC. The recommendations are based on the current literature (until the end of 2018), with emphasis on high-level data from randomised clinical trials and meta-analyses. Stratification of patients into low-, intermediate-, and high-risk groups is essential for deciding appropriate use of adjuvant intravesical chemotherapy or bacillus Calmette-Guérin (BCG) instillations. Surgical removal of the bladder should be considered in case of BCG-unresponsive tumours or in NMIBCs with the highest risk of progression.\n Copyright © 2019. Published by Elsevier B.V.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n76966\nMental disorders in general hospital patients\n\nRothenhäusler, HB\n\nBeiträge in Fachzeitschriften\nNone\n17099609.0\nNone\nNone\nTwo major epidemiological studies using standardized instruments for diagnosis have revealed that the prevalence of mental disorders in general hospital inpatients range from 41.3% to 46.5%. The most prevalent groups of psychiatric disorders among general hospital inpatients are organic mental illness, depressive disorders, and alcohol dependence or abuse. The prevalence rates of organic brain syndromes, adjustment disorders with depressed mood, and alcohol dependence in general hospital inpatients are above those of the general population. In nearly half of the studied general hospital inpatients receiving a psychiatric diagnosis Consultation-Liaison (C-L) psychiatry interventions were found to be necessary. However, psychiatric consultation rates found in most recently presented studies in Germany and Austria range from 2.66% to 3.30%, and remain low when compared to the reported prevalence figures of psychiatric disorders and the demonstrated necessity for specific therapeutic interventions among general hospital inpatients. There is also evidence stemming from newly presented C-L follow-up studies that the remarkable advances in intensive care treatment, organ transplantation medicine and cardiac surgery with cardiopulmonary bypass within the past decade have an important impact on the general hospital inpatients; psychosocial outcome. One follow-up study of long-term acute respiratory distress syndrome (ARDS) survivors using the Structural Clinical Interview for the DSM-IV (SCID) has shown that 43.5% of these patients met the criteria for a full posttraumatic stress disorder (PTSD), 8.9% of these patients for a subthreshold or partial PTSD (sub-PTSD) at hospital discharge, and 23.9% of them still suffered from full PTSD, 17.8% of them from sub-PTSD. ARDS-Patients with PTSD symptomatology exhibited major impairments in a variety of dimensions of health-related quality of life. Another outcome study examining concurrently psychiatric morbidity and quality of life in intermediate-term survivors of orthotopic liver transplantation (OLT) survivors has documented that 5.4% of these patients had a full PTSD, and 17.3% of them a sub-PTSD at 4 year-follow-up. OLT- related PTSD symptomatology was associated with maximal decrements in health-related quality of life. The duration of intensive care treatment, the number of medical complications, and the occurrence of acute rejection were positively correlated with the risk of PTSD symptoms subsequent to OLT. Finally, one prospective 1-year outcome study has focused on psychiatric morbidity including postoperative delirium in patients who had undergone cardiac surgery employing cardiopulmonary bypass. Postoperative delirium developed in 32.4% of these patients, however, only in 5.9% of them severe delirium was noted. Short-term consequences of cardiac surgery included adjustment disorders with depressed features (32.4%), acute full in-hospital PTSD (17.6%), and in-hospital major depression (17.6%). The diagnostic status of in-hospital PTSD was linked to postoperative delirium. At 12 months, the severity of depression and anxiety disorders including PTSD improved and returned to the preoperative level. However, patients who were found to have major depression or PTSD before discharge, C-L psychiatric consultations were conducted. In conclusion, PTSD symptoms following medical illness and treatment are not rare. If they are untreated, PTSD symptoms such as intrusive recollections, avoidance and hyper-arousal may impair the patients; quality of life more than the primary disease. This seems to be also true for a subthreshold PTSD. To adequately diagnose and treat patients at risk of developing PTSD, close collaboration between physicians of all subspecialties and C-L psychiatrists will be necessary.\n\nRothenhäusler, Hans-Bernd\n\n\n"
},
{
"text": "\n1748\nSubmaximal stimulation of porcine endothelial cells causes focal Ca2+ elevation beneath the cell membrane.\n\nGraier, WF\n\nPaltauf-Doburzynska, J\n\nHill, BJ\n\nFleischhacker, E\n\nHoebel, BG\n\nKostner, GM\n\nSturek, M\n\nBeiträge in Fachzeitschriften\nISI:000071648500009\n9481676.0\n10.1111%2Fj.1469-7793.1998.109bx.x\nPMC2230695\n1. Endothelial cell activation is correlated with increased cytosolic Ca2+ concentration, often monitored with cytoplasmic Ca2+ dyes, such as fura-2 and Calcium Green-1. We tested the hypothesis that during weak stimulation of porcine coronary artery endothelial cells, focal, subplasmalemmal Ca2+ elevations occur which are controlled by cell membrane Na(+)-Ca2+ exchange near mitochondrial membrane and superficial endoplasmic reticulum (SER). 2. Bulk Ca2+ concentration ([Ca2+]b) was monitored using fura-2 or Calcium Green-1 and subplasmalemmal Ca2+ concentration ([Ca2+]sp) was determined with FFP-18. The distribution of the SER network was estimated using laser scanning and deconvolution microscopy. 3. Sodium fluoride (10 mmol l-1) and submaximal concentrations of bradykinin (Bk; 1 nmol l-1) stimulated Ca2+ entry with no increase in [Ca2+]b. Although inositol 1, , -trisphosphate formation and intracellular Ca2+ release in response to both stimuli were similar, Ca2+ entry in response to NaF exceeded that in response to 1 nmol l-1 BK by fourfold, suggesting additional effects of NaF on Ca+ entry pathways but stimulation via intracellular Ca2+ release. 4. Prevention of Na(+)-Ca2+ exchange activity by decreasing extracellular Na+ unmasked intracellular Ca2+ release in response to NaF and 1 nmol l-1 Bk, indicated by an increase in [Ca2+]b. Thereby, NaF depleted Bk-releasable Ca2+ pools, while mitochondrial Ca2+ content (released with FCCP or oligomycin) and the amount of Ca2+ stored within the cells (released with ionomycin) was increased compared with cells treated with NaF under normal Na+ conditions. The NaF-initiated increase in [Ca2+]b and depletion of Bk-releasable Ca2+ pool(s) in the low-Na+ condition was diminished by 25 mumol l-1 ryanodine, indicating the involvement of Ca(2+)-induced Ca2+ release (CICR). 5. In simultaneous recordings of [Ca2+]sp (with FFP-18) and [Ca2+]b (with Calcium Green-1), 1 nmol l-1 Bk or 10 mmol l-1 NaF yielded focal [Ca2+] elevation in the subplasmalemmal region with no increase in the perinuclear area. 6. Treatment with 10 mumol-1 nocodazole caused the SER to collapse and unmasked Ca2+ release in response to 1 nmol l-1 Bk and 10 mmol l-1 NaF, similar to low-Na+ conditions, while the effect of thapsigargin was not changed. 7. These data show that in endothelial cells, focal, subplasmalemmal Ca2+ elevations in response to small or slow IP3 formation occur due to vectorial Ca2+ release from the SER towards the plasmalemma followed by Ca2+ extrusion by Na(+)-Ca2+ exchange. While these local Ca2+ elevations are not detectable with Ca2+ dyes for the determination of [Ca2+]b, prevention of Ca2+ extrusion or SER disruption yields increases in [Ca2+]b partially due to CICR. 8. All of the data support our hypothesis that in weakly stimulated endothelial cells, intracellular Ca2+ release and [Ca2+] elevation are limited to the subplasmalemmal region. We propose that the SER co-operates with associated parts of the plasma membrane to control Ca2+ homeostasis, Ca2+ distribution and Ca2+ entry. The existence of such a subplasmalemmal Ca2+ control unit (SCCU) needs to be considered in discussions of Ca2+ signalling, especially when cytoplasmic Ca2+ dyes, such as fura-2 or Calcium Green-1, are used.\n\nGraier, Wolfgang\n\nKostner, Gerhard\n\n\n"
},
{
"text": "\n114127\nLong-term effects of weight-reducing diets in hypertensive patients\n\nSiebenhofer, A\n\nJeitler, K\n\nBerghold, A\n\nWaltering, A\n\nHemkens, LG\n\nSemlitsch, T\n\nPachler, C\n\nStrametz, R\n\nHorvath, K\n\nBeiträge in Fachzeitschriften\nISI:000294642700046\n21901719.0\n10.1002/14651858.CD008274.pub2\nNone\nBackground All major guidelines for antihypertensive therapy recommend weight loss. Thus dietary interventions that aim to reduce body weight might be a useful intervention to reduce blood pressure and adverse cardiovascular events associated with hypertension. Objectives Primary objectives To assess the long-term effects of weight-reducing diets in hypertensive patients on - all cause mortality - cardiovascular morbidity - adverse events (including total serious adverse events, withdrawal due to adverse events and total non-serious adverse events) Secondary objectives To assess the long-term effects of weight-reducing diets in hypertensive patients on - change from baseline in systolic blood pressure - change from baseline in diastolic blood pressure - body weight reduction Search strategy Studies were obtained from computerised searches of Ovid MEDLINE, EMBASE, CENTRAL and from searches in reference lists and systematic reviews. Selection criteria Randomised controlled trials (RCT) in adult hypertensive patients were included if they had a study duration of at least 24 weeks and compared weight reducing dietary interventions to no dietary intervention in adult patients with primary hypertension. Data collection and analysis Two authors independently assessed risk of bias and extracted data. Studies were pooled using fixed- effect meta- analysis. In case of moderate or larger heterogeneity as measured by Higgins I2, a random effects model was used. Main results Eight studies involving a total of 2100 participants with high blood pressure and a mean age of 45 to 66 years met our inclusion criteria. Mean treatment duration was 6 to 36 months. No study included mortality as a pre- defined outcome. One RCT evaluated the effects of dietary weight loss on a combined endpoint, consisting of the necessity of reinstating antihypertensive therapy and severe cardiovascular complications. In this RCT weight reducing diet lowered the endpoint, hazard ratio 0.70 (95% confidence interval [CI], 0.57 to 0.87) compared to no diet. None of the studies evaluated adverse events as designated in our protocol. Blood pressure was reduced in patients assigned to weight loss diets as compared to controls: systolic blood pressure (SBP): weighted mean difference (WMD): -4.5 mm Hg; 95% CI, -7.2 to -1.8 mm Hg (3 of 8 studies included in analysis), and diastolic blood pressure (DBP): WMD -3.2 mm Hg; 95% CI, -4.8 to -1.5 mm Hg (3 of 8 studies included in analysis). Patients' body weight was also reduced in dietary weight loss groups as compared to controls, WMD of -4.0 kg (95% CI: -4.8 to -3.2) (5 of 8 studies included in analysis). Two studies used withdrawal of antihypertensive medication as their primary outcome. Even though this was not considered a relevant outcome for this review, the results of these studies strengthen the finding of reduction of blood pressure by dietary weight loss interventions. Authors' conclusions In patients with primary hypertension, weight loss diets reduced body weight and blood pressure, however the magnitude of the effects are uncertain as a result of the small number of patients and studies that could be included in the analyses. It is not known whether weight loss reduces mortality and morbidity. No useful information on adverse effects was reported in the relevant trials.\n\nBerghold, Andrea\n\nHorvath, Karl\n\nJeitler, Klaus\n\nSemlitsch, Thomas\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n152346\nPhysical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.\n\nKilpeläinen, TO\n\nQi, L\n\nBrage, S\n\nSharp, SJ\n\nSonestedt, E\n\nDemerath, E\n\nAhmad, T\n\nMora, S\n\nKaakinen, M\n\nSandholt, CH\n\nHolzapfel, C\n\nAutenrieth, CS\n\nHyppönen, E\n\nCauchi, S\n\nHe, M\n\nKutalik, Z\n\nKumari, M\n\nStančáková, A\n\nMeidtner, K\n\nBalkau, B\n\nTan, JT\n\nMangino, M\n\nTimpson, NJ\n\nSong, Y\n\nZillikens, MC\n\nJablonski, KA\n\nGarcia, ME\n\nJohansson, S\n\nBragg-Gresham, JL\n\nWu, Y\n\nvan Vliet-Ostaptchouk, JV\n\nOnland-Moret, NC\n\nZimmermann, E\n\nRivera, NV\n\nTanaka, T\n\nStringham, HM\n\nSilbernagel, G\n\nKanoni, S\n\nFeitosa, MF\n\nSnitker, S\n\nRuiz, JR\n\nMetter, J\n\nLarrad, MT\n\nAtalay, M\n\nHakanen, M\n\nAmin, N\n\nCavalcanti-Proença, C\n\nGrøntved, A\n\nHallmans, G\n\nJansson, JO\n\nKuusisto, J\n\nKähönen, M\n\nLutsey, PL\n\nNolan, JJ\n\nPalla, L\n\nPedersen, O\n\nPérusse, L\n\nRenström, F\n\nScott, RA\n\nShungin, D\n\nSovio, U\n\nTammelin, TH\n\nRönnemaa, T\n\nLakka, TA\n\nUusitupa, M\n\nRios, MS\n\nFerrucci, L\n\nBouchard, C\n\nMeirhaeghe, A\n\nFu, M\n\nWalker, M\n\nBorecki, IB\n\nDedoussis, GV\n\nFritsche, A\n\nOhlsson, C\n\nBoehnke, M\n\nBandinelli, S\n\nvan Duijn, CM\n\nEbrahim, S\n\nLawlor, DA\n\nGudnason, V\n\nHarris, TB\n\nSørensen, TI\n\nMohlke, KL\n\nHofman, A\n\nUitterlinden, AG\n\nTuomilehto, J\n\nLehtimäki, T\n\nRaitakari, O\n\nIsomaa, B\n\nNjølstad, PR\n\nFlorez, JC\n\nLiu, S\n\nNess, A\n\nSpector, TD\n\nTai, ES\n\nFroguel, P\n\nBoeing, H\n\nLaakso, M\n\nMarmot, M\n\nBergmann, S\n\nPower, C\n\nKhaw, KT\n\nChasman, D\n\nRidker, P\n\nHansen, T\n\nMonda, KL\n\nIllig, T\n\nJärvelin, MR\n\nWareham, NJ\n\nHu, FB\n\nGroop, LC\n\nOrho-Melander, M\n\nEkelund, U\n\nFranks, PW\n\nLoos, RJ\n\nBeiträge in Fachzeitschriften\nISI:000298133100003\n22069379.0\n10.1371/journal.pmed.1001116\nPMC3206047\nThe FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218, 66) and nine studies of children and adolescents (n = 19, 68).\n All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents.\n The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.\n\nSilbernagel, Günther\n\n\n"
},
{
"text": "\n2192\nRandomized open label phase III trial of CEOP/IMVP-Dexa alternating chemotherapy and filgrastim versus CEOP/IMVP-Dexa alternating chemotherapy for aggressive non-Hodgkin's lymphoma (NHL). A multicenter trial by the Austrian Working Group for Medical Tumor Therapy.\n\nFridrik, MA\n\nGreil, R\n\nHausmaninger, H\n\nKrieger, O\n\nOppitz, P\n\nStöger, M\n\nKlocker, J\n\nNeubauer, M\n\nHelm, W\n\nPont, J\n\nFazeny, B\n\nHudec, M\n\nSimonitsch, I\n\nRadaszkiewicz, T\n\nBeiträge in Fachzeitschriften\nISI:A1997YJ51900001\n9402845.0\n10.1007%2Fs002770050330\nNone\nPrimary end point of this trial was to reduce neutropenic infections during the treatment of aggressive NHL with CEOP/IMVP-Dexa (cyclophosphamide, epirubicin, vincristine, prednisolone ifosfamide, methotrexate, VP-16, and dexamethasone). Further, we studied the influence of filgrastim on dose intensity of CEOP/IMVP-Dexa, on the rate of complete remissions, on the time to relapse, and on survival. Eighty-five patients with untreated large-cell NHL were randomized to one of two treatment arms; 74 patients were eligible. Thirty-eight patients in arm 1 were treated with CEOP/IMVP-Dexa chemotherapy and filgrastim, 36 in arm 2 with CEOP/IMVP-Dexa chemotherapy alone. In arm 1 filgrastim was self-injected by the patients at 5 micrograms/kg body wt. s.c. daily, except on the days when cytotoxic drugs were given. During treatment we did weekly complete blood counts. Median leukocyte counts were 10.91 x 10(9)/l and 5.46 x 10(9)/l in arm 1 and 2, respectively (p = 10(-6)). Median neutrophil counts were 7.7 x 10(9)/l in arm 1 and 2.72 x 10(9)/l in arm 2 (p < 10(-6)). Median neutrophil nadirs were 0.199 x 10(9)/l and 0.213 x 10(9)/l in arm 1 and 2, respectively (p = 0.09). Mean platelet nadirs were 95 and 152 x 10(9)/l (p = 0.000004) and mean hemoglobin nadirs 83.95 g/l and 92.78 g/l (p = 0.00558) in arm 1 and 2, respectively. Dose intensity of CEOP/IMVP-Dexa was 82.3% and 76.2% in arm 1 and 2, respectively (p = 0.041). Forty-two percent and 58% of patients experienced a febrile neutropenia in arm 1 and 2, respectively (not significant, NS). Median time to first neutropenic infection was in treatment week 11 and 6 in arm 1 and 2, respectively (NS). There was no significant difference in rate, duration, and kind of infection, duration of hospitalization, or antibiotic treatment. Seven toxic deaths occurred, all due to neutropenic infection, 6 and 1 in arm 1 and 2, respectively (p = 0.0732). Four of the six patients, who died of infection in arm 1 were older than 60 years. Complete remission rate was 83% and 66.7% in arm 1 and 2, respectively (NS). After a median observation time of 3 years there was no difference in time to relapse or survival. Filgrastim increases leukocyte and neutrophil counts and dose intensity, if used with CEOP/IMVP-Dexa chemotherapy in high-grade lymphomas. There was no significant effect on febrile neutropenia or infections. The more frequent fatal neutropenic infection rate in the filgrastim arm was not statistically significant. It is most appropriate to explain it by the patient's age in combination with the high dose intensity. The small increase in dose intensity had no effect on survival but probably decreased hemoglobin levels and platelet counts in arm 1. We were unable to show a benefit for filgrastim in combination with CEOP/IMVP-Dexa.\n\n\n"
},
{
"text": "\n95955\nRecombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients.\n\nGovender, S\n\nCsimma, C\n\nGenant, HK\n\nValentin-Opran, A\n\nAmit, Y\n\nArbel, R\n\nAro, H\n\nAtar, D\n\nBishay, M\n\nBörner, MG\n\nChiron, P\n\nChoong, P\n\nCinats, J\n\nCourtenay, B\n\nFeibel, R\n\nGeulette, B\n\nGravel, C\n\nHaas, N\n\nRaschke, M\n\nHammacher, E\n\nvan der Velde, D\n\nHardy, P\n\nHolt, M\n\nJosten, C\n\nKetterl, RL\n\nLindeque, B\n\nLob, G\n\nMathevon, H\n\nMcCoy, G\n\nMarsh, D\n\nMiller, R\n\nMunting, E\n\nOevre, S\n\nNordsletten, L\n\nPatel, A\n\nPohl, A\n\nRennie, W\n\nReynders, P\n\nRommens, PM\n\nRondia, J\n\nRossouw, WC\n\nDaneel, PJ\n\nRuff, S\n\nRüter, A\n\nSantavirta, S\n\nSchildhauer, TA\n\nGekle, C\n\nSchnettler, R\n\nSegal, D\n\nSeiler, H\n\nSnowdowne, RB\n\nStapert, J\n\nTaglang, G\n\nVerdonk, R\n\nVogels, L\n\nWeckbach, A\n\nWentzensen, A\n\nWisniewski, T\n\nBMP-2 Evaluation in Surgery for Tibial Trauma (BESTT) Study Group\n\nBeiträge in Fachzeitschriften\nISI:000179617500001\n12473698.0\n10.2106/00004623-200212000-00001\nNone\nBACKGROUND: The treatment of open fractures of the tibial shaft is often complicated by delayed union and nonunion. The objective of this study was to evaluate the safety and efficacy of the use of recombinant human bone morphogenetic protein-2 (rhBMP-2; dibotermin alfa) to accelerate healing of open tibial shaft fractures and to reduce the need for secondary intervention. METHODS: In a prospective, randomized, controlled, single-blind study, 450 patients with an open tibial fracture were randomized to receive either the standard of care (intramedullary nail fixation and routine soft-tissue management [the control group]), the standard of care and an implant containing 0.75 mg/mL of rhBMP-2 (total dose of 6 mg), or the standard of care and an implant containing 1.50 mg/mL of rhBMP-2 (total dose of 12 mg). The rhBMP-2 implant (rhBMP-2 applied to an absorbable collagen sponge) was placed over the fracture at the time of definitive wound closure. Randomization was stratified by the severity of the open wound. The primary outcome measure was the proportion of patients requiring secondary intervention because of delayed union or nonunion within twelve months postoperatively. RESULTS: Four hundred and twenty-one (94%) of the patients were available for the twelve-month follow-up. The 1.50-mg/mL rhBMP-2 group had a 44% reduction in the risk of failure (i.e., secondary intervention because of delayed union; relative risk = 0.56; 95% confidence interval = 0.40 to 0.78; pairwise p = 0.0005), significantly fewer invasive interventions (e.g., bone-grafting and nail exchange; p = 0.0264), and significantly faster fracture-healing (p = 0.0022) than did the control patients. Significantly more patients treated with 1.50 mg/mL of rhBMP-2 had healing of the fracture at the postoperative visits from ten weeks through twelve months (p = 0.0008). Compared with the control patients, those treated with 1.50 mg/mL of rhBMP-2 also had significantly fewer hardware failures (p = 0.0174), fewer infections (in association with Gustilo-Anderson type-III injuries; p = 0.0219), and faster wound-healing (83% compared with 65% had wound-healing at six weeks; p =0.0010). CONCLUSIONS: The rhBMP-2 implant was safe and, when 1.50 mg/mL was used, significantly superior to the standard of care in reducing the frequency of secondary interventions and the overall invasiveness of the procedures, accelerating fracture and wound-healing, and reducing the infection rate in patients with an open fracture of the tibia.\n\n\n"
},
{
"text": "\n177422\nHow to Avoid Posterior Interosseous Nerve Injury During Single-Incision Distal Biceps Repair Drilling.\n\nBecker, D\n\nLopez-Marambio, FA\n\nHammer, N\n\nKieser, D\n\nBeiträge in Fachzeitschriften\nISI:000472544900031\n30444757.0\n10.1097/CORR.0000000000000534\nPMC6370103\nThe posterior interosseous nerve (PIN) is occasionally damaged during distal biceps tendon repair. But to our knowledge, no studies have examined the position of the PIN in relation to the bicipital tuberosity in full supination, which is the recommended position during single-incision distal biceps repair or reconstruction QUESTIONS/PURPOSES: (1) What is the anterior safe zone when exposing the anterior tuberosity with the arm in supination? (2) When drilling the radial tuberosity for bicortical button placement in full supination, how should the drill be angled to avoid PIN injury?\n Fifteen adult cadaver elbows had the PIN dissected around the proximal radius. The position of the PIN was measured relative to the most ulnar aspect of the radius at three sites in full supination: at the bicipital tuberosity (bicipital tuberosity-PIN), 10 mm proximal to the bicipital tuberosity (bicipital tuberosity-proximal), and 10 mm distal to the bicipital tuberosity (bicipital tuberosity-distal). We made another measurement by drawing a line from the lateral humeral epicondyle to the radial styloid. The point where the PIN intersects this line, when viewed laterally and measured from the lateral humeral epicondyle, was marked and measured to indicate where it wraps around the radius laterally (PIN-lateral). The last measurement (bicipital tuberosity-lateral) was made where the line from the lateral humeral epicondyle to the radial styloid intersected the position of the bicipital tuberosity. This was determined by the point where a perpendicular line from the bicipital tuberosity was drawn laterally to meet with the lateral line. We did this to establish if the PIN adopts its most lateral position on the radius at the same level as the bicipital tuberosity.\n The anterior safe zone in the approach to the biceps tuberosity extends approximately 15 mm from its prominence (mean, 20.7 mm; range, 16.0-24.1 mm). The PIN crosses the lateral midline from anterior to posterior at 46.0 mm (range, 31.2-67.0 mm) from the lateral epicondyle (lying directly opposite the bicipital tuberosity at nearly the same level); therefore, the drill exit should be posterior to lateral midline while aiming proximally to the bicipital tuberosity.\n Our anterior safe zone found that the PIN travels from an anterior position on the radius, when measuring 1 cm proximal to the bicipital tuberosity to a lateral position on the radius at the level of the bicipital tuberosity prominence (on the contralateral cortex), to a slightly more posterior position on the radius 1 cm distal to the bicipital tuberosity. Typically, the PIN sits directly opposite the biceps tuberosity, often directly on the cortex of the radius when the forearm is in full supination.\n Because of these findings, perpendicular bicortical drilling starting at the bicipital tuberosity should be avoided. A more proximal and ulnar drilling angle is recommended. Defining a safe zone for an anterior approach seems to be clinically unhelpful due to the high anatomical variability that exists for the position of the PIN around the proximal radius. Future studies could attempt to confirm our findings with the analysis of noncadaveric imaging in three different planes using such modalities as MRI to avoid the effects of tissue distortion during cadaveric preparation and dissection.\n\nHammer, Niels\n\n\n"
},
{
"text": "\n146604\nDiagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline.\n\nStratigos, A\n\nGarbe, C\n\nLebbe, C\n\nMalvehy, J\n\ndel Marmol, V\n\nPehamberger, H\n\nPeris, K\n\nBecker, JC\n\nZalaudek, I\n\nSaiag, P\n\nMiddleton, MR\n\nBastholt, L\n\nTestori, A\n\nGrob, JJ\n\nEuropean Dermatology Forum (EDF)\n\nEuropean Association of Dermato-Oncology (EADO)\n\nEuropean Organization for Research and Treatment of Cancer (EORTC)\n\nBeiträge in Fachzeitschriften\nISI:000360081300017\n26219687.0\n10.1016/j.ejca.2015.06.110\nNone\nCutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in Caucasian populations, accounting for 20% of all cutaneous malignancies. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing guidelines and the expert's experience. The diagnosis of cSCC is primarily based on clinical features. A biopsy or excision and histologic confirmation should be performed in all clinically suspicious lesions in order to facilitate the prognostic classification and correct management of cSCC. The first line treatment of cutaneous SCC is complete surgical excision with histopathological control of excision margins. The EDF-EADO-EORTC consensus group recommends a standardised minimal margin of 5 mm even for low-risk tumours. For tumours, with histological thickness of >6 mm or in tumours with high risk pathological features, e.g. high histological grade, subcutaneous invasion, perineural invasion, recurrent tumours and/or tumours at high risk locations an extended margin of 10 mm is recommended. As lymph node involvement by cSCC increases the risk of recurrence and mortality, a lymph node ultrasound is highly recommended, particularly in tumours with high-risk characteristics. In the case of clinical suspicion or positive findings upon imaging, a histologic confirmation should be sought either by fine needle aspiration or by open lymph node biopsy. In large infiltrating tumours with signs of involvement of underlying structures, additional imaging tests, such as CT or MRI imaging may be required to accurately assess the extent of the tumour and the presence of metastatic spread. Current staging systems for cSCC are not optimal, as they have been developed for head and neck tumours and lack extensive validation or adequate prognostic discrimination in certain stages with heterogeneous outcome measures. Sentinel lymph node biopsy has been used in patients with cSCC, but there is no conclusive evidence of its prognostic or therapeutic value. In the case of lymph node involvement by cSCC, the preferred treatment is a regional lymph node dissection. Radiation therapy represents a fair alternative to surgery in the non-surgical treatment of small cSCCs in low risk areas. It generally should be discussed either as a primary treatment for inoperable cSCC or in the adjuvant setting. Stage IV cSCC can be responsive to various chemotherapeutic agents; however, there is no standard regimen. EGFR inhibitors such as cetuximab or erlotinib, should be discussed as second line treatments after mono- or polychemotherapy failure and disease progression or within the framework of clinical trials. There is no standardised follow-up schedule for patients with cSCC. A close follow-up plan is recommended based on risk assessment of locoregional recurrences, metastatic spread or development of new lesions.\n Copyright © 2015 Elsevier Ltd. All rights reserved.\n\nZalaudek, Iris\n\n\n"
}
]
}