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AIMS: Despite relatively favourable outcomes associated with IDH-mutant grade 3 gliomas, many patients present with diffuse non-enhancing disease involving multiple brain regions, prompting concern over both durable disease control and the morbidity associated with large volume radiation therapy. This study audits volumetric response, survival and functional outcomes in this 'large volume' subgroup that undergoes intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: From a prospective database of 187 patients with IDH-mutant grade 3 gliomas managed with IMRT between 2008 and 2020, recorded PTV was divided into quartiles. The top quartile, termed the 'large volume cohort' (LVC), was identified. IMRT involved FET-FDG guided integrated boost (59.4/54Gy in 33 fractions). Manual volumetric segmentation of baseline, four months and 13 months post-IMRT tumour were performed for T1, T2 and T1gd MRI sequences. The primary endpoint was volumetric reduction on the T1 and T2 sequences at 13 months and analysed with relapse-free survival (RFS) and overall survival (OS). Morbidity endpoints were assessed at year four post-IMRT and included performance status (ECOG PS) and employment outcomes. RESULTS: The fourth quartile (LVC) identified 44 patients for whom volumetric analysis was available. The LVC had median PTV of 320cm3 compared to 186.2cm3 for the total group. Anaplastic astrocytoma and oligodendroglioma were equally distributed and tumour sites were frontal (54%), temporal (18%) and parietal lobes (16%). Median follow-up for survivors was 71.5 months. Projected 10-year RFS and OS in LVC was 40% and 62%, compared to 53% and 62% respectively in the overall cohort. The RFS (p = 0.06) and OS (p = 0.65) of the LVC was not significantly different to other PTV quartiles; however the impact of PTV volume reached significance when analysed as a continuous variable (RFS p < 0.01; OS p = 0.02). Median T1 volumes were 26.1cm3, 8.0cm3 and 5.3cm3 at months +0, +3 and +12, respectively. The corresponding T2 volumes were 120.8cm3, 29.1cm3 and 26.3cm3. The median T1 and T2 volume reductions were 77% (q1-3: 57-92%) and 78% (q1-3: 60-85%) at 13 months post-IMRT. Initial T2 volume was associated with worse RFS (p = 0.04) but not OS (p = 0.96). There was no association between median T2 volume reduction and RFS (p = 0.77). For patients assessable at year 4 post-IMRT, no late CTCAE Grade 3/4 toxicity events were recognised. 92% of patients were ECOG PS 0-1, 45% were employed at prior capacity and 28% were working with impairment. CONCLUSION: Patients with large volume IDH-mutant Grade 3 glioma demonstrated significant tumour reduction post-IMRT, and good long-term outcomes with respect to survival and functional status. Although larger IMRT volumes were associated with poorer RFS, this was also associated with the initial volume of non-enhancing tumour.
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Neoplasias Encefálicas , Fluorodesoxiglucosa F18 , Glioma , Isocitrato Deshidrogenasa , Radioterapia de Intensidad Modulada , Humanos , Masculino , Femenino , Radioterapia de Intensidad Modulada/métodos , Persona de Mediana Edad , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Glioma/radioterapia , Glioma/patología , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/mortalidad , Isocitrato Deshidrogenasa/genética , Adulto , Anciano , Mutación , Estudios Prospectivos , Radiofármacos/uso terapéutico , Clasificación del TumorRESUMEN
A 73-year-old woman underwent an awake craniotomy for the resection of a supratentorial brain tumour. We provided sedation for the surgery using a dexmedetomidine target controlled infusion using the Dyck pharmacokinetic model. Using a target controlled infusion allowed more rapid titration to the desired plasma level compared with a manual infusion, without any unexpected cardiovascular, respiratory or other complications. Rapid titration of sedation during awake craniotomy is desirable, allowing deeper sedation during stimulating parts of the surgery, followed by lighter sedation - or absence of sedation - during cortical mapping. While this can be performed manually, we found utilising the Dyck model in this case simple and quick to use, avoiding the need to manually calculate infusion rates. We believe this is the first report of using a target controlled infusion model to administer dexmedetomidine for awake craniotomy, and suggest it could be considered as an alternative to administering a manual infusion.
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Success as a dancer is closely associated with positive dance judgments by perceivers. Although dancers' physical appearance (attractiveness, style) might affect dance judgments beyond dance-specific attributes (technique, expression), they have largely been unconsidered in previous studies. To contribute to a comprehensive explanation of real-life dance judgments, we applied the lens model, an approach explicitly developed to explain the emergence of social judgments by multiple attributes. Therefore, video-records of 70 solo performances were (1) rated regarding dancers' physical appearance, technique, and expression and (2) judged by 33 perceivers. Results of cross-classified mixed-effects models revealed that attributes of all domains were significantly related to dance judgements. Considered simultaneously, however, only dance-specific attributes contributed to the prediction of dance judgments. Additional moderation analyses underscored the importance of perceivers' expertise in judging dance. We discuss the lens model as suitable framework for a naturalistic approach to the study of aesthetic experiences and sports performances.
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Rendimiento Atlético , Baile , Cristalino , Lentes , Unionidae , Animales , JuicioRESUMEN
PURPOSE: H3K27M- and H3G34R-mutant gliomas are recently-classified subgroups of high-grade gliomas (HGGs) affecting younger adults. This study aimed to describe patterns of infiltration and failure, and the volumetric response of these tumours to radiotherapy. METHODS: Patients with histone-mutant gliomas aged 16-50 years, managed from 2009 to 2021 were identified and clinical, radiological and histopathological characteristics collected. Tumour volume was assessed on MRI at diagnosis, pre-radiotherapy, month + 1, + 3 and + 5 post-radiation and at relapse. RESULTS: Of 538 IDH1/2 wild-type HGGs, 18(15%) had a histone alteration. Eleven were H3K27M- and 7 H3G34R-mutant respectively. Median age at diagnosis was 20 years (range17-48 years). Median overall survival was 20 months (95%CI 14-29 months). Both H3K27M- and H3G34R-mutant tumours exhibited extensive T2F infiltration involving a median of 4 neuroanatomical subsites at diagnosis. Median volume of disease pre-radiotherapy on T1gd and T2F respectively was 0.5cm3 (IQR:0-1.7cm3) and 11.9 cm3 (IQR:7.5-29.6cm3) for H3K27M and 0.9cm3 (IQR:0-8.4cm3) and 43.8cm3 (IQR:25.2-86.6 cm3) for H3G34R tumours. T2F volume reduction > 50% was observed 3-months post-IMRT in 7(64%) patients with H3K27M and 1(14%) with H3G34R tumours. Fourteen patients had relapsed. Relapse was local-only, distant-only and both in 4(44%), 3(33%) and 2(22%) H3K27M-mutant and 1(20%), 2(40%), and 2(40%) H3G34R-mutant tumours. On last scan before death, leptomeningeal spread was present in 4/8(50%) and 1/5(20%) and subependymal spread in 4/8 (50%) and 0/5 H3K27M- and G34R-mutant cases respectively. CONCLUSION: H3K27M-mutant gliomas are highly responsive to radiotherapy but exhibit high propensity for subsequent leptomeningeal and subependymal spread. H3G34R-mutant tumours exhibit lesser early volumetric response to radiotherapy and propensity for distant in-brain failure.
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Neoplasias Encefálicas , Glioma , Humanos , Adulto , Adolescente , Adulto Joven , Persona de Mediana Edad , Histonas/genética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Pronóstico , Mutación , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/radioterapia , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/radioterapiaRESUMEN
BACKGROUND: Following surgical resection of oligometastatic disease to the brain there is a high rate of local relapse which is reduced by the addition of focal radiation therapy, often delivered as single fraction stereotactic radiosurgery (SRS) to the surgical cavity. This study audited the outcomes of an alternative approach using hypofractionated radiation therapy (HFRT) to the surgical resection cavity. METHODS AND MATERIALS: Seventy-nine patients who received surgical resection and focal radiation therapy to the surgical cavity using HFRT with intensity modulated radiation therapy with or without stereotactic radiotherapy were identified. Doses were delivered in five fractions every second day for 10 days. Follow-up involved MRI surveillance with three-monthly MRI scans post resection. The major endpoints were local control at the surgical cavity site, and presence of radiation necrosis at the treated site. RESULTS: Seventy-nine patients were included for the analysis with a median follow-up of 10.8 months. Of the cohort, 56% experienced intracranial progression, with all patients progressing distant to the resection cavity, and 7% progressing locally in addition. The one-year local control rate was 89.8%. The median progression-free survival was 10.0 months and median overall survival was 14.3 months. There was one CTCAE grade 3 toxicity of symptomatic radiation necrosis with no grade 4-5 toxicities seen. CONCLUSIONS: The rate of local relapse following HFRT to the surgical cavity is low with minimal risk of radiation necrosis. HFRT can be considered as an alternative to SRS for focal radiotherapy after brain metastasis resection.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Hipofraccionamiento de la Dosis de Radiación , Adulto , Anciano , Encéfalo , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Radiocirugia , Radioterapia de Intensidad Modulada , Estudios RetrospectivosRESUMEN
Large-scale health crises, such as the COVID-19 pandemic, may evoke negative affective responses, which are linked to psychological maladjustment and psychopathology. Here, we shed light on the role of the personality trait neuroticism in predicting who experiences negative affective responses. In a large-scale experience-sampling study (N = 1,609; 38,120 momentary reports), we showed that individuals high in neuroticism experienced more negative affect and higher affective variability in their daily lives. Individuals high in neuroticism also (a) paid more attention to COVID-19-related information and worried more about the consequences of the pandemic (crisis preoccupation), and (b) experienced more negative affect during this preoccupation (affective reactivity). These findings offer new insights into the consequences and dynamics of neuroticism in extreme environmental contexts.
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PURPOSE: The current study aimed to assess patterns of failure (PoF) in anaplastic glioma (AG) patients managed with intensity-modulated radiation therapy (IMRT) and their relationship to molecular subtype. METHODS: The outcomes of AG patients managed between 2008 and 2014 and entered into a prospective database were assessed, including PoF. AG was initially defined using the WHO 2007 classification, but for analysis, patients were subsequently recategorised based on WHO 2016 as anaplastic oligodendroglioma (AOD), astrocytoma isocitrate dehydrogenase (IDH) mutant (AAmut) or astrocytoma IDH wildtype (AAwt). Management involved IMRT and temozolomide (TMZ), including from 2011 patients with an IDH mutation (IDHmut) planned with 18F-fluoroethyltyrosine (FET) and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET). PoF was local, marginal or distant in relation to the IMRT volume. Relapse-free survival (RFS) was calculated from the start of IMRT. RESULTS: A total of 156 patients were assessed, with median follow-up of 5.1 years. Of these patients, 75% were IDHmut, 44% were managed at first or later relapse and 73% received TMZ. Relapse occurred in 68 patients, with 6year RFS of 75.0, 48.8 and 2.5% for AOD, AAmut and AAwt, respectively (pâ¯< 0.001). There was a component of local relapse in 63%, of marginal relapse in 19% and of distant relapse in 37% of relapses. Isolated local, marginal and distant relapse was evident in 51, 9 and 22%, respectively. A distant relapse pattern was more frequent in IDHmut compared to IDHwt patients (26% vs. 45%, pâ¯= 0.005), especially within the first 2 years post-IMRT. In multivariate analysis, distant relapse remained associated with AAmut (pâ¯< 0.002) and delayed IMRT until the second relapse (pâ¯< 0.001). CONCLUSION: Although patients with IDH-mutated AG have improved outcomes, there was a higher proportion of distant relapses occurring during the 2 years after IMRT.
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Astrocitoma , Neoplasias Encefálicas , Isocitrato Deshidrogenasa/genética , Recurrencia Local de Neoplasia , Oligodendroglioma , Adulto , Astrocitoma/genética , Astrocitoma/mortalidad , Astrocitoma/radioterapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/radioterapia , Terapia Combinada , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/radioterapia , Oligodendroglioma/genética , Oligodendroglioma/mortalidad , Oligodendroglioma/radioterapia , Tomografía de Emisión de Positrones , Radioterapia de Intensidad Modulada , Factores de Riesgo , Tasa de Supervivencia , Temozolomida/uso terapéutico , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Chemerin is an adipokine that signals through the G protein-coupled receptor ChemR23 and is associated with inflammation, glucose homeostasis, lipid metabolism and renal function, all of which strongly influence cardiovascular risk. However, elevated chemerin provides a survival advantage in patients with chronic kidney disease (CKD), but how this relates to the cardiovascular phenotype is unknown. OBJECTIVES: The aim of the present study was to establish the association of chemerin with coronary calcification and to determine the effects of chemerin signalling, through ChemR23, in vascular smooth muscle cell (VSMC) calcification. METHODS: Plasma chemerin was measured in 113 patients with CKD and 50 healthy controls. All patients underwent computed tomography to determine coronary artery calcium (CAC) score. VSMCs were isolated from wild-type and ChemR23 knock-out mice and treated with chemerin. RESULTS: Multivariate analyses established creatinine, cholesterol, body mass index and tumour necrosis factor as significant confounders for circulating chemerin levels. Despite these positive associations with renal function, cardiometabolic risk factors and inflammation, chemerin was inversely associated with CAC both in an age- and sex-adjusted analysis and in a multivariate analysis adjusting for the aforementioned confounders. In addition, circulating chemerin levels were associated with the calcification inhibitors matrix gla protein (MGP) and fetuin-A. Finally, chemerin significantly reduced phosphate-induced calcification and increased MGP expression in VSMCs, whereas chemerin was devoid of these effects in VSMCs lacking ChemR23. CONCLUSION: In conclusion, these results suggest that chemerin signalling through ChemR23 in VSMCs protects against vascular calcification in CKD.
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Calcinosis/sangre , Calcinosis/tratamiento farmacológico , Quimiocinas/sangre , Quimiocinas/farmacología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Animales , Índice de Masa Corporal , Calcinosis/diagnóstico por imagen , Estudios de Casos y Controles , Colesterol/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Inflamación , Pruebas de Función Renal , Trasplante de Riñón , Masculino , Ratones Noqueados , Persona de Mediana Edad , Transducción de Señal , Tomografía Computarizada por Rayos XRESUMEN
The recognition of specific molecular prognostic factors has altered the management of primary brain tumours over the past decade. These factors have allowed stratification of morphologically similar tumours into different prognostic groups and are now also being used to determine clinical trial eligibility. Many of these factors have been included in the revised fourth edition of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System, released in May 2016. This revised edition places greater emphasis on molecular testing and, for certain tumour types, molecular testing is required for diagnosis. Many pathology departments have also adopted the four-tiered report format suggested in the Haarlem guidelines, and provide a final 'integrated diagnosis' incorporating a morphological diagnosis, the WHO grade and molecular findings. Pathologists need to perform and report these molecular tests in a timeframe that is relevant for clinical decision-making. Clinicians need to understand and incorporate these changes into their daily practice, as they have direct effects on both the type and intent of therapeutic interventions.
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Neoplasias del Sistema Nervioso Central/clasificación , Neoplasias del Sistema Nervioso Central/genética , Glioma/clasificación , Glioma/genética , Biomarcadores de Tumor/genética , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/terapia , Toma de Decisiones Clínicas , Pruebas Genéticas , Glioma/diagnóstico , Glioma/terapia , Humanos , Organización Mundial de la SaludRESUMEN
BACKGROUND: Eldercare and care of people with functional impairments is organized by the municipalities in Sweden. Improving care in these areas is complex, with multiple stakeholders and organizations. Appropriate strategies to develop capability for continuing organizational improvement and learning (COIL) are needed. The purpose of our study was to develop and pilot-test a flexible, multilevel approach for COIL capability building and to identify what it takes to achieve changes in key actors' approaches to COIL. The approach, named "Sustainable Improvement and Development through Strategic and Systematic Approaches" (SIDSSA), was applied through an action-research and action-learning intervention. METHODS: The SIDSSA approach was tested in a regional research and development (R&D) unit, and in two municipalities handling care of the elderly and people with functional impairments. Our approach included a multilevel strategy, development loops of five flexible phases, and an action-learning loop. The approach was designed to support systems understanding, strategic focus, methodological practices, and change process knowledge - all of which required double-loop learning. Multiple qualitative methods, i.e., repeated interviews, process diaries, and documents, provided data for conventional content analyses. RESULTS: The new approach was successfully tested on all cases and adopted and sustained by the R&D unit. Participants reported new insights and skills. The development loop facilitated a sense of coherence and control during uncertainty, improved planning and problem analysis, enhanced mapping of context and conditions, and supported problem-solving at both the individual and unit levels. The systems-level view and structured approach helped participants to explain, motivate, and implement change initiatives, especially after working more systematically with mapping, analyses, and goal setting. CONCLUSIONS: An easily understood and generalizable model internalized by key organizational actors is an important step before more complex development models can be implemented. SIDSSA facilitated individual and group learning through action-learning and supported systems-level views and structured approaches across multiple organizational levels. Active involvement of diverse organizational functions and levels in the learning process was facilitated. However, the time frame was too short to fully test all aspects of the approach, specifically in reaching beyond the involved managers to front-line staff and patients.
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Atención a la Salud/organización & administración , Servicios de Salud para Ancianos/organización & administración , Mejoramiento de la Calidad , Desarrollo de Personal , Anciano , Personas con Discapacidad , Investigación sobre Servicios de Salud , Humanos , Aprendizaje , Proyectos Piloto , SueciaRESUMEN
BACKGROUND AND AIMS: Coffee contains many biologically active compounds with potential adverse or beneficial effects on the cardiovascular system. Whether coffee consumption is associated with the risk of aortic valve stenosis (AVS) is unknown. The purpose of this study was therefore to examine the association between coffee consumption and AVS incidence. METHODS AND RESULTS: This prospective study included 71 178 men and women who provided information on their coffee consumption through a questionnaire at baseline. Incident cases of AVS were identified through linkage with the Swedish National Patient and Cause of Death Registers. During a mean follow-up of 15.2 years, 1295 participants (777 men and 518 women) were diagnosed with AVS. Coffee consumption was positively associated with risk of AVS in a dose-response manner after adjustment for age, sex, smoking, and other risk factors (P-trend = 0.005). The multivariable hazard ratios were was 1.11 (95% confidence interval 1.04-1.19) per 2 cups/day increase of coffee consumption and 1.65 (95% confidence interval 1.10-2.48) when comparing the highest (≥6 cups/day) with the lowest (<0.5 cup/day) category of coffee consumption. The association was not modified by other risk factors. CONCLUSIONS: This study provides novel evidence that high coffee consumption is associated with an increased risk of AVS.
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Estenosis de la Válvula Aórtica/epidemiología , Café/efectos adversos , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Suecia/epidemiologíaRESUMEN
OBJECTIVE: To establish how guided physical activity in patients with rheumatoid arthritis (RA) without known cardiovascular disease affected vascular and cardiac function, and how these two entities were prospectively interconnected in this patient group. METHODS: Prospective substudy of 29 participants in the Physical Activity in RA (PARA) 2010 trial. All subjects were examined at baseline, at year 1 and 2 with measures of pulse wave velocity and arterial augmentation index, as well as echocardiographic evaluation of diastolic parameters and ventricular-arterial coupling. Muscle strength and aerobic exercise capacity were assessed at baseline and yearly. All participants performed physiotherapist-guided aerobic and muscle strength exercise during 2 years and were reminded through SMS to report physical activity progress. RESULTS: This cohort of patients with RA exhibited increased vascular stiffness despite normal blood pressure. At baseline, lower muscle strength was associated with increased vascular stiffness (ß = 0.68; P = 0.004), whereas lower aerobic working capacity was associated with left ventricular diastolic dysfunction (ß = 0.85; P = 0.03). There was a significant positive correlation between vascular stiffness and diastolic dysfunction at baseline (R2 = 0.64) and for the changes in those parameters observed during 2 years of guided physical activity. Finally, a significant improvement in ventricular-arterial coupling was observed after exercise (P < 0.001). CONCLUSION: These results indicate that although differentially associated with physical capacity parameters, improved vascular stiffness and improved diastolic dysfunction are interrelated, and that an optimization of the ventricular-arterial coupling may contribute to the beneficial effects of physical activity in patients with RA.
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Artritis Reumatoide/terapia , Terapia por Ejercicio/métodos , Rigidez Vascular , Disfunción Ventricular Izquierda/fisiopatología , Anciano , Artritis Reumatoide/fisiopatología , Presión Sanguínea , Ecocardiografía , Ejercicio Físico/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Entrenamiento de Fuerza , Resistencia Vascular , Rigidez Vascular/fisiologíaRESUMEN
BACKGROUND: Alcohol consumption and cigarette smoking are modifiable lifestyle factors with important impact on public health. It is unclear whether these factors influence the risk of aortic valve stenosis (AVS). OBJECTIVE: To investigate the associations of alcohol consumption and smoking, including smoking intensity and time since cessation, with AVS incidence in two prospective cohorts. METHODS: This analysis was based on data from the Swedish Mammography Cohort and the Cohort of Swedish Men, comprising 69 365 adults without cardiovascular disease at baseline. Participants were followed for AVS incidence and death by linkage to the Swedish National Patient and Causes of Death Registers. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards regression. RESULTS: Over a mean follow-up of 15.3 years, 1249 cases of AVS (494 in women and 755 in men) were recorded. Compared with never drinkers of alcohol (lifelong abstainers), the risk of AVS was significantly lower in current light drinkers (1-6 drinks per week [1 drink = 12 g alcohol]; multivariable HR 0.82; 95% CI: 0.68-0.99). The risk of AVS increased with increasing smoking intensity. Compared with never smokers, the HR was 1.46 (95% CI: 1.16-1.85) in current smokers of ≥30 pack-years. Former smokers who had quit smoking 10 or more years previously had similar risk for AVS as never smokers. CONCLUSIONS: This study suggests that current light alcohol consumption is associated with a lower risk of AVS, and indicates that the association between smoking and AVS risk is reversible.
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Consumo de Bebidas Alcohólicas/efectos adversos , Estenosis de la Válvula Aórtica/etiología , Fumar/efectos adversos , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Estenosis de la Válvula Aórtica/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Fumar/epidemiología , Encuestas y Cuestionarios , Suecia/epidemiologíaRESUMEN
In the field of novel applications involving upconverting processes, the determination of new strategies for realizing emission-tunable nanomaterials is a challenge. In this work the design of Y3+ and Er3+ codoped bismuth oxide-based upconverting nanoparticles is presented, evidencing that the active role of the matrix allows for the emission selectivity with chromaticity control. The bandgap of the bismuth oxide-based host can be manipulated in the range of 0.65 eV, consequently leading to upconversion emission color tunability from red to yellow-greenish. The resulting fine control of the nanoparticle chromaticity through accurate host bandgap engineering reveals a novel concept for the development of a new generation of upconverting nanophosphors.
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AIM: In patients with isocitrate dehydrogenase (IDH) mutated anaplastic glioma determine the dosimetric benefits of delivering radiation therapy using a PET guided integrated boost IMRT technique (ib-IMRT) compared with standard IMRT (s-IMRT) in reducing dose to normal brain. METHODS: Ten patients with anaplastic glioma, identified as a favourable molecular subgroup through presence of IDH mutation, and managed with radiation therapy using an ib-IMRT were enrolled into a dosimetric study comparing two RT techniques: s-IMRT to 59.4Gy or ib-IMRT with 59.4/54Gy regions. Gross Tumour volume (GTV) and Clinical Target Volumes (CTV) were determined by MRI, 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET imaging. A standard risk Planning Target Volume (PTVsr) receiving 59.4Gy (PTV59.4) in the s-IMRT technique was determined by MRI T2Flair and FET PET. For the ib-IMRT technique this PTVsr volume was treated to 54Gy, and the high-risk PTV (PTVhr) receiving 59.4Gy was determined as a higher risk region by FDG PET and MRI gadolinium enhancement. Standard dosimetric criteria and normal tissue constraints based on recent clinical trials were used in target delineation and planning. Normal Brain was defined as Brain minus CTV. Endpoints for dosimetric evaluation related to mean Brain dose (mBrainDose), brain volume receiving 40Gy (Brainv40) and 20Gy (Brainv20). The variation between the dosimetric endpoints for both techniques was examined using Wilcoxon analysis. RESULTS: The 10 patients had tumours located in temporal (1), parietal (3), occipital (2) and bifrontal (4) regions. In ib-IMRT technique the median volume of PTVhr was 25.5 cm3 compared with PTVsr of 300.0 cm3. For dose to PTVhr the two treatments were equivalent (p = 0.33), and although the ibIMRT had a prescribed 10% dose reduction from 59.4Gy to 54Gy the median reduction was only 5.9%. The ib-IMRT dosimetry was significantly improved in normal brain endpoints specifically mBrainDose (p = 0.007), Brainv40 (p = 0.005) and Brainv20 (p = 0.001), with a median reduction of 9.3%, 19.0 and 10.8% respectively. After a median follow-up of 38 months two patients have progressed, with no isolated relapse in the dose reduction region. CONCLUSION: An approach using ib-IMRT for anaplastic glioma produces significant dosimetric advantages in relation to normal brain dose compared with s-IMRT plan. This is achieved without a significant reduction to the target volume dose despite the reduction in prescribed dose. This technique has advantages to minimise potential late neurocognitive effects from high dose radiation in patients with favorable subtype anaplastic glioma with predicted median survival beyond ten years.
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Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Radioterapia de Intensidad Modulada/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
The aim of this review is to explore the changing utility of radiotherapy in the treatment of patients with glioblastoma over the past 60 years. Together with surgery, radiotherapy has always been the cornerstone of treatment of glioblastoma, but techniques have significantly advanced over this time. The exploration of early two-dimensional techniques, investigation of dose escalation, concomitant chemotherapy and modern techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and volumetric-modulated arc therapy will be covered. In addition, current controversies including decreasing margin size, re-irradiation, treatment of elderly patients, and novel imaging tracers will be discussed. Future directions including immunotherapy and tumour treating fields are examined. Radiotherapy-based treatments cannot rely solely on advances in chemotherapy or immunotherapy to improve the overall survival of patients with glioblastoma. Radiation oncology needs to continue to develop and improve the delivery, target definition, and dose of radiotherapy to these patients to improve their survival and the toxicity associated with treatment.
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Glioblastoma/radioterapia , Oncología por Radiación/tendencias , Anciano , Terapia Combinada , HumanosRESUMEN
AIMS: To determine pathological features that predict survival in patients having repeat craniotomy within 6 months of radiotherapy for high-grade glioma (HGG). MATERIALS AND METHODS: HGG patients (World Health Organization grade 3/4) managed with repeat craniotomy within 6 months of completing radiotherapy between 2008 and 2012 were included. Based on the presence of residual tumour cells, the pathology was reported as pathological progression or pathological pseudoprogression. The proliferation index (Ki67) was reported and compared with initial pathology as a percentage change. Tumour necrosis was estimated as a percentage of the specimen. Overall survival was calculated in months. RESULTS: Of 327 patients managed with HGG, 27 patients underwent repeat craniotomy within 6 months of radiotherapy. The median survival after reoperation was 11 months (95% confidence interval 1-22). Ki67 at reoperation of 0%, 1-9% and >10% was associated with survival with a median survival of 13, 13 and 3 months, respectively (P = 0.007). Change in Ki67 was also associated with median survival, with <50% reduction median survival 3 months, 50-80% median survival 7 months and >80% reduction median survival 13 months, P = 0.02. Widespread treatment-related necrosis improved outcome, with >80% necrosis having a median survival of 13 months versus 3 months in those with <80% necrosis (P = 0.003). CONCLUSION: The presence of residual tumour at repeat craniotomy within 6 months of radiotherapy is not an independent indicator of prognosis. Patients with residual tumour that had a low Ki67 had a similar median survival as those with only treatment necrosis. Reduced proliferation of residual tumour cells and widespread necrosis may be more important indicators for future outcome.
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Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/mortalidad , Proliferación Celular , Craneotomía/mortalidad , Glioma/mortalidad , Neoplasia Residual/mortalidad , Radioterapia Adyuvante/mortalidad , Adulto , Anciano , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Terapia Combinada , Femenino , Glioma/patología , Glioma/radioterapia , Glioma/cirugía , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Necrosis , Clasificación del Tumor , Neoplasia Residual/patología , Neoplasia Residual/radioterapia , Neoplasia Residual/cirugía , Pronóstico , Reoperación , Tasa de SupervivenciaRESUMEN
The immune reactions that regulate atherosclerotic plaque inflammation involve chemokines, lipid mediators and costimulatory molecules. Chemokines are a family of chemotactic cytokines that mediate immune cell recruitment and control cell homeostasis and activation of different immune cell types and subsets. Chemokine production and activation of chemokine receptors form a positive feedback mechanism to recruit monocytes, neutrophils and lymphocytes into the atherosclerotic plaque. In addition, chemokine signalling affects immune cell mobilization from the bone marrow. Targeting several of the chemokines and/or chemokine receptors reduces experimental atherosclerosis, whereas specific chemokine pathways appear to be involved in plaque regression. Leukotrienes are lipid mediators that are formed locally in atherosclerotic lesions from arachidonic acid. Leukotrienes mediate immune cell recruitment and activation within the plaque as well as smooth muscle cell proliferation and endothelial dysfunction. Antileukotrienes decrease experimental atherosclerosis, and recent observational data suggest beneficial clinical effects of leukotriene receptor antagonism in cardiovascular disease prevention. By contrast, other lipid mediators, such as lipoxins and metabolites of omega-3 fatty acids, have been associated with the resolution of inflammation. Costimulatory molecules play a central role in fine-tuning immunological reactions and mediate crosstalk between innate and adaptive immunity in atherosclerosis. Targeting these interactions is a promising approach for the treatment of atherosclerosis, but immunological side effects are still a concern. In summary, targeting chemokines, leukotriene receptors and costimulatory molecules could represent potential therapeutic strategies to control atherosclerotic plaque inflammation.
Asunto(s)
Endotelio Vascular/metabolismo , Inflamación , Comunicación Paracrina , Placa Aterosclerótica , Inmunidad Adaptativa , Animales , Quimiocinas/clasificación , Quimiocinas/metabolismo , Humanos , Inmunidad Celular , Inflamación/inmunología , Inflamación/fisiopatología , Leucotrienos/metabolismo , Lipoxinas/metabolismo , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/fisiopatología , Receptores de Quimiocina/clasificación , Receptores de Quimiocina/metabolismoRESUMEN
Systematic assessments of cathodoluminescence (CL) spectroscopy, Raman spectroscopy (RS), and X-ray diffraction (XRD) are presented for pure zirconia and for a series of Y-doped zirconia powders (henceforth, simply referred to as undoped ZrO2 and YSZ powders, respectively) synthesized according to a coprecipitation method of Zr and Y chlorides. Emphasis is placed here on spectral emissions related to oxygen-vacancy sites (i.e., oxygen hole states) equally detected from undoped and Y-doped ZrO2 samples, either as intrinsic defects or, extrinsically induced, by means of cathodoluminescence. Most counterintuitively, the undoped ZrO2 sample (i.e., the one with presumably the lowest amount of oxygen vacancies) experienced the strongest CL emission. A progressive "quenching" effect on CL emission with increasing the fraction of Y(3+) dopant could also be observed because the intrinsic vacancies present in the undoped lattice are the most efficient since they can trap two electrons to gain electrical neutrality. However, as soon as Y(3+) ions are introduced in the system, those intrinsic vacancies migrate to Y-sites in next-nearest-neighbor locations, namely in a less efficient lattice location. This phenomenon is tentatively referred to as "delocalization" of vacancy sites. Moreover, the fact that Y-doped zirconia series presents quite similar CL spectra compared to the undoped zirconia could be an evidence that the radiative centers of undoped and Y-doped ZrO2 are basically the same. A fitting procedure has been made aiming to give a rational description of the variation of the spectra morphology, and a parameter able to describe the monoclinic to tetragonal phase transformation has been found. This parameter and the overall set of CL data enabled us to quantitatively assess polymorphic phase fractions by CL spectroscopy in the scanning electron microscope.