Revisión del intervalo de referencia del recuento plaquetario: ¿son adecuados los valores que estamos utilizando? / Review of the platelet count reference range: are the values we are using appropriate?

Los intervalos de referencia (IR) dependen de la población y de las características metrológicas del procedimiento de medida utilizado. A pesar de las recomendaciones internacionales, son pocos los laboratorios que establecen sus propios IR para cada magnitud por la dificultad para conseguir voluntarios de referencia y el elevado costo económico asociado. La International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) acepta la adopción de IR bibliográficos o su cálculo por métodos indirectos dado su bajo costo y fácil obtención. Existen varias fuentes confiables de IR bibliográficos para el hemograma. No obstante, para el recuento plaquetario, es una práctica común de los laboratorios emplear el rango de valores de 150-450.109 /L independiente de la metodología utilizada y grupo etario. El objetivo de este trabajo fue revisar los IR bibliográficos disponibles para el recuento plaquetario y estimarlo empleando el método indirecto de Hoffmann a partir de nuestra población. Los métodos indirectos se basan en aplicar criterios de exclusión y cálculos matemáticos sobre los resultados de una base de datos de laboratorio. Nuestros IR para el recuento plaquetario se comparan con los bibliográficos, que han sido establecidos por técnicas de muestreo directo. Por este motivo y dado que no existen estudios poblacionales que lo avalen, sería apropiado reemplazar el rango de 150-450.109 / L. Estos límites podrían seguir empleándose como puntos de corte o niveles de decisión médica para definir, según la clínica y otros resultados de laboratorio, los pacientes que ameritan un seguimiento posterior (AU)

Reference ranges (RR) depend on the population and the metrological characteristics of the measurement procedure used. Despite international recommendations, few laboratories establish their own RRs for each magnitude because of the difficulty in obtaining reference volunteers and the associated high economic cost. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) accepts the use of literaturebased RRs or RRs calculated by indirect methods because of their low cost and easy collection. There are several reliable sources of literature-based RRs for the Cell Blood Count. However, for platelet count, it is common laboratory practice to use the range of 150-450,109 /L regardless of the methodology used and age group. The aim of this study was to review the available literature regarding RRs for platelet count and to establish it using the indirect Hoffmann method in our population. Indirect methods are based on applying exclusion criteria and mathematical calculations on the results of a laboratory database. Our RRs for platelet counts are compared with those in the literature, which have been established by direct sampling techniques. Therefore, and given that there are no population studies to support these findings, it would be appropriate to replace the 150-450,109 /L range. These limits may continue to be used as cut-off points or medical decision levels to define, according to clinical manifestations and other laboratory results, patients who warrant further follow-up (AU)

Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

Determination of essential biomarkers in lung cancer: a real-world data study in Spain with demographic, clinical, epidemiological and pathological characteristics.

BACKGROUND: The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. PATIENTS AND METHODS: The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. RESULTS: Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. CONCLUSIONS: Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer.

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC-a systematic review and meta-analysis.

BACKGROUND: The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory subgroup analysis, however, suggested a PFS benefit of the combination in patients with a smoking history and prompted us to do this study. METHODS: A systematic review and meta-analysis to evaluate the differential effect of smoking status on the benefit of adding an angiogenesis inhibitor to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy was carried out. All relevant randomized controlled trials appearing in main oncology congresses or in PubMed as of 1 November 2021 were used according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Primarily PFS according to smoking status, and secondarily overall survival (OS) were of interest. Pooled and interaction hazard ratios (HRs) were estimated by fixed or random effects models, depending on the detected degree of heterogeneity. Bias was assessed using the revised Cochrane tool for randomized controlled trials (RoB 2). RESULTS: Information by smoking was available for 1291 patients for PFS (seven studies) and 678 patients for OS (four studies). The risk of bias was low for all studies. Combination treatment significantly prolonged PFS for smokers [n = 502, HR = 0.55, 95% confidence interval (CI): 0.44-0.69] but not for nonsmokers (n = 789, HR = 0.92, 95% CI: 0.66-1.27; treatment-by-smoking interaction P = 0.02). Similarly, a significant OS benefit was found for smokers (n = 271, HR = 0.66, 95% CI: 0.47-0.93) but not for nonsmokers (n = 407, HR = 1.07, 95% CI: 0.82-1.42; treatment-by-smoking interaction P = 0.03). CONCLUSION: In advanced EGFR-non-small-cell lung cancer patients, the addition of an angiogenesis inhibitor to EGFR-tyrosine kinase inhibitor therapy provides a statistically significant PFS and OS benefit in smokers, but not in non-smokers. The biological basis for this observation should be pursued and could determine whether this might be due to a specific co-mutational pattern produced by tobacco exposure.

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.

The additional value of weight-bearing and gravity stress ankle radiographs in determining stability of isolated type B ankle fractures.

GOAL: The aim of this study is to investigate whether weight-bearing and gravity stress radiographs have additional value in predicting concomitant deep deltoid ligamentous (DDL) injury in case of isolated Weber type B fibular fractures. This may help to make the clinically relevant distinction between unstable fractures and fractures that can be treated conservatively. METHODS: In this prospective cohort study, 90 patients with an isolated type B ankle fracture, without a medial or posterior fracture, and a medial clear space (MCS) < 6 mm on the regular mortise (RM) view were included. In all patients, an additional gravity stress (GS) view and an MRI scan were performed. Furthermore, in 51 patients, an additional weight-bearing (WB) radiograph was performed. The MCS and superior clear space (SCS) measurements of these radiographs were compared with MRI findings to measure sensitivity and specificity in excluding deep deltoid ligament (DDL) rupture. RESULTS: The mean MCS on the RM view was 3.32 mm (1.73-5.93) compared to 4.75 mm (2.33-10.40) on the GS view and 3.18 mm (1.93-6.9) on the WB radiograph. MRI showed a high-grade or complete deltoid ligament tear in 25 (28%) patients. Using an MCS cut-off value of ≥ SCS + 2 mm, the RM view showed 0% sensitivity and 97% specificity in diagnosing a DDL rupture. Both the GS view (with MCS ≥ SCS + 3 mm as cut-off value) and the WB radiograph (with cut-off value MCS ≥ SCS + 2 mm) showed 6% sensitivity and 100% specificity. CONCLUSION: The gravity stress and weight-bearing radiograph can accurately exclude DDL injury. They might have extra value in addition to the conventional mortise view in assessing the stability of isolated type B ankle fractures. This helps in deciding whether patients should be selected for operative or safe conservative treatment.

Malignant pleural mesothelioma: Treatment patterns and outcomes from the Spanish Lung Cancer Group.

BACKGROUND: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain. MATERIAL AND METHODS: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments. RESULTS: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy. CONCLUSIONS: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.

[Factors that influence compliance with hand hygiene in healthcare professionals: A concept mapping study]. / Factores que influyen en el cumplimiento de la higiene de manos en profesionales sanitarios: un estudio de mapeo de conceptos.

OBJECTIVE: To identify factors that may influence hand hygiene compliance by professional category and clinical department. MATERIALS AND METHODS: Use was made of concept mapping methodology, a tool that combines a qualitative analysis with a quantitative statistical analysis, in order to identify the most influential and important factors for the fulfilment of hand hygiene in 2 clinical departments (Infectious and General Surgery) of the Hospital del Mar. RESULTS: The study included a total of 42 volunteer professionals from General Surgery (6 doctors and 10 nurses) and from Infectious Diseases (11 doctors and 10 nurses) clinical departments, as well as 5 hospital porters. High correlations of influential and important factors for hand hygiene compliance were observed between nurses and doctors in the Infectious Diseases Department (r=0.93 vs. r=0.69, respectively). In contrast, the correlation was lower among surgical professionals (r=-0.17 for influence and r=0.51 for importance). Professionals identified the most influential factors in compliance as training and adequate resources, taking into account professional category and clinical department. CONCLUSION: The design of interventions to improve compliance with hand hygiene should take into account the perceptions of different professionals in order to adapt actions to each professional group.

Cancer-related fatigue and its determinants in a cohort of women with breast cancer: the DAMA Cohort.

Cancer-related fatigue (CRF) is one of the most prolonged discomforts suffered by people who have had cancer. Seventy-eight to ninety-six percent of cancer patients experience fatigue, especially while undergoing treatment. CRF is related to insomnia, anxiety, depression, and also varies depending on age. However, little is known about the factors contributing to CRF and better understanding of determinants of CRF makes it easier to identify early patients at risk and in designing intervention planning. The aim of this study was to assess the influence of precipitating factors (diagnosis of breast cancer and other clinical aspects) and perpetuating factors (social network, quality of life, mental disorders) on the presence of chronic fatigue in women from our cultural context, by social class each other determinants. METHODS: It was carried out a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were data from the Brief Fatigue Inventory questionnaire and hospital medical records. The dependent variable was fatigue and the independent variables were age, social class, time since diagnoses, cohabitation, comorbidity, relapse, body mass index, mental health (anxiety and depression), social network, social support, and quality of life. RESULTS: Seventy-two percent of the women in the DAMA cohort reported moderate to severe fatigue. Risk of suffering from severe fatigue was greatest among individuals with low social class, those aged under 50 years, those with chronic disorders who had relapsed, and those with symptoms of anxiety and depression. In our study, CRF did not appear to be related to the stage of the cancer at diagnosis, or to the time since diagnosis. CONCLUSIONS: CRF is an element that the professionals responsible for the control and monitoring of women should take into account as another element to be taken into consideration.

Impact of an osteoporosis specialized unit on bone health in breast cancer survivals treated with aromatase inhibitors.

OBJECTIVE: Considering the increased fracture risk in early breast cancer patients treated with aromatase inhibitors (AI), we assessed the impact of a preventive intervention conducted by a specialized osteoporosis unit on bone health at AI treatment start. MATERIAL AND METHODS: Retrospective cohort of postmenopausal women who started treatment with AI after breast cancer surgical/chemotherapy treatment and were referred to the osteoporosis unit for a comprehensive assessment of bone health. Bone densitometry and fracture screening by plain X-ray were performed at the baseline visit and once a year for 5 years. RESULTS: The final record included 130 patients. At AI treatment start, 49% had at least one high-risk factor for fractures, 55% had osteopenia, and 39% osteoporosis. Based on the baseline assessment, 79% of patients initiated treatment with bisphosphonates, 88% with calcium, and 79% with vitamin D. After a median of 65 (50-77) months, 4% developed osteopenia or osteoporosis, and 14% improved their densitometric diagnosis. Fifteen fractures were recorded in 11 (8.5%) patients, all of them receiving preventive treatment (10 with bisphosphonates). During the follow-up period, patients with one or more high-risk factors for fracture showed a greater frequency of fractures (15% vs. 3%) and experienced the first fracture earlier than those without high-risk factors (mean of 99 and 102 months, respectively; P=0.023). CONCLUSIONS: The preventive intervention of a specialized unit at the start of AI treatment in breast cancer survivors allows the identification of patients with high fracture risk and may contribute to preventing bone events in these patients.

Metástasis de carcinoma diferenciado de tiroides en localizaciones infrecuentes: serie de 30 pacientes / Unusual metastases from differentiated thyroid carcinoma: series of 30 patients and review of literature

RESUMEN Introducción Las metástasis son la principal causa de mortalidad específica en carcinoma diferenciado de tiroides (CDT). Las localizaciones más frecuentes son el pulmón y el hueso. El compromiso de otros sitios es inusual. Se desconoce el impacto que tienen en la evolución y sobrevida de los pacientes. Objetivos Evaluar la prevalencia de metástasis infrecuentes (MI) en pacientes con CDT, sus características clínico-patológicas y el impacto en la mortalidad. Material y métodos: Estudio multicéntrico retrospectivo. Se incluyeron pacientes con CDT y MI (diferentes de pulmón y hueso). Se analizaron las características basales, las localizaciones de las MI, el subtipo histológico, el tiempo de aparición desde el diagnóstico inicial (sincrónicas o metacrónicas), sintomatología asociada. Resultados La localización más frecuente fue el sistema nervioso central (31%). El 76,6% fueron metacrónicas, y presentaron criterios de refractariedad al yodo en 76,6% de los casos. La mitad de los pacientes presentó síntomas específicos. En 73,28% de los casos implicaron cambios en la conducta terapéutica. 19 pacientes (63,3%) fallecieron a causa de la enfermedad, con una mediana de sobrevida desde el diagnóstico de la MI de 11 meses. La sobrevida fue menor en pacientes con MI yodorefractarias y sintomáticas. Conclusiones: Las MI tuvieron una prevalencia baja, y se presentaron en forma metacrónica. Determinaron cambios en la estrategia terapéutica y se relacionaron con la mortalidad específica en más de la mitad de los casos, lo que resalta la importancia de una estadificación precisa en pacientes con enfermedad avanzada.

ABSTRACT Introduction Complications related to metastatic disease are the main cause of specific mortality in differentiated thyroid cancer (DTC.) The most common sites of metastses are lung and bone. Other localizations are infrequent and they have been reported as isolated cases or small series. The impact of unusual metastases (UM) in patient management and prognosis remains largely unknown. Objectives To retrospectively evaluate the prevalence of UM in DTC patients, define their clinical-pathological characteristics and analyze its relevance in management and mortality. Patients and methods: We retrospectively reviewed file records from 7 databases. DTC patients who had metastatic disease in sites different from lung or bone were included. UM were diagnosed by: i) biopsy and/or ii) radioiodine (RAI) bone uptake + elevated thyroglobulin (Tg) levels and/or c) bone uptake of 18-FDG in the PET-CT scan + elevated Tg levels. We analyzed histopathologic characteristics, clinical presentation, localization, time of diagnosis (synchronic vs. metachronic presentation), diagnostic and therapeutic modalities and final outcome of patients. Results UM were diagnosed in 30 out of 2986 DTC patients (1%). The most common site of UM was the central nervous system (CNS 31%). Twenty percent of the patients had more than one UM. In 93% of the cases, UM coexisted with either lung and/or bone metastases and/or locoregional disease. Papillary histology was found in 75% of cases; 76.6% were metachronic with DTC diagnosis, and 76.6% fulfilled radioiodine refractoriness criteria. Half of the patients reported symptoms related to the UM. In 73.2% of the cases, therapeutic decisions were influenced by the diagnosis of the UM. Nineteen patients (63.3%) died of DTC related causes, with a mean survival of 11 months. The most frequent cause of death was CNS progression. Survival was shorter in patients with radioiodine refractory and symptomatic lesions. Conclusions Prevalence of UM was low; they were predominantly metachronic and iodine refractory. UM were found in patients with widespread disease, however, treatment strategies were modified by their diagnosis. UM were associated with poor survival and disease specific mortality.

Anxiety and depression in women with breast cancer: Social and clinical determinants and influence of the social network and social support (DAMA cohort).

BACKGROUND: Anxiety and depression are the most prevalent mental health pathologies among women with breast cancer. Social, clinical and contextual variables may influence emotional stress among women with breast cancer. The aim of this work is to study anxiety and depression in a cohort of women diagnosed with breast cancer between 2003 and 2013 in Barcelona. We evaluate social and clinical determinants. METHODS: We performed a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were the Hospital Anxiety and Depression questionnaire and hospital medical records. Dependent variables were anxiety and depression; independent variables were social class, age, employment status, tumour stage at diagnosis, time since diagnosis, social network and social support. We performed a descriptive analysis, a bivariate analysis, and a multivariate logistic regression analysis. RESULTS: A total of 1086 (48.6%) women had some degree of anxiety-related problem. As for depression. In the case of depression, 225 (15%) women had some degree of depression-related problem. Low emotional support and social isolation were clear risk factors for having more anxiety and depression. Low social class was also a risk factor, and age also played a role. DISCUSSION: Our results show that women long period of cancer survival have high prevalences of anxiety than depression, and this prevalence of anxiety is higher than the general population. In addition, we found inequalities between social classes and the isolation and social support are worse too in low social class.

A high-energy-resolution resonant inelastic X-ray scattering spectrometer at ID20 of the European Synchrotron Radiation Facility.

An end-station for resonant inelastic X-ray scattering and (resonant) X-ray emission spectroscopy at beamline ID20 of ESRF - The European Synchrotron is presented. The spectrometer hosts five crystal analysers in Rowland geometry for large solid angle collection and is mounted on a rotatable arm for scattering in both the horizontal and vertical planes. The spectrometer is optimized for high-energy-resolution applications, including partial fluorescence yield or high-energy-resolution fluorescence detected X-ray absorption spectroscopy and the study of elementary electronic excitations in solids. In addition, it can be used for non-resonant inelastic X-ray scattering measurements of valence electron excitations.

Frameless stereotactic radiotherapy alone and combined with temozolomide for presumed canine gliomas.

We evaluated stereotactic volume modulated arc radiotherapy (VMAT) for canine gliomas, alone (radiotherapy [RT]) and in combination with temozolomide (RT + TMZ), compared with palliation. Overall and disease-specific survival times were estimated. Thirty dogs were palliated, 22 dogs were treated with RT and 20 with RT + TMZ. Complete and partial responses were observed in 63.2% and 90.9% of patients in the RT and RT + TMZ arms, respectively, that were alive at 1 year. Median survival in the palliation arm was 94 days (95% conformity index [CI] 87÷101). Median survivals of the RT arm (383 days, 95% CI 276÷490) and RT+TMZ arm (420 days, 95% CI 280÷560) were not significantly different (P = .61). Positive correlation with survival was found both for the ratio between target and brain (relative) volume of the tumour of <5% (P = .013) and for a clinical presentation with normal mentation (P = .032). VMAT is feasible and effective for canine brain gliomas. Combining this therapy with TMZ did not elicit any additional improvement in survival time.

Cumulative risk of breast cancer screening outcomes according to the presence of previous benign breast disease and family history of breast cancer: supporting personalised screening.

BACKGROUND: Our aim was to assess the cumulative risk of false-positive screening results, screen-detected cancer, and interval breast cancer in mammography screening among women with and without a previous benign breast disease and a family history of breast cancer. METHODS: The cohort included 42 928 women first screened at the age of 50-51 years at three areas of the Spanish Screening Programme (Girona, and two areas in Barcelona) between 1996 and 2011, and followed up until December 2012. We used discrete-time survival models to estimate the cumulative risk of each screening outcome over 10 biennial screening exams. RESULTS: The cumulative risk of false-positive results, screen-detected breast cancer, and interval cancer was 36.6, 5.3, and 1.4 for women with a previous benign breast disease, 24.1, 6.8, and 1.6% for women with a family history of breast cancer, 37.9, 9.0, and 3.2%; for women with both a previous benign breast disease and a family history, and 23.1, 3.2, and 0.9% for women without either of these antecedents, respectively. CONCLUSIONS: Women with a benign breast disease or a family history of breast cancer had an increased cumulative risk of favourable and unfavourable screening outcomes than women without these characteristics. A family history of breast cancer did not increase the cumulative risk of false-positive results. Identifying different risk profiles among screening participants provides useful information to stratify women according to their individualised risk when personalised screening strategies are discussed.

A large-solid-angle X-ray Raman scattering spectrometer at ID20 of the European Synchrotron Radiation Facility.

An end-station for X-ray Raman scattering spectroscopy at beamline ID20 of the European Synchrotron Radiation Facility is described. This end-station is dedicated to the study of shallow core electronic excitations using non-resonant inelastic X-ray scattering. The spectrometer has 72 spherically bent analyzer crystals arranged in six modular groups of 12 analyzer crystals each for a combined maximum flexibility and large solid angle of detection. Each of the six analyzer modules houses one pixelated area detector allowing for X-ray Raman scattering based imaging and efficient separation of the desired signal from the sample and spurious scattering from the often used complicated sample environments. This new end-station provides an unprecedented instrument for X-ray Raman scattering, which is a spectroscopic tool of great interest for the study of low-energy X-ray absorption spectra in materials under in situ conditions, such as in operando batteries and fuel cells, in situ catalytic reactions, and extreme pressure and temperature conditions.

Tuberculosis, Brucellosis and Leucosis in Cattle: A Cost Description of Eradication Programmes in the Region of Lazio, Italy.

The eradication of tuberculosis, brucellosis and leucosis in cattle has not yet been achieved in the entire Italian territory. The region of Lazio, Central Italy, represents an interesting case study to evaluate the evolution of costs for these eradication programmes, as in some provinces the eradication has been officially achieved, in some others the prevalence has been close to zero for years, and in still others disease outbreaks have been continuously reported. The objectives of this study were i) to describe the costs for the eradication programmes for tuberculosis, brucellosis and leucosis in cattle carried out in Lazio between 2007 and 2011, ii) to calculate the ratio between the financial contribution of the European Union (EU) for the eradication programmes and the estimated total costs and iii) to estimate the potential savings that can be made when a province gains the certification of freedom from disease. For the i) and ii) objectives, data were collected from official sources and a costing procedure was applied from the perspective of the Regional Health Service. For the iii) objective, a Bayesian AR(1) regression was used to evaluate the average percentage reduction in costs for a province that gained the certification. The total cost for the eradication programmes adjusted for inflation to 1 January 2016 was estimated at 18 919 797 euro (5th and 95th percentiles of the distribution: 18 325 050-19 552 080 euro). When a province gained the certification of freedom from disease, costs decreased on average by (median of the posterior distribution) 47.5%, 54.5% and 54.9% for the eradication programmes of tuberculosis, brucellosis and leucosis, respectively. Information on possible savings from the reduction of control costs can help policy makers operating under budget constraints to justify the use of additional resources for the final phase of eradication.

Volumetric-modulated arc stereotactic radiotherapy for canine adrenocortical tumours with vascular invasion.

OBJECTIVES: To evaluate the feasibility and efficacy of hypofractionated stereotactic volumetric-modulated arc radiotherapy in treating canine adrenal tumours with vascular invasion. METHODS: A single-arm clinical study was performed. The dogs underwent total body computed tomography, brain and abdomen magnetic resonance imaging and endocrine assay. Adrenal masses were classified as cortisol-secreting adrenal tumour or non-secreting adrenal tumour. Radiotherapy treatments were delivered by hypofractionated stereotactic volumetric-modulated arc radiotherapy via a linear accelerator. The overall survival was estimated by the Kaplan-Meier method. The overall response and radio-toxicity effects were determined. RESULTS: Nine dogs were enrolled. Three dogs were affected by cortisol-secreting adrenal tumours and the remaining dogs had non-secreting adrenal tumours. The prescribed doses ranged from 30 to 45 Gy in three or five consecutive daily fractions. The median overall survival time was 1030 days, and the overall mean reduction of the diameter and volume were ~32 and 30% respectively. The endocrine profile normalised in two dogs with cortisol-secreting adrenal tumours. Radio-toxicities were mild and self-limiting. Seven deaths were recorded during the follow-up period and two dogs were censored. CLINICAL SIGNIFICANCE: Hypofractionated stereotactic volumetric-modulated arc radiotherapy should be considered as a feasible and effective therapeutic option for adrenal tumours with vascular invasion.

Advances in psoriasis physiopathology and treatments: Up to date of mechanistic insights and perspectives of novel therapies based on innovative skin drug delivery systems (ISDDS).

Psoriasis is a chronic inflammatory disease affecting mainly the skin but which can be complicated by psoriatic arthritis (PsA).This autoimmune skin disorder concerns 2-5% of the world population. To date, the physiopathology of psoriasis is not still completely elucidated but many researches are ongoing which have led for example to the discovery of the Th17/Th22 pathway. The conventional therapeutic approaches (local or systemic route) appeal to various classes of drugs with complex mechanisms of action and non-negligible side effects. Although there is no therapy capable to cure psoriasis, the current goal is to relieve symptoms as longer as possible with a good benefit/risk ratio. That is one of the principal limits of conventional antipsoriatic drugs. New formulations based on nanoencapsulation are a promising opportunity to answer to this limit by offering an optimization of the conventional antipsoriatic drug use (higher activity, lower side effects and frequency of application, etc.). Herein, we tried to put in perspective the mechanistic insights (histological and immunological views) proposed into scientific literature these last years in order to have a better comprehension of psoriasis physiopathology resulting in skin lesions and PsA. The therapeutic armamentarium and the different strategies in the management of psoriasis are discussed in greater details. To finish, the field of encapsulation in nanoparticles is broached in order to put forward recent advances in innovative skin drug delivery systems (ISDDSs) of antipsoriatic active agents for a better efficacy, safety and compliance.