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Immunotherapy has been one of the great advances in the recent years for the treatment of advanced tumors, with nonsmall-cell lung cancer (NSCLC) being one of the cancers that has benefited most from this approach. Currently, the only validated companion diagnostic test for first-line immunotherapy in metastatic NSCLC patients is testing for programmed death ligand 1 (PD-L1) expression in tumor tissues. However, not all patients experience an effective response with the established selection criteria and immune checkpoint inhibitors (ICIs). Liquid biopsy offers a noninvasive opportunity to monitor disease in patients with cancer and identify those who would benefit the most from immunotherapy. This review focuses on the use of liquid biopsy in immunotherapy treatment of NSCLC patients. Circulating tumor cells (CTCs), cell-free DNA (cfDNA) and exosomes are promising tools for developing new biomarkers. We discuss the current application and future implementation of these parameters to improve therapeutic decision-making and identify the patients who will benefit most from immunotherapy.

espanolPresentamos una investigacion aplicada y comparativa, relacionada con dos escenarios de la vida del Ecuador, ocurridos en octubre del 2019 y marzo del 2020. Donde se presentaron pacientes con traumatismos faciales. El objetivo de la investigacion fue establecer la prevalencia de las fracturas faciales en los pacientes de estos dos eventos. Se encontraron similitudes en los dos casos y se comparo con los datos mundiales, sacandose como conclusion que los traumatismos orbito-cigomaticos fueron los mas comunes, lo que nos obliga a estar preparados para atender estos pacientes que seguramente se presentaran con mayor regularidad en las salas de emergencia de nuestros hospitales. EnglishWe present an applied and comparative research related to two life scenarios of Ecuador, which occurred in October 2019 and March 2020. Where patients with facial trauma were presented. The objective of the investigation was to establish the prevalence of facial fractures in the patients of these two events. Similarities were found in the two cases and it was compared with world data, concluding that orbito-zygomatic trauma was the most common, which forces us to be prepared to attend to these patients who will surely present themselves more regularly in wards emergency of our hospitals.

Immune checkpoint inhibitors, such as pembrolizumab, are revolutionizing therapeutic strategies for different cancer types, including non‐small‐cell lung cancer (NSCLC). However, only a subset of patients benefits from this therapy, and new biomarkers are needed to select better candidates. In this study, we explored the value of liquid biopsy analyses, including circulating free DNA (cfDNA) and circulating tumour cells (CTCs), as a prognostic or predictive tool to guide pembrolizumab therapy. For this purpose, a total of 109 blood samples were collected from 50 patients with advanced NSCLC prior to treatment onset and at 6 and 12 weeks after the initiation of pembrolizumab. Plasma cfDNA was measured using hTERT quantitative PCR assay. The CTC levels at baseline were also analysed using two enrichment technologies (CellSearch® and Parsortix systems) to evaluate the efficacy of both approaches at detecting the presence of programmed cell death ligand 1 on CTCs. Notably, patients with high baseline hTERT cfDNA levels had significantly shorter progression‐free survival (PFS) and overall survival (OS) than those with low baseline levels. Moreover, patients with unfavourable changes in the hTERT cfDNA levels from baseline to 12 weeks showed a higher risk of disease progression. Additionally, patients in whom CTCs were detected using the CellSearch® system had significantly shorter PFS and OS than patients who had no CTCs. Finally, multivariate regression analyses confirmed the value of the combination of CTCs and cfDNA levels as an early independent predictor of disease progression, identifying a subgroup of patients who were negative for CTCs, who presented low levels of cfDNA and who particularly benefited from the treatment., In the present work, we demonstrated that liquid biopsy, through the combinatory analyses of circulating free DNA (cfDNA) and circulating tumour cells and the monitoring of cfDNA during the treatment, could help to select advanced non‐small‐cell lung cancer patients who will benefit from pembrolizumab treatment as first line, providing a promising non‐invasive strategy for improving the clinical management of this tumour.

There is a particular approach to the energy performance and indoor microclimate of historic buildings. However, the implementation of energy efficiency in historic buildings is limited, given that the materials, structure, geometry and artworks to be conserved inhibit the improvement of microclimate parameters or energy performance. The main aim of this work is to study the use of environmental conditioning techniques in a historic building and its impact on the conservation of artworks prior to the refurbishment project. This study describes experimental research carried out on the church of Nuestra Senora de la Merced, a historic building in a Mediterranean climate. The building was monitored and measured to validate numerical codes using Design Builder 4.7.027 and Energy Plus 8.3. Software building models made it possible to evaluate the implementation of different environmental techniques – passive, active and combined – in the church with a view to conserving artworks. This study concluded that the use of passive environmental techniques does not completely eliminate the mechanical risk or bio-deterioration that are inherent to movable heritage. Proposals for the use of active systems in combination with passive techniques improve the initial conservation of artworks and decrease the risk of biological degradation. Although energy consumption is high due to the large size and thermal inertia of the building, consumption is considerably reduced when active and passive systems are combined.

Background:CTCs have extensively used for the monitoring and characterization of metastatic prostate cancer, but their use in the clinic is still very scarce. Besides, the resistance mechanisms linked to prostate cancer treatment remain unclear. Liquid biopsies represent the most promising alternative due to the complexity of biopsying bone metastasis and the duration of the disease. Prostate cancer can last from a few months to many years, where the primary tumour does not represent the molecular features of the advanced stage. Methods:We performed a prospective longitudinal study in CTCs from 20 castration-resistant prostate cancer patients treated with docetaxel. For that, we used CellSearch® technology and a custom gene expression panel with qRT-PCR using a CTCs negative enrichment approach.Results:We found that CTCs showed a hybrid phenotype during the disease, where epithelial features were associated with the presence of ≥ 5 CTCs/7.5 mL of blood, while high relative expression of the gene MYCL was observed preferentially in the set of samples with < 5 CTCs/7.5 mL of blood. At baseline, patients whose CTCs had epithelial features showed an early progression. After 1 cycle of docetaxel, high relative expression of ZEB1 indicated worse outcome, while KRT19 and KLK3 high expression predisposed the patients to a worse prognosis at clinical progression.Conclusions:In the present work we describe biomarkers with clinical relevance for the prediction of early response or resistance in castration-resistant prostate cancer patients. Besides, we question the utility of targeted isolated CTCs and the use of a limited number of markers to define the CTCs population.

The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57–0.65, p < 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67–0.86; p < 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70–2.63, p < 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC.

Background. Human papillomavirus (HPV) infection has been recognized as an important risk factor in cancer. The purpose of this systematic review and meta-analysis was to determine the prevalence and effect size of association between salivary HPV DNA and the risk of developing oral and oropharyngeal cancer. Methods. A systematic literature search of PubMed, EMBASE, Web of Science, LILACS, Scopus and the Cochrane Library was performed, without language restrictions or specified start date. Pooled data were analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Quality assessment was performed using the Newcastle–Ottawa Scale (NOS). Results. A total of 1672 studies were screened and 14 met inclusion criteria for the meta-analysis. The overall prevalence of salivary HPV DNA for oral and oropharyngeal carcinoma was 43.2%, and the prevalence of salivary HPV16 genotype was 27.5%. Pooled results showed a significant association between salivary HPV and oral and oropharyngeal cancer (OR = 4.94; 2.82−8.67), oral cancer (OR = 2.58; 1.67−3.99) and oropharyngeal cancer (OR = 17.71; 6.42−48.84). Significant associations were also found between salivary HPV16 and oral and oropharyngeal cancer (OR = 10.07; 3.65−27.82), oral cancer (OR = 2.95; 1.23−7.08) and oropharyngeal cancer (OR = 38.50; 22.43−66.07). Conclusions. Our meta-analysis demonstrated the association between salivary HPV infection and the incidence of oral and oropharyngeal cancer indicating its value as a predictive indicator.

MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We analyzed MET amplification in circulating free DNA (cfDNA) from 174 patients with cancer and 49 healthy controls and demonstrated the accuracy of the analysis to detect its alteration in patients. Importantly, a significant correlation between cfDNA concentration and MET copy number (CN) in cancer patients (r = 0.57, p &lt, 10&minus, 10) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch&reg, and Parsortix systems and monitored patients under anti-EGFR treatment (n = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of MET CN assessment when patients develop resistance to anti-EGFR therapy and a significant association between the presence of CTCs MET+ and the Overall Survival (OS) in head and neck cancer patients (P = 0.05, HR = 6.66). In conclusion, we develop specific and noninvasive assays to monitor MET status in cfDNA/CTCs and demonstrate the utility of plasma MET CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy.

Aim: To report results from the Spanish subset included in the radium-223 international early access program (iEAP). Patients & methods: Ninety patients with castration-resistant prostate cancer and bone metastases received radium-223 55 kBq/kg every 4 weeks for six cycles. Results: The median time to disease progression was 8 months and to prostate-specific antigen progression was 4 months. The percentage of patients with ≥50% confirmed declines in prostate-specific antigen was 9%. The median overall survival was 14 months. Grade 3 or 4 treatment emergent adverse events (TEAEs) occurred in 34% of patients (serious TEAEs 28%, TEAEs leading to discontinuation 27%). Conclusion: Outcomes of the Spanish subset are consistent with the iEAP. Radium-223 was generally well tolerated with no safety concerns.

// Luis Leon-Mateos 1, * , Helena Casas 2, * , Alicia Abalo 2, 3 , Maria Vieito 6 , Manuel Abreu 2, 3 , Urbano Anido 3 , Antonio Gomez-Tato 4 , Rafael Lopez 2, 3, 5 , Miguel Abal 3 and Laura Muinelo-Romay 3 1 Axencia Galega de Conecemento en Saude (ACIS), SERGAS, Santiago de Compostela, Spain 2 Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), CIBERONC, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain 3 Translational Medical Oncology Group, Health Research Institute of Santiago (IDIS), CIBERONC, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain 4 School of Mathematics, University of Santiago de Compostela (Campus Vida), Santiago de Compostela, Spain 5 Roche-Chus Joint Unit for Precision Oncology, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain 6 Research Unit for Molecular Therapy of Cancer, CNS Tumors, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain * Co first-authors Correspondence to: Luis Leon-Mateos, email: Luis.Leon.Mateos@sergas.es Laura Muinelo-Romay, email: lmuirom@gmail.com Keywords: prostate cancer, circulating tumour cells (CTCs), prognostic markers, taxanes resistance Received: January 17, 2017 Accepted: May 02, 2017 Published: May 19, 2017 ABSTRACT Introduction: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring. Materials and Methods: CTCs isolation was carried out in peripheral blood samples from 29 mCRPC patients that undergo systemic chemotherapy based on taxanes (docetaxel/cabazitaxel) and 19 healthy controls using in parallel CellSearch and an alternative EpCAM-based immunoisolation followed by RT-qPCR analysis to characterize the CTC population. A panel of 17 genes related with prostate biology, hormone regulation, stem properties, tumor aggressiveness and taxanes responsiveness was analysed to identify an expression signature characterizing the CTCs. Results: Patients with ≥ 5 CTCs/7.5ml of peripheral blood at baseline and during the treatment showed lower progression free survival (PFS) and overall survival (OS). Changes of CTCs levels during the treatment were also associated with the patient’s outcome. These results confirmed previous data obtained using CellSearch in mCRPC. In addition, we found a CTC profile mainly characterized by the expression of relevant genes for the hormone dependent regulation of PCa such as AR and CYP19 together with genes strongly implicated in PCa progression and resistance development such as BIRC5 , TUB1A , GDF15 , RAB7 and SPINK1 . Our gene-expression profiling also permitted the identification of valuable prognostic biomarkers. Thus, high levels of AR, CYP19 and GDF15 were associated with poor PFS rates while AR, GDF15 and BIRC5 were also found as reliable predictors of OS. Besides, a logistic model using KLK3 and BIRC5 showed a high specificity and sensitivity compared to CellSearch to discriminate patients with a more aggressive evolution. Conclusions: The molecular characterization of CTCs from advanced mCRPC patients provided with a panel of specific biomarkers, including genes related to taxanes resistance, with a promising applicability as “liquid biopsy” for the management of these patients.

Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

Churches, chapels and other places of worship are a major part of European cultural heritage which modern society has decided should be preserved for future generations. The indoor environment of these buildings crucial to conserving construction elements and movable artefacts. In addition, in the Mediterranean the growing demand for thermal comfort from society has made the use of active environmental conditioning systems more common in spaces of worship. However, most of these techniques cannot simultaneously satisfy the needs of heritage preservation, human comfort and energy efficiency. In addition, energy consumption in such spaces tends to be high due to their large size and high thermal inertia. In some Mediterranean countries including Spain the thermal envelopes of these buildings are not contemplated in current environmental conditioning regulations. However, all thermal installations must ensure conditions of wellbeing, safety and energy efficiency. Studies such as European Project Friendly-Heating highlight the problems caused by installing heating in old churches. The case of the Spanish churches in Mediterranean climate is very different from that of the churches in northern Europe. Due to the temperate climate, heating demand is much lower in winter, while in spring and summer the demand for cooling and dehumidification is greater due to the high temperatures and outdoor humidity. This article describes research on environmental conditioning techniques, both passive and active, in spaces of worship in temperate climates. The main aim is to describe different environmental techniques to improve the thermal comfort conditions of the faithful while preserving the cultural heritage of these buildings. Different strategies and regimes were tested using monitoring and simulation. The software used was Design Builder version 3.4.0.041, EnergyPlus 8.1 and the simulation model was validated through measurement. Currently, the church does not present comfort conditions and preservation of the artworks throughout the year. In addition, the exclusive use of passive environmental techniques does not completely eliminate the risks. Finally, the detailed knowledge about the hygrothermal response of the church with a validated simulation model after installing HVAC could lead to energy savings and the improvement of conservation and thermal comfort.

Prostate cancer is the most prevalent male urogenital malignancy. Approximately 30% of patients with prostate cancer will develop advanced disease. Androgen deprivation therapy achieves disease control in about 90% of these patients, but the majority of them will eventually develop progressive disease, a status called castration-resistant prostate carcinoma (CRPC). However, in recent years, several new therapy strategies, such as immunotherapy, hormonal manipulations, chemotherapy agents and some bone-targeted therapies, have demonstrated an improvement in terms of overall survival in controlled trials. In 2012, the Spanish Oncology Genitourinary Group (SOGUG) published its recommendations for the treatment of patients with CRPC. Due to the recent appearance of important new data and the complexity of decision-making in this field, SOGUG herein provides updated recommendations for the treatment of patients with metastatic prostate cancer.

Càncer de pròstata resistent a la castració (CRPC); Cèl·lules tumorals circulants (CTC); Marcadors tumorals Cáncer de próstata resistente a la castración (CRPC); Células tumorales circulantes (CTC); Marcadores tumorales Castration-resistant prostate cancer (CRPC); Circulating tumor cells (CTCs); Tumor markers Background: Current therapeutic options in the course of metastatic castration-resistant prostate cancers (mCRPC) reinforce the need for reliable tools to characterize the tumor in a dynamic way. Circulating tumor cells (CTCs) have emerged as a viable solution to the problem, whereby patients with a variety of solid tumors, including PC, often do not have recent tumor tissue available for analysis. The biomarker characterization in CTCs could provide insights into the current state of the disease and an overall picture of the intra-tumor heterogeneity. Methods: in the present study, we applied a global gene expression characterization of the CTC population from mCRPC (n = 9), with the goal to better understand the biology of these cells and identify the relevant molecules favoring this tumor progression. Results: This analysis allowed the identification of 50 genes specifically expressed in CTCs from patients. Six of these markers (HOXB13, QKI, MAOA, MOSPD1, SDK1, and FGD4), were validated in a cohort of 28 mCRPC, showing clinical interest for the management of these patients. Of note, the activity of this CTC signature was related to the regulation of MYC, a gene strongly implicated in the biology of mCRPC. Conclusions: Overall, our results represent new evidence on the great value of CTCs as a non-invasive biopsy to characterize PC. This work was partially financed with the “liquid Biopsy crowdfunding, 2017”. L.M-L. is supported by AECC.

The increase in the average temperature of the planet due to global warming has serious repercussions on buildings, affecting indoor environmental quality and thermal comfort. Currently, one of the building stocks most at risk is that of the residential sector in southern Spain, given the high sensitivity of the Mediterranean climate to the effects of climate change and the massive volume of this built environment with obsolete energy conditions. However, it is crucial to carry out an in-depth assessment of the necessary retrofitting strategies for implementation in this existing stock, with an overall analysis of building characterisation and current state of the building stock. This research takes these aspects into consideration, using statistical descriptive techniques to evaluate the building characterisation of public social housing in southern Spain. This public sector is managed by the Regional Government of Andalusia and is made up of 39.486 social housing units. Results reported in this research make it possible to establish which buildings require short-term and priority retrofitting actions, thus creating a useful tool for decision-making within the political context.

The energy problem, one the most important on a global scale, greatly affects the environment. Much of the current energy consumption occurs in existing buildings, including heritage buildings with varying protected status. Energy intervention and heritage conservation conflict to some extent, as research focuses more on the search for improved energy efficiency solutions for materials and systems than on their application to heritage buildings. This study describes experimental research on environmental conditioning techniques in spaces of worship in a temperate climate in southern Spain. Buildings were monitored and assessed in the implementation of different environmental techniques&mdash, active and combined (passive and active)&mdash, with the aim of improving the thermal comfort conditions of the faithful while preserving the cultural heritage of these buildings. The need for a control system of RH and the air system was concluded, as well as radiant floors and radiators, which, in the considered case studies, would barely affect the artworks. 24- and 12-h operation are better suited to heritage preservation than occasional use. All operation schedules are valid for thermal comfort.

Most educational buildings in southern Spain do not meet current energy requirements as weak thermal envelopes and the lack of cooling systems lead to severe discomfort in classrooms, especially when temperatures are above 30 &deg, C. Given that global warming is expected to worsen this situation in coming decades, one of the first steps to be taken is to protect window openings from high levels of solar radiation by adding shading devices to reduce indoor temperatures and improve visual comfort. The aim of this research is to evaluate the reduction in thermal and lighting consumption in a classroom where a solar protection system in the form of an egg-crate shading device was installed. Two classrooms&mdash, one with an egg-crate device and another with no shading system&mdash, were monitored and compared for a whole year. The use of an egg-crate device in these classrooms reduced indoor operative temperatures during warmer periods while also improving indoor natural illuminance levels. Moreover, annual electric air conditioning consumption decreased by approximately 20%, with a 50% reduction in electric lighting consumption. These savings in electricity were largely conditioned by the use patterns observed in these ambient systems.

International audience; AimThe benefit of the lipid-lowering drug fenofibrate on cardiovascular outcomes is controversial. Our aim was to find new circulating markers to identify those patients most likely to benefit from fenofibrate prescription.MethodsAnalyses were conducted of plasma samples collected from 102 patients with type 2 diabetes, enrolled in the FIELD trial, before and after fenofibrate treatment (200 mg/day). Non-targeted and targeted lipid analyses and apolipoprotein measurements were made using mass spectrometry methods.ResultsLipidomics revealed a global decrease in ceramide after fenofibrate treatment confirmed by quantitative analysis (−18.2%, P < 0.001). These changes were strongly associated with those found for plasma sphingomyelin (r = 0.80, P < 0.001) and, to a lesser extent, for sphingosine-1-phosphate (r = 0.34, P < 0.001). Ceramide levels decreased in 73.5% of patients. In addition to the expected lipid changes (decreases in triglycerides, total cholesterol and LDL cholesterol, and increase in HDL cholesterol), fenofibrate also lowered plasma apoC-II (−11.1%, P < 0.01), apoC-III (−24.6%; P < 0.001), apoB100 (−27.0%, P < 0.01) and sphingomyelinase (−7.6%, P < 0.001), and increased plasma apoA-II (22.4%, P < 0.001) as well as adiponectin (11.4%, P < 0.001). No significant association was found between ceramide decrease and these modulations except for total cholesterol (r = 0.20, P = 0.047) and HDL protein components. At baseline, only elevated sphingolipid levels were significantly associated with ceramide reduction after fenofibrate treatment.ConclusionFenofibrate lowers plasma ceramide independently of the usual lipid parameters. As ceramide is a strong marker of atherosclerosis, our study underpins the need to further evaluate its contribution to cardiovascular events in fenofibrate-treated patients.AimThe benefit of the lipid-lowering drug fenofibrate on cardiovascular outcomes is controversial. Our aim was to find new circulating markers to identify those patients most likely to benefit from fenofibrate prescription.MethodsAnalyses were conducted of plasma samples collected from 102 patients with type 2 diabetes, enrolled in the FIELD trial, before and after fenofibrate treatment (200 mg/day). Non-targeted and targeted lipid analyses and apolipoprotein measurements were made using mass spectrometry methods.ResultsLipidomics revealed a global decrease in ceramide after fenofibrate treatment confirmed by quantitative analysis (−18.2%, P < 0.001). These changes were strongly associated with those found for plasma sphingomyelin (r = 0.80, P < 0.001) and, to a lesser extent, for sphingosine-1-phosphate (r = 0.34, P < 0.001). Ceramide levels decreased in 73.5% of patients. In addition to the expected lipid changes (decreases in triglycerides, total cholesterol and LDL cholesterol, and increase in HDL cholesterol), fenofibrate also lowered plasma apoC-II (−11.1%, P < 0.01), apoC-III (−24.6%; P < 0.001), apoB100 (−27.0%, P < 0.01) and sphingomyelinase (−7.6%, P < 0.001), and increased plasma apoA-II (22.4%, P < 0.001) as well as adiponectin (11.4%, P < 0.001). No significant association was found between ceramide decrease and these modulations except for total cholesterol (r = 0.20, P = 0.047) and HDL protein components. At baseline, only elevated sphingolipid levels were significantly associated with ceramide reduction after fenofibrate treatment.ConclusionFenofibrate lowers plasma ceramide independently of the usual lipid parameters. As ceramide is a strong marker of atherosclerosis, our study underpins the need to further evaluate its contribution to cardiovascular events in fenofibrate-treated patients.

The current European energy policies have an influence on the need to rehabilitate the housing stock in order to meet the objectives of the European Union. Most of this housing stock was built without any type of energy regulation in adverse technical and economic conditions and thus is now energetically obsolete. The major rehabilitation effort required must be approached through actions based on previous quantitative energy knowledge of the existing buildings in order to guarantee the efficiency of energy-retrofitted solutions. This assessment can be carried out through monitoring dwellings conditioned by use patterns; through simulation programs, which do not usually offer faithful representations of energy conditions; or by using test cells, which allow us to evaluate a controlled indoor environment without the influence of users. The objective of this paper is to present the design and performance of test cells as an experimental method for vertical facade analysis in order to tackle the problem of retrofitting residential buildings in a Mediterranean climate, taking into account energy and environment. With this equipment, efficiency and energy savings, as well as illumination and interior air quality, can be simultaneously and comprehensively evaluated.

Los autores presentan un caso de hernia perineal. La predisposición congénita es el factor principal. El diagnóstico clínico se hizo en este caso. El tratamiento quirúrgico se realizó mediante la técnica abdominal.

Se establece que los restos mesonéfricos resto del margen lateral del cuello del útero, pueden sufrir cambios malignos. Mesonéfrico adenocarcinoma de cuello uterino, es una lesión poco frecuente, y su incidencia en el Instituto Nacional de Enfermedades Neoplásicas, es de 0,03% en más de todos los carcinomas cervicales, y el 1,9% en los adenocarcinomas de cuello uterino. Estudios citológicos cervicales tienen poco valor en la detección del proceso de la enfermedad temprana. Consideramos que un tratamiento combinado de radio más cirugía radical para endocervical y adenocarcinoma mesonéfrico en estadio clínico I y II, es el mejor procedimiento.

Los autores han estudiado 68 casos de carcinoma del muñón cervical tratados en el Instituto Nacional de Enfermedades Neoplásicas, Lima, entre 1952 - 1967. Mediante la aplicación de los criterios de dos años, intervalo libre, 49 de estos casos eran "auténticas" y 19 eran de el tipo coincidente. Estos 68 casos representaron 0,7% de las 9.197 casos de carcinoma del cuello uterino tratado en el período de 15 años. La tasa de supervivencia global para el grupo tratado quirúrgico fue de 50% y 47% para los que recibieron la terapia roentgen; sin embargo, después de un análisis de las etapas clínicas de los casos en ambos grupos los autores Suport radioterapia como el procedimiento más adecuado.

Los autores han estudiado 9 casos de carcinoma primario de la trompa de Falopio; esto significa una incidencia de 0,09% en un total de 9.266 tumores malignos del tracto genital observado en el Instituto Nacional de Enfermedades Neoplásicas, Lima Perú, entre 1952 y 1966. Los pacientes tenían una edad media de 50 años, rango 33-70; el tratamiento fue quirúrgico y la radiación, y la tasa de supervivencia global fue del 22%.

ResumenEl diagnóstico etiológico es un objetivo primordial para el manejo clínico de cada paciente. Algunos niños con cuadros clínicos complejos son objeto de una lista interminable de exámenes, lo que se ha denominado “odisea diagnóstica”, y que, sin embargo, muchas veces no deja resultados concluyentes. En los últimos años, estamos siendo testigos de una verdadera revolución de la medicina genómica con la incorporación al ámbito clínico de tecnologías que prometen aumentar la capacidad de hacer diagnóstico y disminuir los tiempos. Con énfasis en pediatría, se actualizan conceptos sobre las principales ventajas y limitaciones del diagnóstico genómico, en contraposición con las metodologías usuales.AbstractEtiological diagnosis is essential in the clinical management of individual patients. Some children with complex medical conditions are subjected to numerous testing, known as “diagnostic odyssey”, which often gives no conclusive results. In recent years, a revolution in genomic medicine is underway with the use of technologies that promise to increase the ability to make a diagnosis and reduce the time involved. The main advantages and limitations of genomic diagnosis, as opposed to usual methodologies are reviewed with an emphasis on Pediatrics.

[Abstract] Background: Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Patients and methods: Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. Results: 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Conclusions: Certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers of sunitinib response. PPfizer; SOGUG-2011-05 Ministerio de Economía, Industria y Competitividad; SAF2015-66015-R Ministerio de Economía, Industria y Competitividad; ISCIII-RETIC RD12/0036/0009 Ministerio de Economía, Industria y Competitividad; PIE 15/00076

The proposal of potential strategies of Energy Conservation Measures for the improvement of the energy performance in hospitals, as established by the European policies of the Horizon 2020 Project, considerably challenges current knowledge and methodology. In this paper, we review state-of-the-art tools applied to energy models validated with onsite measured data, for energy consumption quantification and evaluation of different energy retrofit alternatives. The goal of this work is to propose a methodological approach adapted to the specific case of existing hospitals of Andalusia, focusing on the optimisation of the passive systems and thermal envelope against energy, comfort and thermo-economic criteria. This methodology is based on geographic location, typology, construction and functional characteristics of hospital buildings; and on the assessment of energy performance by means of onsite data collection, monitoring , construction and calibration of energy models that allows the implementation of energy retrofit strategies for the existing hospital stock of the Mediterranean area.

Purpose: Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT-Scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. Methods: PrediCTC constitutes a panel of genes for the assessment of Circulating Tumor Cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT-Scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. Results: This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. Conclusion: The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease. pre-print 533 KB

Docetaxel is the standard first-line chemotherapy for men with metastatic castration-resistant prostate cancer. Until recently, there was no standard therapy after failure of docetaxel treatment. Cabazitaxel has been shown to improve overall survival in this setting. As a result, the treatment paradigm for mCRPC is changing rapidly. The improved survival shown with cabazitaxel provides an important new opportunity to treat men with mCRPC after docetaxel treatment. Despite the toxicity recorded in the pivotal study, subsequent trials have shown that cabazitaxel is a safe drug. Patient selection and the optimal interval between prior docetaxel treatment and cabazitaxel remain the critical issues. According to a subanalysis of the various studies discussed in this review, there is a patient profile that will probably benefit from use of cabazitaxel after docetaxel failure. Cabazitaxel represents a new treatment option for patients with prostate cancer.

Prostate cancer is the most common cancer in men worldwide. To improve future drug development and patient management, surrogate biomarkers associated with relevant outcomes are required. Circulating tumour cells (CTCs) are tumour cells that can enter the circulatory system, and are principally responsible for the development of metastasis at distant sites. In recent years, interest in detecting CTCs as a surrogate biomarker has ghiiukjrown. Clinical studies have revealed that high levels of CTCs in the blood correlate with disease progression in patients with prostate cancer; however, their predictive value for monitoring therapeutic response is less clear. Despite the important progress in CTC clinical development, there are critical requirements for the implementation of their analysis as a routine oncology tool. The goal of the present review is to provide an update on the advances in the clinical validation of CTCs as a surrogate biomarker and to discuss the principal obstacles and main challenges to their inclusion in clinical practice.

Background Markers able to predict the response to antiangiogenics in metastatic clear cell renal cell carcinoma (ccRCC) are not available. The development of new treatment options like immunotherapy are reaching the clinic; therefore, predictors of benefit from these different available treatments are increasingly needed. Objective In this study, we prospectively assessed the association of circulating endothelial cells (CECs) in peripheral blood with long-term benefit from first-line treatment in ccRCC. Design, setting, and participants A prospective observational study was designed involving 13 institutions of the Spanish Oncology Genitourinary Group. Adult patients diagnosed with advanced ccRCC who had achieved response or disease stabilization after 3 mo on first-line therapy were eligible. Outcome measurements and statistical analysis CECs were isolated from peripheral blood, captured with ferrofluids coated with monoclonal antibodies directed against the CD146 antigen, and assessed centrally with an automated standardized system. CECs were defined as 4′,6-diamidino-2-phenylindole+, CD105+, and CD45–. Blood samples were systematically taken every 6 wk for 15 mo or until tumor progression, whichever occurred first. Clinical data were externally monitored at all centers. Results and limitations From August 9, 2011, to January 17, 2013, 75 patients were enrolled in the study. Patients with baseline CECs above the median showed a significantly longer progression-free survival than those with low CECs (22.2 mo vs 12.2 mo) with a hazard ratio of 2.5 (95% confidence interval: 1.2–5.3, p =0.016). There was no difference between CEC levels at baseline and at tumor progression (medians of 50 CECs/4ml and 52 CECs/4ml, respectively). Conclusions Under antiangiogenic treatment, the detection of higher CEC levels is associated with clinical benefit in terms of progression-free survival in ccRCC. Patient summary Antiangiogenics are the cornerstone of treatment in kidney cancer. Since they target endothelial rather than tumor cells, we studied the correlation between levels of circulating endothelial cells in peripheral blood and long-term benefit in patients on antiangiogenic therapy. Higher levels were associated with long-term benefit, suggesting that this determination could help to separate best responders from those who could require a more intensive approach.

Background: The impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice. Methods: Data on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle. Results: Adverse event (AE) management was consistent with the Guidelines as a whole for 28.7 % out of 966 post-implementation cycles compared with 23.1 % out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non-compliant cycles showed significant changes in appropriate management of hypertension (33 % pre-implementation vs. 44.5 % post-implementation cycles; p < 0.0001), diarrhea (74.0 % vs. 80.5 %; p = 0.011) and dyslipemia (25.0 % vs. 44.6 %; p < 0.001). Conclusions: Slight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction., This study was funded by Pfizer, S.L.U. Medical writing assistance was provided by Esther Tapia, PhD and was founded by Pfizer. The authors gratefully say thanks to Ma Luz Samaniego for his help with the statistical analyses.

The accuracy in the diagnosis of metastatic colorectal cancer (mCRC) represents one of the challenges in the clinical management of patients. The detection of circulating tumour cells (CTC) is becoming a promising alternative to current detection techniques, as it focuses on one of the players of the metastatic disease and it should provide with more specific and sensitive detection rates. Here, we describe an improved method of detection of CTC from mCRC patients by combining immune-enrichment, optimal purification of RNA from very low cell numbers, and the selection of accurate PCR probes. As a result, we obtained a logistic model that combines GAPDH and VIL1 normalized to CD45 rendering powerful results in the detection of CTC from mCRC patients (AUROC value 0.8599). We further demonstrated the utility of this model at the clinical setting, as a reliable prognosis tool to determine progression-free survival in mCRC patients. Overall, we developed a strategy that ameliorates the specificity and sensitivity in the detection of CTC, resulting in a robust and promising logistic model for the clinical management of metastatic colorectal cancer patients.

The aim of this study was to evaluate efficacy and safety of first-line treatment with bevacizumab, cisplatin and vinorelbine and bevacizumab maintenance in non-squamous, non-small cell lung cancer (NSCLC).Forty-nine patients with stage IIIB plus pleural effusion or stage IV NSCLC were included in a Phase II clinical trial. Treatment consisted of 3-week cycles of bevacizumab (15 mg/kg on day 1), cisplatin (80 mg/m(2) on day 1) and vinorelbine (25 mg/m(2) on days 1 and 8). After 6 cycles, non-progressing patients received bevacizumab maintenance therapy. The primary end point was progression-free survival (PFS), calculated using the Kaplan-Meier method.Thirteen (29%) of 45 evaluable patients presented a partial response. PFS and overall survival were 6.0 months (95% confidence interval (CI) 4.5 - 7.5) and 14.7 months (95% CI 8.4 - 21), respectively. Fourteen patients (28%) experienced grade 3 - 4 neutropenia and 7 (14%) experienced febrile neutropenia during the combination treatment. During the maintenance phase, the most frequent grade 3 - 4 adverse event was hypertension. Neither grade 3 - 4 thrombocytopenia nor toxic death was observed.The studied regimen achieved a similar efficacy to other regimens containing platinum doublets. The data provide further evidence that bevacizumab may be used in combination with multiple standard platinum-based doublets in this setting.

Tyrosine kinase inhibitors (TKIs) are beneficial for the treatment of renal cell carcinoma (RCC), gastrointestinal stromal tumors (GIST), pancreatic neuroendocrine tumors (pNETs), and other tumors. The antitumor activity of sunitinib has been based on time-related parameters such as progression-free survival (PFS) and overall survival (OS). Advances in knowledge of the molecular mechanisms and oncogenic processes associated with RCC have enabled the availability of rational targets for pharmacotherapy. Although each small molecule is modeled to block the activity of selected kinase signaling enzymes, it is increasingly evident that many have nontargeted effects (on other kinases) that may cause unexpected complications. The recommended dose for sunitinib in patients with advanced RCC is a 50 mg oral daily dose, with or without food, on a 4/2 week schedule (4 weeks "on" vs. 2 weeks "off") until progression. An alternative continuous 37.5 mg/day dosing schedule has also been evaluated and appears to be well tolerated, allowing the maintenance of the dose density of sunitinib with a similar outcome. The continuous administration schedule provides a constant exposure to the drug, and may prevent potential tumor regrowth and angiogenesis recovery. Most side effects are reversible and should not result in sunitinib discontinuation. In this article, the body of evidence behind the use of sunitinib in metastatic RCC (mRCC) compared to other targeted agents that have recently come into the field is summarized, and the need for correct management of an adverse event profile in order to better optimize available treatment options is underlined.

Introducción: Los estreptococos β-hemolíticos del grupo A (Streptococcus pyogenes), C o G, secretan estreptolisina O, toxina que causa en el individuo infectado una respuesta inmune adaptativa humoral con producción de anticuerpos séricos denominados antiestreptolisina O (ASO). Objetivos: Determinar el valor referencial de ASO en una muestra poblacional de 159 individuos con edades comprendidas entre 16 y 72 años del municipio Francisco Linares Alcántara, estado Aragua mediante aglutinación (pasiva) indirecta. También se determinó la frecuencia de portadores asintomáticos de estreptococos β-hemolíticos utilizando una muestra de exudado faríngeo que se sembró en agar sangre de cordero al 5%. Resultados y Discusión: Como valor referencial para la determinación de ASO por el método de aglutinación se obtuvo un título de hasta 200 UI/mL, valor que difiere del recomendado por el kit comercial. La frecuencia de portadores fue 21,2% (n = 34). La distribución de los estreptococos β-hemolíticos aislados fue: grupo A (17,6%), grupo B (32,3%), grupo C (20,5%), grupo D (2,9%), grupo F (8,8%), grupo G (14,7%) y no agrupable (2,9%). Conclusiones: El nuevo valor referencial de ASO para adolescentes y adultos del municipio mencionado es hasta 200 UI/mL. Streptococcus β-hemolítico del grupo B fue el grupo más frecuentemente aislado.

Metastatic renal cell carcinoma is resistant to conventional treatment with chemotherapy. Recently the use of molecular-targeted therapies with multikinase inhibitors has been recommended as first-choice therapy because they inhibit cell proliferation and tumour angiogenesis. Sorafenib is a well tolerated tyrosine kinase inhibitor that initially demonstrated efficacy in the treatment of patients with metastatic RCC who progressed after immunotherapy. Expanded-access studies in Europe and North America showed the safety and efficacy of sorafenib in special populations such as elderly, renal failure and cerebral metastases, as well as patients with no prior therapy. No cross-resistance has been suggested in non-randomized trials when used in second line treatment after other targeted therapies. Ongoing clinical trials will better define the role of sorafenib in first and second line either as monotherapy or in combination, as well as the best strategies for the sequential use of this drug.

TO THE EDITOR: In the March 1, 2010, issue of Journal of Clinical Oncology, Kantoff et al reported the results of a phase II randomized trial of a poxviral-based prostate-specific antigen vaccine (PROSTVAC) in metastatic castration-resistant prostate cancer. Eighty-two patients received PROSTVAC and 40 received control vectors. The primary end point was progression-free survival, which was similar in both groups (hazard ratio, 0.884; 95% CI, 0.568 to 1.375; P .6), but overall survival (OS) favored PROSTVAC arm (25.1 v 16.6 months). The authors conclude that PROSTVAC immunotherapy is associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS. Although these data merit further exploration, we have concerns about whether both study arms are comparable. First, the difference in median age (71.6 v 79 years), percentage of lymph node involvement only (9.8% v 0%), and median survival estimated by Halabi nomogram may favor the PROSTVAC arm. Second, as Kantoff et al point out, the lack of treatment data after initial progression limits the interpretation of the survival result. PROSTVAC plus subsequent treatment improved in 3 months the survival predicted by Halabi. In the control arm, OS is reduced by 4 months as estimated by the Halabi nomogram. Half of the patients in the control arm received PROSTVAC as second-line treatment. An interesting question is whether a higher percentage of patients in the PROSTVAC arm received second-line docetaxel, obtaining a benefit in survival. Third, Kantoff et al mentioned that only docetaxel has been shown to affect survival in metastatic prostate cancer, by approximately 3 months. In the TAX 327 study, an OS of 19.2 months was reported in the every-3-weeks docetaxel arm. Nevertheless, patients included in the TAX 327 had an disfavorable prognosis when compared with the PROSTVAC study. Patients in TAX 327 were more symptomatic with a higher median prostate-specific antigen, Eastern Cooperative Oncology Group performance status of 2 was permitted, and 30% of patients had a Gleason score of 8 to 10. In a retrospective subanalysis of 110 minimally symptomatic patients, Berthold et al reported an OS of 28.4, 25.9, and 22 months for docetaxel every 3 weeks, docetaxel every week, or mitoxantrone, respectively. These differences did not reach statistical significance as a result of the small number of patients, and the results should be interpreted with caution. These data suggest than docetaxel should offer similar results to PROSTVAC in this population and should be the control arm in a phase III study. We agree with Kantoff et al that their findings are regarded as hypothesis generating, but OS data should be interpreted with caution in the absence of treatment information after progression to PROSTVAC or placebo.

We have studied the possible relationship between the immunohistochemical expression of p16 INK4a and the maximum standardized uptake value (SUV max) of F-18 fluorodeoxyglucose-positron emission tomography (F-18 FDG- PET) in 49 patients with non-small cell lung cancer (NSCLC). Immunohistochemical negativity of p16 INK4a was verified in 71.4 % of the patients, higher in squamous cell carcinomas than in adenocarcinomas (p: 0.033). The SUV max corre- lates with negativity for p16 INK4a (p: 0.042) and was higher (p: 0.024) in cases with p16 INK4a -negative (17.3 ± 8.3) than in cases with p16 INK4a -positive (12.7 ± 5.2). We can conclude that inactivation of the p16 INK4a gene is very frequent in NSCLC, with higher values in squamous cell carcinomas. SUV max correlated positively and statistically with negativity for p16 INK4a , which could explain why higher estimates of SUV max are found in squamous cell carcinomas when com- pared to adenocarcinomas. Only the clinical stage was found to be an independent prognostic value after multivariate analysis.

Objective: To study the expression of COX-2 and its possible relationship with the maximum standardized uptake value (SUV) in FDG-PET, and EGFR, p16 and MIB1 expression in patients with NSCLC. Material and method: 45 patients (12 adenocarcinomas and 33 squamous cell carcinomas) were included in this study; the immunohistochemical expression of COX-2, MIB-1, p16 and EGFR was determined using tissue-array. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. Results: COX-2 expression was detected in 35 out of 45 cases, and was very significant (> ++) in 12 of them. SUV values were lower in the COX-2 > ++ cases that in the remaining cases (13.4 ± 1.2 vs. 12.9 vs. 17.1 ± 1.5; p = 0.059). COX-2 > ++ expression and maxSUV values were not correlated with the clinical stage. The expression of COX-2 > ++ was correlated positively with p16 (r = 0.36; p = 0.014) and negatively with MIB1 (r = -0.32; p = 0.041) expression, whereas the SUV was correlated positively with EGFR (r = 0.44; p = 0.004) and negatively with p16 (r = -0.29; p = 0.041) expression. Conclusions: Our results suggest that: a) the expression of COX-2 > ++ is often found in this kind of lung cancer and is not associated with the clinical stage; b) the maxSUVs were not related to the stage and were lower in COX-2 > ++ tumours than in the other cases; and c) the different behaviour of both parameters can be explained by their correlation with cell proliferation (MIB1), EGFR and p16 expression.

A high proportion of plant species is predicted to be threatened with extinction in the near future. However, the threat status of only a small number has been evaluated compared with key animal groups, rendering the magnitude and nature of the risks plants face unclear. Here we report the results of a global species assessment for the largest plant taxon evaluated to date under the International Union for Conservation of Nature (IUCN) Red List Categories and Criteria, the iconic Cactaceae (cacti). We show that cacti are among the most threatened taxonomic groups assessed to date, with 31% of the 1,478 evaluated species threatened, demonstrating the high anthropogenic pressures on biodiversity in arid lands. The distribution of threatened species and the predominant threatening processes and drivers are different to those described for other taxa. The most significant threat processes comprise land conversion to agriculture and aquaculture, collection as biological resources, and residential and commercial development. The dominant drivers of extinction risk are the unscrupulous collection of live plants and seeds for horticultural trade and private ornamental collections, smallholder livestock ranching and smallholder annual agriculture. Our findings demonstrate that global species assessments are readily achievable for major groups of plants with relatively moderate resources, and highlight different conservation priorities and actions to those derived from species assessments of key animal groups., La lista completa de autores que integran el documento puede consultarse en el archivo., Facultad de Ciencias Naturales y Museo

This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed.

Pancreatic adenocarcinoma remains a devastating disease with almost equal rates of incidence and mortality. We have seen how a large amount of agents have failed in showing improved survival over gemcitabine alone in randomized clinical trials conducted in the last couple of decades. More recently, the FOLFIRINOX chemotherapy scheme has shown improvement in overall survival (OS) over the single agent gemcitabine, but unfortunately the high rates of severe adverse events make this regimen to be very difficult to use in the standard daily practice. A new agent created by nano-technology, nab-paclitaxel has recently shown in combination with gemcitabine to improve overall survival in a statistical and clinical manner over gemcitabine alone. In the last years, the molecular and biologic understanding of pancreatic cancer has advanced substantially. This includes understanding the potential importance of the tumor microenvironment, the metabolic adaptation of pancreatic cancer cells to a hypoxic environment, and the role of pancreatic cancer stem and stellate cells. In this chapter, we summarize the implications of molecular biology in clinical research and provide insights for future development of novel agents.

The management of patients with metastatic prostate cancer is initially based on the use of hormonal treatment. After progression to hormones, the combination of docetaxel and prednisone was considered as the standard first-line chemotherapy. In the last years, other different drugs such as cabazitaxel, abiraterone, enzalutamide or radium 223 have showed activity in these patients in the pre- or post-chemotherapy scenario. In this chapter, we review new alternatives of treatment for patients with metastatic prostate cancer, including androgen-directed new strategies, non-AR-mediated therapies, targeted treatments immunotherapy, and bone targeted treatments.

Treatment of metastatic renal cell carcinoma (mRCC) has evolved rapidly over the last years, from the era of immunological therapies to targeted agents. New drugs, vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR), as well as previous immunological therapies, are associated with important toxicity, which may require a physician with experience in the treatment of these side effects. Proper management of these adverse effects (AEs) is essential to ensure the optimal therapeutic dosage and improve patient outcomes, including enhanced survival and quality of life.

To the Editor: Domestic dogs live in close association with humans and livestock, participating in the transmission of diseases of zoonotic, veterinary, and conservation interest (1,2). Most households in Uganda have traditionally kept dogs for hunting and for help with herding, security, and guarding livestock. Most dogs receive no prophylactic measures (e.g., vaccinations) and roam freely; this situation exposes them to pathogens from eating garbage, rodents, and stillborn animals and other carcasses and through inhalation during scent communication. Thus, dogs are a reservoir for certain pathogens and a useful sentinel for others (3). In 2011, serum samples were obtained from 116 mixed-breed dogs during a rabies vaccination campaign in and near 3 national parks in southwestern Uganda; the dogs were >4 months of age and were voluntarily brought in by their owners (Figure, Appendix, Table). Two of the parks, Bwindi Impenetrable (BI) and Mgahinga Gorilla (MG), have some of the most biologically diverse tropical forests in eastern Africa and are home to mountain gorillas. The third park, Queen Elizabeth (QE), is home to populations of protected carnivores and ungulates. The parks lie within a densely populated rural landscape; in some areas, the population is as high as 500 persons/km2. Figure Map of Uganda showing 3 areas where a serosurvery for human and animal pathogens was conducted among dogs. 1, Queen Elizabeth National Park; 2, Bwindi Impenetrable National Park; 3, Mgahinga Gorilla National Park. Table Methodology and seroprevalence for selected pathogens in rural dogs in 3 national parks, Uganda, 2011* Of the 116 sampled dogs, 4 had been vaccinated against rabies by the authors in 2010 in QE (not included in rabies results), and 11 (all males) had been castrated by local animal healers before serum samples were obtained. The samples were used to test for seroprevalence rates to rabies virus (RABV), canine distemper virus (CDV), canine parvovirus (CPV), Leptospira interrogans, Leishmania sp., Toxoplasma gondii, and Neospora caninum (Table). Seroprevalence rates ranged from 20% to 100% (Table). CPV seroprevalence was higher in BI and QE than in MG (χ2 >12.6, p

Periprosthetic knee fractures following total knee arthroplasty are increasing proportionally to the number of primary procedures done. We performed a retrospective review of Rorabeck type II fractures treated with a retrograde nail, trying to find the relationship between failure and the number of distal locking screws used. Twenty-six patients were included. The number of distal interlocking screws (patients with one or two distal interlocking screws and patients with three screws) correlated with nonunion (p0.1), did not correlate with the malunion rate (p0.1) and correlated with the reintervention rate (p0.1).