Impaired intratumoral dendritic cell function and potential predictive value of dendritic cell markers for metastasis in malignant salivary gland tumors.

BACKGROUND: The differentiation between primary and metastatic salivary gland neoplasms (SGNs) helps in determining appropriate management strategies, including the need for additional diagnostic tests, surveillance, or aggressive treatment. The purpose of this study was to identify and quantify the immature and mature dendritic cells (DCs) in metastatic and no metastatic SGNs and determine its association with clinicopathological findings. MATERIAL AND METHODS: Cross-sectional, observational, and descriptive study that includes 33 malignant salivary gland neoplasms [MSGN (6, 18.1% metastatic)], and 22 pleomorphic adenomas (PA), as a control group. Clinical and histopathological characteristics were obtained. Immunohistochemistry for human leukocyte antigen D-related (HLA-DR), CD1a, CD83, and Ki-67 proteins was done. Positive intra- and peritumoral DCs were counted. RESULTS: Individuals with MSGN had a lower density of intratumoral HLA-DR+ cells than those with PA (p=0.001), Ki-67 immunostaining was significantly higher in MSGN than in PA (6% vs. 1.4%, p<0.001). Metastatic MSGN showed less intratumoral CD1a+ than non-metastatic (3.2 vs. 165.1, p=0.001). No differences in intra- and peritumoral CD83+ cells were found between benign and malignant SGN. CONCLUSIONS: These results suggest that the immune-protective function of intratumoral DCs is compromised in MSGNs. DCs markers may represent useful prediction tools for metastases in salivary gland malignancies, with crucial implications in the implementation of appropriate disease management strategies.

Una actualización en el protocolo en cáncer de próstata metastásico hormonosensible / Hormone sensitive protocol for metastatic prostate cancer, an update

Revisar y actualizar los últimos protocolos en cáncer de próstata metastásico hormonosensible para mejorar su manejo clínico en la práctica clínica. Realizar un análisis de los datos y los protocolos más recientes en el cáncer de próstata metastásico hormonosensible según paneles de expertos en este ámbito. Actualmente se necesita un grupo de consenso nominal para unificar y mejorar las recomendaciones para el manejo de pacientes sensibles con cáncer de próstata metastásico. Este documento unifica y mejora el manejo de los pacientes con cáncer de próstata metastásico hormonosensible, con una metodología que combina datos cuantitativos y cualitativos, y basada en la participación de un amplio comité científico designado por la Asociación Española de Urología (AU)

To review and update last protocols in hormone sensitive metastatic prostate cancer for improving clinical management in routine. Evidence analysis available about recent updates protocols in hormone sensitive metastatic prostate cancer according to expert panel of clinicians about this field. A nominal consensus group for unify and improve the recommendations to the management of sensitive metastatic prostate cancer patients is currently needed. This document unifies and improve the management of patients with hormone sensitive metastatic prostate cancer, with a methodology that combines data quantitative and qualitative and based on the participation of a broad scientific committee appointed by the Spanish Association of Urology (AU)

Hormone sensitive protocol for metastatic prostate cancer, an update.

To review and update last protocols in hormone sensitive metastatic prostate cancer for improving clinical management in routine. Evidence analysis available about recent updates protocols in hormone sensitive metastatic prostate cancer according to expert panel of clinicians about this field. A nominal consensus group for unify and improve the recommendations to the management of sensitive metastatic prostate cancer patients is currently needed. This document unifies and improve the management of patients with hormone sensitive metastatic prostate cancer, with a methodology that combines data quantitative and qualitative and based on the participation of a broad scientific committee appointed by the Spanish Association of Urology.

Health-related quality of life of X-linked hypophosphatemia in Spain.

BACKGROUND: Health-related quality of life (HRQoL) of patients with X-linked hypophosphatemia (XLH) is lower than that of both the general population and the patients with other chronic diseases, mainly due to diagnostic delay, treatment difficulties, poor psychosocial support, and problems with social integration. Early diagnosis and optimal treatment are paramount to control the disease in patients with XLH, avoid complications, and maintain or improve their HRQoL. We, therefore, analyzed the HRQoL of pediatric and adult patients with XLH treated with conventional therapy in Spain. RESULTS: We used several versions of the EuroQol-5 dimensions (EQ-5D) instrument according to the age of patients with XLH. Then we compared the HRQoL of patients to that of the general Spanish population. Children with XLH (n = 21) had moderate problems in walking about (61.9%), washing or dressing themselves (9.52%), and performing their usual activities (33.33%). They also felt moderate pain or discomfort (61.9%) and were moderately anxious or depressed (23.81%). Adults with XLH (n = 29) had lower HRQoL, with problems in walking (93%, with 3.45% unable to walk independently), some level of pain (86%, with 3.45% experiencing extreme pain), problems with their usual activities (80%) and self-care (> 50%), and reported symptoms of anxiety and/or depression (65%). There were important differences with the general Spanish population. CONCLUSIONS: XLH impacts negatively on physical functioning and HRQoL of patients. In Spanish patients with XLH, the HRQoL was reduced despite conventional treatment, clearly indicating the need to improve the therapeutic approach to this disorder.

X-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affectingX-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affecting bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.

A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper.

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

Nutritional Risk and Mortality at One Year for Elderly Patients Hospitalized with Nonvalvular Atrial Fibrillation. Nonavasc Registry.

OBJECTIVES: To determine whether nutritional risk is associated with the mortality of elderly patients hospitalized with nonvalvular atrial fibrillation (NVAF). DESIGN: Prospective, multicenter cohort study. SETTING: Internal medicine departments in Spain. PARTICIPANTS: Inpatients >75 years with NVAF. MEASUREMENTS: We measured the thrombotic and hemorrhagic risk at admission using the CHA2DS2-VASc and HAS-BLED scales, respectively, and the nutritional risk with the controlling nutritional status (CONUT) index. We established 4 degrees of nutritional risk: null (CONUT score 0-1 point), low (2-4 points), moderate (5-8 points) and high (9-12 points). We also conducted a 1-year follow-up. RESULTS: We included 449 patients, with a mean age of 85.2(5.2) years. The nutritional risk was null for 70(15.6%) patients, low for 206 45.9%), moderate for 152(33.8%) and high for 21(4.7%). At the end of one year, 177(39.4%) patients had died. The score on the CONUT index was higher for the deceased patients (4.6 vs. 3.6, p<0.001). The CONUT score (HR, 1.076; 95%CI 1.009-1.148; p=0.025), the Charlson index (HR, 1.080; 95%CI 1.017-1.148; p=0.013) and the presence of pressure ulcers (HR, 1.700; 95%CI 1.028-2.810; p=0.039) were independently associated with increased mortality at one year of follow-up. The prescription of oral anticoagulants at discharge was associated with lower mortality (HR, 0.440; 95%CI 0.304-0.638; p<0.001). CONCLUSIONS: More than a third of elderly patients hospitalized with NVAF have a moderate to high nutritional risk. These patients have greater mortality at the end of one year.

The role of seagrass vegetation and local environmental conditions in shaping benthic bacterial and macroinvertebrate communities in a tropical coastal lagoon.

We investigated the influence of seagrass canopies on the benthic biodiversity of bacteria and macroinvertebrates in a Red Sea tropical lagoon. Changes in abundance, number of taxa and assemblage structure were analyzed in response to seagrass densities (low, SLD; high, SHD; seagrasses with algae, SA), and compared with unvegetated sediments. Biological and environmental variables were examined in these four habitats (hereafter called treatments), both in the underlaying sediments and overlaying waters, at three randomly picked locations in March 2017. Differences between treatments were more apparent in the benthic habitat than in the overlaying waters. The presence of vegetation (more than its cover) and changes in sedimentary features (grain size and metals) at local scales influenced the observed biological patterns, particularly for macroinvertebrates. Of note, the highest percentage of exclusive macroinvertebrate taxa (18% of the gamma diversity) was observed in the SHD treatment peaking in the SA for bacteria. Benthic macroinvertebrates and bacteria shared a generally low number of taxa across treatments and locations; approximately, 25% of the gamma diversity was shared among all treatments and locations for macrofauna, dropping to 11% for bacteria. Given the low overlap in the species distribution across the lagoon, sustaining the connectivity among heterogeneous soft sediment habitats appears to be essential for maintaining regional biodiversity. This study addresses a current scientific gap related to the relative contributions of vegetated and unvegetated habitats to biodiversity in tropical regions.

Sarcopenia, frailty, cognitive impairment and mortality in elderly patients with non-valvular atrial fibrillation. / Sarcopenia, fragilidad, deterioro cognitivo y mortalidad en pacientes ancianos con fibrilación auricular no valvular.

OBJECTIVES: To determine the prevalence of sarcopenia, frailty and cognitive impairment in elderly patients with nonvalvular atrial fibrillation (NVAF) and the factors' influence on survival. METHODS: Prospective, multicentre cohort study of patients older than 75 years with NVAF hospitalised in internal medicine departments in Spain. For each patient, we recorded the creatinine, haemoglobin and platelet levels, the scores on the CHA2DS2-VASc and HAS-BLED scales and Charlson index, as well as the use of oral anticoagulants. We measured sarcopenia with the SARC-F scale, frailty with the FRAIL scale and cognitive impairment with the Short Portable Mental State Questionnaire. We also conducted a 1-year follow-up. RESULTS: The study included 596 patients with NVAF, with a mean age of 84.9 (SD: 5.2) years. Of these, 295 (49.5%) presented sarcopenia, 305 (51.2%) presented frailty, and 251 (42.1%) presented cognitive impairment. At the end of 1year, 226 (37.9%) patients had died. Mortality was greater for the patients with sarcopenia, frailty and cognitive impairment. In the multivariate analysis, sarcopenia (HR: 1.775; 95%CI: 1.270-2.481), age, comorbidity and a history of peripheral embolism were associated with increased mortality, and the use of oral anticoagulants at discharge (HR: 0.415; 95%CI: 0.307-0.560) was associated with lower mortality. CONCLUSIONS: Sarcopenia, frailty and cognitive impairment are very common in elderly patients with NVAF and are frequently associated. Sarcopenia was associated with increased mortality.

Water associated with residential areas and tourist resorts is the key predictor of Asian tiger mosquito presence on a Mediterranean island.

The Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae), is a highly invasive species and a vector of several viruses of serious concern to public health. Investigating the habitat selection of this species at small to medium scales is essential to the planning of effective prevention and control campaigns. The present group considered detailed data for this species' presence/absence collected at 228 sites on Mallorca Island (Spain) in autumn 2015, 3 years after the first detection of the species on the island. Site occupancy models accounting for false negative detections and imperfect monitoring were used to evaluate the relationships between mosquito presence and habitat variables. In the study area, mosquito presence was negatively associated with altitude, probably as a result of greater human presence at low altitudes near the coast. Moreover, the presence of Ae. albopictus was positively associated with swimming pools as a result of associated gardens, plants and sources of fresh water. These two variables were combined to predict the presence of the species across the entire island.

Proposal for the creation of a national strategy for precision medicine in cancer: a position statement of SEOM, SEAP, and SEFH.

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational, and knowledge-related challenges. Without a national strategy, precision medicine, which will be implemented one way or another, could take place without the appropriate planning that can guarantee technical quality, equal access of all citizens to the best practices, violating the rights of patients and professionals, and jeopardizing the solvency of the healthcare system. With this paper from the Spanish Societies of Medical Oncology, Pathology, and Hospital Pharmacy, we highlight the need to institute a consensual national strategy for the development of precision medicine in our country, review the national and international context, comment on the opportunities and challenges for implementing precision medicine, and outline the objectives of a national strategy on precision medicine in cancer.

Perfil epidemiológico del paciente pediátrico intoxicado atendido en urgencias / Epidemiological profile of the paediatric patient managed at the emergency unit due to intoxication

Objetivo: describir el perfil epidemiológico del paciente pediátrico intoxicado, atendido en el servicio de urgencias del Hospital Infantil Universitario Miguel Servet de Zaragoza durante los años 2012-2014, analizando los factores asociados. Método: estudio descriptivo transversal. Se seleccionó la población que cumplía criterios CIE-9 E850-E858, E860-E869 y E905. Variables: edad, sexo, utilización de recursos sanitarios, contacto con el servicio de información toxicológica (SIT), tóxico involucrado, tipo de fármaco, voluntariedad en la exposición, procedencia del paciente, lugar de exposición, pruebas complementarias, hora y día de atención. Para el análisis estadístico se utilizó la prueba de H de Kruskal Wallis y el test de Chi cuadrado con un p valor < 0,001. Resultados: se detectaron 482 episodios de intoxicaciones. El 67,7% era menor de 5 años y el 48,5% acudió por intoxicaciones farmacológicas, principalmente psicofármacos. La razón de masculinidad fue 0,508. El 72% de los pacientes no había hecho uso de otros recursos sanitarios previamente. La voluntariedad en la exposición a tóxicos supuso el 17% y el principal tóxico implicado fueron los fármacos (48,5%), especialmente los psicofármacos (27,2%). Un 97,3% no entró en contacto con el SIT. El 62% de los mayores de 12 años llegó en ambulancia, con una asociación estadísticamente significativa con el alcohol. Conclusiones: el perfil epidemiológico de las intoxicaciones agudas fue de niño menor de 5 años, atendido en fin de semana, a causa de la ingesta de psicofármacos y con apenas actuación de primeros intervinientes. La prevención primaria en centros de salud debería ser una actuación clave para la disminución de las intoxicaciones pediátricas (AU)

Objective: to describe the epidemiological profile of the paediatric patient managed due to intoxication at the Emergency Unit of the Hospital Infantil Universitario Miguel Servet in Zaragoza during the years 2012 to 2014, analyzing all associated factors. Method: a descriptive transversal study. The population selected met the CIE-9 E850-E858, E860-E869 and E905 criteria. Variables: age, gender, use of healthcare resources, contact with the Toxicological Information Services (TIS), toxic substance involved, type of drug, voluntary exposure, origin of the patient, place of exposure, complementary tests, hour and day of medical care. Kruskal-Wallis H Test and Chi Square test were used for statistical analysis, with p value < 0.001. Results: in total, 482 intoxication episodes were detected; 67.7% were <5-year old, and 48.5% consulted due to pharmacological intoxications, mainly by psychotropic drugs. There was a 0.508 rate of male patients. Overall, 72% of patients had not used any healthcare resources previously. There was a 17% voluntary exposure to toxic substances, and medical drugs were the main substance involved (48.5%), particularly psychotropic agents (27.2%). In 97.3% of cases there was no contact with the TIS; 62% of > 12-year-old patients arrived by ambulance, with a statistically significant association with alcohol. Conclusions: the epidemiological profile of acute intoxications consisted in a < 5-year-old boy, seen during the weekend, due to the intake of psycotropic drugs, and with little action by the first responders. Primary prevention in health centres should be a key action for the reduction in paediatric intoxications (AU)

[Benign late onset Parkinson's disease]. / Enfermedad de Parkinson senil benigna.

TITLE: Enfermedad de Parkinson senil benigna.

Enfermedad de Parkinson senil benigna / Benign late onset Parkinsons disease

No disponible

Static and elevated pollen traps do not provide an accurate assessment of personal pollen exposure.

SUMMARY: Background. Volumetric pollen traps are commonly used to assess pollen exposure. These traps are well suited for estimating the regional mean airborne pollen concentration but are likely not to provide an accurate index of personal exposure. In this study, we tested the hypothesis that hair sampling may provide different pollen counts from those from pollen traps, especially when the pollen exposure is diverse. Methods. We compared pollen counts in hair washes to counts provided by stationary volumetric and gravimetric pollen traps in 2 different settings: urban with volunteers living in short distance from one another and from the static trap and suburban in which volunteers live in a scattered environment, quite far from the static trap. Results. Pollen counts in hair washes are in full agreement with trap counts for uniform pollen exposure. In contrast, for diverse pollen exposure, .individual pollen counts in hair washes vary strongly in quantity and taxa composition between individuals and dates. These results demonstrate that the pollen counts method (hair washes vs. stationary pollen traps) may lead to different absolute and relative contributions of taxa to the total pollen count. Conclusions. In a geographic area with a high diversity of environmental exposure to pollen, static pollen traps, in contrast to hair washes, do not provide a reliable estimate of this higher diversity.

Mass and stiffness spectrometry of nanoparticles and whole intact bacteria by multimode nanomechanical resonators.

The identification of species is a fundamental problem in analytical chemistry and biology. Mass spectrometers identify species by their molecular mass with extremely high sensitivity (<10-24 g). However, its application is usually limited to light analytes (<10-19 g). Here we demonstrate that by using nanomechanical resonators, heavier analytes can be identified by their mass and stiffness. The method is demonstrated with spherical gold nanoparticles and whole intact E. coli bacteria delivered by electrospray ionization to microcantilever resonators placed in low vacuum at 0.1 torr. We develop a theoretical procedure for obtaining the mass, position and stiffness of the analytes arriving the resonator from the adsorption-induced eigenfrequency jumps. These results demonstrate the enormous potential of this technology for identification of large biological complexes near their native conformation, a goal that is beyond the capabilities of conventional mass spectrometers.

How two-dimensional bending can extraordinarily stiffen thin sheets.

Curved thin sheets are ubiquitously found in nature and manmade structures from macro- to nanoscale. Within the framework of classical thin plate theory, the stiffness of thin sheets is independent of its bending state for small deflections. This assumption, however, goes against intuition. Simple experiments with a cantilever sheet made of paper show that the cantilever stiffness largely increases with small amounts of transversal curvature. We here demonstrate by using simple geometric arguments that thin sheets subject to two-dimensional bending necessarily develop internal stresses. The coupling between the internal stresses and the bending moments can increase the stiffness of the plate by several times. We develop a theory that describes the stiffness of curved thin sheets with simple equations in terms of the longitudinal and transversal curvatures. The theory predicts experimental results with a macroscopic cantilever sheet as well as numerical simulations by the finite element method. The results shed new light on plant and insect wing biomechanics and provide an easy route to engineer micro- and nanomechanical structures based on thin materials with extraordinary stiffness tunability.

Spatially multiplexed dark-field microspectrophotometry for nanoplasmonics.

Monitoring the effect of the substrate on the local surface plasmon resonance (LSPR) of metallic nanoparticles is key for deepening our understanding of light-matter interactions at the nanoscale. This coupling gives rise to shifts of the LSPR as well as changes in the scattering pattern shape. The problem requires of high-throughput techniques that present both high spatial and spectral resolution. We present here a technique, referred to as Spatially Multiplexed Micro-Spectrophotometry (SMMS), able to perform polarization-resolved spectral and spatial analysis of the scattered light over large surface areas. The SMMS technique provides three orders of magnitude faster spectroscopic analysis than conventional dark-field microspectrophotometry, with the capability for mapping the spatial distribution of the scattered light intensity with lateral resolution of 40 nm over surface areas of 0.02 mm(2). We show polarization-resolved dark-field spectral analysis of hundreds of gold nanoparticles deposited on a silicon surface. The technique allows determining the effect of the substrate on the LSPR of single nanoparticles and dimers and their scattering patterns. This is applied for rapid discrimination and counting of monomers and dimers of nanoparticles. In addition, the diameter of individual nanoparticles can be rapidly assessed with 1 nm accuracy.

Detection of cancer biomarkers in serum using a hybrid mechanical and optoplasmonic nanosensor.

Blood contains a range of protein biomarkers that could be used in the early detection of disease. To achieve this, however, requires sensors capable of detecting (with high reproducibility) biomarkers at concentrations one million times lower than the concentration of the other blood proteins. Here, we show that a sandwich assay that combines mechanical and optoplasmonic transduction can detect cancer biomarkers in serum at ultralow concentrations. A biomarker is first recognized by a surface-anchored antibody and then by an antibody in solution that identifies a free region of the captured biomarker. This second antibody is tethered to a gold nanoparticle that acts as a mass and plasmonic label; the two signatures are detected by means of a silicon cantilever that serves as a mechanical resonator for 'weighing' the mass of the captured nanoparticles and as an optical cavity that boosts the plasmonic signal from the nanoparticles. The capabilities of the approach are illustrated with two cancer biomarkers: the carcinoembryonic antigen and the prostate specific antigen, which are currently in clinical use for the diagnosis, monitoring and prognosis of colon and prostate cancer, respectively. A detection limit of 1 × 10(-16) g ml(-1) in serum is achieved with both biomarkers, which is at least seven orders of magnitude lower than that achieved in routine clinical practice. Moreover, the rate of false positives and false negatives at this concentration is extremely low, ∼10(-4).

Physics of nanomechanical spectrometry of viruses.

There is an emerging need of nanotools able to quantify the mechanical properties of single biological entities. A promising approach is the measurement of the shifts of the resonant frequencies of ultrathin cantilevers induced by the adsorption of the studied biological systems. Here, we present a detailed theoretical analysis to calculate the resonance frequency shift induced by the mechanical stiffness of viral nanotubes. The model accounts for the high surface-to-volume ratio featured by single biological entities, the shape anisotropy and the interfacial adhesion. The model is applied to the case in which tobacco mosaic virus is randomly delivered to a silicon nitride cantilever. The theoretical framework opens the door to a novel paradigm for biological spectrometry as well as for measuring the Young's modulus of biological systems with minimal strains.