[Inhaled levodopa: from evidence to experience]. / Levodopa inhalada: de la evidencia a la experiencia.

Most patients with Parkinson's disease experience motor fluctuations or 'off' periods, which impact on their daily activities, increase their disability and diminish their quality of life. They suffer from these fluctuations despite multiple adjustments to the schedules, doses and intake of medication. In this context, on-demand or rescue treatments are necessary to attempt to improve 'off' periods, with drugs that have the pharmacokinetic advantage of a much faster onset of action because their routes of administration are not oral. There are currently three on-demand therapies for the treatment of fluctuations: subcutaneous apomorphine, inhaled levodopa and sublingual apomorphine. Of the three alternatives, subcutaneous apomorphine generally has the fastest onset of action, sublingual apomorphine provides the longest clinical effect, and inhaled levodopa has the most favourable side effect profile. Each of these drugs has its own characteristics: the time before onset of action, the duration of action and different side effect profiles. The choice for each patient will depend on their individual needs and circumstances. To mark the first year of the introduction of inhaled levodopa, we review these therapies, focusing on the experience with this new dosage form of levodopa.

TITLE: Levodopa inhalada: de la evidencia a la experiencia.La mayoría de los pacientes con enfermedad de Parkinson sufren fluctuaciones motoras o períodos off, que impactan en sus actividades cotidianas, aumentan su discapacidad y empeoran su calidad de vida. A pesar de realizar múltiples ajustes en los horarios, en las dosis y en las tomas de medicación, no se consigue que estén libres de estas fluctuaciones. Es en este contexto en el que son necesarios los tratamientos a demanda o de rescate para tratar de mejorar los períodos off, con fármacos que tienen la ventaja farmacocinética de un inicio de acción mucho más rápido debido a que sus vías de administración no son orales. En la actualidad existen tres terapias a demanda para el tratamiento de las fluctuaciones: apomorfina subcutánea, levodopa inhalada y apomorfina sublingual. En general, la apomorfina subcutánea tiene un inicio de efecto más rápido, la apomorfina sublingual ofrece el efecto clínico más prolongado y la levodopa inhalada tiene el perfil de efectos secundarios más favorable entre las tres opciones. Cada uno de estos medicamentos tiene características únicas: tiempo de inicio, duración de acción y diferentes perfiles de efectos secundarios. La elección para cada paciente dependerá de sus necesidades y circunstancias individuales. Aprovechando el primer año de la introducción de la levodopa inhalada, revisamos estas terapias, centrándonos en la experiencia acumulada con esta nueva presentación galénica de levodopa.

Laparoscopic intracorporeal rectus aponeuroplasty (LIRA) technique versus intraperitoneal onlay mesh (IPOM plus) for ventral hernia repair: a comparative analysis.

PURPOSE: Primary aim of this study is to compare the postoperative outcomes of the laparoscopic intracorporeal rectus aponeuroplasty (LIRA) technique to the intraperitoneal onlay mesh closing the defect (IPOM plus), in terms of recurrence and bulging rates at one-year follow-up; secondary aim is to compare the postoperative complications, seroma and pain at 30 days and one-year after surgery. METHODS: Patients with midline ventral hernia of 4-10 cm in width were included. Computed tomography scan was performed before, 1 and 12 months after surgery. Pain was evaluated using the visual analogue scale. RESULTS: Forty-five and forty-seven consecutive patients underwent LIRA and IPOM plus, respectively. Preoperatively, smoke habits and chronic obstructive pulmonary disease rates were statistically significantly higher in the LIRA group (p = 0.0001 and p = 0.012, respectively). Two bulgings (4.4%) occurred in the LIRA group, while in the IPOM plus group occurred 10 bulgings (21.3%) and three recurrences (6.4%) (p = 0.017 and p = 0.085, respectively). Postoperatively, seven (15.6%, Clavien-Dindo I) and four complications (8.5%, two Clavien-Dindo I, two Clavien-Dindo III-b) occurred in the LIRA and in the IPOM plus group, respectively (p = 0.298). One month after surgery, clinical seroma, occurred in five (11.1%) and eight patients (17%) in the LIRA and in the IPOM plus group, respectively (p = 0.416). During follow-up, pain reduction occurred, without statistically significant differences. CONCLUSIONS: In this study, even if we analysed a small series, LIRA showed lower bulging and recurrence rates in comparison to IPOM plus at one-year follow-up. Further prospective studies, with a large sample of patients and longer follow-up are required to draw definitive conclusions.

Interactive impacts of boron and organic amendments in plant-soil microbial relationships.

Water shortage and low organic carbon content in soil limit soil fertility and crop productivity. The use of desalinated seawater is increasing as an alternative source of irrigation water. However, it has a high boron (B) content that could cause toxicity in the plant-soil microbial system. Here, we evaluated the responses of the soil microbiota and lemon trees to 3 irrigation B doses (0.3, 1, and 15 mg L-1) under two types of soil management (conventional, CS; and organic, OS) in a 180-days pot experiment. High B doses promoted B accumulation in soil, reaching harmful concentrations that affected soil biodiversity. Our results suggest a close interaction between B and organic labile fractions that increased B availability in soil solution. Besides, B addition to soil impacted on microbial biomass. The bacterial community showed sensitivity to the B dose. Organic amendment did not increase B soil adsorption but it favored B plant uptake. The highest B dose had a detrimental impact on plant physiology, finally resulting lethal for the plants. Our study provides a comprehensive assessment of the microbes-plant interactions in soils irrigated with water with high B content. This will be fundamental in the design of future fertirrigation strategies.

Leukoaraiosis May Confound the Interpretation of CT Perfusion in Patients Treated with Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Leukoaraiosis frequently coexists in patients with acute stroke. We studied whether leukoaraiosis could confound the interpretation of CTP findings in patients treated with mechanical thrombectomy. MATERIALS AND METHODS: We analyzed 236 patients with stroke treated with mechanical thrombectomy and studied with CTP, of whom 127 (53.8%) achieved complete reperfusion. Periventricular white matter hyperintensities on MR imaging and hypodensities on NCCT were assessed through the Fazekas score. CTP-predicted nonviable tissue was defined as relative CBF <30%, and final infarct volume was quantified in DWI. We estimated mean MTT, CBV, and CBF in the asymptomatic hemisphere. In patients achieving complete reperfusion, we assessed the accuracy of nonviable tissue to predict final infarct volume using the intraclass correlation coefficient across periventricular hyperintensity/hypodensity Fazekas scores and variable relative CBF cutoffs. RESULTS: MTT was longer (Spearman ρ = 0.279, P < .001) and CBF was lower (ρ = -0.263, P < .001) as the periventricular hyperintensity Fazekas score increased, while CBV was similar across groups (ρ = -0.043, P = .513). In the subgroup of patients achieving complete reperfusion, nonviable tissue-final infarct volume reliability was excellent in patients with periventricular hyperintensity Fazekas score grade 0 (intraclass correlation coefficient, 0.900; 95% CI, 0.805-0.950), fair in patients with periventricular hyperintensity Fazekas scores 1 (intraclass correlation coefficient, 0.569; 95% CI, 0.327-0.741) and 2 (intraclass correlation coefficient, 0.444; 95% CI, 0.165-0.657), and poor in patients with periventricular hyperintensity Fazekas score 3 (intraclass correlation coefficient, 0.310; 95% CI, -0.359-0.769). The most accurate cutoffs were relative CBF <30% for periventricular hyperintensity Fazekas score grades 0 and 1, relative CBF <25% for periventricular hyperintensity Fazekas score 2, and relative CBF <20% for periventricular hyperintensity Fazekas score 3. The reliability analysis according to periventricular hypodensity Fazekas score grades on NCCT was similar to that in follow-up MR imaging. CONCLUSIONS: In patients with stroke, the presence of leukoaraiosis confounds the interpretation of CTP despite proper adjustment of CBF thresholds.

Boron in soil: The impacts on the biomass, composition and activity of the soil microbial community.

The high boron (B) content in desalinated seawater is a concern for crop development. However, in spite of the importance of the soil microbial community in soil fertility, the below-ground impacts of B are still unknown. Here, in a soil-ryegrass model system, the activity, biomass and diversity of the soil microbial community were evaluated in response to irrigation with: i) 0.3 mg B L-1; ii) 1 mg B L-1; and iii) 50 mg B L-1. We assessed two different compounds of boron: boric acid (H3BO3) and disodium tetraborate decahydrate (Na2B4O7·10H2O). Overall, the 1 mg B L-1 dose was identified as the threshold limit that did not irreversibly harm soil sustainability. In contrast, the highest B dose had a noticeable impact on the nitrogen (N) cycle of the soil, as demonstrated by an increase in the water-soluble N content and a decrease in urease activity. Analysis of the phospholipid fatty acids (PLFAs) revealed that the effect of B on the soil microbial biomass was dependent on the chemical form used. High B doses reduced soil microbial respiration and influenced the composition of the bacterial and fungal communities, with fungal diversity being diminished, as revealed by sequencing approaches.

Real-time incidence of travel-related symptoms through a smartphone-based app remote monitoring system: a pilot study.

Trip Doctor®, a Smartphone-based app monitoring system, was developed to detect infections among travelers in real-time. For testing, 106 participants were recruited (62.2% male, mean age 36 years (SD = 11)). Majority of trips were for tourism and main destinations were in South East Asia. Mean travel duration was 14 days (SD = 10). Diarrhea was the most frequently reported symptom (15.5%). The system demonstrated adequate usability and is ready to be used on a larger scale.

Plant-plant competition outcomes are modulated by plant effects on the soil bacterial community.

Competition is a key process that determines plant community structure and dynamics, often mediated by nutrients and water availability. However, the role of soil microorganisms on plant competition, and the links between above- and belowground processes, are not well understood. Here we show that the effects of interspecific plant competition on plant performance are mediated by feedbacks between plants and soil bacterial communities. Each plant species selects a singular community of soil microorganisms in its rhizosphere with a specific species composition, abundance and activity. When two plant species interact, the resulting soil bacterial community matches that of the most competitive plant species, suggesting strong competitive interactions between soil bacterial communities as well. We propose a novel mechanism by which changes in belowground bacterial communities promoted by the most competitive plant species influence plant performance and competition outcome. These findings emphasise the strong links between plant and soil communities, paving the way to a better understanding of plant community dynamics and the effects of soil bacterial communities on ecosystem functioning and services.

Estudio multicéntrico no intervencional en pacientes con artritis reumatoidea tratados con tocilizumab / Non-interventional multicenter study in patients with arthritis rheumatoid treated with tocilizumab

Introducción: Tocilizumab es un anticuerpo monoclonal humanizado anti-receptor de IL-6 que ha demostrado eficacia y seguridad en artritis reumatoidea (AR). Métodos y objetivos: Estudio observacional de cohorte en pacientes con AR moderada a severa tratados con tocilizumab con 6 meses de seguimiento. El objetivo primario fue establecer la adherencia al tratamiento y secundariamente estudiar la efectividad y seguridad. Resultados: Cincuenta pacientes fueron tratados con tocilizumab (86% asociados a DMAR y 14% a monoterapia). La adherencia fue 42/50 (84%; IC 95%: 71-93%) y el porcentaje de respuesta luego de 6 meses según criterios de la ACR20/50/70/90 fueron 68,2%, 40,9%, 13,6% y9,1% respectivamente. El recuento de 28 articulaciones dolorosas (TJC28) e inflamadas (SJC28) se redujo significativamente de 12 y 8 en el momento basal a 5 y 2 a los 6 meses respectivamente (p <0,001). Se observó una reducción significativa en los parámetros de evaluación de actividad del médico y en las evaluaciones reportadas por el paciente. No se registraron eventos adversos de intensidad severa ni eventos adversos serios relacionados con la medicación. Conclusiones: Se observó que 42/50 pacientes adhirieron al tratamiento con una respuesta significativa en los parámetros de efectividad y adecuado perfil de seguridad consistente con los estudios publicados previamente

The composition and depth of green roof substrates affect the growth of Silene vulgaris and Lagurus ovatus species and the C and N sequestration under two irrigation conditions.

Extensive green roofs are used to increase the surface area covered by vegetation in big cities, thereby reducing the urban heat-island effect, promoting CO2 sequestration, and increasing biodiversity and urban-wildlife habitats. In Mediterranean semi-arid regions, the deficiency of water necessitates the use in these roofs of overall native plants which are more adapted to drought than other species. However, such endemic plants have been used scarcely in green roofs. For this purpose, we tested two different substrates with two depths (5 and 10 cm), in order to study their suitability with regard to adequate plant development under Mediterranean conditions. A compost-soil-bricks (CSB) (1:1:3; v:v:v) mixture and another made up of compost and bricks (CB) (1:4; v:v) were arranged in two depths (5 and 10 cm), in cultivation tables. Silene vulgaris (Moench) Garcke and Lagurus ovatus L. seeds were sown in each substrate. These experimental units were subjected, on the one hand, to irrigation at 40% of the registered evapotranspiration values (ET0) and, on the other, to drought conditions, during a nine-month trial. Physichochemical and microbiological substrate characteristics were studied, along with the physiological and nutritional status of the plants. We obtained significantly greater plant coverage in CSB at 10 cm, especially for L. ovatus (80-90%), as well as a better physiological status, especially in S. vulgaris (SPAD values of 50-60), under irrigation, whereas neither species could grow in the absence of water. The carbon and nitrogen fixation by the substrate and the aboveground biomass were also higher in CSB at 10 cm, especially under L. ovatus - in which 1.32 kg C m(-2) and 209 g N m(-2) were fixed throughout the experiment. Besides, the enzymatic and biochemical parameters assayed showed that microbial activity and nutrient cycling, which fulfill a key role for plant development, were higher in CSB. Therefore, irrigation of 40% can maintain an adequate plant cover of both endemic species, particularly in a deeper and soil-containing substrate.

Análisis de los factores que permiten e impiden la evolución de la hernioplastia inguinal laparoscópica en CMA en un hospital comarcal / Analysis of the factors promote and difficult the evolution of Ambulatory Surgery of the laèaroscopic inguinal hernia repair in district hospital

Introducción: La cirugía laparoscópica ha avanzado en todos los campos quirúrgicos. En el campo de la hernia inguinal la realización de TEP y TAPP es diaria en nuestro centro. La ambulatorización de estos enfermos está en aumento, puesto que cuando iniciamos la implantación de la cirugía laparoscópica de la hernia todos permanecían entre 24-48 horas postoperatorias. Actualmente el alta es en 12 horas y se ha iniciado el proceso de ambulatorización (sin pernocta) en pacientes seleccionados. Material y métodos: Analizamos nuestros resultados desde el 2007 (fecha en la que comenzamos a realizar técnicas endoscópicas en hernias inguinales) hasta 2013. Realizamos un análisis en nuestra serie de pacientes con criterios de inclusión para cirugía laparoscópica de la hernia inguinal y exclusión de cara a fomentar la ambulatorización del proceso. Además realizamos un análisis del contexto hospitalario y extrahospitalario que han influido tanto positiva como negativamente (con significación estadística y sin significación) en el desarrollo de las técnicas laparoscópicas en la hernia inguinal. Resultados: Las circunstancias principales que nos impiden actualmente aumentar las altas en CMA en hospital comarcal son la dispersión geográfica de los pacientes y la falta de medios de atención en las proximidades de sus domicilios. La correcta selección de los pacientes ha hecho posible que la técnica se implante en nuestro centro y se realice en términos de hospitalización de corta estancia, con una visión más cercana de la ambulatorización del proceso. Conclusiones: En conclusión debemos ir progresando hasta conseguir un índice de ambulatorización cercano al 40-50 % (como objetivo real), aunque conocemos que algunas de las dificultades son grandes (siendo la principal la gran distancia entre el domicilio y el hospital). Los óptimos resultados, con una tasa de recidiva menor del 0,2 %, tasa de infección del O %, tasa de complicaciones menores muy baja, hacen que nuestro futuro vaya encaminado a seguir aplicando las técnicas endoscópicas en la cirugía de la hernia inguinal (AU)

Introduction: Laparoscopic surgery has advanced in all surgical fields. Inguinal hernia laparoscopic repair (TEP and TAPP) is a common procedure in our center. The ambulatory surgery of these patients is increasing, because when we started the introduction of laparoscopic hernia surgery all remained within 24-48 hours after surgery. Today the outcome is at 12 hours and only out-patient (no overnight) process in selected patients. Material and methods: We analyze our results from 2007 (the date we started performing endoscopic techniques in inguinal hernias) until 2013. We analyzed our series of patient looking for inclusion criteria for Laparoscopic Inguinal hernia surgery and exclusion, in order to promote one day surgery. Furthermore we analyze the hospital and social setting which influenced both positively and negatively (statistically significant and not significant) in the development of laparoscopic techniques for inguinal hernia. Results: The main current circumstances which limit the ambulatory surgery are the geographic dispersion of patients and the lack of health center in the proximity of their homes (AU)

[Biomarkers in Alzheimer's disease]. / Biomarcadores en la enfermedad de Alzheimer.

The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.

TITLE: Biomarcadores en la enfermedad de Alzheimer.Los nuevos criterios diagnosticos para la enfermedad de Alzheimer (EA) incluyen la posibilidad de practicar tecnicas de neuroimagen o analisis del liquido cefalorraquideo con el objeto de aumentar la certeza de que un paciente presenta un proceso neuropatologico relacionado con la EA. Tres biomarcadores del liquido cefalorraquideo (Aß42, tau total y tau fosforilada) reflejan las caracteristicas patologicas centrales de la EA. Estos procesos neuropatologicos se inician decadas antes de que sean detectables sintomas, por lo que se esta determinando si estos biomarcadores pueden ser utiles en la deteccion precoz y prevencion de la demencia. Podemos definir tres estadios de la EA: estadio preclinico, deterioro cognitivo leve debido a EA y demencia por EA. En esta revision, se resumen las evidencias de biomarcadores en cada uno de estos estadios. Tambien se revisan los estudios que investigan biomarcadores para la EA en sangre. Los estudios en ancianos asintomaticos y en portadores de mutaciones autosomicas dominantes de EA han mostrado alteraciones en los biomarcadores que permiten la segregacion en estos estadios preclinicos. Estos estudios permitiran identificar las poblaciones diana de los ensayos clinicos futuros y evaluar de manera objetiva si se producen modificaciones sobre el proceso patologico de la EA. El desarrollo de los biomarcadores del liquido cefalorraquideo requiere unos procedimientos normalizados preanaliticos y analiticos estrictos que hagan fiables los estudios multicentricos y universalicen los puntos de corte de la tecnica en los distintos estadios de la EA.

El control de la calidad en las compresiones torácicas y su relación con la recuperación de pulso / Feedback on chest compression quality variables and their relationship to rate of return of spontaneous circulation

Objetivos: Varios estudios demuestran el incumplimiento de las recomendaciones internacionales en la ejecución de las compresiones torácicas durante la reanimación cardiopulmonar(RCP). Existen dispositivos de ayuda para la realización de la RCP y SAMUR Protección Civil ha implementado uno de ellos (Q-CPR®). El presente estudio analiza si existe asociación entre uso del dispositivo y la recuperación de pulso (RP), describe la ejecución de las compresiones en relación a los estándares de calidad y verifica si alguno de los parámetros medidos puede relacionarse con la RP. Método: Estudio prospectivo de cohortes. El periodo de reclutamiento fue de noviembre de 2007 a diciembre de 2010. Se incluyó a todo paciente atendido por una parada cardiorrespiratoria (PCR), y el factor de exposición fue el uso de dispositivo Q-CPR®. Resultados: Se atendieron 892 PCR: 108 con Q-CPR® y 784 sin Q-CPR®. Las dos poblaciones fueron comparables en cuanto a las variables predictoras analizadas. Se encontró (..) (AU)

Background: Studies have revealed failure to follow international guidelines for performing chest compressions in cardiopulmonary resuscitation (CPR). Certain feedback devices are available for use. One such device (the Q-CPR) has been used in the Madrid Emergency and Rescue Service (SAMUR).Objectives. To analyze whether there is an association between the rate of return of spontaneous circulation (ROSC) and the use of a feedback device, to describe the performance of compressions in comparison with quality standards, and to determine whether any of the measured variables are related to the rate of ROSC. Methods: Prospective cohort study. Recruitment period: November 2007 to December 2010. Inclusion criteria: patients with cardiorespiratory arrest attended by the SAMUR. Exposure factor: use of a CPR measurement and feedback device. Results: SAMUR attended 892 cases of cardiorespiratory arrest: the Q-CPR was used in 108 patients and 784 were given (AU)

NO dissociation on Cu(111) and Cu2O(111) surfaces: a density functional theory based study.

NO dissociation on Cu(111) and Cu(2)O(111) surfaces is investigated using spin-polarized density functional theory. This is to verify the possibility of using Cu-based catalyst for NO dissociation which is the rate limiting step for the NO(x) reduction process. The dissociation of molecularly adsorbed NO on the surface is activated for both cases. However, from the reaction path of the NO-Cu(2)O(111) system, the calculated transition state lies below the reference energy which indicates the possibility of dissociation. For the NO-Cu(111) system, the reaction path shows that NO desorption is more likely to occur. The geometric and electronic structure of the Cu(2)O(111) surface indicates that the surface Cu atoms stabilize themselves with reference to the O atom in the subsurface. The interaction results in modification of the electronic structure of the surface Cu atoms of Cu(2)O(111) which greatly affects the adsorption and dissociation of NO. This phenomenon further explains the obtained differences in the dissociation pathways of NO on the surfaces.

[Watchful waiting in incidental adenocarcinoma of the prostate]. / Actitud expectante en el adenocarcinoma incidental de próstata.

OBJECTIVE: To describe the outcome of patients diagnosed of incidental prostate adenocarcinoma managed by watchful waiting. MATERIAL AND METHODS: We included patients with PSA< 4 ng/mL or higher with previous negative biopsy, who underwent surgery for BPH being diagnosed of incidental prostate adenocarcinoma. We performed a descriptive and retrospective study in patients with this diagnosis between 1992 and 2007. Salvage curative treatment was offered to those patients who progressed. Statistical analysis was performed using SPSS program. Progression variables were: age, preoperative and postoperative PSA, stage, Gleason score, prostate volume, initial treatment, PSA evolution and salvage treatment if necessary. RESULTS: 47 patients were diagnosed of incidental prostatic adenocarcinoma, finding an incidence of 4.25%. The medium follow up was 37 months. Of the patients who opted for watchful waiting, 72.5% remain on it. 11 patients progressed. Postoperative PSA and Gleason score showed up as prognostic variables of progression in T1a stage and postsurgery PSA did so in T1b patients. CONCLUSION: Watchful waiting is a useful option in patients with incidental prostate adenocarcinoma and favourable prognostic criteria. Postoperative PSA and Gleason score can predict progression in T1a stage and postoperative PSA in T1b stage.

Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer.

ADAMs (a disintegrin and metalloprotease) are transmembrane proteins involved in a variety of physiological processes and tumorigenesis. Recently, ADAM8 has been associated with poor prognosis of lung cancer. However, its contribution to tumorigenesis in the context of lung cancer metastasis remains unknown. Native ADAM8 expression levels were lower in lung cancer cell lines. In contrast, we identified and characterized two novel spliced isoforms encoding truncated proteins, Delta18a and Delta14', which were present in several tumor cell lines and not in normal cells. Overexpression of Delta18a protein resulted in enhanced invasive activity in vitro. ADAM8 and its Delta14' isoform expression levels were markedly increased in lung cancer cells, in conditions mimicking tumor microenvironment. Moreover, addition of supernatants from Delta14'-overexpressing cells resulted in a significant increase in tartrate-resistant acid phosphatase+ cells in osteoclast cultures in vitro. These findings were associated with increased pro-osteoclastogenic cytokines interleukin (IL)-8 and IL-6 protein levels. Furthermore, lung cancer cells overexpressing Delta14' increased prometastatic activity with a high tumor burden and increased osteolysis in a murine model of bone metastasis. Thus, the expression of truncated forms of ADAM8 by the lung cancer cells may result in the specific upregulation of their invasive and osteoclastogenic activities in the bone microenvironment. These findings suggest a novel mechanism of tumor-induced osteolysis in metastatic bone colonization.

[Prospective validation of a nomogram predictive of a positive initial prostate biopsy]. / Validación prospectiva de un nomograma predictivo de la presencia de cáncer de próstata en pacientes que se someten a biopsia transrectal ecodirigida de 10 cilindros.

INTRODUCTION: Ultrasound-guided transrectal prostate biopsy is currently an indispensable test for diagnosing prostate cancer. Many variables have been related to the presence of cancer in the biopsy (e.g. digital rectal examination [DRE], serum levels of prostate-specific antigen [PSA], free PSA fraction [PSAI/PSAt]). Multivariate mathematical models integrating these variables (nomograms, artificial network models) and improving the capacity to predict tests results are currently available. OBJECTIVE: To develop a nomogram for predicting the probability of a positive prostate biopsy in patients in whom this test is requested, and to use such nomogram in subsequent patients to assess its predictive ability. MATERIAL AND METHODS: A total of 410 consecutive patients undergoing biopsy due to a suspicious digital rectal examination or two serum PSA values higher than 4 ng/mL were enrolled into the study. Ten cores were taken in the prostate biopsy. Patients with both PSA levels >20 ng/ml and prior biopsies were excluded. The following variables were recorded in each patient: age, total PSA, free PSA fraction, prostate volume, transition zone volume, PSA density, PSA density adjusted by transition zone volume, digital rectal examination, and findings suggesting cancer during transrectal ultrasound (hypoechogenic nodules). Prospective external validation was performed with 185 patients who met the same inclusion criteria. Statistical analysis consisted of four phases: a univariate study, a multivariate logistic regression study which was used to develop the nomogram, internal validation, and prospective external validation. S-Plus#r Programme Design and SPSS 12.0#r software was used for the procedure. RESULTS: Variables found to be independently and significantly associated to the presence of cancer included age, digital rectal examination, trnsition zone volume, PSA density, and the presence of hypoechogenic nodules during transrectal ultrasound. Such variables were therefore used to develop the nomogram. The goodness-of-fit of the nomogram was 84%. Validation with an external sample showed a 73% concordance index. CONCLUSION: A nomogram having a satisfactory predictive ability and fit that allows for predicting the prostate biopsy result with a high accuracy rate was developed.