Real-world experience of abiraterone acetate plus prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: long-term results of the prospective ABItude study.

BACKGROUND: Limited real-world data exist on the effectiveness and safety of abiraterone acetate plus prednisone (abiraterone hereafter) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naive to chemotherapy. Most of the few available studies had a retrospective design and included a small number of patients. In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median follow-up of 18 months. PATIENTS AND METHODS: We evaluated clinical and patient-reported outcomes (PROs) of chemotherapy-naive mCRPC patients treated with abiraterone as for clinical practice in the Italian, observational, prospective, multicentric ABItude study. mCRPC patients were enrolled at abiraterone start (February 2016-June 2017) and followed up for 3 years; clinical endpoints and PROs, including quality of life (QoL) and pain, were prospectively collected. Kaplan-Meier curves were estimated. RESULTS: Of the 481 patients enrolled, 454 were assessable for final study analyses. At abiraterone start, the median age was 77 years, with 58.6% elderly patients and 69% having at least one comorbidity (57.5% cardiovascular diseases). Visceral metastases were present in 8.4% of patients. Over a median follow-up of 24.8 months, median progression-free survival (any progression reported by the investigators), time to abiraterone discontinuation, and overall survival were, respectively, 17.3 months [95% confidence interval (CI) 14.1-19.4 months], 16.0 months (95% CI 13.1-18.2 months), and 37.3 months (95% CI 36.5 months-not estimable); 64.2% of patients achieved ≥50% reduction in prostate-specific antigen. QoL assessed by Functional Assessment of Cancer Therapy-Prostate, the European Quality of Life 5 Dimensions 3 Level, and European Quality of Life Visual Analog Scale remained stable during treatment. Median time to pain progression according to Brief Pain Inventory data was 31.1 months (95% CI 24.8 months-not estimable). Sixty-two patients (13.1%) had at least one adverse drug reaction (ADR) and 8 (1.7%) one serious ADR. CONCLUSION: With longer follow-up, abiraterone therapy remains safe, well tolerated, and active in a large unselected population.

Factor de crecimiento epidermal y proteínas totales en saliva de fumadores y no fumadores / Epidermal growth factor and total protein in saliva of smokers and non smokers

La función del Factor de Crecimiento Epidermal (EGF) es mantener la integridad de los tejidos, su receptor se localiza en superficies celulares y se expresa principalmente en epitelios. Nuestro objetivo fue determinar la asociación entre el tabaquismo crónico, el pH, las proteínas totales (PT) y el EGF en saliva de fumadores. Se seleccionaron pacientes masculinos, entre 20 y 60 años, de la clínica de Registro del Postgrado de Odontología de la Universidad. Se tomaron muestras de saliva total estimulada (STHe) y no estimulada (STH) a un grupo de fumadores y no fumadores. Se midió el pH, se cuantificaron las PT por el método de Bradford y para el EGF la técnica de ELISA (ELISA Kit KHG0061 biosource). Los resultados fueron: el pH se encontró ligeramente alcalino en STHe en ambos grupos, la cantidad de PT fue de 1,11 ± 0,71 en no fumadores y 0,87 ± 0,31mg/mL en STH de fumadores. En STHe también existió un decremento en la cantidad de PT de 0,94 ± 0,470,66 ± 0,21 mg/mL. El EGF fue en STH de no fumadores 14,8 ± 5,62 comparado con los fumadores con un promedio de 11,4 ± 5,45. En STHe, el promedio del mismo factor fue en los no fumadores de 7,8 ± 5,60 yen los fumadores a 9,1 ± 6,53 ng/mL. Con una con una confiabilidad del 90% (AU)

The role of Epidermal Growth Factor (EGF) is to maintain tissue’s integrity. It’s receptor is located on cell surfaces and mainly expressed in epithelia. The aim of this study was to determine the association between chronicle tabaquism, pH, total proteins (TP) and EGF in smoker’s saliva. There were selected male volunteers between 20and 60 years old from the Registration Clinic of the Postgrade Division of UNAM’s Dentistry School. There were taken stimulated (sWHS) and not stimulated whole saliva (WHS) samples from groups of smokers and non-smokers. Total proteins (Bradford method), pH and EGF (ELISA Kit KHG0061 biosource) were measured. Results: Slightly alkaline pH in sWHS in both groups. TP were 1.11 ± 0.71 for non-smokers WHS and 0.87 ± 0.31 mg/mL for smokers WHS. In non-smokers WHS EGF were 14.8 ± 5.62 compared to smokers WHS which showed 11.4± 5.45. For sWHS the values were 7.8 ± 5.60 in non-smokers group and 9.10 ± 6.53 ng/mL in smokers group (AU)

Randomized phase II three-arm trial with three platinum-based doublets in metastatic non-small-cell lung cancer. An Italian Trials in Medical Oncology study.

BACKGROUND: Many patients with advanced non-small-cell lung cancer (NSCLC) do not tolerate cisplatin-based regimens because of its nonhemathological toxicity. PATIENTS AND METHODS: We evaluated the response rate safety of new platinum analogue regimens, randomizing 147 patients with nonoperable IIIB/IV NSCLC to (i) carboplatin (area under the curve = 5 mg min/ml) on day 1 plus gemcitabine (GEM) (1000 mg/m(2)) on days 1 and 8 for six cycles; (ii) same regimen for three cycles followed by docetaxel (Taxotere) (40 mg/m(2)) on days 1 and 8 plus GEM (1250 mg/m(2)) on days 1 and 8 for three cycles; (iii) oxaliplatin (130 mg/m(2)) on day 1 plus GEM (1250 mg/m(2)) on days 1 and 8 for six cycles. RESULTS: Intention-to-treat objective response rates were 25%, 25% and 30.6% in arms A, B and C, respectively. Median survival was 11.9, 9.2 and 11.3 months in arms A, B and C, respectively. Grade 3/4 neutropenia/anemia occurred in 29%/12.5%, 10%/16.5% and 8%/6% of arms A, B and C, respectively; grade 3/4 thrombocytopenia in 20.5%, 16.5% and 6%; grade 1/2 neurological toxicity in 43% of arm C. CONCLUSIONS: Oxaliplatin/GEM (arm C) had similar activity to carboplatin/GEM (arm A), but milder hematological toxicity and may be worth testing in a phase III study against carboplatin/GEM in patients not suitable for cisplatin. The sequential regimen gave no additional benefit.

Pacientes sin domicilio fijo en un servicio de urgencias hospitalarias / Patients with no fixed domicile in a hospital-based emergency service

Introducción: La importante y reiterada demanda asistencial por parte de los pacientes sin domicilio fijo (SDF) en los Servicios de Urgencias Hospitalarios (SUH) crea sobrecarga de trabajo en los equipos de salud y dificulta la objetividad en el triaje. Métodos: Estudio descriptivo, retrospectivo y transversal. Los pacientes del estudio fueron atendidos en un periodo de tiempo de tres meses. Incluyéndose todos los pacientes SDF que pedían una consulta médica. Las variables del estudio fueron: edad, sexo, forma de llegar al SUH, grado de triaje, horario de llegada, motivo de consulta, tiempo pasado en el SUH y destino del paciente. Resultados: Se atendieron 125 pacientes SDF. Por grupos de edad, los SDF se distribuyeron en 0,8% menores de 20 años, 9,6% entre 20 y 30 años, 19,2% de 31 a 40 años, 31,2% de 41 a 50 años, 21,6% de 51 a 60 años, 9,6% de 61 a 70 años y 3,2% mayores de 70 años, y un 4,8% del que desconocemos la edad. Un 88% fue hombres. El 56% de pacientes llegó al SUH con los bomberos, el 18% por su propio pie, otro 18% por el SAMU social, un 3% por la Cruz Roja, otro 3% por la policía y un 2% por Protección Civil. Por grado de triaje no hubo ningún caso clasificado con grado 1 (urgencia vital), hubo un 5,6% con un grado 2, un 24% con un grado 3, 51,2% un grado 4 y un 20% con un grado 5. Por motivo de consulta el 22% fue por embriaguez, el 19% por traumatismos, el 12% por dolor, el 8% por crisis convulsivas, el 7% por disnea y el 22% restante por diversos motivos que individualmente no llegan al 3%. La estancia media en el SUH fue de 10,50 horas. Destino del paciente: un 69% alta médica, el 18% fueron hospitalizados, el 6% partieron antes de consulta, el 2% fuga, el 1% alta voluntaria y el 4% no sabemos. Conclusión: Observamos una gran demanda social, muchas veces enmascarada por problemas sanitarios que genera servicios de urgencias saturados y un considerable aumento de la carga de trabajo del equipo de salud. Extraemos de este estudio que, en muchas ocasiones, el derivar estos pacientes al SUH es inapropiado puesto que no es posible dar una solución inmediata a problemas sociales que requieren la intervención de todo un dispositivo especial (trabajadores sociales, psicólogos…) por lo que rentabilizaría mucho el tener estructuras sociales mayores o más numerosas que pudiesen dar respuesta a la magnitud del problema (AU)

I ntroduction: The important and reiterated demand for health care on the part of patients without fixed abode (WFA) in the hospital emergency departments (HED) originates a work surcharge in the health teams and difficults objectivity in triage. Methods: Retrospective and cross-sectional study. Subjects of this study were attended in a 3 months period. All WFA patients who attended a doctor’s surgery were included. Variables of the study were: age, gender, way to come to the HED, triage degree, arriving time, reason of consultation, time spent at the HED and patient’s destination. Results: 125 WFA patients were evaluated. 0.8% WFAwere younger than 20 years old, 9.6% between 20 and 30 years old, 19.2% between 31 and 40 years old, 31.2% between 41 and 50 years old, 21.6% between 51 nad 60 years old, 9.6% between 61 and 70 years old, 3.2% older than 70 years old and 4.8% from which we do’nt know their age. By gender, 88% were men and 12% women. By the way to come to the HED, 56% of patients arrived at the HED by firemen, 18% by walking, 18% by the social SAMU (Medical Ambulance Service) 3% by the Red Cross, 3% by the police and 2% by Civil Protection. By triage degree, none case was classificated with a 1st degree (vital emergency), 5.6% was 2nd degree, 24% was 3rd degree, 51.2% was 4th degree and 20% was 5th degree. By reason of consultation, 22% was drunkenness, 19% traumatisms, 12% pain, 8% convulsions, 7% dyspnoea, 22% for other reasons, each one representing less than 3%. By time spent at the HED, the mean stay was 10.50 hours. By the patient’s destination, 69% were discharged. 18% were hospitalised. 6% leaved before physician’s evaluation. 2% escaped. 1% voluntary discharge and 4% unknown. Conclusions: A high social demand has been seen. Mostly, it is masked with health problems and as a result of this emergency departments are saturated and the work charge at the health team is highly increased. By this study we can take out that derivation of these patients to the HED is unappropiated because it is impossible to give an immediate solution to these social problems. Problems which require the intervention of a full special device (social workers...). Bigger or more numerous social structures would be able to solve the magnitude of this problem (AU)

Multicenter phase III randomized trial of polychemotherapy (CVD regimen) versus the same chemotherapy (CT) plus subcutaneous interleukin-2 and interferon-alpha2b in metastatic melanoma.

BACKGROUND: The addition of cytokines to chemotherapy (CT) has obtained encouraging but contradictory results in metastatic melanoma. In this phase III trial, we compared the effects of CT [cisplatin, vindesine and dacarbazine (CVD)] with those of concurrent biochemotherapy (bioCT) consisting of CVD plus interleukin-2 and interferon-alpha2b. PATIENTS AND METHODS: A total of 151 untreated metastatic melanoma patients were randomized, 75 on arm A (cisplatin 30 mg/m2 on days 1-3, vindesine 2.5 mg/m2 on day 1 and dacarbazine 250 mg/m2 on days 1-3), and 76 on arm B (same CVD scheme plus interferon-alpha2b on days 1-5 and interleukin-2 on days 1-5 and 8-15, both administered subcutaneously), either recycled every 3 weeks. Response was assessed every two cycles. RESULTS: Ten percent of the patients were alive at a median of 52 months from start of therapy. We observed a response rate (RR) of 21% on arm A versus 33% on arm B; three patients (4%) given bioCT had complete responses (CRs). Median time to progression (TTP) was identical; median overall survival (OS) time was 12 months on arm A and 11 months on arm B. CONCLUSIONS: BioCT is not better than CT alone; the trend in favor of the bioCT in terms of RR did not translate into better TTP or OS. Therefore, bioCT cannot be recommended as standard first-line therapy for metastatic melanoma.

Sex-chromosome heterochromatin variation in the wood mouse, Apodemus sylvaticus.

Variation in heterochromatin content, as revealed by G- and C-banding, was studied in the sex chromosomes of the wood mouse, Apodemus sylvaticus. The sex-chromosome heterochromatin was also characterized by DAPI staining. Variation in sex chromatin was recorded in extremely large (giant) sex chromosomes in certain individuals and populations. In some individuals, the Y chromosome was the largest element of the complement. Different variants of both the X and Y chromosomes were found within a single population. The variation is therefore a type of population polymorphism and should not be used for taxonomic discrimination.

AFLP-based analysis to study genetic variability and relationships in the Spanish species of the genus Aegilops.

Amplified fragment length polymorphism (AFLP) DNA markers were used to characterize the genetic diversity and relationships in wild species of the genus Aegilops. Fifty populations, which included the species Aegilops biuncialis (UUMM), Ae. neglecta (UUMMNN), Ae. ovata (UUMM), Ae. ventricosa (DDNN) and Ae. triuncialis (UUCC) were selected. These populations are distributed in the Iberian peninsula and Balearic islands. Five AFLP selective primer combinations generated a total of 527 amplification products of which 517 (98.10%) detected polymorphisms. Aegilops neglecta showed the least variation in contrast with Ae. biuncialis that presented the highest degree of polymorphism. Genetic relationships within the populations were evaluated by generating a similarity matrix based on the Jaccard index. In the resulting phenogram Ae. ventricosa appears segregated from the other species, probably owing to the influence of the D genome. The species sharing the U genome are located in the main cluster. The branching pattern of the U genome group reflects the proximity of the species sharing the M genome. Ae. biuncialis and Ae. ovata are clearly separated suggesting that the super index system should be used to differentiate the M genomes of both species. The variation among populations within species in relation to their geographical origin and results previously obtained by the authors using biochemical and molecular markers are discussed.

Identification of the Ndh (NAD(P)H-plastoquinone-oxidoreductase) complex in etioplast membranes of barley: changes during photomorphogenesis of chloroplasts.

In the last few years the presence in thylakoid membranes of chloroplasts of a NAD(P)H-plastoquinone oxidoreductase complex (Ndh complex) homologous to mitochondrial complex I has been well established. Herein, we report the identification of the Ndh complex in barley etioplast membranes. Two plastid DNA-encoded polypeptides of the Ndh complex (NDH-A and NDH-F) were relatively more abundant in etioplast membranes than in thylakoids from greening chloroplasts. Conversion of etioplast into chloroplast, after light exposure of barley seedlings grown in the dark, was accompanied by a decrease in the NADH dehydrogenase activity associated to plastid membranes. Using native-PAGE and immunolabelling techniques we have determined that a NADH specific dehydrogenase activity associated with plastid membranes, which was more active in etioplasts than in greening chloroplasts, contained the NDH-A and NDH-F polypeptides. These results complemented by those obtained through blue-native-PAGE indicated that NDH-A and NDH-F polypeptides are part of a 580 kDa NADH dependent dehydrogenase complex present in etioplast membranes. This finding proves that accumulation of the Ndh complex is independent of light. The decrease in the relative levels and specific activity of this complex during the transition from etioplast to chloroplasts was accompanied by a parallel decrease in the specific activity of peroxidase associated to plastid membranes. Based on the mentioned observations it is proposed that an electron transport chain from NADH to H2O2 could be active in barley etioplasts.

Purification and characterization of a novel valine dehydrogenase from Streptomyces aureofaciens.

The first valine dehydrogenase of S. aureofaciens had been described (Vancurová, I., Vancura, A., Volc, J., Neuzil, J., Flieger, M., Basarová, G. and Behal, V. (1988) J. Bacteriol. 170, 5192-5196). In the present work, a second valine dehydrogenase was detected and purified by hydrophobic and fast protein liquid chromatographies. The enzyme has a relative molecular mass (M(r)) of 240,000 and is composed of 6 identical subunits, each of M(r) 41,000. In the presence of NAD, the enzyme catalyzes the reversible deamination of several branched- and straight-chain amino acids. The enzyme activities with L-2-aminobutyrate and deamino-NAD+ are markedly higher than those with L-valine and NAD+, respectively. The enzyme synthesis is significantly induced by L-valine but severely repressed by ammonia. Molecular and catalytic properties of the enzyme distinguish it from the other described valine dehydrogenases. The results directly demonstrate the presence of two valine dehydrogenases in a single Streptomyces species.