Immunotherapy in patients with brain metastasis: advances and challenges for the treatment and the application of circulating biomarkers.

The central nervous system (CNS) is one of the most frequent metastatic sites of various cancers, including lung cancer, breast cancer and melanoma. The development of brain metastases requires a specific therapeutic approach and is associated with high mortality and morbidity in cancer patients. Advances in precision medicine and the introduction in recent years of new drugs, such as immunotherapy, have made it possible to improve the prognosis of these patients by improving survival and quality of life. New diagnostic techniques such as liquid biopsy allow real-time monitoring of tumor evolution, providing molecular information on prognostic and predictive biomarkers of response to treatment in blood or other fluids. In this review, we perform an exhaustive update of the clinical trials that demonstrate the utility of immunotherapy in patients with brain metastases and the potential of circulating biomarkers to improving the results of efficacy and toxicity in this subgroup of patients.

Comparison of knowledge, attitudes and hand hygiene behavioral intention in medical and nursing students.

INTRODUCTION: Hand hygiene is crucial to prevent cross infection. Healthcare students are in a prime position to learn hand hygiene skills. The aim of this study was to analyze hand hygiene behavioral intentions of healthcare students before and after contact with the patient and to compare the knowledge of and attitude towards hand hygiene between medical and nursing students. METHODS: In a descriptive survey research design, convenience selection of a sample of medical students (n=657) and nursing students (n=303) was done from modules taught by the Department of Preventive Medicine and Public Health in both Medicine and Nursing undergraduate degrees in four Spanish universities. The hand hygiene Questionnaire, a validated instrument to evaluate behavior, knowledge, and attitudes, was used. RESULTS: A significantly lower percentage of students reported always or almost always carrying out hand hygiene before contact with the patient or invasive procedures in comparison to the percentage complying after contact with secretions or with the patient. Although hand hygiene knowledge appears acceptable, its importance is not sufficiently valued. CONCLUSIONS: There are deficiencies in behavioral intention, knowledge, and attitudes related to hand hygiene in medical and nursing students. Better results are observed among nursing students, especially those who have received specific training.

A giant exoplanet orbiting a very-low-mass star challenges planet formation models.

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.

Demencia rápidamente progresiva como forma de presentación del síndrome de Cushing / Rapidly progressing dementia as a form of presentation of Cushing síndrome

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A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

Infected malnourished children displayed changes in early activation and lymphocyte subpopulations.

AIM: Malnutrition and infections cause immunological changes in lymphocyte subpopulations and their functionality. We evaluated the activation capacity of lymphocytes and memory cells in 10 well nourished, seven well-nourished infected and eight malnourished infected children before and after treatment. METHODS: All the children were patients in Mexico City and were less than three years of age. The expression of various cluster of differentiation (CD) cells was assessed by flow cytometry: CD45RA (naïve) and CD45RO (memory) antigens on CD4 lymphocytes and CD69 in all lymphocytes. RESULTS: Well-nourished infected children showed a higher percentage of activated T lymphocyte (T cells), CD8+ and CD4+ memory cells during the infectious phase, suggesting that the activation mechanisms were triggered by infection. T cells from malnourished infected children showed a lower percentage of activated and memory cells. The T cell population size returned to baseline during the resolution phase of the infection in well-nourished infected children, but their T, B lymphocyte and natural killer (NK) cell counts remained high. In malnourished infected children, activated NK cells counts were low before and after therapy. CONCLUSION: After therapy, malnourished infected children showed poor NK cell responses during the infection's resolution phase, suggesting a persistent malnutrition-mediated immunological deficiency.

Trends in the dispensation of antidepressant drugs over the past decade (2000-2010) in Andalusia, Spain.

PURPOSE: To study antidepressant drug dispensation in the Spanish region of Andalusia and in the Almeria Health Area (AHA) over the past decade, analyzing the variability, trends, and influential factors. METHODS: We conducted an observational ecological study of antidepressant drug dispensation between 2000 and 2010 in Andalusia. Dispensation was measured as Defined Daily Dose (DDD) per 1,000 inhabitants per day. A multilevel analysis (STATA 11.1) was performed to determine the variability among the basic health zones (BHZs) (2004-2010) and influential factors. RESULTS: Between 2000 and 2010, the total dispensation of antidepressant drugs increased by more than 100 % in Andalusia and in the AHA. This increase was primarily caused by the greater dispensation of selective serotonin reuptake inhibitors (ATC-N06AB) and other antidepressants (ATC-N06AX). Multilevel analysis revealed a wide variability in the levels and trends of antidepressant dispensation among BHZs. Urbanicity and the percentage of immigrants in the BHZ were negatively associated with their dispensation, which was positively influenced by a higher proportion of women and over 65-year-olds in the population. CONCLUSIONS: The elevated dispensation of several groups of antidepressant drugs in this study population indicates the need for health policies to rationalize their use. Further research is required into the differences in antidepressant dispensations between immigrant and native populations and the implications for public health policies.

Agomelatine for the treatment of patients with fibromyalgia and depressive symptomatology: an uncontrolled, 12-week, pilot study.

INTRODUCTION: Agomelatine, a melatonin agonist and selective 5-HT2C antagonist, is a novel antidepressant with sleep-enhancing properties. The purpose of this study was to assess the efficacy and tolerability of agomelatine among patients with fibromyalgia and depression. METHODS: 23 patients with fibromyalgia and depressive symptomatology received 25-50 mg of agomelatine daily for 12 weeks. The primary outcome measure was the change of the Beck depression inventory score. Secondary outcome measures included the hospital anxiety and depression scale, Pittsburgh sleep quality index, Fibromyalgia Impact Questionnaire, short-form health survey, brief pain inventory and patient's global impression scale. RESULTS: Agomelatine significantly improved depression, global fibromyalgia severity and pain intensity but effect sizes were small. No improvement was seen in sleep quality. Patients categorized as responders to treatment had milder disease severity than non-responders. Agomelatine therapy was well tolerated and patients only reported mild and transient side effects. DISCUSSION: Agomelatine slightly improved depressive and fibromyalgia symptomatology but did not improve sleep quality. Our data do not support agomelatine as a first-line treatment option for the treatment of fibromyalgia and depression.

Infección nosocomial del tracto urinario en niños críticos / Nosocomial urinary tract infection in critical pediatric patients

Objetivos: Determinar la densidad de incidencia, etiología y factores de riesgo de la infección de orina nosocomial (ITUn) en una UCIP de segundo nivel. Diseño: Estudio prospectivo descriptivo durante un periodo de 1 año que incluyó a 104 pacientes ingresados durante más de 48 h en nuestra UCIP. Se recogieron urocultivos diarios a los pacientes con sonda vesical hasta su retirada y cada 48 h a los no sondados hasta el alta. Ámbito: Unidad de cuidados intensivos pediátricos de segundo nivel. Pacientes: Se incluyó a todos los pacientes que ingresaron por más de 48 h en el año 2009. Se excluyó a los menores de 15 días y a los que presentaban una infección de orina o pielonefritisal ingreso o antes de las 48 h tras su ingreso. Resultados: Seis pacientes presentaron una ITUn (el 5,8% de los ingresos), con una densidad de incidencia de 5/1.000 pacientes/día y de 12,19/1.000 días de sonda. Se identificaron 4casos por Escherichia coli (uno, multirresistente) y 2 por Candida albicans. Los niños con ITUn tuvieron significativamente más antecedentes personales y mayor estancia que los niños sin infección y, aunque sin significación estadística, menor edad y mayor número de días con sonda. Conclusiones: Nuestra densidad de incidencia de infección de orina asociada a dispositivo es superior a la publicada; esto puede deberse, entre otras causas, a las características de los pacientes atendidos y al método exhaustivo empleado para su detección (AU)

Objective: To determine the incidence, etiology and risk factors of nosocomial urinary tractinfections (nUTI) in a second level Pediatric Intensive Care Unit (PICU).Patients and methods: A prospective study of 104 patients admitted to the PICU with a length of stay of more than 48 hours was carried out over a one year period (January to December2009) to study the incidence and risk factors of nUTI. Urine samples were collected and cultured in all patients admitted for more than 48 hours to our PICU. Those needing indwelling urinary catheters had urine samples collected upon admission and every 24 hours until catheterretrieval, while those who did not need catheters had samples collected upon admission and every 48 hours until discharge from the PICU. Results: Six patients (5.8% of those admitted) were diagnosed of nUTI, with an incidence density of 5/1000 patients/day and 12.2/1000 catheterization days. Four of these were caused byE. coli (including a multiresistant strain), and two by C. albicans. Patients suffering nUTIs had significantly more relevant medical antecedents and a longer period of admittance than patients without nUTI. A statistically non significant tendency towards increased infection risk was also found in younger patients and in those who needed an indwelling catheter for longer periods. Conclusions: We found a higher incidence density of catheter associated nUTI than in other reports. This at least partially could be due to the characteristics of our patients, and to the exhaustive methodology used for detection (AU)

[Nosocomial urinary tract infection in critical pediatric patients]. / Infección nosocomial del tracto urinario en niños críticos.

OBJECTIVE: To determine the incidence, etiology and risk factors of nosocomial urinary tract infections (nUTI) in a second level Pediatric Intensive Care Unit (PICU). PATIENTS AND METHODS: A prospective study of 104 patients admitted to the PICU with a length of stay of more than 48 hours was carried out over a one year period (January to December 2009) to study the incidence and risk factors of nUTI. Urine samples were collected and cultured in all patients admitted for more than 48 hours to our PICU. Those needing indwelling urinary catheters had urine samples collected upon admission and every 24 hours until catheter retrieval, while those who did not need catheters had samples collected upon admission and every 48 hours until discharge from the PICU. RESULTS: Six patients (5.8% of those admitted) were diagnosed of nUTI, with an incidence density of 5/1000 patients/day and 12.2/1000 catheterization days. Four of these were caused by E. coli (including a multiresistant strain), and two by C. albicans. Patients suffering nUTIs had significantly more relevant medical antecedents and a longer period of admittance than patients without nUTI. A statistically nonsignificant tendency towards increased infection risk was also found in younger patients and in those who needed an indwelling catheter for longer periods. CONCLUSIONS: We found a higher incidence density of catheter associated nUTI than in other reports. This at least partially could be due to the characteristics of our patients, and to the exhaustive methodology used for detection.

Pregabalin augmentation of quetiapine therapy in the treatment of fibromyalgia: an open-label, prospective trial.

INTRODUCTION: Quetiapine has been shown to improve fibromyalgia symptoms, especially sleep disturbance, fatigue, morning stiffness, and mental well-being, but lacks an effect on pain. The purpose of this study was to evaluate if pregabalin, which has shown antialgic activity in fibromyalgia, added to quetiapine treatment additionally improved fibromyalgia symptomatology. METHODS: This was an open-label, 12-week study. Pregabalin was administered to 19 female fibromyalgia patients at a starting dose of 75 mg/day subsequently adjusted in according to the drug's efficacy and tolerability. Outcome measures included the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, the State and Trait Anxiety Inventory, and the SF-12 Health Survey. RESULTS: Data analysis was done on the Intention-To-Treat sample which included 18 patients. Pregabalin significantly improved the pain and tiredness after awakening subscales of the FIQ as well as the physical component of the SF-12. Six patients withdrew from the study, 3 because of side effects. CONCLUSIONS: Our results suggest that the use of pregabalin can be a useful augmentation strategy in fibromyalgia patients partially responding to quetiapine.

[Lipid peroxidation in adult epileptic patients treated with valproic acid]. / Peroxidación lipídica en pacientes epilépticos adultos tratados con ácido valproico.

INTRODUCTION: Free radicals play an important role as regulatory mediators in cellular signalling processes; however, when overproduced or when antioxidant defence systems are weakened, they are cause of cellular damage. Excessive amount of free radical production has been related with a variety conditions, like aging, different kind of diseases, and xenobiotics biotransformation; this last process includes the metabolism of lipid soluble drugs. An increase in oxidative stress has been described in series of treated epileptic patients. OBJECTIVE: To evaluate the susceptibility to plasma lipid peroxidation in samples from epileptic patients treated with valproic acid monotherapy, studying if the formation of lipid peroxides was related with plasma drug concentration, patients' sex or the kind of epilepsy suffered. PATIENTS AND METHODS: Peroxidated lipids (LPO) were measured by spectrofluorometry before and after induction of an oxidative Fenton reaction in 76 epileptic patients and 4 healthy subjects. RESULTS: After induction of the Fenton reaction, but not in basal conditions, lipid peroxidation showed a lineal relationship with valproate plasma levels. Oxidized LPO values were also significantly higher in samples from patients with partial epilepsies than in those with generalized epilepsies. Likewise, a significant gender effect was observed, being values from epileptic women noticeably higher than those of epileptic men. CONCLUSIONS: Plasma from epileptic patients receiving valproic acid evidences an increased vulnerability to lipid peroxidation which seems to be related with drug amount in the body, subject's sex, and epilepsy type.

[Serum lipids. lipoproteins, and apolipoproteins in adult epileptics treated with carbamazepine, valproic acid, or phenytoin]. / Lípidos, lipoproteínas y apolipoproteínas séricas en epilépticos adultos tratados con carbamacepina, ácido valproico o fenitoína.

INTRODUCTION: It is known that anticonvulsants are able to modify lipid profile; nevertheless the initial studies were performed in patients or polytherapy whereas later investigations were carried out mostly in children. OBJECTIVES: To evaluate serum lipids, lipoproteins and apolipoproteins in adult epileptic patients on monotherapy. MATERIAL AND METHODS: Total cholesterol, triglycerides, low- and high-density lipoprotein cholesterol (including the HDL2 and the HDL3 subfractions) and apolipoproteins A1 and B were measured in 120 epileptics patients treated with carbamazepine (n = 42), sodium valproate (n = 38) and phenytoin (n = 40) and compared with the values of 48 healthy subjects. RESULTS: Most of the measured parameters were significantly higher in patients receiving carbamazepine or phenytoin; carbamazepine-treated subjects showed specifically an increase in HDL2 lipoprotein cholesterol, whereas phenytoin-treated subjects showed specifically an increase of triglycerides; all of the observed alterations, save the increase in HDL lipoprotein cholesterol and apolipoprotein A1, were significant in women but not in men. Carbamazepine nor phenytoin related changes showed any correlation with the dose or the plasma levels of the drugs. No relevant modifications of serum lipids were seen in patients who received sodium valproate. CONCLUSIONS: The observed alterations in serum lipids were associated to the use of anticonvulsants with enzyme inducing activity and showed significant differences between both sexes.

[Chemoprophylaxis of tuberculosis: compliance to treatment in the pediatric population]. / Quimioprofilaxis tuberculosa: grado de cumplimiento en la población pediátrica.

We have reviewed the success of tuberculosis chemoprophylaxis in 369 children. These children ranged from 4 months to 14 years of age and had been prescribed chemoprophylaxis with Isoniazide at 10 mg/kg/day. Out of these, 258 (69.91%) finished the prophylaxis and 111 (30.08%) did not. Taking into account the reason for the consultation, of those who sought assistance due to contact with a patient with tuberculosis, 70.33% performed the treatment and 29.60% did not. For those in which the reason was a positive Mantoux, the data were 68.1% and 30.8%, respectively. No statistically significant differences were found between the two groups. We feel that the relatively high rate of noncompliance in our patients is a matter of concern. At the present time, chemoprophylaxis with Isoniazide is the best method available for the prevention of tuberculosis. We emphasize the need for its proper performance. We report several measures, such as the determination of Isoniazide metabolites in urine, which may be beneficial for better control and follow-up of these patients.

[Use of aminoglycoside antibiotics in a general hospital: kinetics consequences in those patients whose blood levels are not monitored]. / Utilización de antibióticos aminoglucósidos en un hospital general: consecuencias cinéticas en aquellos pacientes en los que no se monitorizan sus niveles plasmáticos.

A surprise monitoring of plasma aminoglycoside level was carried out in our Hospital in 55 patients. Basal samples and samples one hour after i.m. or i.v. administration were obtained. A protocol sheet with personal, clinical and therapeutic data was filled for each patient. The FPIA analysis technique (CV less than 5%) was used. Only the data related to gentamicin were evaluated, because the number of patients receiving other aminoglycosides was very low (5 cases). The most usual dose and interval were 80 mg (91%) and 12 hours (69%), respectively. The administration routes were i.v. (52%) and i.m. (48%). Blood urea and/or creatinine levels were not measured in 22% of patients. The baseline gentamicin levels were subtherapeutic in 30%, therapeutical in 57%, and toxic in 13%, and 50%, 46% and 4%, respectively, for the levels after one hour. In patients with abnormal renal function a good correlation could be demonstrated (r = 0.96; p less than 0.001) between creatinine level and gentamicin 1/2 time. This correlation was absent in patients with normal renal function. When the dose of the antibiotic was adjusted to the weight of the patient, the frequency of therapeutic levels was higher (47%; p less than 0.03); in these cases, the most common administration interval was 8 hours (p less than 0.01). We emphasize the lack of control of the renal function in 22% of patients, stressing that the lack of monitoring systematically results in potentially subtherapeutic levels in more than one half of the investigated patients (57%).