Infección por virus pandémico (H1N1) 2009 en Andalucía

In April 2009, in response to the WHO's alert due to the existence of human infection cases with a new AH1N1 influenza virus, known as swine flu, Andalusian Health Authorities trigger an specific action plan. The surveillance actions developped provided us with appropriate clinical, epidemiological and virological characteristics of the disease. During the first few days, contingency plans were set up based on epidemiological surveillance and outbreak control measures were adopted through early alert and rapid response systems. After phase 6 was declared, influenza sentinel and severe cases surveillance were used in order to plan healthcare services, to reduce transmission and to identify and protect the most vulnerable population groups. Behaviour of pandemic influenza in Andalusia was similar to that observed in the rest of the world. Atack rate was similar to a seasonal flu and the peak was reached at the 46th/2009 week. Most of them were mild cases and affected particularly to young people. The average age of hospitalised patients was 32. Prior pulmonary disease, smoking and morbid obesity (BMI>40) were the most common pathologies and risk factors in severe cases. An impact scenario of pandemic wave in Andalusia, with an expected attack rate from 2 to 5%, was prepared considering watt observed in the southern hemisphere. Characteristics of the epidemic concerning its extent, severity and mortality rate were adjusted to this scenario.

Estrategia de Bioética del Sistema Sanitario Público de Andalucía: 2011 - 2014

COORDINACIÓN: Pablo Simón Lorda, María Sagrario Esteban López. Publicado en la página web de la Consejería de Salud: www.juntadeandalucia.es/salud (Consejería de Salud / Ciudadanía / Nuestro Compromiso por la Calidad / Estrategia de Bioética del Sistema Sanitario Público de Andalucía)

Association of Patients' Geographic Origins with Viral Hepatitis Co-infection

To determine if hepatitis C virus seropositivity and active hepatitis B virus infection in HIV-positive patients vary with patients' geographic origins, we studied co-infections in HIV-seropositive adults. Active hepatitis B infection was more prevalent in persons from Africa, and hepatitis C seropositivity was more common in persons from eastern Europe.

The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53-Independent Manner in Colon and Breast Cancer Cells

The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR)as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNalpha treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner,inducing phosphorylation of the protein synthesis translation initiation factor eIF-2alpha and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNalpha combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug.

Memoria de la actividad de hospitales concertados de Andalucía 2010 [Recurso electrónico]

Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud

Análisis de la actividad realizada por hospitales concertados 2005 - 2007

Libro y tablas

Conjunto mínimo básico de datos al alta hospitalaria [Recurso electrónico] : grupos relacionados por el diagnóstico (GRDs) : hospitales concertados 2010

En la port.: Dirección General de Planificación e Innovación Sanitaria, Servicio de Conciertos Sanitarios

Angina estable : proceso asistencial integrado. 2ª ed

Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Salud / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

Immune Microenvironment in Colorectal Cancer: A New Hallmark to Change Old Paradigms

Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells.

Combinatorial effects of splice variants modulate function of Aiolos

The transcription factor Aiolos (also known as IKZF3), a member of the Ikaros family of zinc-finger proteins, plays an important role in the control of B lymphocyte differentiation and proliferation. Previously, multiple isoforms of Ikaros family members arising from differential splicing have been described and we now report a number of novel isoforms of Aiolos. It has been demonstrated that full-length Ikaros family isoforms localize to heterochromatin and that they can associate with complexes containing histone deacetylase (HDAC). In this study, for the first time we directly investigate the cellular localization of various Aiolos isoforms, their ability to heterodimerize with Ikaros and associate with HDAC-containing complexes, and the effects on histone modification and binding to putative targets. Our work demonstrates that the cellular activities of Aiolos isoforms are dependent on combinations of various functional domains arising from the differential splicing of mRNA transcripts. These data support the general principle that the function of an individual protein is modulated through alternative splicing, and highlight a number of potential implications for Aiolos in normal and aberrant lymphocyte function.

Assessment of Severe Apnoea through Voice Analysis, Automatic Speech, and Speaker Recognition Techniques

This study is part of an ongoing collaborative effort between the medical and the signal processing communities to promote research on applying standard Automatic Speech Recognition (ASR) techniques for the automatic diagnosis of patients with severe obstructive sleep apnoea (OSA). Early detection of severe apnoea cases is important so that patients can receive early treatment. Effective ASR-based detection could dramatically cut medical testing time. Working with a carefully designed speech database of healthy and apnoea subjects, we describe an acoustic search for distinctive apnoea voice characteristics. We also study abnormal nasalization in OSA patients by modelling vowels in nasal and nonnasal phonetic contexts using Gaussian Mixture Model (GMM) pattern recognition on speech spectra. Finally, we present experimental findings regarding the discriminative power of GMMs applied to severe apnoea detection. We have achieved an 81% correct classification rate, which is very promising and underpins the interest in this line of inquiry.

Genetic analysis of caveolin-1 and eNOS genes in colorectal cancer.

Caveolae are involved in physical compartmentalization between different groups of signaling events. Its main component, CAV1, modulates different pathways in cellular physiology. The emerging evidence pointing to the role of CAV1 in cancer led us to study whether different alleles of this gene are associated with colorectal cancer (CRC). Since one of the most characterized enzymes regulated by CAV1 is eNOS, we decided to include both genes in this study. We analyzed five SNPs in 360 unrelated CRC patients and 550 controls from the general population. Two of these SNPs were located within eNOS and three within the CAV1 gene. Although haplotype distribution was not associated with CRC, haplotype TiA (CAV1) was associated with familiar forms of CRC (p<0.05). This was especially evident in CRC antecedents and nuclear forms of CRC. If both CG (eNOS) and TiA (CAV1) haplotypes were taken together, this association increased in significance. Thus, we propose that CAV1, either alone or together with eNOS alleles, might modify CRC heritability.

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury

BACKGROUND Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. METHODS Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). RESULTS 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. CONCLUSION This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness. TRIAL REGISTRATION This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.

Cerebral perfusion pressure and risk of brain hypoxia in severe head injury: a prospective observational study

INTRODUCTION Higher and lower cerebral perfusion pressure (CPP) thresholds have been proposed to improve brain tissue oxygen pressure (PtiO2) and outcome. We study the distribution of hypoxic PtiO2 samples at different CPP thresholds, using prospective multimodality monitoring in patients with severe traumatic brain injury. METHODS This is a prospective observational study of 22 severely head injured patients admitted to a neurosurgical critical care unit from whom multimodality data was collected during standard management directed at improving intracranial pressure, CPP and PtiO2. Local PtiO2 was continuously measured in uninjured areas and snapshot samples were collected hourly and analyzed in relation to simultaneous CPP. Other variables that influence tissue oxygen availability, mainly arterial oxygen saturation, end tidal carbon dioxide, body temperature and effective hemoglobin, were also monitored to keep them stable in order to avoid non-ischemic hypoxia. RESULTS Our main results indicate that half of PtiO2 samples were at risk of hypoxia (defined by a PtiO2 equal to or less than 15 mmHg) when CPP was below 60 mmHg, and that this percentage decreased to 25% and 10% when CPP was between 60 and 70 mmHg and above 70 mmHg, respectively (p < 0.01). CONCLUSION Our study indicates that the risk of brain tissue hypoxia in severely head injured patients could be really high when CPP is below the normally recommended threshold of 60 mmHg, is still elevated when CPP is slightly over it, but decreases at CPP values above it.

Role of Immune Escape Mechanisms in Hodgkin's Lymphoma Development and Progression: A Whole New World with Therapeutic Implications.

Hodgkin's lymphoma represents one of the most frequent lymphoproliferative syndromes, especially in young population. Although HL is considered one of the most curable tumors, a sizeable fraction of patients recur after successful upfront treatment or, less commonly, are primarily resistant. This work tries to summarize the data on clinical, histological, pathological, and biological factors in HL, with special emphasis on the improvement of prognosis and their impact on therapeutical strategies. The recent advances in our understanding of HL biology and immunology show that infiltrated immune cells and cytokines in the tumoral microenvironment may play different functions that seem tightly related with clinical outcomes. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of HL microenvironment. This new knowledge will probably translate into a change in the antineoplastic treatments in HL in the next future and hopefully will increase the curability rates of this disease.