Hospital Universitario Puerta del Mar

Bibliometrics has become an essential tool for assessing and analyzing the output of scientists, cooperation between universities, the effect of state-owned science funding on national research and development performance and educational efficiency, among other applications. Therefore, professionals and scientists need a range of theoretical and practical tools to measure experimental data. This review aims to provide an up-to-date review of the various tools available for conducting bibliometric and scientometric analyses, including the sources of data acquisition, performance analysis and visualization tools. The included tools were divided into three categories: general bibliometric and performance analysis, science mapping analysis, and libraries; a description of all of them is provided. A comparative analysis of the database sources support, pre-processing capabilities, analysis and visualization options were also provided in order to facilitate its understanding. Although there are numerous bibliometric databases to obtain data for bibliometric and scientometric analysis, they have been developed for a different purpose. The number of exportable records is between 500 and 50,000 and the coverage of the different science fields is unequal in each database. Concerning the analyzed tools, Bibliometrix contains the more extensive set of techniques and suitable for practitioners through Biblioshiny. VOSviewer has a fantastic visualization and is capable of loading and exporting information from many sources. SciMAT is the tool with a powerful pre-processing and export capability. In views of the variability of features, the users need to decide the desired analysis output and chose the option that better fits into their aims.

Introduction: Intravenous(IV) immunoglobulin(Ig) treatment is known to alleviate behavioral deficits in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Methods: Sepsis was induced by cecal ligation perforation(CLP) in rats. The animals were divided into five groups; sham, control, CLP + saline, CLP + immunoglobulin G IgG(250 mg/kg,iv), and CLP + immunoglobulins enriched with immunoglobulin M-IgGAM(250 mg/kg,iv). Blood and brain samples were taken in two sets of experiments after CLP to see the early(24 hrs) and late(10 days) effects of treatment. Total complement activity, complement 3(C3) and soluble complement C5b-9 levels were measured in sera of rats using ELISA-based methods. Cerebral complement content was analyzed by Western Blot. Immune cell infiltration and gliosis were examined by immunohistochemistry using cluster of differentiation 3, CD4, CD8, CD11b, CD19 and glial fibrillary acidic protein antibodies. Apoptotic neuronal death was investigated by TUNEL staining and Western Blot-based semi-quantitative evaluation of brain homogenates by bax and bcl-2 antibodies. Results: IV IgG and IgGAM administration significantly reduced systemic complement activity but increased serum C3 and soluble C5b-9 levels. Likewise, Western Blot data showed slightly increased C5b-9 expression and significantly reduced C1q expression in brain samples of IgGAM-treated but not IgG-treated septic rats especially in the first day of administration. No cerebral cellular infiltrates were observed in treated and non-treated septic rats. By contrast, IV IgG and IgGAM treatment induced considerable amelioration in glial cell proliferation which was increased in non-treated rats. IgG and IgGAM treated rats exhibited significantly reduced numbers of apoptotic neurons and cerebral expression levels of bax and bcl-2 as compared to nontreated rats. Conclusions: We suggest that IV IgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation. IgGAM treatment might be suppressing classical complement pathway by reducing C1q expression.

INTRODUCTION: Patients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain. METHODS: We used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay. RESULTS: Illness onset of the 32 patients occurred between 23 June and 31 July, 2009. The median age was 36 years (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%) secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%) required mechanical ventilation. Six patients died within 28 days, with two additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received high-dose (300 mg/day), and treatment duration ranged from 5 to 10 days (mean 8.0 +/- 3.3). CONCLUSIONS: Over a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate. Clinicians should be aware of pulmonary complications of influenza A (H1N1)v infection, particularly in pregnant and young obese but previously healthy persons.

a) Describir la metodología seguida en la construcción de un índice de privación por sección censal en ciudades, que permite identificar las secciones con situaciones socioeconómicas más desfavorables, y b) analizar la relación de este índice con la mortalidad general. Se elaboraron diversos indicadores socioeconómicos (Censo 2001) correspondientes a las secciones censales de las ciudades de Barcelona, Bilbao, Madrid, Sevilla y Valencia. Se estudiaron sus correlaciones con la razón estandarizada de mortalidad (1996-2003), así como sus dimensiones conceptuales. Finalmente, mediante el análisis de componentes principales, se agregaron en un índice los indicadores seleccionados, usando como valores de peso las saturaciones correspondientes al primer eje. Los indicadores que presentaron mayores correlaciones con la mortalidad general fueron los referidos a trabajo, educación, vivienda-entorno y hogares monoparentales. En el análisis dimensional de los indicadores aparece una primera dimensión que contiene los indicadores relativos a trabajo (desempleo, trabajadores manuales y eventuales) y educación (instrucción insuficiente total y en jóvenes). El índice elaborado con estos 5 indicadores recoge, en todas las ciudades estudiadas, más del 75% de la variabilidad de los indicadores que lo componen. Las correlaciones de este índice con la mortalidad muestran, en general, mayores valores que las obtenidas individualmente con cada indicador. El índice de privación que se propone puede ser un instrumento útil para la planificación sanitaria al detectar áreas pequeñas de grandes ciudades con una situación socioeconómica desfavorable, que se relaciona con la mortalidad, y puede contribuir al estudio de las desigualdades sociales en salud en España. a) To describe the methodology used to construct a deprivation index by census tract in cities, to identify the tracts with the least favorable socioeconomic conditions, and b) to analyze the association between this index and overall mortality. Several socioeconomic indicators (Census 2001) were defined by the census tracts of the following cities: Barcelona, Bilbao, Madrid, Seville and Valencia. The correlations with the standardized mortality ratio (1996-2003), and the dimensionality of the socioeconomic indicators were studied. Finally, the selected indicators were aggregated in an index, in which the results of the factor loadings from extraction of a factor by principal components were used as weighting values. The indicators with the strongest correlations with overall mortality were those related to work, education, housing conditions and single parent homes. In the analysis of dimensionality, a first dimension appeared that contained indicators related to work (unemployment, manual and eventual workers) and education (insufficient education overall and in young people). In all the cities studied, the index created with these 5 indicators explained more than 75% of their variability. The correlations between this index and mortality generally showed higher values than those obtained with each indicator separately. The deprivation index proposed could be a useful instrument for health planning as it detects small areas of large cities with unfavorable socioeconomic characteristics and is associated with mortality. This index could contribute to the study of social inequalities in health in Spain.

Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other μ-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full μ-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain.

Plasma cells (PCs) are the final B-cell differentiation stage. Recent evidence reveals relevant functional differences within the PC compartment. In rodents, early PCs formed in secondary lymphoid tissues show enhanced apoptosis and short life span, whereas PCs present in a final destination organ, such as the bone marrow (BM), have reached a stable prolonged survival state. BM PCs arrive at this organ as a circulating precursor whose cellular nature remains uncertain. An initial aim of this study was to characterize this circulating cell. We hypothesized that antibody-secreting cells detectable in the human blood after immunization might be a candidate precursor. These cells were obtained from the blood of volunteers immunized 6 days earlier with tetanus toxoid (tet), and they were unambiguously identified as PCs, as demonstrated by their expression of the CD38(h) phenotype, by morphology, by immunoglobulin (Ig) intracytoplasmic staining, and by IgG-tet-secreting capacity in vitro. In addition, by using the common CD38(h) feature, human PCs from tonsil (as a possible source of early PCs), from blood from tet-immunized donors (as the putative precursors of BM PCs), and from BM (as a deposit organ) have been purified and their phenotypes compared. The results show that a variety of differentiation molecules, proteins involved in the control of apoptosis, the B-cell transcription factors, positive regulatory domain I-binding factor 1/B lymphocyte-induced maturation protein 1 and B cell-specific activating protein and, at least partially, the chemokine receptor CXCR4 were expressed by human PCs following a gradient of increasing maturity in the direction: tonsil-->blood-->BM. However, PCs from these different organs showed a local pattern of adhesion molecule expression. These observations are discussed in light of the complex physiology of the human PC compartment.

The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]); Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.

A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.

UNLABELLED: A few studies have assessed the observed fibrosis progression between serial liver biopsies (LB) in human immunodeficiency virus (HIV) / hepatitis C virus (HCV)-coinfected patients. Approximately half of the patients progressed at least one fibrosis stage over a short period of time. The risk factors for this fast progression need clarification. Because of this, we evaluated the observed fibrosis progression rates of HIV/HCV-coinfected patients and the risk factors for accelerated progression. Overall, 135 HIV-infected patients with positive serum HCV RNA, without other possible causes of liver disease, who underwent two LB, separated at least by 1 year, were included in this retrospective cohort study. The median (Q1-Q3) time between both LBs was 3.3 (2.0-5.2) years. Patients showed the following changes in fibrosis stage: regression >or =1 stage: 23 (17%), no change: 52 (39%), progression 1 stage: 38 (28%), and progression > or =2 stages: 22 (16%). Seventeen (13%) patients had cirrhosis in the second biopsy. Factors independently associated with progression > or =1 stage were undetectable plasma HIV RNA during the follow-up (relative risk [RR] [95% confidence interval, 95% CI] 0.61 [0.39-0.93], P = 0.03), moderate-to-severe lobular necroinflammation (1.77 [1.16-2.7], P = 0.009), time between biopsies (1.11 [1.08-1.2], P = 0.01), and end of treatment response to anti-HCV therapy (0.41 [0.19-0.88], P = 0.02). CONCLUSION: Fibrosis progresses with high frequency in HIV/HCV-coinfected patients over a period of time of 3 years. Absent-to-mild lobular necroinflammation at baseline, achievement of response with anti-HCV treatment, and effective antiretroviral therapy are associated with slower fibrosis progression.

OBJECTIVE: To evaluate the T helper 1 (T(H)1)/T helper 2 (T(H)2) lymphocyte cytokine profiles in women and men and to study the in vitro effects of sex hormones on lymphocyte secretion of cytokines. METHODS: Analysis of serum concentration and lymphocyte synthesis of T(H)1 (gamma interferon (INF-gamma) and interleukin 2 (IL-2)) and T(H)2 (interleukin 4 (IL-4) and interleukin 10 (IL-10)) cytokines was performed in 20 women and 15 men. Analysis of modifications in cytokine secretion induced by supplementation of lymphocyte culture with increasing concentrations of sex hormones was carried out. RESULTS: Higher levels of INF-gamma and IL-2 and lower levels of IL-4 and IL-10 were detected in the phytohemagglutinin-stimulated lymphocyte culture supernatants of men compared with women; the INF-gamma:IL-4 ratio was significantly higher in men. In women, similar concentrations of all the cytokines were detected in culture supernatants obtained during the follicular and the luteal phases. The addition of sex hormones did not modify the concentration of cytokines in supernatants of phytohemagglutinin-stimulated T-cell cultures. CONCLUSIONS: Women present a predominant T(H)2 cytokine profile, which could be involved in immune responses characterized principally by the secretion of antibodies. This could be a factor implicated in the higher concentration of immunoglobulins or the increased prevalence of autoimmune diseases detected in females.

To evaluate the factors associated with the evolution of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients, a cross-sectional analysis of 41 HIV-infected patients with chronic hepatitis C (known as "HIV-HCV [hepatitis C virus]-coinfected patients") and a control group of patients with chronic hepatitis C who did not have HIV infection (known as "non-HIV-infected patients") was performed. The association of histological variables with demographic parameters, HCV load and genotype, HIV load, CD4(+) T cell count, and response to highly active antiretroviral therapy (HAART) was evaluated. HIV-HCV-coinfected patients showed a significantly higher HCV load, more-advanced fibrosis, and a higher liver fibrosis progression rate (FPR) than did non-HIV-infected patients. A high HCV load and a low CD4(+) T cell count were associated with a higher FPR. The immune response induced by HAART did not influence this progression. In conclusion, HIV-HCV-infected patients, mainly such patients with a high HCV load and an immunodepressed state, have a higher FPR. An independent effect of the immune response to HAART was not evident.

The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14- and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented.

Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.

Surveys evaluating pain in hospitals keep on showing that postoperative pain (POP) remains undertreated. At the time when guidelines are edited and organisational changes are implemented, more recent data are necessary to check the impact of these measures on daily practice and needs for improvement. This prospective, cross-sectional, observational, multi-centre practice survey was performed in 2004-2005 in 7 European countries. It was conducted in surgical wards of a randomised sample of hospitals. Data on POP management practices following surgery in adult in-patients were collected anonymously via a standardised multiple choice questionnaire. Among 1558 questionnaires received from 746 European hospitals, 59% were provided by anaesthetists and 41% by surgeons. There are no regular on-site staff training programmes on POP management in the institution for 34% of the respondents, patients are systematically provided with POP information before surgery for 48% of respondents; balanced analgesia following major surgery and regular administration of analgesics are largely used; 25% of respondents have specific written POP management protocols for all patients in their ward; 34% of respondents say that pain is not assessed and 44% say that pain scores are documented in the patient's chart. This largest ever performed survey confirms the extensive body of evidence that current POP management remains suboptimal and identifies needs for improvement on European surgical wards. However, the wide use of balanced analgesia and the regular administration of analgesics are indicators of ongoing change.

We carried out a prospective analysis of clinical and analytical findings in individuals with antiphospholipid antibodies (aPL).We prospectively studied 404 individuals, classified in 2 groups: (1) patients with primary or secondary antiphospholipid syndrome (APS, n = 226); and (2) asymptomatic carriers of aPL (n = 178). Patients with APS and thrombosis were treated with dicumarin, and an international normalized ratio around 3.0 (range 2.5-3.5) was targeted. Asymptomatic carriers were not treated, but specific prophylaxis with low molecular weight heparin or aspirin was prescribed for the periods when individuals were at increased risk of thrombosis. Both groups of individuals were followed up at semester intervals for 36 months.Patients with APS presented with venous (n = 106, 46.9%) and/or arterial (n = 70. 31%) thrombosis or fetal loss (n = 58 out of 112 women of fertility age, 51.8%). At the time of the first thrombotic event, 50.0% of patients with APS had coincident risk factors for thrombosis (previous surgery and prolonged immobilization were significantly associated with venous thrombosis, and hypercholesterolemia and arterial hypertension with arterial thrombosis). Eighteen patients with APS died during the study period. Recurrence of thrombosis in patients with APS was linked to insufficient anticoagulation. During the followup, no episode of thrombosis was detected in any asymptomatic carrier. The proportion of subjects with aPL was similar in patients and in asymptomatic carriers. The proportion of subjects with aPL decreased during the followup, in both patients and carriers.Differences between patients and asymptomatic carriers with aPL are at least partially dependent on the proportion of coincident vascular risk factors. The decline in aPL during the followup defines a subgroup in which an anticoagulation suppression assay could be tried.

Importance: Studies of socioeconomic status and neurodevelopmental outcome in very preterm neonates have not sensitively accounted for brain injury. Objective: To determine the association of brain injury and maternal education with motor and cognitive outcomes at age 4.5 years in very preterm neonates. Design, Setting, and Participants: Prospective cohort study of preterm neonates (24-32 weeks' gestation) recruited August 16, 2006, to September 9, 2013, at British Columbia Women's Hospital in Vancouver, Canada. Analysis of 4.5-year outcome was performed in 2018. Main Outcomes and Measures: At age 4.5 years, full-scale IQ assessed using the Wechsler Primary and Preschool Scale of Intelligence, Fourth Edition, and motor outcome by the percentile score on the Movement Assessment Battery for Children, Second Edition. Results: Of 226 survivors, neurodevelopmental outcome was assessed in 170 (80 [47.1%] female). Based on the best model to assess full-scale IQ accounting for gestational age, standardized β coefficients demonstrated the effect size of maternal education (standardized β = 0.21) was similar to that of white matter injury volume (standardized β = 0.23) and intraventricular hemorrhage (standardized β = 0.23). The observed and predicted cognitive scores in preterm children born to mothers with postgraduate education did not differ in those with and without brain injury. The best-performing model to assess for motor outcome accounting for gestational age included being small for gestational age, severe intraventricular hemorrhage, white matter injury volume, and chronic lung disease. Conclusions and Relevance: At preschool age, cognitive outcome was comparably associated with maternal education and neonatal brain injury. The association of brain injury with poorer cognition was attenuated in children born to mothers of higher education level, suggesting opportunities to promote optimal outcomes.

BACKGROUND: Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph(+) ALL. DESIGN AND METHODS: This was a phase II study of patients with newly diagnosed Ph(+) ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease. RESULTS: Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively. CONCLUSIONS: These results confirm that imatinib is an effective first-line treatment for adult Ph(+) ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post-transplantation imatinib administration was limited, mainly because of transplantation-derived complications rather than drug-specific toxicity.

BACKGROUND: Although there are solid findings regarding the detrimental effect of alcohol consumption, the existing evidence on the effect of other dietary factors on breast cancer (BC) risk is inconclusive. This study aimed to evaluate the association between dietary patterns and risk of BC in Spanish women, stratifying by menopausal status and tumour subtype, and to compare the results with those of Alternate Healthy Index (AHEI) and Alternate Mediterranean Diet Score (aMED). METHODS: We recruited 1017 incident BC cases and 1017 matched healthy controls of similar age (±5 years) without a history of BC. The association between 'a priori' and 'a posteriori' developed dietary patterns and BC in general and according to menopausal status and intrinsic tumour subtypes (ER+/PR+ and HER2-; HER2+; and ER-/PR- and HER2-) was evaluated using logistic and multinomial regression models. RESULTS: Adherence to the Western dietary pattern was related to higher risk of BC (OR for the top vs the bottom quartile 1.46 (95% CI 1.06-2.01)), especially in premenopausal women (OR=1.75; 95% CI 1.14-2.67). In contrast, the Mediterranean pattern was related to a lower risk (OR for the top quartile vs the bottom quartile 0.56 (95% CI 0.40-0.79)). Although the deleterious effect of the Western pattern was similarly observed in all tumour subtypes, the protective effect of our Mediterranean pattern was stronger for triple-negative tumours (OR=0.32; 95% CI 0.15-0.66 and Pheterogeneity=0.04). No association was found between adherence to the Prudent pattern and BC risk. The associations between 'a priori' indices and BC risk were less marked (OR for the top vs the bottom quartile of AHEI=0.69; 95% CI 0.51-0.94 and aMED=0.74; 95% CI 0.46-1.18)). CONCLUSIONS: Our results confirm the harmful effect of a Western diet on BC risk, and add new evidence on the benefits of a diet rich in fruits, vegetables, legumes, oily fish and vegetable oils for preventing all BC subtypes, and particularly triple-negative tumours.

BACKGROUND: The Brugada syndrome is an arrhythmogenic disease caused in part by mutations in the cardiac sodium channel gene, SCN5A. The electrocardiographic pattern characteristic of the syndrome is dynamic and is often absent in affected individuals. Sodium channel blockers are effective in unmasking carriers of the disease. However, the value of the test remains controversial. METHODS AND RESULTS: We studied 147 individuals representing 4 large families with SCN5A mutations. Of these, 104 were determined to be at possible risk for Brugada syndrome and underwent both electrocardiographic and genetic evaluation. Twenty-four individuals displayed an ECG diagnostic of Brugada syndrome at baseline. Of the remaining, 71 received intravenous ajmaline. Of the 35 genetic carriers who received ajmaline, 28 had a positive test and 7 a negative ajmaline test. The sensitivity, specificity, and positive and negative predictive values of the drug challenge were 80% (28:35), 94.4% (34:36), 93.3% (28:30), and 82.9% (34:41), respectively. Penetrance of the disease phenotype increased from 32.7% to 78.6% with the use of sodium channel blockers. In the absence of ST-segment elevation under baseline conditions, a prolonged P-R interval, but not incomplete right bundle-branch block or early repolarization patterns, indicates a high probability of an SCN5A mutation carrier. CONCLUSIONS: In families with Brugada syndrome, the data suggest that ajmaline testing is valuable in the diagnosis of SCN5A carriers. In the absence of ST-segment elevation at baseline, family members with first-degree atrioventricular block should be suspected of carrying the mutation. An ajmaline test is often the key to making the proper diagnosis in these patients.

OBJECTIVE: To find the survival and the predictors of death of HIV-infected patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD). DESIGN AND METHODS: A prospective cohort study set in the infectious diseases units of four tertiary care public hospitals in Andalucía, Spain. From a multicentric cohort of 2664 HIV/HCV-co-infected patients, all consecutive patients with HCV-related cirrhosis who presented with the first hepatic decompensation from January 1997 to June 2004 were followed-up and 153 patients were included. The survival and the demographic, HIV-related and liver-related factors associated with death were evaluated. RESULTS: Ninety-five (62%) patients died during the follow-up. In 79 (85%) individuals, the cause of death was liver related. The median survival time was 13 months. Independent predictors of survival were Child score [hazard ratio (HR), 1.2; 95% confidence interval (CI), 1.08-1.37; P = 0.001], CD4+ cell count at decompensation lower than 100 cells/microl (HR, 2.48; 95% CI, 1.52-4.06; P < 0.001) and hepatic encephalopathy as the first hepatic decompensation (HR, 2.45; 95% CI, 1.41-4.27; P = 0.001). HAART was prescribed to 101 (66%) patients. The cumulative probability of survival in patients under HAART was 60% at 1 year and 40% at 3 years, versus 38 and 18%, respectively, in patients not treated with HAART (P < 0.0001). The HR (95% CI) of death in patients on HAART was 0.5 (0.3-0.9), (P = 0.03). CONCLUSIONS The survival of HIV/HCV-co-infected patients with ESLD is extremely poor. Immunosuppression and markers of severe liver disease predict liver-related mortality in these patients. HAART seems to be associated with a reduced liver-related mortality.