Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis.

OBJECTIVE Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. METHODS Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. RESULTS A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. CONCLUSION Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.

Characteristics and effectiveness of diabetes self-management educational programs targeted to racial/ethnic minority groups: a systematic review, meta-analysis and meta-regression.

BACKGROUND It is not clear to what extent educational programs aimed at promoting diabetes self-management in ethnic minority groups are effective. The aim of this work was to systematically review the effectiveness of educational programs to promote the self-management of racial/ethnic minority groups with type 2 diabetes, and to identify programs' characteristics associated with greater success. METHODS We undertook a systematic literature review. Specific searches were designed and implemented for Medline, EMBASE, CINAHL, ISI Web of Knowledge, Scirus, Current Contents and nine additional sources (from inception to October 2012). We included experimental and quasi-experimental studies assessing the impact of educational programs targeted to racial/ethnic minority groups with type 2 diabetes. We only included interventions conducted in countries members of the OECD. Two reviewers independently screened citations. Structured forms were used to extract information on intervention characteristics, effectiveness, and cost-effectiveness. When possible, we conducted random-effects meta-analyses using standardized mean differences to obtain aggregate estimates of effect size with 95% confidence intervals. Two reviewers independently extracted all the information and critically appraised the studies. RESULTS We identified thirty-seven studies reporting on thirty-nine educational programs. Most of them were conducted in the US, with African American or Latino participants. Most programs obtained some benefits over standard care in improving diabetes knowledge, self-management behaviors and clinical outcomes. A meta-analysis of 20 randomized controlled trials (3,094 patients) indicated that the programs produced a reduction in glycated hemoglobin of -0.31% (95% CI -0.48% to -0.14%). Diabetes knowledge and self-management measures were too heterogeneous to pool. Meta-regressions showed larger reduction in glycated hemoglobin in individual and face to face delivered interventions, as well as in those involving peer educators, including cognitive reframing techniques, and a lower number of teaching methods. The long-term effects remain unknown and cost-effectiveness was rarely estimated. CONCLUSIONS Diabetes self-management educational programs targeted to racial/ethnic minority groups can produce a positive effect on diabetes knowledge and on self-management behavior, ultimately improving glycemic control. Future programs should take into account the key characteristics identified in this review.

Popliteal pseudoaneurysm after unicompartmental knee replacement: a case report.

Popliteal pseudoaneurysm is a rare but important complication of knee arthroplasties. To our knowledge, this complication has not been reported previously in the literature after unicompartmental knee arthroplasty. Apart from intraoperatively caused arterial injuries, obese patients and other previous cardiovascular diseases may be potential factors of risks for pseudoaneurysm in knee surgeries. As it is an uncommon complication and it has inconspicuous symptoms, both diagnosis and treatment can be delayed. This means that a high level of suspicion is necessary to prevent serious complications derived from pseudoaneurysms. LEVEL OF EVIDENCE Level IV.

Could radiotherapy effectiveness be enhanced by electromagnetic field treatment?

One of the main goals in radiobiology research is to enhance radiotherapy effectiveness without provoking any increase in toxicity. In this context, it has been proposed that electromagnetic fields (EMFs), known to be modulators of proliferation rate, enhancers of apoptosis and inductors of genotoxicity, might control tumor recruitment and, thus, provide therapeutic benefits. Scientific evidence shows that the effects of ionizing radiation on cellular compartments and functions are strengthened by EMF. Although little is known about the potential role of EMFs in radiotherapy (RT), the radiosensitizing effect of EMFs described in the literature could support their use to improve radiation effectiveness. Thus, we hypothesized that EMF exposure might enhance the ionizing radiation effect on tumor cells, improving the effects of RT. The aim of this paper is to review reports of the effects of EMFs in biological systems and their potential therapeutic benefits in radiotherapy.

New clinical practice guideline on enteral feeding in very low birth wieght infants; second part

INTRODUCTION: The nutrition of very low birth weight (VLBW) infants is aimed at promoting a similar growth to that occurring in the uterus. However, in practice this is difficult to achieve and extrauterine growth restriction is frequent. The current tendency is to avoid this restriction by means of early parenteral and enteral nutrition. Nonetheless, uncertainty about many of the practices related with nutrition has resulted in a great variation in the way it is undertaken. In 2009 and 2011 in our hospital there was an unexpected increase in necrotizing enterocolitis. To check to see wether our nutrition policy was involved, we underlook a systematic review and drewup clinical practice guidelines (CPG) about enteral feeding in VLBW infants. New considerations about the duration of the fortification and the use of probiotics have led to an update of these CPG. METHODS: A total of 21 clinical questions were designed dealing with the type of milk, starting age, mode of administration, rate and volume of the increments, fortification, use of probiotics and protocol. Afete conducting a systematic search of the available evidence, the information was contrasted and summarized in order to draw up the recommendations. The quality of the evidence and the strength of the recommendations were determined from the SIGN scale. COMMENT: These CPG aim to help physicians in their decision making. The protocolized application of wellproven measurements reduces the variation in clinical practice and improves results.

Camino de Gibraltar : dependencia y sustento en La Línea y Gibraltar

Vol. 2 del proyecto de investigación: "La sobremortalidad por cáncer en El Campo de Gibraltar. Mirar el pasado para explicar el presente".

Estudio de las prescripciones farmacológicas en niños a nivel de atención primaria: evaluación de los usos off-label o fuera de ficha técnica.

OBJECTIVE to evaluate the prescription profile and to assess the off-label and unlicensed uses of medicines among non-hospitalised pediatric patients. DESIGN cross-sectional study. SETTING pediatric units in two urban health centers and general emergency room (Hospital Materno-Infantil, Málaga). MAIN MEASUREMENTS sociodemographics variables, reasons for consultation and information about therapeutic medications. The classification of prescriptions was established according to information requirements contained in the Summary of Products Characteristics (SPC). RESULTS A total of 388 children were included (a subsample of 105 treated in the emergency room). Four hundred sixty-two prescriptions (involving 74 different active ingredients) were evaluated. Each infant received and average of 1,7 drugs (95% CI: 1,6-1,9). The most prescribed medicines were ibuprofen, paracetamol, amoxicillin-clavulanate and budesonide. The therapeutic group with the greatest variety of drugs was the respiratory group. 27,4% (95% CI: 23,5-31) of prescriptions were off-label and the main cause was different age (60%; 95% CI: 54,1-63), followed by different dose (21,5%; 95% CI: 18-25), different indication (12%; 95% CI: 9,2-15) and different route of administration (7%; 95% CI: 5,4-10). CONCLUSIONS The rate of off-label uses presents intermediate figures. Around one third of the paediatric outpatients in our sample are exposed to at least one off-label or unlicensed prescription. We should, however, point out that such usage is based on scant official, quality information, although it is not necessarily incorrect. Evidence-based medicine should be encouraged to improve drug therapy in children, as well as following the rules on drugs in special situations.

Expression profiling of rectal tumors defines response to neoadjuvant treatment related genes.

To date, no effective method exists that predicts the response to preoperative chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless, identification of patients who have a higher likelihood of responding to preoperative CRT could be crucial in decreasing treatment morbidity and avoiding expensive and time-consuming treatments. The aim of this study was to identify signatures or molecular markers related to response to pre-operative CRT in LARC. We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10 responders and 16 non-responders) without metastasis using Human WG CodeLink microarray platform. Two hundred and fifty seven genes were differentially over-expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed a significant ratio of differentially expressed genes related to cancer, cellular growth and proliferation pathways, and c-Myc network. We demonstrated that high Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic factor for response to treatment in LARC patients (p<0.05). Using this gene set, we were able to establish a new model for predicting the response to CRT in rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect the value of gene expression profiling to gain insight about the molecular pathways involved in the response to treatment of LARC patients. These findings could be clinically relevant and support the use of mRNA levels when aiming to identify patients who respond to CRT therapy.

Hidratos de carbono: actualización de su papel en la diabetes mellitus y la enfermedad metabólica.

BACKGROUND: There is a prevalence of diabetes mellitus (DM), unknown DM and stress hyperglycemia among hospital patients, and the nutritional treatment is a key part of care, where carbohydrates (CH) intake is a controversial issue. There is also a discussion on the increase of prevalence for DM, obesity and metabolic disease with refined CH or sugar. OBJECTIVES: This review examines the recommendations from different scientific societies about the percentage of CH in the total calorie intake of the diabetic patient, the CH value in the glycemic index and glycemic load, the new CH included in enteral formulae and the association of refined CH with the high prevalence of DM and metabolic disease. METHODS: Systematic review of literature using the electronic scientific databases Pubmed, Science Direct, Scielo, Scopus and Medline. CONCLUSIONS: Scientific societies are flexible about the CH intake in the diet of diabetic patients, suggesting to customize it according to each metabolic profile. Using the glycemic index and glycemic load can provide an extra benefit in the postprandial glycemic control. The new diabetes-specific enteral formulae, with fructooligosaccharides, resistant maltodextrins and fructose-free show efficacy in improving the glycemic control, although more controlled and long-term studies are needed. There is still some controversy about the links between sugar intake and DM, obesity and metabolic disease, although this relationship would be more linked to an increase of the total calorie intake than to a specific nutrient. .

Adecuación de la medicación cardiovascular en los diabéticos tipo 2 de Torrejoncillo (Cáceres) según los criterios STOP/STAR.

Financiación Proyecto de Investigación DIAB06/2012 «Detección y control de factores de riesgo y complicaciones vasculares en los pacientes diabéticos de la zona de salud de Torrejoncillo(Cáceres)». Fundación para la Formación y la Investigación de los Profesionales de Salud de Extremadura.

Conocimientos y actitudes de los profesionales sanitarios en el proceso de declaración de las voluntades vitales anticipadas.

Objective: To identify the underlying interests of the Living Will Declaration (LWD) process and to determine the consensus, using a questionnaire, of the knowledge and attitudes of health professionals. Design: A study was performed in two phases using a Delphi technique with a Rand method. 1. Dimensions proposed: generation of ideas and their subsequent prioritizing; 2. Proposal andprioritizing of items grouped into blocks of Knowledge and Attitudes, developed between August 2012 and January 2013.Setting: The work was carried out by initial telephone contact with panellists, and then later by the panellists belonged to the Andalusia Public Health System.Participants: The criteria for selecting the eight components of the panel were knowledge andexperience in the field of the freedom of the patient in Andalusia. Results: The Knowledge identified included: 1 A) Legal and general aspects; 2 A) A conceptual definition; 3 A) Standardised LWD documents: 4 A) Practical experience; 5 A) Procedure and registering of the LWDs. The second block included Attitudes: 1 B) Attitudes of the professional in the application of LWDs in clinical practice, and 2 B) Attitudes of the professional in «complex» ethical scenarios The 7 panellists who finally took part proposed 165 items. After applying the prioritizing criteria, scores, and scenario selection, 58 (35.2%) items were identified as suitable scenarios. Conclusions: The proposed questionnaire included wide parcels of concepts and contents that, once validated, will help to measure the training interventions carried out on health professionals in order to improve knowledge and attitudes on the subject of LWDs.

EMT and EGFR in CTCs cytokeratin negative non-metastatic breast cancer.

Circulating tumor cells (CTCs) are frequently associated with epithelial-mesenchymal transition (EMT).The objective of this study was to detect EMT phenotype through Vimentin (VIM) and Slug expression in cytokeratin (CK)-negative CTCs in non-metastatic breast cancer patients and to determine the importance of EGFR in the EMT phenomenon. In CK-negative CTCs samples, both VIM and Slug markers were co-expressed in the most of patients. Among patients EGFR+, half of them were positive for these EMT markers. Furthermore, after a systemic treatment 68% of patients switched from CK- to CK+ CTCs. In our experimental model we found that activation of EGFR signaling by its ligand on MCF-7 cells is sufficient to increase EMT phenotypes, to inhibit apoptotic events and to induce the loss of CK expression. The simultaneous detection of both EGFR and EMT markers in CTCs may improve prognostic or predictive information in patients with operable breast cancer.

Una declaración de amor a la ciencia en Andalucía

Boletín semanal para profesionales sanitarios de la Secretaría General de Calidad, Innovación y Salud Pública de la Consejería de Igualdad, Salud y Políticas Sociales

Epidemiological and clinical data of hospitalizations associated with respiratory syncytial virus infection in children under 5 years of age in Spain: FIVE multicenter study.

BACKGROUND Respiratory syncytial virus (RSV) is an important pathogen in lower respiratory tract infections (LRTI) in infants, but there are limited data concerning patients with underlying conditions and children older than 2 years of age. METHODS We have designed a prospective observational multicenter national study performed in 26 Spanish hospitals (December 2011-March 2012). Investigational cases were defined as children with underlying chronic diseases and were compared with a group of previously healthy children (proportion 1:2). Clinical data were compared between the groups. RESULTS A total of 1763 children hospitalized due to RSV infection during the inclusion period were analyzed. Of them, 225 cases and 460 healthy children were enrolled in the study. Underlying diseases observed were respiratory (64%), cardiovascular (25%), and neurologic (12%), as well as chromosomal abnormalities (7·5%), immunodeficiencies (6·7%), and inborn errors of metabolism (3·5%). Cases were statistically older than previously healthy children (average age: 16·3 versus 5·5 months). Cases experienced hypoxemia more frequently (P < 0·001), but patients with respiratory diseases required oxygen therapy more often (OR: 2·99; 95% CI: 1·03-8·65). Mechanical ventilation was used more in patients with cardiac diseases (OR: 3·0; 95% CI: 1·07-8·44) and in those with inborn errors of metabolism (OR: 12·27; 95% CI: 2·11-71·47). This subgroup showed a higher risk of admission to the PICU (OR: 6·7, 95% CI: 1·18-38·04). Diagnosis of pneumonia was more frequently found in cases (18·2% versus 9·3%; P < 0·01). CONCLUSIONS A significant percentage of children with RSV infection have underlying diseases and the illness severity is higher than in healthy children.