Diversity of nitrogen-fixing and phosphorus-solubilizing bacteria associated with the rhizosphere of Andean maize in Ecuador.

A great diversity of microorganisms in the soil plays an important role in the sustainability of agricultural production systems. Among these microorganisms are bacteria that have the ability to fix atmospheric nitrogen or mineralize phosphorus, thus making it easily assimilable for plants. Maize is the main crop in the highlands of Ecuador (above 2000 meters) and it is predominantly traditional, using native seeds and very little or no agrochemicals. The National Institute of Agricultural Research (INIAP) has a collection of bacteria collected from the rhizosphere of maize in the highlands of Ecuador that has not been taxonomically identified. This research aimed to carry out a biochemical and genetic characterization to establish the identity of the collected nitrogen-fixing and phosphorus-solubilizing bacteria and to understand better the diversity of microorganisms present in the root biome of Andean maize. The hypothesis consisted of determining if there is a difference in the bacteria associated with the rhizosphere of maize in the Andean region of Ecuador compared with other regions. The bacteria underwent classical biochemical characterization based on catalase, oxidase, urease, sulfates, indole, sulfate-indole motility (SIM), and lactose, among others, and genetic identification by 16S rDNA ribosomal gene sequencing, PCR, and SANGER sequencing. A great diversity of microorganisms associated with the rhizosphere of the crop was found, including the genera Agrobacterium, Bacillus, Stenotrophomonas, Acinetobacter, Brevundimonas, Pseudomonas, and Pseudoxanthomonas. INIAP conserves these bacteria in a bank of microorganisms associated with crops of economic importance. They are useful for the development of biofertilizers that could contribute to a more sustainable agriculture in the region.

Maternal sedation during scheduled versus unscheduled cesarean delivery: implications for skin-to-skin contact.

BACKGROUND: Early maternal skin-to-skin contact confers numerous benefits to the newborn, but maternal sedation during cesarean delivery could have safety implications for early skin-to-skin contact in the operating room. We compared patient-reported and observer-assessed levels of sedation during unscheduled and scheduled cesarean deliveries. METHODS: Laboring women undergoing unscheduled cesarean delivery with epidural anesthesia, and scheduled cesarean delivery with spinal anesthesia were enrolled. Sedation levels, measured using patient-reported (1=least sedated to 10=most sedated) and observer-assessed (0=most sedated to 5=least sedated) scales, were evaluated at baseline and 15, 30, 45, and 60min following a T4 sensory level. The primary outcomes were patient-reported sedation at 45min and the areas under the sedation curves. RESULTS: Patient-reported levels of sedation were greater at 45min in laboring women undergoing unscheduled (median 7.5, IQR 5-9) versus scheduled cesarean delivery (median 4, IQR 3-6) (difference in medians 3.5, 99% CI 0 to 5). Observer-assessed sedation was not different between groups. The area under the time curve for patient-reported sedation was greater in the unscheduled group, median difference 162 score min (95% CI 52 to 255). The area under the time curve for observer-assessed sedation was greater in the unscheduled group, median difference 26 score min (99% CI 0 to 41). Times to skin-to-skin contact and breastfeeding were not different. CONCLUSIONS: Women undergoing unscheduled cesarean deliveries are more sedated than women undergoing scheduled cesarean deliveries. Skin-to-skin protocols for cesarean deliveries must consider maternal sedation and anesthesiologists should use sedating medications judiciously.

Tuberculosis in Anti-Tumour Necrosis Factor-treated Inflammatory Bowel Disease Patients After the Implementation of Preventive Measures: Compliance With Recommendations and Safety of Retreatment.

BACKGROUND AND AIMS: Despite having adopted preventive measures, tuberculosis (TB) may still occur in patients with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor (anti-TNF). Data on the causes and characteristics of TB cases in this scenario are lacking. Our aim was to describe the characteristics of TB in anti-TNF-treated IBD patients after the publication of the Spanish TB prevention guidelines in IBD patients and to evaluate the safety of restarting anti-TNF after a TB diagnosis. METHODS: In this multicentre, retrospective, descriptive study, TB cases from Spanish hospitals were collected. Continuous variables were reported as mean and standard deviation or median and interquartile range. Categorical variables were described as absolute and relative frequencies and their confidence intervals when necessary. RESULTS: We collected 50 TB cases in anti-TNF-treated IBD patients, 60% male, median age 37.3 years (interquartile range [IQR] 30.4-47). Median latency between anti-TNF initiation and first TB symptoms was 155.5 days (IQR 88-301); 34% of TB cases were disseminated and 26% extrapulmonary. In 30 patients (60%), TB cases developed despite compliance with recommended preventive measures; *not performing 2-step TST (tuberculin skin test) was the main failure in compliance with recommendations. In 17 patients (34%) anti-TNF was restarted after a median of 13 months (IQR 7.1-17.3) and there were no cases of TB reactivation. CONCLUSIONS: Tuberculosis could still occur in anti-TNF-treated IBD patients despite compliance with recommended preventive measures. A significant number of cases developed when these recommendations were not followed. Restarting anti-TNF treatment in these patients seems to be safe.

Effective utilization of flue gases in raceway reactor with event-based pH control for microalgae culture.

This work addresses effective utilization of flue gases through the proper pH control in raceway reactors. The pH control problem has been addressed with an event-based control approach using a Generalized Predictive Controller (GPC) with actuator deadband. Applying this control strategy it is possible to reduce the control effort, and at the same time saving control resources. In the pH process case, the event-based controller with actuator deadband can be tuned to supply only necessary amount of CO2 to keep the pH close to its optimal value. On the other hand, the evaluated control algorithm significantly improves the pH control accuracy, what has a direct influence on biomass production. In order to test the performance of the event-based GPC controller, several experiments have been performed on a real raceway reactor. Additionally, several control performance indexes have been used to compare the analyzed technique with commonly used on/off controller.

Role of TNFRSF1B polymorphisms in the response of Crohn's disease patients to infliximab.

Infliximab (IFX) is a valid treatment for Crohn's disease (CD), but a relevant percentage of patients do not benefit from this therapy. In the Japanese population, the response to IFX was associated with markers in the TNF receptor superfamily 1A (TNFRSF1A) and 1B (TNFRSF1B) genes. We aimed to replicate the association previously described in the Japanese population and to ascertain the role of TNF receptors as modulators of the response to IFX. We studied 297 white Spanish CD patients with a known response to IFX: 238 responders and 59 primary nonresponders. Four single nucleotide polymorphisms (SNPs) were analyzed: rs767455 in TNFRSF1A and rs1061622, rs1061624, and rs3397 in TNFRSF1B. Comparisons between groups were performed with chi-square tests or the Fisher's exact test. Different features (sex, age, disease duration, smoking among others) were evaluated as possible confounding factors. No significant association was found between the studied TNFRSF1A polymorphisms and response to IFX. In the TNFRSF1B gene, the haplotype rs1061624_A-rs3397_T was significantly increased in nonresponders: p = 0.015, OR = 1.78, 95% CI 1.09-2.90; and an increased frequency of rs1061622_G carriers was observed in patients with remission: p = 0.033 vs nonresponders and p = 0.023 vs patients with a partial response. Our results support a role of TNFRSF1B gene variants in the response to IFX in CD patients.

Evaluation of carbon dioxide mass transfer in raceway reactors for microalgae culture using flue gases.

Mass transfer of CO2 from flue gas was quantified in a 100m(2) raceway. The carbonation sump was operated with and without a baffle at different liquid/gas ratios, with the latter having the greatest influence on CO2 recovery from the flue gas. A rate of mass transfer sufficient to meet the demands of an actively growing algal culture was best achieved by maintaining pH at ∼8. Full optimisation of the process required both pH control and selection of the best liquid/gas flow ratio. A carbon transfer rate of 10gCmin(-1) supporting an algal productivity of 17gm(-2)day(-1) was achieved with only 4% direct loss of CO2 in the sump. 66% of the carbon was incorporated into biomass, while 6% was lost by outgassing and the remainder as dissolved carbon in the liquid phase. Use of a sump baffle required additional power without significantly improving carbon mass transfer.

[Satisfaction rating in a group of women from Granada on birthing care, support and breastfeeding length]. / Valoración del nivel de satisfacción en un grupo de mujeres de Granada sobre atención al parto, acompañamiento y duración de la lactancia.

INTRODUCTION: The satisfaction's analysis is being used as an instrument to create different sanitary reforms to improve the quality and numerous studies aim to the increase the mother's satisfaction directly related to the maternity care. OBJECTIVES: [corrected] Identify the woman satisfaction's degree about birth attention, accompaniment during nativity and the breastfeeding's term. MATERIAL AND METHOD: [corrected] Descriptive transversal study in the university hospital San Cecilio in Granada (España), during the time of August 2011 to 2012, it performed with a second prospective tracing phase to a N = 60 mothers. It used a protocol (Annex 1) after 24 hours in hospital and at 14 days by telephone. After 3 months, it performed a tracing pertaining to the baby food. RESULTS: The global satisfaction's level about birth is high in study population. It has been shown that breastfeeding (P = 0,514) and vaginal birth without epidural (P = 0,320) creates higher satisfaction for mother. On the other hand, birth satisfaction related with duration of breastfeeding. CONCLUSION: Satisfactory mothers' opinion related with birth care and accompaniment during nativity increases in women whose birth happened in a uncomplicated way without epidural and they started early breastfeeding.

Introducción: El análisis de la satisfacción se está utilizando como instrumento para crear diferentes reformas sanitarias para la mejora de la calidad y numerosos estudios apuntan al incremento de la satisfacción de la madre en relación directa con el cuidado en la maternidad. Objetivos: Identificar el grado de satisfacción de la mujer sobre la atención al parto, el acompañamiento durante el nacimiento y la duración de la lactancia materna. Material y método: Estudio descriptivo transversal en el Hospital Universitario San Cecilio de Granada (España), durante el periodo de tiempo Agosto del 2011 al 2012, se realizo con una segunda fase de seguimiento prospectivo a una N = 60 madres. Se utilizó un protocolo (Anexo 1) a las 24 horas en el hospital y a los 14 días por teléfono. A los 3 meses, se realizó un seguimiento relacionado con la alimentación del bebe. Resultados: El nivel de satisfacción global sobre el parto es alto en la población estudiada. Se ha demostrado que la lactancia materna (P = 0,514) y el parto vía vaginal sin epidural (P = 0,320) crea una mayor satisfacción en la madre. Por otro lado, la satisfacción sobre el parto guarda relación con la duración de la lactancia materna. Conclusión: La opinión satisfactoria de las madres relacionadas con la atención al parto y el acompañamiento durante el nacimiento se incrementa en aquellas mujeres cuyo parto ocurrió de forma eutócica sin epidural e iniciaron la lactancia materna precoz.

Oxygen transfer and evolution in microalgal culture in open raceways.

The mass transfer characteristics of all sections of a 100 m(2) raceway were evaluated. The efficiency of different diffusers was determined dynamically and the most effective was used for steady state system characterisation at water depth 0.2 m and velocity 0.22 m s(-1). Mass transfer coefficients at a gas flow rate of 6 m(3) h(-1) were 164.50, 63.66, 0.87 and 0.94 h(-1) for the paddlewheel, sump, straight and curved channel sections, with associated oxygen transfer rates of 106, 172, 27 and 39 g h(-1). Oxygen supersaturation during algal cultivation led to a reduction in biomass productivity, which was more severe with pure CO2 than flue gas. Simulations showed the energy required to increase mass transfer and reduce oxygen concentrations was more than compensated for by increased biomass and potential energy yields. Oxygen removal is likely to be a critical criterion, and maintenance of mass transfer by sparging may be necessary even when CO2 is not required.

Evaluation of liver fibrosis by transient elastography (Fibroscan®) in patients with inflammatory bowel disease treated with methotrexate: a multicentric trial.

BACKGROUND: Methotrexate is an effective treatment for inflammatory bowel disease (IBD). However, long-term treatments have been associated with the development of liver fibrosis. FibroScan® is a noninvasive, safe, and effective technique to evaluate liver fibrosis. AIM: To evaluate the presence of significant liver fibrosis by transient elastography (FibroScan®) in IBD patients treated with methotrexate. METHODS: Cross-sectional study including IBD patients treated with methotrexate from different hospitals. Clinical and analytical data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®. The cutoff value for significant liver fibrosis (according to METAVIR) was F ≥ 2: 7.1 kPa. Results. In the study, 46 patients were included, 30 women (65%), with a mean age of 43 ± 10 years. 31 patients had Crohn's disease (67.4%), 13 ulcerative colitis (28.3%), and 2 indeterminate colitis (4.3%). The mean cumulative dose of methotrexate was 1242 ± 1349 mg, with a mean treatment duration of 21 ± 24 months. The mean value of liver stiffness was 4.7 ± 6.9 kPa. There were 35 patients (76.1%) with F01, 8 patients (17.4%) with F = 2, and 3 patients with F ≥ 3 (6.5%). There were no differences in liver stiffness depending on sex, age, type of IBD, or cumulative dose of methotrexate. CONCLUSIONS: (1) Development of advanced liver fibrosis in IBD patients treated with methotrexate is exceptional. (2) There were no differences in liver stiffness depending on the type of IBD or the cumulative dose of methotrexate. (3) FibroScan® may be potentially useful for evaluation and follow-up of liver fibrosis in methotrexate-treated patients.

Infliximab salvage therapy after failure of ciclosporin in corticosteroid-refractory ulcerative colitis: a multicentre study.

BACKGROUND: Ciclosporin has proven to be effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with this drug fails, infliximab can be considered to avoid colectomy. The efficacy and safety of this sequential approach remain unknown. AIM: To assess the efficacy and safety profile of treatment with infliximab after failure of ciclosporin in patients with a corticosteroid-refractory flare of UC. METHODS: Retrospective review of medical records of patients with a corticosteroid-refractory flare of UC who did not respond to ciclosporin and received salvage therapy with infliximab within a month of discontinuing ciclosporin. The severity of the flare and response to the treatment were graded using the Lichtiger index. Cumulative rates of colectomy were calculated using Kaplan-Meier analysis. Cox regression analysis was performed to identify predictors of colectomy. To evaluate the safety profile of this treatment strategy, any adverse event occurring after the first infusion of infliximab was considered. RESULTS: The study population comprised 47 patients with corticosteroid-refractory UC treated with infliximab after failure of ciclosporin. The median baseline Lichtiger index was 13. The mean time from the last ciclosporin dose to the first infliximab infusion was 6 days. After the first infliximab infusion, 13% of patients achieved remission, and 74% partial response. Of the 35 patients who received the third infliximab infusion, 60% achieved remission, and 37% partial response. Fourteen patients (30%) underwent colectomy. The rate of adverse events was 23%. One death occurred in a 40-year-old man who failed ciclosporin and infliximab and underwent surgery 10 days after the first infliximab infusion; he died of nosocomial pneumonia. CONCLUSIONS: Treatment with infliximab makes it possible to avoid colectomy in two-thirds of corticosteroid-refractory UC patients in whom ciclosporin fails. However, the rates of adverse events and mortality mean that the decision to administer sequential therapy (ciclosporin-infliximab) should be taken on an individual basis.

Long-term durability of response to adalimumab in Crohn's disease.

BACKGROUND: Adalimumab is an effective treatment for Crohn's disease (CD), but may also be associated with loss of response. Few reports provide insight into the durability of treatment of CD with adalimumab for periods longer than 12 months in clinical practice. AIMS: To evaluate the long-term durability of adalimumab maintenance treatment and to identify predictive factors associated with loss of response. METHODS: CD patients who initially responded to adalimumab were evaluated in a historical cohort study. Maintenance of long-term response was estimated using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors for loss of efficacy. RESULTS: In all, 380 CD patients were included (mean age, 38 years; 52% female). Of these, 43% had ileocolic CD, 50% inflammatory CD, and 41% perianal CD. Median follow-up with adalimumab was 8 months (range, 4-75 months). The annual risk of loss of response to adalimumab was 18% per patient-year of follow-up. Twenty-eight percent of patients were anti-TNF-naïve and 72% anti-TNF-experienced. The loss of efficacy was 8% per patient-year of follow-up in the anti-TNF-naïve patients and 22% in the anti-TNF-experienced group (P < 0.01). In the multivariate analysis, the presence of extraintestinal manifestations (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.02-2.9) and previous experience with other anti-TNF agents (HR = 2.5,95% CI = 1.2-5.3) were associated with higher risk of loss of efficacy. CONCLUSIONS: A relevant proportion of CD patients on long-term adalimumab lost response. The risk of loss of response was higher (more than 2-fold) in anti-TNF-experienced than in anti-TNF-naïve patients (22% vs. 8% per patient-year of treatment). Having extraintestinal manifestations seems to increase the risk of loss of efficacy.

[Obesity in a school children population from Granada: assessment of the efficacy of an educational intervention]. / Obesidad de una población de escolares de Granada: evaluación de la eficacia de una intervención educativa.

OBJECTIVES: The objective of this research was to study the prevalence of obesity and excess weight in a population of school children and adolescents, and to verify the effectiveness of an educational intervention, as reflected in the variation of their body mass index values. MATERIALS: The population sample was composed of 977 school children and adolescents from 9 to 17 years of age, belonging to 13 public elementary schools and high schools in the city and province of Granada (Spain). METHODOLOGY: This longitudinal cohort study was analytical, muticentric, and observational. It was carried out in three phases. The first phase involved the evaluation of the nutritional state of the sample population by means of anthropometric measurements (weight, height, body mass index, six skin folds and four body perimeters) as well as arterial blood pressure. The second phase entailed an educational intervention focusing on good nutritional habits and physical exercise. The third and final phase evaluated the effectiveness of the intervention. RESULTS: A higher obesity prevalence (15.1%) was found in school girls between 12 and 13. In the case of boys, obesity prevalence was lower up to age 13 though afterwards, it progressively increased (12.6%). The educational intervention produced an important reduction in body mass index values in both sexes though this reduction was more significant in young females. CONCLUSIONS: There is a currently an alarming increase in obesity and overweight prevalence among the population evaluated in this study. The significant reduction in body mass index values resulting from this research confirmed the effectiveness of the educational intervention to reduce excess weight.

Systematic review: the use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn's disease.

BACKGROUND: Cross-sectional imaging techniques, including ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), are increasingly used for evaluation of Crohn's disease (CD). Aim To perform an assessment of the diagnostic accuracy of cross-sectional imaging techniques for diagnosis of CD, evaluation of disease extension and activity and diagnosis of complications, and to provide recommendations for their optimal use. METHODS: Relevant publications were identified by literature search and selected based on predefined quality parameters, including a prospective design, sample size and reference standard. A total of 68 publications were chosen. RESULTS: Ultrasonography is an accurate technique for diagnosis of suspected CD and for evaluation of disease activity (sensitivity 0.84, specificity 0.92), is widely available and non-invasive, but its accuracy is lower for disease proximal to the terminal ileum. MRI has a high diagnostic accuracy for the diagnosis of suspected CD and for evaluation of disease extension and activity (sensitivity 0.93, specificity 0.90), and is less dependent on the examiner and disease location compared with US. CT has a similar accuracy to MRI for assessment of disease extension and activity. The three techniques have a high accuracy for identification of fistulas, abscesses and stenosis (sensitivities and specificities >0.80), although US has false positive results for abscesses. As a result of the lack of radiation, US or MRI should be preferred over CT, particularly in young patients. CONCLUSIONS: Cross-sectional imaging techniques have a high accuracy for evaluation of suspected and established CD, reliably measure disease severity and complications; they may offer the possibility to monitor disease progression.

Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab.

BACKGROUND: The long-term efficacy of adalimumab in patients with ulcerative colitis is not well known. AIM: To evaluate the short- and long-term outcomes of adalimumab in ulcerative colitis patients previously treated with infliximab. METHODS: Patients with active ulcerative colitis were treated with adalimumab after failure of other therapies including infliximab. Short-term clinical response and remission were assessed at weeks 4 and 12. The proportion of patients who continued on adalimumab and the proportion of patients who remained colectomy free were assessed over the long term. RESULTS: Clinical response at weeks 4 and 12 was achieved in 16 (53%) and 18 (60%) patients, respectively, and clinical remission was obtained in 3 (10%) and 8 (27%) patients, respectively. After a mean 48 weeks' follow-up, 15 patients (50%) continued on adalimumab. Six patients (20%) required colectomy. All patients who achieved clinical response at week 12 were colectomy free at long term. CONCLUSIONS: Adalimumab was well tolerated and induced durable clinical response in many patients with otherwise medically refractory ulcerative colitis. Patients achieving clinical response at week 12 avoided colectomy over the long term.

NOD2/CARD15: geographic differences in the Spanish population and clinical applications in Crohn's disease.

Crohn's disease (CD) is a genetically complex disease in which both genetic susceptibility and environmental factors play key roles in the development of the disorder. NOD2/CARD15 mutations are associated with CD. NOD2 encodes for a protein that is an intracellular receptor for a bacterial product (muramyl dipeptide), though the exact functional consequences of these mutations remain the subject of debate. NOD2/CARD15 mutations are associated with ileal CD, with stricturing behavior, and possibly with a more complicated course of CD. NOD2/CARD15 mutations associated with CD have demonstrated heterogeneity across ethnicities and populations throughout the world, with regional variations across Europe and Spain. However, "NOD2/CARD15 testing" is not yet ready for use in the clinical setting. One of the reasons is that we know that these genetic variants increase the risk of disease only marginally, and many healthy individuals carry the risk alleles, at present it is not recommended to screen first-degree relatives, because we do not have the ability to prevent the disease at the present time.

STAT3 locus in inflammatory bowel disease and multiple sclerosis susceptibility.

STAT3 (signal transducer and activator of transcription 3) signaling is a critical component of Th17-dependent autoimmune processes. Genome-wide association studies (GWAS) have revealed the role of the STAT3 gene in inflammatory bowel disease (IBD) susceptibility, although confirmation in clinical subphenotypes is warranted. Mice with targeted deletion of Stat3 in T cells are resistant to experimental autoimmune encephalomyelitis, which is a multiple sclerosis (MS) model. Moreover, increased phosphorylated STAT3 was reported in T cells of patients evolving from clinically isolated syndrome to defined MS and in relapsing patients. These evidences led us to analyze the role of STAT3 in Crohn's disease (CD), ulcerative colitis (UC) and MS risk. Polymorphisms in the STAT3 region (rs3809758/rs744166/rs1026916/rs12948909) were genotyped and the inferred haplotypes were subsequently analyzed in 860 IBD and 1540 MS Spanish patients and 1720 ethnically matched controls. The haplotype conformed by the risk alleles of each polymorphism was significantly associated with both clinical phenotypes of IBD (CD: P=0.005, odds ratio 1.25, 95% confidence interval 1.06-1.46; and UC: P=0.002, odds ratio 1.19, 95% confidence interval 1.02-1.38). No evidence of association was detected for MS. The originally described association of IBD with STAT3 polymorphisms is corroborated for the two clinical phenotypes, CD and UC, in an independent population. A major role of this gene in MS seems unlikely.

Effect of BSN-MST1 locus on inflammatory bowel disease and multiple sclerosis susceptibility.

Genome-wide studies highlighted the effect in Crohn's disease (CD) and ulcerative colitis (UC) susceptibility of single nucleotide polymorphisms (SNPs) in 3p21, where BSN (bassoon), MST1 (macrophage stimulating-1) and MST1R (MST1 Receptor) genes map. MST1R expression was significantly downregulated in multiple sclerosis (MS) compared with control brains, resembling findings in the MS mouse model. We pursued to replicate the effect of this locus on inflammatory bowel diseases and to evaluate its contribution to MS risk. Polymorphisms rs9858542, rs2131109 and rs1128535 were analysed by TaqMan assays in Spanish patients (370 CD, 405 UC and 415 MS) and 800 ethnically matched controls. Allele frequencies of these SNPs were significantly different in CD patients compared with controls [rs9858542: P=0.001, Odds ratio (OR)=1.35; rs2131109: P=0.0005, OR=1.37; rs1128535: P=0.007, OR=0.78] and, specifically, in the ileal phenotype [rs9858542: P=0.0004, OR=1.47; rs2131109: P=0.00009, OR=1.52; rs1128535: P=0.02, OR=0.69]. No differences were detected between UC or MS patients and control individuals. The effect of this locus on CD predisposition was replicated, but no influence on UC or MS predisposition could be detected. This susceptibility locus seems to affect mainly to the ileal CD subphenotype, although this point awaits further corroboration in independent cohorts.

Biological markers in inflammatory bowel disease: practical consideration for clinicians.

The biomarkers are important in the Inflammatory Bowel Disease (IBD) to gain an objective measurement of disease activity and severity, as well as prognostic indicator and outcome of therapy. And they can be helpful to avoid invasive procedures. The ideal biomarker does not exist for IBD and it is likely that more than one biomarker will be needed. Biological markers potentially useful in IBD include acute-phase proteins, fecal markers, several antibodies and novel genetic determinants. The C-reactive protein (CRP) is the most studied and has been shown to be an objective marker of inflammation. CRP is a good marker of measuring disease activity in Crohn's disease (CD) and its levels can be used to guide therapy. The fecal markers (calprotectin and lactoferrin) may be helpful in differentiating patients with IBD from those with functional disorders and to predict clinical relapse. The panel of serologic markers (anti-Saccharomyces cerevisiae antibody, perinuclear anti-neutrophil cytoplasmic antibody, anti-OmpC and anti-I2 and antiglycan antibodies) for IBD can be used to stratify IBD patients into more homogeneous subgroups with respect to disease progression. Correlating serologic markers with genotypes and clinical phenotypes should enhance our understanding of the pathophysiology of IBD. The development of biomarkers in IBD will be very important in the future with the increasing utilization of novel methodological approaches like genomics and proteomics.

Association of the STAT4 gene with increased susceptibility for some immune-mediated diseases.

OBJECTIVE: The STAT4 gene encodes a transcription factor involved in the signaling pathways of several cytokines, including interleukin-12 (IL-12), the type I interferons, and IL-23. Recently, the association of a STAT4 haplotype marked by rs7574865 with rheumatoid arthritis (RA) and systemic lupus erythematosus was reported. The aim of this study was to investigate the role of this STAT4 tagging polymorphism in other immune-mediated diseases. METHODS: The study group comprised 2,776 consecutively recruited Spanish individuals: 575 with RA, 440 with multiple sclerosis, 700 with inflammatory bowel disease, 311 with type 1 diabetes, and 723 ethnically matched healthy control subjects. The STAT4 polymorphism rs7574865 was genotyped using a predesigned TaqMan assay. Allele and genotype frequencies in patients and control subjects were compared by chi-square test. RESULTS: The association of STAT4 polymorphism rs7574865 with RA was validated in patients of Spanish origin (for T versus G, P = 1.2 x 10(-6), odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.31-1.92), and the association was described for the first time in both clinical forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis (for T versus G, P = 0.006, OR 1.29, 95% CI 1.07-1.55), and in type 1 diabetes mellitus (for T versus G, P = 0.008, OR 1.36, 95% CI 1.07-1.71). In contrast, the genotypic distribution of this polymorphism showed no difference between patients with multiple sclerosis and healthy control subjects (for T versus G, P = 0.83, OR 1.02, 95% CI 0.82-1.28). CONCLUSION: The STAT4 gene is emerging as a novel common risk factor for diverse complex diseases.

Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis.

BACKGROUND: Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis. AIM: To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease. METHODS: Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid (n = 5073). RESULTS: A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n = 46, mesalazine (mesalamine) n = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3-9.3; P = 0.012) and Crohn's disease (CD) (OR 5.8 95% CI: 1.6-20.6; P = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP (n = 1477) (OR 5.2 95% CI: 1.8-14; P = 0.002). CONCLUSIONS: The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD.