Summary
Background
Proton pump inhibitors (PPIs) are the most commonly used first‐line therapy for patients with eosinophilic oesophagitis (EoE). However, many aspects related to PPIs in EoE are ...still unknown.
Aims
To assess the effectiveness of PPI therapy for EoE in real‐world practice.
Methods
This cross‐sectional study collected data on PPI efficacy from the multicentre EoE CONNECT database. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom score; histological remission was defined as a peak eosinophil count below 15 eosinophils per high‐power field. Factors associated with effectiveness of PPI therapy were identified by binary logistic regression multivariate analyses.
Results
Overall, 630 patients (76 children) received PPI as initial therapy (n = 600) or after failure to respond to other therapies (n = 30). PPI therapy achieved eosinophil density below 15 eosinophils per high‐power field in 48.8% and a decreased symptom score in 71.0% of patients. More EoE patients with an inflammatory rather than stricturing phenotype accomplished clinico‐histological remission after PPI therapy (OR 3.7; 95% CI, 1.4‐9.5); as well as those who prolonged treatment length from 8 to 12 weeks (OR 2.7; 95% CI, 1.3‐5.3). After achieving clinico‐histological remission of EoE, PPI dosage reduction was effectively maintained in 69.9% of patients, but tended to be less effective among those with a stricturing phenotype.
Conclusions
Inflammatory EoE phenotype and treatment duration up to 12 weeks correlated with greater chance for inducing remission of EoE. A stricturing phenotype decreased response rates to PPI therapy both initially and in the long term.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
It is widely accepted that the relationship between phytophagous insects and their host plants influences insect diversification. However, studies addressed at documenting host‐associated genetic ...differentiation (HAD) and the mechanisms that drive reproductive isolation in host‐associated lineages (or host races) are still scarce relative to insect diversity. To uncover further evidence on the HAD processes in Lepidoptera, we investigated the genetic structure of the geranium argus butterfly (Eumedonia eumedon) and tested for isolation by ecology (IBE) vs. isolation by distance (IBD). Genomic data revealed an array of host races (three of them in the same mountain range, the Cantabrian Mountains, northern Iberia) at apparently distinct levels of reproductive isolation. We found a pattern of IBE mediated by HAD at both local and European scales, in which genetic differentiation between populations and individuals correlated significantly with the taxonomic relatedness of the host plants. IBD was significant only when considered at the wider European scale. We hypothesize that, locally, HAD between Geranium‐feeding populations was caused (at least partially) by allochrony, that is via adaptation of adult flight time to the flowering period of each host plant species. Nevertheless, the potential reproductive isolation between populations using Erodium and populations using Geranium cannot be explained by allochrony or IBD, and other mechanisms are expected to be at play.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Asturias is one of the communities with the highest rates of hospital admission for asthma in Spain. The environmental pollution or people lifestyle are some of the factors that contribute to the ...appearance or aggravation of this illness. The aim of this study was to show the spatial distribution of asthma admissions risks in the central municipalities of Asturias and to analyze the observed spatial patterns.
Urgent hospital admissions for asthma and status asthmaticus occurred between 2016 to 2018 on the public hospitals of the central area of Asturias were used. Population data were assigned in 5 age groups. Standardised admission ratio (SAR), smoothed relative risk (SRR) and posterior risk probability (PP) were calculated for each census tract (CT). A spatial trend analysis was run, a spatial autocorrelation index (Morans I) was calculated and a cluster and outlier analysis (Anselin Local Morans I) was finally performed in order to analyze spatial clusters.
The total number of hospital urgent asthma admissions during the study period was 2324, 1475 (63.46%) men and 849 (36.56%) women. The municipalities with the highest values of SRR and PP were located on the northwest area: Avilés, Gozón, Carreño, Corvera de Asturias, Castrillón and Illas. A high risk cluster was found for the municipalities of Avilés, Gozón y Corvera de Asturias.
The spatial analysis showed high risk of hospitalization for asthma on the municipalities of the northwest area of the study, which highlight the existence of spatial inequalities on the distribution of urgent hospital admissions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Little is known about the impact of Epstein‐Barr virus (EBV) infection on clinical outcomes in adults with inflammatory bowel disease (IBD).
Aim
To evaluate seroprevalence, ...seroconversion rate and complications associated with EBV infection in an adult IBD cohort attending a tertiary care hospital in Spain between 2006 and 2016.
Methods
EBV serological status was determined. In seronegative patients, the seroconversion rate was evaluated. The complications associated with primary and latent EBV infection are described.
Results
One thousand four hundred and eighty‐three patients over the age of 17 were included in the study (mean age at EBV serological status determination was 48.3). Overall seroprevalence of EBV was 97.4% (95% CI: 96.6%‐98.2%). The seroconversion rate was 29.7% (95% CI: 16.2‐45.9) after a mean of 47.5 months. There were no differences in seroconversion rates between patients 35 years or younger and patients older than 35 years. A 66‐year‐old man, on treatment with thiopurines, developed lymphoma and a hemophagocytic syndrome during a primary EBV infection. Overall, six patients (one with primary infection and five with prior EBV infection) developed lymphoma. In three of five patients with lymphoma and thiopurine use, EBV was associated to the development of lymphoma.
Conclusions
There is a small percentage of adults with IBD at risk of primary EBV infection. The risks of seroconversion and its complications remain through adulthood. Our results suggest that, when considering the use of thiopurines in IBD, the information on EBV serological status should be taken into account at any age.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Enhanced Recovery After Surgery (ERAS) programs have been shown to minimize the surgical inflammatory response in colorectal cancer. Our objective was to determine the association ...between an ERAS program for colorectal cancer surgery and oncologic recurrence and survival.
Methods
A before‐after intervention study was designed, including patients who underwent colorectal cancer surgery between November 2010 and March 2016. Cox hazard regression analysis was performed per cumulative year of follow‐up to evaluate the association between ERAS program exposure and overall survival. Subgroup analysis was performed by cancer stage (low I/II vs. advanced III/IV).
Results
In total, 646 patients were included, of which 339 were pre‐ERAS and 307 were ERAS. Our overall median compliance rate with ERAS interventions was 90% (interquartile range: 85%–95%). Overall survival rates were higher in the ERAS group within the first 2 years after surgery (89.2% vs. 83.2%; p = 0.04). Multivariable analysis revealed that the ERAS enrollment was associated with a significantly lower risk in 5‐year oncologic recurrence (adjusted hazard ratio aHR: 0.55; 95% confidence interval CI: 0.33–0.94; p = 0.03) and higher 3‐year survival (aHR: 0.55; 95% CI: 0.33–0.93; p = 0.03) among patients with advanced cancer stage compared to pre‐ERAS counterparts.
Conclusions
Patients with advanced colorectal cancer were less likely to suffer oncologic recurrence when managed during the ERAS period.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Background
Crohn's disease (CD) with upper gastrointestinal involvement (UGI) may have a more aggressive and refractory course. However, evidence on this phenotype of patients is scarce.
Aims
...To identify the clinical characteristics, therapeutic requirements and complications associated with UGI in CD
Methods
Nationwide study of cases (UGI, UGI plus ileal/ileocolonic involvement) paired with controls (ileal/ileocolonic involvement) from the ENEIDA registry. Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location or complex perianal fistula were excluded.
Results
Of 24 738 patients with CD in the ENEIDA registry, we identified 4058 with UGI (16% of the total CD cohort). Finally, 854 cases and 1708 controls were included. Cases were independently associated to extensive involvement (OR 2.7 2.2‐3.3, P < 0.0001), strictures OR 1.8 (1.5‐2.2), P < 0.0001, chronic iron deficiency anaemia OR 2.2 (1.3‐3.2), P < 0.001 and use of second‐line biologics OR 1.7 (1.1‐2.6), P = 0.021. The median stricture‐free time was 14 years (95% CI, 12‐16) for cases vs 21 years (95% CI, 19‐23) for controls (P < 0.0001). Cases with isolated UGI compared to UGI plus ileal/ileocolonic more frequently had localised disease OR 0.5(0.3‐0.8), P = 0.003 and underwent more endoscopic stricture dilations OR 2.7(1.3‐5.4), P = 0.006.
Conclusions
The largest cohort of patients with CD and UGI provides information on the natural history of this particular phenotype. Increased awareness of the clinical picture and therapeutic requirements of these patients could lead to earlier diagnosis and treatment of upper gastrointestinal lesions, preventing the structural damage frequently seen in these patients at diagnosis and during follow‐up.
Clinical features, therapeutic requirements and evolution of patients with Crohn's disease and upper gastrointestinal involvement (CROHNEX study)Study population: Cases: patients with Crohn'sdisease and upper gastrointestinal involvement (n = 854).Controls: patients with Crohn's disease and ileal/ilecocolonic involvement (n = 1708). Patients were identified from the ENEIDA registry (Spanish cohort of patients with inflammatory bowel disease). Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location and those with complex perianal fistula were excluded. Results:
Cases were more likely to have:
Extensive involvement (OR 2.7 2.2‐3.3, P < 0.0001).
Strictures (OR 1.8 1.5‐2.2, P < 0.0001).
Chronic iron deficiency anaemia (OR 2.2 1.3‐3.2, P < 0.001).
Use of second‐line biologics (OR 1.7 1.12.6, P = 0.021).
The median stricture‐free time was 14 years (95% CI, 12‐16) for cases vs 21 years (95% CI, 19‐23) for controls (P < 0.0001).
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Indole-3-acetic acid (IAA) is a widespread phytohormone among plant-associated bacteria, including the tumour-inducing pathogen of woody hosts, Pseudomonas savastanoi pv. savastanoi. A ...phylogenetic analysis of the iaaM/iaaH operon, which is involved in the biosynthesis of IAA, showed that one of the two operons encoded by Pseudomonas savastanoi pv. savastanoi NCPPB 3335, iaaM-1/iaaH-1, is horizontally transferred among bacteria belonging to the Pseudomonas syringae complex. We also show that biosynthesis of the phytohormone, virulence and full fitness of this olive pathogen depend only on the functionality of the iaaM-1/iaaH-1 operon. In contrast, the iaaM-2/iaaH-2 operon, which carries a 22-nt insertion in the iaaM-2 gene, does not contribute to the production of IAA by this bacterium. A residual amount of IAA was detected in the culture supernatants of a double mutant affected in both iaaM/iaaH operons, suggesting that a different pathway might also contribute to the total pool of the phytohormone produced by this pathogen. Additionally, we show that exogenously added IAA negatively and positively regulates the expression of genes related to the type III and type VI secretion systems, respectively. Together, these results suggest a role of IAA as a signalling molecule in this pathogen.
Effect of the endogenous and exogenous IAA in the pathogenesis of Pseudomonas savastanoi pv. savastanoi.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Chronic obstructive pulmonary disease (COPD) is one of the major causes of mortality worldwide and also reports high morbidity rates and the global burden COPD has continued to rise over the last ...several decades. The best-known COPD risk factors are tobacco smoke and air pollution, but genetics, age, sex, and socioeconomic status are additional factors. This study aimed to assess the spatial distribution of unscheduled COPD hospital admissions of men and women in the central area of Asturias during 2016-2018 and identify trends, spatial patterns, or clusters in the area.
Unscheduled COPD hospital admissions in the central area of Asturias were registered, geocoded, and grouped by census tracts (CTs), age, and sex. Standardized admission ratio, smoothed relative risk, posterior risk probability, and spatial clusters between relative risks throughout the study area were calculated and mapped.
The spatial distribution of COPD hospital admissions differed between men and women. For men, high-risk values were located primarily in the northwestern area of the study, whereas for women the cluster pattern was not as clear and high-risk CTs also reached central and southern areas. In both men and women, the north-northwest area included the majority of CTs with high-risk values.
The present study showed the existence of a spatial distribution pattern of unscheduled COPD hospital admissions in the central area of Asturias that was more pronounced for men than for women. This study could provide a starting point for generating knowledge about COPD epidemiology in Asturias.
Summary
The CbrAB two‐component system has been described as a high‐ranked element in the regulatory hierarchy of Pseudomonas putida that controls a variety of metabolic and behavioural traits ...required for adaptation to changing environmental conditions. We show that the response regulatory protein CbrB, an activator of σN‐dependent promoters, directly controls the expression of the small RNAs CrcZ and CrcY in P. putida. These two RNAs sequester the protein Crc, which is a translational repressor of multiple pathways linked to carbon catabolite repression. We characterized the in vivo and in vitro activation by CbrB at both crcZ and crcY promoters, and identified new DNA sequences where the protein binds. IHF, a co‐activator at many σN‐dependent promoters, also binds to the promoter regions and contributes to the activation of the sRNAs. CbrB phosphorylation is necessary at physiological activation conditions, but a higher dose of the protein allows in vitro transcriptional activation in its non‐phosphorylated form. We also show there is some production of CrcY coming from an upstream promoter independent of CbrB. Thus, CbrAB constitute a global signal transduction pathway integrated in a higher regulatory network that also controls catabolite repression through the expression of the two regulatory RNAs CrcZ and CrcY.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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