Caracterización fenotípica y bases moleculares de los pacientes con eosinofilia esofágica respondedora a fármacos inhibidores de la bomba de protones

La esofagitis eosinofílica (EEo) es una enfermedad esofágica alérgica de creciente incidencia. Afecta a niños y adultos jóvenes, principalmente hombres (razón 3:1), encontrándose enfermedades atópicas subyacentes (asma y/o rinoconjuntivitis estacional, dermatitis atópica, alergia alimentaria) en el 80%-90% de los casos. Los primeros criterios diagnósticos para la EEo, publicados en el año 2007, se basaban en la conjunción de tres criterios mayores: datos clínicos (síntomas de disfunción esofágica), datos histológicos (infiltración epitelial esofágica por eosinófilos > 15 eos/cga) y ausencia de respuesta a inhibidores de la bomba de protones (IBP) o pHmetría esofágica normal. Sin embargo, la gran mayoría de los pacientes con síntomas de disfunción esofágica e inflamación esofágica eosinofílica eran diagnosticados de EEo sin confirmación de la respuesta a IBP o realización de pHmetría. Por tanto, existía un riesgo evidente de infraestimación de la respuesta a IBP en estos pacientes. Este incumplimiento de las premisas diagnósticas de consenso no sólo impedía cuantificar el porcentaje de pacientes que eran respondedores a IBP, sino que hacía que pacientes potencialmente respondedores a IBP recibieran otros tratamientos específicos para la EEo (corticoides tópicos, dietas de eliminación), los cuales, comparados con los IBP, provocan mayor cantidad de efectos adversos o podían limitar notablemente la calidad de vida de los pacientes. Inmediatamente después de la publicación de las primeras recomendaciones diagnósticas en el año 2007, se comunicaron pequeñas series retrospectivas de pacientes pediátricos con eosinofilia esofágica sintomática que alcanzaron remisión completa con IBP, tanto con pHmetría normal como patológica. Por tanto, estas series iniciales comenzaron cuestionar el papel diagnóstico de la pHmetría y su capacidad para predecir la respuesta a IBP..

Eosinophilic esophagitis: What can we learn from Crohn’s disease?

Eosinophilic esophagitis (EoE) is an emerging esophageal inflammatory disorder affecting children and young adults. As a relatively new disease, EoE is still burdened by frequent diagnostic and therapeutic pitfalls in clinical practice. This manuscript posits a number of similarities with Crohn’s disease, which may help optimize EoE patient management. Commonalities include epidemiologic trends (Westernized diseases, rising incidence, early-life risk factors), diagnostic considerations (symptoms are poor predictors of disease activity, difficulties in disease activity assessment) and therapeutic issues (similar natural history and therapeutic goals, induction and maintenance phases, combination of drug and endoscopic treatment, potential drug interchangeability, long-term unsolved issues). Physicians devoted to EoE should learn from the extraordinary achievements fulfilled in Crohn’s disease: increased disease awareness, multidisciplinary specialized clinics, structured childhood and transition programs, and an ongoing roadmap for personalized treatments, including genetic susceptibility, risk factors for progression, genotype-phenotype correlation, drug monitoring and microbial data

Relationship between the Duration of the Second Stage of Labour and Neonatal Morbidity

(1) Background: To assess the relationship between the duration of the second stage of labour and the neonatal morbidity risk; (2) Methods: An observational, analytical, retrospective cohort study was performed at the “Mancha-Centro” Hospital (Spain) during the 2013–2016 period. Data were collected from 3863 women who gave a vaginal birth. The studied neonatal morbidity variables were umbilical cord arterial pH, 5-min Apgar score, need for advanced neonatal resuscitation, and a composite neonatal morbidity variable on which the multivariate analysis was done. A univariate analysis was used for the potential risk factors and a multivariate analysis with binary logistic regression to control for possible confounding factors; (3) Results: The univariate analysis showed a statistically significant relationship between the duration of the second stage of labour and a high risk of advanced neonatal resuscitation and composite neonatal morbidity in multiparous women. However, after performing the multivariate analysis for the variable “composite neonatal morbidity”, we observed no relationship with the duration of the second stage of labour in either nulliparous or multiparous women; (4) Conclusions: The duration of the second stage of labour was not related to an increased risk of neonatal morbidity in our study population

The role of statins on helicobacter pylori eradication : Results from the european registry on the management of h. pylori (hp-eureg)

Funding: This project was promoted and funded by the European Helicobacter and Microbiota Study Group (EHMSG), the Spanish Association of Gastroenterology (AEG), and the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd).Peer reviewedPublisher PD

European Registry on Helicobacter pylori Management: Effectiveness of First and Second-Line Treatment in Spain

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. "Optimized" H. pylori therapies achieve over 90% success in Spain

Artificial intelligence within the interplay between natural and artificial computation:Advances in data science, trends and applications

Artificial intelligence and all its supporting tools, e.g. machine and deep learning in computational intelligence-based systems, are rebuilding our society (economy, education, life-style, etc.) and promising a new era for the social welfare state. In this paper we summarize recent advances in data science and artificial intelligence within the interplay between natural and artificial computation. A review of recent works published in the latter field and the state the art are summarized in a comprehensive and self-contained way to provide a baseline framework for the international community in artificial intelligence. Moreover, this paper aims to provide a complete analysis and some relevant discussions of the current trends and insights within several theoretical and application fields covered in the essay, from theoretical models in artificial intelligence and machine learning to the most prospective applications in robotics, neuroscience, brain computer interfaces, medicine and society, in general.BMS - Pfizer(U01 AG024904). Spanish Ministry of Science, projects: TIN2017-85827-P, RTI2018-098913-B-I00, PSI2015-65848-R, PGC2018-098813-B-C31, PGC2018-098813-B-C32, RTI2018-101114-B-I, TIN2017-90135-R, RTI2018-098743-B-I00 and RTI2018-094645-B-I00; the FPU program (FPU15/06512, FPU17/04154) and Juan de la Cierva (FJCI-2017–33022). Autonomous Government of Andalusia (Spain) projects: UMA18-FEDERJA-084. Consellería de Cultura, Educación e Ordenación Universitaria of Galicia: ED431C2017/12, accreditation 2016–2019, ED431G/08, ED431C2018/29, Comunidad de Madrid, Y2018/EMT-5062 and grant ED431F2018/02. PPMI – a public – private partnership – is funded by The Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbott, Biogen Idec, F. Hoffman-La Roche Ltd., GE Healthcare, Genentech and Pfizer Inc

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio