Increasing Incidence of Pediatric Eosinophilic Esophagitis in the Southwest of Madrid, Spain.

Objectives: The incidence of eosinophilic esophagitis is unknown in our area. The aim of our study was to determine the incidence of eosinophilic esophagitis and its possible association with the most frequent absolute annual pollen counts. Methods: A descriptive retrospective multicenter observational study was designed to calculate the incidence of eosinophilic esophagitis in children aged under 15 years in the southwest region of Madrid, Spain in 2002-2013 (data were provided by the Statistics Institute of Madrid). We collected data on age, sex, clinical presentation, and date of endoscopic diagnosis. Relative risk (RR) was estimated (Stata v.11) using negative binomial regression models to assess the association between incidence and pollen counts (provided by Subiza Clinic). Results: The study population comprised 254 patients (192 male [75.6%], aged 0.5-14.99 years). The clinical presentation was esophageal impaction in 23.6%, dysphagia in 22%, gastroesophageal reflux–like symptoms in 44.9%, and other findings in 9.4%. The annual incidence from 2002 to 2013 per 100 000 children aged <15 years per year was, respectively, 0.81, 1.5, 0.37, 3.17, 3.07, 4.36, 6.87, 7.19, 8.38, 9.05, 9.14, and 9.68. The incidence of eosinophilic esophagitis increased by an average of 19% annually (RR, 1.19; 95%CI, 1.14-1.25;P1 (1.17 and 1.06, respectively) (P<.05). Conclusion: The incidence of diagnosis of pediatric eosinophilic esophagitis increased by an average of 19% annually. No significant association was found between incidence and pollen counts, except for a weak association with Platanus species.post-print359 K

Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections.

MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.We are grateful to members of the D.S. laboratory for discussions and critical reading of the manuscript. We thank the CNIC facilities and personnel for assistance. P.B. is funded by grant BES-2014-069933 (‘‘Ayudas para Contratos Predoctorales para la Formacio´ n de Doctores 2014’’) from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO). L.C. was a recipient of a European Respiratory Society Fellowship (RESPIRE2-2013- 3708). G.D. is supported by a European Molecular Biology Organization Long-term Fellowship (ALTF 379-2019). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sk1odowska-Curie grant agreement No. 892965. Work in the D.S. laboratory is funded by the CNIC; by the European Research Council (ERC-2016-consolidator grant 725091); by the European Commission (635122-PROCROP H2020); by Ministerio de Ciencia e Innovacio´ n (MICINN), Agencia Estatal de Investigacio´ n (AEI), and Fondo Europeo de Desarrollo Regional (FEDER) (SAF2016-79040-R); by AEI (PID2019-108157RB); by Comunidad de Madrid (B2017/BMD-3733 Immunothercan-CM); by FIS-Instituto de Salud Carlos III, MICINN and FEDER (RD16/0015/0018-REEM); by a collaboration agreement with Inmunotek; by Atresmedia (Constantes y Vitales prize); by Fundacio´ La Marato´ de TV3 (201723); and by Fondo Solidario Juntos (Banco Santander). The CNIC is supported by the Instituto de Salud Carlos III, the MICINN, and the Pro CNIC Foundation.S

A note on adjusting correlation matrices

A new algorithm for adjusting correlation matrices and for comparison with Finger's algorithm, which is used to compute Value-at-Risk in RiskMetrics for stress test scenarios. The solution proposed by the new methodology is always better than Finger's approach in the sense that it alters as little as possible those correlations that one would wish not to alter, but they change in order to obtain a consistent Finger correlation matrix.Correlation Matrix, Kuhn-TUCKER Conditions, Eigenvalue, Value-AT-RISK,