Viewpoints on Acid-Induced Inflammatory Mediators in Esophageal Mucosa

We have focused on understanding the onset of gastroesophageal reflux disease by examining the mucosal response to the presence of acid in the esophageal lumen. Upon exposure to HCl, inflammation of the esophagus begins with activation of the transient receptor potential channel vanilloid subfamily member-1 (TRPV1) in the mucosa, and production of IL-8, substance P (SP), calcitonin gene related peptide (CGRP) and platelet activating factor (PAF). Production of SP and CGRP, but not PAF, is abolished by the neural blocker tetrodotoxin suggesting that SP and CGRP are neurally released and that PAF arises from non neural pathways. Epithelial cells contain TRPV1 receptor mRNA and protein and respond to HCl and to the TRPV1 agonist capsaicin with production of PAF. PAF, SP and IL-8 act as chemokines, inducing migration of peripheral blood leukocytes. PAF and SP activate peripheral blood leukocytes inducing the production of H2O2. In circular muscle, PAF causes production of IL-6, and IL-6 causes production of additional H2O2, through activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Among these, NADPH oxidase 5 cDNA is significantly up-regulated by exposure to PAF; H2O2 content of esophageal and lower esophageal sphincter circular muscle is elevated in human esophagitis, causing dysfunction of esophageal circular muscle contraction and reduction in esophageal sphincter tone. Thus esophageal keratinocytes, that constitute the first barrier to the refluxate, may also serve as the initiating cell type in esophageal inflammation, secreting inflammatory mediators and pro-inflammatory cytokines and affecting leukocyte recruitment and activity

Electroesophagogram in gastroesophageal reflux disease with a new theory on the pathogenesis of its electric changes

BACKGROUND: In view of the disturbed esophageal peristaltic activity and abnormal esophageal motility in gastroesophageal reflux disease, (GERD), we investigated the hypothesis that these changes result from a disordered myoelectric activity of the esophagus. METHODS: The electric activity of the esophagus (electroesophagogram, EEG) was studied in 27 patients with GERD (16 men, 11 women, mean age 42.6 ± 5.2 years) and 10 healthy volunteers as controls (6 men, 4 women, mean age 41.4 ± 4.9 years). According to the Feussner scoring system, 7 patients had a mild (score 1), 10 a moderate (score 2) and 10 a severe (score 3) stage of the disease. One electrode was applied to the upper third and a second to the lower third of the esophagus, and the electric activity was recorded. The test was repeated after the upper electrode had been moved to the mid-esophagus. RESULTS: The EEG of the healthy volunteers showed slow waves and exhibited the same frequency, amplitude and conduction velocity from the 2 electrodes of the individual subject, regardless of their location in the upper, middle or lower esophagus. Action potentials occurred randomly. In GERD patients, score 1 exhibited electric waves' variables similar to those of the healthy volunteers. In score 2, the waves recorded irregular rhythm and lower variables than the controls. Score 3 showed a "silent" EEG without waves. CONCLUSION: The electric activity in GERD exhibited 3 different patterns depending on the stages of GERD. Score 1 exhibited a normal EEG which apparently denotes normal esophageal motility. Score 2 recorded irregular electric waves variables which are presumably indicative of decreased esophageal motility and reflux clearance. In score 3, a "silent" EEG was recorded with probably no acid clearance. It is postulated that the interstitial cells of Cajal which are the electric activity generators, are involved in the inflammatory process of GERD. Destruction of these cells appears to occur in grades that are in accordance with GERD scores. The EEG seems to have the potential to act as an investigative tool in the diagnosis of GERD stages

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]