Subcutaneous implant with etonogestrel (Implanon®) for catamenial exacerbations in a patient with cystic fibrosis: a case report.

BACKGROUND: Cystic Fibrosis (CF) is a genetic disease with equal prevalence across sexes. However, women present worse lung function with faster function decline, earlier onset of bacterial colonization, more frequent pulmonary exacerbations (PE), greater bronchial hyper-responsiveness, and higher mortality rates after puberty than men. The etiology of this gender disparity remains elusive but female hormones have been implicated in several studies. CASE PRESENTATION: A 20-year-old female with CF with severe recurrent PE, always related to the menstrual cycle since menarche, combined with lung function decline requiring multiple courses of intravenous antibiotics. We report the cessation of PE and recovery of pulmonary function following the insertion of a subcutaneous implant with 68 mg of etonogestrel (Implanon®, Organon Española S.A. Laboratories, Madrid, Spain). CONCLUSION: Our case report supports the key role of female hormones in the development of PE and in the decline of lung function in a woman with CF. When appropriate, hormonal manipulation through contraceptive methods should be considered as potential treatment.

Emergence of a mutL mutation causing multilocus sequence typing-pulsed-field gel electrophoresis discrepancy among Pseudomonas aeruginosa isolates from a cystic fibrosis patient.

A multilocus sequence type (MLST) shift (from ST242 to ST996) was detected in Pseudomonas aeruginosa isolates with a uniform pulsed-field gel electrophoresis (PFGE) pattern obtained from a chronically colonized patient. MLST mutational change involved the mutL gene with the consequent emergence of a hypermutable phenotype. This observation challenges the required neutrality of mutL as an appropriate marker in MLST and alerts researchers to the limitations of MLST-only-based population studies in chronic infections under constant antibiotic selective pressure.

Long-term docosahexaenoic acid (DHA) supplementation in cystic fibrosis patients: a randomized, multi-center, double-blind, placebo-controlled trial.

BACKGROUND: Cystic fibrosis (CF) patients have an alteration in fatty acid (FA) metabolism, associated with increased omega-6 and low omega-3 FA. Previous studies on supplementation with omega-3 FA in CF had contradictory results, and to date there is no evidence to recommend routine use of omega-3 supplements in CF patients. We hypothesized that long-term supplementation with docosahexaenoic acid (DHA) will have beneficial effects in these patients, by reducing pulmonary, systemic and intestinal inflammation. METHODS: This was a randomized, double-blind, parallel, placebo-controlled trial. CF patients (age >2 months) were randomized to receive a seaweed DHA oil solution (50 mg/Kg/day) or matching placebo for 48 weeks. Primary outcomes were pulmonary (interleukin [IL]-8), systemic (IL-8) and intestinal (calprotectin) inflammatory biomarkers. Secondary outcomes included other pulmonary (IL-1ß, IL-6, neutrophil elastase, lactate and calprotectin) and systemic (serum-IL-1ß, IL-6) inflammatory biomarkers, as well as clinical outcomes (FEV1, pulmonary exacerbations, antibiotic use, nutritional status and quality of life). RESULTS: Ninety six CF patients, 44 female, age 14.6±11.9 years (48 DHA and 48 placebo) were included. At trial completion, there were no differences in all primary outcomes [serum-IL-8 (p=0.909), respiratory-IL-8 (p=0.384) or fecal calprotectin (p=0.948)], all secondary inflammatory biomarkers, or in any of the clinical outcomes evaluated. There were few adverse events, with similar incidence in both study groups. CONCLUSION: In this study, long-term DHA supplementation in CF patients was safe, but did not offer any benefit on inflammatory biomarkers, or in clinical outcomes compared with placebo. (NCT01783613).

[Aspergillus fumigatus and Candida albicans in cystic fibrosis: clinical significance and specific immune response involving serum immunoglobulins G, A, and M]. / Aspergillus fumigatus y Candida albicans en la fibrosis quística: significado clínico e inmunorrespuestas séricas específicas de inmunoglobulinas G, A y M.

OBJECTIVE: The aim of this study was to analyze the clinical significance of Aspergillus fumigatus and Candida albicans in respiratory secretions from patients with cystic fibrosis and to assess the immune response to these fungi in serum. PATIENTS AND METHODS: The study included 66 patients with cystic fibrosis (34 men; mean age, 16.2 years). Sera from 15 healthy individuals were used as controls. RESULTS: The serum concentrations of immunoglobulin (Ig) G, IgA, and IgM against A fumigatus and C albicans were higher in patients than in the control group. There was no correlation between the presence of A fumigatus in respiratory secretions and the immune response to the fungus measured in serum. In contrast, the presence of C albicans in respiratory secretions was correlated with the immune response to that fungus. The likelihood of obtaining A fumigatus cultures from respiratory secretions increased with age. The presence of these fungi in respiratory samples was not a risk factor for greater respiratory impairment. CONCLUSIONS: In response to increased colonization of the lower respiratory tract by A fumigatus and C albicans, patients with cystic fibrosis have elevated serum levels of IgG, IgA, and IgM against those fungi. In patients with cystic fibrosis, culture of sputum and oropharyngeal secretions is adequate for the assessment of lower respiratory tract colonization by C albicans but not A fumigatus. Fungal colonization of the lower respiratory tract is not a risk factor for greater respiratory impairment in patients with cystic fibrosis.

Individual Patterns of Complexity in Cystic Fibrosis Lung Microbiota, Including Predator Bacteria, over a 1-Year Period.

Cystic fibrosis (CF) lung microbiota composition has recently been redefined by the application of next-generation sequencing (NGS) tools, identifying, among others, previously undescribed anaerobic and uncultivable bacteria. In the present study, we monitored the fluctuations of this ecosystem in 15 CF patients during a 1-year follow-up period, describing for the first time, as far as we know, the presence of predator bacteria in the CF lung microbiome. In addition, a new computational model was developed to ascertain the hypothetical ecological repercussions of a prey-predator interaction in CF lung microbial communities. Fifteen adult CF patients, stratified according to their pulmonary function into mild (n = 5), moderate (n = 9), and severe (n = 1) disease, were recruited at the CF unit of the Ramón y Cajal University Hospital (Madrid, Spain). Each patient contributed three or four induced sputum samples during a 1-year follow-up period. Lung microbiota composition was determined by both cultivation and NGS techniques and was compared with the patients' clinical variables. Results revealed a particular microbiota composition for each patient that was maintained during the study period, although some fluctuations were detected without any clinical correlation. For the first time, Bdellovibrio and Vampirovibrio predator bacteria were shown in CF lung microbiota and reduced-genome bacterial parasites of the phylum Parcubacteria were also consistently detected. The newly designed computational model allows us to hypothesize that inoculation of predators into the pulmonary microbiome might contribute to the control of chronic colonization by CF pathogens in early colonization stages.IMPORTANCE The application of NGS to sequential samples of CF patients demonstrated the complexity of the organisms present in the lung (156 species) and the constancy of basic individual colonization patterns, although some differences between samples from the same patient were observed, probably related to sampling bias. Bdellovibrio and Vampirovibrio predator bacteria were found for the first time by NGS as part of the CF lung microbiota, although their ecological significance needs to be clarified. The newly designed computational model allows us to hypothesize that inoculation of predators into the lung microbiome can eradicate CF pathogens in early stages of the process. Our data strongly suggest that lower respiratory microbiome fluctuations are not necessarily related to the patient's clinical status.

Innovative approach for self-management and social welfare of children with cystic fibrosis in Europe: development, validation and implementation of an mHealth tool (MyCyFAPP).

INTRODUCTION: For the optimal management of children with cystic fibrosis, there are currently no efficient tools for the precise adjustment of pancreatic enzyme replacement therapy, either for advice on appropriate dietary intake or for achieving an optimal nutrition status. Therefore, we aim to develop a mobile application that ensures a successful nutritional therapy in children with cystic fibrosis. METHODS AND ANALYSIS: A multidisciplinary team of 12 partners coordinate their efforts in 9 work packages that cover the entire so-called 'from laboratory to market' approach by means of an original and innovative co-design process. A cohort of 200 patients with cystic fibrosis aged 1-17 years are enrolled. We will develop an innovative, clinically tested mobile health application for patients and health professionals involved in cystic fibrosis management. The mobile application integrates the research knowledge and innovative tools for maximising self-management with the aim of leading to a better nutritional status, quality of life and disease prognosis. Bringing together different and complementary areas of knowledge is fundamental for tackling complex challenges in disease treatment, such as optimal nutrition and pancreatic enzyme replacement therapy in cystic fibrosis. Patients are expected to benefit the most from the outcomes of this innovative project. ETHICS AND DISSEMINATION: The project is approved by the Ethics Committee of the coordinating organisation, Hospital Universitari La Fe (Ref: 2014/0484). Scientific findings will be disseminated via journals and conferences addressed to clinicians, food scientists, information and communications technology experts and patients. The specific dissemination working group within the project will address the wide audience communication through the website (http://www.mycyfapp.eu), the social networks and the newsletter.

Antibiotic resistance and population structure of cystic fibrosis Pseudomonas aeruginosa isolates from a Spanish multi-centre study.

The first Spanish multi-centre study on the microbiology of cystic fibrosis (CF) was conducted from 2013 to 2014. The study involved 24 CF units from 17 hospitals, and recruited 341 patients. The aim of this study was to characterise Pseudomonas aeruginosa isolates, 79 of which were recovered from 75 (22%) patients. The study determined the population structure, antibiotic susceptibility profile and genetic background of the strains. Fifty-five percent of the isolates were multi-drug-resistant, and 16% were extensively-drug-resistant. Defective mutS and mutL genes were observed in mutator isolates (15.2%). Considerable genetic diversity was observed by pulsed-field gel electrophoresis (70 patterns) and multi-locus sequence typing (72 sequence types). International epidemic clones were not detected. Fifty-one new and 14 previously described array tube (AT) genotypes were detected by AT technology. This study found a genetically unrelated and highly diverse CF P. aeruginosa population in Spain, not represented by the epidemic clones widely distributed across Europe, with multiple combinations of virulence factors and high antimicrobial resistance rates (except for colistin).

Improvement of digestive health and reduction in proteobacterial populations in the gut microbiota of cystic fibrosis patients using a Lactobacillus reuteri probiotic preparation: a double blind prospective study.

BACKGROUND: Although scientific knowledge about the benefits of probiotic use in cystis fibrosis (CF) is scarce, their expectative is promising. The aim of this work was to analyze the effect of a Lactobacillus reuteri probiotic preparation versus placebo in CF patients. METHODS: A prospective, double blind, crossover and with placebo study was carried out in 30 CF patients from two Spanish hospitals. Patients were randomized in Group A (6 months of probiotic followed by 6 months of placebo) and Group B (6 months of placebo followed by 6 months of probiotic). GIQLI (gastrointestinal) and SF-12 (general) health tests were performed after probiotic and placebo intakes. Fat absorption coefficient, calprotectin, and inflammatory interleukin quantification were determined in fecal samples. Total fecal DNA was obtained and metagenomic 454-pyrosequencing was applied to analyze the microbiome composition. STATA v12 MP software was used for statistical analyses. RESULTS: Statistically significant improvement in the gastrointestinal health and decrease of the calprotectin levels were demonstrated in patients after probiotic exposure, in comparison with placebo. All CF subjects reported good tolerance to L. reuteri without secondary effects. Metagenomic analysis showed an important dysbiosis in CF gut microbiota associated with a high concentration of Proteobacteria. Probiotic intake was followed by a reduction in the total bacterial density, mostly due to a considerable reduction in the γ-Proteobacteria phylum; and an important increase of the microbial diversity with a higher representation of Firmicutes. CONCLUSIONS: Probiotics might ameliorate the dysbiosis of CF gut microbiota, characterized by a high density of Proteobacterial organisms. L. reuteri significantly decrease intestinal inflammation and increase digestive comfort.

Unorthodox long-term aerosolized ampicillin use for methicillin-susceptible Staphylococcus aureus lung infection in a cystic fibrosis patient.

Staphylococcus aureus is a significant cause of pulmonary colonization in cystic fibrosis (CF) patients. The optimal strategy of therapy in chronically infected patients with this pathogen is not yet established. We report a successful long-term aerosolized ampicillin treatment of a 14-year-old girl with chronic symptomatic S. aureus lung infection.

Enfermedad Celíaca: diagnostico y nuevas formas de presentación / Celiac disease: diagnosis and new forms of presentation

Es posible que la Enfermedad Celíaca (EC) en algunos países esté aún subdiagnosticada, y Colombia no es la excepción. Hay diversas formas de presentación. en cualquiera de los casos, es necesario las pruebas de anticuerpos y la toma de biopsia intestinal para su diagnóstico. El diagnóstico de EC, según lo recomendado desde el año 1989 por ESPGHAN, con la toma de unabiopsia intestinal ante la presencia de síntomas, para luego del retiro del gluten esperar reversiónde la sintomatología junto con seronegatividad de los anticuerpos.

Celiac Disease (CD) in some countries is still underdiagnosed, and Colombia is no exception. There are different forms. In either case, it is necessary antibody testing and intestinal biopsy for diagnosis. The diagnosis of CD, is checked as recommended since 1989 by ESPGHAN, with the capture of an intestinal biopsy in the presence of symptoms, then removal of gluten expected reversal of symptoms with seronegative for antibodies.

Enfermedad inflamatoria intestinal: situación actual de las alternativas terapéuticas / Inflammatory bowel diseases: an update of current treatment alternatives

La enfermedad inflamatoria intestinal (EII) se caracteriza por tener un curso clínico impredecible alternando recaídas con períodos de inactividad, una respuesta muy variable a la terapia y la constante aparición de complicaciones diversas. Su manejo es particularmente complejo en el niño y si bien existen diferentes guías y recomendaciones disponibles, los ensayos clínicos realizados en este grupo de edad son limitados y la evidencia científica es contradictoria, por lo cual aún no se cuenta con un consenso terapéutico aceptado internacionalmente. Los objetivos generales del tratamiento consisten en inducir y mantener la enfermedad en remisión el mayor tiempo posible, conseguir un adecuado crecimiento y  prevenir  posibles complicaciones. En años recientes, la aparición de nuevas alternativas terapéuticas ha permitido darle un enfoque más integral al manejo de estos pacientes tomando también en consideración el estado nutricional y psicológico además de su calidad de vida. Estos tratamientos, si bien consiguen en muchos casos controlar la inflamación intestinal curando las lesiones de la mucosa, no están exentos de efectos secundarios a corto y largo plazo, motivo por el cual es imprescindible tomar en cuenta las características de cada paciente para poder ofrecer un tratamiento individualizado que sea capaz de modificar la evolución natural de la enfermedad.

Inflammatory bowel diseases (IBD) are characterized for having an unpredictable clinical course with periods of inactivity alternating with relapses, a very variable response to treatment and the constant threat of diverse complications. Management of IBD in children may be of particular complexity, added to the fact that published clinical trials are limited, and scientific evidence  seems contradictory, explain in part why to current date there is no international consensus regarding treatment in this age group. A suitable therapy should aim at inducing and maintaining remission for as long as possible, encourage adequate growth and preventing potential complications from appearing. In more recent years, development of new therapeutic agents has allowed a more integrative approach which takes in consideration other aspects of the disease such as nutritional status, psychological welfare and general quality of life. One must also keep in mind that none of these therapeutic resources is exempt of side effects on short and long term basis, consequently, it is imperative to be thoughtful of individual features in order to make accurate clinical decisions and offer a tailored management plan which should be able to modify the disease evolution.

Experiencia endoscópica en una Unidad de Gastroenterología Pediátrica

Se analizan los resultados de las exploraciones endoscópicas realizadas en un período de 7 años en la Unidad de Gastroenterología del servicio de Pediatría del Hospital Ramón Cajal, Madrid-España. Hernia hiatal, esofagitis péptica