Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

BACKGROUND: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

Complete Genome Sequences of Four Mycobacteriophages Involved in Directed Evolution against Undisputed Mycobacterium abscessus Clinical Strains.

Phage therapy is still in its infancy, but it is increasingly promising as a future alternative for treating antibiotic-resistant bacteria. To investigate the effect of phages on Mycobacterium abscessus complex (MABC), we isolated 113 environmental phages, grown them to high titres, and assayed them on MABC clinical strains through the spot test. Of all the phages, only 16 showed killing activity. Their activity was so temperate to MABC that they could not generate any plaque-forming units (PFUs). The Appelmans method of directed evolution was carried out to evolve these 16 phages into more lytic ones. After only 11 of 30 rounds of evolution, every single clinical strain in our collection, including those that were unsusceptible up to this point, could be lysed by at least one phage. The evolved phages were able to form PFUs on the clinical strains tested. Still, they are temperate at best and require further training. The genomes of one random parental phage and three random evolved phages from Round 13 were sequenced, revealing a diversity of clusters and genes of a variety of evolutionary origins, mostly of unknown function. These complete annotated genomes will be key for future molecular characterisations.

Effect of a topical silicone gel and a polyurethane dressing on the evolution of scars.

OBJECTIVE: To assess the effectiveness and safety of a topical silicone gel (BE + Gel reductor y reparador de cicatrices) and a polyurethane dressing (BE + Apósito reductor y reparador de cicatrices) on the evolution of scars of patients who were previously recruited in the emergency care unit while seeking wound care. METHOD: A single center, stratified observational, open label study was performed in the emergency care unit of Donostia Universitary Hospital (recruitment) and in the Biodonostia Health Research Institute (intervention). Scars located in unexposed body areas with the dressing, and scars located in exposed areas with either the gel or the dressing. Investigators assessed interventions at day 1 and on weeks 4, 8 and 12. Vancouver Scar Scale (VSS) and a photographical assessment were used to determine the scars evolution, and the subjective perception of the scar was evaluated by means of a questionnaire administered to the patients. RESULTS: Patients whose scars were treated with the silicone gel had an average initial VSS score of 5.4 ± 2.08. This value was reduced to 0.86 ± 1.17 after 90 days of treatment. Patients treated with the polyurethane dressing had an average initial VSS score of 5.8 ± 2.29. After 90 days of treatment, this average score was reduced to 0.33 ± 0.66. Positive evolution of scars was also supported by photographs and by a patient questionnaire. CONCLUSIONS: Both treatments appear to be safe and effective, objectively, and subjectively, in the context of scar evolution.

Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment.

Objectives: The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. Methods: PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients. Results: Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI. Conclusions: We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.

Swallowed topical corticosteroids for eosinophilic esophagitis: Utilization and real-world efficacy from the EoE CONNECT registry.

BACKGROUND: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses. OBJECTIVE: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice. METHODS: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations. RESULTS: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness. CONCLUSION: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.

Analysis of Phenotypic and Genotypic Susceptibility to Clarithromycin and Amikacin of Mycobacterium abscessus Complex Strains Isolated from Cystic Fibrosis Patients.

Mycobacterium abscessus complex infections are ever on the rise. To curb their increasing evolution, we performed an in-depth study of 43 clinical isolates of cystic fibrosis patients obtained from 2009 to 2020. We identified their subspecies, uncovered their genotypic resistance profiles, characterised their antibiotic-resistant genes, and assessed their phenotypic antibiotic susceptibilities. The phenotypic and genotypic methods showed total agreement in terms of resistance to clarithromycin and amikacin. Of the 43 clinical strains, 28 belonged to M. abscessus subsp. abscessus (65.1%), 13 to M. abscessus subsp. massiliense (30.2%), and 2 to M. abscessus subsp. bolletii (4.6%). The resistant rates for clarithromycin and amikacin, the two main drugs against M. abscessus complex pulmonary infections, were 64.2% and 14.2%, respectively. We found three strains of M. abscessus subsp. abscessus that showed heteroresistance in the rrl and rrs genes, and these strains also presented double-resistance since they were macrolide- and aminoglycoside-resistant. M. abscessus subsp. abscessus showed a high minimum inhibitory concentration (MIC) and a resistant percentage larger than or equal to 88% to cefoxitin, ciprofloxacin, moxifloxacin, doxycycline, imipenem, and trimethoprim-sulfamethoxazole. These results show a panorama of the high resistance of Mycobacterium abscessus complex to current drugs for cystic fibrosis patients. Thus, other treatment methods are urgently needed.

Arteriopatía periférica y alcoholismo / Peripheral arteriopathy and alcoholism

Se realizó un estudio analítico transversal a un grupo de 48 pacientes atendidos consecutivamente en el servicio de alcoholismo del Hospital Provincial Docente Psiquiátrico René Vallejo Ortiz de Camagüey desde febrero a mayo de 2005.La muestra estuvo constituida por 48 pacientes, 44 hombres (91.7 por ciento) y cuatro mujeres (8.3 por ciento).Se consideraron criterios de exclusión del estudio la diabetes mellitus, hipertensión arterial, enfermedad vascular periférica previa o cualquier enfermedad endocrina debidamente diagnosticada. Se le realizó prueba de Allen bajo control fotopletismográfico con compresiones alternas de las arterias radial y cubital. El tiempo de adicción fue entre cinco y 42 años. De los pacientes estudiados 33 consumieron bebidas alcohólicas artesanales (69,1 por ciento).En los miembros superiores 44 (91,7 por ciento), tenían afectación de las arterias del antebrazo, y los más afectados fueron los consumidores de bebidas artesanales. En el estudio Doppler de los miembros inferiores encontramos 18,7 por ciento de oclusión de la arteria tibial posterior y en el 12,5 por ciento oclusión combinada o alta. El 29,2 por ciento tenía rigidez vascular

Diferenças no metabolismo de adolescentes com doença gordurosa do fígado de causa não alcóolica, detectada por ultra-som / Metabolic differences in adolescents with non-alcoholic fatty liver disease detected by ultrasound

As adolescentes com doença gordurosa do fígado de causa não alcóolica (DGFCNA) mostraram um comportamento metabólico diferente dos meninos. Futuros estudos podem aprofundar o papel das diferenças metabólicas existentes entre os sexos na gênese da DGFCNA.

Indicadores de colaboración científica inter-centros en los países de América Latina / Indicators of inter-center scientific co-operation in Latin American countries

Se presentan indicadores de colaboración científica de 24 países de América Latina y el Caribe, obtenidos a través de sus publicaciones en revistas científicas de difusión internacional firmadas por autores de dos o más instituciones diferentes durante el periodo 1999-2002, empleando técnicas de análisis bibliométrico de coautoría. Para cada país se establecieron tres tipos de colaboración: nacional, regional e internacional, diferenciando las colaboraciones bi y trilaterales de las grandes redes formadas por 6 o más países. Se destacan las áreas científicas de mayor presencia en relación con el tipo de colaboración y tamaño de las redes. Los trabajos en colaboración representan el 65 por ciento del total de los publicados y aumentan cada año, correspondiendo la mayor proporción a la colaboración internacional, mientras que la regional es muy escasa. Los países más productivos en ciencia presentan una colaboración relativamente menor que los pequeños productores. Se analiza la evolución de los hábitos de colaboración internacional entre los periodos 1991-1995 y 1999-2002

Claudicación intermitente por arteriopatía oclusiva progresiva de los miembros inferiores (AOPMI). Resultados del tratamiento homeopático (parte 1) / Claudication intermittent arterial occlusive progressive of the lower limbs (AOPMI). Results of homeopathic treatment (part 1)

Se realizó un estudio observacional descriptivo con el objetivo de mostrar el resultados del tratamiento conservador en un grupo de pacientes con Insuficiencia Arterial Crónica (IAC) sin criterios de operabilidad, atendidos en el servicio de Angiología del Hospital Provincial"Manuel Ascunce D." y seguidos en la consulta de Homeopatía de la Clínica de la Universidad Médica "Carlos J. Finlay", en el período comprendido entre Noviembro del 2004 a Julio 2005.

Claudicación intermitente por arteriopatía oclusiva progresiva de los miembros inferiores (AOPMI). Resultados del tratamiento homeopático (parte 1) / Claudication intermittent arterial occlusive progressive of the lower limbs (AOPMI). Results of homeopathic treatment (part 1)

Se realizó un estudio observacional descriptivo con el objetivo de mostrar el resultados del tratamiento conservador en un grupo de pacientes con Insuficiencia Arterial Crónica (IAC) sin criterios de operabilidad, atendidos en el servicio de Angiología del Hospital Provincial"Manuel Ascunce D." y seguidos en la consulta de Homeopatía de la Clínica de la Universidad Médica "Carlos J. Finlay", en el período comprendido entre Noviembro del 2004 a Julio 2005.(AU)