Eosinophilic esophagitis (EoE) is a chronic non-IgE-mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal ...epithelium. Additionally, an RNAseq-based transcriptomic analysis in paired samples was also carried out.
Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE-specific mRNA panels (EDP and Eso-EoE panel).
A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA-proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil-related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome.
We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
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.
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.
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.
colon lymphoma (CL) is an uncommon variety of non-Hodgkin lymphoma (NHL) that represents less than 0.6% of all primary colonic neoplasms. Early diagnosis is challenging as clinical manifestations are ...non-specific. The goal of this review was to discuss our experience over the last few years regarding the clinical, endoscopic, histological, diagnostic, therapeutic and evolutionary characteristics of CL.
a retrospective, descriptive analysis of patients with CL diagnosed from 1994 to 2016 at the Hospital Universitario de La Princesa (Madrid, Spain) was performed.
a total of 29 patients with CL were identified, with a median age of 67 years; 18 were male (62%). The most common clinical manifestations included abdominal pain, constitutional syndrome, diarrhea and a palpable abdominal mass. Eight (27.6%) patients were asymptomatic and six (20.6%) initially presented with surgical complications. A colonoscopy was performed in 24 patients and the most common findings included diffuse infiltration and solid growth. The most common location was the descending and sigmoid colon. The most common histological subtypes included mantle B-cell NHL and diffuse large B-cell lymphoma. Chemotherapy was administered to 28 patients (96.5%), surgery was performed in six (20.7%) and combined chemo-radiotherapy was administered to one patient. Median survival was 156 months. Survival was 100.0% at one year and 55.0% at ten years.
due to the variable aspects of CL on endoscopy, a histological study of all colonic segments is required. Chemotherapy is the treatment of choice and emergency surgery followed by chemotherapy is required for complications. Primary factors associated with poorer survival include age above 65 years, relapsing disease and partial or nil responses.
Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of alterations that go from simple steatosis to steatohepatitis and cirrhosis. Type 2 diabetes mellitus (DM-2) and obesity are the ...principle factors associated to NAFLD. A 20-30 % prevalence in general population has been described. The survival of this type of patient is lower than the general population's, showing a higher incidence of hepatic and cardiovascular complications. The aetiopathogenesis is still unclear, but we know the intervention of different factors that produce fatty-acid accumulation in hepatic parenchyma, causing oxidative stress, oxygen-free radicals and the synthesis of an inflammatory cascade, that determine the progression of this disease from steatosis up to advanced fibrosis.The diagnostic gold-standard is still the liver biopsy, even though the development of newer non-invasive techniques, like serological and imaging (radiology), have opened a new field for research that allows bloodless testing of these patients and better study of the natural history of this disease. Nowadays, there is still no specific treatment for NAFLD. The development of healthy life habits and moderate exercise continue to be the pillars of treatment. Different pharmacological approaches have been studied and applied, such as the control of insulin resistance, lowering cholesterol levels, antioxidants, and other alternatives in experimental trials.
Background
Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings.
...Objective
To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE.
Methods
Cross‐sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset.
Results
Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7‐6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub‐score decreased from a median (IQR) of 2 (1‐2) to 0 (0‐1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively).
Conclusion
The diagnostic work‐up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
RESUMEN Introducción: el linfoma de colon (LC) es una variedad poco frecuente de los linfomas no Hodgkin (LNH) que representa menos del 0,6% de todas las neoplasias primarias del colon. Realizar un ...diagnóstico precoz es difícil debido a que las manifestaciones clínicas son inespecíficas. El objetivo de esta revisión fue presentar nuestra experiencia en los últimos años en cuanto a características clínicas, endoscópicas, histológicas, diagnóstico, tratamiento y evolución de los LC. Pacientes y métodos: se realizó un análisis retrospectivo y descriptivo de pacientes con LC diagnosticados desde 1994 hasta 2016 en el Hospital Universitario de la Princesa, Madrid. Resultados: se identificaron 29 pacientes con LC (mediana de edad 67 años, 18 hombres 62%). Las manifestaciones clínicas más comunes fueron dolor abdominal, síndrome constitucional, diarrea y masa abdominal palpable. Ocho (27,6%) pacientes se encontraban asintomáticos y seis (20,6%) debutaron con complicaciones quirúrgicas. En 24 pacientes se realizó colonoscopia y los hallazgos más frecuentes fueron infiltración difusa y tumoración. La localización más común fue el colon descendente y sigma. Los subtipos histológicos más frecuentes fueron: LNH de células B del manto y linfoma difuso de células grandes tipo B. Se trató con quimioterapia a 28 pacientes (96,5%), con cirugía a seis (20,7%) y uno recibió quimio y radioterapia. La mediana del tiempo de supervivencia fue de 156 meses. La supervivencia al año fue del 100,0% y a los diez años, del 55,0%. Conclusiones: debido al aspecto endoscópico variable del LC, es necesario el estudio histológico de todos los segmentos del colon. El tratamiento de elección es la quimioterapia y en casos de complicaciones es necesaria la cirugía urgente con quimioterapia posterior. Los principales factores asociados a peor supervivencia son la edad mayor de 65 años, la existencia de recidiva y las respuestas parciales o nulas.
Portal hypertensive polyps, a new entity? Martín Domínguez, Verónica; Díaz Méndez, Ariel; Santander, Cecilio ...
Revista española de enfermedades digestivas
108, Issue:
5
Journal Article
Peer reviewed
We present a case of a 62 year old woman with history of liver cirrhosis secondary to autoimmune hepatitis, with portal hypertension and coagulopathy. Gastroscopy findings were a polypoid and ...polylobed lesions in the gastric antrum. These were removed and the pathological study described hyperplastic polyps with edema, vascular congestion and hyperplasia of smooth muscle, corresponding to "portal hypertensive polyps" (PHP).
Hypercontractile esophagus (HE) is a primary hypercontractile disorder of the esophageal musculature not frequently seen in the general population. It is characterized by the presence of at least one ...contraction with a very high amplitude and duration (DCI > 8,000 mmHg/s/cm) in patients with esophageal symptoms. The aim of our study was to assess the clinical context and manometric characteristics in patients with HE using highresolution manometry (HRM).
We thoroughly reviewed the clinical features and manometric findings of a total of 720 patients with esophageal symptoms that were attended in the Department of Gastroenterology of our hospital between June 2011 and June 2013.
We found seven patients that met criteria for HE according to the Chicago Classification (2012). All of the patients were women (100%). Mean age was 64 years old. Most frequent symptoms were: Chest pain, dysphagia and heartburn.In one patient (14%) the HE was related to a gastroesophageal reflux disease (GERD) and gastroesophageal junction (GEJ) outflow obstruction. Three patients (43%) had more than one hypercontractile contraction in the study. Four patient (57%) hade multipeaked pattern (Jackhammer esophagus) and y two of them were synchronized with respiration. Two patients (29%) were diagnosed with hiatus hernias. Integrated relaxation pressure (IRP) was not higher in hypercontractile contractions than in normal contractions. Only one patient presented a slight alteration of the relaxation (IRP-4s = 15 mmHg) with normal peristalsis, GEJ outflow obstruction and not multipeakeded pattern. One patient presented pathological acid exposure (PAE) in 24-hours pH-metry.
HE is a rare disorder and HRM is essential for its correct diagnosis and characterization. The treatment of HE should achieve the disappearance or at least improvement of the patient´s symptoms and avoid unnecessary diagnostic testing.
This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in ...pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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