miR-24-3p regulates CDX2 during intestinalization of cardiac-type epithelium in a human model of Barrett's esophagus

Background: Cardiac-type epithelium has been proposed as the precursor of intestinal metaplasia in the development of Barrett's esophagus. Dysregulation of microRNAs (miRNAs) and their effects on CDX2 expression may contribute to intestinalization of cardiac-type epithelium. The aim of this study was to examine the possible effect of specific miRNAs on the regulation of CDX2 in a human model of Barrett's esophagus. Methods: Microdissection of cardiac-type glands was performed in biopsy samples from patients who underwent esophagectomy and developed cardiac-type epithelium in the remnant esophagus. OpenArray™ analysis was used to compare the miRNAs profiling of cardiac-type glands with negative or fully positive CDX2 expression. CDX2 was validated as a miR-24 messenger RNA target by the study of CDX2 expression upon transfection of miRNA mimics and inhibitors in esophageal adenocarcinoma cell lines. The CDX2/miR-24 regulation was finally validated by in situ miRNA/CDX2/MUC2 co-expression analysis in cardiac-type mucosa samples of Barrett's esophagus. Results: CDX2 positive glands were characterized by a unique miRNA profile with a significant downregulation of miR-24-3p, miR-30a-5p, miR-133a-3p, miR-520e-3p, miR-548a-1, miR-597-5p, miR-625-3p, miR-638, miR-1255b-1, and miR-1260a, as well as upregulation of miR-590-5p. miRNA-24-3p was identified as potential regulator of CDX2 gene expression in three databases and confirmed in esophageal adenocarcinoma cell lines. Furthermore, miR-24-3p expression showed a negative correlation with the expression of CDX2 in cardiac-type mucosa samples with different stages of mucosal intestinalization. Conclusion: These results showed that miRNA-24-3p regulates CDX2 expression, and the downregulation of miRNA-24-3p was associated with the acquisition of the intestinal phenotype in esophageal cardiac-type epithelium

Postoperative complications do not impact on recurrence and survival after curative resection of gastric cancer.

BACKGROUND: We assessed the impact of complications on recurrence and survival after curative gastric cancer resection. METHODS: Patients undergoing R0 resections between 1990 and 2009 were identified in a prospectively maintained database and were categorized by presence of any complication Clavien-Dindo (CD) ≥ II, sepsis or intra-abdominal sepsis. Cox regression analyses to relate complications and clinico-pathological variables to time to recurrence (TTR) and overall survival (OS) were performed. RESULTS: A total of 271 patients were included with a median follow-up of 149.9 months (range 140.1-159.9). complications CD ≥ II occurred in 162 (59.8%) patients, sepsis in 66 (22.5%), and intra-abdominal sepsis in 37 (13.6%). Recurrence developed in 88 (32.4%) patients. Independent predictors of short TTR were pTNM stage (IIIB-IIIC vs. IA-IIA) (hazard ratio [HR] = 37.55, 95% confidence interval [CI] 17.57-80.24; p < 0.001), D1 lymphadenectomy (HR = 3.14, 95% CI 1.94-5.07; p < 0.001), and male gender (HR = 1.65, 95% CI 1.06-2.57; p = 0.026). pTNM stage (IIIB-IIIC vs. IA-IIA, HR = 10.28, 95% CI 6.51-16.23; p < 0.001), male gender (HR = 1.64, 95% CI 1.17-2.31; p = 0.005), age (HR = 1.03, 95% CI 1.02-1.05; p < 0.001), and adjuvant therapy (HR = 0.55, 95% CI 0.37-0.83; p = 0.004) were identified as independent predictors of OS../nCONCLUSIONS: Evidence provided by this study does not support a negative impact of postoperative complications CD ≥ II, sepsis, and intra-abdominal sepsis on the oncologic outcome after curative gastric cancer resection

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective