Altered Regulation of mRNA and miRNA Expression in Epithelial and Stromal Tissue of Keratoconus Corneas

PurposeEvaluation of mRNA and microRNA (miRNA) expression in epithelium and stroma of patients with keratoconus.MethodsThe epithelium and stroma of eight corneas of eight patients with keratoconus and eight corneas of eight non-keratoconus healthy controls were studied separately. RNA was extracted, and mRNA and miRNA analyses were performed using microarrays. Differentially expressed mRNAs and miRNAs in epithelial and stromal keratoconus samples compared to healthy controls were identified. Selected genes and miRNAs were further validated using RT-qPCR.ResultsWe discovered 170 epithelial and 1498 stromal deregulated protein-coding mRNAs in KC samples. In addition, in epithelial samples 180 miRNAs and in stromal samples 379 miRNAs were significantly deregulated more than twofold compared to controls. Pathway analysis revealed enrichment of metabolic and axon guidance pathways for epithelial cells and enrichment of metabolic, mitogen-activated protein kinase (MAPK), and focal adhesion pathways for stromal cells.ConclusionsThis study demonstrates significant differences in the expression and regulation of mRNAs and miRNAs in the epithelium and stroma of Patients with KC. Also, in addition to the well-known target candidates, we were able to identify further genes and miRNAs that may be associated with keratoconus. Signaling pathways influencing metabolic changes and cell contacts are affected in epithelial and stromal cells of patients with keratoconus.     

TP53 mutation and survival in aggressive B cell lymphoma

TP53 is mutated in 20–25% of aggressive B‐cell lymphoma (B‐NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B‐NHL, we investigated TP53 gene mutations within the RICOVER‐60 trial. Of 1,222 elderly patients (aged 61–80 years) enrolled in the study and randomized to six or eight cycles of CHOP‐14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index‐Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B‐symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event‐free (EFS), progression‐free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI‐factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed.     

Polycystic ovarian syndrome: an evidence-based approach to evaluation and management of diabetes and cardiovascular risks for today's clinician

This review systematically addresses the evidence confirming polycystic ovary syndrome (PCOS) as a cardiovascular health threat. Literature in this area is void of long-term prospective studies to adequately evaluate outcome, but there is important evidence using surrogate markers for future development of and presence of cardiovascular disease and diabetes in women with PCOS. In addition, this article reviews the evidence regarding evaluation and management of cardiovascular risk factors in the population of women with PCOS. We seek to review the literature to determine when or if recommendations for management of women with PCOS should deviate from guidelines for the population at large.     

Krebsbekämpfung,allgemeine und operative herapie

Ohne Zusammenfassung     

Value and consequences of routine intraoperative cholangiography during cholecystectomy

Since the introduction of laparoscopic cholecystectomy (LC), an increase in accidental common bile duct (CBD) injuries of up to 1.2-1.6% has been reported. In the present prospective study of 1,710 patients undergoing cholecystectomy (1,241 LC procedures and 469 open cholecystectomies [OC]), we tested the predicative value of routine intraoperative cholangiography (IOC). The IOC was feasible in 92.4% of the cases in the LC group and in 83% of cases in the OC group and presented a complete depiction of the extrahepatic bile system in 98.3%. Anatomic variations of the bile duct system, which influenced the operative management, were found in 13.2% of cases (13.4% LC versus 12.8% OC). In 2.5% of the patients, preoperatively undetected CBD stones were also found. Method-specific complications did not occur in any of the patients. Additionally, in a controlled subgroup analysis of 163 patients, we evaluated preoperative intravenous cholangiography (IVC) and IOC. Intravenous cholangiography showed only 72.4% of the operation-relevant anatomic variations (vs. 100% by IOC); in 6.1% of the cases, there were reactions to the dye (vs. none in IOC), and in only 28.6% of the patients, CBD stones were detected (vs. 71.4% IOC). There were four bile duct injuries (0.29%) during LC and two (0.4%) during OC. All injuries were detected intraoperatively and fixed in the same setting without postoperative complications. In conclusion, we recommend the use of routine IOC during cholecystectomy. By this technique, anatomic variations of the bile duct system will be visualized and therefore accidental injuries will be avoided.