Limitations in Prehospital Communication Between Trauma Helicopter,Ambulance Services,and Dispatch Centers

Background

Prehospital communication with Emergency Medical Services (EMS) is carried out in hectic situations. Proper communication among all medical personal is required to enhance collaboration, to provide the best care and enable shared situational awareness.

Focal aberrations indicate EYA2 and hsa‐miR‐375 as oncogene and tumor suppressor in cervical carcinogenesis

Cervical cancer results from persistent infection with high‐risk human papillomavirus (hrHPV). Common genetic aberrations in cervical (pre)cancers encompass large genomic regions with numerous genes, hampering identification of driver genes. This study aimed to identify genes functionally involved in HPV‐mediated transformation by analysis of focal aberrations (<3 Mb) in high‐grade cervical intraepithelial neoplasia (hgCIN). Focal chromosomal aberrations were determined in high‐resolution array comparative genomic hybridization data of 60 hgCIN. Genes located within focal aberrations were validated using 2 external gene expression datasets or qRT‐PCR. Functional roles of candidate genes EYA2 (20q13) and hsa‐miR‐375 (2q35) were studied by siRNA‐mediated knock‐down and overexpression, respectively, in hrHPV‐containing cell lines. We identified 74 focal aberrations encoding 305 genes. Concurrent altered expression in hgCIN and/or cervical carcinomas compared with normal cervical samples was shown for ATP13A3, HES1, OPA1, HRASLS, EYA2, ZMYND8, APOBEC2, and NCR2. Gene silencing of EYA2 significantly reduced viability, migratory capacity, and anchorage‐independent growth of HPV16‐transformed keratinocytes. For hsa‐miR‐375, a direct correlation between a (focal) loss and significantly reduced expression was found. Downregulation of hsa‐miR‐375 expression was confirmed in an independent series of cervical tissues. Ectopic expression of hsa‐miR‐375 in 2 cervical carcinoma cell lines reduced cellular viability. Our data provide a proof of concept that chromosomal aberrations are actively contributing to HPV‐induced carcinogenesis and identify EYA2 and hsa‐miR‐375 as oncogene and tumor suppressor gene, respectively. © 2012 Wiley Periodicals, Inc.     

Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3A(mutant) AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3A(wild-type) AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3A(mutant) AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3A(wild-type) AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.     

Diagnostic challenges of respiratory adverse events during everolimus treatment

Everolimus has important clinical activity in various malignancies, but its use can be complicated by respiratory adverse events. Important everolimus-induced respiratory adverse events are interstitial lung disease (ILD) and infections, either typical or opportunistic. Furthermore, non-everolimus-related respiratory events can occur. Due to the non-specific presentation of most of these respiratory disorders, it is often not possible to differentiate between these causes on clinical and radiological grounds only. Considering the potential fatal nature of opportunistic infections, these are especially important to recognize. To be able to distinguish between ILD and (opportunistic) infections as the underlying cause, an aggressive diagnostic workup, including bronchoalveolar lavage, should be performed in patients treated with everolimus who develop respiratory disease. We report three cases of severe opportunistic pulmonary infections during everolimus treatment, concerning two Pneumocystis jirovecii pneumonia infections. These cases illustrate the diagnostic challenges of respiratory adverse events and the importance of a thorough diagnostic workup for correct diagnosis and treatment.