Focus on the Tumour Periphery in MRI Evaluation of Soft Tissue Sarcoma: Infiltrative Growth Signifies Poor Prognosis

Purpose. Infiltrative microscopical peripheral growth of soft tissue sarcomas (STS) has been shown to be of prognostic importance and preoperative risk stratification could individualize neoadjuvant treatment. Patients and methods. We assessed peripheral tumour growth pattern on preoperative MRI from 78 STS. The findings were correlated to histopathology and to outcome. Results. The MRI-based peripheral tumour growth pattern was classified as pushing in 34 tumours, focally infiltrative in 25, and diffusely infiltrative in 19. All tumours with diffuse infiltration on MRI also showed microscopical infiltration, whereas MRI failed to identify infiltration in two-thirds of the microscopically infiltrative tumours. Diffusely infiltrative growth on MRI gave a 2.5 times increased risk of metastases (P = .01) and a 3.7 times higher risk of local recurrence (P = .02). Discussion. Based on this observation we suggest that MRI evaluation of STS should focus on the peripheral tumour growth pattern since it adds prognostic information of value for decisions on neoadjuvant therapies

Improved quality and efficiency after the introduction of physician-led team triage in an emergency department

Background: Overcrowding in the emergency department (ED) may negatively affect patient outcomes, so different triage models have been introduced to improve performance. Physician-led team triage obtains better results than other triage models. We compared efficiency and quality measures before and after reorganization of the triage model in the ED at our county hospital. Materials and methods: We retrospectively compared two study periods with different triage models: nurse triage in 2008 (baseline) and physician-led team triage in 2012 (follow-up). Physician-led team triage was in use during day-time and early evenings on weekdays. Data were collected from electronic medical charts and the National Mortality Register. Results: We included 20,073 attendances in 2008 and 23,765 in 2012. The time from registration to physician presentation decreased from 80 to 33 min (P <0.001), and the length of stay decreased from 219 to 185 min (P <0.001) from 2008 to 2012, respectively. All of the quality variables differed significantly between the two periods, with better results in 2012. The odds ratio for patients who left before being seen or before treatment was completed was 0.62 (95% confidence interval 0.54-0.72). The corresponding result for unscheduled returns was 0.36 (0.32-0.40), and for the mortality rates within 7 and 30 days 0.72 (0.59-0.88) and 0.84 (0.73-0.97), respectively. The admission rate was 37% at baseline and 32% at follow-up (P <0.001). Conclusion: Physician-led team triage improved the efficiency and quality in EDs.Peer reviewe

Combining the in vivo comet and micronucleus assays: a practical approach to genotoxicity testing and data interpretation

Despite regulatory directives requiring the reduction of animal use in safety testing, recent modifications to genotoxicity testing guidelines now propose the use of two in vivo genotoxicity assays as a follow-up to an in vitro positive (International Conference on Harmonization Consensus Draft Guidance S2[R1] released March, 2008). To address both goals, the in vivo comet and micronucleus (MN) assays can be successfully combined into one informative study. Combining these two assays with such differences in sensitivity, endpoints measured and the type of data generated significantly improves upon the current standard capabilities for detecting genotoxicity without requiring additional animals. But to take full advantage of the benefits of incorporating the comet assay in safety testing, these same differences must be recognized and considered. Developed from over 15 years experience using the in vivo comet and MN assays in genotoxicity testing of chemicals and pharmaceuticals, this paper presents guidelines for the appropriate experimental design, dose selection and data interpretation for combined in vivo comet/MN assay studies. To illustrate the approach, data from combined assay studies are presented and discussed

Deliberate perioperative systems design improves operating room throughput

Background: New operating room (OR) design focuses more on the surgical environment than on the process of care. The authors sought to improve OR throughput and reduce time per case by goal-directed design of a demonstration OR and the perioperative processes occurring within and around it. Methods: The authors constructed a three-room suite including an OR, an induction room, and an early recovery area. Traditionally sequential activities were run in parallel, and nonsurgical activities were moved from the OR to the supporting spaces. The new workflow was supported by additional anesthesia and nursing personnel. The authors used a retrospective, case-and surgeon-matched design to compare the throughput, cost, and revenue performance of the new OR to traditional ORs. Results: For surgeons performing the same case mix in both environments, the new OR processed more cases per day than traditional ORs and used less time per case. Throughput improvement came from superior nonoperative performance. Nonoperative Time was reduced from 67 min (95% confidence interval, 64 -70 min) to 38 min (95% confidence interval, 35-40 min) in the new OR. All components of Nonoperative Time were meaningfully reduced. Operative Time decreased by approximately 5%. Hospital and anesthesia costs per case increased, but the increased throughput offset costs and the global net margin was unchanged. Conclusions: Deliberate OR and perioperative process redesign improved throughput. Performance improvement derived from relocating and reorganizing nonoperative activities. Better OR throughput entailed additional costs but allowed additiona

Lack of association between polymorphisms of the IL18R1 and IL18RAP genes and cardiovascular risk: the MORGAM Project

<p>Abstract</p> <p>Background</p> <p>Interleukin-18 is a pro-inflammatory cytokine suspected to be associated with atherosclerosis and its complications. We had previously shown that one single nucleotide polymorphism (SNP) of the <it>IL18 </it>gene was associated with cardiovascular disease (CVD) through an interaction with smoking. As a further step for elucidating the contribution of the IL-18 pathway to the etiology of CVD, we here investigated the association between the genetic variability of two IL-18 receptor genes, <it>IL18R1 </it>and <it>IL18RAP</it>, with the risk of developing CVD.</p> <p>Methods</p> <p>Eleven tagging SNPs, 5 in <it>IL18R1 </it>and 6 in <it>IL18RAP</it>, characterizing the haplotypic variability of the corresponding genes; were genotyped in 5 European prospective CVD cohorts including 1416 cases and 1772 non-cases, as part of the MORGAM project. Both single-locus and haplotypes analyses were carried out to investigate the association of these SNPs with CVD.</p> <p>Results</p> <p>We did not find any significant differences in allele, genotype and haplotype frequencies between cases and non-cases for either of the two genes. Moreover, the search for interactions between SNPs located in different genes, including 5 <it>IL18 </it>SNPs previously studied in the MORGAM project, and between SNPs and environmental factors remained unfruitful.</p> <p>Conclusion</p> <p>Our analysis suggests that the variability of <it>IL18R1 </it>and <it>IL18RAP </it>genes are unlikely to contribute to modulate the risk of CVD.</p

Characterizing Associations and SNP-Environment Interactions for GWAS-Identified Prostate Cancer Risk Markers—Results from BPC3

Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade) and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10−28). Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test), where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade <8) tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined

The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor.

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families

Fecundity selection theory: concepts and evidence

Fitness results from the optimal balance between survival, mating success and fecundity. The interactions between these three components of fitness vary importantly depending on the selective context, from positive covariation between them, to antagonistic pleiotropic relationships when fitness increases in one reduce fitness of others. Therefore, elucidating the routes through which selection shapes life history and phenotypic adaptations via these fitness components is of primary significance to understand ecological and evolutionary dynamics. However, while the fitness components mediated by natural (survival) and sexual (mating success) selection have extensively been debated from most possible perspectives, fecundity selection remains considerably less studied. Here, we review the theory, evidence and implications of fecundity selection as a driver of sex-specific adaptive evolution. Based on accumulating literature on the life-history, phenotypic and ecological aspects of fecundity, we (i) suggest that ‘fecundity’ is restricted to refer to brood size per reproductive episode, while ‘annual’ and ‘lifetime fecundity’ should not be used interchangeably with ‘fecundity’ as they represent different life history parameters; (ii) provide a generalized redefinition of fecundity selection that encompasses any traits that influence fecundity in any direction (from high to low) and in either sex; (iii) review the (macro)ecological basis of fecundity selection (e.g., ecological pressures that influence predictable spatial variation in fecundity); (iv) suggest that most ecological theories of fecundity selection should be tested in organisms other than birds; (v) argue that the longstanding fecundity selection hypothesis of female-biased sexual size dimorphism (SSD) has gained inconsistent support, that strong fecundity selection does not necessarily drive female-biased SSD, and that this form of SSD can be driven by other selective pressures; and (vi) discuss cases in which fecundity selection operates on males