Quality measures in breast cancer surgery.

The development of accurate quality performance measures in breast cancer surgery is extremely challenging as highlighted by Monica Morrow in a recent editorial. Traditional quality measures in surgical oncology have focused on 30-day morbidity and mortality which are not relevant to breast cancer surgery which is typically associated with low morbidity and mortality. Dr Morrow suggests that the recent study by McCahill et al which uses re-excision of margins following breast conserving surgery (BCS) as an indicator of surgical quality fails the lithmus test as a quality measure for a variety of reasons. Essentially, there are too many variables that may influence the decision to proceed with breast conserving surgery in the first place such as patients’ age, surgeons’ bias and appropriate preoperative imaging. Using re-excision of margins as a tool to measure quality would encourage breast surgeons to perform a wider excision than is oncologically necessary and compromise the aesthetic appearance of the breast. In addition the quality of pathological margin processing may also vary considerably between institutions. It is therefore essential that any proposed quality measure in breast cancer surgery is evidence based and compliments our understanding of modern breast cancer biology. It is equally important that any proposed quality indicator is reliable and appropriately validated and is cost-effective in terms of collecting the relevant data

Using biomarker signature patterns for an mRNA molecular diagnostic of mouse embryonic stem cell differentiation state

BACKGROUND: The pluripotency and self-renewal capabilities, which define the 'stemness' state, of mouse embryonic stem (ES) cells, are usually investigated by functional assays or quantitative measurements of the expression levels of known ES cell markers. Strong correlations between these expression levels and functional assays, particularly at the early stage of cell differentiation, have usually not been observed. An effective molecular diagnostic to properly identify the differentiation state of mouse ES cells, prior to further experimentation, is needed. RESULTS: A novel molecular pattern recognition procedure has been developed to diagnose the differentiation state of ES cells. This is based on mRNA transcript levels of genes differentially expressed between ES cells and their differentiating progeny. Large publicly available ES cell data sets from various platforms were used to develop and test the diagnostic model. Signature patterns consisting of five gene expression levels achieved high accuracy at determining the cell state (sensitivity and specificity > 97%). CONCLUSION: The effective ES cell state diagnostic scheme described here can be implemented easily to assist researchers in identifying the differentiation state of their cultures. It also provides a step towards standardization of experiments relying on cells being in the stem cell or differentiating state.published_or_final_versio

Chlorhexidine-alcohol versus povidone-iodine for pre-operative skin preparation: A systematic review and meta-analysis.

Background: Surgical site infection (SSI) is a dreaded postoperative complication. Although preoperative skin cleansing in order to prevent surgical site infection (SSI) is standard surgical practice, there is clinical equipoise concerning whether povidone iodine (PI) or chlorhexidine alcohol (CHA) is the antiseptic agent of choice. Objectives: To determine whether CHA or PI is the preferred preoperative skin preparation for reducing SSI in clean, clean-contaminated and contaminated surgery. Search methods: PubMed, Embase, and gray literature sources were searched for randomized controlled trials (RCTs) comparing both CHA and PI between 1980 and 2014. Comparative RCTs of preoperative CHA versus PI studying SSI in clean, clean-contaminated and contaminated surgery were included. Risk of bias was assessed using Cochrane risk of bias. Main result: We identified six eligible studies with an overall 2484 participants. The overall rate of SSI was 6.8% in the CHA group versus 11.0% in the PI group (P \u3c 0.0002). CHA was superior to PI in the prevention of SSI with a pooled RR of 0.62 (95% CI, 0.48–0.81). Conclusions: Preoperative surgical skin preparation with CHA is more effective than PI in preventing SSI across clean and clean-contaminated surgery. Further studies should evaluate the effectiveness of CHA versus PI in contaminated surgery

Breaking Barriers to Successful Implementation of Day Case Laparoscopic Cholecystectomy.

Laparoscopic cholecystectomy is a common procedure performed in both emergency and elective settings. Our aim was to analyse the trends in laparoscopic surgery in Ireland in the public and private healthcare systems. In particular we studied the trend in day case laparoscopic cholecystectomy. National HIPE data for the years 2010-2012 was obtained. Similar datasets were obtained from the three main health insurers. 19,214 laparoscopic cholecystectomies were carried out in Ireland over the 3-year period. More procedures were performed in the public system than the private system from 2010-2012. There was a steady increase in surgeries performed in the public sector, while the private sector remained static. Although the ALOS was significantly higher in the public sector, there was an increase in the rate of day case procedures from 416 (13%) to 762 (21.9%). The day case rates in private hospitals increased only slightly from 29 (5.1%) in 2010 to 40 (5.9%) in 2012. Day case laparoscopic cholecystectomy has been shown to be a safe procedure, however significant barriers remain in place to the implementation of successful day case units nationwide

Bare Below the Elbows: A comparative study of a tertiary and district general hospital.

A \u27Bare Below the Elbows\u27 (BBTE) dress code policy has been introduced by the majority of NHS trusts in the UK. The aim of this Irish study was to evaluate the impact of an educational intervention on perception of medical attire. The study was carried out in two centres: a tertiary referral centre (Beaumont Hospital) and a district hospital (MRH, Portlaoise). Two questionnaires, incorporating photographic evaluation of appropriate attire for consultants and junior doctors, were completed pre and post BBTE education. One hundred and five patients participated. Analysis pre BBTE education indicated patients considered formal attire and white coats most appropriate for consultants and junior doctors respectively. Post-intervention analysis revealed a significant reduction in the popularity of both (

Preparing students to be doctors: introduction of a sub-internship program.

Preparing graduates for the transformation from medical student to doctor provides medical schools with a real challenge. Medical educators advocate a process of graduated delegation of responsibility in the clinical years of medical school. This is best exemplified in the North American system of sub-internship programmes; an educational approach which European medical schools have been slow to adopt. This study reports on the introduction of an intensive two-week surgical sub-internship for final medical year students. \u22Sub-interns\u22 were asked to complete pre and post sub-internship online questionnaires assessing their readiness to perform clinical and practical skills, attitudes towards the program, and how well it prepared students for internship. Forty-nine students completed a questionnaire pre sub-internship and 47 completed the post-questionnaire. Student confidence towards practical and clinical skills and their first day at work increased over the two weeks. Mean Iikert scores for all 6 practical and clinical skills improved post sub-internship. The introduction of a surgical sub-internship is timely and welcomed by medical students. Its development helps bridge the gap in responsibilities between medical student and doctor

Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase

ABSTRACT: INTRODUCTION: The adhesion protein junctional adhesion molecule-A (JAM-A) regulates epithelial cell morphology and migration, and its over-expression has recently been linked with increased risk of metastasis in breast cancer patients. As cell migration is an early requirement for tumor metastasis, we sought to identify the JAM-A signalling events regulating migration in breast cancer cells. METHODS: MCF7 breast cancer cells (which express high endogenous levels of JAM-A) and primary cultures from breast cancer patients were used for this study. JAM-A was knocked down in MCF7 cells using siRNA to determine the consequences for cell adhesion, cell migration and the protein expression of various integrin subunits. As we had previously demonstrated a link between the expression of JAM-A and β1-integrin, we examined activation of the β1-integrin regulator Rap1 GTPase in response to JAM-A knockdown or functional antagonism. To test whether JAM-A, Rap1 and β1-integrin lie in a linear pathway, we tested functional inhibitors of all three proteins separately or together in migration assays. Finally we performed immunoprecipitations in MCF7 cells and primary breast cells to determine the binding partners connecting JAM-A to Rap1 activation. RESULTS: JAM-A knockdown in MCF7 breast cancer cells reduced adhesion to, and migration through, the β1-integrin substrate fibronectin. This was accompanied by reduced protein expression of β1-integrin and its binding partners αV- and α5-integrin. Rap1 activity was reduced in response to JAM-A knockdown or inhibition, and pharmacological inhibition of Rap1 reduced MCF7 cell migration. No additive anti-migratory effect was observed in response to simultaneous inhibition of JAM-A, Rap1 and β1-integrin, suggesting that they lie in a linear migratory pathway. Finally, in an attempt to elucidate the binding partners putatively linking JAM-A to Rap1 activation, we have demonstrated the formation of a complex between JAM-A, AF-6 and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. CONCLUSIONS: Our findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and β1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis

P7C3-A20 neuroprotection is independent of Wallerian degeneration in primary neuronal culture

The antiapoptotic, neuroprotective compound P7C3-A20 reduces neurological deficits when administered to murine in-vivo models of traumatic brain injury. P7C3-A20 is thought to exert its activity through small-molecule activation of the enzyme nicotinamide phosphoribosyltransferase. This enzyme converts nicotinamide to nicotinamide mononucleotide, the precursor to nicotinamide adenine dinucleotide synthesis. Alterations to this bioenergetic pathway have been shown to induce Wallerian degeneration (WD) of the distal neurite following injury. This study aimed to establish whether P7C3-A20, through induction of nicotinamide phosphoribosyltransferase activity, would affect the rate of WD. The model systems used were dissociated primary cortical neurons, dissociated superior cervical ganglion neurons and superior cervical ganglion explants. P7C3-A20 failed to show any protection against WD induced by neurite transection or vincristine administration. Furthermore, there was a concentration-dependent neurotoxicity. These findings are important in understanding the mechanism by which P7C3-A20 mediates its effects - a key step before moving to human clinical trials

Using Social Media to Increase Accessibility to Online Teaching Resources.

The key learning points of Surgical Grand Rounds (SGR) are often not accessible at times of exam revision for students. We sought to use Twitter as an online teaching repository. A SGR Twitter profile was created. 23 SGR presentations were made accessible on Twitter over a 3 month period. 93 students were invited to complete a questionnaire assessing usage of the repository. 84 (90%) in total responded, of these, 25 (80.6%) felt that the online provision of SGR through twitter was useful . The majority (71%) felt that the online content was easily accessible. The novel use of social media is a useful adjunctive educational tool in accessing an online repository of SGR presentations

Prevalence and predictors of initial oral antibiotic treatment failure in adult emergency department patients with cellulitis: a pilot study.

INTRODUCTION: Assessment of cellulitis severity in the emergency department (ED) setting is problematic. Given the lack of research performed to describe the epidemiology and management of cellulitis, it is unsurprising that heterogeneous antibiotic prescribing and poor adherence to guidelines is common. It has been shown that up to 20.5% of ED patients with cellulitis require either a change in route or dose of the initially prescribed antibiotic regimen. The current treatment failure rate for empirically prescribed oral antibiotic therapy in Irish EDs is unknown. The association of patient risk factors with treatment failure has not been described in our setting. Lower prevalence of community-acquired methicillin-resistant Staphylococcus aureus-associated infection, differing antibiotic prescribing preferences and varying availability of outpatient intravenous therapy programmes may result in different rates of empiric antibiotic treatment failure from those previously described. METHODS AND ANALYSIS: Consecutive ED patients with cellulitis will be enrolled on a 24/7 basis from 3 Irish EDs. A prespecified set of clinical variables will be measured on each patient discharged on empiric oral antibiotic therapy. A second independent study recruiter will assess at least 10% of cases for each of the predictor variables. Follow-up by telephone call will occur at 14 days for all discharged patients where measurement of the primary outcome will occur. Our primary outcome is treatment failure, defined as a change in route of antibiotic administration from oral to intravenous antibiotic. Our secondary outcome is change in dose or type of prescribed antibiotic. A cohort of approximately 152 patients is required to estimate the proportion of patients failing oral antibiotic treatment with a margin of error of 0.05 around the estimate. ETHICS AND DISSEMINATION: Full ethics approval has been granted. An integrated dissemination plan, involving diverse clinical specialties and enrolled patients, is described. TRIAL REGISTRATION NUMBER: NCT 02230813