Oriented Immobilization on Gold Nanoparticles of a Recombinant Therapeutic Zymogen.

Direct immobilization of functional proteins on gold nanoparticles (AuNPs) affects their structure and function. Changes may vary widely and range from strong inhibition to the enhancement of protein function. More often though the outcome of direct protein immobilization results in protein misfolding and the loss of protein activity. Additional complications arise when the protein being immobilized is a zymogen which requires and relies on additional protein-protein interactions to exert its function. Here we describe molecular design of a glutathione-S-transferase-Staphylokinase fusion protein (GST-SAK) and its conjugation to AuNPs. The multivalent AuNP-(GST-SAK)n complexes generated show plasminogen activation activity in vitro. The methods described are transferable and could be adapted for conjugation and functional analysis of other plasminogen activators, thrombolytic preparations or other functional enzymes.

Management of concomitant cancer and abdominal aortic aneurysm.

Background. The coexistence of neoplasm and abdominal aortic aneurysm (AAA) presents a real management challenge. This paper reviews the literature on the prevalence, diagnosis, and management dilemmas of concurrent visceral malignancy and abdominal aortic aneurysm. Method. The MEDLINE and HIGHWIRE databases (1966-present) were searched. Papers detailing relevant data were assessed for quality and validity. All case series, review articles, and references of such articles were searched for additional relevant papers. Results. Current challenges in decision making, the effect of major body-cavity surgery on an untreated aneurysm, the effects of major vascular surgery on the treatment of malignancy, the use of EVAR (endovascular aortic aneurysm repair) as a fairly low-risk procedure and its role in the management of malignancy, and the effect of other challenging issues such as the use of adjuvant therapy, and patients informed decision-making were reviewed and discussed. Conclusion. In synchronous malignancy and abdominal aortic aneurysm, the most life-threatening lesion should be addressed first. Endovascular aneurysm repair where possible, followed by malignancy resection, is becoming the preferred initial treatment choice in most centres.

Radical cystectomy: defining the threshold for a surgeon to achieve optimum outcomes.

BACKGROUND: The reorganisation of cancer services in England will result in the creation of specialist high volume cancer surgery centres. Studies have suggested a relationship between increasing surgical volume and improved outcomes in urological pelvic cancer surgery, although to date, they have pre-defined the definition of "high" and "low" volume surgeons. AIM: To derive the minimum caseload a surgeon requires to achieve optimum outcomes and to examine the effect of the operating centre size upon individual surgeon's outcomes. METHODS: All cystectomies performed for bladder cancer in England over 5 years were analysed from Hospital Episode Statistics (HES) data. Statistical analysis was undertaken to describe the relationship between each surgeon's annual case volume and two OUTCOME MEASURES: in-hospital mortality rate, and hospital stay. The surgeon's outcomes were then analysed with respect to the overall level of activity in their operating centre. RESULTS: A total of 6308 cystectomies were performed; the mean number of surgeons performing them annually was 327 with an overall mortality rate of 5.53%. A significant inverse correlation (-0.968, p<0.01) was found between case volume and mortality rate. Applying 95% confidence interval estimation, the minimum caseload required to achieve the lowest mortality rate was eight procedures per year. Increasing caseload beyond eight operations per year did not produce a significant reduction in mortality rate. CONCLUSION: Analysis of HES data confirms an inverse relationship between surgeon's caseload and mortality for radical cystectomy. A caseload of eight operations per year is associated with the lowest mortality rate.

Defining the minimum hospital case-load to achieve optimum outcomes in radical cystectomy.

OBJECTIVE: To define 'high-' and 'low-' volume hospitals for radical cystectomy, and the minimum caseload required for a hospital to achieve optimum outcomes, as a relationship between increasing surgical case volume and improved outcomes in radical urological surgery has been suggested in recent North American studies. METHODS: All cystectomies for urological cancer in England over 5 years were analysed from Hospital Episode Statistics (HES) data. The data were analysed statistically to describe the relationship between each hospital's annual case volume and two outcome measures: in-hospital mortality rate (MR) and hospital stay. RESULTS: In all, there were 6317 cystectomies in 210 centres, with an overall MR of 5.6%. There was a significant inverse correlation (-0.733, P < 0.01) between hospital case volume and MR. Applying 95% confidence intervals, the minimum caseload required to achieve optimum outcomes was 11 procedures/year. Increasing the caseload beyond this minimum did not produce a significant reduction in MR. CONCLUSION: Analysis of HES data confirms an inverse relationship between hospital caseload and mortality for radical cystectomy. A caseload of 11 operations/year is associated with the lowest MR.