Surgical therapy in patients with active infective endocarditis: seven-year single centre experience in a subgroup of 255 patients treated with the Shelhigh stentless bioprosthesis

OBJECTIVE: We investigated outcomes after surgical therapy in patients with active infective endocarditis (AIE) with regard to survival in relation to surgical urgency, valve position, number of valves implanted and abscess formation. We aimed to identify independent risk factors for early mortality. METHODS AND RESULTS: Two hundred and fifty-five patients received Shelhigh bioprostheses between February 2000 and March 2007. A total of 74.1% had native and 25.9% prosthetic AIE. Surgery was regarded as urgent in 57.3% and as an emergency procedure in 38.4%. There was a highly significant difference in survival rate between patients who were operated on urgently versus in an emergency (p<0.0001), between single and double valve replacement (p=0.0206) and between patients with and without abscess formation (p=0.0245). There were two cases of early reinfection (0.78%) and six of late reinfection (2.35%) leading to re-operation. CONCLUSIONS: The survival of patients differs significantly in dependence on their surgical urgency. Better outcome could have been achieved if patients had been referred earlier for surgery and operated upon before heart failure or septic shock developed. Long-term survival was better in patients without abscess formation. The low reinfection rate of Shelhigh bioprostheses in AIE is promising and the early and mid-term results achieved need to be verified in the long-term course.     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.     

Moderation of hemophilia A phenotype by the factor V R506Q mutation

Although many examples of unrelated hemophilia A patients carrying identical point mutations in the factor VIII (FVIII) gene have been reported, the clinical phenotype is not always the same among patients sharing the same molecular defect. Possible explanations for this discrepancy include undetected additional mutations in the FVIII gene or coinheritance of mutations at other genetic loci that modulate FVIII function. We report molecular genetic analysis of potential modifying genes in two sets of unrelated patients carrying common FVIII missense mutations but exhibiting different levels of clinical severity. Both mutations (FVIII R1689C and R2209Q) are associated with severe hemophilia A in some patients and mild/moderate disease in others. The common von Willebrand disease type 2N mutation (R91Q) was excluded as a modifying factor in these groups of patients. However, analysis of the recently described factor V (FV) R506Q mutation (leading to activated protein C resistance) identified a correlation of inheritance of this defect with reduced hemophilia A severity. Two moderately affected hemophilia A patients, each with either of two FVIII gene mutations, were heterozygous for FV R506Q, whereas two severely affected patients and two moderately affected patients were homozygous normal at the FV locus. Our results suggest that coinheritance of the FV R506Q mutation may be an important determinant of clinical phenotype in hemophilia A and that modification of the protein C pathway may offer a new strategy for the treatment of FVIII deficiency.     

Wound infection,dressings and pain,is there a relationship in the chronic wound?

The focus on quality of life issues in wound care has justly taken a far greater importance. With the acceptance that pain can be a major factor to the patient, and in particular, pain at dressing change comes the opportunity for avoidance and/or reduction strategies. Whilst pain has been associated with wound infection for millennia, it is only much more recently that this has received due attention from research and clinical practice. In this study, the nature of pain, changes in pain and pain associated with infection are the focal points. A Delphi approach, now a frequently used tool in wound care research, has been used to obtain expert opinion on these aspects of management.