The Role of Streptococcal Cell-Envelope Proteases in Bacterial Evasion of the Innate Immune System

Bacteria possess the ability to evolve varied and ingenious strategies to outwit the host immune system, instigating an evolutionary arms race. Proteases are amongst the many weapons employed by bacteria, which specifically cleave and neutralize key signalling molecules required for a coordinated immune response. In this article, we focus on a family of S8 subtilisin-like serine proteases expressed as cell-envelope proteases (CEPs) by group A and group B streptococci. Two of these proteases known as Streptococcus pyogenes CEP (SpyCEP) and C5a peptidase cleave the chemokine CXCL8 and the complement fragment C5a, respectively. Both CXCL8 and C5a are potent neutrophil-recruiting chemokines, and by neutralizing their activity, streptococci evade a key defence mechanism of innate immunity. We review the mechanisms by which CXCL8 and C5a recruit neutrophils and the characterization of SpyCEP and C5a peptidase, including both in vitro and in vivo studies. Recently described structural insights into the function of this CEP family are also discussed. We conclude by examining the progress of prototypic vaccines incorporating SpyCEP and C5a peptidase in their preparation. Since streptococci-producing SpyCEP and C5a peptidase are responsible for a considerable global disease burden, targeting these proteases by vaccination strategies or by small-molecule antagonists should provide protection from and promote the resolution of streptococcal infections.     

Reproducibility of the Banff schema in reporting protocol biopsies of stable renal allografts.

BACKGROUND: There is evidence that biopsy of stable renal allografts may be of value in predicting chronic allograft nephropathy, the main cause of graft loss. However, the reproducibility of such histological evaluation has not been tested in this setting. We tested the reproducibility of the Banff schema for this purpose. METHODS: We rated acute and chronic changes in 184 protocol biopsies. Individual pathologists at two different Canadian transplant centres reported independently. RESULTS: There was agreement in 73.53, 42.86, and 77.08% of cases in assigning a diagnosis of acute rejection, borderline changes (as defined in the schema), and no acute rejection, respectively. Applying kappa statistics, there was very good agreement in making the diagnosis of acute rejection vs no acute rejection (kappa 0.77). There was good inter-observer agreement in scoring glomerulitis, intimal arteritis, interstitial infiltrates, tubulitis, and arteriolar hyalinosis. Rating chronic changes also gave good inter-observer agreement (kappa=0.53, 0.65, and 0.62, respectively, for mild, moderate, and severe chronic allograft nephropathy). Agreement on transplant glomerulopathy was, however, poor. CONCLUSIONS: We conclude that the Banff classification provides a reproducible method for the histological assessment of protocol renal allograft biopsies in stable grafts. Such biopsies may be valuable in detecting subclinical rejection and early chronic allograft nephropathy and may also be used as surrogate end-points in the evaluation of therapy to prevent the latter.     

Gastrointestinal symptoms and patient satisfaction more than 1?year after laparoscopic Nissen fundoplication

Background  

Symptoms from poorly controlled gastroesophageal reflux disease (GERD) such as heartburn and regurgitation often resolve after laparoscopic Nissen fundoplication. Unfortunately, new gastrointestinal symptoms such as bloating may occur for some patients. Accurate data regarding the gastrointestinal symptoms experienced by patients who have had a laparoscopic fundoplication may help patients to make more informed decisions about pursuing surgery for their reflux disease.     

Liver Transplantation for Cystic Fibrosis in Adults

Purpose To expand our knowledge on liver transplantation for cirrhosis associated with cystic fibrosis in adults. Methods Five patients who underwent a liver transplantation due to cystic fibrosis were reviewed. The outcome of the patients in terms of age, immunosuppression regimen, patient and graft survival, and pre- and post-transplant complications were investigated. Results Five adult liver transplant patients had cystic fibrosis (0.2%). These included 4 men and 1 woman with a mean age of 31 ± 10, ranging from 22 to 52 years old at the time of transplantation. All patients had lung problems. Four patients had exocrine and two had endocrine pancreatic insufficiency. Two are currently alive with a follow-up of 5.8 years and 4 months after transplantation, respectively. There were three deaths from pulmonary embolism at 4.5 years, myocardial infarction with cyclosporine nephrotoxicity at 10.7 years, and lymphoproliferative disorder at 5 months after transplantation. No deaths occurred from lung infection. Only one patient had postoperative pulmonary infectious complications, which were successfully treated with antibiotics and did not result in mortality. Conclusion Adult liver transplantation for end-stage liver disease associated with cystic fibrosis offers encouraging results with a rapid general improvement after surgery and it is now considered to be a safe and acceptable treatment for this disease population.     

Changing concepts concerning the management of vesicoureteral reflux

PURPOSE: Conservative estimates indicate that up to 54% of patients who present with vesicoureteral reflux have dysfunction voiding. Children with voiding dysfunction and vesicoureteral reflux historically have a high breakthrough infection rate of 34% to 43%. Breakthrough infection represents significant morbidity and it is the most common indication for surgical intervention for vesicoureteral reflux. Voiding dysfunction is present in 79% of patients who proceed to reflux surgery. We evaluated the impact of pelvic floor muscle retraining combined with a medical program in patients with voiding dysfunction and vesicoureteral reflux. MATERIALS AND METHODS: Children with a history consistent with voiding dysfunction and vesicoureteral reflux were screened by uroflowmetry/electromyography, bladder scan for post-void residual urine, renal ultrasound and voiding cystourethrography. Confirmed cases of voiding dysfunction and vesicoureteral reflux were prospectively enrolled in this study. Children participated in an interactive, computer assisted, pelvic floor muscle retraining program that involved a conservative medical regimen and pelvic floor muscle retraining. All patients received prophylactic antibiotics. We evaluated the rate of breakthrough urinary tract infection, reflux outcome and surgical intervention. A literature review with the key words vesicoureteral reflux, voiding dysfunction and urinary tract infection was performed to identify historical control cases for comparison. RESULTS: Study enrollment criteria were fulfilled by 49 girls and 4 boys 4 to 13 years old (average age 8.8), representing 72 units with low grades I to II (48) and high grades III to V (24) reflux. Mean followup was 24 months. Initial uroflowmetry/electromyography and bladder scan revealed a staccato flow pattern and normal post-void residual urine in 11% of cases, staccato flow pattern and elevated post-void residual urine in 10%, flattened flow pattern and normal post-void residual urine in 28%, and flattened flow pattern and elevated post-void residual urine in 51%. Breakthrough infection developed in 5 patients (10%), including 1 in whom reflux had resolved and 1 with grade I reflux who underwent observation. The parents of 2 patients elected to complete biofeedback without surgical intervention and these patients did not have a repeat infection. Reimplantation was performed in 1 case (2%). There was resolution in 18 low and 7 high grade refluxing units, including 2 older patients with a long history of high grade bilateral disease. Average time to resolution was 7.8 months. We noted elevated post-void residual urine in 88% of the patients with high grade reflux. Average age at resolution was 9.2 years. During a 24-month period one of us (P. H. M.) noted a greater than 90% decrease in surgical intervention. CONCLUSIONS: A combined conservative medical and computer game assisted pelvic floor muscle retraining program appears to have decreased the incidence of breakthrough urinary tract infections and facilitated reflux resolution in children with voiding dysfunction and vesicoureteral reflux. Patients with high grade reflux and voiding dysfunction commonly present with elevated post-void residual urine, contraindicating the indiscriminate administration of anticholinergics. Decreasing the rate of urinary tract infections may have a dramatic impact on the need for surgical intervention and enable the reflux resolution rate to approximate that in patients without voiding dysfunction. Prospective controlled trials are needed to determine whether pelvic floor muscle retraining combined with a conservative medical regimen alters the natural history of vesicoureteral reflux in patients with voiding dysfunction.     

Prevention of nosocomial pressure ulcers: a process improvement project.

Nosocomial pressure ulcers (PU) occur in approximately 12% of all hospitalized patients. The risk can be determined by a variety of intrinsic and extrinsic factors. As a first line of defense against nosocomial PU, we use the Braden Scale to determine the potential risk of PU development during hospitalization. Once risk was identified, our standard was to implement an individualized plan of care. However, consistent implementation of PU preventative measures was lacking. As a result, a process improvement project was developed and implemented. The purpose of this process improvement project was to increase communication about and awareness of the need to vigorously intervene and document whenever there is risk of, or development of, a nosocomial PU. By initiating consistent use of a PU Tracking Form, developing unit-based wound champions that serve as experts in ulcer prevention, and creating an individual case analysis process, PU prevention and tracking was institutionalized. Results indicate that our nosocomial PU rate has declined from 7% to 4%.     

Methods for siting emergency stomas in the absence of a stoma therapist

Introduction

Stomas often have to be sited in emergencies by trainees who may have had little training in this. Emergency stomas and stomas where the site has not been marked preoperatively by a stoma therapist are more prone to complications. These complications may severely affect a patient’s quality of life. Advice in the literature on how to best site stomas is conflicting. We compared two easy anatomical methods of siting stomas to sites chosen by a stoma therapist and looked at how this site was affected by the patients’ body mass index (BMI).

Methods

Patients undergoing elective colorectal surgery were seen either pre or postoperatively. Each patient’s BMI was recorded and the positions of three different potential stoma positions (site G: the gold standard, marked by a stoma therapist; site S: marked using a pair of scissors against the umbilicus; site H: halfway between the umbilicus and anterior superior iliac spine) were compared.

Results

The two fixed anatomical methods described (method S and method H) both gave poor results. The most common reason for poor siting was the proximity of a skin crease. There was a statistically significant correlation between the patient’s BMI and the laterality of the gold standard site.

Conclusions

The two simple anatomical methods described here do not provide a shortcut to effective siting. A more effective method may be calculating the laterality of the site using the patient’s BMI, and then moving up/down to avoid a skin crease and improve the patient’s view for changing the bag. This deserves further study.