Topical oxygen therapy results in complete wound healing in diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are a significant problem in an aging population. Fifteen percent of diabetics develop a DFU over their lifetime, which can lead to potential amputation. The 5-year survival rate after amputation is 31%, which is greater than the lifetime risk of mortality from cancer. Topical oxygen is a promising technique for the adjunctive therapy of chronic wounds including DFUs, but few controlled studies exist to support its clinical adoption. The aim of this study was to compare a portable topical oxygen delivery system in patients with nonhealing DFUs to standard best practice. Twenty patients were randomized into a topical oxygen group (n = 10), and a nonplacebo control group with regular dressings and standard care (n = 10), and attended the diabetic foot clinic once weekly for 8 weeks. Ulcer surface area over time was analyzed using standardized digital imaging software. DFUs were present without healing for a mean duration of 76 weeks prior to the study. They found a significant difference in healing rate between patients receiving topical oxygen and those receiving standard care. Topical oxygen, therefore, represents a potentially exciting new technology to shorten healing time in patients with nonhealing DFUs. More prospective randomized and powered studies are needed to determine the benefits of topical oxygen, but our current results are very promising.

Forces shaping the antibiotic resistome.

Antibiotic resistance has become a problem of global scale. Resistance arises through mutation or through the acquisition of resistance gene(s) from other bacteria in a process called horizontal gene transfer (HGT). While HGT is recognized as an important factor in the dissemination of resistance genes in clinical pathogens, its role in the environment has been called into question by a recent study published in Nature. The authors found little evidence of HGT in soil using a culture-independent functional metagenomics approach, which is in contrast to previous work from the same lab showing HGT between the environment and human microbiome. While surprising at face value, these results may be explained by the lack of selective pressure in the environment studied. Importantly, this work suggests the need for careful monitoring of environmental antibiotic pollution and stringent antibiotic stewardship in the fight against resistance.

Peptide alarmone signalling triggers an auto-active bacteriocin necessary for genetic competence.

The induction of genetic competence is a strategy used by bacteria to increase their genetic repertoire under stressful environmental conditions. Recently, Streptococcus pneumoniae has been shown to co-ordinate the uptake of transforming DNA with fratricide via increased expression of the peptide pheromone responsible for competence induction. Here, we document that environmental stress-induced expression of the peptide pheromone competence-stimulating peptide (CSP) in the oral pathogen Streptococcus mutans. We showed that CSP is involved in the stress response and determined the CSP-induced regulon in S. mutans by microarray analysis. Contrary to pneumococcus, S. mutans responds to increased concentrations of CSP by cell lysis in only a fraction of the population. We have focused on the mechanism of cell lysis and have identified a novel bacteriocin as the 'death effector'. Most importantly, we showed that this bacteriocin causes cell death via a novel mechanism of action: intracellular action against self. We have also identified the cognate bacteriocin immunity protein, which resides in a separate unlinked genetic locus to allow its differential regulation. The role of the lytic response in S. mutans competence is also discussed. Together, these findings reveal a novel autolytic pathway in S. mutans which may be involved in the dissemination of fitness-enhancing genes in the oral biofilm.

Nutrition and the Plastic Surgeon: Possible Interventions and Practice Considerations.

The objective of this article is to convey the importance of nutrition in plastic surgery, to offer possible outpatient nutritional interventions within the surgical care setting, and to guide the plastic surgeon in integrating nutrition as a key practice enhancement strategy for the care of wound patients and beyond. The impact of nutritional status on surgical outcomes is well recognized. Malnutrition is very frequent among the hospitalized patient population and up to 1 in 4 plastic surgery outpatient is at risk for malnutrition. Micro- and macronutrients are both essential for optimal wound healing and although specific patient populations within the field of plastic surgery are more at risk of malnutrition, universal screening, and actions should be implemented. Outpatient interventions to promote adequate nutritional intake and address barriers to the access of fruits and vegetables have included both exposure and incentive interventions. In the clinical setting, universal screening using validated and rapid tools such as the Canadian Nutritional Screening Tool are encouraged. Such screening should be complemented by appropriate blood work, body mass index measurements, and prompt referral to a dietician when appropriate. The notion of prehabilitation has also emerged with impetus in surgery and encompasses the nutritional optimization of patients by promoting the enhancement of functional capacity preoperatively.

Cost-effectiveness of telemonitoring screening for diabetic foot ulcer: a mathematical model.

BACKGROUND: One of the most common (and costly) complications of diabetes are diabetic foot ulcers, which often result in lower-extremity amputation. Regular foot care can reduce complications; however, roughly half of Canadians with diabetes do not participate in screening. We sought to evaluate the economic effects of using telemonitoring for diabetic foot ulcer prevention using mathematical modelling. METHODS: We used Markov modelling to compare current screening standards (standard care) to population-wide and targeted (high-risk) telemonitoring programs in a hypothetical cohort of Canadian patients aged 60 years. We varied the effectiveness (or outcome), defined as the proportion of diabetic foot ulcers prevented, to explore cost-effectiveness using model parameters from published literature and clinical experts. RESULTS: At 20%-40% effectiveness, population-based prevention resulted in 0.00399-0.00790 quality-adjusted life years (QALYs) gained per person over 5 years and an incremental cost of $479-$402 compared to standard care. At 15%-40% effectiveness, high-risk prevention resulted in a cost decrease per person over 5 years ($1.26-$25.55), with health benefits of 0.000207-0.00058 QALYs gained. INTERPRETATION: The use of telemonitoring in the diabetic lower extremity can offer patients better quality of life and can be cost-effective compared to current Canadian screening practices. Future work should focus on developing and validating technologies based on objective outcome measures for remote monitoring of the diabetic foot.

Development of a Universal Nutritional Screening Platform for Plastic Surgery Patients.

Plastic surgeons routinely see patients with complex or chronic wounds of all etiology. In a previous study, we found that up to 1 in 4 of these patients is at risk for malnutrition, which may be influencing their ability to heal. The goal of this study was to develop and validate a universal screening protocol that would be fast and accurate and allow for effective intervention and optimization of nutrition before plastic surgery. METHODS: To accomplish these goals, we adopted a 2-part screening algorithm using the Canadian Nutritional Screening Tool (CNST) to triage patients in our outpatient clinics and then further screened those identified as being at risk using the Subjective Global Assessment (SGA) tool and blood work. RESULTS: We screened 111 patients with diagnoses related to breast cancer (n = 10; 9.01%), elective surgery (n = 38; 34.23%), emergency surgery (n = 8; 7.21%), fractures (n = 15; 13.51%), and wounds (n = 40; 36.04%). Of the screened subjects, 15.32% (n = 17) were found to be at nutritional risk using the CNST, and 13 were confirmed to be moderately or severely malnourished using the SGA. Importantly, there were no positive correlations between nutritional status and smoking, diabetes, body mass index, or age, indicating that a universal screening protocol is needed to effectively screen a diverse plastic surgery population for malnutrition. CONCLUSIONS: Screening patients with both the CNST and the SGA is an effective way to identify patients before surgery to improve outcomes.

A macrophage-stimulating compound from a screen of microbial natural products.

Rising rates of antibiotic resistance in bacterial pathogens is a medical crisis of global concern that necessitates the development of new treatment strategies. We have isolated a natural product with macrophage-stimulating activity from a screen of microbially produced bioactive molecules. Streptazolin increased bacterial killing and elaboration of immunostimulatory cytokines by macrophages in vitro. Furthermore, we show that streptazolin stimulates the macrophage nuclear factor κB (NF-κB) pathway via phosphatidylinositide 3-kinase (PI3K) signaling, and that the conjugated diene moiety is essential for stimulatory activity. Immunostimulatory molecules like streptazolin represent entries into new treatment paradigms to address the challenge of antibiotic resistance.

The antibiotic resistance "mobilome": searching for the link between environment and clinic.

Antibiotic resistance is an ancient problem, owing to the co-evolution of antibiotic-producing and target organisms in the soil and other environments over millennia. The environmental "resistome" is the collection of all genes that directly or indirectly contribute to antibiotic resistance. Many of these resistance determinants originate in antibiotic-producing organisms (where they serve to mediate self-immunity), while others become resistance determinants only when mobilized and over-expressed in non-native hosts (like plasmid-encoded ß-lactamases). The modern environmental resistome is under selective pressure from human activities such as agriculture, which may influence the composition of the local resistome and lead to gene transfer events. Beyond the environment, we are challenged in the clinic by the rise in both frequency and diversity of antibiotic resistant pathogens. We assume that clinical resistance originated in the environment, but few examples of direct gene exchange between the environmental resistome and the clinical resistome have been documented. Strong evidence exists to suggest that clinical aminoglycoside and vancomycin resistance enzymes, the extended-spectrum ß-lactamase CTX-M and the quinolone resistance gene qnr have direct links to the environmental resistome. In this review, we highlight recent advances in our understanding of horizontal gene transfer of antibiotic resistance genes from the environment to the clinic. Improvements in sequencing technologies coupled with functional metagenomic studies have revealed previously underappreciated diversity in the environmental resistome, and also established novel genetic links to the clinic. Understanding mechanisms of gene exchange becomes vital in controlling the future dissemination of antibiotic resistance.

Cell death in Streptococcus mutans biofilms: a link between CSP and extracellular DNA.

Streptococcal competence-stimulating peptides (CSPs) were once thought to passively communicate population density in a process known classically as quorum sensing. However, recent evidence has shown that these peptides may also be inducible 'alarmones,' capable of conveying sophisticated messages in a population including the induction of altruistic cellular suicide under stressful conditions. We have previously characterized the alarmone response in Streptococcus mutans, a cariogenic resident of the oral flora, in which a novel bacteriocin-like peptide causes cell death in a subset of the population. Our objective in this work was to characterize the mechanism of immunity to cell death in S. mutans. Toward this goal, we have identified the conditions under which immunity is induced, and identified the regulatory system responsible for differential (and protective) expression of immunity. We also showed that CSP-induced death contributes to S. mutans biofilm formation through the release of chromosomal DNA into the extracellular matrix, providing a long sought-after mechanistic explanation for the role of CSP in S. mutans biofilm formation.