A Rat Model of Diabetic Wound Infection for the Evaluation of Topical Antimicrobial Therapies

Diabetes mellitus is an epidemic multisystemic chronic disease that frequently is complicated by complex wound infections. Innovative topical antimicrobial therapy agents are potentially useful for multimodal treatment of these infections. However, an appropriately standardized in vivo model is currently not available to facilitate the screening of these emerging products and their effect on wound healing. To develop such a model, we analyzed, tested, and modified published models of wound healing. We optimized various aspects of the model, including animal species, diabetes induction method, hair removal technique, splint and dressing methods, the control of unintentional bacterial infection, sampling methods for the evaluation of bacterial burden, and aspects of the microscopic and macroscopic assessment of wound healing, all while taking into consideration animal welfare and the '3Rs' principle. We thus developed a new wound infection model in rats that is optimized for testing topical antimicrobial therapy agents. This model accurately reproduces the pathophysiology of infected diabetic wound healing and includes the current standard treatment (that is, debridement). The numerous benefits of this model include the ready availability of necessary materials, simple techniques, high reproducibility, and practicality for experiments with large sample sizes. Furthermore, given its similarities to infected-wound healing and treatment in humans, our new model can serve as a valid alternative for applied research.

Long-Term Evaluation of Recurrence after Photodynamic Therapy with Topical Methyl Aminolevulinate for Non-Melanoma Skin Cancer: a Hospital-Based Study

Introduction & Objectives: Several factors may influence the decision to pursue nonsurgical modalities for the treatment of non-melanoma skin cancer. Topical photodynamic therapy (PDT) is a non-invasive alternative treatment reported to have a high efficacy when using standardized protocols in Bowen’s disease (BD), superficial basal cell carcinoma (BCC) and in thin nodular BCC. However, long-term recurrence studies are lacking. The aim of this study was to evaluate the long-term efficacy of PDT with topical methylaminolevulinate (MAL) for the treatment of BD and BCC in a dermato-oncology department. Materials & Methods: All patients with the diagnosis of BD or BCC, treated with MAL-PDT from the years 2004 to 2008, were enrolled. Treatment protocol included two MAL-PDT sessions one week apart repeated at three months when incomplete response, using a red light dose of 37-40 J/cm2 and an exposure time of 8’20’’. Clinical records were retrospectively reviewed, and data regarding age, sex, tumour location, size, treatment outcomes and recurrence were registered. Descriptive analysis was performed using chi square tests, followed by survival analysis with the Kaplan-Meier and Cox regression models. Results: Sixty-eight patients (median age 71.0 years, P25;P75=30;92) with a total of 78 tumours (31 BD, 45 superficial BCC, 2 nodular BCC) and a median tumour size of 5 cm2 were treated. Overall, the median follow-up period was 43.5 months (P25;P75=0;100), and a total recurrence rate of 33.8% was observed (24.4 % for BCC vs. 45.2% for BD). Estimated recurrence rates for BCC and BD were 5.0% vs. 7.4% at 6 months, 23.4% vs. 27.9% at 12 months, and 30.0% vs. 72.4% at 60 months. Both age and diagnosis were independent prognostic factors for recurrence, with significantly higher estimated recurrence rates in patients with BD (p=0.0036) or younger than 58 years old (p=0.039). The risk of recurrence (hazard ratio) was 2.4 times higher in patients with BD compared to superficial BCC (95% CI:1.1-5.3; p=0.033), and 2.8 times higher in patients younger than 58 years old (95% CI:1.2-6.5; p=0.02). Conclusions: In the studied population, estimated recurrence rates are higher than those expected from available literature, possibly due to a longer follow-up period. To the authors’ knowledge there is only one other study with a similar follow-up period, regarding BCC solely. BD, as an in situ squamous cell carcinoma, has a higher tendency to recur than superficial BCC. Despite greater cosmesis, PDT might no be the best treatment option for young patients considering their higher risk of recurrence.