Erythropoietin Improves the Survival of Fat Tissue after Its Transplantation in Nude Mice

Background: Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Methodology/Principal Findings: Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPOtreated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Conclusions/Significance: Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fa

De l'infection des plaies chroniques

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Failure rates of artificial dermis products in treatment of diabetic foot ulcer: A systematic review and network meta-analysis

International audienceDiabetic foot ulcer (DFU) is a frequent complication in diabetic patients, occurring in up to 25% of those affected. Among the treatments available to clinicians, the use of bioengineered skin substitutes is an attractive alternative. Artificial dermis functions as a matrix, covering the wound and supporting healing and reconstruction of the lost tissue. This study was aimed at reviewing the use of five regeneration matrices (namely, Integra, Nevelia, Matriderm, Pelnac, and Renoskin) as reported by clinical trials. We searched Medline, Embase, ISI Web of Science, Scopus, and Cochrane Central Register of Controlled Trials databases for relevant studies. Risk of failure rates was analysed by relative risk ratio method and complete ulcer healing was studied using network meta-analysis. Thirteen studies (12 randomized clinical trials and one cohort study) were eligible for analysis. The network meta-analysis based on a single study for Matriderm and 12 studies for other products showed that Matriderm was statistically inferior in achieving complete ulcer healing, as compared to all other products combined. In the second phase analysis, which was limited to three studies using artificial dermis products, there was a 57% reduction in the risk of reepithelialization failure for DFU patients who used Matriderm or Pelnac, compared to those who used Pelnac with basic fibroblast growth factor spray or skin grafting. The data showed an overall low failure rate suggesting that these bioengineered skin products provide a suitable support and microenvironment for healing of DFUs with low ulcer recurrence rates. This systematic review with meta-analysis highlights the pressing need for more studies investigating the safety, efficacy and failure rates of regeneration matrices in the treatment of DFUs

REAL-WORLD CLINICAL EVALUATION AND COSTS OF TELEMEDICINE FOR CHRONIC WOUND MANAGEMENT

International audienc

Effect of EPO treatment on fat graft weight and volume in all treatment groups in the two experiments.

<p><b><u>Footnotes</u></b></p><p>Values are presented as mean ± SD.</p><p>n  =  number of mice.</p><p>EPO  =  erythropoietin.</p><p>VEGF  =  vascular endothelial growth factor.</p><p>**P<0.01, ***P<0.001, for the difference between either the low-dose- or the high-dose EPO-treated fat grafts and the PBS-treated grafts.</p

Silver Sulfadiazine and Cerium Nitrate in Ischemic Skin Necrosis of the Leg and Foot: Results of a Prospective Randomized Controlled Study

International audienceFlammacerium is a topical treatment composed of silver sulfadiazine and cerium nitrate initially used in burns. The objective was to assess the effectiveness of silver sulfadiazine and cerium nitrate on ischemic necrosis wounds of the lower limb as an alternative to amputation for a period of 12 weeks. Patients were prospectively randomized to receive silver sulfadiazine and cerium nitrate or standard care. Patients included adults with an ischemic wound of the lower limb, with necrosis covering over at least 50%. Critical ischemia limb was confirmed by an ankle-brachial index \textless0.7 or \textgreater1.3 with radiological confirmation. Patient demographic data, amputations procedures, wound area, Visual Analogue Scale pain rating, clinical infection, and adverse events were recorded. Fifty patients, 34 males and 16 females, were recruited between January 2010 and April 2014, 25 in each group. The mean age was 75.14 years (\textpm11.64). Nine amputations (36%) occurred in each group. Amputation-free survival was superior in the active treatment group versus the standard group (169 393 days, 95% confidence interval = 134.926-203.861, vs 169 393 days, 95% confidence interval = 134.926-203.861). It was not statistically significant (log-rank, P = .958). Wound area reduction between both groups was not statistically different ( P = .651). Less adverse events of the lower limb occurred in the active treatment group ( P = .001). Our study showed that silver sulfadiazine and cerium nitrate is not inferior to standardized care on ischemic necrotic wounds of the lower extremity. Further studies are still needed to confirm its effectiveness

Effect of EPO on the extent of apoptosis in the fat grafts.

<p>PBS (100 µl), 20 IU EPO/100 µl PBS (low-dose), or 100 IU EPO/100 µl PBS (high-dose) were injected into fat grafts in three different groups of mice on the day of the fat injection and then repeated every three days for 18 days. (A) The extent of apoptosis was measured by the TUNEL assay, and is expressed as a percentage of the presence of apoptosis in the PBS-treated fat grafts. Each bar represents the mean extent of apoptosis ± SD in the fat graft in each treatment group at the end of the 15-week study period. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 for the difference between either the low-dose- or the high-dose EPO-treated fat grafts and the PBS-treated grafts. (B) Representative western blots of the expression levels of caspase 3 (Casp 3) and cytochrome c (Cyt c) in the PBS- and EPO-treated fat grafts at the end of the 15-week study period.</p

Histological analysis of the dissected fat grafts in all treatment groups in the two experiments.

<p><b><u>Footnotes</u></b></p><p>Values are presented as mean ± SD.</p><p>n  =  number of mice.</p><p>EPO  =  erythropoietin.</p><p>VEGF  =  vascular endothelial growth factor.</p><p>*P<0.05, **P<0.01 for the difference between either the low-dose- or the high-dose EPO-treated fat grafts and the PBS-treated grafts.</p