Health-related quality of life outcomes and hospitalization length of stay after micro-fragmented autologous adipose tissue injection in minor amputations for diabetic foot ulceration (MiFrAADiF Trial): results from a randomized controlled single-center clinical trial.

BACKGROUND: The diabetic foot ulcer (DFU) is a high prevalence complication that significantly impairs the health-related quality of life (HRQoL) and is characterized by prolonged hospital length of stay (LOS). The impact of the micro-fragmented autologous adipose tissue injection at the minor amputation wound in the case of DFU (MiFrAADiF) on HRQoL and LOS compared to the standard care has not been determined yet. METHODS: This was a two-arm, 6-month, individually-randomized controlled single-center clinical trial. A 1:1 randomization to local injection of autologous micro-fragmented adipose tissue (treatment group; N.=57) or standard clinical care (control group; N.=57) was performed. The primary objective was the HRQoL. The secondary endpoint was the LOS. HRQoL was assessed with the Medical Outcomes Study 36-item Short-Form Health Survey which provides 2 scores focused on physical (PCS) and mental functioning (MCS). The trial was registered in ClinicalTrials.gov (NCT03276312). RESULTS: The type of treatment (P=0.009) and the time elapsed since surgery (P=0.0000) demonstrated a significant improvement on PCS. The MCS improvements resulted in a non-significant association with treatment (P=0.21). The time elapsed since surgery showed a significant influence on the MCS (P=0.0000). The mean LOS was 16.2 days and 24.4 days for the treatment and the control group respectively (P=0.025). CONCLUSIONS: The MiFrAADiF Trial demonstrated a significant improvement in terms of physical HRQoL and a significant reduction of the hospital length of stay after injection of micro-fragmented autologous adipose tissue in diabetic patients' minor amputations wound.

Autologous micro-fragmented adipose tissue for the treatment of diabetic foot minor amputations: a randomized controlled single-center clinical trial (MiFrAADiF).

BACKGROUND: The diabetic foot ulcer (DFU) is one of the most prevalent complications of diabetes mellitus and often develops severe effects that can lead to amputation. A non-healing "minor" amputation often precedes a major amputation resulting in a negative impact on the function and quality of life of the patients. Stem cell-based therapies have emerged as a promising option to improve healing, and the adipose tissue is an abundant and easy to access source. The injection of autologous micro-fragmented adipose tissue at the amputation stump of a diabetic population undergoing a lower limb minor amputation was evaluated and compared with the standard care. METHODS: In this randomized controlled trial with two arms (parallel assignment) and no masking, 114 patients undergoing a lower limb minor amputation were randomized to standard of care or to micro-fragmented adipose tissue injection prepared using a minimal manipulation technique (Lipogems®) in a closed system. Clinical outcomes were determined monthly up to 6 months. Primary endpoint of the study was the evaluation of the healing rate and time after the minor amputation. Secondary endpoints included the assessment of safety, feasibility, technical success, relapse rate, skin tropism, and intensity of pain. RESULTS: At 6 months, 80% of the micro-fragmented adipose tissue-treated feet healed and 20% failed as compared with the control group where 46% healed and 54% failed (p = 0.0064). No treatment-related adverse events nor relapses were documented, and technical success was achieved in all cases. The skin tropism was improved in the treatment group, and the pain scale did not differ between the two groups. CONCLUSION: The results of this randomized controlled trial suggest that the local injection of autologous micro-fragmented adipose tissue is a safe and valid therapeutic option able to improve healing rate following minor amputations of irreversible DFU. The technique overcomes several stem cell therapy-related criticisms and its potential in wound care should be better evaluated and the therapeutic indications could be expanded. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT03276312. Date of registration: September 8, 2017 (retrospectively registered).

Does stem cell therapy induce myocardial neoangiogenesis? Histological evaluation in an ischemia/reperfusion animal model.

BACKGROUND: In an experimental model in the rabbit, a myocardial ischemia-reperfusion injury was obtained. Subsequently, the effects of homologous bone marrow stem cell (BMSC) administration were studied. METHODS: In 21 New Zealand adult rabbits, ischemia/reperfusion damage was induced by temporary occlusion of the anterior descending coronary artery. Homologous BMSCs were isolated, cultured and re-suspended for injection at the level of the ischemic zone. We evaluated the proangiogenetic effect of intramyocardial injections of BMSC at the peri-infarcted area. Histological evaluations were made after 20 days from the surgical procedure. RESULTS: In rabbits treated with intramyocardial BMSC administration, we demonstrated histologically capillary neoangiogenesis, without signs of tissue immunological reaction or of generation of new myocardial cells. On the contrary, only minimal neovascular supply was detected in rabbits treated with intravenous administration of BMSC. Only typical signs of ischemic myocardium injury were observed in the control group. CONCLUSION: These observations suggest that the effect of direct BMSC administration in ischemic myocardium could promote a capillary neoangiogenesis, which helps to prevent ischemic myocardial damage.

Surgical approach to intramyocardial administration of bone marrow stem cells in an animal model.

AIM: The aim of the study was to evaluate the surgical approach to intramyocardial (i.m.) injection of Bone Marrow Stem Cells (BMSCs) in a pre-clinical model and its complications. MATERIAL OF STUDY: In New Zealand rabbits an ischemia reperfusion injury lasting 20 min was induced by temporary ligation of anterior descending coronary artery during cardiac surgical procedure. Homologous BMSCs were isolated from the posterior iliac crest, cultured and re-suspended for injection. BMSC were injected at the peri-infarcted area and side effects were evaluated. A control group with myocardial infarction was treated with i.m. injections of saline, to evaluate possible side effects of injection. Comparison of ventricular premature contractions (VPC), ventricular tachycardia and ventricular fibrillation were recorded during surgery and after 7 and 21 days. RESULTS: Seven rabbits developed intractable ventricular fibrillation during the experimental protocol, three during coronary ligation but before cell injections and four following i.m. injections. At day 7, hourly PVC were more frequent in the groups of animals that received i.m. injections of BMSCs (132 ± 19 beats) compared to saline injections. (54 ± 14). CONCLUSIONS: Intramyocardial injections of BMSCs induced an electrical instability as shown by a high number of PVC as compared with intramyocardial injections of saline.

Neodymium:YAG laser treatment of lower leg telangiectasia: a new minimally invasive approach.

The aim of this study was to validate the safety and effectiveness of a new therapeutic procedure for the treatment of lower leg telangiectasia without clinical vein insufficiency. A group of 20 healthy women aged between 24 and 47 years (mean±sem 37.05 ± 1.47) with lower leg telangiectasia without clinical vein insufficiency, previously investigated by echo colour Doppler sonography, were recruited and were treated with neodymium:YAG laser (mean±sem 2.5 ± 0.11 sessions). Good or excellent results were obtained in 16 patients and the improvements were statistically significant (p < 0.01). Out of the 20 patients, 16 were satisfied with the procedure. We strongly support laser treatment of lower leg telangiectasia since it allows injection of chemicals to be avoided, and changes the stromal microarchitecture rearranging the fibroblast network into a more resistant pattern reducing the likelihood of relapse.