Results of a prospective observational study of autologous peripheral blood mononuclear cell therapy for no-option critical limb-threatening ischemia and severe diabetic foot ulcers.

BACKGROUND: Cell therapy with autologous peripheral blood mononuclear cells (PB-MNCs) may help restore limb perfusion in patients with diabetes mellitus and critical limb-threatening ischemia (CLTI) deemed not eligible for revascularization procedures and consequently at risk for major amputation (no-option). Fundamental is to establish its clinical value and to identify candidates with a greater benefit over time. Assessing the frequency of PB circulating angiogenic cells and extracellular vesicles (EVs) may help in guiding candidate selection. METHODS: We conducted a prospective, non-controlled, observational study on no-option CLTI diabetic patients that underwent intramuscular PB-MNCs therapy, which consisted of more cell treatments repeated a maximum of three times. The primary endpoint was amputation rate at 1 year following the first treatment with PB-MNCs. We evaluated ulcer healing, walking capability, and mortality during the follow-up period. We assessed angiogenic cells and EVs at baseline and after each cell treatment, according to primary outcome and tissue perfusion at the last treatment [measured as transcutaneous oxygen pressure (TcPO2)]. RESULTS: 50 patients were consecutively enrolled and the primary endpoint was 16%. TcPO2 increased after PB-MNCs therapy (17.2 ± 11.6 vs 39.1 ± 21.8 mmHg, p < .0001), and ulcers healed with back-to-walk were observed in 60% of the study population (88% of survivors) during follow-up (median 1.5 years). Patients with a high level of TcPO2 (≥ 40 mmHg) after the last treatment showed a high frequency of small EVs at enrollment. CONCLUSIONS: In no-option CLTI diabetic patients, PB-MNCs therapy led to an improvement in tissue perfusion, a high rate of healing, and back-to-walk. Coupling circulating cellular markers of angiogenesis could help in the identification of patients with a better clinical benefit over time.

Square, Random Fasciocutaneous Plantar Flaps for Treating Noninfected Diabetic Plantar Ulcers: A Patient Series.

In patients with diabetes, the off-loading cast has not been widely used to treat plantar ulcers because of its poor acceptance by patients and the high risk of side effects. We evaluated the safety and efficacy of an alternative surgical treatment: a square, fasciocutaneous random plantar flap to cover plantar ulcers. From December 2012 to February 2013, we enrolled 23 consecutive diabetic patients with deep neuropathic or neuroischemic plantar ulcers. Of these 23 patients, 9 underwent percutaneous transluminal angioplasty, 10 had the metatarsal removed, 3 underwent dorsiflexory, distal metatarsal osteotomies, 2 underwent first metatarsophalangeal joint resection and ray stabilization with Kirschner wires, and 1 each underwent midfoot exostectomy, sesamoidectomy, and partial calcanectomy. A square random fasciocutaneous plantar flap was created for all 23 patients. Two patients were excluded from the analysis for weightbearing on the involved foot within 24 hours of surgery. The healing rate was 100% for the remaining 21 patients, with healing by first intention in 15 (mean ± standard deviation time to healing 30 ± 13 days), by second intention in 5 (86 ± 40 days), and by surgical revision in 1. The overall mean healing time was 44 ± 31 days. During a mean follow-up of 724 ± 275 days, no ulcer recurred; however, 1 transfer ulcer appeared on an adjacent metatarsal head. The use of a square random fasciocutaneous plantar flap is a safe and effective surgical option for treating neuropathic plantar ulcers, offering a high healing rate, a short healing time, and a low rate of recurrence.

The management of the infected diabetic foot.

Diabetes is a chronic disease with a worldwide increasing trend. Foot complications, closely related to neuropathy and obstructive peripheral vascular disease, are responsible for more than 1 million of leg amputations every year. Foot infection can dramatically increase the risk of amputation. Although many ulcer classification systems have been proposed to stratify the severity of the infectious process, the definition of a specific therapeutic approach still remains an unsolved problem. A Diabetic Foot Triage and an Integrated Surgical Protocol are proposed to identify a diagnostic flowchart and a step-by-step surgical protocol that can be applied in the treatment of diabetic foot infection. Considering the rapid climbing of multidrug resistant strains it is very important to rationalize the use of antibiotics utilizing them only for the treatment of true infected ulcers. PAD is widely considered the most important factor conditioning the outcome of a diabetic foot ulcer. Currently no randomized control trials are reported in the international literature directly comparing open versus endovascular revascularisation in diabetic patients with CLI. Insufficient data are available to demonstrate whether open bypass surgery or endovascular interventions are more effective in these patients. A decisional flow chart in choosing the best revascularization strategy in diabetic patients with CLI is proposed. Goals and technical aspects of emergency and elective surgical procedures in diabetic foot are analysed to evaluate critical aspects and to suggest proper surgical choices.

Long-term follow-up of tibiocalcaneal arthrodesis in diabetic patients with early chronic Charcot osteoarthropathy.

Charcot osteoarthropathy with severe ankle instability and deformity is often managed with below-the-knee amputation if deformity and cutaneous compromise result in osteomyelitis. Recently, some surgeons have reported satisfactory outcomes with ankle arthrodesis in the coalescence or remodeling (subacute and chronic) stages of the disease before the onset of joint instability, severe deformity, and ulcer formation. This observational study describes the clinical outcomes of ankle arthrodesis in a cohort of 45 diabetic patients who underwent unilateral ankle arthrodesis for Charcot neuroarthropathic ankle deformity before the development of ulceration and bone infection. Two (4.44%) of the patients were lost to follow-up, whereas 2 (4.44%) others underwent below-the-knee amputation shortly after the ankle arthrodesis because of postoperative infection. After a mean follow-up duration of 5 ± 2.85 years, 39 (86.67%) patients returned to independent ambulation wearing custom-made shoes with molded insoles, whereas 2 (4.44%) others required pneumatic casts for ambulation.