Role of Hybrid Interventions in Management of Critical Lower Limb Ischemia

Aims: To evaluate safety and efficacy of the hybrid technique in revascularization of multilevel lower limb arterial occlusive disease in patients with critical lower limb ischemia. Study Design: A prospective non comparative interventional study. Place and Duration of Study: It was conducted between February 2017 and June 2019 in the Department of Vascular Surgery, Tanta University hospital. Methodology: The study included 23 patients were treated with hybrid intervention techniques, and data were collected prospectively. Detailed history was taken and clinical examination was done for every patient along with routine laboratory investigations and radiological work up like duplex scanning with or without CT angiography. All patients were undergone hybrid interventions in an operating room with imaging facilities (mobile c-arm device) where both surgical and endovascular interventions were done simultaneously. Results: Twenty three patients were treated for unilateral critical lower limb ischemia using single session elective hybrid intervention. The patients age ranged from 46 to 76 (mean 62.6) with 19 males. 8 patients (34.8%) presented with ischemic rest pain and the remainder (65.2%) presented with tissue loss (ischemic ulcer or gangrene). most common inflow procedure was femoro-popliteal supragenicular bypass, and the commonest outflow procedure was tibial angioplasty. Technical success was achieved in 22 patients. Mean ABI was improved from 0.49 preoperatively to 0.84 in early post-operative measurements. Out of 23 limbs treated there were 20 limbs saved from amputation (87% limb salvage rate). We had three mortalities from other co-morbidities and four minor complications treated conservatively and resolved. Conclusion: Hybrid interventions were proved to be reasonable, effective and safe option for treatment of critical lower limb ischemia.

Combined Analysis of Clinical Data on HGF Gene Therapy to Treat Critical Limb Ischemia in Japan

Objectives: The objective of this combined analysis of data from clinical trials in Japan, using naked plasmid DNA encoding hepatocyte growth factor (HGF), was to document the safety and efficacy of intramuscular HGF gene therapy in patients with critical limb ischemia (CLI). Methods: HGF gene transfer was performed in 22 patients with CLI in a single-center open trial at Osaka University; 39 patients in a randomized, placebo-controlled, multi-center phase III trial, 10 patients with Buerger’s disease in a multi-center open trial; and 6 patients with CLI in a multi-center open trial using 2 or 3 intramuscular injections of naked HGF plasmid at 2 or 4 mg. Resting pain on a visual analogue scale (VAS) and wound healing as primary endpoints were evaluated at 12 weeks after the initial injection. Serious adverse events caused by gene transfer were detected in 7 out of 77 patients (9.09%). Only one patient experienced peripheral edema (1.30%), in contrast to those who had undergone treatment with VEGF. At 12 weeks after gene transfer, combined evaluation of VAS and ischemic ulcer size demonstrated a significant improvement in HGF gene therapy group as compared to the placebo group (P=0.020). Results: The long-term analysis revealed a sustained decrease in the size of ischemic ulcer in HGF gene therapy group. In addition, VAS score over 50 mm at baseline (total 27 patients) demonstrated a tendency (P=0.059), but not significant enough, to improve VAS score in HGF gene therapy as compared to the placebo group. Conclusions: The findings indicated that intramuscular injection of naked HGF plasmid tended to improve the resting pain and significantly decreased the size of the ischemic ulcer in the patients with CLI who did not have any alternative therapy, such as endovascular treatment (EVT) or bypass graft surgery. An HGF gene therapy product, CollategeneTM, was recently launched with conditional and time-limited approval in Japan to treat ischemic ulcer in patients with CLI. Further clinical trials would provide new therapeutic options for patients with CLI.

Limb Revascularization in Patients with Diabetes Mellitus

The review describes morbidity, mortality and possible complication rates for diabetic patients with peripheral arteries disease. The article demonstrates the modern tendency in the surgical treatment of peripheral arteries atherosclerosis, shows and compares worldwide results of endovascular and open revascularization. The authors have assessed the risk of amputation for patients with diffuse peripheral arteries disease and described basic treatment principals for better chronic ischemic ulcer healing.

A multi centric study of diabetic foot ulcer: causes and complications

Background: Diabetes mellitus is a metabolic disorder and has become an epidemic. 73 million people in India have diabetes mellitus. Presently India has ranked the second highest country with diabetics in the world. Diabetic foot ulcer is a result of one or both of the complications of diabetes such as neuropathy and ischemia. The objective of the study was to study the causes for the ulcer formation on the toes.Methods: A prospective study was carried out from January 2016 to August 2018 from multiple diabetic clinics in Hyderabad, India. All the patients had undergone the following tests. 1) X-ray foot, 2) ABI (ankle brachial index) test, 3) Neuropathy test by VPT (vibration perception test) and monofilament.Results: The age of the patients mostly ranged from 50 to 70 years. 61% of the patients had neuropathic ulcer, 20% had ischemic ulcer, 19% had neuro-ischemic ulcer. 69% of these patients had osteomyelitis. 52% had ulcer on the right foot and 48% on the left. 15% had dry gangrene with ulcer where as 85% had infected ulcers. 60% of the ulcers were only on the plantar aspect and 24% had ulcers all around the toe. ABI (ankle brachial index) was normal 0.9 to 1.2 in 80% of patients whereas 20% had abnormal (<0.9). 60% of patients had ulcers involving the 1st and 2nd toes and both feet were almost equally affected.Conclusions: Neuropathy is the leading cause for ulcers on the toes followed by ischemia and then infection. Treating the neuropathic ulcer early can bring down the amputation rate of the toes by 50%.

An inflammatory memory and angiogenic self-assembling nanofiber hydrogel scaffold seeded with Akkermansia muciniphila to accelerate the healing of diabetic ischemic ulcers

In this research, a polypeptide skeleton was synthesized based on 3,4-dihydroxyphenylalanine (DOPA) and conjugated with inflammatory and angiogenesis peptides, combined with A. Muciniphila as a novel strategy for diabetic ischemic ulcer treatment.