1. Introduction
mellitus, diabetic foot syndrome, depression, macroangiopathic complications, PAD, necrotic, chronic limb-threatening ischemia, diabetes, DFUs, amputation, ulcerative, Diabetic foot syndrome, infection, neuropathic diabetic foot, diabetic foot disease, DFS, neuropathy, pain, diabetic macroangiopathy, Neuropathy
DIABETIC MACROANGIOPATHY, NEUROPATHY, CRITICAL LIMB ISCHEMIA, ULCERATIVE, CHRONIC LIMB-THREATENING ISCHEMIA, NECROTIC, INFECTION, PAD, NEUROPATHY, ULCERATION, COMPLICATIONS, DIABETES
Diabetic foot syndrome (DFS) is one of the most serious macroangiopathic complications of diabetes. The primary treatment option is revascularization, but complementary therapies are still being sought. The study group consisted of 18 patients diagnosed with ischemic ulcerative and necrotic lesions in DFS. Patients underwent revascularization procedures and, due to unsatisfactory healing of the lesions, were randomly allocated to two groups: a group in which bicistronic VEGF165/HGF plasmid was administered and a control group in which saline placebo was administered. Before gene therapy administration and after 7, 30, 90, and 180 days, color duplex ultrasonography (CDU) was performed, the ankle-brachial index (ABI) and transcutaneous oxygen pressure (TcPO2) were measured, and DFS changes were described and documented photographically. In the gene therapy group, four out of eight patients (50%) healed their DFS lesions before 12 weeks. During this time, the ABI increased by an average of 0.25 and TcPO2 by 30.4 mmHg. In the control group, healing of the lesions by week 12 occurred in six out of nine patients (66.67%), and the ABI increased by an average of 0.14 and TcPO2 by 27.1 mmHg. One major amputation occurred in each group. Gene therapy may be an attractive option for complementary treatment in DFS.Diabetes mellitus, a global epidemic, is currently diagnosed in half a billion people. It is estimated that this number will increase by one-quarter by 2030 and double by 2040 [One of the most serious complications of diabetes is diabetic foot syndrome (DFS). By definition, it is an infection, ulceration, or tissue destruction of the foot in a person with currently or previously diagnosed diabetes, usually accompanied by neuropathy and/or PAD in the lower limb [Neuropathy of the distal parts of the limbs leads to a reduction or loss of superficial sensitivity (pressure, touch), as well as a vibration sensation. The result is a reduction in pain sensation and a greater risk of injury and ultimately a hard-to-heal infection, resulting in a neuropathic diabetic foot [In diabetic macroangiopathy, which can occur separately or coexist with neuropathy, there is multisegmental vascular involvement, especially below the knee, with impaired collateral circulation [The presence of DFS significantly Impairs quality of life, limiting life activities as well as psychosocial functioning. The prolonged healing process, often without favorable results, increases patient frustration and stress, and in many cases, leads to depression [On a societal level, the negative effects of the ever-increasing number of DFS and DFUs include the ever-increasing burden on national health care systems. In 2017, diabetes care costs in the US totaled USD 237 billion, with one-third of the costs attributable to the need to treat diabetic foot disease [In accordance with the Hippocratic maxim that prevention is better than cure, special emphasis should be placed on primary prevention. It should include education on diabetes management, the principles of a healthy diet and appropriate physical activity, the prohibition of smoking, and direct foot protection against injury. A well-educated patient can not only have metabolically well-balanced diabetes, but also significantly delay or prevent the development of complications. Unfortunately, in many cases, when it is too late for primary prevention, diabetes and its complications, including DFS, must be intensively treated.For ischemic lesions, patients are eligible for revascularization treatment. Vascular treatments, due to the peripherally dominant nature of the lesions, are mostly endovascular. They offer a chance of postoperative blood supply to the ischemic area and can accelerate the tissue healing process. However, these procedures are not always technically feasible or, when ultimately performed, do not have the intended beneficial effect. “Patients not eligible for revascularization” (NCR) are left with good diabetic metabolic control, use of statins, antiplatelet drugs, or smoking cessation. Such a conservative treatment strategy is not a part of active treatment. Therefore, in addition to improving endovascular techniques, new treatments for DFS are being sought for NCR patients.Alternative treatments for the chronic limb-threatening ischemia (CLTI) patients are still being sought. Vasoactive drugs have not been proven to have a beneficial effect on wound healing and amputation rates in CLTI [For many years, attempts have been made to treat critical limb ischemia with gene therapy using plasmids encoding growth factors or autologous stem cells obtained from bone marrow or adipose tissue [