One-year Results of pCMV-VEGF165 Gene Transfer in Patients with Critical Lower Limb Ischemia Due to Peripheral Atherosclerosis and Diabetes Mellitus

Aim. To evaluate various parameters of walking using the Walking Impairment Questionnaire (WIQ) in patients with critical lower limb ischemia (CLLI) before and one year after spinal cord stimulation (SCS). Methods. In 46 patients with CLLI aged 64.5 (54.9–72.6) years, the following parameters were assessed before and one year after SCS using the WIQ questionnaire: pain, distance, speed, stairs, where 100% no restrictions when walking. Results. In patients with CLLI, low WIQ values were initially identified for the scales of distance, speed, and stairs, less than 10%, and about 30% for the pain scale. One year after SCS, the values of pain, distance, and speed increased to 83.3% (68.4%–100%), 39.5% (17.9%–55.2%), and 24.4% (17.3%–35.8%), respectively, with significance at p < 0.001, p = 0.004, and p = 0.005, respectively. The lowest rates were on the scale of stairs: 6.2% (3.4%–7.3%), p = 0.06. Before the SCS, the factor adversely affecting the indicators of the distance scale was diabetes mellitus (β = –0.417; p = 0.002), and the age factor adversely affected the walking speed (β = –0.544; p = 0.005). After SCS, age exerted a negative effect on the walking speed (β = –0.497; p = 0.002). The scale for stairs was negatively affected by the presence of coronary heart disease (β = –0.421; p = 0.001) or diabetes mellitus (β = –0.325; p = 0.032). Conclusion. The use of SCS in patients with CLLI improves the parameters of walking in the long-term follow up after treatment, except for the ability to climb stairs. Age and the presence of diabetes mellitus or coronary heart disease are adverse factors that affect the walking parameters, both before and in the long-term period after SCS.Received 14 March 2019. Accepted 25 July 2019.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.

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pCMV-vegf165Intramuscular Gene Transfer is an Effective Method of Treatment for Patients With Chronic Lower Limb Ischemia

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248415574336 ◽

2015 ◽

Vol 20 (5) ◽

pp. 473-482 ◽

Cited By ~ 34

Author(s):

Roman V. Deev ◽

Ilia Y. Bozo ◽

Nina D. Mzhavanadze ◽

Dmitriy A. Voronov ◽

Aleksandr V. Gavrilenko ◽

...

Keyword(s):

Gene Transfer ◽

Lower Limb ◽

Limb Ischemia ◽

Lower Limb Ischemia

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Emerging Therapies for Chronic Lower Limb Ischemia (Novel Strategies Using Growth Factors, Gene Transfer, and Cellular Techniques to Promote Angiogenesis)

Endovascular Intervention for Vascular Disease ◽

10.3109/9781420020953-11 ◽

2007 ◽

pp. 89-96

Keyword(s):

Growth Factors ◽

Gene Transfer ◽

Lower Limb ◽

Limb Ischemia ◽

Lower Limb Ischemia ◽

Emerging Therapies

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Hyperfibrinogenemia in Peripheral Arterial Disease: Coexistent and Independent Risk Factor (A Report of Two Cases and Review of Literature)

PRILOZI ◽

10.2478/prilozi-2018-0046 ◽

2018 ◽

Vol 39 (2-3) ◽

pp. 93-96

Author(s):

Marijan Bosevski ◽

Gorjan Krstevski ◽

Irena Mitevska ◽

Emilija Antova ◽

Golubinka Bosevska

Keyword(s):

Diabetes Mellitus ◽

Risk Factor ◽

Lower Limb ◽

Case Reports ◽

Limb Ischemia ◽

Arterial Disease ◽

Lower Limb Ischemia ◽

Left Limb ◽

Peripheral Arterial

Abstract These case reports aim to show that hyperfibrinogenemia is a risk factor for the progression and prognosis of peripheral arterial disease (PAD), in patients with and without diabetes mellitus type 2. We present a patient with PAD who has type 2 diabetes mellitus, who has previously been repeatedly treated for lower limb ischemia with multiple vascular surgeries performed. A few weeks before admission the patient developed critical lower limb ischemia, which was treated with an iliaco-popliteal and femorofemoral bypass. The patient had elevated serum fibrinogen values. In the current admission, renewed left limb ischemia was diagnosed, and surgically evaluated with a recommendation for amputation of the left limb as a surgical recommendation. Our second patient had a stable intermittent claudication, dyslipidemia and hyperfibrinogenemia. He was successfully treated for those risk factors. Regular monitoring of the patient showed improved claudication distance and quality of life Our case reports, supported by a literature review, demonstrate that hyperfibrinogenemia is a possible risk factor for progression and the prognosis of PAD.

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Long-term results of pl-VEGF165 intramuscular gene transfer in patients with atherosclerotic chronic lower limb ischemia

Kardiologiya i serdechno-sosudistaya khirurgiya ◽

10.17116/kardio20158443-49 ◽

2015 ◽

Vol 8 (4) ◽

pp. 43 ◽

Cited By ~ 1

Author(s):

R. V. Deev ◽

R. E. Kalinin ◽

Yu. V. Chervyakov ◽

I. N. Staroverov ◽

I. L. Plaksa ◽

...

Keyword(s):

Gene Transfer ◽

Lower Limb ◽

Limb Ischemia ◽

Long Term Results ◽

Lower Limb Ischemia

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186. Long-Term Results of pCMV-vegf165 Intramuscular Gene Transfer in Patients With Chronic Lower Limb Ischemia

Molecular Therapy ◽

10.1016/s1525-0016(16)33791-1 ◽

2015 ◽

Vol 23 ◽

pp. S74-S75 ◽

Cited By ~ 3

Author(s):

Ilia Y. Bozo ◽

Roman V. Deev ◽

Igor L. Plaksa ◽

Nina D. Mzhavanadze ◽

Yuriy V. Chervyakov ◽

...

Keyword(s):

Gene Transfer ◽

Lower Limb ◽

Limb Ischemia ◽

Long Term Results ◽

Lower Limb Ischemia

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Contrast-Associated Acute Kidney Injury in Patients with and without Diabetes Mellitus Undergoing Computed Tomography Angiography and Local Thrombolysis for Acute Lower Limb Ischemia

Vascular and Endovascular Surgery ◽

10.1177/15385744211051503 ◽

2021 ◽

pp. 153857442110515

Author(s):

Talha Butt ◽

Leena Lehti ◽

Jan Apelqvist ◽

Anders Gottsäter ◽

Stefan Acosta

Keyword(s):

Diabetes Mellitus ◽

Acute Kidney Injury ◽

Lower Limb ◽

Kidney Injury ◽

Limb Ischemia ◽

Lower Limb Ischemia ◽

Iodinated Contrast ◽

Increased Risk ◽

And Gender ◽

Iodine Dose

Purpose Repetitive iodinated contrast media exposure may be harmful for the kidneys. The aim of the present study was to evaluate if patients with diabetes mellitus (DM) undergoing CT angiography (CTA) and local continuous thrombolysis for acute lower limb ischemia (ALI) had an increased risk of developing contrast-associated acute kidney injury (CA-AKI) compared to patients without DM. Methods: This is a retrospective study of patients undergoing CTA and local continuous thrombolysis due to ALI between 2001 and 2018. CA-AKI was defined as a 25% increase in serum creatinine within 72 hours after latest contrast administration. Results: There was no difference ( P = .30) in the frequency of CA-AKI between patients with (27.9%; n = 43) and without DM (20.6%; n = 170). Among patients with CA-AKI, patients with DM had a lower ( P < .001) estimated glomerular filtration rate (eGFR) at discharge (55 ml/min/1.73 m2) than at admission (70 ml/min/1.73 m2), while no such difference was found in the group without DM ( P = .20). The gram-iodine dose/eGFR ratio was higher ( P < .001) in patients with CA-AKI (median 1.49, [IQR 1.34-1.81]) than in those who did not develop CA-AKI (median 1.05 [IQR 1.00-1.13]). There was a trend that gram-iodine dose/eGFR ratio (OR 1.42/standard deviation increment, 95% CI 1.00-2.02; P = .050) was associated with an increased risk of CA-AKI, after adjusting for DM, age, and gender. Conclusions: The frequency of CA-AKI was high after CTA and local continuous thrombolysis for ALI without shown increased frequency for the DM group. Among patients with CA-AKI, however, patients with DM had worse renal function at discharge than those without DM. The gram-iodine dose/eGFR ratio in these patients needs to be lower to improve renal outcomes, particularly in patients with DM.

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Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in patients with critical limb ischemia and type 2 diabetes with no possibility of revascularization: Study protocol for a randomized controlled double-blind phase II clinical trial (The NOMA Trial).

10.21203/rs.3.rs-321347/v1 ◽

2021 ◽

Author(s):

Barbara Soria-Juan ◽

Mariano Garcia-Arranz ◽

Lucía Llanos ◽

César Aparicio ◽

Alejandro Gonzalez ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Cell Therapy ◽

Stromal Cells ◽

Lower Limb ◽

Limb Ischemia ◽

Therapeutic Angiogenesis ◽

Double Blind ◽

Lower Limb Ischemia

Abstract Background: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. Methods: A multicenter, randomized double-blind, placebo-controlled trial has been designed. 90 eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: the control group (n=30), low cell dose treatment group (n=30), and high cell dose treatment group (n=30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. Discussion: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future.Trial registration: ClinicalTrials.gov NCT04466007. Registered on January 07, 2020.

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The role of hypoxia-inducible factorin the syndrome of chronic lower limb ischemia and influence of diabetes mellitus on process of angiogenesis

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2017-16-3-4-9 ◽

2017 ◽

Vol 16 (3) ◽

pp. 4-9 ◽

Cited By ~ 1

Author(s):

M. N. Kudykin ◽

V. V. Beschastnov ◽

R. A. Deryabin ◽

G. E. Sheiko ◽

L. M. Celousova ◽

...

Keyword(s):

Diabetes Mellitus ◽

Lower Limb ◽

Hypoxia Inducible Factor ◽

Limb Ischemia ◽

Peripheral Artery ◽

Lower Limb Ischemia ◽

Cell Responses ◽

Patients With Diabetes ◽

Artery Disease

In this review, we pay attention to the role of the hypoxia-inducible factor (HIF) in the development of response of the organism to hypoxia. Special attention is given to the regulation of the cell responses to hypoxia in chronic peripheral artery disease in patients with diabetes mellitus (DM). Cells can survive by activation of a transcription of genes, involved in angiogenesis, glucose metabolism and cell proliferation. Artificial rising of concentration and activity of HIF stimulates an angiogenesis and improves ulcers healing of the lower extremities. The data of the literature are provided on the possible methods of increasing HIF concentration in tissues, which could be a new way to stimulate wound healing in the patients with DM.

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Erosive and ulcerative lesions of the gastrointestinal tract and bleeding in patients with critical lower limb ischemia and diabetes mellitus underwent endovascular interventions

Grekov s Bulletin of Surgery ◽

10.24884/0042-4625-2021-180-1-65-72 ◽

2021 ◽

Vol 180 (1) ◽

pp. 65-72

Author(s):

A. A. Poliantsev ◽

D. V. Frolov ◽

A. M. Linchenko ◽

S. N. Karpenko ◽

A. A. Chernovolenko ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Lower Limb ◽

Limb Ischemia ◽

Lower Limb Ischemia ◽

Endovascular Interventions ◽

Ulcerative Lesions ◽

The Relationship

The objective was to study the prevalence of erosive and ulcerative gastroduodenal lesions, bleedings of this localization and the relationship with factors predisposing to them in patients with critical lower limb ischemia and type 2 diabetes mellitus who underwent endovascular intervention for limb revascularization.Methods and materials. The study included 81 patients aged 67.5±6.8 years, hospitalized in the department of vascular surgery with critical lower limb ischemia of atherosclerotic genesis and type 2 diabetes mellitus to perform revascularization by means of transluminal balloon angioplasty with stenting when indicated. In the preoperative period, all patients underwent fibrogastroduodenoscopy, according to the results of which a scoring assessment of the lesion of the gastric mucosa and duodenum was presented.Results. All patients participating in the study were diagnosed with pathology of the gastroduodenal zone: in 95.1 % of the inflammatory nature, in 4.9 % of the ulcer. The relationship between the duration of rest pain, the fact of damage to the mucous membrane of the upper gastrointestinal tract and its severity was not revealed, but the relationship of erosive and ulcerative lesions of the stomach and duodenum with the number of taken pain pills was determined. In patients with repeated endovascular intervention and / or amputation, gastrointestinal bleedings were more often recorded compared with study participants who underwent a single revascularization – 11.1 and 1.6 % of patients, respectively.Conclusion. Erosive and ulcerative lesions of varying severity are present in all patients with critical lower limb ischemia on the background of diabetes mellitus. At the same time, patients with repeated endovascular interventions and / or amputations are more susceptible to bleeding. For the prevention of pathology of the stomach and duodenum, an in-depth diagnosis and a differentiated approach are required.

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