Therapeutic Angiogenesis in Critical Limb Ischemia by Implantation of Autologous Hematopoietic Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4222-4222
Author(s):  
Juan Besalduch ◽  
Raul Lara ◽  
Antonia Sampol ◽  
Antonio Gutierrez ◽  
Pacual Lozano ◽  
...  
Keyword(s):  
Critical Limb Ischemia ◽  
Blood Cells ◽  
Gastrocnemius Muscle ◽  
Hematopoietic Cells ◽  
Limb Ischemia ◽  
Therapeutic Angiogenesis ◽  
Peripheral Mononuclear Blood ◽  
Pain At Rest ◽  
Walking Time

Abstract Patients with critical limb ischemia in whom surgical repair is not possible because bad distal vasculature, have an ominous prognosis. This study describes a technique for treatment of patients with critical limb ischemia with implantation of autologous peripheral mobilized hematopoietic cells, with the aim to stimulate angiogenesis. Twelve patients (9M, 3F), with a median age of 58 years (22–78) with critical limb ischemia were treated by injections of peripheral mobilized blood cells in the gastrocnemius muscle of the affected limb. The inclusion criteria were patients with chronic limb ischemia grade III-IV by Doppler examination, plethismography and angiography, with failure to respond to non-surgical treatment and some with previous surgery, and that were no candidates for surgical revascularization. The patients were treated by G-CSF (Neupogen, Amgen) 5μ /kg weight/d during 5 days. At day fifth and sixth we obtained peripheral mononuclear blood cells by means of a CS-3000 Plus (Baxter) blood cell separator. The unmanipulated cells were injected in the affected limb in 2 ml aliquots into the gastrocnemius muscle. Each product of a single apheresis (volume 50 ml) were injected in a sole limb. Six patients received injections only in one limb. Each patient were evaluated regularly for rest pain, amount of required analgesia, healing of the ulcers, peak walking time and, Doppler, plethismographic and angiographic findings. The mean number of injected CD34+ cells in each limb was 0.77 x 106/kg. There were no secondary effects for the mobilization and injection of cells in the 12 studied patients. Moreover, in 7 patients studied with a median follow-up of 1 year, 5 showed an improvement of all parameters, specially pain at rest, peak walking time and skin throphic lesions. Two patients suffered early amputation of the affected extremity because obstruction of an old by-pass. Despite the short follow-up and small patient series, this technique is expected to achieve relief of pain and decrease in major amputations in this critical population. However, comparative studies with longer follow-up should be done to confirm the benefits of this technique.

scholarly journals Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients with No-Option Critical Limb Ischemia

2021 ◽  
Vol 10 (10) ◽  
pp. 2213
Author(s):  
Alessia Scatena ◽  
Pasquale Petruzzi ◽  
Filippo Maioli ◽  
Francesca Lucaroni ◽  
Cristina Ambrosone ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Critical Limb Ischemia ◽  
Diabetic Foot ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Limb Ischemia ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group (p = 0.0037). The Kaplan–Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group (p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group (p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group (p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.

Early outcomes of novel Temren atherectomy device combined with drug-coated balloon angioplasty for treatment of femoropopliteal lesions

Vascular ◽  
2021 ◽  
pp. 170853812110298
Author(s):  
Görkem Yiğit
Keyword(s):  
Critical Limb Ischemia ◽  
Bypass Graft ◽  
Ankle Brachial Index ◽  
Limb Ischemia ◽  
Rotational Atherectomy ◽  
Total Occlusion ◽  
The Mean ◽  
Knee Pathology ◽  
Drug Coated Balloon

Objectives In this study, perioperative properties and early outcomes of patients who underwent combined Temren rotational atherectomy (RA) and drug-coated balloon (DCB) angioplasty treatment for complex femoropopliteal lesions in a single center were reported. Methods Between June 2019 and February 2020, 40 patients who underwent combined Temren RA and DCB treatment due to critical lower limb ischemia or claudication-limiting daily living activities were retrospectively evaluated. Results The mean age of patients was 73.2 ± 7.8 years and the majority of the patients were male (65%). Of the patients, 17 had critical limb ischemia and 23 had lifestyle-limiting claudication. Pathologies were total occlusion in 33 limbs and critical stenosis in seven limbs. Nine patients previously underwent endovascular intervention or surgery. The mean total occlusion length was 140.9 ± 100.9 (range, 20–360) mm in patients with chronic total occlusion. There was an additional iliac artery pathology in 5 and below the knee pathology in 8 patients. Rotational atherectomy was possible in all cases. Flow-limiting dissection was seen in six patients (15%). Provisional stent was performed to these patients. Following Temren RA, all patients underwent DCB. Adequate vascular lumen (less than 30% stenosis) was provided in all patients and the symptoms regressed. No distal embolization was encountered. Access site complications (17.5%) were small hematoma in four patients, ecchymosis in two patients, and pseudoaneurysm of the femoral artery in one patient. The mean follow-up was 13.55 ± 4.2 (range, 1–18) months. Re-occlusion was seen in three patients (7.5%) ( n = 2 at 2 months and n = 1 at 4 months). Of these patients, two had required open revascularization via femoropopliteal bypass graft with common, superficial femoral, and popliteal artery endarterectomy and one had required femoro-posterior tibial artery bypass. Four minor toe amputations (10%) were performed to reach complete wound healing in the critical limb ischemia patients. A below-knee amputation was performed in a 94-year-old patient with long segment stenosis at the end of a 1-month follow-up period. There was no mortality after follow-ups. The Kaplan–Meier estimator estimated the rate of freedom from target lesion revascularization (TLR) which was 92.3%. The decrease in the Rutherford levels after the procedure was found to be statistically significant in 36 patients ( p < 0.001). The increase in the ankle–brachial index after the procedure was found to be statistically significant in 36 patients ( p < 0.001). Conclusions Combined use of Temren RA with adjunctive DCB is safe and effective method with high rates of primary patency and freedom from TLR and low rates of complication in the treatment of femoropopliteal lesions.

scholarly journals SIMULTANEOUS REVASCULARIZATION OF AORTOFEMORAL AND FEMOROPOPLITEAL ARTERIAL SEGMENTS BY SEMICLOSED LOOP ENDARTERECTOMY

2017 ◽  
Vol 176 (2) ◽  
pp. 28-32
Author(s):  
V. V. Shlomin ◽  
A. V. Gusinskiy ◽  
M. L. Gordeev ◽  
I. V. Mikhailov ◽  
D. N. Maistrenko ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Arterial Occlusive Disease ◽  
Long Term Results ◽  
Single Level ◽  
Individual Approach ◽  
Chronic Limb Ischemia

OBJECTIVE. The authors would like to consider the possibility and feasibility of simultaneous revascularization of two arterial segments in patients with lower extremity arterial occlusive disease by method of semiclosed loop endarterectomy. MATERIALS AND METHODS. The research included 143 patients. Revascularization of aortofemoral segment was performed on 67 patients. The simultaneous revascularization of aortofemoral and femoropopliteal segments was carried out for 76 patients. The follow-up period was 5 years. RESULTS. There was revealed that the long-term results of multilevel reconstruction were worse that single-level reconstruction. This method requires an individual approach. The best results of simultaneous interventions were obtained in patients aged 60 and older with the III stage of chronic limb ischemia and 2 or 3 working shin arteries. The worst results were observed in patients younger than 50 year old with IV stage of critical limb ischemia and significant lesions of shin arteries.

Abstract 14293: Time to Wound Healing and Major Adverse Limb Events in Patients With Critical Limb Ischemia Treated With Endovascular Therapy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Grant W Reed ◽  
Negar Salehi ◽  
Pejman Raeisi-Giglou ◽  
Umair Malik ◽  
Rami Kafa ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endovascular Therapy ◽  
Critical Limb Ischemia ◽  
Proportional Hazards ◽  
Limb Ischemia ◽  
Major Amputation ◽  
Cox Proportional Hazards ◽  
Time Dependent ◽  
Kaplan Meier

Introduction: There have been few studies evaluating the influence of time to wound healing on outcomes in patients with critical limb ischemia (CLI) after endovascular therapy. Methods: In this prospective study, patients with CLI treated with endovascular therapy were assessed for comorbidities, presence of wounds, wound healing, and major adverse limb events (MALE; major amputation, surgical endartectomy, or bypass) over time. The incidence of MALE was compared across patient and wound characteristics by Kaplan-Meier analysis. Associations between these variables and MALE were determined by Cox proportional hazards analysis. Results: A total of 252 consecutive patients with CLI were treated between November 1, 2011 and April 1, 2015; 179 (71%) had wounds, of which 97 (54%) healed. During median follow-up of 12.7 months (interquartile range 3.9 - 23.9 months), 46 (18%) had MALE. Wounds were associated with a greater risk of MALE (Hazard Ratio [HR] 3.5; 95% Confidence Interval [CI] 1.4-8.9; p=0.008). As a time-dependent covariate, wound healing was associated with less MALE (HR 0.23; 95% CI 0.10-0.53; p<0.001), and MALE was more frequent in patients with unhealed wounds (23% vs 11%; p<0.0001) (Figure - A). There was significantly less MALE in patients whose wounds healed within 4 months (24% vs 10%; p=0.032) (Figure - B), and less major amputation in those with healed wounds within 3 months (16% vs 5%; p=0.033). After multivariate adjustment for age, presence of diabetes, renal function, wound size, and procedural failure, independent predictors of MALE were wound healing as a time-dependent covariate (HR 0.18; 95% CI 0.08 - 0.40; p<0.0001), and creatinine ≥ 2 (HR 2.3; 95% CI 1.3-4.2; p=0.005). Conclusions: A shorter time to wound healing is associated with less MALE in patients with CLI after endovascular therapy. Efforts should be made to achieve wound healing as quickly as possible in this population, especially in those with renal dysfunction.

Gene therapy for critical limb ischemia: Per aspera ad astra

2021 ◽  
Vol 21 ◽  
Author(s):  
Vyacheslav Z. Tarantul ◽  
Alexander V. Gavrilenko
Keyword(s):  
Gene Therapy ◽  
Critical Limb Ischemia ◽  
Viral Vectors ◽  
Ex Vivo ◽  
Single Gene ◽  
Public Health Problem ◽  
Limb Ischemia ◽  
Therapeutic Angiogenesis ◽  
Effective Treatment Option

: Peripheral artery diseases remain a serious public health problem. Although there are many traditional methods for their treatment using conservative therapeutic techniques and surgery, gene therapy is an alternative and potentially more effective treatment option especially for “no option” patients. This review treats the results of many years of research and application of gene therapy as an example of treatment of patients with critical limb ischemia. Data on successful and unsuccessful attempts to use this technology for treating this disease are presented. Trends in changing the paradigm of approaches to therapeutic angiogenesis are noted: from viral vectors to non-viral vectors, from gene transfer to the whole organism to targeted transfer to cells and tissues, from single gene use to combination of genes; from DNA therapy to RNA therapy, from in vivo therapy to ex vivo therapy.

P942Impact of left ventricular ejection fraction in patients with critical limb ischemia: from I-PAD registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Fujimori ◽  
A Nagae ◽  
T Miura ◽  
T Katoh ◽  
M Hirabayashi ◽  
...  
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
End Point

Abstract Introduction In patients with critical limb ischemia (CLI) it is known that malnutrition, low BMI, inflammation and so on are prognostic factors. But, it is unclear whether left ventricular ejection fraction (LVEF) affects prognosis of CLI patients. So we investigated that LVEF affects prognosis of CLI patients. Methods From July 2015 to July 2016, 371 consecutive peripheral artery disease patients who performed endovascular treatment (EVT) were enrolled in I-PAD registry. 179 of them were patients with CLI. We could conduct follow up survey about 126 (age 75.5±11.1, men 63.5%) and divided two groups according to their LVEF (group with LVEF≤40%, n=13, group without LVEF≤40%, n=113). The primary end point was major adverse limb events (MALE: TLR, TVR, major amputations) and secondary end point was all-cause death. Results The median follow-up period was 11.5±6.7 months. The 18 months MALE rate was significant higher in the group with low LVEF than group without low LVEF (76.9% vs 37.2% p<0.05). The 18months all-cause death tended to be higher in the group with low LVEF, however there was not statistical significance in the two groups (53.8% vs 24.8% p=0.09). Conclusion LVEF was associated with MALE in patients with CLI.

Peripheral endothelial progenitor cells (CD133+) for therapeutic vasculogenesis in a patient with critical limb ischemia. One year follow-up

Cytotherapy ◽  
2007 ◽  
Vol 9 (1) ◽  
pp. 99-102 ◽  
Author(s):  
M.C. Cañizo ◽  
F. Lozano ◽  
J.R. González-Porras ◽  
M. Barros ◽  
N. López-Holgado ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Endothelial Progenitor ◽  
One Year
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