Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have b...Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have been administering continuous sciatic nerve block (CSNB) for patients with CLI whose pain could not be relieved by other analgesic tools. The aim of this retrospective study was to investigate the efficacy and safety of CSNB for patients with CLI. Method: We retrospectively investigated 99 patients who received CSNB for the relief of severe pain in the lower limb associated with CLI. Patient demographics, neurological history, complications, and subjective evaluation of the effectiveness of CSNB were investigated from their clinical records. The distal tips of 108 catheters were cultured. Result: One hundred and seventy-two catheters were placed in 99 patients. More than 90% of the patients enjoyed considerable relief of severe pain. The analgesic effect of CSNB was greater in patients with older age and hemodialysis. Thirty-one catheters had positive bacterial colonization. However, no severe infectious complication was found. There was no relationship between the co-existence of diabetes and positive bacterial colonization. We encountered a patient with ASO and diabetes who suffered from persistent motor weakness and hypesthesia even after 3 months of CSNB placement. Conclusions: CSNB provided good pain control for patients with severe pain caused by CLI. Although catheters were frequently found to be colonized, infection at the catheter site was self-limiting even in patients with diabetes.展开更多
BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patie...BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patients,who are younger at the diagnosis of UC than their Western counterparts.AIM To conduct a nationwide population-based study to assess the risk of CLI in UC long-term survivors.METHODS UC survivors,defined as those who survived for longer than 5 years after the diagnosis,were identified and matched at a 1:4 ratio with normal controls.Stratified Cox models were used to assess the risk of CLI.RESULTS From 2000 to 2005,1889 UC survivors who received surgery alone or surgery combined with radiotherapy(RT)were classified into younger(onset age<50 years,n=894)and older(onset age≥50 years,n=995)groups.While compared with normal controls,the younger patients with diabetes,hypertension,and receiving hormone replacement therapy(HRT)were more likely to develop CLI.In contrast,the risk of CLI was associated with adjuvant RT,obesity,hypertension,and HRT in the older group.Among the UC survivors,those who were diagnosed at an advanced age(>65 years,aHR=2.48,P=0.011),had hypertension(aHR=2.18,P=0.008)or received HRT(aHR=3.52,P=0.020)were at a higher risk of CLI.CONCLUSION In this nationwide study,we found that the risk factors associated with CLI were similar in both cohorts except for adjuvant RT that was negligible in the younger group,but positive in the older group.Among the survivors,hypertension,advanced age,and HRT were more hazardous than RT.Secondary prevention should include CLI as a late complication in UC survivorship programs.展开更多
Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularizatio...Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.展开更多
Critical limb ischemia(CLI)is a devastating disease characterized by the progressive blockage of blood vessels.Although the paracrine effect of growth factors in stem cell therapy made it a promising angiogenic therap...Critical limb ischemia(CLI)is a devastating disease characterized by the progressive blockage of blood vessels.Although the paracrine effect of growth factors in stem cell therapy made it a promising angiogenic therapy for CLI,poor cell survival in the harsh ischemic microenvironment limited its efficacy.Thus,an imperative need exists for a stem-cell delivery method that enhances cell survival.Here,a collagen microgel(CMG)cell-delivery scaffold(40×20μm)was fabricated via micro-fragmentation from collagen-hyaluronic acid polyionic complex to improve transplantation efficiency.Culturing human adipose-derived stem cells(hASCs)with CMG enabled integrin receptors to interact with CMG to form injectable 3-dimensional constructs(CMG-hASCs)with a microporous microarchitecture and enhanced mass transfer.CMG-hASCs exhibited higher cell survival(p<0.0001)and angiogenic potential in tube formation and aortic ring angiogenesis assays than cell aggregates.Injection of CMG-hASCs intramuscularly into CLI mice increased blood perfusion and limb salvage ratios by 40%and 60%,respectively,compared to cell aggregate-treated mice.Further immunofluorescent analysis revealed that transplanted CMG-hASCs have greater muscle regenerative and angiogenic potential,with enhanced cell survival than cell aggregates(p<0.05).Collectively,we propose CMG as a cell-assembling platform and CMG-hASCs as promising therapeutics to treat CLI.展开更多
AIM To examine the efficacy and safety of the 6 French(6F) Rotarex~S catheter system in patients with acute limb ischemia(ALI) involving thromboembolic occlusion of the proximal and mid-crural vessels.METHODS The fi...AIM To examine the efficacy and safety of the 6 French(6F) Rotarex~S catheter system in patients with acute limb ischemia(ALI) involving thromboembolic occlusion of the proximal and mid-crural vessels.METHODS The files of patients in our department with ALI between 2015 and 2017 were examined. In seven patients, the Rotarex~S catheter was used in the proximal segment of the crural arteries. Data related to the clinical examination, Doppler sonography, angiography and followup from these patients were further used for analysis.RESULTS Two patients(29%) had thrombotic occlusion of the common femoral artery, and the remaining five exhibited thrombosis of the superficial femoral artery and popliteal artery. Mechanical thrombectomy was performed in all cases using a 6F Rotarex~S catheter. Additional Rotarex~S catheter thrombectomy due to remaining thrombus formation with no reflow was performed in the anterior tibial artery in two of seven cases(29%), in the tibiofibular tract and posterior tibial artery in two of seven cases(29%) and in the tibiofibular tract and fibular artery in the remaining three of seven cases(43%). Ischemic symptoms resolved promptly in all, and none of the patients experienced a procedural complication, such as crural vessel dissection, perforation or thrombus embolization.CONCLUSION Mechanical debulking using the 6F Rotarex~S catheter system may be a safe and effective treatment option in case of thrombotic or thromboembolic occlusion of the proximal and mid-portion of crural arteries.展开更多
Objective： To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods： Fifty Type 2 diabetic patients with lower limb ...Objective： To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods： Fifty Type 2 diabetic patients with lower limb ischemia were enrolled and randomized to either transplanted group or control group. Patients in both group received the same conventional treatment. Meanwhile, 20 ml bone marrow from each transplanted patient were collected, and the mesenchymal stem cells were separated by density gradient centrifugation and cultured in the medium with autologous serum. After three-weeks adherent culture in vitro, 7.32×10^8-5.61×10^9 mesenchymal stem cells were harvested and transplanted by multiple intramuscular and hypodermic injections into the impaired lower limbs. Results： At the end of 12-week follow-up, 5 patients were excluded from this study because of clinical worsening or failure of cell culture. Main ischemic symptoms, including rest pain and intermittent claudication, were improved significantly in transplanted patients. The ulcer healing rate of the transplanted group （1 5 of 18, 83.33%） was significantly higher than that of the control group （9 of 20, 45.00%, P=0.012）.The mean of resting ankle-brachial index （ABI） in transplanted group significantly was increased from 0.61±0.09 to 0.74±0.11 （P〈0.001）. Magnetic resonance angiography （MRA） demonstrated that there were more patients whose score of new vessels exceeded or equaled to 2 in the transplant patients （11 of 15） than in control patients （2 of 14, P=0.001）. Lower limb amputation rate was significantly lower in transplanted group than in the control group （P=0.040）. No adverse effects was observed in transplanted group. Conclusion： These results indicate that the autologous transplantation of bone marrow mesenchymal stem cells relieves critical lower limb ischemia and promotes ulcers healing in Type 2 diabetic patients.展开更多
Despite a lack of solid evidence in applying the angiosome concept (AC) in current chronic limb threatening ischemia (CLTI) treatment, several encouraging results for improved wound healing and less for limb preservat...Despite a lack of solid evidence in applying the angiosome concept (AC) in current chronic limb threatening ischemia (CLTI) treatment, several encouraging results for improved wound healing and less for limb preservation were reported in various consistency studies. Direct revascularization (DR) following the foot angiosomes distribution (whenever feasible) may afford better clinical results compared to angiosome indifferent, or indirect revascularization (IR), however without clear benefit on survival and for major adverse limb events (MALE). Inside this interrogation,?the notable influence of the remnant collaterals, the foot arches, the wound characteristics, and the type of revascularization (bypass versus endovascular) still remain ardent topics. Current evidence suggests that applying DR in daily vascular practice requires practitioners to be committed to every individual hemodynamic variable in a thorough macro- and micro-vascular evaluation of the ischemic foot. It becomes clearer nowadays that not all CLTI foot ulcers hold same ischemic burden and seemingly need specific DR. In the same setting,?a novel wound targeted revascularization (WTR) design was proposed assembling wider circulatory targets than genuine DR notion, as used by some authors. Beyond specific angiosomal artery reperfusion, WTR associates the available arches, the large- and medium-sized collaterals, and the arterial-arterial communicants, in an intentional “source artery” and “collateral” topographic foot revascularization. However,?up to date, the notion of angiosome wound-guided revascularization (DR and WTR) detains only a reserved level of confirmation. As for DR, the WTR equally needs higher levels of evidence allowed by standardized definition, uniform indications, and pertinent results from multicenter larger prospective analysis, before large application.展开更多
Background Amputation-free survival （AFS） has been recommended as the gold standard for evaluating No-Option Critical Limb Ischemia （NO-CLI） therapy. Early-phase clinical trials suggest that autologous bone-marrow...Background Amputation-free survival （AFS） has been recommended as the gold standard for evaluating No-Option Critical Limb Ischemia （NO-CLI） therapy. Early-phase clinical trials suggest that autologous bone-marrow derived cells （BMCs） transplantation may have a positive effect on patients with NO-CLI, especially decreasing the incidence of amputation. However, the BMCs therapeutic efficacy remains controversial and whether BMCs therapy is suitable for all CLI patients is unclear. Methods We conducted a meta-analysis using data from randomized controlled trials （RCTs） by comparing autologous BMCs therapy with controls in patients with critical limb ischemia, and the primary endpoint is the incidence of amputation. Pubmed, EBSCO and the Cochrane Central Register of Controlled Trials （to approximately July 25, 2012） were searched. Results Seven RCTs with 373 patients were enrolled in the meta-analysis. Because serious disease was the main reason leading to amputation in one trial, six studies with 333 patients were finally included in the meta-analysis. Pooling the data of the final six studies, we found that BMCs therapy significantly decreased the incidence of amputation in patients with CLI （odds ratio （OR）, 0.37; 95% confidence interval （CI）, 0.22 to 0.62; P=-0.0002）, and the efficacy had not significantly declined within 6 months after BMCs were transplanted; OR, 0.33; 95% CI, 0.16 to 0.70; P=0.004 within 6 months and OR, 0.30; 95% CI, 0.11 to 0.79; P=0.01 within 3 months. The rate of AFS after BMCs therapy was significantly increased in patients with Rutherford class 5 CLI （OR 3.28; 95% CI, 1.12 to 9.65; P=0.03）, while there was no significant improvement in patients with Rutherford class 4 （OR 0.35; 95% CI, 0.05 to 2.33; P=0.28） compared with controls. The BMCs therapy also improved ulcer healing （OR, 5.83; 95% CI, 2.37 to 14.29; P=-0.0001）. Conclusions Our analysis suggests that autologous BMCs therapy has a beneficial effect in decreasing the incidence of amputation and the efficacy does not decrease significantly within 6 months after BMCs transplantation. Patients with Rutherford class 5 are suitable for BMCs therapy, while the efficiency in patients with Rutherford 4 needs further evaluation.展开更多
As the global burden of diabetes is rapidly increasing,the incidence of diabetic foot ulcers is continuously increasing as the mean age of the world population increases and the obesity epidemic advances.A significant...As the global burden of diabetes is rapidly increasing,the incidence of diabetic foot ulcers is continuously increasing as the mean age of the world population increases and the obesity epidemic advances.A significant percentage of diabetic foot ulcers are caused by mixed micro and macro-vascular dysfunction leading to impaired perfusion of foot tissue.Left untreated,chronic limb-threatening ischemia has a poor prognosis and is correlated with limb loss and increased mortality;prompt treatment is required.In this review,the diagnostic challenges in diabetic foot disease are discussed and available data on minimally invasive treatment options such as endovascular revascularization,stem cells,and gene therapy are examined.展开更多
文摘Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have been administering continuous sciatic nerve block (CSNB) for patients with CLI whose pain could not be relieved by other analgesic tools. The aim of this retrospective study was to investigate the efficacy and safety of CSNB for patients with CLI. Method: We retrospectively investigated 99 patients who received CSNB for the relief of severe pain in the lower limb associated with CLI. Patient demographics, neurological history, complications, and subjective evaluation of the effectiveness of CSNB were investigated from their clinical records. The distal tips of 108 catheters were cultured. Result: One hundred and seventy-two catheters were placed in 99 patients. More than 90% of the patients enjoyed considerable relief of severe pain. The analgesic effect of CSNB was greater in patients with older age and hemodialysis. Thirty-one catheters had positive bacterial colonization. However, no severe infectious complication was found. There was no relationship between the co-existence of diabetes and positive bacterial colonization. We encountered a patient with ASO and diabetes who suffered from persistent motor weakness and hypesthesia even after 3 months of CSNB placement. Conclusions: CSNB provided good pain control for patients with severe pain caused by CLI. Although catheters were frequently found to be colonized, infection at the catheter site was self-limiting even in patients with diabetes.
基金Supported by the Chang Gung Medical Foundation,Taiwan,No.CMRPD1J0101-0102。
文摘BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patients,who are younger at the diagnosis of UC than their Western counterparts.AIM To conduct a nationwide population-based study to assess the risk of CLI in UC long-term survivors.METHODS UC survivors,defined as those who survived for longer than 5 years after the diagnosis,were identified and matched at a 1:4 ratio with normal controls.Stratified Cox models were used to assess the risk of CLI.RESULTS From 2000 to 2005,1889 UC survivors who received surgery alone or surgery combined with radiotherapy(RT)were classified into younger(onset age<50 years,n=894)and older(onset age≥50 years,n=995)groups.While compared with normal controls,the younger patients with diabetes,hypertension,and receiving hormone replacement therapy(HRT)were more likely to develop CLI.In contrast,the risk of CLI was associated with adjuvant RT,obesity,hypertension,and HRT in the older group.Among the UC survivors,those who were diagnosed at an advanced age(>65 years,aHR=2.48,P=0.011),had hypertension(aHR=2.18,P=0.008)or received HRT(aHR=3.52,P=0.020)were at a higher risk of CLI.CONCLUSION In this nationwide study,we found that the risk factors associated with CLI were similar in both cohorts except for adjuvant RT that was negligible in the younger group,but positive in the older group.Among the survivors,hypertension,advanced age,and HRT were more hazardous than RT.Secondary prevention should include CLI as a late complication in UC survivorship programs.
文摘Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.
基金supported by a grant from the Korean Fund for Regenerative Medicine,funded by the Ministry of Science and ICT,and the Ministry of Health&Welfare of Korea[22C0620L1-11].
文摘Critical limb ischemia(CLI)is a devastating disease characterized by the progressive blockage of blood vessels.Although the paracrine effect of growth factors in stem cell therapy made it a promising angiogenic therapy for CLI,poor cell survival in the harsh ischemic microenvironment limited its efficacy.Thus,an imperative need exists for a stem-cell delivery method that enhances cell survival.Here,a collagen microgel(CMG)cell-delivery scaffold(40×20μm)was fabricated via micro-fragmentation from collagen-hyaluronic acid polyionic complex to improve transplantation efficiency.Culturing human adipose-derived stem cells(hASCs)with CMG enabled integrin receptors to interact with CMG to form injectable 3-dimensional constructs(CMG-hASCs)with a microporous microarchitecture and enhanced mass transfer.CMG-hASCs exhibited higher cell survival(p<0.0001)and angiogenic potential in tube formation and aortic ring angiogenesis assays than cell aggregates.Injection of CMG-hASCs intramuscularly into CLI mice increased blood perfusion and limb salvage ratios by 40%and 60%,respectively,compared to cell aggregate-treated mice.Further immunofluorescent analysis revealed that transplanted CMG-hASCs have greater muscle regenerative and angiogenic potential,with enhanced cell survival than cell aggregates(p<0.05).Collectively,we propose CMG as a cell-assembling platform and CMG-hASCs as promising therapeutics to treat CLI.
文摘AIM To examine the efficacy and safety of the 6 French(6F) Rotarex~S catheter system in patients with acute limb ischemia(ALI) involving thromboembolic occlusion of the proximal and mid-crural vessels.METHODS The files of patients in our department with ALI between 2015 and 2017 were examined. In seven patients, the Rotarex~S catheter was used in the proximal segment of the crural arteries. Data related to the clinical examination, Doppler sonography, angiography and followup from these patients were further used for analysis.RESULTS Two patients(29%) had thrombotic occlusion of the common femoral artery, and the remaining five exhibited thrombosis of the superficial femoral artery and popliteal artery. Mechanical thrombectomy was performed in all cases using a 6F Rotarex~S catheter. Additional Rotarex~S catheter thrombectomy due to remaining thrombus formation with no reflow was performed in the anterior tibial artery in two of seven cases(29%), in the tibiofibular tract and posterior tibial artery in two of seven cases(29%) and in the tibiofibular tract and fibular artery in the remaining three of seven cases(43%). Ischemic symptoms resolved promptly in all, and none of the patients experienced a procedural complication, such as crural vessel dissection, perforation or thrombus embolization.CONCLUSION Mechanical debulking using the 6F Rotarex~S catheter system may be a safe and effective treatment option in case of thrombotic or thromboembolic occlusion of the proximal and mid-portion of crural arteries.
基金the Clinical Research Fund of Southwest Hospital at Third Military Medical University (SWH2005A109)
文摘Objective： To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods： Fifty Type 2 diabetic patients with lower limb ischemia were enrolled and randomized to either transplanted group or control group. Patients in both group received the same conventional treatment. Meanwhile, 20 ml bone marrow from each transplanted patient were collected, and the mesenchymal stem cells were separated by density gradient centrifugation and cultured in the medium with autologous serum. After three-weeks adherent culture in vitro, 7.32×10^8-5.61×10^9 mesenchymal stem cells were harvested and transplanted by multiple intramuscular and hypodermic injections into the impaired lower limbs. Results： At the end of 12-week follow-up, 5 patients were excluded from this study because of clinical worsening or failure of cell culture. Main ischemic symptoms, including rest pain and intermittent claudication, were improved significantly in transplanted patients. The ulcer healing rate of the transplanted group （1 5 of 18, 83.33%） was significantly higher than that of the control group （9 of 20, 45.00%, P=0.012）.The mean of resting ankle-brachial index （ABI） in transplanted group significantly was increased from 0.61±0.09 to 0.74±0.11 （P〈0.001）. Magnetic resonance angiography （MRA） demonstrated that there were more patients whose score of new vessels exceeded or equaled to 2 in the transplant patients （11 of 15） than in control patients （2 of 14, P=0.001）. Lower limb amputation rate was significantly lower in transplanted group than in the control group （P=0.040）. No adverse effects was observed in transplanted group. Conclusion： These results indicate that the autologous transplantation of bone marrow mesenchymal stem cells relieves critical lower limb ischemia and promotes ulcers healing in Type 2 diabetic patients.
文摘Despite a lack of solid evidence in applying the angiosome concept (AC) in current chronic limb threatening ischemia (CLTI) treatment, several encouraging results for improved wound healing and less for limb preservation were reported in various consistency studies. Direct revascularization (DR) following the foot angiosomes distribution (whenever feasible) may afford better clinical results compared to angiosome indifferent, or indirect revascularization (IR), however without clear benefit on survival and for major adverse limb events (MALE). Inside this interrogation,?the notable influence of the remnant collaterals, the foot arches, the wound characteristics, and the type of revascularization (bypass versus endovascular) still remain ardent topics. Current evidence suggests that applying DR in daily vascular practice requires practitioners to be committed to every individual hemodynamic variable in a thorough macro- and micro-vascular evaluation of the ischemic foot. It becomes clearer nowadays that not all CLTI foot ulcers hold same ischemic burden and seemingly need specific DR. In the same setting,?a novel wound targeted revascularization (WTR) design was proposed assembling wider circulatory targets than genuine DR notion, as used by some authors. Beyond specific angiosomal artery reperfusion, WTR associates the available arches, the large- and medium-sized collaterals, and the arterial-arterial communicants, in an intentional “source artery” and “collateral” topographic foot revascularization. However,?up to date, the notion of angiosome wound-guided revascularization (DR and WTR) detains only a reserved level of confirmation. As for DR, the WTR equally needs higher levels of evidence allowed by standardized definition, uniform indications, and pertinent results from multicenter larger prospective analysis, before large application.
基金LIU Fu-peng and DONG Jian-jun contributed equally to this work. This study was supported by grants from the Natural Science Foundation of Shandong Province （No. Y2008C73, ZR2010HM044）, the National Natural Science Foundation of China （No. 81070637）, Science and Technology Development Program of Shandong Province （No. 2010GSF10228）, Clinical Medical Scientific Research Foundation of Chinese Medical Association （No. 0910340189）.
文摘Background Amputation-free survival （AFS） has been recommended as the gold standard for evaluating No-Option Critical Limb Ischemia （NO-CLI） therapy. Early-phase clinical trials suggest that autologous bone-marrow derived cells （BMCs） transplantation may have a positive effect on patients with NO-CLI, especially decreasing the incidence of amputation. However, the BMCs therapeutic efficacy remains controversial and whether BMCs therapy is suitable for all CLI patients is unclear. Methods We conducted a meta-analysis using data from randomized controlled trials （RCTs） by comparing autologous BMCs therapy with controls in patients with critical limb ischemia, and the primary endpoint is the incidence of amputation. Pubmed, EBSCO and the Cochrane Central Register of Controlled Trials （to approximately July 25, 2012） were searched. Results Seven RCTs with 373 patients were enrolled in the meta-analysis. Because serious disease was the main reason leading to amputation in one trial, six studies with 333 patients were finally included in the meta-analysis. Pooling the data of the final six studies, we found that BMCs therapy significantly decreased the incidence of amputation in patients with CLI （odds ratio （OR）, 0.37; 95% confidence interval （CI）, 0.22 to 0.62; P=-0.0002）, and the efficacy had not significantly declined within 6 months after BMCs were transplanted; OR, 0.33; 95% CI, 0.16 to 0.70; P=0.004 within 6 months and OR, 0.30; 95% CI, 0.11 to 0.79; P=0.01 within 3 months. The rate of AFS after BMCs therapy was significantly increased in patients with Rutherford class 5 CLI （OR 3.28; 95% CI, 1.12 to 9.65; P=0.03）, while there was no significant improvement in patients with Rutherford class 4 （OR 0.35; 95% CI, 0.05 to 2.33; P=0.28） compared with controls. The BMCs therapy also improved ulcer healing （OR, 5.83; 95% CI, 2.37 to 14.29; P=-0.0001）. Conclusions Our analysis suggests that autologous BMCs therapy has a beneficial effect in decreasing the incidence of amputation and the efficacy does not decrease significantly within 6 months after BMCs transplantation. Patients with Rutherford class 5 are suitable for BMCs therapy, while the efficiency in patients with Rutherford 4 needs further evaluation.
文摘As the global burden of diabetes is rapidly increasing,the incidence of diabetic foot ulcers is continuously increasing as the mean age of the world population increases and the obesity epidemic advances.A significant percentage of diabetic foot ulcers are caused by mixed micro and macro-vascular dysfunction leading to impaired perfusion of foot tissue.Left untreated,chronic limb-threatening ischemia has a poor prognosis and is correlated with limb loss and increased mortality;prompt treatment is required.In this review,the diagnostic challenges in diabetic foot disease are discussed and available data on minimally invasive treatment options such as endovascular revascularization,stem cells,and gene therapy are examined.
