Background-Bone-marrow mononuclear cell (BM-MNC) implantation improves ischemic symptoms in patients withcritical limb ischemia (CLI). The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI. Methods and Results-We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI, including 25 patients with peripheral arterial disease (PAD) and 26 patients with Buerger disease. Forty-six CLI patients who had no BM-MNC implantation served as control subjects. Median follow-up period was 4.8 years. The 4-year amputation-free rates after BM-MNC implantation were 48% in PAD patients and 95% in Buerger disease, and they were 0% in control PAD patients and 6% in control Buerger disease. The 4-year overall survival rates after BM-MNC implantation were 76% in PAD patients and 100% in Buerger disease, and they were 67% in control PAD patients and 100% in control Buerger disease. Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation. In Buerger disease, ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up. However, in patients with PAD, ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels.
Conclusions-These
Response:As the first step in the decision to perform amputation, the surgeon consults with the patient. In our hospital, the final decision for major amputation is made by mutual consent of cardiologists, surgeons, dermatologists, and anesthetists on the peripheral arterial disease committee. However, our study was not a randomized and placebocontrol trial. It was difficult to compare the decisions for major amputation between the control group and the bone marrow mononuclear cell (BM-MNC) implantation group. We cannot deny the possibility of decision bias.In the atherosclerotic peripheral arterial disease control group, all patients with Rutherford category 4 or 5 who were enrolled in the present study had severe rest pain that required the use of a suppository or oral morphine and epidural administration of a sedative, and in some patients, severe rest pain led to ulcers and gangrene, resulting in major amputation within 8 months. 1 In addition, we agree with the comment that smoking plays an important role in limb survival. Smoking cessation reduces the progression of critical limb ischemia. 2 Patients without BM-MNC implantation also stopped smoking at least after the decision for major amputation.Visual analog pain scores were assessed by research nurses who did not know the study protocol. They interviewed patients who had undergone BM-MNC implantation and checked visual analog pain scores every month.Multivariable Cox proportional hazards analysis revealed that hemodialysis and diabetes mellitus were independent predictors of major amputation after BM-MNC implantation. Indeed, all 8 patients with critical limb ischemia and diabetes mellitus who were undergoing hemodialysis underwent major amputation during the follow-up period.Unfortunately, we do not have refined parameters for assessing limb ischemia. Observable findings of limb ischemia rather than findings of angiography and parameters such as ankle-brachial pressure index, transcutaneous oxygen pressure, and skin perfusion pressure might be the best at present. Development of new modalities for accurate assessment of the severity of limb ischemia is expected.
Critical limb ischemia (CLI) is associated with a high risk of limb amputation. It has been shown that cell therapy is safe and has beneficial effects on ischemic clinical symptoms in patients with CLI. The aim of this study was to further investigate the outcomes of intramuscular injection of autologous bone-marrow mononuclear cells (BM-MNCs) in a long-term follow-up period in atherosclerotic peripheral arterial disease (PAD) patients who have no optional therapy. This study was a retrospective and observational study that was carried out to evaluate long-term clinical outcomes in 42 lower limbs of 30 patients with atherosclerotic PAD who underwent BM-MNC implantation. The median follow-up period was 9.25 (range, 6–16) years. The overall amputation-free rates were 73.0% at 5 years after BM-MNC implantation and 70.4% at 10 years in patients with atherosclerotic PAD. The overall amputation-free rates at 5 years and at 10 years after implantation of BM-MNCs were significantly higher in atherosclerotic PAD patients than in internal controls and historical controls. There were no significant differences in amputation rates between the internal control group and historical control group. The rate of overall survival was not significantly different between the BM-MNC implantation group and the historical control group. Implantation of autologous BM-MNCs is feasible for a long-term follow-up period in patients with CLI who have no optional therapy.
The likelihood of a pre-hypertensive young adult to develop hypertension has been steadily increasing over the past few years. Aerobic exercise training (AET) has been found to reduce high blood pressure, however, efficacy of different types of aerobic exercise is yet to be determined among the pre-hypertensive young adults. The objective of this study was to evaluate the effectiveness of high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) on blood pressure (BP) in young physically inactive pre-hypertensive adults. 32 adults (age 20.0±1.1) were randomly assigned into 3 groups; HIIT, CMT, and control (CON). HIIT and CMT groups participated in 5 weeks of AET with CON group not participating in any exercise. The HIIT protocol consisted of 1:4 minute work to rest ratio of participants 80%-85% heart rate reserve (HR-reserve) and 40%-60% HR-reserve respectively for 20 minutes, CMT group exercised at 40%-60% of HR-reserve continuously for 20 minutes. In both HIIT and CMT groups, systolic blood pressure (SBP) (3.8±2.8 mmHg, P=0.002 VS 1.6±1.5 mmHg, P=0.011) was significantly reduced. While, significant reductions were noted in the diastolic blood pressure (DBP) (2.9±2.2 mmHg, P=0.002) and mean arterial pressure (MAP) (3.1±1.6mmHg, P<0.0005) only in the HIIT group. No significant difference in SBP (-0.4±3.7 mmHg, P=0.718), DBP (0.4±3.4 mmHg, P=0.714), or MAP (0.1±2.5mmHg, P= 0.892) was observed in the CON group. Both HIIT and CMT decreased the BP in physically inactive pre-hypertensive young adults; however, HIIT yielded more beneficial results in terms of reducing the SPB, DBP, and MAP.
The likelihood of a pre-hypertensive young adult to develop hypertension has been steadily increasing over the past few years. Aerobic exercise training (AET) has been found to reduce high blood pressure, however, efficacy of different types of aerobic exercise is yet to be determined among the pre-hypertensive young adults. The objective of this study was to evaluate the effectiveness of high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) on blood pressure (BP) in young physically inactive pre-hypertensive adults. 32 adults (age 20.0±1.1) were randomly assigned into 3 groups; HIIT, CMT, and control (CON). HIIT and CMT groups participated in 5 weeks of AET with CON group not participating in any exercise. The HIIT protocol consisted of 1:4 minute work to rest ratio of participants 80%-85% heart rate reserve (HR-reserve) and 40%-60% HR-reserve respectively for 20 minutes, CMT group exercised at 40%-60% of HR-reserve continuously for 20 minutes. In both HIIT and CMT groups, systolic blood pressure (SBP) (3.8±2.8 mmHg, P=0.002 VS 1.6±1.5 mmHg, P=0.011) was significantly reduced. While, significant reductions were noted in the diastolic blood pressure (DBP) (2.9±2.2 mmHg, P=0.002) and mean arterial pressure (MAP) (3.1±1.6mmHg, P<0.0005) only in the HIIT group. No significant difference in SBP (-0.4±3.7 mmHg, P=0.718), DBP (0.4±3.4 mmHg, P=0.714), or MAP (0.1±2.5mmHg, P= 0.892) was observed in the CON group. Both HIIT and CMT decreased the BP in physically inactive pre-hypertensive young adults; however, HIIT yielded more beneficial results in terms of reducing the SPB, DBP, and MAP.
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