Quality of Life and Traditional Outcome Results at 1 Year in Elderly Patients Having Critical Limb Ischemia and the Role of Conservative Treatment.

INTRODUCTION: Revascularization is the cornerstone of the treatment of critical limb ischemia (CLI), but the number of elderly frail patients increase. Revascularization is not always possible in these patients and conservative therapy seems to be an option. The goals of this study are to analyze the 1-year quality of life (QoL) results and mortality rates of elderly patients with CLI and to investigate if conservative treatment could be an acceptable treatment option. METHODS: Patients with CLI ≥70 years old were included in a prospective observational cohort study in 2 hospitals in the Netherlands between 2012 and 2016 and were divided over 3 treatment modalities: endovascular therapy, surgical revascularization, and conservative treatment. The World Health Organization Quality of Life (WHOQoL-Bref) instrument, a generic QoL assessment tool that includes components of physical, psychological, social relationships and environment, was used to evaluate QoL at baseline, 6 months, and 1 year. RESULTS: In total, 195 patients (56% male, 33% Rutherford 4, mean age of 80) were included. Physical QoL significantly increased after surgical (10.4 vs 14.9, P < .001), endovascular (10.9 vs 13.7, P < .001), and conservative therapy (11.6 vs 13.2, P = .01) at 1 year. One-year mortality was relatively low after surgery (10%) compared to endovascular (40%) and conservative therapy (37%). CONCLUSION: The results of this study could not be used to designate the superior treatment used in elderly patients with CLI. Conservative treatment could be an acceptable treatment option in selected patients with CLI unfit for revascularization. Treatment of choice in elderly patients with CLI is based on multiple factors and should be individualized in a shared decision-making process.

Critical limb ischemia: current challenges and future prospects.

Critical limb ischemia (CLI) is considered the most severe pattern of peripheral artery disease. It is defined by the presence of chronic ischemic rest pain, ulceration or gangrene attributable to the occlusion of peripheral arterial vessels. It is associated with a high risk of major amputation, cardiovascular events and death. In this review, we presented a complete overview about physiopathology, diagnosis and holistic management of CLI. Revascularization is the first-line treatment, but several challenging cases are not treatable by conventional techniques. Unconventional techniques for the treatment of complex below-the-knee arterial disease are described. Furthermore, the state-of-the-art on gene and cell therapy for the treatment of no-option patients is reported.

Impact of Nutritional State on Critical Limb Ischemia Early Outcomes (DENUCRITICC Study).

BACKGROUND: Despite current progress, the prognosis of critical limb ischemia (CLI) remains poor. The ageing of the population, the increasing prevalence of diabetes mellitus, and the stability of tobacco use will increase the prevalence of CLI. CLI patients have risk factors for malnutrition, and the impact of malnutrition on morbidity and mortality has been demonstrated in the general population. However, we have little information on the consequences of undernutrition in the CLI population. The aim of this study is to assess the impact of malnutrition on the early outcomes in CLI patients. METHODS: This is a double-center prospective study that included all consecutive hospitalized patients with CLI. All patients were screened for malnutrition and divided into 2 groups: severe malnourished patients (group A) and moderate malnourished and well-nourished (group B). This distribution was based on age-indexed clinical and biological data and the patient's general condition: the Nutritional Risk Index for patients younger than 75 years, the Mini Nutritional Assessment, or the Geriatric Nutritional Risk Index for those older than 75 years. The primary end point was defined as the rate of 30-day death. Outcomes were compared in a univariate analysis. Stepwise logistic regression was used for the multivariate analysis. Variables with a P value <0.2 in the univariate analysis were introduced in the multivariate model. RESULTS: We included 106 patients. The prevalence of malnutrition was 75.5%, divided into moderate malnutrition (51.9%) and severe malnutrition (23.6%). Six patients (24%) died in group A compared with 8 in group B (4.9%) (P = 0.01). By univariate analysis, severe malnutrition was the only factor associated with death at 30 days. By stepwise logistic regression, severe malnutrition (odds ratio 6.1, 95% confidence interval 1.6-23.7, P = 0.006) was found to be the significant risk factors for death at 30 days. CONCLUSIONS: This study is the first to demonstrate prospectively the major importance of malnutrition in the early prognosis of CLI patients.

The Geriatric Nutritional Risk Index is Independently Associated with Prognosis in Patients with Critical Limb Ischemia Following Endovascular Therapy.

OBJECTIVES: Patients with critical limb ischemia (CLI) have poor overall and limb prognosis. Although nutritional status influences overall prognosis, and the Geriatric Nutritional Risk Index (GNRI) is a widely used, simple and well established nutritional status screening method, the association between the GNRI and the overall and limb prognosis of patients with CLI following endovascular therapy (EVT) has not been explored. METHODS: Clinical outcomes were retrospectively evaluated in 473 consecutive patients (74 ± 10 years; 59% male) with CLI who underwent EVT. The GNRI on admission was calculated as follows: [14.89 × albumin (g/dL)] + [41.7 × (body weight/ideal body weight)]. Cox proportional hazard analysis was performed to explore the independent association between the GNRI and mortality and major amputation. RESULTS: Patients (53% ambulatory, 38% wheelchair bound, and 9% bedridden) were divided into two groups based on the median GNRI: the higher group (GNRI ≥ 91.2, n = 237) and the lower group (GNRI < 91.2, n = 236). Median follow up duration after EVT was 11.3 months. Three years after EVT, the survival rate (74% in the higher GNRI, and 48% in the lower GNRI, respectively), and limb salvage rate (92% in the higher GNRI, and 84% in the lower GNRI) were significantly lower in the lower GNRI group. GNRI (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.05), along with being wheelchair bound (HR, 1.87; 95% CI 1.17-2.97; vs. ambulatory status), being bedridden (HR, 3.10; 95% CI, 1.63-2.97; vs. ambulatory status), being on hemodialysis (HR, 2.33; 95% CI, 1.49-3.64), and having chronic heart failure (HR, 2.22; 95% CI, 1.44-3.43) were the independent predictors of mortality. The GNRI (HR, 1.04; 95% CI, 1.01-1.07), being bedridden (HR, 4.15; 95% CI, 1.67-10.3; vs. ambulatory status), isolated below knee disease (HR, 2.49; 95% CI, 1.30-4.77), and hemodialysis (HR, 2.44; 95% CI, 1.23-4.85) were independently associated with major amputation. CONCLUSIONS: The GNRI on admission was independently associated with mortality and major amputation after EVT in patients with CLI.

The Effect of Coffee and Quantity of Consumption on Specific Cardiovascular and All-Cause Mortality: Coffee Consumption Does Not Affect Mortality.

Previous studies have examined whether or not an association exists between the consumption of caffeinated coffee to all-cause and cardiovascular mortality. This study aimed to delineate this association using population representative data from the National Health and Nutrition Examination Survey III. Patients were included in the study if all the following criteria were met: (1) follow-up mortality data were available, (2) age of at least 45 years, and (3) reported amount of average coffee consumption. A total of 8608 patients were included, with patients stratified into the following groups of average daily coffee consumption: (1) no coffee consumption, (2) less than 1 cup, (3) 1 cup a day, (4) 2-3 cups, (5) 4-5 cups, (6) more than 6 cups a day. Odds ratios, 95% confidence intervals, and P values were calculated for univariate analysis to compare the prevalence of all-cause mortality, ischemia-related mortality, congestive heart failure-related mortality, and stroke-related mortality, using the no coffee consumption group as reference. These were then adjusted for confounding factors for a multivariate analysis. P < 0.05 were considered statistically significant. Univariate analysis demonstrated an association between coffee consumption and mortality, although this became insignificant on multivariate analysis. Coffee consumption, thus, does not seem to impact all-cause mortality or specific cardiovascular mortality. These findings do differ from those of recently published studies. Coffee consumption of any quantity seems to be safe without any increased mortality risk. There may be some protective effects but additional data are needed to further delineate this.

Hybrid revascularization of complex multilevel disease: a paradigm shift in critical limb ischemia treatment.

Critical limb ischemia frequently occurs on a background of extensive co-morbidities and carries a poor prognosis which requires urgent management. Disease severity and patient comorbidity influence the initial choice of management which according to traditional paradigms, is a choice between open or endovascular repair. Over the last decade hybrid intervention, which is the planned combined use of both open and endovascular techniques, has increasingly been used to tackle multilevel disease. In this review we look at the techniques and results of hybrid surgery. This technique is ideal for multilevel lesions, as it is minimally invasive, allows prompt limb revascularization as opposed to the delays inherent in staged procedures and it appears to be more convenient to patients. It also leads to reduced length of hospital stay and reduces overall cost. Most importantly it offers an alternative to open revascularization in medically high risk patients. The success and popularity of hybrid interventions has been underpinned by advances in stent and balloon technology and the advent of the hybrid operating theatre which has allowed multiple techniques to be used simultaneously. Iliac angioplasty and stenting is now the first line of treatment for TASC C/D iliac lesions with good technical success and long-term patency. In patients who also have common femoral disease, endarterectomy can be combined with iliac stenting and this has now almost replaced open bypass. Most series for a variety of hybrid procedures report good limb salvage rates, with morbidity and mortality data considered equal to or better than open bypass procedures. Careful patient selection and detailed preoperative planning are essential to achieve these excellent results. Studies have reported on prospective series or retrospective analysis for various hybrid techniques, including non randomized trials comparing hybrid and open surgical treatment. Ideally, a randomized controlled trial comparing open and hybrid treatment is needed to minimize confounding variables.

Critical limb ischemia-need to look beyond limb salvage.

BACKGROUND: Revascularization is the optimal treatment for critical limb ischemia (CLI). Traditional measures of outcome of intervention are as follows: graft patency, limb salvage rates, and patient survival rates; however, these have little meaning for a patient if he/she cannot ambulate independently or go back to work. This study was undertaken to assess the functional outcome of intervention in these patients. METHODS: Fifty patients with CLI treated over a 3-year period were included in this prospective clinical study. After evaluation, treatment was given to each patient on the basis of the Transatlantic Inter-society Consensus II guidelines. The outcome of treatment and the functional restoration to pre-illness lifestyle were assessed at the end of 1 month, and then at 6 months. RESULTS: Fifty patients with CLI were included in the study; male to female ratio was 9:1, and the mean age at presentation was 45 years. After evaluation, only 38 patients (76%) were found suitable for revascularization. Traditional measures of success showed a graft patency rate of 75%, limb salvage rate of 89.5%, and patient survival rate of 96% at 6 months after treatment. All eight parameters of quality-of-life analysis showed significant improvement as assessed by the Research and Development (RAND) 36-Item Health Survey 1.0 form. However, among the 38 patients who were revascularized, 20 (52.6%) went back to their initial occupation after 6 months, 12 (31.6%) remained at home even though they were ambulant, and five (13.2%) were able to manage only limited activities; one patient succumbed to death. CONCLUSION: With only 53% of revascularized patients returning to work, a salvaged leg does not equate with return to premorbid ambulatory/occupational status, although there might be improvement in quality of life because of other reasons. As surgeons, we need to look beyond leg salvage and graft patency and take on a more holistic approach.

A comparison of endovascular revascularization with traditional therapy for the treatment of acute mesenteric ischemia.

OBJECTIVES: Few centers have adopted endovascular therapy for the treatment of acute mesenteric ischemia (AMI). We sought to evaluate the effect of endovascular therapy on outcomes for the treatment of AMI. METHODS: A single-center, retrospective cohort review was performed on all consecutive patients with thrombotic or embolic AMI presenting between 1999 and 2008. Patients with mesenteric venous thrombosis, nonocclusive mesenteric ischemia, and ischemia associated with aortic dissection were excluded. Demographic factors, preoperative metabolic status, and etiology were compared. Primary clinical outcomes included endovascular technical success, operative complications, and in-hospital mortality. RESULTS: Seventy consecutive patients were identified with AMI (mean age, 64 ± 13 years). Etiology of mesenteric ischemia was 65% thrombotic and 35% embolic occlusions. Endovascular revascularization was the preferred treatment (81%) vs operative therapy (19%). Successful endovascular treatment was achieved in 87%. Endovascular therapy required laparotomy in 69% vs traditional therapy in 100% (P < .05), with a median 52-cm necrotic bowel resected (interquartile range [IQR], 11-140 cm) vs 160 cm (IQR, 90-250 cm; P < .05), respectively. Acute renal failure and pulmonary failure occurred less frequently with endovascular therapy (27% vs 50%; P < .05 and 27% vs 64%; P < .05). Successful endovascular treatment resulted in a mortality rate of 36% compared with 50% (P < .05) with traditional therapy, whereas the mortality rate for endovascular failures was 50%. Endovascular therapy was associated with improved mortality in thrombotic AMI (odds ratio, 0.10; 95% confidence interval, 0.10-0.76; P < .05). CONCLUSIONS: Endovascular therapy has altered the management of AMI, and there are measurable advantages to this approach. Using endovascular therapy as the primary modality for AMI reduces complications and improves outcomes.

What is the evidence on efficacy of spinal cord stimulation in (subgroups of) patients with critical limb ischemia?

The use of spinal cord stimulation (SCS) has been advocated for the management of ischemic pain and the prevention of amputations in patients with inoperable critical limb ischemia (CLI), although data on benefit are conflicting. Several reports described apparently differential treatment effects in subgroups. The purpose of this study was to analyze the data on the efficacy of SCS and to clarify preselection issues. Five randomized trials have been performed with a total number of 332 patients. Primary outcome measures were mortality and limb survival. In the largest multicenter randomized trial (n = 120), which compared SCS treatment and best medical treatment alone in patients with inoperable CLI, we determined the incidence of amputation and its relation to various predefined risk factors. We used Kaplan-Meier and Cox regression analyses to quantify prognostic effects and differential treatment effects. Meta-analysis yielded a relative risk for amputation of 0.79 and a risk difference of -0.07 (p = 0.15). The risk factor analysis clearly showed that patients with ischemic skin lesions (ulcerations or gangrene) had a worse prognosis (i.e., higher risk of amputation) (relative risk 2.30, p = 0.01). We did not observe significant interactions between this prognostic factor (or any other) and the effect of SCS. The analysis did not indicate a subgroup of patients who might specifically be helped by SCS. Meta-analysis including all randomized data shows insufficient evidence for higher efficacy of SCS treatment compared with best medical treatment alone. Although some factors provide prognostic information as to the risk of amputation in patients with CLI, there are no data supporting a more favorable treatment effect in any group.

Design and rationale of a randomized, double-blind, placebo-controlled phase III study for autologous bone marrow cell transplantation in critical limb ischemia: the BONe Marrow Outcomes Trial in Critical Limb Ischemia (BONMOT-CLI).

BACKGROUND: Critical limb ischemia (CLI) is the end-stage of peripheral artery disease. Only about two thirds of patients with CLI can be revascularised, one third progresses to leg amputation with high associated morbidity and mortality. Therapeutic angiogenesis with bone marrow cells has shown promising improvement in less severe stages of peripheral ischemia. Our study evaluates the therapeutic value of bone marrow cell induced angiogenesis and arteriogenesis in severe, limb-threatening ischemia. PATIENTS AND METHODS: the BONe Marrow Outcome Trial in Critical Limb Ischemia (BONMOT-CLI) is a investigator-initiated, double-blinded, 1:1 randomized, placebo-controlled multi-centre study at 4 sites in Germany. Only patients with no option for revascularisation or after failed revascularisation will be included. A total of 90 patients is to be included. One arm with 45 subjects will be treated with a concentrate of autologous bone marrow cells which will be injected at 40 sites into the ischemic limb. In the placebo arm, study subjects will undergo a sham bone marrow punction and 40 saline injections. At three months, a combined primary endpoint of major amputation or persisting critical limb ischemia (no clinical or perfusion improvement) will be evaluated. Secondary endpoints are death, changes in perfusion, quality of life, walking distance, minor amputations, wound healing, collateral density and cancer incidence. Post-study follow-up is up to two years. CONCLUSIONS: The results of this first randomized placebo-controlled trial for autologous bone marrow cell therapy in CLI will clarify the value of this new therapeutic modality in a patient population with no other alternatives except major amputation.

[Effects of streptokinase and hyperbaric oxygen therapy on venous occlusion after limb reimplantation in rats]. / Estreptoquinase e oxigênio hiperbárico em congestão após reimplante de membro.

OBJECTIVE: The effectiveness of streptokinase and hyperbaric oxygen therapy on venous occlusion after limb reimplantation was tested in rats. METHODS: Amputation with preservation of vessels and nerves of the right hind limb was carried out in 140 rats. Groups MG0, MG1, MG2, MG3 and MG4 were submitted to 0, 1, 2, 3 and 4 hours of venous occlusion. MG3 was elected as control for the experimental groups. Groups EG1 and EG2 were submitted to 3 hours of venous occlusion and were treated with streptokinase and hyperbaric oxygen therapy. Limbs were observed for 7 days and their mortality and survival rates were studied. RESULTS: Trans-operatory mortality rates in groups MG0, MG1, MG2, MG3 and MG4 were 0, 10, 15, 30 and 60% respectively and the postoperative mortality rates were 5; 11.1; 11.7; 14.2 and 100% respectively. The limb survival rates were 100%, 87.5%, 80% and 66.67% respectively and 76.9% and 100% in EG1 and EG2. Model groups were statistically different, except for MG1 and MG2 in trans-operatory mortality rates. There were no statistical differences in postoperative mortality rates between model groups except for MG3 and MG4. Model groups were statistically different, with the exception of MG1 and MG2, in limb survival rates. EG1 and MG3 showed no statistical difference in limb survival and EG2 had a better limb survival than MG3. CONCLUSION: Results suggest that the administration of streptokinase does not change effects of venous occlusion and that hyperbaric oxygen therapy may decrease the effects of venous occlusion in limbs.

Estreptoquinase e oxigênio hiperbárico em congestão após reimplante de membro / Effects of streptokinase and hyperbaric oxygen therapy on venous occlusion after limb reimplantation in rats

OBJETIVO: Foram testados os efeitos do fármaco estreptoquinase e da terapia com oxigênio hiperbárico em modelo experimental de oclusão venosa após reimplante de membro. MÉTODOS: Foram realizadas amputações com preservação de vasos e nervos dos membros posteriores direitos de 140 ratos. Os grupos GM0, GM1, GM2, GM3 e GM4 foram submetidos a tempos de oclusão venosa de zero, uma, duas, três e quatro horas. Os grupos GE1 e GE2 foram tratados com estreptoquinase e terapia com oxigênio hiperbárico, respectivamente, após oclusão venosa de três horas. Os resultados foram analisados estatisticamente pelo teste do Qui-quadrado (p<0,05). RESULTADOS: As taxas de mortalidade transoperatórias dos grupos GM0, GM1, GM2, GM3 e GM4 foram 0 por cento, 10 por cento, 15 por cento, 30 por cento e 60 por cento e as pós-operatórias foram 5 por cento; 11,1 por cento; 11,7 por cento; 14,2 por cento e 100 por cento, respectivamente. As taxas de viabilidade dos membros isquêmicos após sete dias de avaliação foram 100 por cento, 87,5 por cento, 80 por cento e 66,67 por cento. As taxas de viabilidade dos grupos GE1 e GE2 foram 76,9 por cento e 100 por cento, respectivamente. As taxas de mortalidade transoperatórias foram diferentes estatisticamente com exceção de GM1 e GM2. As taxas de mortalidade pós-operatórias não foram diferentes com exceção de GM3 e GM4. As taxas de viabilidade dos grupos modelo foram diferentes entre si, exceto os grupos GM1 e GM2. GE1 resultou em uma viabilidade de membros sem diferença estatística e GE2 em uma viabilidade de membros maior que GM3. CONCLUSÃO: A estreptoquinase não alterou os efeitos da oclusão venosa e a terapia com oxigênio hiperbárico aumentou a viabilidade dos membros.

OBJECTIVE: The effectiveness of streptokinase and hyperbaric oxygen therapy on venous occlusion after limb reimplantation was tested in rats. METHODS: Amputation with preservation of vessels and nerves of the right hind limb was carried out in 140 rats. Groups MG0, MG1, MG2, MG3 and MG4 were submitted to 0, 1, 2, 3 and 4 hours of venous occlusion. MG3 was elected as control for the experimental groups. Groups EG1 and EG2 were submitted to 3 hours of venous occlusion and were treated with streptokinase and hyperbaric oxygen therapy. Limbs were observed for 7 days and their mortality and survival rates were studied. RESULTS: Trans-operatory mortality rates in groups MG0, MG1, MG2, MG3 and MG4 were 0, 10, 15, 30 and 60 percent respectively and the postoperatory mortality rates were 5; 11.1; 11.7; 14.2 and 100 percent respectively. The limb survival rates were 100 percent, 87.5 percent, 80 percent and 66.67 percent respectively and 76.9 percent and 100 percent in EG1 and EG2. Model groups were statistically different, except for MG1 and MG2 in trans-operatory mortality rates. There were no statistical differences in postoperatory mortality rates between model groups except for MG3 and MG4. Model groups were statistically different, with the exception of MG1 and MG2, in limb survival rates. EG1 and MG3 showed no statistical difference in limb survival and EG2 had a better limb survival than MG3. CONCLUSION: Results suggest that the administration of streptokinase does not change effects of venous occlusion and that hyperbaric oxygen therapy may decrease the effects of venous occlusion in limbs.

An integrated care pathway to save the critically ischaemic diabetic foot.

This prospective study describes and evaluates the efficacy of an integrated care pathway for the management of the critically ischaemic diabetic foot patients by a multidisciplinary team. A weekly joint diabetes/vascular/podiatry ward round and outpatient clinic was established where patients were assessed within 7 days of referral by clinical examination, ankle-brachial-index-pressures, duplex angiogram and transcutaneous oxygen pressures. An angiogram +/- angioplasty or alternatively a magnetic resonance angiography prior to surgical revascularisation was performed in patients deemed not suitable for angioplasty based on the above vascular assessment. Between January 2002 and June 2003(18 months), 128 diabetic patients with lower limb ischaemia were seen. Thirty-four (26.6%) patients received medical treatment alone, and 18 (14.1%) were deemed 'palliative' due to their significant co-morbidities. The remaining 76 (59.4%) patients underwent either angioplasty (n = 56), surgical reconstruction (n = 18), primary major amputation (n = 2) or secondary amputation after surgical revascularisation (n = 1). Minor toe amputations were required in 35 patients. The mortality in the intervention group was 14% (11/76). This integrated multidisciplinary approach offers a consistent and equitable service to diabetic patients with critically ischaemic feet and appears to have a beneficial major/minor amputation ratio.

Spinal cord stimulation is not cost-effective for non-surgical management of critical limb ischaemia.

OBJECTIVE: To quantify the costs of treatment in critical limb ischaemia (CLI) and to compare costs and effectiveness of two treatment strategies: spinal cord stimulation (SCS) and best medical treatment. METHODS: One hundred and twenty patients with CLI not suitable for vascular reconstruction were randomised to either SCS in addition to best medical treatment or best medical treatment alone. Primary outcomes were mortality, amputation and cost. Cost analysis was based on resources used by patients for 2 years after randomisation. Both medical and non-medical costs were included. RESULTS: Patient and limb survival were similar in the two treatment groups. Costs of in-hospital-stay and institutional rehabilitation constituted the predominant part (+/-70%) of the total costs of medical care in CLI. Cost of SCS-implantation and complications (7950 euro per patient) exceeded by far cost due to amputation procedures (410 euro per patient). The total costs of treatment were 36,600 euro per patient over 2 years for the SCS-group vs. 28,700 euro for best medical treatment alone (28% higher for SCS-group, p=0.009). CONCLUSIONS: Total costs of treatment in CLI are high. Major components are hospital and rehabilitation costs. In contrast to recent reviews, there were no long-term benefits of SCS-treatment. Therefore, cost-effectiveness is reduced to cost-minimisation and SCS-treatment is considerably more expensive than best medical treatment.

Impact of different therapeutic alternatives in treatment of severe limb ischemia: experiences on 190 consecutive patients at a department of medical angiology.

BACKGROUND: Different therapies in consecutive patients (1987-1992) with chronic critical limb ischemia at a department of medical angiology, their short- and long-term outcome were investigated. PATIENTS AND METHODS: 190 patients (112 males, 78 females; age: 67 +/- 12 years); 78 in grade II, 112 in grade III according to Rutherford's classification. Therapeutic regimen: 1. vascular recanalisation by percutaneous transluminal angioplasty [PTA], local or systemic lysis; 2. surgical vascular reconstruction in case of impossibility or failure of catheter procedures; 3. prostanoids and/or antibiotics; 4. local wound treatment including amputations. RESULTS: Vascular recanalisation was attempted in 156/190 (82.1%): PTA in 116/190, surgical vascular reconstruction in 50/190, local in 24/190 and systemic lysis in 8/190 patients. Prostanoids were applied in 89/190 and antibiotics in 73/190 patients. At the time of dismissal 164/190 (86.3%) patients were clinically improved; 11/190 (5.8%) unchanged, 13/190 (6.8%) had undergone major amputations and 2/190 (1.1%) had died. After 2.6 +/- 2.2 years 77 of the 141 patients, who were still alive, were reexamined. Among these 77 patients 84.4% were in grade 0 or 1, 15.6% in chronic critical limb ischemia. Furthermore 13.0% had been amputated since dismissal. Forty-nine of 190 (25.8%) patients had died 3.2 +/- 1.9 years after dismissal from hospital. CONCLUSION: Catheter techniques, mostly PTA, is possible in the majority of patients with chronic critical limb ischemia. Cooperation with vascular surgeons in case of technical impossibility or failure of catheter recanalisation is mandatory. Such a regimen yields satisfactory short- and long-term results and a low rate of complications.

Spinal-cord stimulation in critical limb ischaemia: a randomised trial. ESES Study Group.

BACKGROUND: For patients with critical limb ischaemia, spinal-cord stimulation has been advocated for the treatment of ischaemic pain and the prevention of amputation. We compared the efficacy of the addition of spinal-cord stimulation to best medical treatment in a randomised controlled trial. METHODS: 120 patients with critical limb ischaemia not suitable for vascular reconstruction were randomly assigned either spinal-cord stimulation in addition to best medical treatment or best medical treatment alone. Primary outcomes were mortality and amputation. The primary endpoint was limb survival at 2 years. FINDINGS: The mean (SD) age of the patients was 72.6 years (10.3). Median (IQR) follow-up was 605 days (244-1171). 40 (67%) of 60 patients in the spinal-cord-stimulator group and 41 (68%) of 60 patients in the standard group were alive at the end of the study, (p=0.96). There were 25 major amputations in the spinal-cord-stimulator group and 29 in the standard group, (p=0.47). The hazard ratio for survival at 2 years without major amputation in the spinal-cord stimulation group compared with the standard group was 0.96 (95% CI 0.61-1.51). INTERPRETATION: Spinal-cord-stimulation in addition to best medical care does not prevent amputation in patients with critical limb ischaemia.

[Regional hyperthermic fibrinolytic perfusion as ultima ratio in critical ischemia of the lower extremities]. / Regionale hypertherme Fibrinolytika-Perfusion als ultima ratio bei kritischer Ischämie der unteren Extremitäten.

In 19 patients (male-female: ratio 10:9; median age 67.1 (42-90) years) with a critical ischaemia of the lower extremities either after failed attempt of revascularization (n = 4) or because of lacking possibility for vessel reconstruction measures (n = 16) a regional extremity perfusion with a fibrinolytic agent has been performed using a heart lung machine. In one patient both lower extremities were treated. In the first 30 minutes of the total 60 minutes perfusion time on average 31 mg (20-50 mg) of recombinant tissue-plasminogen activator (Actilyse) have been added to the perfusion solution. In order to enhance the fibrinolysis-activity the perfusion solution was warmed up to 40 degrees C. Systemic side effects have not been observed. Two patients died postoperatively because of their underlying diseases (mesenteric artery embolism, myocardial infarction), two patients experienced postoperative haemorrhage and one patient had a wound infection. In 11 cases (55%) an opening of the stem-arteries has been reached. Seven of these were successfully revascularized with a femoro-crural bypass in a following operation. Nine extremities (45%) remained without opening of the stem-arteries, however, in four cases (20%) an improved radiographic contrast of the collaterals has been reached. 11 (61%) of the followed-up extremities were successfully revascularized. Amputation has been performed in seven cases (39%). The regional hyperthermic perfusion with fibrinolytic drugs enables a reopening of the stem-arteries and the creation of accepting vessels for vascular procedures in primarily inoperable arterial occlusions.

Role of P-selectin in total hepatic ischemia and reperfusion.

BACKGROUND: Ischemia and reperfusion of the liver are associated with changes in the interaction of leukocyte-endothelium cells. The role of an adhesion molecule, P-selectin, is studied in ischemia and reperfusion injury of the liver. STUDY DESIGN: Total hepatic ischemia was produced in the rat for 90 minutes, using a portosystemic shunt. To determine the role of P-selectin in ischemia and reperfusion, a murine IgG1 monoclonal antibody to P-selectin (1 mg/kg) was used at different times (30 minutes before and at reperfusion and five minutes and 24 hours after reperfusion). Rats survived for seven days, and tests showing hepatic injury, myeloperoxidase in hepatic tissue, and histologic studies were analyzed at four hours postreperfusion. RESULTS: Survival improved from 15 percent for the rats in the ischemia control group to 55 percent for those in the group receiving anti-P-selectin antibody given 30 minutes before reperfusion (p < 0.05). We observed an improved statistically significant difference in tests demonstrating hepatic injury, myeloperoxidase in hepatic tissue, and histologic studies in the treated and ischemia control groups. The other groups did not show consistent significant differences. CONCLUSIONS: P-selectin has a significant role in ischemia and reperfusion injury of the liver. Early modulation of the interaction between P-selectin and its ligand decreased neutrophil adhesion and migration and consequently diminished damage to the liver.

Attenuation of renal reperfusion injury in rats by the 21-aminosteroid U74006F.

PURPOSE: The 21-aminosteroids represent a new class of compounds that serve as potent inhibitors of iron-dependent lipid peroxidation, the latter being an important component of ischemia-reperfusion tissue injury. It is hypothesized that reperfusion injury accompanies renal ischemia, and postischemic administration of one of these steroids, U74006F, will reduce renal damage in a rodent model, as assessed by renal function (plasma creatinine), histologic evidence of renal injury, and animal survival during a 72-hour interval. METHODS: Fifty-one rats subjected to 45 minutes of renal ischemia were treated on clamp release with 3 or 10 mg/kg U74006F intravenously (n = 5 and 19, respectively), an inactive vehicle (n = 23), or sham operation (n = 4). RESULTS: Both doses of U74006F improved morphologic outcome compared with vehicle-treated animals. Statistically significant improvement in renal function was observed with the 10 mg/kg dose of U74006F (p = 0.029, 0.014, and 0.065 at 24, 48, and 72 hours, respectively) but not with the 3 mg/kg dose. Only one (5.2%) of 19 rats receiving high-dose U74006F (10 mg/kg) died within 72 hours after ischemia, compared with five deaths (29.4%) in 17 rats receiving citrate vehicle alone (p = 0.060). All sham-operated animals survived 72 hours with normal morphology and plasma creatinine levels. CONCLUSION: These data suggest that iron-dependent lipid peroxidation is a component of reperfusion injury and indicate that U74006F may be useful in reducing this form of renal ischemic damage.

Ischemic colitis: patterns and prognosis.

We identified 47 patients with nonocclusive ischemia of the large intestine over a seven-year period. The mean age at presentation was 56.2 years, with a 2:2:1 male predominance. Associated medical illnesses were diabetes (17 percent), renal failure (5 percent), and hematologic disorders (5 percent). Six patients developed ischemic colitis after aortic surgery. The mean delay in diagnosis was 1.8 days (range, three hours to 23 days). The right colon was involved in 21 patients (46 percent). Overall, 15 of 16 patients were successfully treated nonoperatively with bowel rest and antibiotics; one patient who was managed nonoperatively died. Among the 31 requiring intestinal resection, enteric continuity was reestablished in 14. Second-look laparotomy in eight patients revealed further ischemia in two (20 percent). Mortality in the operative group was 29 percent (9 of 31). No patient has developed recurrent ischemia (mean follow-up, 5.3 years). Ischemic colitis often occurs without an obvious predisposing event, may involve all segments of the large intestine, and frequently requires surgery. While its course may be self-limited, elderly and diabetic patients, as well as those developing ischemia following aortic surgery or hypotension, continue to have a poor prognosis.