Prosthetic outcomes after amputation and the impact of mobility level on survival.

OBJECTIVE: Lower extremity amputation continues to be necessary in a significant number of patients with peripheral vascular disease. The 5-year survival following lower limb loss is markedly reduced. Many of these patients are never fitted with a prosthesis, and there is a dearth of knowledge regarding the barriers to prosthetic attainment. The goal of this study was to identify the risk factors for not receiving a prosthesis and the effect of mobility level on survival following major amputation. METHODS: This was a retrospective analysis of all patients that underwent lower extremity amputation by surgeons in our practice from January 1, 2010, to December 31, 2019. Abstracted data included: age, sex, race, body mass index, comorbidities, American Society of Anesthesiologists score, statin use, level of amputation, stump revision, fitting for prosthesis, type of prosthesis, and the United States' Medicare Functional Classification Level, also called K level. Survival was determined using a combination of sources, including the Social Security Death Master File, searches of multiple genealogic registries, and general internet searches. Multivariable logistic regression was used to determine risk factors associated with prosthesis attainment. Multivariable Cox proportional hazard regression with time-dependent covariates was performed to assess risk factors associated with 5-year mortality. RESULTS: A total of 464 patients were included in this study. The mean age was 65 years, and mean body mass index was 27 kg/m2. The majority of patients were male (68%), White (56%), diabetic (62%), and hypertensive (76%), and underwent below-the-knee amputation (69%). Prosthetic attainment occurred in 185 (40%). On multivariable analysis, age >81 years and current tobacco use were associated with no prosthetic fitting. Overall 5-year survival was 41.9% (95% confidence interval [CI], 37.6%-46.6%) (below-the-knee amputation, 47.7% [95% CI, 42.5%-53.5%]; above-the-knee amputation, 28.7% [95% CI, 22.1%-37.2%]). On multivariable analysis, age >60 years, congestive heart failure, above-the-knee amputation, and no prosthetic attainment were associated with decreased survival. Increasing K level was incrementally associated with improved survival. CONCLUSIONS: This study has identified several patient factors associated with prosthetic attainment, as well as multiple factors predictive of reduced survival after amputation. Being referred for prosthetic fitting was associated with improved survival not explained by patient characteristics and comorbidities. The Medicare Functional Classification Level K level predicts survival. More research is needed to determine the barriers to prosthetic attainment and if improving a patients K level will improve survival.

Pre-operative Neutrophil to Lymphocyte Ratio is Associated With 30 Day Death or Amputation After Revascularisation for Acute Limb Ischaemia.

OBJECTIVE: Inflammation is an early feature of acute limb ischaemia (ALI), hence the potential prognostic significance of inflammatory biomarkers. This study aimed to assess the value of pre-operative inflammatory biomarkers, specifically the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), for predicting an adverse outcome after revascularisation for ALI. METHODS: All patients submitted to lower limb revascularisation for Rutherford IIa or IIb ALI at the authors' institution between 2009 and 2019 were screened retrospectively. Pre-operative NLR and PLR were analysed, along with other known prognostic factors. Primary outcome was the composite endpoint of 30 day death or amputation. RESULTS: A total of 345 patients were included, 84 of whom suffered the primary outcome (24.3%). The median follow up was 23.1 months (3.1 - 52.2). Higher age (OR 1.05 per year increase, 95% CI 1.01 - 1.09), diabetes (OR 2.63, 95% CI 1.14 - 6.06), Rutherford grade IIb vs. IIa (OR 5.51, 95% CI 2.11 - 14.42), higher NLR (OR 1.28 per unit increase, 95% CI 1.12 - 1.47), and fasciotomy need (OR 3.44, 95% CI 1.14 - 10.34) were independently associated with 30 day death or amputation, whereas pre-operative statin or anticoagulant medication were associated with a risk reduction (OR 0.23, 95% CI 0.53 - 0.96 and OR 0.20, 95% CI 0.05 - 0.84, respectively). PLR did not show an independent effect on this population. Pre-operative NLR presented a good discriminative ability (AUC 0.86, 95% CI 0.82 - 0.90). A cut off NLR level ≥ 5.4 demonstrated a 90.5% sensitivity and 73.6% specificity for 30 day death or amputation. Kaplan-Meier analysis showed that patients with pre-operative NLR ≥ 5.4 had significantly lower 30 day, six month and one year amputation free survival when compared with those with NLR < 5.4 (64.8 ± 4.0%, 44.1 ± 4.1%, and 37.5 ± 4.1% vs. 98.5 ± 0.9%, 91.9 ± 2.0%, and 85.9 ± 2.5%, log rank p < .001). CONCLUSION: In this study, higher pre-operative NLR was associated with 30 day death or amputation following intervention for Rutherford grade IIa or IIb ALI. NLR potentially stands as a simple, widely available and inexpensive biomarker that can refine decision making and possibly contribute to ALI morbidity and mortality reduction.

A meta-analysis of mortality after minor amputation among patients with diabetes and/or peripheral vascular disease.

OBJECTIVE: Foot complications in patients with diabetes or peripheral artery disease (PAD) are serious events in the life of these patients that often lead to amputations and mortality. No evidence synthesis has been reported on the mortality rates after minor lower extremity amputation; thus, a quantitative evidence synthesis was needed. METHODS: A systematic literature search was performed to identify studies that had reported the survival or mortality rates after a minor LEA. The studies were required to include one or more of the following primary outcomes: mortality rate at 30 days, 1 year, 3 years, 5 years, 6 to 7 years, or 8 to 9 years. The secondary outcomes were the mortality rates according to the anatomic location of the amputation in the foot and the independent risk factors for mortality. RESULTS: A total of 28 studies with 17,325 subjects fulfilled the inclusion criteria. The meta-analytical results of the mortality rates were as follows: 3.5% at 1 month, 20% at 1 year, 28% at 3 years, 44.1% at 5 years, 51.3% at 6 to 7 years, and 58.5% at 8 to 9 years. From these studies of diabetic patients, age was the most consistent independent risk factor, followed by chronic kidney disease, PAD, and coronary artery disease. One study of patients with PAD had reported diabetes as an independent risk factor for mortality. The subgroup analysis of the four studies reporting the outcomes of patients with PAD showed greater 3- and 5-year mortality rates compared with the overall and "diabetic" results. CONCLUSIONS: Mortality after minor amputation for patients with diabetes and/or PAD was found to be very high. Compared with the reported cancer data, survival was worse than that for many cancers. Just as in the case of major amputations, minor amputations should be considered a pivotal event in the life of these patients.

Outcomes for Angioplasty and Bypass Lower Limb Revascularisation Procedures for Limb Salvage in England: Findings From the Getting It Right First Time Programme.

OBJECTIVE: The aim of this study was to investigate outcomes for lower limb revascularisation for limb salvage within the National Health Service (NHS) in England. METHODS: This was a retrospective observational study of administrative data. Data were extracted from the Hospital Episodes Statistics database for England. Data were included for a seven year period (1 April 2011-31 March 2018 inclusive) for all patients aged ≥ 18 years receiving surgery for peripheral arterial occlusive disease. Data were extracted for patient age, sex and frailty level, the NHS trusts undertaking the procedure, the technique used (angioplasty, bypass, endarterectomy, or hybrid), the mode of admission (elective or emergency), the surgical speciality, the financial year of admission, length of hospital stay during the procedure, subsequent emergency re-admission, revascularisation procedures within 30 days and subsequent amputation and mortality within one year and within five years. The primary outcome was one year amputation free survival. For analysis, data were separated into diabetic and non-diabetic patients. Multilevel modelling was used to adjust for hierarchy and observed confounding when investigating outcomes. RESULTS: Data were available for 98 109 procedures across 124 hospital trusts. For non-diabetic patients (odds ratio 1.142, 95% confidence interval 1.068-1.222), one year amputation free survival was higher for angioplasty than for bypass. For diabetic patients, there was no difference in the primary outcome. One year amputation rates, 30 day emergency re-admission rates, and length of stay were all lower for angioplasty, and 30 day revascularisation rates were lower for bypass for both diabetic and non-diabetic patients. CONCLUSION: Outcomes were generally better for angioplasty than for bypass surgery for lower limb revascularisation for both diabetic and non-diabetic patients. The findings should be interpreted with caution given the likely different clinical presentations of those selected for each procedure. Future clinical trials may provide more definitive data.

Chelation therapy for atherosclerotic cardiovascular disease.

BACKGROUND: Chelation therapy is promoted and practiced around the world as a form of alternative medicine in the treatment of atherosclerotic cardiovascular disease. It has been suggested as a safe, relatively inexpensive, non-surgical method of restoring blood flow in atherosclerotic vessels. However, there is currently limited high-quality, adequately-powered research informing evidence-based medicine on the topic, specifically regarding clinical outcomes. Due to this limited evidence, the benefit of chelation therapy remains controversial at present. This is an update of a review first published in 2002. OBJECTIVES: To assess the effects of ethylene diamine tetra-acetic acid (EDTA) chelation therapy versus placebo or no treatment on clinical outcomes among people with atherosclerotic cardiovascular disease. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 6 August 2019. We searched the bibliographies of the studies retrieved by the literature searches for further trials. SELECTION CRITERIA: We included studies if they were randomised controlled trials of EDTA chelation therapy versus placebo or no treatment in participants with atherosclerotic cardiovascular disease. The main outcome measures we considered include all-cause or cause-specific mortality, non-fatal cardiovascular events, direct or indirect measurement of disease severity, and subjective measures of improvement or adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality using standard Cochrane procedures. A third author considered any unresolved issues, and we discussed any discrepancies until a consensus was reached. We contacted study authors for additional information. MAIN RESULTS: We included five studies with a total of 1993 randomised participants. Three studies enrolled participants with peripheral vascular disease and two studies included participants with coronary artery disease, one of which specifically recruited people who had had a myocardial infarction. The number of participants in each study varied widely (from 10 to 1708 participants), but all studies compared EDTA chelation to a placebo. Risk of bias for the included studies was generally moderate to low, but one study had high risk of bias because the study investigators broke their randomisation code halfway through the study and rolled the placebo participants over to active treatment. Certainty of the evidence, as assessed by GRADE, was generally low to very low, which was mostly due to a paucity of data in each outcome's meta-analysis. This limited our ability to draw any strong conclusions. We also had concerns about one study's risk of bias regarding blinding and outcome assessment that may have biased the results. Two studies with coronary artery disease participants reported no evidence of a difference in all-cause mortality between chelation therapy and placebo (risk ratio (RR) 0.97, 95% CI 0.73 to 1.28; 1792 participants; low-certainty). One study with coronary artery disease participants reported no evidence of a difference in coronary heart disease deaths between chelation therapy and placebo (RR 1.02, 95% CI 0.70 to 1.48; 1708 participants; very low-certainty). Two studies with coronary artery disease participants reported no evidence of a difference in myocardial infarction (RR 0.81, 95% CI 0.57 to 1.14; 1792 participants; moderate-certainty), angina (RR 0.95, 95% CI 0.55 to 1.67; 1792 participants; very low-certainty), and coronary revascularisation (RR 0.46, 95% CI 0.07 to 3.25; 1792 participants). Two studies (one with coronary artery disease participants and one with peripheral vascular disease participants) reported no evidence of a difference in stroke (RR 0.88, 95% CI 0.40 to 1.92; 1867 participants; low-certainty). Ankle-brachial pressure index (ABPI; also known as ankle brachial index) was measured in three studies, all including participants with peripheral vascular disease; two studies found no evidence of a difference in the treatment groups after three months after treatment (mean difference (MD) 0.02, 95% CI -0.03 to 0.06; 181 participants; low-certainty). A third study reported an improvement in ABPI in the EDTA chelation group, but this study was at high risk of bias. Meta-analysis of maximum and pain-free walking distances three months after treatment included participants with peripheral vascular disease and showed no evidence of a difference between the treatment groups (MD -31.46, 95% CI -87.63 to 24.71; 165 participants; 2 studies; low-certainty). Quality of life outcomes were reported by two studies that included participants with coronary artery disease, but we were unable to pool the data due to different methods of reporting and varied criteria. However, there did not appear to be any major differences between the treatment groups. None of the included studies reported on vascular deaths. Overall, there was no evidence of major or minor adverse events associated with EDTA chelation treatment. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of people with atherosclerotic cardiovascular disease. More high-quality, randomised controlled trials are needed that assess the effects of chelation therapy on longevity and quality of life among people with atherosclerotic cardiovascular disease.

A systematic review and meta-analysis of bivalirudin application in peripheral endovascular procedures.

OBJECTIVE: The direct thrombin inhibitor bivalirudin (BIV) was shown to be superior to unfractionated heparin (UFH) in percutaneous coronary interventions for reducing procedural blood loss. The aim of this study was to compare outcome profiles of BIV and UFH in peripheral endovascular procedures (PEPs) by synthesizing the currently available data. METHODS: Following the PRISMA statement, we conducted a comprehensive literature search using Medline, Cochrane CENTRAL, PubMed, EMBASE, CINAHL Google scholar, and clinicaltrials.gov. We recruited randomized, controlled trials and well-conducted observational studies that compared UFH and BIV in PEPs requiring anticoagulation, excluding endovascular cardiac procedures and coronary interventions. Random-effects meta-analyses were conducted to compare the outcome profiles of these two agents. RESULTS: Thirteen articles containing 14 studies involving a total of 21,057 patients were enrolled. Of these, 2 were randomized controlled trials, 2 were prospective cohort studies, and 10 were retrospective studies. There were no significant differences between BIV and UFH in terms of procedural success rates, major and minor perioperative bleeding, transfusion, perioperative transient ischemic attack, or hemorrhagic strokes. However, compared with UFH, BIV had significantly lower odds ratios (OR) of perioperative mortality (OR, 0.58; 95% confidence interval [CI], 0.40-0.86), major adverse cardiovascular events (OR, 0.65; 95% CI, 0.51-0.83), net adverse clinical events (OR, 0.75; 95% CI, 0.63-0.88), perioperative myocardial infarction (OR, 0.73; 95% CI, 0.55-0.98), major vascular complications (OR, 0.59; 95% CI, 0.39-0.91), and minor vascular complications (OR, 0.58; 95% CI, 0.40-0.84). CONCLUSIONS: Compared with UFH, PEPs using BIV had comparable procedural success rates and odds of perioperative transient ischemic attack and hemorrhagic stroke. However, procedures with BIV had a lower but nonsignificant odds of perioperative bleeding and transfusion. Depending on the procedures conducted, the patients who received BIV will have reduced or comparable odds of perioperative mortality, myocardial infarction, major adverse cardiovascular events, net adverse clinical events, and major and minor vascular complications. Therefore, BIV may be chosen solely as an alternative procedural anticoagulant to UFH for PEPs.

Outcomes in patients with peripheral vascular disease following percutaneous coronary intervention.

OBJECTIVES: To evaluate the clinical characteristics and outcomes of patients with peripheral vascular disease (PVD) undergoing percutaneous coronary intervention (PCI) in a contemporary setting, and to determine whether use of drug-eluting stents (DESs) improves outcomes. BACKGROUND: PVD was an independent risk factor for adverse outcomes following PCI in the bare-metal stent (BMS) era. It is not known whether outcomes in these patients have improved with advances in interventional techniques and stent technology, as they have for the general population. METHODS: Eighteen thousand three hundred and eighty patients undergoing PCI from an Australian registry between 2005 and 2013 were studied. Clinical and procedural data, 30-day and 12-month outcomes were compared in those with and without a reported history of PVD. Outcomes were also compared between patients with PVD who received DES and those who received BMS. Long-term mortality was compared using Australian National Death Index (NDI) linkage. RESULTS: Patients with PVD (n = 1,251, 6.8%) were older and had more prevalent diabetes, hypertension, cerebrovascular disease, heart failure, renal impairment, ostial lesions, left main, and multi-vessel disease (p < 0.001). Patients with PVD had significantly higher rates of major adverse cardiovascular events (MACEs) compared with those without PVD, in-hospital (5.7% vs. 4.1%, p < 0.008), at 30-days (8.6% vs. 5.8%, p < 0.001) and at 12-months (24.6% vs. 13.2%, p < 0.001). At 4.9 ± 2.6 years follow-up, there was significantly greater mortality in the PVD group. PVD patients who received DES experienced significantly less MACE than PVD patients treated with BMS at 30-days (4.8 vs. 10.1%, p < 0.001) and 12-months (19.4 vs. 26.4%, p < 0.005). CONCLUSIONS: PVD is an independent predictor of adverse outcomes in patients undergoing PCI. PVD patient who received DES had improved outcomes compared with those receiving BMS.

Initiating haemodialysis twice-weekly as part of an incremental programme may protect residual kidney function.

BACKGROUND: Initiating twice-weekly haemodialysis (2×HD) in patients who retain significant residual kidney function (RKF) may have benefits. We aimed to determine differences between patients initiated on twice- and thrice-weekly regimes, with respect to loss of kidney function, survival and other safety parameters. METHODS: We conducted a single-centre retrospective study of patients initiating dialysis with a residual urea clearance (KRU) of ≥3 mL/min, over a 20-year period. Patients who had 2×HD for ≥3 months during the 12 months following initiation of 2×HD were identified for comparison with those dialysed thrice-weekly (3×HD). RESULTS: The 2×HD group consisted of 154 patients, and the 3×HD group 411 patients. The 2×HD patients were younger (59 ± 15 versus 62 ± 15 years: P = 0.014) and weighed less (70 ± 16 versus 80 ± 18 kg: P < 0.001). More were females (34% versus 27%: P = 0.004). Fewer had diabetes (25% versus 34%: P = 0.04) and peripheral vascular disease (PVD) (13% versus 23%: P = 0.008). Baseline KRU was similar in both groups (5.3 ± 2.4 for 2 × HD versus 5.1 ± 2.8 mL/min for 3 × HD: P = 0.507). In a mixed effects model correcting for between-group differences in comorbidities and demographics, 3×HD was associated with increased rate of loss of KRU and separation of KRU. In separate mixed effects models, group (2×HD versus 3×HD) was not associated with differences in serum potassium or phosphate, and the groups did not differ with respect to total standard Kt/V. Survival, adjusted for age, gender, weight, baseline KRU and comorbidity (prevalence of diabetes, cardiac disease, PVD and malignancy) was greater in the 2×HD group (hazard ratio 0.755: P = 0.044). In sub-analyses, the survival benefit was confined to women, and those of less than median bodyweight. CONCLUSION: 2×HD initiation as part of an incremental programme with regular monthly monitoring of KRU was safe and associated with a reduced rate of loss of RKF early after dialysis initiation and improved survival. Randomized controlled trials of this approach are indicated.

Stenting for Inferior Vena Cava Stenosis After Liver Transplant.

OBJECTIVE. A case series analysis and meta-analysis were performed to assess the efficacy of stenting for inferior vena cava (IVC) stenosis after liver transplant; a secondary analysis assessed demographic factors as potential predictors of all-cause mortality. MATERIALS AND METHODS. Liver transplant recipients treated for symptomatic IVC stenosis at a major medical center from 1996 to 2017 were assessed. The main medical databases were searched for studies evaluating stenting in liver transplant recipients with IVC stenosis. Cox proportional hazards regression analysis was used to determine predictors of survival (age, sex, reason for transplant, stent size and number, publication year). Univariate and multivariable models were constructed. Because patients in the case series and meta-analysis had similar demographics and outcomes, the results were pooled. RESULTS. The case series included 40 patients (31 treated with stents; nine, without stents). Meta-analysis of 5277 records identified 17 eligible studies involving 73 patients. Stenting was effective in resolving the gradient in 100% of patients and in relieving symptoms in 85% of patients. Primary stent patency at latest follow-up (median, 556 days) was seen in 113 of 118 stents (96%; some patients had multiple stents). Reason for transplant was the only significant predictor of all-cause mortality; patients with hepatocellular carcinoma had a higher hazard of death than those undergoing transplant for other reasons (hazard ratio = 3.23; 95% CI, 1.40-7.42; p = 0.006). CONCLUSION. Stenting for IVC stenosis after liver transplant is clinically effective and durable, with 96% of stents showing long-term patency and 85% of patients experiencing symptom relief.

Objective Performance Goals for Surgical Treatment of Critical Limb Ischemia.

BACKGROUND: Based on prospective vein bypass trials for lower leg ischemia, objective performance goals (OPG) were established by the Society for Vascular Surgery (SVS) and are used as a benchmark tool for open and endovascular treatments. This study aims to analyze OPG of all patients with critical limb ischemia (CLI) treated by open revascularization techniques at a tertiary care facility in routine practice. METHODS: From January 2005 to March 2013, 315 patients (mean age 72 years) with CLI were retrospectively included in this study. Inclusion criteria were patients with Fontaine stage III and IV, realized revascularization with open surgical procedures (bypass grafting or endarterectomy), or hybrid method (open + endovascular). Exclusion criteria were primary major amputations, patients with revascularization treatments of the index leg within the last 3 months, and missing aftercare. Primary end point was "amputation-free survival" (AFS), and secondary end point was "freedom from major adverse limb event + perioperative death (30 days)" (MALE + POD) according to the SVS. The technical end point was primary patency. Mean follow-up was 34 months. The following variables were studied: clinical stage (Fontaine), previous interventions, bypass material used, and site of the distal anastomosis. The statistical evaluation and preparation was carried out using the Kaplan-Meier estimator and the log-rank test. A multivariate analysis was performed using the Cox proportional hazards model. A P value ≤0.05 was considered to be statistically significant. RESULTS: A total of 128 patients (31%) fulfilling the adjusted SVS OPG criteria showed significantly better results for AFS, MALE + POD, and primary patency (P = 0.013, P = 0.015, P = 0.002, respectively). Regarding the AFS (1 year: 74%), multivariate analysis displayed significant worse results for patients with end-stage renal disease (hazard ratio [HR] 2.90, 95% confidence interval [CI] 1.83-4.60, P < 0.001) and Fontaine stage IV (HR 1.69, 95% CI 1.11-2.57, P = 0.015). Regarding MALE + POD (1 year: 64%), male patients (HR 0.64, 95% CI 0.46-0.90, P = 0.011) showed a significantly better outcome and patients without previous interventions of the index leg (HR 1.51, 95% CI 1.09-2.09, P = 0.013) showed a significantly worse outcome. CONCLUSIONS: In this study, we were able to show that it is possible to reach the efficacy of OPGs set by SVS in a surgically treated all-comers cohort of CLI patients. Nevertheless, patients who did not fulfill the SVS OPG criteria showed significantly worse results for AFS and MALE + POD.

Effects of simultaneous pancreas-kidney transplantation and kidney transplantation alone on the outcome of peripheral vascular diseases.

BACKGROUND: The effects of Simultaneous Pancreas Kidney Transplantation (SPKT) on Peripheral Vascular Disease (PVD) warrants additional study and more target focus, since little is known about the mid- and long-term effects on the progression of PVD after transplantation. METHODS: 101 SPKT and 26 Kidney Transplantation Alone (KTA) recipients with insulin-dependent diabetes mellitus (IDDM) were retrospectively evaluated with regard to graft and metabolic outcome. Special subgroup analysis was directed towards the development and progression of peripheral vascular complications (PVC) (amputation, ischemic ulceration, lower extremity angioplasty/ bypass surgery) after transplantation. RESULTS: The 10-year patient survival was significantly higher in the SPKT group (SPKT: 82% versus KTA 40%; P < 0.001). KTA recipients had a higher prevalence of atherosclerotic risk factors, including coronary artery disease (P < 0.001), higher serum triglyceride levels (P = 0.049), higher systolic (P = 0.03) and diastolic (P = 0.02) blood pressure levels. The incidence of PVD before transplantation was comparable between both groups (P = 0.114). Risk factor adjusted multivariate analysis revealed that patients with SPKT had a significant lower amount (32%) of PVCs (32 PVCs in 21 out of 101 SPKT; P < 0.001) when compared to the KTA patients who developed a significant increase in PVCs to 69% of cases (18 PVCs in 11 out of 26 KTA; P < 0.001). In line mean values of HbA1c (P < 0.01) and serum triglycerides (P < 0.01) were significantly lower in patients with SPKT > 8 years after transplantation. CONCLUSION: SPKT favorably slows down development and progression of PVD by maintaining a superior metabolic vascular risk profile in patients with IDDM1.

A systematic review of isolated radial artery harvesting as a conduit for lower limb bypass grafting.

BACKGROUND: Whilst autologous vein conduits have been heralded as the first-line approach for patients undergoing lower limb bypass grafting procedures, patients with peripheral arterial occlusive disease may have exhausted venous options given prior use for cardiac surgery, varicose vein surgery, or lower limb revascularization. Hence, the use of a radial artery graft may serve as a viable alternative. METHODS: The systematic review was performed in accordance to the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. An electronic search was performed on the following databases: Medline (via PubMed); EMBASE; Cochrane library to search for relevant publications. A narrative analysis was conducted. RESULTS: Four publications were included in this review including two retrospective cohort studies, one case series, and one case report, with a total of 43 patients. The most common indication for lower limb bypass grafting was critical limb ischemia, and the radial artery was chosen as graft conduit, most commonly due to the absence of suitable arm or leg vein. There was one case of 30-day mortality and 11 reinterventions. CONCLUSION: Despite the encouraging results, the paucity of high-quality studies prevents the establishment of any firm conclusion. This warrants the need for appropriately conducted randomized controlled trials to compare the radial artery graft to autologous vein grafts and prosthetic grafts for lower limb bypass grafting.

Influence of specific comorbidities on survival after early-stage breast cancer.

BACKGROUND: While comorbidity indices are useful for describing trends in survival, information on specific comorbidities is needed for the clinician advising the individual breast cancer patient on her treatment. Here we present an analysis of overall survival, breast cancer-specific mortality, and effect of medical adjuvant treatment among breast cancer patients suffering from 12 major comorbidities compared with breast cancer patients without comorbidities. MATERIAL AND METHODS: The study population was identified from the Danish Breast Cancer Cooperative Group and included 59,673 women without prior cancer diagnosed with early-stage breast cancer in Denmark from 1990 to 2008 with an estimated median potential follow-up of 14 years and 10 months. Information on comorbidity and causes of death was derived from population-based registries. Multivariable proportional hazards regression models were used to assess the effect of comorbidities on mortality, all-cause and breast cancer specific, using patients without comorbidity as reference. RESULTS: At breast cancer diagnosis, 16% of patients had comorbidities and 84% did not. Compared with the latter, the risk of dying from all causes was significantly increased for all types of comorbidity, but the risk of dying from breast cancer was significantly increased only for peripheral vascular disease, dementia, chronic pulmonary disease, liver, and renal diseases. Comorbidities diagnosed within 5 years of breast cancer diagnosis correlated with a greater risk of dying than comorbidities diagnosed more than 5 years before breast cancer diagnosis. With a few exceptions, the effect of adjuvant treatment on breast cancer mortality was similar among patients with and without comorbidity. CONCLUSION: Breast cancer mortality was not significantly elevated for patients with prior myocardial infarction, congestive heart failure, cerebrovascular disease, connective tissue disease, ulcer disease, and diabetes. The similar effect of adjuvant treatment in patients with and without comorbidity underlines the importance of adhering to guideline therapy.

Predictors of complication following lower extremity amputation in diabetic end-stage renal disease.

AIM: Patients with diabetic end-stage renal disease (ESRD) are at increased risk of lower extremity amputation (LEA) and postoperative complications compared to those without diabetic ESRD. This study sought to determine the factors that influence complications following LEA in patients with diabetic ESRD. METHODS: A total of 41 patients with diabetic ESRD (total of 46 amputations) who underwent LEA were enrolled in this study. The electronic medical records were retrospectively reviewed to identify the predictors of postoperative complications. The outcomes were divided into three categories: no complications, minor complications (wounds requiring only local care or oral antibiotics), and major complications (requiring surgical intervention, further amputations, or inducing life-threatening morbidities and mortalities). RESULTS: Multivariate logistic regression analysis demonstrated that underlying sepsis (P = 0.007) was the only significant risk factor for major complications, with an odds ratio demonstrating an 8.16 times increased risk of requiring another surgery or mortality compared to those without sepsis. CONCLUSION: Preoperative sepsis is an independent risk factor for major complications after LEA in patients with diabetic ESRD. We advise particular caution when performing LEA in diabetic ESRD patients who are also septic. Early amputation, prior to the development of sepsis, is preferable.

[Gene-mediated induction of angiogenesis in inoperable patients with atherosclerosis and diabetes mellitus]. / Gennaia induktsiia angiogeneza u neoperabel'nykh patsientov s aterosklerozom i sakharnym diabetom.

Analysed in the article are the results of a comprehensive approach to treatment of patients presenting with lower limb critical ischaemia and diabetes mellitus by means of gene-induced angiogenesis. The study comprised a total of 65 patients found to have an ill-suited for surgical reconstruction peripheral arterial bed and undergoing conservative therapy. The patients were divided into two groups. The Study Group patients additionally to the conventional conservative therapy received 2 intramuscular injections of therapeutic agent Neovasculgen at a course dose of 2.4 mg. The active period of follow up amounted to 6 months followed by evaluating limb salvage and lethal outcomes at a further 6 months thereafter. Efficacy of treatment was determined both by primary criteria (lethality rate, amputations, dynamics of necrosis healing, clinical relief of critical ischaemia) and secondary criteria (pain-free walking distance, ankle-brachial index, transcutaneous oxygen tension, linear velocity of blood flow, the Michigan Neuropathy Screening Instrument (MNSI) and Neurological Symptom Score (NSS) scale). After 6 months of follow up, the statistical significance in the intragroup and intergroup comparisons was reached for the pain-free walking distance (increment up to 72.9±9.2 m, p=0.032), transcutaneous oxygen tension (increment by 34.4%, p=0.028), linear velocity of blood flow (increment by 65.3%, p=0.047). Induction of angiogenesis also made it possible to statistically significantly decrease the manifestations of diabetic neuropathy, as was evidenced by the data of the MSNI (p=0.009) and the NSS scale (p=0.044). The findings of the study also demonstrated the best value of the limb salvage rate (p=0.049) and a lower number of lethal complications at 1 year of follow up.

A Meta-analysis of Long-term Mortality and Associated Risk Factors following Lower Extremity Amputation.

BACKGROUND: A majority of patients undergoing lower limb amputations have diabetes or peripheral artery disease. Despite improvements in care, there remains a substantial perioperative mortality associated with these procedures. Less well-defined is the mortality risk to these patients going forward, once outside the perioperative period. The aim of this systematic review is to summarize and pool the available data to determine the long-term mortality associated with amputation in the diabetic and peripheral vascular patient, as well as to define specific factors associated with increased mortality risk. METHODS: Four databases were searched from January 2005 through July 2015 using the Medical Subject Headings terms "amputation," "lower extremity," and "mortality." Inclusion criteria were observational and cohort studies where ≥50% of amputations were attributable to diabetic or vascular etiologies. Final article inclusion was approved by reviewer consensus. Bias was assessed with the Joanna Briggs Institute Critical Appraisal Tool for cohort studies. RESULTS: Of the 365 unique records screened, 43 abstracts and 21 full articles were reviewed and 16 studies ultimately included. The overall mortality rate was 47.9%, 61.3%, 70.6%, and 62.2% at 1-, 2-, 3- and 5-year follow-up, respectively. In addition to diabetes and peripheral vascular disease, comorbid factors associated with at least a 2-fold increased mortality were coronary artery disease, cerebrovascular disease, renal dysfunction, American Society of Anesthesiologists class ≥4, dementia, and nonambulatory status. Surgical factors, including higher amputation level and need for staged surgery with up-front guillotine amputation, were also correlated with increased mortality. CONCLUSIONS: The overall mortality rate after primary lower limb amputation in the diabetic and peripheral vascular population is substantial, and should not be underestimated when making decisions regarding limb salvage. Similar to patients undergoing revascularization, comorbid conditions associated with higher mortality should be optimized before surgery whenever possible.

Cost-Effectiveness Analysis of the Use of a Prophylactic Antibiotic for Patients Undergoing Lower Limb Amputation due to Diabetes or Vascular Illness in Colombia.

BACKGROUND: The use of a prophylactic antibiotic in an amputation surgery is a key element for the successful recovery of the patient. We aim to determine, from the perspective of the Colombian health system, the cost-effectiveness of administering a prophylactic antibiotic among patients undergoing lower limb amputation due to diabetes or vascular illness in Colombia. METHODS: A decision tree was constructed to compare the use and nonuse of a prophylactic antibiotic. The probabilities of transition were obtained from studies identified from a systematic review of the clinical literature. The chosen health outcome was reduction in mortality due to prevention of infection. The costs were measured by expert consensus using the standard case methodology, and the resource valuation was carried out using national-level pricing manuals. Deterministic sensitivity, scenarios, and probabilistic analyses were conducted. RESULTS: In the base case, the use of a prophylactic antibiotic compared with nonuse was a dominant strategy. This result was consistent when considering different types of medications and when modifying most of the variables in the model. The use of a prophylactic antibiotic ceases to be dominant when the probability of infection is greater than 48%. CONCLUSIONS: The administration of a prophylactic antibiotic was a dominant strategy, which is a conclusion that holds in most cases examined; therefore, it is unlikely that the uncertainty around the estimation of costs and benefits change the results. We recommend creating policies oriented toward promoting the use of a prophylactic antibiotic during amputation surgery in Colombia.

Intravascular Ultrasound in Lower Extremity Peripheral Vascular Interventions: Variation in Utilization and Impact on In-Hospital Outcomes From the Nationwide Inpatient Sample (2006-2011).

PURPOSE: To examine the impact of intravascular ultrasound (IVUS) utilization during lower limb endovascular interventions as regards postprocedural complications and amputation. METHODS: The study cohort was derived from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database between the years 2006 and 2011. Peripheral endovascular interventions were identified using appropriate ICD-9 procedure codes. Two-level hierarchical multivariate mixed models were created. The co-primary outcomes were in-hospital mortality and amputation; the secondary outcome was postprocedural complications. Model results are given as the odds ratio (OR) and 95% confidence interval (CI). Hospitalization costs were also assessed. RESULTS: Overall, among the 92,714 patients extracted from the database during the observation period, IVUS was used in 1299 (1.4%) patients. IVUS utilization during lower extremity peripheral vascular procedures was independently predictive of a lower rate of postprocedural complications (OR 0.80, 95% CI 0.66 to 0.99, p=0.037) as well as lower amputation rates (OR 0.59, 95% CI 0.45 to 0.77, p<0.001) without any significant impact on in-hospital mortality. Multivariate analysis also revealed IVUS utilization to be predictive of a nonsignificant increase in hospitalization costs ($1333, 95% CI -$167 to +$2833, p=0.082). CONCLUSION: IVUS use during lower limb endovascular interventions is predictive of lower postprocedural complication and amputation rates with a nonsignificant increase in hospitalization costs.

Results of Infrainguinal Bypass in Acute Limb Ischaemia.

OBJECTIVE/BACKGROUND: To assess the outcomes of infrainguinal bypass performed for acute limb ischaemia, as well as the predictors of patency, mortality, and amputation. METHODS: This was a retrospective cohort study of patients undergoing infrainguinal bypass between 1998 and 2014. The cohort was stratified according to the indication for surgery into two groups: group A (acute limb ischaemia) and group B (chronic lower extremity ischaemia). Comparative analysis was performed on comorbidities, surgical technique, and outcomes, as well as prognostic factors in group A. RESULTS: In total, 702 bypasses were performed (group A, n = 107; group B, n = 595). Differences between groups were detected in age (65.9 vs. 70.9 years; p = .03), diabetes (16% vs. 49%; p < .01), renal insufficiency (6% vs. 13%; p = .05), stroke (7% vs. 14%; p = .04), and coronary artery disease (13% vs. 28%; p < .01). Patients with acute limb ischaemia more often required general anaesthesia (47% vs. 12%; p < .01) and a short bypass was more often performed (32% vs. 7%; p < .01). Median follow up was 23 and 24 months for groups A and B, respectively. No differences were found in patency rates at 1, 12, and 24 months between groups, but group B had a higher re-intervention rate during follow up. Primary patency in group A was 84%, 63%, and 58%, and in group B it was 88%, 62%, and 53% at 1, 12, and 24 months, respectively (p = .77). Assisted primary patency in group A was 85%, 72%, and 67%, and in group B it was 90%, 74%, and 66% at 1, 12, and 24 months, respectively (p = .61). Secondary patency in group A was 90%, 78%, and 75%, and in group B it was 94%, 80%, and 74% at 1, 12, and 24 months, respectively (p = .80). The freedom from re-intervention rate in group A was 91%, 74%, and 68%, and in group B it was 92%, 76%, and 71%, respectively (p = .04). Acute limb ischaemia was an independent risk factor for amputation (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.74-14.09; p < .01) and mortality (OR 4.13, 95% CI 1.53-11.14; p = .01) at 30 days. In group A, female sex, prosthetic conduit, and need of distal thrombectomy were independently associated with worse patency rates. Poor intra-operative runoff was correlated with higher amputation rates. CONCLUSION: Among those undergoing infrainguinal bypass, patients who present with acute limb ischaemia constitute a subset showing higher early rates of amputation and death. In this subset of patients, worse outcomes may be expected for women, prosthetic conduits, need for distal thrombectomy, and patients with poor intra-operative runoff.