Direct Immunoassay for Free Pregnancy-Associated Plasma Protein A (PAPP-A).

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A), especially in its noncomplexed form (fPAPP-A), is linked to vulnerable atherosclerotic plaques and risk of cardiac events. An assay for sensitive detection of fPAPP-A has been lacking. Our aim was to develop and validate a direct fPAPP-A assay to meet this need. METHODS: Monoclonal antibodies binding exclusively fPAPP-A were produced by immunizing mice with recombinant PAPP-A. In the optimized immunoassay, we used an fPAPP-A-specific capture antibody together with a lanthanide-chelate-labeled monoclonal antibody recognizing all PAPP-A forms. The assay was evaluated with CLSI guidelines and compared to a 2-assay subtractive fPAPP-A approach. Clinical performance was assessed with acute coronary syndrome patients. RESULTS: The limits of detection and quantitation were 0.4 mIU/L and 1.3 mIU/L, respectively, and the assay was linear up to 1000 mIU/L (R2 = 0.999). Both serum and heparin plasma were suitable matrices, and the complexed form of PAPP-A caused no significant interference. Correlation between the developed assay and the 2-assay approach was fair (Pearson's r = 0.819). Median concentration in healthy individuals was 1.0 mIU/L. fPAPP-A concentration was higher in patients who had myocardial infarction or died during the 1-year follow-up period than in those who did not (1.13 mIU/L vs 0.82 mIU/L, P = 0.008, model adjusted with age and sex). fPAPP-A measured with this direct assay predicted this end point as well as (follow-up 1 year) or better (30 days) than the 2-assay fPAPP-A alone or in combination with cTnI. CONCLUSIONS: The new assay enables sensitive and reliable measurement of low cardiac-related fPAPP-A concentrations from blood samples.

Magnetic Resonance Imaging of Internal Jugular Veins in Multiple Sclerosis: Interobserver Agreement and Comparison with Doppler Ultrasound Examination.

BACKGROUND: Doppler ultrasound (US) has been widely used to evaluate the cervical venous system of multiple sclerosis patients according to the hypothesis of chronic cerebrospinal venous insufficiency with contradictory results. Venous anatomy and pathology can be examined with less operator-dependent magnetic resonance imaging (MRI). Our aim is to assess the interobserver agreement in measuring internal jugular vein (IJV) cross-sectional area (CSA) in MR images and to explore the agreement between US and MRI in the detection of calibers of ≤0.3 cm2 in the IJV CSA in the prospective study. METHODS: Thirty-seven multiple sclerosis patients underwent MRI of the cervical venous system. Two independent neuroradiologists measured the CSA of IJV at the mid-thyroid level. Furthermore, the time from contrast enhancement of common carotid arteries to that of each IJV (transit time in seconds) was assessed, and recorded whether IJV or the vertebral plexus visualized first during the contrast passage. US examination had been performed earlier. RESULTS: Interobserver agreement for assessing IJV CSA in MR images was substantial: the measurements differed >0.5 cm2 between the examiners in only 5 IJVs (7%), Cohen's kappa 0.79. Transit times from common carotid artery to IJV varied between 5.1 and 14.1 sec. Fifteen patients had left-to-right asymmetry in the speed of IJV contrast filling. IJV CSA ≤ 0.3 cm2 was found in 51 IJVs on the basis of US. Ten of these IJVs (19.6%) showed IJV CSA ≤ 0.3 cm2 also in MRI. All IJVs defined as CSA ≤ 0.3 cm2 in MRI met this caliber criterion also in US. CONCLUSIONS: Interobserver agreement at the thyroid level of the IJV was good at MRI measurements. The US defines more IJVs as narrow (CSA ≤ 0.3 cm2) than MRI. The US measurements for IJV CSA are not comparable with these methods. The US seems too sensitive in terms of finding venous stenosis.

Temporary Axillorenal Bypass in Complex Aorto-Renal Surgery.

BACKGROUND: Prolonged renal ischemia during vascular surgery carries high morbidity and mortality. We report an alternative technique for maintaining renal circulation during suprarenal aortic or renal artery clamping. METHODS: Between October 2007 and May 2012, 16 patients undergoing aorto-renal surgery (13 men, 3 women) were operated using temporary axillorenal bypass. Operations were performed for supra- and juxtarenal aortic aneurysms (11), occlusive aortic disease (2), renal artery stenoses (2), and abdominal myofibroblastic tumor (1). In elective cases, axillorenal bypass was planned, when prolonged renal ischemia was expected based on preoperative information. Preoperative risk factors (renal dysfunction, hypertension, coronary disease, diabetes, smoking) and intraoperative variables (operating time, blood loss, renal ischemia time) were assessed and compared with postoperative kidney function (serum creatinine, urine output, dialysis) and in-hospital or 30-day-mortality. Even though renal blood flow was restored between clampings, the total cumulative ischemia time was used in analysis. Acute renal failure postoperatively was based on RIFLE criteria. RESULTS: Preoperatively, 44% (7) of the patients had normal renal function (S-crea ≤ 100 mmol/L). Renal function was moderately present in 50% (8) (S-crea 100-200 mmol/L) and severely in 6% (1) (S-crea ≥ 200 mmol/L). Median operation time was 393 min (251-535 min) and median renal ischemia time was 24.5 min (range 8-50 min). Transient acute renal dysfunction occurred in 6 (38%) patients, and 4 of them had renal insufficiency preoperatively. Transient renal replacement therapy was needed in 1 (6%) patient only. In 1-month control, postoperative renal function had returned to its baseline level or improved and in-hospital or 30-day mortality was zero. CONCLUSIONS: Temporary axillorenal bypass is a considerable option to minimize renal ischemia time during high-risk vascular surgery.

[Assessment of ischaemia of ulcerated diabetic foot and its treatment according to recent international guidelines]. / Verenkierron arviointi ja hoito diabeettisen jalkahaavan yhteydessi kansainvailisten tuoreiden hoitosuositusten valossa.

Half of diabetic ulcers are ischaemic, almost all neuropathic and the problem is often worsened by infection. Ischaemia can often be repaired if diagnosed and treated early enough. At present, ischaemia is often diagnosed far too late. International recommendations emphasize an immediate need for a paradigm change. Ischaemia should always be suspected as a cause of diabetic ulcer unless proven otherwise. Every diabetic patient with a foot ulcer should undergo an immediate clinical and noninvasive vascular assessment. Early diagnosis and undelayed treatment with vascular consultation and necessary revascularizations are prerequisites for successful treatment as "time is tissue".

Therapeutic approach to CLI with tissue loss--a comparative prospective cohort study in Finland and Japan.

BACKGROUND: To compare the demographics, chosen treatment options, and 1-year outcome of patients with severe critical limb ischemia (Fontaine IV) in 2 different patient cohorts. METHODS: A total of 118 consecutive patients with an ischemic tissue lesion in a lower extremity referred for the first time to the vascular surgery outpatient clinic of Helsinki University Hospital and 96 patients referred to the Division of Vascular Surgery of the Tokyo Medical and Dental University Hospital were included in this comparative analysis. Kaplan-Meier estimates were used to assess survival, leg salvage, and amputation-free survival (AFS). Propensity score analysis was used to adjust for differences between the study groups. RESULTS: The median age of the study cohorts was greater in Finland than in Japan (80 vs. 69 years, P < 0.001). The prevalence of coronary artery disease and hypertension were greater in the Finnish cohort (72% vs. 41%, P < 0.001 and 86% vs. 51%, P < 0.001, respectively). The prevalence of male gender (77% vs. 42%, P < 0.001), cerebrovascular disease (35% vs. 20%, P = 0.015), end-stage renal disease (35% vs. 5%, P < 0.001), and current smoking (64% vs. 21%, P < 0.001) was greater in the Japanese cohort. The prevalence of diabetes did not differ between the cohorts (52% vs. 47%, P = 0.286). The proportion of independently ambulant patients at referral was greater in Finland (80% vs. 54%, P < 0.001). In Helsinki and Tokyo, the initial treatment was bypass, an endovascular procedure, conservative treatment, and amputation in 42% vs. 41%, 24% vs. 14%, 24% vs. 41%, and 10% vs. 5% of the cases, respectively. One-year survival, leg salvage, and AFS were 65% vs. 71% (P = 0.326), 82% vs. 74% (P = 0.216), and 59% vs. 55% (P = 0.573) in the Finnish and Japanese cohorts, respectively. AFS was significantly better in ambulant than in nonambulant patients in the combined data (68% vs. 36%, P < 0.001). Adjusted propensity score analysis showed no statistical difference in survival between the study cohorts. CONCLUSIONS: The pattern of comorbid conditions in these 2 patient cohorts is significantly different, but the outcome did not differ significantly between cohorts.

Clinical implications of the angiosome model in peripheral vascular disease.

Vascular surgery has seen a revolutionary transformation in its approach to peripheral vascular disease over the last 2 decades, fueled by technological innovation and a willingness by the field to adopt these changes. However, the underlying pathology behind critical limb ischemia and the significant rate of unhealed wounds and secondary amputations despite apparently successful revascularization needs to be addressed. In seeking to improve outcomes, it may be beneficial to examine our approach to vascular disease at the fundamental level of anatomy, the angiosome, to better dictate reperfusion strategies beyond a simple determination of open vs endovascular procedure. We performed a systematic review of the current literature concerning the significance of the angiosome concept in the realm of vascular surgery. The dearth of convincing evidence in the form of prospective trials and large patient populations, and the lack of a consistent, comparable vocabulary to contrast study findings, prevent recommendation of the conceptual model at a wider level for guidance of revascularization attempts. Further well-structured, prospective studies are required as well as emerging imaging strategies, such as indocyanine green dye-based fluorescent angiography or hyperspectral imaging, to allow wider adoption of the angiosome model in vascular operations.

A quantitative method for evaluating local perfusion using indocyanine green fluorescence imaging.

BACKGROUND: The purpose of this study is to introduce a new method, indocyanine green fluorescence imaging (ICG-FI), as an adjunct to distal pressure measurements in patients with peripheral arterial disease and symptomatic lower limb ischemia. METHODS: A total of 34 patients with peripheral arterial disease, including 11 with claudication (Fontaine II), 7 with rest pain (FIII), and 16 with an ulcer or gangrene (FIV), were enrolled. After an intravenous injection of ICG (0.1 mg/kg), foot perfusion was recorded by an infrared light camera. Fluorescence intensity was plotted on a time-intensity curve using recorded images, allowing the calculation of new parameters. Severity of ischemia was assessed as the duration between the rising point and half value of maximum brightness (T½). The difference in the fluorescence intensity between 10 seconds after the rising point and baseline (PDE10) was compared with the transcutaneous oxygen pressure (tcPO2) at the same site (n=51). RESULTS: Median T½ was 23 seconds in FII, 41 seconds in FIII (P<0.05), and 17 seconds in FIV patients. PDE10 correlated moderately with tcpO2 (r2=0.5). A cut-off value (PDE10=28) predicted a critically ischemic limb (FIII and FIV), defined as tcpO2<30 mm Hg with a sensitivity of 100% and specificity of 86.6%. CONCLUSIONS: Local tissue perfusion can be quantitatively evaluated by using ICG fluorescence imaging. It is a safe, fast, noncontact method of imaging, which may be useful even at the ulcer itself and in the circumferential area.

Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.

OBJECTIVE: Because of the prolonged healing time of diabetic foot ulcers, methods for identifying ways to expedite the ulcer healing process are needed. The angiosome concept delineates the body into three-dimensional blocks of tissue fed by specific source arteries. The aim of this study was to evaluate the benefit of infrapopliteal endovascular revascularization guided by an angiosome model of perfusion in the healing process of diabetic foot ulcers. METHODS: A total of 250 consecutive legs with diabetic foot ulcers in 226 patients who had undergone infrapopliteal endovascular revascularization in a single center were evaluated. Patient records and periprocedural leg angiograms were reviewed. The legs were divided into two groups depending on whether direct arterial flow to the site of the foot ulcer based on the angiosome concept was achieved (direct group) or not achieved (indirect group). Ulcer healing time was compared between the two groups. A propensity score was used for adjustment of differences in pretreatment covariables in multivariate analysis and for 1:1 matching. RESULTS: Direct flow to the angiosome feeding the ulcer area was achieved in 121 legs (48%) compared with indirect revascularization in 129 legs. Foot ulcers treated with angiosome-targeted infrapopliteal percutaneous transluminal angioplasty healed better. The ulcer healing rate was mean (standard deviation) 72% (5%) at 12 months for the direct group compared with 45% (6%) for the indirect group (P < .001). When adjusted for propensity score, the direct group still had a significantly better ulcer healing rate than the indirect group (hazard ratio, 1.97; 95% confidence interval, 1.34-2.90; P = .001). CONCLUSIONS: Attaining a direct arterial flow based on the angiosome model of perfusion to the foot ulcer appears to be important for ulcer healing in diabetic patients.

Lower extremity bypass vs endovascular therapy for young patients with symptomatic peripheral arterial disease.

The uncertainty continues over the best approach to patients with symptomatic peripheral arterial disease. Medical therapy and risk factor modification is part of any treatment regimen; with this there is little disagreement. However, with the introduction of lesser invasive percutaneous technologies, the discussion regarding surgical and endovascular therapies has become more and more complicated. Unfortunately, there is a relative shortage of robust outcomes data to support many of our specific treatment recommendations. Younger patients are an especially troublesome patient cohort. They have consistently shown poorer outcomes after any intervention compared with older patients and may represent a subset of more aggressive atherosclerotic disease. Our debaters will discuss their preferred approaches to these difficult patients in the context of the currently available supporting literature.

Medical treatment of carotid endarterectomy patients requires attention.

OBJECTIVES: The benefits of prophylactic carotid endarterectomy (CEA) together with best medical treatment (BMT) are well-established. Early initiation of proper medical treatment reduces the risk of new strokes as waiting periods for CEA operation can be considerably long. We investigated: (1) preoperative medical treatment of CEA patients at our hospital and (2) how well the present medical treatment coheres with national and international secondary prevention guidelines and other CEA cohorts. METHODS: A retrospective study cohort of 135 consecutive patients planned for CEA in a tertiary center because of symptomatic (n = 100) or asymptomatic (n = 35) carotid artery stenosis during a 14-month period (2007-2008). RESULTS: One hundred and twenty-six of 135 (93.3%) patients received antiplatelet therapy at the time of surgery, 125/135 (92.6%) were on statin, and 121/135 (89.6%) used antihypertensive medications. Ten of the 100 symptomatic patients had recurrence or progression in their ischemic symptoms while waiting for the operation, with a median time of 8.5 days (range 1-30 days). DISCUSSION: Carotid artery stenosis patients are considered high-risk patients regardless of symptomatology. The high proportion of medication use exceeds the use in the past proof-of-concept randomized controlled trials on the benefit of CEA+BMT over BMT. Nevertheless, there is room for improvement.

Reliability and repeatability of toe pressures measured with laser Doppler and portable and stationary photoplethysmography devices.

BACKGROUND: There are two principally different methods for measuring toe pressures (TP)-photoplethysmography (PPG) and laser Doppler (LD). PPG is based on detecting changes in the blood filling of the digital arteries and arterioles, and the LD perfusion signal is derived from the Doppler shift undergone by the emitted infrared laser light after reflection from moving particles (red blood cells). The aim of the study was to compare two PPG devices and one LD device in TP measurement. The PPG devices used were the Nicolet VasoGuard (Nicolet Vascular Inc, Madison, WI; PPG1) and Systoe (Atys Medical, France; PPG2), and the LD device was the Perimed system 5000 (Perimed, Stockholm, Sweden). MATERIALS AND METHODS: TPs were measured from 54 nonselected consecutive patients who visited the vascular surgical outpatient clinic or underwent an endovascular procedure owing to chronic lower limb ischemia. A total of 107 toes were measured. The symptoms were claudication in 51.4% (n = 55), rest pain in 4.7% (n = 5), and ulcer or gangrene in 14.0% (n = 15) of the legs. Of the measured legs, 29.9% (n = 32) were asymptomatic. Forty patients had undergone endovascular revascularization immediately before the TP measurement. The limits of agreement show the estimated range within which the differences between measurements by the two devices would fall in approximately 95% of the measurements. The approximate 95% limits of agreement were calculated as the mean difference ± 2 standard deviation and presented in the Bland-Altman scatter plots. RESULTS: For PPG1 versus LD, the mean difference between two measurements was 14 mm Hg and the limits of agreement were 38 mm Hg. In 47% of the toes, the difference was ≥10 mm Hg, and in 37% of the toes, it was ≥15 mm Hg. For PPG2 versus LD, the mean difference between the TPs was 12 mm Hg and the limits of agreement were 24 mm Hg. In 44% of the cases, the difference was ≥10 mm Hg, and in 30%, it was ≥15 mm Hg. For PPG1 versus PPG2, the mean difference between two measurements was 14 mm Hg and the limits of agreement were 24 mm Hg. In 50% of the cases, the difference between the two machines was ≥10 mm Hg, and in 33%, it was ≥15 mm Hg. Repeatability measured with LD, PPG1, and PPG2 showed that the difference between the first and second measurement was <10 mm Hg in 93%, 86%, and 78% of the cases, respectively, and <15 mm Hg in 98%, 94%, and 88% of the cases, respectively. CONCLUSIONS: TP values vary greatly depending on the device used. However, the repeatability seemed to be acceptable with LD and PPG1. We recommend using same device when circulation is repeatedly assessed in the same patient. Also, we emphasize the importance of clinical examination and low threshold for angiography and revascularization especially in diabetics with wound healing problems.

Outcome of infrainguinal single-segment great saphenous vein bypass for critical limb ischemia is superior to alternative autologous vein bypass, especially in patients with high operative risk.

BACKGROUND: Single-segment great saphenous vein (ssGSV) is the conduit of choice in infrainguinal bypass for critical limb ischemia (CLI). The aim of this study was to assess results of other autologous vein grafts and risk factors for graft stenosis development and graft failure. The purpose was also to evaluate outcome of patients with high operative risk undergoing infrainguinal alternative autologous vein bypass for CLI. METHODS: We retrospectively reviewed 1,109 consecutive infrainguinal bypasses performed between 2000 and 2007 for CLI. Rate and type of operations needed to maintain graft patency were evaluated. Outcome of different types of vein grafts in terms of primary patency, assisted primary patency, secondary patency, and limb salvage was assessed using Kaplan-Meier method. Predictors of poor outcome as well as patient- and graft-related risk factors for graft revision and graft failure were analyzed using multivariate analysis. RESULTS: Median follow-up period was 37 (0-121) months. Primary patency, assisted primary patency, secondary patency, and limb salvage at 1 and 3 years were significantly better in ssGSV graft group than in alternative autologous vein graft (AAVG) group-74.4% and 67.1% versus 53.7% and 42.0% (P < 0.0001), 82.8% and 78.2% versus 67.2% and 57.8% (P < 0.0001), 84.8% and 80.8% versus 69.9% and 61.4% (P < 0.0001), and 88.9% and 86.9% versus 83.0% and 77.2% (P < 0.0001), respectively. In multivariate analysis, non-ssGSV graft was the only independent risk factor for the graft stenosis development (relative risk [RR]: 2.62, 95% confidence interval [CI]: 1.56-4.38, P < 0.0001), for graft occlusion (RR: 2.27, 95% CI: 1.52-3.40, P < 0.0001), and for graft failure (stenosis or occlusion) (RR: 2.00, 95% CI: 1.39-2.88, P < 0.0001). Revision rate of non-ssGSV conduits was higher than that of ssGSV grafts (18% vs. 12%, P = 0.007). High-risk patients (age of >80 years, coronary artery disease, estimated glomerular filtration rate of <30 mL/min/1.73 m(2)) who underwent bypass with arm vein or spliced vein had extremely poor outcome (1-year leg salvage rate and survival rate of 71.4% and 28.6%, respectively). CONCLUSION: The ssGSV graft is superior to any other autologous vein graft in terms of midterm patency and leg salvage. It also needs less maintenance procedures than AAVGs. Non-ssGSV graft is independent predictor of both graft stenosis development and graft failure. Acceptable patency and leg salvage rates can also be achieved with AAVGs. However, patients with high operative risk and non-ssGSV graft bypass have poor outcome.

Peripheral arterial disease in diabetic patients with renal insufficiency: a review.

Peripheral arterial disease is common among diabetic patients with renal insufficiency, and most of the diabetic patients with end-stage renal disease (ESRD) have peripheral arterial disease. Ischaemia is probably overrepresented as an etiological factor for a diabetic foot ulcer in this group of patients compared with other diabetic patients. ESRD is a strong risk factor for both ulceration and amputation in diabetic patients. It increases the risk of nonhealing of ulcers and major amputation with an OR of 2.5-3. Renal disease is a more important predictor of poor outcome after revascularizations than commonly expected. Preoperative vascular imaging is also affected by a number of limitations, mostly related to side effects of contrast agents poorly eliminated because of kidney dysfunction. Patients with renal failure have high perioperative morbidity and mortality. Persistent ischaemia, extensive infection, forefoot and heel gangrene, poor run-off, poor cardiac function, and the length of dialysis-dependent renal failure all affect the outcome adversely. Despite dismal overall outcome, recent data indicate that by proper selection, favourable results can be obtained even in ESRD patients, with the majority of studies reporting 1-year limb salvage rates of 65-75% after revascularization among survivors. High 1-year mortality of 38% reported in a recent review has to be taken into consideration, though. The preferential use of endovascular-first approach is attractive in this vulnerable multimorbid group of patients, but the evidence for endovascular treatment is very scarce. The need for complete revascularization of the foot may be even more important than in other patients with ischaemic ulcerated diabetic foot because there are a number of factors counteracting healing in these patients. Typically, half of the patients are reported to lose their legs despite open bypass. To control tissue damage and improve chances of ulcer healing, one should understand that early referral to vascular consultation is necessary.

Single nucleotide polymorphism -799C/T in matrix metalloproteinase-8 promoter region in arterial disease.

Arterial disease is associated with elevated serum matrix metalloproteinase (MMP)-8 concentration. We studied the role of two promoter region single nucleotide polymorphisms (SNPs) of MMP-8 gene in the arterial disease. The population comprised patients with arterial disease (n = 124) and healthy blood donors (n = 100) as a reference group for MMP-8 SNPs (-799C/T and -381A/G) genotypes and serum concentrations. Genotype frequencies for MMP-8 -799C/T SNP in arterial disease were C/C (43.5%), C/T (32.3%) and T/T (24.2%), and in the reference group they were C/C (50.0%), C/T (40.0%) and T/T (10.0%; P = 0.012). The -799C allele frequency was lower in the patients (59.7%) than in the reference group (70.0%; P = 0.023). The -799C allele showed protective effects against the arterial disease with an odds ratio [95% confidence interval (CI)] of 0.372 (0.141-0.980, P = 0.045) after adjustment for age, gender, and serum MMP-8 and TIMP-1 concentrations. Only in the reference group and whole study population (n = 224), the -799TT genotype significantly associated with an increase in serum MMP-8 concentrations (P = 0.047, 0.025). The -799C allele appeared protective against the arterial disease. The genotype may have an effect on systemic MMP-8 levels which could not, however, be seen in the arterial disease patients probably as a result of the strong inflammation involved in the disease pathogenesis.

Outcome after open repair of ruptured abdominal aortic aneurysm in patients>80 years old: a systematic review and meta-analysis.

BACKGROUND: The role of open repair in the management of ruptured abdominal aortic aneurysm (RAAA) in patients>80 years old is questioned by the perceived high operative risk of these patients. This issue has been investigated in the present meta-analysis of observational studies. METHODS: Studies on open repair of RAAA in patients>80 years old were identified in July 2010. The immediate and intermediate results were expressed as pooled proportions with 95% confidence interval (95% CI). Linear regression and meta-regression were performed to evaluate the impact of variables on the immediate postoperative mortality. RESULTS: Pooled analysis of 29 studies showed that the risk of immediate postoperative mortality in patients>80 years old was significantly higher than in younger patients (risk ratio 1.440, 95%CI 1.365-1.519, I2 36.8%, P=0.002; risk difference 19.4%, 95% CI 16.4-22.4%, I2 38.8%, P=0.019). Pooled analysis of 36 studies showed an immediate postoperative mortality rate of 59.2% (95% CI 55.7-62.5, I2 35.62). Immediate postoperative mortality in patients<80 years old positively correlated with that of patients>80 years old (rho: 0.686, P<0.0001). Intermediate survival data of 111 operative survivors were available from six studies, and their pooled survival rates at 1-, 2-, and 3-year were 82.4, 75.6, and 68.7%, respectively. CONCLUSIONS: Immediate and intermediate survival rates of patients>80 years old after open repair of RAAA are acceptable. These findings suggest a more confident approach toward emergency repair of RAAA in the very elderly.

Studies on the effects of heparin products on pregnancy-associated plasma protein A.

BACKGROUND: Intravenous low molecular weight (LMWH) and unfractionated heparin (UFH) increase the circulating concentrations of pregnancy-associated plasma protein A (PAPP-A), a novel cardiac risk marker, in haemodialysis and coronary angiography patients. METHODS: To further investigate the mechanisms of heparin effects, free PAPP-A was analysed in serial serum samples collected during haemodialysis (intravenous LMWH), carotid endarterectomy or abdominal aortic aneurysm surgery (intravenous UFH), treatment at intensive care unit (subcutaneous LMWH), and coronary angiography (intravenous bivalirudin). PAPP-A was extracted from plaque tissue samples of endarterectomy and aneurysm patients. The interaction between heparin products and free PAPP-A was studied with gel filtration. RESULTS: After intravenous UFH and LMWH free PAPP-A increased significantly but bivalirudin had no effect. After LMWH bolus in haemodialysis patients 85% of free PAPP-A was cleared with a half-life of 13.1 min and the rest with a half-life of 96.6 min. Subcutaneous LMWH led to lower and slower free PAPP-A elevation. PAPP-A extracted from plaque tissues was in free form and extraction was strongly enhanced by LMWH. Heparin products increased the molecular size of free PAPP-A. CONCLUSIONS: The heparin-induced PAPP-A elevation is seen in various patients and should be taken into account when PAPP-A is studied as a biomarker.

Tertiary patency as a measure of active revascularization policy for leg salvage.

BACKGROUND: An active surgical strategy to save lower limbs of patients with critical leg ischemia includes not only infrainguinal bypass surgery but also repeated surgery when needed. A failed infrainguinal bypass often threatens viability of the patient's legs, at which point a redo bypass procedure with a new graft may be the only alternative to major amputation. We assessed tertiary patency, defined as the whole period of time with a patent infrainguinal graft in a leg, to illustrate future potential of limb salvage surgery after a failed bypass. METHODS: A total of 593 patients with critical leg ischemia and tissue defects (Fontaine IV) who underwent infrainguinal bypass surgery between January 2000 and December 2005 at our institution were included in this retrospective study. RESULTS: Secondary and tertiary patency rates were 95 ± 1% and 96 ± 3% at 1 month, 75 ± 2% and 82 ± 2% at 1 year, and 61 ± 2% and 70 ± 3% at 5 years, respectively, p = 0.003. Leg salvage rate was 94 ± 1% at 1 month, 83 ± 2% at 1 year, and 78 ± 2% at 5 years. There was no significant difference between leg salvage and tertiary patency rates, p = 0.281. CONCLUSION: Tertiary patency rate was higher than the secondary patency rate. This result might reflect active limb salvage surgery with satisfactory results. The absence of a gap between tertiary patency and leg salvage rates indicates the importance of a patent infrainguinal bypass graft to save lower limbs of patients with ischemic tissue defects.

Infrapopliteal percutaneous transluminal angioplasty versus bypass surgery as first-line strategies in critical leg ischemia: a propensity score analysis.

INTRODUCTION: Recently, endovascular revascularization (percutaneous transluminal angioplasty [PTA]) has challenged surgery as a method for the salvage of critically ischemic legs (CLI). Comparison of surgical and endovascular techniques in randomized controlled trials is difficult because of differences in patient characteristics. To overcome this problem, we adjusted the differences by using propensity score analysis. MATERIALS AND METHODS: The study cohort comprised 1023 patients treated for CLI with 262 endovascular and 761 surgical revascularization procedures to their crural or pedal arteries. A propensity score was used for adjustment in multivariable analysis, for stratification, and for one-to-one matching. RESULTS: In the overall series, PTA and bypass surgery achieved similar 5-year leg salvage (75.3% vs 76.0%), survival (47.5% vs 43.3%), and amputation-free survival (37.7% vs 37.3%) rates and similar freedom from any further revascularization (77.3% vs 74.4%), whereas freedom from surgical revascularization was higher after bypass surgery (94.3% vs 86.2%, P < 0.001). In propensity-score-matched pairs, outcomes did not differ, except for freedom from surgical revascularization, which was significantly higher in the bypass surgery group (91.4% vs 85.3% at 5 years, P = 0.045). In a subgroup of patients who underwent isolated infrapopliteal revascularization, PTA was associated with better leg salvage (75.5% vs 68.0%, P = 0.042) and somewhat lower freedom from surgical revascularization (78.8% vs 85.2%, P = 0.17). This significant difference in the leg salvage rate was also observed after adjustment for propensity score (P = 0.044), but not in propensity-score-matched pairs (P = 0.12). CONCLUSIONS: When feasible, infrapopliteal PTA as a first-line strategy is expected to achieve similar long-term results to bypass surgery in CLI when redo surgery is actively utilized.

Finnvasc score and modified Prevent III score predict long-term outcome after infrainguinal surgical and endovascular revascularization for critical limb ischemia.

BACKGROUND: Estimation of the risk of adverse long-term outcome is of paramount importance in the treatment of critical limb ischemia (CLI). METHODS: We evaluated the accuracy of two specific risk score systems, the Finnvasc score and the modified Prevent III (mPIII) score, in 1425 CLI patients who underwent unilateral, infrainguinal surgical (47.6%) or endovascular (52.4%) revascularization. The receiver operating characteristic (ROC) curve analysis was used to estimate the predictive value of these risk scoring methods. RESULTS: The area under the ROC curve of Finnvasc score for prediction of 30-day amputation was 0.609 (95% confidence interval [CI] 0.549-0.677) and of mPIII score 0.533 (95% CI 0.457-0.609). The area under ROC curve of Finnvasc score for prediction of 30-day amputation-free survival was 0.622 (95% CI 0.573-0.671) and of mPIII score 0.588 (95% CI 0.533-0.642). The area under the ROC curve of Finnvasc score for prediction of 1-year amputation-free survival was 0.630 (95% CI 0.597-0.663, P<.0001) and of mPIII score 0.634 (95% CI 0.600-0.667, P<.0001). Finnvasc score predicted leg salvage (relative risk [RR] 1.431, 95% CI 1.319-1.551), survival (RR 1.233, 95% CI 1.116-1.363), and amputation-free survival (RR 1.422, 95% CI 1.319-1.534). mPIII score also predicted leg salvage (RR 1.190, 95% CI 1.108-1.277), survival (RR 1.245, 95% CI 1.193-1.300), and amputation-free survival (RR 1.223, 95% CI 1.176-1.272). CONCLUSIONS: Finnvasc and modified PIII risk scoring methods predict long-term outcome of patients undergoing infrainguinal revascularization for CLI. Finnvasc score seems to perform well also in predicting immediate postoperative outcome.

Arm vein conduit vs prosthetic graft in infrainguinal revascularization for critical leg ischemia.

BACKGROUND: One-piece great saphenous vein (GSV) is the conduit of choice in infrainguinal revascularizations for critical limb ischemia (CLI). Unfortunately, adequate length of usable GSV is not always available. Despite inferior patency rates compared with GSV, prosthetic and arm vein conduits are generally considered usable. The purpose of this study was to compare the outcome of infrainguinal arm vein and prosthetic bypass. MATERIAL AND METHODS: We retrospectively reviewed 290 consecutive infrainguinal bypasses for CLI using arm vein conduit (n = 130) or prosthetic graft (n = 160) during January 2000 and December 2006 at our institution. The groups were compared for risk factors, indication for surgery, and runoff score. Survival, leg salvage, and patency rates were calculated with the Kaplan-Meier method. RESULTS: Median surveillance time was 35 months (range 0-118 months). The age, gender, and usual risk factors were similar in arm vein and prosthetic groups, except cerebrovascular disease that was more common in the prosthetic group (P = .011). Indication for surgery was CLI. In the arm vein group, more than two-thirds (70.2%) of the procedures were for ischemic ulcer or gangrene, whereas in the prosthetic group the main indication was ischemic rest pain (51.3%). When the outcome of femoropopliteal bypasses was analyzed, the difference between groups was not statistically significant. However, in infrapopliteal revascularizations primary patency, assisted primary patency, and secondary patency rates at 3 years were significantly better in the arm vein group: 28.3% (SE +/- 6.3%) vs 9.6% (SE +/- 8.1%) (P = .031), 56.8% (SE +/- 6.6%) vs 10.4% (SE +/- 8.7%) (P = .000), and 57.4% (SE +/- 6.6) vs 11.2% (SE +/- 9.3%) (P = .000), respectively. Leg salvage and survival at 3 years were 75.0% (SE +/- 4.9%) vs 57.1% (SE +/- 8.8%) (P = .005) and 58.8% (SE +/- 5.1%) vs 39.5% (SE +/- 7.7%) (P = .007), respectively. CONCLUSION: Arm vein conduits, even when spliced, are superior to prosthetic grafts in terms of midterm assisted primary patency, secondary patency, and leg salvage in infrapopliteal bypasses for CLI.