Components of carotid atherosclerotic plaque in spectral photon-counting CT with histopathologic comparison.

OBJECTIVES: This study aimed to demonstrate the effectiveness of spectral photon-counting CT (SPCCT) in quantifying fibrous cap (FC) thickness, FC area, and lipid-rich necrotic core (LRNC) area, in excised carotid atherosclerotic plaques by comparing it with histopathological measurements. METHODS: This is a single-center ex vivo cross-sectional observational study. Excised plaques of 20 patients (71 +/- 6 years; 13 men), obtained from carotid endarterectomy were scanned with SPCCT using standardized acquisition settings (120k Vp/19 µA; 7-18 keV, 18-30 keV, 30-45 keV, 45-75 keV, and 75-118 keV). FC thickness, FC area, and LRNC area were quantified and compared between high-resolution 3D multi-energy CT images and histopathology using the Wilcoxon signed-ranks test and Bland-Altman analysis. Images were interpreted twice by two radiologists separately, blinded to the histopathology; inter- and intra-rater reliability were assessed with the intra-class correlation coefficients (ICC). RESULTS: FC thickness and FC area did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements (p value range 0.15-0.51 for FC thickness and 0.053-0.30 for FC area). For the LRNC area, the p value was statistically non-significant for reader 1 (range 0.36-0.81). The Bland-Altman analysis showed mean difference and 95% confidence interval for FC thickness, FC area, and LRNC area, 0.04 (-0.36 to 0.12) square root mm, -0.18 (-0.34 to -0.02) log10 mm2 and 0.10 (-0.088. to 0.009) log10 mm2 respectively. CONCLUSION: The result demonstrated a viable technique for quantifying FC thickness, FC area, and LRNC area due to the combined effect of high spatial and energy resolution of SPCCT. KEY POINTS: • SPCCT can identify and quantify different components of carotid atherosclerotic plaque in ex vivo study. • Components of atherosclerotic plaque did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements.

Early Relative Growth Rate of Abdominal Aortic Aneurysms and Future Risk of Rupture or Repair.

OBJECTIVE: This study aimed to test whether the relative growth rate of subthreshold abdominal aortic aneurysms (AAAs) in the first 24 months of surveillance predicts the risk of future rupture or repair. METHODS: This was a single centre retrospective observational analysis of all small (< 45 mm diameter) and medium (45 - 54 mm in men, 45 - 50 mm in women) AAAs entered into ultrasound surveillance between January 2002 and December 2019, which received ≥ 24 months of surveillance. Relative growth rates were calculated from measurements taken in the first 24 months of surveillance. The Kaplan-Meier method was used to estimate intervention and rupture free proportions five years following diagnosis for AAAs growing by < 5% and by ≥ 5% in the first 24 months of surveillance. Multivariable Cox regression analysis was used to further analyse this relationship by adjusting for factors found to be significantly associated with outcome in univariable analysis. RESULTS: A total of 556 patients with AAAs (409 men, 147 women) were followed for ≥ 24 months. This included 431 small AAAs. Of these, 109 (25.3%) grew by < 5% in the first 24 months of surveillance and had a cumulative event free proportion of 0.98 ± 0.05 at five years compared with 0.78 ± 0.05 for the ≥ 5% growth group (p < .001). Of 125 medium AAAs, 26 (20.8%) grew by < 5% in the first 24 months of surveillance and had a cumulative event free proportion of 0.73 ± 0.11 at five years compared with 0.29 ± 0.13 for the ≥ 5% growth group (p = .024). Baseline diameter and early relative growth rate were strongly and independently predictive of future intervention or rupture with hazard ratios of 9.16 (95% CI 5.98 - 14.03, p < .001) and 4.46 (95% CI 2.45 - 8.14, p < .001), respectively. CONCLUSION: The results suggest that slow expansion of small (< 45 mm) AAAs observed over an isolated 24 month period is indicative of a very low risk of rupture or repair in the medium term. Isolated growth rates may be a useful tool with which to triage low risk AAAs and prevent unnecessary surveillance.

An exploratory study of vibration therapy on muscle function in patients with peripheral artery disease.

OBJECTIVE: The purpose of this exploratory study was to determine whether a single session of vibration therapy (VT) would improve muscular and functional performance in individuals with symptomatic peripheral artery disease (PAD). METHODS: In a randomized, balanced cross-over design fourteen PAD participants with intermittent claudication (mean ± standard deviation; age, 73.9 ± 4.6 years; height, 172.6 ± 68.4 cm; body mass, 85.2 ± 15.7 kg) performed VT and control that involved repeated chair rises, timed up-and-go test, and 6-minute walk test. Each intervention was separated by at least 2 days. Wearable VT devices were positioned on the right and left lower limbs that were turned on during functional testing but were turned off for the control intervention. RESULTS: VT significantly improved (P < .05) repeated chair rises and timed up-and-go test compared with control with a small effect size of 0.46 and 0.45, respectively. Similarly, a significant (P < .01) and meaningful change in 6-minute walk test was noted in VT compared with control. CONCLUSIONS: This exploratory study suggest that VT may enhance functional strength, mobility, and walking performance by extending the onset of claudication and increasing walking distance in PAD with intermittent claudication. However, further study is required to confirm and extend these preliminary findings and determine the potential mechanisms of action in VT.

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.

RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies. METHODS AND RESULTS: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. CONCLUSIONS: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.

Development and Validation of a Predictive Model to Aid in the Management of Intact Abdominal Aortic Aneurysms.

OBJECTIVE/BACKGROUND: Predicting outcomes prior to elective abdominal aortic aneurysm repair (AAA) requires critical decision making, as the treatment offered is a prophylactic procedure to prevent death from a ruptured AAA. The aim of this work was to develop and validate a model that may predict outcomes for patients with an AAA and hence aid in clinical decision making. METHODS: A discrete event simulation model was built to simulate the natural history of a patient with an AAA and to predict the 30 day and 2-5 year survival of patients undergoing treatment and surveillance. The input parameters of AAA behavior and impact of comorbidities on survival were derived from the published literature and the New Zealand national life tables. The model was externally validated using a cohort of patients that underwent AAA repair (n = 320) and a cohort of patients undergoing small AAA surveillance (n = 376). All patients had completed at least 5 years of follow up. RESULTS: The model was run three times for each data set to test. This produced a SD < 1%, indicating excellent reproducibility. The observed 30 day mortality for the patients undergoing AAA repair was 9/320 (2.8%) and the expected (model predicted) mortality was 3.8% (c-statistic 0.87 [95 confidence interval 0.75-1.0]). The c-statistic for the predicted 2-5 year survival ranged from 0.68 to 0.71 for the repaired AAA cohort and 0.69 to 0.73 for patients with a small AAA on surveillance. CONCLUSION: The AAA clinical decision tool has the ability to accurately predict the 5 year survival of patients with an AAA. This tool can be used during clinical decision making to better inform clinicians and patients of long-term outcomes. Further validation studies in a wider AAA population are required to test the broader clinical utility of this AAA clinical decision tool.

Survival Disparity Following Abdominal Aortic Aneurysm Repair Highlights Inequality in Ethnic and Socio-economic Status.

OBJECTIVES: Socio-economic status (SES) and ethnicity have been reported as markers influencing the likelihood of increased mortality. The aim of this study was to investigate how SES and ethnicity impacted patient survival after abdominal aortic aneurysm (AAA) repair. METHODS: Consecutive patients undergoing open and endovascular AAA repair during a 14.5 year period were identified. Ethnicity was defined as recorded on health records and SES (a score of 10, where 1 is least deprived and 10 being most deprived) and was linked to census data. Operative outcomes were reported at 30 days and a medium-term survival analysis used the Cox model to report adjusted hazard ratios (HR). RESULTS: A total of 6239 patients with a median age of 75 years and 78.7% males were included. The majority (5,654) were identified as New Zealand (NZ) Europeans, with 421 identified as NZ Maori, 97 identified as belonging to a Pacific ethnic group, and 67 identified as an Asian ethnic group. The median survival follow-up period was 5 years and after adjusting for confounders, those who identified as NZ Maori had the lowest survival compared with all other ethnic groups with a HR of 1.46 (95% CI 1.23-1.72). Living in areas of high social deprivation ≥ 7 was an independent predictor of short and medium-term overall mortality when compared with living in deprivation deciles 1 or 2. CONCLUSIONS: Low SES was identified as a marker of risk for all ethnic groups in relation to both reduced short and medium-term survival. However, regardless of SES, NZ Maori had worse overall medium-term survival following AAA repair than the other ethnic groups. Therefore it appears that both SES and being Maori were markers of increased exposure to risk that negatively impact upon survival after AAA repair. There is a need to ensure systemic processes support initiatives that reduce this inequality.

Management of Modifiable Vascular Risk Factors Improves Late Survival following Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-Analysis.

BACKGROUND: The main determinants of survival following abdominal aortic aneurysm (AAA) repair are preexisting risk factors rather than the method of repair chosen. The main aim of this meta-analysis was to assess the effect of modifiable risk factors on late survival following AAA repair. METHODS: Electronic databases were searched to identify all relevant articles reporting the influence of modifiable risk factors on long-term survival (≥1 year) following elective open aneurysm repair and endovascular aneurysm repair. RESULTS: Twenty-four studies which comprised 53,118 patients, published between 1989 and 2015, were included in the analysis. The use of statin, aspirin, beta-blockers, and a higher hemoglobin level was all significant predictors of improved survival following repair with a hazard ratio (HR) and 95% confidence interval (CI) of 0.75 (0.70-0.80), 0.81 (0.73-0.89), 0.75 (0.61-0.93), and 0.84 (0.74-0.96), respectively. Smoking history and uncorrected coronary disease were associated with a worse long-term survival of HR 1.27 (95% CI 1.07-1.51) and HR 2.59 (95% CI 1.14-5.88), respectively. CONCLUSIONS: Addressing cardiovascular risk factors in patients preoperatively improves long-term survival following AAA repair. Global strategies to improve risk factor modifications in these patients are warranted to optimize long-term outcomes.

Does the diameter of abdominal aortic aneurysm influence late survival following abdominal aortic aneurysm repair? A systematic review and meta-analysis.

BACKGROUND: Studies reporting the influence of preoperative abdominal aortic aneurysm diameter on late survival following abdominal aortic aneurysm repair have not been consistent. AIM: To report the influence of abdominal aortic aneurysm diameter on overall long-term survival following abdominal aortic aneurysm repair. METHODS: Embase, Medline and the Cochrane electronic databases were searched to identify articles reporting the influence of abdominal aortic aneurysm diameter on late survival following open aneurysm repair and endovascular aneurysm repair published up to April 2015. Data were extracted from multivariate analysis; estimated risks were expressed as hazard ratio. RESULTS: A total of 2167 titles/abstracts were retrieved, of which 76 studies were fully assessed; 19 studies reporting on 22,104 patients were included. Preoperative larger abdominal aortic aneurysm size was associated with a worse survival compared to smaller aneurysms with a pooled hazard ratio of 1.14 (95% CI: 1.09-1.18), per 1 cm increase in abdominal aortic aneurysm diameter. Subgroup analysis of the different types of repair was performed and the hazard ratio (95% CI), for open aneurysm repair and endovascular aneurysm repair were 1.08 (1.03-1.12) and 1.20 (1.15-1.25), respectively, per 1 cm increase. There was a significant difference between the groups p < 0.02. CONCLUSIONS: This meta-analysis suggests that preoperative large abdominal aortic aneurysm independently influences overall late survival following abdominal aortic aneurysm repair, and this association was greater in abdominal aortic aneurysm repaired with endovascular aneurysm repair.

Ex-vivo atherosclerotic plaque characterization using spectral photon-counting CT: Comparing material quantification to histology.

BACKGROUND AND AIMS: Atherosclerotic plaques are characterized as being vulnerable to rupture based on a series of histologically defined features, including a lipid-rich necrotic core, spotty calcification and ulceration. Existing imaging modalities have limitations in their ability to distinguish between different materials and structural features. We examined whether X-ray spectral photon-counting computer tomography (SPCCT) images were able to distinguish key plaque features in a surgically excised specimen from the carotid artery with comparison to histological images. METHODS: An excised carotid plaque was imaged in the diagnostic X-ray energy range of 30-120 keV using a small-bore SPCCT scanner equipped with a Medipix3RX photon-counting spectral X-ray detector with a cadmium telluride (CdTe) sensor. Material identification and quantification (MIQ) images of the carotid plaque were generated using proprietary MIQ software at 0.09 mm volumetric pixels (voxels). The plaque was sectioned, stained and photographed at high resolution for comparison. RESULTS: A lipid-rich core with spotty calcification was identified in the MIQ images and confirmed by histology. MIQ showed a core region containing lipid, with a mean concentration of 260 mg lipid/ml corresponding to a mean value of -22HU. MIQ showed calcified regions with mean concentration of 41 mg Ca/ml corresponded to a mean value of 123HU. An ulceration of the carotid wall at the bifurcation was identified to be lipid-lined, with a small calcification identified near the breach of the artery wall. CONCLUSIONS: SPCCT derived material identification and quantification images showed hallmarks of vulnerable plaque including a lipid-rich necrotic core, spotty calcifications and ulcerations.

A systematic review of pharmacologic and cell-based therapies for treatment of lymphedema (2010-2021).

BACKGROUND: Lymphedema describes the accumulation of interstitial fluid that results from lymphatic failure. Lymphedema can be of primary or secondary origin and has been estimated to affect 200 million people worldwide. Secondary lymphedema is commonly due to damage to the lymphatic vessels after surgical procedures. Treatments include compression bandaging and exercise regimens. However, at present, no pharmacologic therapy has been approved. We performed a systematic review of randomized controlled trials (RCTs) that had investigated pharmacologic and cell-based therapies for secondary lymphedema. METHODS: We searched the databases MEDLINE, Embase, and ClinicalTrials.gov from January 2010 to May 2021. Only RCTs that had investigated pharmacologic and/or cell-based therapies for secondary lymphedema were eligible for inclusion. Those studies that had examined only active filarial infection were excluded. Two of us (J.W., S.T.) independently screened the studies for eligibility. RESULTS: We identified eight RCTs that met the inclusion criteria. Overall, the studies were of poor quality with a high risk of bias. Ketoprofen demonstrated promising improvements in skin thickness and tissue histopathologic scores. Some evidence was found to suggest that doxycycline might be beneficial for nonfilarial secondary lymphedema, and a single, small RCT demonstrated that selenium might also confer some benefit. Neither synbiotics nor platelet-rich plasma resulted in reduced lymphedema volumes or symptom severity. Also, although bone marrow-derived stem cells resulted in improved symptom scores, no significant volume reduction was detected. Although positive results were demonstrated in trials investigating benzopyrones, previous meta-analyses have cast doubt on their efficacy. No two studies assessed the same intervention; thus, we could not perform a meta-analysis. CONCLUSIONS: Although the results from some studies appeared promising, the available evidence at present is insufficient for any pharmacologic or cell-based therapy for patients with secondary lymphedema. Furthermore, large, high-quality RCTs are required before treatment recommendations will be possible.

Angiogenesis and host immune response contribute to the aggressive character of non-melanoma skin cancers in renal transplant recipients.

AIMS: The aim of this study was to determine the contribution of tumour angiogenesis to the aggressive growth of non-melanoma skin cancers (NMSCs) in renal transplant recipients (RTRs). METHODS AND RESULTS: The study cohort included RTRs (n = 38) with formalin-fixed paraffin-embedded tumour samples available from first post-transplant NMSC (NMSC1) surgically excised at Christchurch Hospital, New Zealand, from 1997 to 2007. Comparable samples excised from immunocompetent individuals (ICIs) (n = 36) were selected to accommodate confounding factors. Markers of tumour angiogenesis were evaluated by immunohistochemistry, and analysed for associations with clinicopathological variables. As compared with ICIs, RTRs had a higher proportion of tumours with high microvessel density (P = 0.008), high proliferating capillary index (P < 0.0001) and low microvessel pericyte coverage index (P < 0.0001), and RTRs had a shorter cumulative second NMSC (NMSC2)-free interval (P < 0.0001). ICIs had a higher proportion of tumours with a 'marked' number of vascular endothelial growth factor (VEGF)-A-positive leukocytes than RTRs (P = 0.04), and RTRs with a 'moderate/marked' number of VEGF-A-positive leukocytes had longer cumulative NMSC2-free intervals than those with a 'minimum' number (P = 0.02). CONCLUSIONS: This study demonstrates increased tumour angiogenesis in NMSC in RTRs, and suggests a role for VEGF-A-positive peritumoural leukocytes in suppressing NMSC development.

Protocol for the Metformin Aneurysm Trial (MAT): a placebo-controlled randomised trial testing whether metformin reduces the risk of serious complications of abdominal aortic aneurysm.

BACKGROUND: Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms. METHODS: MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05). DISCUSSION: Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design. TRIAL REGISTRATION: Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018.

First and subsequent nonmelanoma skin cancers: incidence and predictors in a population of New Zealand renal transplant recipients.

BACKGROUND: Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancers (NMSCs). The aims of this study were to determine the incidence and subsequent history of NMSCs in RTRs, together with risk factors. METHODS: All patients transplanted between July 1972 and March 2007, and followed up at Christchurch Hospital, New Zealand, were studied. Immunosuppression regimens were mostly prednisone, azathioprine, cyclosporine and prednisone, mycophenolate mofetil, cyclosporine since 1998. RESULTS: Of 384 RTRs, 96 developed at least one NMSC. The median time to first NMSC was 18.3 years (95% CI 14.2, 22.9) from transplant, as estimated by survival analysis. Individual predictors of first NMSC in RTRs were older age at first transplant (P < 0.0001), male sex (P = 0.006) and initial immunosuppression regimen (P = 0.001); only age (P < 0.0001) and male gender (P = 0.003) were significant predictors in a joint model. The mean rate of subsequent NMSCs was 1.67 per year (95% CI = 1.32, 2.11). Older age at first renal transplant (P = 0.009) or at discovery of the first NMSC (P = 0.01) was associated with a higher annual rate of new NMSC following the discovery of the first NMSC. The median survival time to a second NMSC was 2.2 years (CI 1.4, 3.0). Fourteen patients died of metastatic squamous cell carcinoma (15% case fatality). CONCLUSIONS: NMSCs are a major health issue for RTRs, especially in older males. Once RTRs have developed their first NMSC, ongoing surveillance and prompt treatment are essential.

Timeliness and outcomes of carotid endarterectomy for symptomatic carotid artery stenosis: a single centre audit.

BACKGROUND: For patients presenting with symptomatic internal carotid artery stenosis, carotid endarterectomy (CEA) surgery is recommended to be performed generally within a 48-hr to 14-day window. This study aimed to assess timeliness of delivery, and outcomes, of CEA surgery in a tertiary vascular centre. METHOD: Patients with symptomatic internal carotid artery stenosis who underwent CEA between 1 June 2014 and 31 June 2017 were identified and data were obtained from hospital records. The timeline of their journey from presentation to surgery was then mapped together with their outcomes. RESULTS: One hundred and seventy-two cases were included in the study. Overall, the median time from development of presenting symptoms to surgery was 9 days and 119 (69%) cases were operated on within 14 days. The median time from development of presenting symptoms to ultrasound imaging was 2 days and the median time from symptoms to vascular referral was also 2 days. There were no deaths, strokes or transient ischaemic attacks within 30 days of CEA. At 1 year, survival was 100% but 15 (8.7%) had experienced at least one transient ischaemic attack or stroke. In the 53 cases operated upon beyond 14 days the dominant cause of delay in 32 (60%) was accessing surgery after review by the vascular service. CONCLUSION: The aim of delivering CEA within 14 days of developing relevant symptoms was achieved in most cases with good outcomes. Nevertheless, points of delay in the patient journey that could be targeted for future quality improvement were identified.

Macrophage mediated protein hydroperoxide formation and lipid oxidation in low density lipoprotein are inhibited by the inflammation marker 7,8-dihydroneopterin.

The formation of oxidised low density lipoprotein (LDL) within the atherosclerotic plaque appears to be a factor in the development of advanced atherosclerotic plaques. LDL oxidation is dependent on the balance of oxidants and antioxidants within the intima. In addition to producing various oxidants, human macrophages release 7,8-dihydroneopterin which in vivo is oxidised to the inflammation marker neopterin. Using macrophage-like THP-1 cells and human monocyte-derived macrophages, we demonstrate that 7,8-dihydroneopterin is a potent inhibitor of cell-mediated LDL oxidation. 7,8-Dihydroneopterin scavenges the chain propagating lipid peroxyl radical, inhibiting both lipid and protein hydroperoxide formation. A significant amount of the hydroperoxide formed during cell-mediated LDL oxidation was protein hydroperoxide. 7,8-Dihydroneopterin oxidation to 7,8-dihydroxanthopterin was only observed in the presence of both cells and LDL, showing that 7,8-dihydroneopterin had no effect on initiating oxidant generation by the cells. 7,8-Dihydroneopterin did not regenerate alpha-tocopherol but competed with it for the lipid peroxyl radical. Although stimulation of both cell types with gamma-interferon failed to produce sufficient 7,8-dihydroneopterin to inhibit LDL oxidation in tissue culture, analysis of advanced atherosclerotic plaque removed from patients showed that total neopterin levels could reach low micromolar concentrations. This suggests that 7,8-dihydroneopterin synthesis by macrophages could play a significant role in the development of atherosclerotic plaques.

The Effect of Vacuum-assisted Closure on the Tissue Oxygenation of Venous Ulcers: A Pilot Study .

UNLABELLED: Background. Vacuum-assisted closure (V.A.C.® Therapy, KCI, San Antonio, TX) has been widely used to increase the healing rate of a variety of wounds. It has been hypothesized that one of the actions of VAC is to increase perfusion and subsequent oxygenation of tissue. The aim of the present study was to investigate the effect of VAC therapy on transcutaneous oximetry measurements (TCOM) of skin surrounding chronic venous ulcers. METHODS: This was a prospective, experimental pilot study. Patients undergoing compression therapy were recruited from a community wound clinic. All patients had ankle-brachial pressure indices (ABPI) > 0.8. Three TCOM values were taken from around the ulcer and a reference TCOM was taken from the chest. Negative pressure was applied on the ulcer at 125-mmHg continuous subatmospheric pressure and four-layer compression bandaging over the VAC drapes. The duration of the study was 6 days. On day 6, dressings were removed and TCOM was repeated at the same skin sites. RESULTS: Fourteen of the 17 patients completed the trial. The median age was 73 years (range 49-85). No significant difference was found in oxygen partial pressure pre-and post-VAC therapy around the ulcer site (mean 41.5 mmHg versus 40 mmHg [P = 0.67]). There was a significant difference in TCOM between the reference point and the periwound area (mean 60.5 versus 40 [P < 0.0005]). CONCLUSION: This pilot study suggests that VAC therapy does not change oxygen partial pressure around venous ulcers. TCOM of the skin around ulcers were low despite normal ABPIs.

Induced macrophage activation in live excised atherosclerotic plaque.

Atherosclerotic plaques are complex tissues containing many different cell types. Macrophages contribute to inflammation, formation of the necrotic core, and plaque rupture. We examined whether macrophages in plaque can be activated and compared this to monolayer cells. The volume of calcium in the plaque was compared to the level of macrophage activation measured by total neopterin output. Carotid plaque samples were cut into 3 mm sections and cultured for up to 96 h. Live sections were stimulated with interferon-γ, phytohaemagglutinin or phorbol 12-myristate 13-acetate. Macrophage activation and oxidative stress were monitored by total neopterin (oxidized and non-oxidized 7,8-dihydroneopterin) and neopterin levels every 24 h for up to 4 d. The calcium content of two plaques was investigated by spectral imaging. Direct stimulation of macrophages in plaque sections with interferon-γ caused a sustained increase in neopterin (p = .037) and total neopterin (p = .003). The addition of phorbol 12-myristate 13-acetate to plaque had no significant effect on total neopterin production (p = .073) but increased neopterin (p = .037) whereas phytohaemagglutinin caused a significant increase in both neopterin and total neopterin (p = .0279 and .0168). There was an inverse association (R2 = 0.91) between the volume of calcium and macrophage activation as measured by total neopterin production in stimulated plaque tissue. Resident macrophages within excised carotid plaque activated either directly or indirectly generate the biomarkers 7,8-dihydroneopterin and neopterin. Macrophage activation rather than the oxidative environment is associated with plaque calcification.

Computed tomography arteriography to assess greater saphenous vein as a conduit for peripheral bypass.

BACKGROUND: To determine whether computed tomography arteriography of the lower extremities (64-slice volume computed tomography (CT)), used in delineating the arterial tree in peripheral vascular disease, is useful in assessing suitability of greater saphenous vein as a vascular conduit for peripheral bypass grafting for limb-threatening lower limb ischaemia. A search of published works in August 2005 showed no similar study has been published. METHODS: A prospective study of nine consecutive patients who had undergone lower limb CT arteriography and long saphenous vein colour duplex ultrasound (U/S) were studied. RESULTS: Good concordance between colour duplex U/S and CT arteriography was obtained. CONCLUSION: Computed tomography images of the long saphenous vein as a part of arterial lower limb CT arteriography correlate well with preoperative conduit assessment colour duplex U/S findings of the long saphenous vein.