Late Radiological and Clinical Outcomes of Traumatic Thoracic Aortic Injury Managed with Thoracic Endovascular Aortic Repair.

PURPOSE: Patients treated with thoracic endovascular aortic repair (TEVAR) for traumatic thoracic aortic injury (TTAI) are often young and data on long-term durability of this treatment is not widely documented. The aims of this study were to report the New Zealand (NZ) national experience of TEVAR and to assess the durability of late outcomes and radiological follow-up of patients treated for TTAI. METHODS: Consecutive patients treated with TEVAR during a 12-year period from all tertiary centers in NZ were included. Early (30-day), late survival and radiological imaging data were recorded to document late graft-related complications and re-interventions. RESULTS: 88 patients with a median (range) age of 35 (15-87) year and 63 (71.6 %) males were included. Eleven patients (12.5 %) died within 30 days, of which three were aortic related deaths. The median (range) follow-up was 76.3 (0.3-164.6) months. Six (7.8 %) patients died during the follow-up period due to non-aortic-related causes. Nine (11.5 %) patients were lost to follow-up of which three emigrated overseas. Of those on surveillance, two patients required TEVAR re-intervention to previously treated aortic segments; one for a type 1b endoleak and the other for a symptomatic pseudo-coarctation. Both were treated successfully with a TEVAR. CONCLUSIONS: This multicenter study suggests that TEVAR is a durable option for treatment of traumatic thoracic aortic injury. Although, stent graft complications were uncommon, but when it occurred, it leads to re-intervention. Further radiological follow-up is required particularly in young patient to document late aortic/stent complications.

Systematic Review and Meta-analysis of Factors Influencing Survival Following Abdominal Aortic Aneurysm Repair.

BACKGROUND: Predicting long-term survival following repair is essential to clinical decision making when offering abdominal aortic aneurysm (AAA) treatment. A systematic review and a meta-analysis of pre-operative non-modifiable prognostic risk factors influencing patient survival following elective open AAA repair (OAR) and endovascular aneurysm repair (EVAR) was performed. METHODS: MEDLINE, Embase and Cochrane electronic databases were searched to identify all relevant articles reporting risk factors influencing long-term survival (≥1 year) following OAR and EVAR, published up to April 2015. Studies with <100 patients and those involving primarily ruptured AAA, complex repairs (supra celiac/renal clamp), and high risk patients were excluded. Primary risk factors were increasing age, sex, American Society of Anaesthesiologist (ASA) score, and comorbidities such as ischaemic heart disease (IHD), cardiac failure, hypertension, chronic obstructive pulmonary disease (COPD), renal impairment, cerebrovascular disease, peripheral vascular disease (PVD), and diabetes. Estimated risks were expressed as hazard ratio (HR). RESULTS: A total of 5,749 study titles/abstracts were retrieved and 304 studies were thought to be relevant. The systematic review included 51 articles and the meta-analysis 45. End stage renal disease and COPD requiring supplementary oxygen had the worst long-term survival, HR 3.15 (95% CI 2.45-4.04) and HR 3.05 (95% CI 1.93-4.80) respectively. An increase in age was associated with HR of 1.05 (95% CI 1.04-1.06) for every one year increase and females had a worse survival than men HR 1.15 (95% CI 1.07-1.27). An increase in ASA score and the presence of IHD, cardiac failure, hypertension, COPD, renal impairment, cerebrovascular disease, PVD, and diabetes were also factors associated with poor long-term survival. CONCLUSION: The result of this meta-analysis summarises and quantifies unmodifiable risk factors that influence late survival following AAA repair from the best available published evidence. The presence of these factors might assist in clinical decision making during discussion with patients regarding repair.

Prevalence of abdominal aortic aneurysm (AAA) in a population undergoing computed tomography colonography in Canterbury, New Zealand.

OBJECTIVE/BACKGROUND: There is compelling level 1 evidence in support of screening men for abdominal aortic aneurysm (AAA) to reduce AAA mortality. However, New Zealand (NZ) lacks data on AAA prevalence, and national screening has not been implemented. The aim of this study was to determine the prevalence of AAA in a population undergoing a computed tomography colonography (CTC) for gastrointestinal symptoms. METHODS: This was an observational study; all consecutive CTCs performed in three regions of the South Island of NZ over a 4 year period were reviewed. Data on abdominal and thoracic aorta diameters ≥30 mm, and iliac and femoral aneurysms ≥20 mm were recorded. Previous aortic surgical grafts or endovascular stents were also documented. Demographics, survival, and AAA related outcomes were collected and used for analysis. RESULTS: Included were 4,893 scans on 4,644 patients (1,933 men [41.6%], 2,711 women [58.4%]) with a median age of 69.3 years (range 17.0-97.0 years). There were 309 scans on 289 patients (75.4% men) who had either an aneurysm or a previous aortic graft with a median age of 79.6 years (range 57.0-96.0 years). Of these, 223 had a native AAA ≥30 mm. The prevalence of AAA rose with age from 1.3% in men aged 55-64 years, to 9.1% in 65-74 year olds, 16.8% in 75-84 year olds, and 22.0% in ≥85 year olds. The corresponding figures in women were 0.4%, 2%, 3.9%, and 6.2%, respectively. CONCLUSION: In this observational study, the prevalence of AAA was high and warrants further evaluation. The results acquired help to define a population that may benefit from a national AAA screening programme.

A nurse-run clinic for patients with incidentally discovered small abdominal aortic aneurysms is feasible and cost-effective.

INTRODUCTION: Patients with incidentally discovered small abdominal aortic aneurysms (AAA) require assessment by a vascular surgery department for possible enrollment in a surveillance programme. Our unit implemented a vascular nurse-run AAA clinic in October 2010. The aim of this study was to assess the feasibility of a specialist nurse-run small AAA clinic. METHODS: Demographic and clinical data were collected prospectively for all patients seen in the new vascular nurse clinic between October 2010 and November 2012. A validated AAA operative mortality score was used to aid decision making by the vascular nurse. RESULTS: Some 250 patients were seen in the clinic. 198 (79.2%) patients were enrolled in surveillance, 40 (16%) declined enrollment and 12 (4.8%) were referred to a consultant clinic for further assessment. The majority of patients were male and the mean age was 73.7 years. Co-morbidities included hypertension, a history of cardiovascular disease, and hyperlipidaemia. The majority of referrals were considered to be low operative risk. No aneurysms ruptured whilst under surveillance. CONCLUSIONS: A nurse-run clinic that assesses patients with incidentally discovered small AAAs for inclusion in AAA surveillance is a feasible alternative to assessment of these patients in a consultant-run clinic.

Spectral CT of carotid atherosclerotic plaque: comparison with histology.

OBJECTIVE: To distinguish components of vulnerable atherosclerotic plaque by imaging their energy response using spectral CT and comparing images with histology. METHODS: After spectroscopic calibration using phantoms of plaque surrogates, excised human carotid atherosclerotic plaques were imaged using MARS CT using a photon-processing detector with a silicon sensor layer and microfocus X-ray tube (50 kVp, 0.5 mA) at 38-µm voxel size. The plaques were imaged, sectioned and re-imaged using four threshold energies: 10, 16, 22 and 28 keV; then sequentially stained with modified Von Kossa, Perl's Prussian blue and Oil-Red O, and photographed. Relative Hounsfield units across the energies were entered into a linear algebraic material decomposition model to identify the unknown plaque components. RESULTS: Lipid, calcium, iron and water-like components of plaque have distinguishable energy responses to X-ray, visible on spectral CT images. CT images of the plaque surface correlated very well with histological photographs. Calcium deposits (>1,000 µm) in plaque are larger than iron deposits (<100 µm), but could not be distinguished from each other within the same voxel using the energy range available. CONCLUSIONS: Spectral CT displays energy information in image form at high spatial resolution, enhancing the intrinsic contrast of lipid, calcium and iron within atheroma. KEY POINTS: Spectral computed tomography offers new insights into tissue characterisation. Components of vulnerable atherosclerotic plaque are spectrally distinct with intrinsic contrast. Spectral CT of excised atherosclerotic plaques can display iron, calcium and lipid. Calcium deposits are larger than iron deposits in atheroma. Spectral CT may help in the non-invasive detection of vulnerable plaques.

Negative pressure wound therapy as an adjunct to compression for healing chronic venous ulcers.

OBJECTIVE: To determine the efficacy of negative pressure wound therapy (NPWT), when used in combination with compression bandaging, for healing chronic resistant venous ulcers. METHOD: In this pilot study, seven patients (with a total of 12 chronic resistant venous ulcers) received adjunctive NPWT and compression bandaging for 4 weeks. Their wounds were monitored for a total of 12 weeks. RESULTS: Dormant ulcers were seen to rapidly develop into healthy wounds, with a granulating base. CONCLUSION: This regimen may have a role in stimulating chronic venous ulcers into healing wounds, or in preparing them for skin grafting.

Effect of TNP on the microbiology of venous leg ulcers: a pilot study.

OBJECTIVE: To investigate the effect of topical negative pressure, delivered using Vacuum Assisted Closure (VAC, KCI), on the microbiology of chronic, non-infected venous leg ulcers (VLUs). METHOD: Patients receiving compression therapy for a chronic VLU were recruited into this prospective pilot study. The ulcer was swabbed and VAC was applied at 125mmHg continuous sub-atmospheric pressure on day 1 for six days. Standard methods for bacteriological sampling and measuring the wound surface area were applied at baseline and at the VAC dressing changes on days 3 and 6. Log median colony forming units (CFUs) per cm2 were used for statistical analyses. The bacterial species were identified. RESULTS: Seven patients were recruited into and completed the study. The median log10 CFU/cm2 on days 1, 3 and 6 were 3.5, 4.7 and 5.1 respectively. There was a significant increase in bacterial colonisation between days 1 and 6 (p<0.02). No change was observed in the identified microbiological species during therapy with VAC. CONCLUSION: This pilot study suggests that VAC therapy increases absolute numbers of bacteria colonising non-infected leg ulcers. DECLARATION OF INTEREST: KCI supplied the VAC equipment and ARANZ the SilhouetteMobile, but both had no other influence on the study.

The effect of Helicobacter pylori infection and dietary iron deficiency on host iron homeostasis: a study in mice.

BACKGROUND: Helicobacter pylori, which requires iron to survive, may cause host iron deficiency by directly competing with the host for available iron or by impairing iron uptake as a consequence of atrophy-associated gastric hypochlorhydria. The aim of this study was to examine the effect of H. pylori infection and dietary iron deficiency on host iron homeostasis in a mouse model. MATERIALS AND METHODS: H. pylori SS1-infected and uninfected C57BL/6 mice, fed either a normal diet or an iron-deficient diet, were assessed for iron status and infection-associated gastritis over a 30-week period. RESULTS: After 10 weeks, serum ferritin values were higher in H. pylori-infected mice than in uninfected controls, irrespective of dietary iron intake (p = .04). The infection-related increase in body iron stores persisted in the iron-replete mice but diminished over time in mice with restricted dietary iron intake (p < .0001). At 30 weeks serum ferritin levels were lower in these animals (p = .063). No significant difference in bacterial numbers was detected at the 30-week time point (p > .05) and the histological changes observed were consistently associated with infection (p < .01) and not with the iron status of the mice (p = .771). CONCLUSIONS: Infection with H. pylori did not cause iron deficiency in iron-replete mice. However, diminished iron stores in mice as a result of limited dietary iron intake were further lowered by concurrent infection, thus indicating that H. pylori competes successfully with the host for available iron.

Nutritional and immune status following spinal cord injury: a case controlled study.

STUDY DESIGN: Case controlled study. OBJECTIVE: To compare nutritional status and immune response in a group of spinal cord injured (SCI) patients with age and gender matched non SCI control subjects. METHOD: Thirty past patients of the Burwood Hospital Spinal Injuries Unit living locally were enrolled in the study. Age and gender matched non SCI control subjects were selected volunteers from hospital staff. Nutritional status was assessed by generating a Nutritional Risk Score (NRS, Appendix 1) and drawing blood for full blood count, iron studies, red blood cell folate, vitamin B12, ferritin, magnesium, and zinc. Immune status was assessed by vaccination response index (VRI) to Pneumovax 23 vaccine. RESULTS: Full blood count, iron studies, and testing for red blood cell folate, albumin, prealbumin, vitamin B12, ferritin, magnesium and zinc were normal range for both groups. The SCI group had significantly different median values than controls (P < 0.01) for haemoglobin concentration, white blood cell count, albumin, prealbumin, serum iron and % saturation. Body Mass Index (weight kg/(height cm(2)) was 22.2 (range 15-30) for the SCI group, significantly less than the paired control group index of 26 (range 20-32, P = 0.0004). Median NRS for SCI patients was 2 (range 0-6), compared to 0 (range 2-4) for paired controls (P < 0.0001). Scores ranged from 0 to 2 for each of the five NRS components for the SCI patients and 0 to 3 for the control group. There was no significant difference in the pre- and post-vaccination ratio for IgG, IgA, and IgM response to Pneumovax 23 vaccine. CONCLUSION: We have not identified any nutritional or immune status abnormality in SCI patients, however the SCI patients have a lower value for certain nutritional parameters and BMI. SCI patients however are at only slight risk of nutritional problems given their NRS and their lower normal values for certain nutritional factors.

Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase.

BACKGROUND: Organs used for transplantation may experience long periods of cold ischemic preservation and consequently oxygen free radical-mediated damage following reperfusion. Lecithinized superoxide dismutase (lec-SOD) is a novel free radical scavenger that has been shown to bind with high affinity to cell membranes. The aim of this study was to determine whether lec-SOD bound to endothelial cells under organ preservation conditions to mediate direct antioxidant activity at the endothelial cell surface and thus offer protection against the harmful effects of ischemia/reperfusion injury. METHODS: An in vitro study was performed on large vessel endothelial cells (HUVEC) and a human microvascular endothelial cell line HMEC-1, to investigate the potential therapeutic benefits of incorporating lec-SOD into organ preservation solution. A cold hypoxia/reoxygenation system was developed to examine lec-SOD binding affinity to endothelial cells, protection against hypoxia/reoxygenation-induced cell death, and neutrophil adhesion. RESULTS: Lec-SOD bound to endothelial cells with higher affinity than unmodified recombinant human superoxide dismutase (rhSOD) and significantly protected both HUVEC and HMEC-1 from cell death following 27 hours of cold hypoxia (P < 0.01). Furthermore, neutrophil adhesion to the endothelium stimulated by hypoxia and reoxygenation was significantly inhibited by treatment with lec-SOD but not by lecithin or rhSOD (P < 0.01). Analysis by flow cytometry demonstrated that E-selectin and ICAM-1 were up-regulated by hypoxia/reoxygenation that was inhibited in part by lec-SOD. CONCLUSIONS: The results from this study suggest that incorporation of lec-SOD into organ preservation solutions provides effective protection to endothelial cells against cold ischemia and reperfusion injury following transplantation.

Does a colostomy alter quality of life in patients with spinal cord injury? A controlled study.

STUDY DESIGN: Prospective controlled comparative analysis. OBJECTIVE: To determine whether a colostomy changes quality of life in patients with a spinal cord injury. METHOD: A previously validated questionnaire designed to assess quality of life in spinal injured patients (Burwood Questionnaire) was sent to 26 spinal cord injured patients with colostomies and 26 spinal cord injured patients without colostomy. The two groups were matched for level of injury, completeness of injury, length of time since injury, age (+/- 5 years) and gender. RESULTS: There was 100% completion of the questionnaire. There was no significant difference (P > 0.05) in the two groups of patients in regard to their general well being, emotional, social, or work functioning. CONCLUSIONS: Patients with colostomy following spinal injury are no worse off in regard to quality of life, than those without. The inference is that perhaps a colostomy should be considered earlier in patients with major bowel dysfunction following spinal cord injury. SPONSORSHIP: Financial support for Dr AC Lynch was provided by Royal Australian College of Surgeons with a Foundation Scholarship and Grant in aid by the Burwood International Spinal Trust. Mr N Randell was supported by the Canterbury Medical Research Foundation with a summer studentship.

Cadaver versus living donor kidneys: impact of donor factors on antigen induction before transplantation.

BACKGROUND: It is widely recognized that living-related donor (LRD) renal allografts have a higher overall graft survival than cadaver donor transplants. We tested the hypothesis that part of this is attributable to LRD kidneys being obtained under optimal conditions from healthy donors, whereas cadaveric kidneys may have experienced injury as a result of inflammatory events around the time of brain death. METHODS: We have performed a comparative immunohistochemical analysis of pretransplant donor biopsies from cadaveric (N = 65) and LRD (N = 29) kidneys to determine any differences that may predispose them to subsequent damage. Cryostat sections were stained with antibodies to leukocytes, adhesion molecules, and human leukocyte antigen (HLA)-DR antigens, and the expression was assessed semiquantitatively. RESULTS: High levels of endothelial E-selectin and proximal tubular expression of HLA-DR antigens, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were detected in biopsies from cadaveric kidneys, whereas expression of these markers was markedly reduced in LRD kidneys. High levels of tubular antigen expression were significantly associated with traumatic death, prolonged ventilation, and episodes of infection in cadaver donors. Furthermore, the expression of pretransplant tubular antigens in cadaver donor kidneys was significantly associated with early acute rejection following transplantation, suggesting that such kidneys are predisposed to subsequent immune-mediated attack following transplantation. CONCLUSIONS: These results may explain, in part, the superior outcome of LRD allografts compared with cadaver renal allografts.

Dendritic cell chemotaxis and transendothelial migration are induced by distinct chemokines and are regulated on maturation.

The capacity of dendritic cells (DC) to initiate immune responses is dependent on their specialized migratory and tissue homing properties. Chemotaxis and transendothelial migration (TEM) of DC were studied in vitro. Immature DC were generated by culture of human monocytes in granulocyte-macrophage colony-stimulating factor and IL-4. These cells exhibited potent chemotaxis and TEM responses to the CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, and monocyte chemotactic protein-3, and weak responses to the CC chemokine MIP-3beta and the CXC chemokine stromal cell-derived factor (SDF)-1alpha. Maturation of DC induced by culture in lipopolysaccharide, TNF-alpha or IL-1beta reduced or abolished responses to the former CC chemokines but markedly enhanced responses to MIP-3beta and SDF-1alpha. This correlated with changes in chemokine receptor expression: CCR5 expression was reduced while CXCR4 expression was enhanced. These findings suggest two stages for regulation of DC migration in which one set of chemokines may regulate recruitment into or within tissues, and another egress from the tissues.

Ischemia/reperfusion injury in human kidney transplantation: an immunohistochemical analysis of changes after reperfusion.

Organs used for transplantation undergo varying degrees of cold ischemia and reperfusion injury after transplantation. In renal transplantation, prolonged cold ischemia is strongly associated with delayed graft function, an event that contributes to inferior graft survival. At present, the pathophysiological changes associated with ischemia/reperfusion injury in clinical renal transplantation are poorly understood. We have performed an immunohistochemical analysis of pre- and postreperfusion biopsies obtained from cadaver (n = 55) and living/related donor (LRD) (n = 11) renal allografts using antibodies to adhesion molecules and leukocyte markers to investigate the intragraft changes after cold preservation and reperfusion. Neutrophil infiltration and P-selectin expression were detected after reperfusion in 29 of 55 (53%) and 24 of 55 (44%) cadaver renal allografts, respectively. In marked contrast, neutrophil infiltration was not observed in LRD allografts, and only 1 of 11 (9%) had an increased level of P-selectin after reperfusion. Immunofluorescent double-staining demonstrated that P-selectin expression resulted from platelet deposition and not from endothelial activation. No statistically significant association was observed between neutrophil infiltration and P-selectin expression in the glomeruli or intertubular capillaries despite the large number of cadaver renal allografts with postreperfusion changes. Neutrophil infiltration into the glomeruli was significantly associated with long cold ischemia times and delayed graft function. Elevated serum creatinine levels at 3 and 6 months after transplantation were also associated with the presence of neutrophils and platelets after reperfusion. Our results suggest that graft function may be influenced by early inflammatory events after reperfusion, which can be targeted for future therapeutic intervention.

Effect of one-HLA-haplotype-matched and HLA-mismatched blood transfusions on recipient T lymphocyte allorepertoires.

BACKGROUND: Pretransplant blood transfusion has a well-known beneficial effect on posttransplant graft survival. Recently, it has been proposed that the clinical benefit of transfusion is due to HLA-DR antigen sharing between the blood donor(s) and the recipient. Immunological studies have suggested that this might result from a functional deletion of donor-reactive cytotoxic T lymphocytes. METHODS: We investigated frequencies of alloreactive lymphocyte precursors with cytotoxic or interleukin-2-producing helper function by limiting dilution analysis in 10 renal dialysis patients before and after transfusion with fresh, allogeneic whole blood. Five patients received blood transfusions from donors matched for one HLA haplotype (or one HLA-B-DR antigen) and the other five patients received blood from fully HLA-mismatched donors. RESULTS: Contrary to some previous reports, frequency analysis of cytotoxic T lymphocyte precursors revealed no significant differences between the two treatment groups in terms of development of blood donor-specific hyporesponsiveness after transfusion. Split-well analysis of cytotoxic T lymphocyte precursors reactive with single-mismatched HLA antigens demonstrated that the effects of transfusion on alloreactive specificity are complex and may vary depending on the particular antigens mismatched between the recipient and blood donor. Analysis of donor-specific helper T lymphocyte precursor frequencies revealed a significant decrease of interleukin-2-producing cells 3 months after transfusion in the total patient population. This effect was most prominent in the recipients of HLA-mismatched blood, but it also exhibited some degree of nonspecificity, as frequencies of third-party reactive helper T lymphocyte precursors were also significantly reduced. CONCLUSIONS: Our overall results suggest that the degree of HLA matching between blood donor and recipient does not greatly influence the effect of blood transfusion on the T lymphocyte allorepertoire. The apparent induced down-regulation of helper T lymphocyte activity may play a role in the reported immunosuppressive effects of allogeneic blood transfusion.