Rozprawy doktorskie na temat „Vascular surgery”

Background - Traditional audit methods are limited in their ability to provide short feedback loop to identify underperforming surgical units in time for them to respond appropriately. Moreover, case mix and other confounding factors limit the usefulness of crude mortality figures. More advanced industrial methods such as cumulative sum method (CUSUM) have therefore become of interest to surgeons. Hypothesis – Continuous monitoring of outcome in aortic aneurysm surgery using CUSUM technique (with optimisation using fractional polynomial mathematical models) can be applied, and do provide significant higher and more accurate detection rate of outliers when compared to traditional audit methods. Methods – Using anonymised records from National Vascular Database (NVD), three monitoring systems were applied in real time: Cumulative mortality (reflecting traditional audit process), funnel plot, and CUSUM (SPRT). VBOHM risk score was used to adjust for case-mix. Outliers were detected using different detection levels (h) and odds ratios (OR) with variable mortality rates (p). Performance of the three monitoring models was compared using direct alarm signals, sensitivity and specificity analysis, receiver operating curve (ROC), and average run length (ARL). Choosing control limits to maximise efficiency was approximated using direct simulation, Markov chain, and fractional polynomial techniques. Results –In-hospital mortality following elective Abdominal Aortic Aneurysm (AAA) repair between 1995 and 2011 in 140 centers were monitored. Compared to traditional audit methods, CUSUM has significant sensitivity to the outlier status of each vascular unit, with average number of CUSUM alerts of 0.89 when there is no outlier status, rising up to 23 alerts when there is an outlier status. Maximising the sensitivity and specificity of detecting outliers by CUSUM technique (also called incontrol ARL) while minimising false alarms (also called out-of-control ARL) was achieved using different range of values for control limits (h) and odds ratios (OR). For best CUSUM performance, values of OR=3, p=3, and h=1.25 has been shown to detect outliers correctly in 53% of case, and reject correctly in 59% of cases. This corresponds with CUSUM sensitivity of 80% and specificity of 80%. CUSUM has a positive predictive value of 78% and negative predictive values of 82%, with accuracy reaching 80%. Fractional polynomial technique and CUSUM simulation behavior were shown to correlate well (R > 0.88, p < 0.05) to the real-time NVD data analysis. Conclusion - To the best of our knowledge, our results demonstrated for the first time that using CUSUM (SPRT) model is both feasible and beneficial when used to comprehensively analyze a national dataset, validating the performance of all contributing Units, triggering alarm signals where necessary, and testing the sensitivity and specificity of each detection method with different decision making thresholds.

In response to improving quality patient care, combined with the growing rates of surgical site infections (SSIs) in vascular patients, the need to explore current practice trends with current evidence has been identified. SSIs affect quality patient care and compromise patient safety. Empirical evidence has recommended the use of a chlorhexidine wash preoperatively to reduce SSIs. Despite this recommended practice, vascular patients were not receiving it in their routine plan of care within a hospital organization in southern Ontario. Guided by Lewin's theory of planned change, this project explored how the planning of a chlorhexidine preoperative surgical skin preparation protocol impacted progress toward improved care of vascular patients. The project was designed as a quality improvement project examining approximately 110 vascular surgical procedures over a 1-month period and staff surveys that were provided to staff in the preoperative (n = 88), same day surgery (n = 68), and inpatient (n = 47) units. These data were analyzed and demonstrated a reduction in vascular SSIs from 4.9% pre-implementation to 2.8% 1-month post-implementation. Major themes generated from the staff surveys demonstrated the nursing staff had a good understanding of the content that was presented in the in-service provided. These findings have implications for social change by highlighting the benefits of incorporating evidence in to practice and further informing the preoperative practice in other surgical specialties.

Arteriovenous fistula (AVF) are widely considered to be the optimal form of vascular access for haemodialysis incurring fewer complications, superior patency, better dialysis quality and a lower mortality than tunnelled central venous catheters (TCVCs). The use of TCVCs is associated with a six-fold increase in the risk of systemic sepsis, long-term morbidity from central vein stenosis and a higher risk of cardiovascular and all-cause mortality compared to AVF. Despite the relative success of strategies such as “Fistula First” and the best practice target in England and Wales (with simultaneous improvement in prevalent autologous access use) there has been no associated improvement in incident vascular access rates. The importance of “getting it right from the start” cannot be overemphasized. Patients who start dialysis via a line are more likely to remain with a line. Data from the UK Renal Registry indicate that 59.8% of patients starting on a TCVC remain dialysing via a TCVC at 3 months and >40% still have their TCVC after 1 year. The legacy of poor early vascular access decision-making remains with the patient throughout their life on dialysis. This thesis sought to evaluate methods for improving vascular access within the incident patient cohort. A multifaceted approach was taken to address several key themes: 1. TCVC complications and central vein stenosis: avoiding problems for the future. 2. Predicting maturation in incident dialysis patients. 3. Promoting maturation: strategies to optimise maturation. 4. Right access, right patient, right time: individualised, patient-centred care. 5. ‘Crashlanders’: managing patients who present without prior warning. The emphasis of this work was directed towards finding pragmatic, patient-focussed solutions to clinically relevant problems. The dogma of “Fistula First at all costs” is challenged.

The recorded use of medical implants dates to before Christ. Synthetic cardiovascular implants, more specifically, have been widely used since the 1960s. While research and emerging technologies have achieved numerous advances in this latter field, the host body still recognizes many implants as "foreign" and initiates a healing response that can ultimately interfere with the long-term function of the prostheses. Particular to the area of synthetic vascular grafts, biological responses include platelet activation, thrombosis, and smooth muscle cell migration and proliferation. These reactions have been, and continue to be, characterized in relation to interpositional synthetic conduits. Translumenally placed endovascular grafts (EVGs), in contrast, are a relatively new treatment modality whose associated healing responses are, as yet, not well described. Endovascular implants are unique in that their surrounding environment can be quite different from that observed in association with open surgical procedures. The endovascular delivery process can preserve viable endothelium, reduce the surgical dissection of an artery, eliminate the placement of a foreign body deep in the arterial wall, and negate flow disturbances with straight inline arterial reconstruction. In addition, the apposition of the EVG to the native vessel is primarily an intimal as opposed to a medial or adventitial interface, potentially influencing the cells that initiate and impact all subsequent events in the healing response. To better characterize the cellular and angiogenic adaptations that occur in association with intimal approximations, experiments were performed to examine the healing responses related to both conventional grafts anastamosed with non-penetrating clips as well as to EVG placement. Research indicates that modulation of endothelial and smooth muscle cell (SMC) phenotypes during healing is a complex process that is likely regulated by multiple environmental cues. Soluble factor communication and cell substrate interactions are two likely signals that may ultimately influence the fate of the involved cells. Data demonstrate that endothelial cells are present and can be the initial cellular responders at the site of vascular intervention. In addition, these cells can directly contribute to neointimal thickening through cellular transmodulation. Alternatively, they can participate in process herein described as "differentiated vasculogenesis," whereby individual and/or groups of endothelial cells are liberated from the luminal monolayer into the provisional matrix that has been deposited around the vascular implants. Here they coalesce into non-patent vascular channels. Longer duration studies further specify that SMCs can be induced to re-attain a contractile state in association with low profile, highly porous endoluminal prostheses. Finally, experimental findings suggest that a preformed endothelial and SMC lining can be established in vitro within a tissue engineered vascular graft (TEVG). Implantation of the TEVGS, however, resulted in the dissolution and eventual re-population of the cellular constituents. Based on this work, it is evident that vascular wall responses to biomedical implants are far more complex than they have appeared in the past. Implant associated vascular wall healing can no longer be considered an ordered orchestration of SMC migration and proliferation followed by endothelial cell sheet migration over the neointimal lining. Future anti-stenosis and anti angiogenic therapies need to take into account the multi-factor/multi-cellular responses that can be involved.

Angiogenesis is essential for physiological processes including embryonic development, tissue regeneration, and reproduction. Under various pathological conditions the same angiogenic process contribute to the onset, development, and progression of many human diseases including cancer, diabetic complications, ocular disease, chronic inflammation and cardiovascular disease. Vascular endothelial growth factor (VEGF) is a key angiogenic factor for physiological and pathological angiogenesis. In addition to its strong angiogenic activity, VEGF also potently induces vascular permeability, often causing tissue edema in various pathological tissues. VEGF transduces its vascular signal through two tyrosine kinase receptors-VEGFR1 and VEGFR2, the latter being a functional receptor that mediates both angiogenic and vascular permeability effects. To study physiological and pathological functions of VEGF, we developed novel zebrafish disease models that permit us to study hypoxia-induced retinopathy and cancer metastasis processes. We have also administered anti-VEGF and anti-VEGFR specific antibodies to healthy mice to study the homeostatic role of VEGF in the maintenance of vascular integrity and its functions in various tissues and organs. Finally, using a zebrafish model, we evaluated if VEGF expression is regulated by circadian clock genes. In paper I, we developed protocols that create hypoxia-induced retinopathy in adult zebrafish. Adult fli1:EGFP zebrafish were placed in hypoxic water for 3-10 days with retinal neovascularization being analyzed using confocal microscopy. This model provides a unique opportunity to kinetically study the development of retinopathy in adult animals using non-invasive protocols and to assess the therapeutic efficacy of orally administered anti-angiogenic drugs. In paper II, we developed a zebrafish metastasis model to dissect the complex events of hypoxia-induced tumor cell invasion and metastasis in association with angiogenesis at the single-cell level. In this model, fluorescent DiI-labeled human or mouse tumor cells were implanted into the perivitelline cavity of 48-hour-old zebrafish embryos, which were subsequently placed in hypoxic water for 3 days. Tumor cell invasion, metastasis and pathological angiogenesis were analyzed using fluorescent microscopy in the living fish. The average experimental time for this model is 7 days. Our protocol offers an opportunity to study molecular mechanisms of hypoxia-induced cancer metastasis. In paper III, we show that systemic delivery of an anti-VEGF or an anti-VEGF receptor (VEGFR)-2 neutralizing antibody cause global vascular regression in mice. Among all examined tissues, the vasculature in endocrine glands, intestinal villi, and the uterus are most affected in response to VEGF or VEGFR-2 blockades. Pro-longed anti-VEGF treatment resulted in a significant decrease in the circulating levels of the predominant thyroid hormone, free thyroxine, but not the minimal isoform of triiodothyronine, suggesting that chronic anti-VEGF treatment impairs thyroid function. These findings provide structural and functional bases of anti-VEGF-specific druginduced side effects in relation to vascular changes in healthy tissues. In paper IV, we show that disruption of the circadian clock by constant exposure to light coupled with genetic manipulation of key genes in the zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. These results offer mechanistic insights into the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis. Overall, the results in this thesis provide further insight to angiogenic mechanistic properties in tissues and suggest possible novel therapeutic targets for the treatment of various angiogenesis-dependent diseases.
Blodkärlsnybildning, så kallad angiogenes, är viktigt för fysiologiska processer vid embryonal utveckling, vävnadsregenerering och reproduktion. Samma angiogena process kan också under olika sjukdomstillstånd bidra till uppkomst, utveckling och progress av många sjukdomar, såsom cancer, diabeteskomplikationer, ögonsjukdomar, kronisk inflammation samt hjärtkärlsjukdom. Vascular endothelial growth factor (VEGF) är mycket viktig för fysiologisk och patologisk angiogenes. Utöver sin starka angiogena effekt inducerar VEGF även ökad kärlpermeabilitet, som ofta orsakar ödem. VEGF utövar sin effekt på kärlen via två tyrosinkinasreceptorer: VEGFR1 och VEGFR2, där den senare är en funktionell receptor som förmedlar både angiogena signaler och har effekter på vaskulär permeabilitet. För att öka möjlgheterna att studera fysiologiska och patologiska funktioner av VEGF, har vi utvecklat sjukdomsmodeller i zebrafisk - hypoxi-inducerad retinopati och metastasering av cancer. Vi har också givit anti-VEGF och anti-VEGFR-specifika antikroppar till friska möss för att utvärdera VEGFs roll vid stabiliseringen av kärlfunktionen i olika vävnader och organ. Slutligen,utvärderade vi om expressionen av VEGF regleras av dygnsrytmen genom så kallade klock-gener. I papper I utvecklade vi en modell för hypoxiinducerad retinopati hos vuxna zebrafiskar. Vuxna fli1:EGFP zebrafiskar placeras i syrefattigt vatten i 3-10 dagar, varpå retinal nybildning av kärl analyserades. Denna modell ger en unik icke-invasiv möjlighet att studera kinetiskt utveckling av retinopati och den möjliggör bedömning av terapeutiska effekter av oralt givna anti-angiogena läkemedel. I papper II utvecklade vi en zebrafiskmodell för utvärdering av cancermetastasering, som möjliggör studier av detaljerade delprocesser vid hypoxi-inducerad tumörcellsinvasion och metastasering i samband med angiogenes på encellig nivå. I denna modell användes fluorescerande Dil-märkta humana- eller mustumörceller som implanterades vid den perivitellina hålighet hos 48-h-gamla zebrafiskembryon placerade i syrefattigt vatten i 3 dagar. Tumörcellinvasion, metastasering och patologisk angiogenes analyserades med mikroskopi i levande fiskar. Vårt protokoll möjliggör studier av molekylära mekanismer bakom hypoxi-inducerad cancermetastasering. I papper III visas, att systemisk administration av anti-VEGF eller anti-VEGF-receptor (VEGFR)-2 neutraliserande antikroppar in en musmodell orsakar generell kärlregression. Bland alla undersökta vävnader påverkades endokrina körtlar, tarmslemhinna och uterus mest av VEGF eller VEGFR-2 blockad. Långvarig anti-VEGF behandling resulterade i en signifikant minskning av cirkulerande nivåer av det dominerande sköldkörtelhormonet, fritt tyroxin, men inte av trijodtyronin, vilket tyder på att kronisk anti-VEGF behandling försämrar sköldkörtelfunktionerna. Resultaten påvisar risken för biverkningar i friska vävnader av anti-VEGF behandling. I papper IV visar vi att störningar i dygnsrytm genom konstant exponering för ljus och genetisk manipulation av nyckelgener i zebrafisk ledde till nedsatt angiogenes under embryonal utveckling. En bmal1-specifik morfolino hämmade angiogenes i zebrafisk utan att orsaka andra kärl-oberoende fenotyper. Omvänt, en period2 morfolino accelererade angiogeneskärltillväxt, vilket tyder på att Bmal1 och Period2 utövar motsatta effekter påkärlstillväxt. Dessa resultat ger mekanistisk kunskap om den roll som dygnsrytmen har i regleringen av angiogenes, och resultat kan rimligen utvidgas till andra typer av fysiologisk eller patologisk angiogenes. Sammanfattningsvis ger resultaten i denna avhandling ytterligare kunskap om angiogenetiska mekanismer och pekar på möjliga nya terapeutiska mål för behandling av olika angiogenes-beroende sjukdomar.

Introduction: Intensive research over the last six decades has resulted in minimal improvement in vascular graft development. Small animal models are the first line of species exposed to vascular graft implantation and invasive monitoring of experimental graft patency may contribute to pain, suffering, higher cost and earlier sacrifice. Non-invasive ultrasonographic evaluation of vascular implants during the conduction of animal studies allows for chronic follow-up with multiple assessments. This study aims to apply and endorse the utilization of ultrasound as a less invasive diagnostic method in determining patency of vascular grafts in units where imaging modalities like Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) are not readily available. Methods: Pre-operative control ultrasound evaluation of the ejection fraction, aortic diameter and aortic velocity were conducted on Wistar rats (250-350g). Infra-renal aortic vascular graft implantation was then performed, with 8 rats receiving straight (1.8mm ID, 18mm length) expanded polytetrafluoroethylene (ePTFE) grafts, while 12 rats received a long (1.8mm ID, 100mm length) looped ePTFE conduit with a sealed mid-graft (10mm length) section. Ultrasonography was conducted on days 1, 3, 7 and weeks 4, 8 and 12 post operatively. Grafts were explanted if there was any ultrasonographic evidence of occlusion or at twelveweek termination of the study. Explant was preceded by angiography and followed by histological assessment of the grafts for patency. Results: Three of the looped and all 8 of the straight grafts were patent at the 12 week explant time point, as correctly assessed by ultrasound and confirmed by angiography and histology. Three of the nine occluded looped grafts were explanted at eight weeks due to early ultrasonographic detection of occlusion; the remaining 6 were explanted at twelve weeks. There were two false positive results, which were incorrectly assessed as patent at twelve weeks of implantation on ultrasonographic evaluation, but confirmed to be occluded on angiography at explant. The results of ultrasonography evaluation of implanted infra-renal vascular grafts had a high specificity of 100% with a sensitivity of 78%. The outcome of the results between ultrasound and angiography corresponded in 18 out of 20 vascular grafts, with a calculated positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 85%. 4 Conclusion: Ultrasound is easily available and a non-invasive diagnostic modality allowing for safe and reliable results, which may be repeated at different time frames following vascular implants in small animal models. Ultrasonographic limitations exist, emphasizing the need for an experienced operator with adequate knowledge and training. Its use may be complicated by tortuous geometries of vessels, which is technically more challenging to evaluate with ultrasound than with imaging techniques like CT and MRI. It does, however, add information without additional loss of life or increased use of animal numbers. Ultrasound is an essential additive diagnostic tool for chronic follow-up and evaluation of vascular graft implants.

A retrospective study was carried out on 535 patients who underwent bypass surgery for peripheral vascular disease. Survival data for 303 patients out of these 535 cases are subjected to quantitative analysis. The main interest is in survival of these patients in order to identify the risk factors. The importance of types of grafting technique in long-term survival is also considered. Statistical methods used to ascertain the important prognostic variables include Cox's proportional hazards model, stepwise regression and all subsets regression in proportional hazards model discussed by Kuk (1984). In descending order of significance, the most important variables are myocardial infarction, presence or absence of hypertension, sex and whether or not a revision operation was done. The variable, history of a previous coronary bypass graft is highly correlated with survival but the comparison of its significance to the other significant variables is not possible with Cox's model. Age is also related to survival in this data set. However, since there is no control group, one cannot make a strong conclusion about the effect of age on survival of the patients who have had surgery for peripheral vascular disease.
Science, Faculty of
Statistics, Department of
Graduate

Iatrogenic vascular injuries (IVIs) and injuries associated with vascular surgery can cause severe morbidity and death. The aims of this thesis were to study those injuries in the Swedish vascular registry (Swedvasc), the Swedish medical injury insurance where insurance claims are registered, the Population and Cause of death registries, and in patient records, in order to explore preventive strategies. Among 87 IVIs during varicose vein surgery 43 were venous, mostly causing bleeding in the groin. Among 44 arterial injuries, only 1/3 were detected intraoperatively. Accidental arterial stripping predominated, with poor outcome. Four patients died, all after venous injuries. IVIs increased over time, and constitute more than half of the vascular injuries registered in the Swedvasc. Lethal outcome was more common (4.9%) among patients suffering IVIs than among non-iatrogenic vascular injuries (2.5%). Risk factors for death were age, diabetes, renal insufficiency and obstructive lung-disease. Fifty-two patients died within 30 days after IVI. The most common lethal IVIs were puncture during endovascular procedures (n=24, 46%), penetrating trauma during open surgery (11) and occlusion after compression (6). Symptoms were peripheral ischemia (n=19), external bleeding (14), and hypovolemic chock without external bleeding (10). Most died within two weeks (n=36, 69%). After >2 weeks the IVI as a cause of death was uncertain. Among 193 insurance claims after vascular surgery during 2002-2007, nerve injuries (91) and wound infections (22) dominated. Most patients suffered permanent injuries, three died. Patients with insurance claims were correctly registered in the Swedvasc in 82%. In 32 cases of popliteal artery injury during knee arthroplasty symptoms were bleeding (n=14), ischaemia (n=7) and false aneurysm formation (n=11). Only twelve injuries (38%) were detected intraoperatively. Patency at 30 days was 97%, but only seven (22%) patients had complete recovery. Six of those had intraoperative diagnosis of popliteal injury and immediate vascular repair. In conclusion, registration of IVIs is increasing and outcome is often negatively affected by diagnostic and therapeutic delay. Not all fatalities after IVIs are attributable to the injury itself. The most common causes of insurance claims after vascular surgery were nerve injuries, and 82% were correctly registered in Swedvasc.

Hong Kong's aging population has, increased demand for vascular services. Currently, vascular surgery is subsumed under general surgery. The workload on both general surgery and vascular surgery is demanding and hence, not conductive to the development of vascular surgery. The volume of surgery, particularly emergency surgery provided by the Hospital Authority units varies significantly. The collaboration and differentiation of labor at present is not well defined in many centers. This may lead to unnecessary competition and duplication of resources in the long run. This project examined if there is room for improvement in the present situation and provides evidence for relevant service reconfiguration and discusses how Hong Kong can learn from some overseas examples to enhance quality of services delivered to patients.
published_or_final_version
Public Health
Master
Master of Public Health

Major vascular surgery is associated with a substantial risk of cardiovascular events and death. This risk is of increased importance in prophylactic elective open Abdominal Aortic Aneurysm (AAA) repair, where a balance of risk of rupture and postoperative outcome is assessed prior to management decisions. Further, the UK Small Aneurysm Trial has shown that prophylactic repair of an AAA has no survival benefit for the first three years due to the major adverse cardiac event (MACE) rate of 5-15%. There is however no ideal method of predicting this risk. Cardiac Troponin I (cTnI) is a contractile protein that is a highly sensitive and specific marker of myocardial necrosis. A few case reports have commented on the finding of preoperative asymptomatic elevated cTnI levels and poor outcome in a small number of patients undergoing major vascular surgery. There are however no studies looking at its incidence in the vascular surgical population or its utility as a preoperative marker. Several studies have noted that B-type natriuretic peptide (BNP), a diagnostic and prognostic marker of heart failure, may have a role in predicting MACE in settings including major vascular surgery. There are no studies that have investigated this role in AAA repair alone. The aim of this thesis is to investigate the incidence of, and to determine a possible role for, preoperative elevated cTnI in major vascular surgery. The further aim is to determine if a single preoperative BNP level correlated with MACE and all-cause mortality in elective open AAA repair in both the short and long-term. Comparisons to current accepted risk indices in AAA, and a possible role for BNP in EndoVascular Aneurysm Repair (EVAR) will also be investigated. Patients were recruited in two cohorts: Firstly, a prospective, 2 year observational single centre cohort study of all patients undergoing a vascular procedure, with an expected cardiac event rate >5%, recruited patients who had no clinical or ECG evidence of myocardial ischaemia. Preoperative cTnI was performed in all and postoperative screening (clinical assessment, ECG and cTnI) for cardiac events was performed at days 2, 5 and 30. 213 patient were recruited, of whom 11 (5.2%) had an asymptomatic elevated preoperative cTnI (>0.02 ng/ml). Eight of these patients proceeded directly to theatre, and 2 were delayed but later underwent surgery with a persistently elevated cTnI. Of these 10 patients, 5 (50%) died and 4 (40%) suffered MACE. The remaining patient was delayed due to the poor outcome of the preceding patients, and later underwent an uncomplicated aortic bifurcation graft with a normal cTnI level which had been preceded by coronary intervention. Secondly, a prospective, 2 year observational multi-centre cohort study in the 3 largest vascular units in Glasgow (Gartnavel General Hospital, Glasgow Royal Infirmary and Southern General Hospital) was performed between August 2005 and August 2007, recruiting all patients who were admitted for both elective open AAA repair and EVAR. Preoperative BNP levels were performed and batch analysed at the end of the study. Postoperative screening for cardiac events was performed as described above. Data was collected to allow calculation of risk indices associated with outcome in AAA repair (Glasgow Aneurysm Score [GAS], Vascular physiology only Physiological and Operative Severity Score for enUmeration of Mortality [V{p}-POSSUM], Vascular Biochemical and Haematological Outcome Model [VBHOM], Revised Cardiac Risk Index [RCRI] and Preoperative Risk Score of the Estimation of Physiological Ability and Surgical Stress Score [PRS of E-PASS]). Follow-up was continued to a minimum of 3 years, where possible, with cause of death recorded. 106 of 111 patients were recruited. The median [interquartile range] BNP concentrations in the 16 patients (15%) who suffered immediate postoperative MACE was 206 [118-454] vs 35 [17-61] pg/ml in the remainder (p=0.001). ROC analysis indicated a BNP concentration of 99.5 pg/ml best predicted MACE (area under the curve 0.927), with sensitivity of 88% and specificity of 89%. The BNP in patients who suffered cardiac death was significantly higher than in those that did not (median BNP 496 [280-881] vs 38 [18-84] pg/ml, p=0.043). ROC analysis revealed a cut-off of 448 pg/ml (AUC 0.963), with sensitivity 80%, specificity 100%, positive predictive value 100% and negative predictive value 99%. Not only did higher values of BNP predict MACE, but it was also found to predict all-cause mortality in the immediate (median BNP 100 [84-521] vs 35 [17-81], p=0.028), intermediate (median BNP 201 [97-496] vs 35 [17-73], p<0.001) and long-term (median BNP 98.5 [58-285] vs 32 [17-71.5], p<0.001) postoperative periods. ROC analysis revealed decreasing BNP levels to predict outcome over time, with a BNP of >60.5 pg/ml (AUC 0.761) found to best predict death at 3 years. Whilst BNP was found to predict outcome, most risk indices performed poorly. The GAS, VBHOM and RCRI performed poorly and did not predict any outcome measure. V(p)-POSSUM was, however, found to predict all outcome measures (p=0.028, p=0.030, p=0.038 for MACE, cardiac death and all-cause mortality respectively). The PRS component of E-PASS was found to predict MACE (p=0.019) and cardiac death (p=0.017). BNP performed better than any risk index. During the study period only 40 of 42 patients admitted for elective EVAR were recruited. Of these 40, only 3 suffered a non-fatal MI and 1 died of respiratory failure. BNP was not found to predict MACE or death in this cohort, and due to the small number of patients, and events, no strong conclusions could be drawn. Whilst preoperative elevated cTnI was found to identify patients that were at an increased risk of both postoperative MACE and death following their major vascular surgical procedure, its use in elective open AAA repair is limited due to infrequent occurrence. Preoperative serum BNP concentration, however, predicted postoperative MACE, cardiac death and all-cause mortality in patients undergoing elective open AAA repair on immediate, intermediate and long term follow-up. Further, BNP performed better than any current risk index for elective open AAA surgery. This simple blood test, therefore, offers valuable information regarding risk stratification of prospective surgical patients and should be considered a part of routine preoperative assessment in this prophylactic procedure.

The effectiveness of image guided neurosurgery (IGNS) depends on the presen-tation of accurate image data to a neurosurgeon for surgical planning and guidance.The blood vessels supplying the brain are of particular importance in IGNS, becausethey densely surround brain lesions and tumours, may themselves be the sites ofpathologies, and need to be carefully considered during surgery.Given the importance of visualizing and identifying vasculature for diagnosis,planning, and guidance, there is a strong need for automated vessel enhancementand registration techniques. Furthermore, tools for the characterization and valida-tion of developed image processing methods are needed. This thesis presents thedevelopment of three separate techniques to address the above stated needs: (1)a vessel-based intraoperative image registration technique, (2) a technique for pro-ducing anatomically realistic multimodality imaging phantoms, and (3) a non-localestimator based vessel structure enhancement technique.For intraoperative registration, where preoperative images are aligned to thepatient on the operating room table, we developed a hybrid non-linear vessel-basedregistration algorithm. Our technique combines the benefits of feature-based andintensity-based vessel registration methods. Raw volumetric images are processedthrough feature enhancement to produce a set of image intensity maps for registra-tion using cross-correlation. By not explicitly extracting discrete vessel features, wecan be assured that removal of important registration information is minimized. Weextensively validated our registration method for robustness and accuracy using alarge number of synthetic images, real physical phantom images, and real clinicalpatient images.In validating our registration technique we realized a need for improved physicalphantoms. As such, we developed a multimodal anthropomorphic brain phantomfor inter-modality image processing validation. The brain phantom (1) has the me-chanical properties and anatomical structures found in live human brain and (2) wasmade from polyvinyl alcohol cryogel. Marker spheres and inflatable catheters werealso implanted to enable good registration comparisons and to simulate tissue defor-mation, respectively. Multiple sets of multimodal data were then acquired from thisphantom and made freely available to the image processing community.Based on our vessel registration work, we also found a need for improved vesselenhancement methods. Therefore, we developed a technique that extends Frangi'svessel enhancement method to improve background suppression. To do this, we ac-count for larger vessel geometries over an extended area rather than solely usinginformation from a small local region. Validation of the technique was performedon 3D synthetic images, and 2D and 3D clinical images. The results revealed thatby analyzing larger image regions to improve background suppression and identifyvessel-like structures, our method can effectively enhance and improve retention ofthin and lower contrast vessels in comparison to Frangi's method.The automated vessel enhancement and vessel-based image registration tech-niques developed in this thesis can be used to improve the effectiveness of surgicalwork-flows in IGNS. Our anthropomorphic phantom can be used to validate andcharacterize novel image processing methods.
L'efficacitée de la neurochirurgie guidée par l'image (IGNS) dépend de la pré sentation au neurochirurgien d'images précises pour la planification chirurgicale et l'orientation. Les vaisseaux sanguins cérébraux sont d'une importance particulière en IGNS, parce qu'ils entourent densément les lésions céreb́rales et les tumeurs, et peuvent eux-mêmes être le siège de pathologies, et doivent être soigneusement examinés durant la chirurgie. Compte tenu de l'importance de la visualisation et de l'identification des vaisseaux cérébraux pour la planification du diagnostique et de l'orientation, il est important de développer des techniques automatisées pour augmenter les contrastes des vaisseaux, ainsi que des méthodes de recalage des images préopératoires. De plus, des outils pour la caractérisation et la validation des méthodes de recalage et de segmentation sont nécessaires. Cette thèse présente le développement de trois techniques différentes pour prendre en comptes ces besoins: (1) une technique qui utilise les in formations des vaisseaux sanguins pour le recalage des images préopératoires, (2) une technique pour produire des fantômes multimodaux avec des structures anatomique ment réalistes, et (3) une technique pour augmentater les contrastes des vaisseaux sanguins avec un estimateur non-local. Pour le recalage d'images préopératoires, où les images sont alignées par rapport au patient sur la table de la salle d'opération, nous avons développé une approche hybride de recalage avec transformation non-linéaire. Notre technique combine les avantages des techniques de recalage basées sur l'intensité et les attributs géométriques. La segmentation des vaisseaux sanguins est appliquée aux images volumétriques natives pour produire un ensemble de cartes d'intensité afin d'utiliser la corrélation croisée pour le recalage. En maintenant les structures sanguines comme cartes d'intensité, au lieu de l'extraction comme les caractéristiques discrètes, nous pouvons être sûr que d'importantes informations de l'image ne sont pas supprimées pour le recalage. En validant notre technique de recalage d'image, nous avons réalisé le besoin d'améliorer les fantômes multimodaux. Pour cela, nous avons développé un fantôme anthropomorphique du cerveau qui peut être efficacement utilisé pour la validation intermodalité du traitement des images. Le fantôme cérébral, qui a les proprietés mécaniques et une anatomie similaire; au cerveau humain in vivo, a été fait à partir d'alcool de polyvinyle cryogel. Des marqueurs sphériques et des cathéters gonflables ont également été implantés pour permettre de simuler la déformation des tissus et de comparer la qualité des recalages. Plusieurs ensembles de données multimodaux ont été acquis avec ce fantôme et ont été mis à la disposition de la communauté qui travaille sur le traitement des images. Notre travail sur le recalage des vaisseaux sanguins nous a également révélé la nécessité d'améliorer les méthodes numérique des vaisseaux. En conséquence, nous avons développé une technique qui pousse la méthode de Frangi en augmentant le contraste et en supprimant les éléments de fond. Ainsi, pour détecter des géométries des vaisseaux sanguins plus grandes, nous considérons une zone de recherche plus grande plutôt qu'une petite zone locale. La validation de la technique a été réalisée avec des images synthétiques 3D, et des images cliniques 2D et 3D. Les techniques automatisées pour le recalage et l'augmentation des contrastes des vaisseaux sanguins développés dans cette thèse peuvent être utilisées pour améliorer l'efficacité des processus chirurgicaux en IGNS. Notre fantôme anthropomorphique peut être quant à lui utilisé pour valider et caractériser de nouvelles méthodes de traitement d'image.

This thesis summarises the deficiencies of current small-diameter synthetic conduits and the approaches to the development of an improved vascular bypass conduit. Evidence for the incorporation of elastin in the design of novel conduits is then presented. We used recombinant human tropoelastin (rhTE) to develop two novel conduits. Firstly we hypothesised that rhTE can be bound to expanded polytetrafluoroethylene (ePTFE) conduits resulting in improved biocompatibility due solely to altered surface composition. rhTE was covalently bound to 6mm-diameter ePTFE and demonstrated uniform and durable protein attachment resulting in enhanced endothelial cell attachment and proliferation. Following a modification of rhTE coating, rhTE-coated ePTFE conduits were implanted in sheep for one month and demonstrated a marked reduction in anastomotic intimal hyperplasia and equivalent patency compared to control ePTFE. In the second part of this project we hypothesised that rhTE can be used to construct an entirely novel elastic conduit (NEC) that shows biocompatibility, and demonstrates mechanical properties matching the internal mammary artery. Using electrospinning we manufactured 2-3mm diameter NECs combining rhTE and polycaprolactone and matched the compliance, burst pressure, and hydraulic permeability of the internal mammary artery. After demonstrating endothelial cell growth and low platelet attachment in vitro we implanted conduits into rabbits for 2 and 4 weeks and showed retention of mechanical properties but loss of patency due to an inflammatory response to the implanted NEC compared to control ePTFE. Several factors serve to impede the design of successful novel vascular conduits and these are discussed including difficulties in the assessment of endothelialisation and compliance, the selection of an appropriate animal model and statistical method, and problems with in vitro techniques for thrombogenicity assessment.

Objectives: Cardiovascular disease is the leading cause of mortality and morbidity in the developed world. Surgery can improve prognosis and relieve symptoms. Risk prediction models are increasingly being used to inform clinicians and patients about the risks of surgery, to facilitate clinical decision making and for the risk-adjustment of surgical outcome data. The importance of risk prediction models in cardiovascular surgery has been highlighted by the publication of cardiovascular surgery outcome data and the need for risk-adjustment. The overall objective of this thesis is to advance risk prediction modelling in cardiovascular surgery with a focus on the development of models for elective AAA repair and assessment of models for cardiac surgery. Methods: Three large clinical databases (two elective AAA repair and one cardiac surgery) were utilised. Each database was cleaned prior to analysis. Logistic regression was used to develop both regional and national risk prediction models for mortality following elective AAA repair. A regional model to identify the risk of developing renal failure following elective AAA repair was also developed. The performance of a widely used cardiac surgery risk prediction model (the logistic EuroSCORE) over time was evaluated using a national cardiac database. In addition an updated model version (EuroSCORE II) was validated and both models’ performance in emergency cardiac surgery was evaluated. Results: Regional risk models for mortality following elective AAA repair (VGNW model) and a model to predict post-operative renal failure were developed. Validation of the model for mortality using a national dataset demonstrated good performance compared to other available risk models. To improve generalisability a national model (the BAR score) with better discriminatory ability was developed. In a prospective validation of both models using regional data, the BAR score demonstrated excellent discrimination overall and good discrimination in procedural sub-groups. The EuroSCORE was found to have lost calibration over time due to a fall in observed mortality despite an increase in the predicted mortality of patients undergoing cardiac surgery. The EuroSCORE II demonstrated good performance for contemporary cardiac surgery. Both EuroSCORE models demonstrated inadequate performance for emergency cardiac surgery. Conclusions: Risk prediction models play an important role in cardiovascular surgery. Two accurate risk prediction models for mortality following elective AAA repair have been developed and can be used to risk-adjust surgical outcomes and facilitate clinical decision making. As surgical practice changes over time risk prediction models may lose accuracy which has implications for their application. Cardiac risk models may not be sufficiently accurate for high-risk patient groups such as those undergoing emergency surgery and specific emergency models may be required. Continuing research into new risk factors and model outcomes is needed and risk prediction models may play an increasing role in clinical decision making in the future.

Dissertation (MD)--Stellenbosch University, 2000.
ENGLISH ABSTRACT: Acute renal failure still is, with the exception of cardiac deaths, the most important pathological process associated with perioperative mortality in patients operated for abdominal aortic aneurysms. The intraoperative change in renal blood flow (RBF) and glomerular function have been investigated in human and animal models, particularly over the past 15 years. Despite large variation in study populations, measurement techniques and study designs in general, a significant body of evidence has developed which suggests infrarenal aortic clamp-induced renal ischemia to be the cause of postoperative acute renal failure when this complication does occur. It is rather surprizing then that, despite some recent studies which have reported on various pharmacological interventions to prevent intraoperative renal ischemia (with variable success), very little has apparently been done to unravel the pathogenesis and exact pathophysiology of this potentially lethal complication. Although a number of investigators suggest the possibility of hormonal involvement (particularly reninangiotensin, antidiuretic hormone (ADH) and catecholamines) in the process, the exact role of these mediators have not been explored (or reported) in a structured fashion. In an initial human study, renal hemodynamics and function were measured from the preoperative period, during the intraoperative phase and at least until 4 hours after aortic unclamping. To investigate the possibility of a temporal relationship between renal changes and fluctuations in hormonal concentrations, plasma concentrations of relevant hormones were determined at every sampling period where renal parameters were measured. The decrease in RBF and glomerular filtration rate (GFR) which we demonstrated to coincide with infrarenal aortic cross clamping, is consistent with results previously published. We demonstrated persistence of the impairment of these parameters as long as 4 hours into the postoperative phase; which has previously only been reported for the period until immediately after aortic unclamping with the abdomen still open. The persistence of a depressed GFR until the time of discharge of patients is cause for concern, particularly in patients with compromised renal function prior to surgery. Of the measured hormones with a potential influence on RBF and nephron function, renin was the only mediator where changes in plasma concentrations coincided with the depression of RBF and GFR after aortic cross clamping. The design of our study did not allow us to conclude whether the concomitant increase in angiotensin II was primarily responsible for the change in renal hemodynamics, or whether the raised renin (and angiotensin) levels were stimulated by the decrease in RBF induced by another mechanism. In another patient group, we demonstrated that the combination of mannitol and dopamine provided no protection against the deleterious effects of aortic cross clamping. In fact, the high urine volumes produced under the influence of these agents (which did not correlate with RBF at the corresponding periods), is likely to prompt a false sense of security. Given the lack of any objective benefit afforded by these agents, their use in these clinical circumstances should be discouraged. The animal studies were aimed at elucidation of the exact role of angiotensin in the pathogenesis and pathophysiology of the renal changes associated with infrarenal aortic clamping, as well as the interaction of angiotensin with other modulators for which an interactive relationship had been described previously under other experimental and/or clinical circumstances. The first study showed that, although renin (and thus angiotensin) concentrations were high after aortic unclamping, the hormone had no pathogenic or pathophysiological role of significance in the observed renal changes during this period (since blocking angiotensin II activation by the prevention of renin release, or by inhibiting the conversion enzyme, did not prevent a substantial decrease in RBF or GFR during that period). Preventing angiotensin II activation did, however, prevent renal changes during aortic clamping. This beneficial effect did not establish a primary role for angiotensin during that period, since the favourable influence could also (at least partially) be explained by prevention of the permissive influence of angiotensin on other vasoconstrictors and/or other vasodilatory influences of ACE inhibition and [1- blockade which are unrelated to angiotensin. This study did indicate that (at least partially) different mechanisms are responsible for the renal changes seen during aortic clamping, and after aortic unclamping. The second study explored the role of calcium in the renal pathophysiological changes during aortic clamping and after unclamping. The protective influence effected by the administration of a Ca2 + -blocker suggest the dependence of the renal vasoconstrictive and glomerular pathophysiological process( es) on the cellular influx of Ca2 + through voltage-gated channels. It unfortunately provides no definitive insight into the primary instigators of these processes. However, it does offer a clinically useful method of preventing these changes and protecting the kidney against ischemic injury during abdominal aortic surgery. The third component of the animal studies demonstrates the importance of the protective effect of renal prostaglandins during the specific experimental (and probably also the clinical) circumstances. Again, it does not provide definitive information on the mediators responsible for the renal changes, since the deleterious effects of numerous endogenous substances have previously been shown to be counterbalanced by intrarenal synthesis of prostaglandins under various experimental and clinical circumstances. The extent of the pathophysiological and ultrastructural changes which occurred under the influence of a NSAID does, however, suggest that these drugs should not be used under these clinical circumstances. The last component of the study provides evidence that angiotensin only plays a secondary/supplementary role in the renal pathophysiological process even during aortic clamping. This may explain the contradictory evidence regarding the potential beneficial effect of ACE inhibition (on renal hemodynamics and glomerular function) during abdominal aortic surgery (Licker et al. 1996, Colson et al. 1992a). Based on our studies, ACE inhibition can not be supported for this purpose.
AFRIKAANSE OPSOMMING: Akute nierversaking is met die uitsondering van kardiale sterftes, steeds die belangrikste patologiese proses wat geassosieer is met perioperatiewe mortaliteit in pasiënte wat opereer word vir abdominale aorta aneurismes. Die intraoperatiewe veranderinge in renale bloedvloei (NBV) en glomerulêre funksie is die afgelope 15 jaar ondersoek en gerapporteer in pasiënte- sowel as diere-modelle. Ten spyte van groot variasies in studie-populasies, meettegnieke en ontwerp van studies in die algemeen, dui 'n wesenlike hoeveelheid getuienis daarop dat infrarenale klemming van die aorta renale isgemie induseer, wat die oorsaak is van postoperatiewe akute nierversaking wanneer hierdie komplikasie voorkom. Dit is verbasend dat, ten spyte van sommige onlangse studies wat rapporteer oor 'n verskeidenheid farmakologiese ingrepe om intraoperatiewe renale isgemie te voorkom (met wisselende sukses), baie min oënskynlik gedoen is om die patogenese en die presiese patofisiologie van hierdie potensieel dodelike komplikasie te ontrafel. Hoewel verskeie outeurs die moontlikheid van hormonale betrokkenheid (veral renienangiotensien, antidiuretiese hormoon en katekolamiene) in hierdie proses suggereer, is die presiese rol van hierdie mediators nog nie op 'n gestruktureerde wyse ondersoek (of rapporteer) nie. In ons aanvanklike pasiënte-studie is renale hemodinamika en -funksie gemeet vanaf die preoperatiewe periode, gedurende die intra-operatiewe fase en tot minstens vier uur na ontklemming van die aorta. Serumkonsentrasies van relevante hormone is bepaal tydens elke metingsperiode waar renale parameters gemeet is, ten einde die moontlikheid van 'n temporale verwantskap tussen renale veranderinge en variasies in hormoonkonsentrasies te ondersoek. Die vermindering in NBV en glomerulêre filtrasiespoed (GFS) wat ons aangetoon het om saam te val met infrarenale aortaklemming, stem ooreen met resultate wat tevore deur ander navorsers publiseer is. Ons het aangetoon dat die inkorting van hierdie parameters voortduur tot minstens vier uur na aorta-ontklemming. Hierdie veranderinge is tevore slegs rapporteer vir periodes tot kort na aorta-ontklemming voor sluiting van die buikwond. Die feit dat die GFS steeds verlaag is met ontslag van hierdie pasiënte, skep rede tot kommer, veral in pasiënte wat alreeds ingekorte nierfunksie het voor die chirurgiese prosedure. Van die gemete hormone wat moontlik 'n invloed sou kon uitoefen op NBV eh nefronfunksie, was renien die enigste waarvan verandering in plasmakonsentrasies saamgeval het met die onderdrukking van NBV en GFS na aortaklemming. Die ontwerp van ons studie het ons nie toegelaat om 'n besliste uitspraak te maak of die geassosieerde verhoging in angiotensien II primêr verantwoordelik was vir die verandering in renale hemodinamika, of dat die verhoogde renien (en angiotensien) bloedvlakke moontlik sekondêr stimuleer is deur die verandering in NBV wat deur 'n ander meganisme induseer is. In 'n ander pasiëntegroep het ons aangetoon dat die kombinasie van mannitol en dopamien geen beskerming verleen het teen die nadelige effekte van aorta-klemming nie. Die groot volumes uriene wat uitgeskei is onder die invloed van hierdie middels (wat nie korreleer het met NBV tydens ooreenstemmende periodes nie), het inderwaarheid 'n ontoepaslike gerustheid uitgelok. Weens die ooglopende gebrek aan objektiewe voordeel wat verleen word deur hierdie middels, behoort hulle gebruik tydens hierdie kliniese omstandighede ontmoedig te word. Die doel van die diere studies was die identifisering van die presiese rol van angiotensien in die patogenese en patofisiologie van die renale veranderinge geassosieer met infrarenale aortaklemming, sowel as die interaksie van angiotensien met ander modulators waarvoor 'n interaktiewe verwantskap voorheen beskryf is onder eksperimentele en/of kliniese omstandighede. Die eerste studie het getoon dat alhoewel renien (en dus angiotensien) konsentrasies hoog was na aorta-ontklemming, die hormone geen betekenisvolle patogenetiese of patofisiologiese rol in die waargenome renale veranderinge gedurende hierdie periode het nie (aangesien blokkade van angiotensien aktivering deur voorkoming van renien vrystelling, of deur inhibisie van angiotensien omsettingsensiem (AOE), nie 'n daling in NBV of GFS kon voorkom nie). Voorkoming van angiotensien II aktivering het egter wel renale verandering voorkom gedurende aortaklemming. Dié voordelige effek het nie 'n primêre rol vir angiotensien gedurende die periode bevestig nie, aangesien die gunstige invloed ook (ten minste gedeeltelik) verduidelik kon word deur die voorkoming van die fassiliterende invloed van angiotensien op ander vasokonstriktore en/of ander vasodilator-invloede van die onderdrukking van AOE en ïs-blokkers (wat geen verband het met angiotensien of die blokkade daarvan nie). Die studie het aangetoon dat (ten minste gedeeltelik) verskillende meganismes verantwoordelik is vir renale veranderinge wat gesien is gedurende aortaklemming en na -ontklemming. Die tweede studie het die rol van kalsium in die renale patofisiologiese veranderinge gedurende aortaklemming en na ontklemming ondersoek. Die beskermende invloed wat deur die toediening van Ca2 + -blokkers bewerkstellig is, het bevestig dat die renale vasokonstriktoriese en glomerulêre patofisiologiese prosesse afhanklik is van sellulêre influks van kalsium deur spannings-afhanklike kannale. Dit het ongelukkig geen definitiewe insig verleen ten opsigte van die primêre inisieerders van die proses nie. Dit verskaf nogtans 'n bruikbare kliniese metode om daardie veranderinge te voorkom en die niere teen isgemiese besering gedurende abdominale aorta-chirurgie te beskerm. Die derde komponent van die diere-studies demonstreer die belangrikheid van die beskermende effek van renale prostaglandiene tydens die spesifieke eksperimentele (en waarskynlik ook die kliniese) omstandighede. Weereens gee dit nie definitiewe inligting oor die bemiddelaars wat verantwoordelik is vir die renale veranderinge nie, aangesien die skadelike effekte van verskeie endogene stowwe voorheen aangetoon is om beperk of voorkom te word deur die intrarenale vrystelling van prostaglandiene. Die omvang van die patofisiologiese en ultrastrukturele veranderinge wat ontstaan het onder die invloed van nie-steroïed anti-inflammatoriese middels (wat gebruik is om prostaglandien sintese te inhibeer), dui aan dat hierdie middels vermy moet word onder soortelyke kliniese omstandighede. Die laaste komponent van die studie verskaf 'n sterk aanduiding dat angiotensien slegs 'n sekondêre/aanvullende rol speel in die renale patofisiologiese proses, selfs gedurende aortaklemming. Dit mag die weersprekende getuienis oor die potensiële voordeel van AOE onderdrukking (op renale hemodinamika en glomerulêre funksie) gedurende abdominale aortachirurgie (Licker et al. 1996, Colson et al. 1992a) verklaar. Gebaseer op ons studies, kan AOE onderdrukking nie ondersteun word vir hierdie doel nie.

In plastic surgery, flap reconstruction has been utilised to repair defects in every part of the body, in an effort to restore form and function to patients. The basis of every flap is its blood supply, therefore this series of studies investigates the vascular territory of named arteries, veins and even perforators, utilizing computer tomography (CT) and TeraRecon software. The latter two is technology which allows appreciation of vascular flow in 3D and 4D (dynamic studies), whereas previous studies of vascularity has only been static and in 2D. Vascular anatomy studies were performed using fresh cadavers. Perforator flaps on the anterior trunk studied were the internal mammary artery perforator (IMAP) flap, the transverse rectus abdominis musculocutaneous (TRAM) flap, the deep inferior epigastric artery perforator (DIEP) flap and the superficial inferior epigastric artery (SIEA) flap. Posterior trunk flaps included the posterior intercostal artery perforator flap, the lumbar artery perforator flap and the superior gluteal artery perforator (SGAP) flap. In the upper extremity, we studied the supraclavicular artery perforator flap. In the lower extremity, we studied the gracilis musculocutaneous flap. Trends and characteristics are noted in the vascular analyses, and four major principles drawn are discussed in the last chapter.

There is a significant need for small diameter vascular grafts to be used in peripheral vascular surgery; however autologous grafts are not always available, synthetic grafts perform poorly and allografts and xenografts degenerate, dilate and calcify after implantation. We hypothesized that chemical stabilization of acellular xenogenic arteries would generate off-the-shelf grafts resistant to thrombosis, dilatation and calcification. To test this hypothesis, we decellularized porcine renal arteries, stabilized elastin with pentagalloyl glucose and collagen with carbodiimide/activated heparin and implanted them as trans- position grafts in the abdominal aorta of rats as direct implants and separately as indirect, isolation-loop implants. All implants resulted in high patency and animal survival rates, ubiquitous encapsulation within a vascularized collagenous capsule, and exhibited lack of lumen thrombogenicity and no graft wall calcification. Peri-anastomotic neo-intimal tissue overgrowth was a normal occurrence in direct implants; however this reaction was circumvented in indirect implants. Notably, implantation of non- treated control scaffolds exhibited marked graft dilatation and elastin degeneration; however PGG significantly reduced elastin degradation and prevented aneurismal dilatation of vascular grafts. Overall these results point to the outstanding potential of crosslinked arterial scaffolds as small diameter vascular grafts.

Vascular surgery is an increasingly data rich speciality. Planning treatment and assessing outcomes are highly dependent on objective assessment of number of imaging modalities including duplex ultrasound, CT scans and angiograms which are almost exclusively digitally created stored and accessed. Developments such as the national vascular registry mean that treatment outcomes are recorded scrutinised electronically. The widespread availability of data which is collected electronically and stored for future clinical use has created the opportunity to examine the efficacy of investigations and treatments in a way which has hitherto not been possible. In addition, new computational methods for data analysis have provided the opportunity for the clinicians and researchers to utilise this data to address pertinent clinical questions.

The educational medium GetWellNetWork (GWNW) in a large magnet teaching facility offered few educational videos specific to vascular patients with a focus on leg elevation after lower extremity bypass surgery. Supplying patient-specific education has the potential for providing cost-effective nursing care to vascular patients and improving hospital reimbursement. Guided by the interactive care model, a storyboard was developed using best-practice evidence for vascular postoperative patients that could lead to the development of a video to address the educational needs of vascular patients upon discharge. The practice focused question asked if a video addressing the importance of leg elevation would improve patients’ use of in-house educational videos and stakeholder satisfaction. A vascular physician (n = 1) and nursing staff (n = 9) provided feedback on the appropriateness of the evidence-based educational content for the storyboard by completing a 9-item, open-ended survey. Survey results supported development of the video and revealed positive feedback on storyboard content and that staff with 1–3 years’ experience or 15+ years’ experience had an increased understanding of the importance of evidence-based guidelines for leg elevation for vascular patients. The feedback will be used to develop a vascular-patient-specific educational video. Encouraging patients to view the video on leg elevation has the potential to improve cost effectiveness of patient care and hospital reimbursement, prevent hospital readmission that could lead to patient and caregiver hardships associated with readmission, and improve the health outcomes for postoperative vascular patients.

Made available in DSpace on 2014-06-11T19:31:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-08-03Bitstream added on 2014-06-13T20:22:22Z : No. of bitstreams: 1 rubira_cj_dr_botfm.pdf: 240856 bytes, checksum: 5f30f1a1d2ce6492fd56a190c587cfc5 (MD5)
Universidade Estadual Paulista (UNESP)
A Coarctação da aorta (CoA) é responsável por 5% a 7% das cardiopatias congênitas, com uma incidência de 0,3 a 0,4 por 1000 nascidos vivos. A cirurgia foi a única forma de terapia para CoA até 1982, quando a angioplastia tornou-se uma alternativa disponível para o seu tratamento. Recoarctação, aneurisma e dissecção da aorta permaneceram desvantagens de ambos os tratamentos. Para evitar estes inconvenientes, em 1990, endopróteses vasculares foram introduzidas para coarctação nativa e recoarctação e desde então, tornaramse uma abordagem alternativa. A melhor abordagem para o tratamento da CoA, se cirurgia aberta ou a colocação de endoprótese vascular, não está estabelecida. Analisar a efetividade e a segurança da colocação de endoprótese vascular em comparação com a cirurgia aberta em pacientes com CoA. O Grupo Peripheral Vascular Diseases da Cochrane realizou a busca em seu Registro Especializado (última busca Setembro de 2011) e na Central (2011, nº 3). Nós também procuramos em MEDLINE, EMBASE, CINAHL, AMED, Web of Science e LILACS (última busca em setembro de 2011). Foram avaliadas as referências encontradas e aplicados os critérios de inclusão para os estudos selecionados. Não houve restrição de linguagem. Ensaios clínicos controlados aleatorizados ou quase-aleatorizados que compararam pacientes com CoA submetidos a cirurgia aberta ou a colocação de endoprótese vascular. Os autores da revisão avaliaram independentemente os estudos identificados para a elegibilidade de inclusão. Nós excluímos estudos após reunião de consenso. Os critérios de seleção foram aplicados para avaliação do título e resumo de todos os estudos identificados. No total, foram selecionados cinco estudos para a análise de texto completo. Após avaliação detalhada, foram excluídos todos os estudos porque não havia...
Coarctation of the aorta (CoA) accounts for 5% to 7% of congenital heart disease, with an incidence of 0.3 to 0.4 per 1000 live births. Surgery was the only choice of therapy for CoA until 1982 when balloon angioplasty became an available alternative for its treatment. Re-coarctation, aneurysm and aortic dissection remain the disadvantages of both treatments. To avoid those disadvantages, in 1990 endovascular stents were introduced for native coarctation and re-coarctation and since then they have become an alternative approach to surgical repair. The best approach to treat the CoA, whether open surgery or by stent placement, is not clear. To analyze the effectiveness and safety of stent placement compared with open surgery in patients with coarctation of the thoracic aorta. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched September 2011) and CENTRAL (2011, Issue 3).We also searched MEDLINE, EMBASE, CINAHL, AMED, Web of Science and LILACS (last searched in September 2011). We evaluated the located references and applied the inclusion criteria to selected studies. There was no restriction on language. Randomized or quasi-randomized controlled clinical trials that compared patients with CoA undergoing open surgery or stent placement. The review authors independently assessed the studies identified for eligibility for inclusion. We excluded studies after a consensus meeting. All identified studies were screened and had the selection criteria applied to the title and abstract. In total, we selected five studies for full-text analysis. After detailed evaluation, we excluded all studies because there was no comparison between stent placement and open surgery. There is insufficient evidence with regards to the best treatment for coarctation of the thoracic aorta. This review... (Complete abstract click electronic access below)

Orientador: Paulo Eduardo de Oliveira Carvalho
Coorientador: Antônio José Maria Catâneo
Banca: Luiz Eduardo Villaça Leão
Banca: Marcos Augusto Moraes Silva
Banca: Olavo Ribeiro Rodrigues
Banca: Rúbio Bombonato
Resumo: A Coarctação da aorta (CoA) é responsável por 5% a 7% das cardiopatias congênitas, com uma incidência de 0,3 a 0,4 por 1000 nascidos vivos. A cirurgia foi a única forma de terapia para CoA até 1982, quando a angioplastia tornou-se uma alternativa disponível para o seu tratamento. Recoarctação, aneurisma e dissecção da aorta permaneceram desvantagens de ambos os tratamentos. Para evitar estes inconvenientes, em 1990, endopróteses vasculares foram introduzidas para coarctação nativa e recoarctação e desde então, tornaramse uma abordagem alternativa. A melhor abordagem para o tratamento da CoA, se cirurgia aberta ou a colocação de endoprótese vascular, não está estabelecida. Analisar a efetividade e a segurança da colocação de endoprótese vascular em comparação com a cirurgia aberta em pacientes com CoA. O Grupo Peripheral Vascular Diseases da Cochrane realizou a busca em seu Registro Especializado (última busca Setembro de 2011) e na Central (2011, nº 3). Nós também procuramos em MEDLINE, EMBASE, CINAHL, AMED, Web of Science e LILACS (última busca em setembro de 2011). Foram avaliadas as referências encontradas e aplicados os critérios de inclusão para os estudos selecionados. Não houve restrição de linguagem. Ensaios clínicos controlados aleatorizados ou quase-aleatorizados que compararam pacientes com CoA submetidos a cirurgia aberta ou a colocação de endoprótese vascular. Os autores da revisão avaliaram independentemente os estudos identificados para a elegibilidade de inclusão. Nós excluímos estudos após reunião de consenso. Os critérios de seleção foram aplicados para avaliação do título e resumo de todos os estudos identificados. No total, foram selecionados cinco estudos para a análise de texto completo. Após avaliação detalhada, foram excluídos todos os estudos porque não havia... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Coarctation of the aorta (CoA) accounts for 5% to 7% of congenital heart disease, with an incidence of 0.3 to 0.4 per 1000 live births. Surgery was the only choice of therapy for CoA until 1982 when balloon angioplasty became an available alternative for its treatment. Re-coarctation, aneurysm and aortic dissection remain the disadvantages of both treatments. To avoid those disadvantages, in 1990 endovascular stents were introduced for native coarctation and re-coarctation and since then they have become an alternative approach to surgical repair. The best approach to treat the CoA, whether open surgery or by stent placement, is not clear. To analyze the effectiveness and safety of stent placement compared with open surgery in patients with coarctation of the thoracic aorta. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched September 2011) and CENTRAL (2011, Issue 3).We also searched MEDLINE, EMBASE, CINAHL, AMED, Web of Science and LILACS (last searched in September 2011). We evaluated the located references and applied the inclusion criteria to selected studies. There was no restriction on language. Randomized or quasi-randomized controlled clinical trials that compared patients with CoA undergoing open surgery or stent placement. The review authors independently assessed the studies identified for eligibility for inclusion. We excluded studies after a consensus meeting. All identified studies were screened and had the selection criteria applied to the title and abstract. In total, we selected five studies for full-text analysis. After detailed evaluation, we excluded all studies because there was no comparison between stent placement and open surgery. There is insufficient evidence with regards to the best treatment for coarctation of the thoracic aorta. This review... (Complete abstract click electronic access below)
Doutor

The work presented includes over thirty peer reviewed published manuscripts based on studies undertaken during my surgical career. As Principal Investigator, I led the study conception/design/data acquisition/analysis/interpretation and was involved with writing the final drafts of all manuscripts prior to their formal submission to high impact factor peer-reviewed specialist journals. The thesis is divided into subsections reflecting my development and different interests within surgery. The subsections start with my learning basic research principles, moving onto clinical problem solving in general surgical dilemmas, followed by a collection of papers in my subspecialty of vascular surgery. The work culminates with a group of papers focused on aneurysmal disease, specifically, abdominal aortic aneurysms (AAA), the clinical impact of which has had a bearing on the introduction of a National AAA Screening Program in Wales in 2013. I conclude these sections with a collection of papers that reflect my long term commitment to surgical training both at regional level (as Secretary and Deputy Chairman to the Higher Surgical Training Committee and Chairman of the Basic Surgical Training Committee) and national level including my involvement with the Four Royal Colleges of Surgeons for the Intercollegiate Examinations in General Surgery. This examination is undertaken at completion of junior surgical training and used to confirm a doctor's competence for safe independent practice as a consultant. In conclusion, over forty years of academic research during my career as a vascular surgeon has provided unique insight into the pathophysiology, treatment and ultimately prevention of artherosclerotic disease. These findings have improved health policies in Wales and significantly reduced patient morbidity and mortality.

Congenital heart disease (CHO) affects 1 % of live births, and remains the primary cause of death among infants in North America and Europe. In congenital heart defect corrective surgery, the commonly used prosthetic replacement grafts have limited durability and often require repeat operations because of their lack of growth potential. Using the child's autologous stem cells to produce tissue engineered vascular grafts holds promise for the creation of living grafts for surgery. It is therefore essential to identify a readily available autologous stem cell source that is able to produce sufficient functional endothelial cells (ECs) and vascular smooth muscle cells (SMCs) for vascular tissue regeneration. Human endothelial progenitor cells (UCB-EPCs) and mesenchymal stem cells (UCBMSCs) were isolated from umbilical cord blood by density gradient centrifugation and selective medium incubation. Meanwhile, another type of multipotent stem cells (WJPVCs) were isolated from perivascular regions among the umbilical cord by outgrowth methods. Functional EC were derived from UCB-EPCs and characterised by their surface markers and angiogenesis assay. UCB-MSCs and WJPVCs were induced by TGF-β1 to differentiate into SMC like cells, which also obtained a similar SMC phenotype. These matured cells showed great cell-matrix compatibility, satisfactory proliferative ability, when seeded onto a decellularised scaffold. Porcine EPCs and MSCs were isolated from newborn piglet peripheral blood by a similar methodology derived human UCB-EPCs and UCB-MSCs. The matured vascular cells derived from these porcine stem cells were applied in constructing a dual cell seeded tissue engineered conduit. The graft was implanted into the left pulmonary of a 30kg weight piglet, and then harvested 3 months later. Immunohistological tests revealed that the graft had a good patency, had been well integrated with adjacent artery tissues and was able to form natural-artery like structure, including endothelium and media SMC-like layers. These results revealed that perinatal tissue is a viable readily available source of autologous stem cells for use in generating living tissue engineered vascular graft for paediatric congenital heart surgery.