Cell Viability Assessment Using Fluorescence Vital Dyes and Confocal Microscopy in Evaluating Freezing and Thawing Protocols Used in Cryopreservation of Allogeneic Venous Grafts.

The authors present their contribution to the improvement of methods suitable for the detection of the freezing and thawing damage of cells of cryopreserved venous grafts used for lower limb revascularization procedures. They studied the post-thaw viability of cells of the wall of cryopreserved venous grafts (CVG) immediately after thawing and after 24 and 48 h culture at +37 °C in two groups of six CVG selected randomly for slow thawing in the refrigerator and rapid thawing in a water bath at +37 °C. The grafts were collected from multi-organ and tissue brain-dead donors, cryopreserved, and stored in a liquid nitrogen vapor phase for five years. The viability was assessed from tissue slices obtained by perpendicular and longitudinal cuts of the thawed graft samples using in situ staining with fluorescence vital dyes. The mean and median immediate post-thaw viability values above 70% were found in using both thawing protocols and both types of cutting. The statistically significant decline in viability after the 48-h culture was observed only when using the slow thawing protocol and perpendicular cutting. The possible explanation might be the "solution effect damage" during slow thawing, which caused a gentle reduction in the graft cellularity. The possible influence of this phenomenon on the immunogenicity of CVG should be the subject of further investigations.

Saphenous vein valve assessment utilizing upright CT to potentially improve graft assessment for bypass surgery.

Saphenous veins (SVs) are frequently employed as bypass grafts. The SV graft failure is predominantly seen at the valve site. Avoiding valves during vein harvest would help reduce graft failure. We endeavored to detect SV valves, tributaries, and vessel size employing upright computed tomography (CT) for the raw cadaver venous samples and in healthy volunteers. Five cadaver legs were scanned. Anatomical analysis showed 3.0 (IQR: 2.0-3.0) valves and 13.50 (IQR: 10.00-16.25) tributaries. The upright CT completely detected, compared to 2.0 (IQR: 1.5-2.5, p = 0.06) valves and 9.5 (IQR: 7.5-13.0, p = 0.13) tributaries by supine CT. From a total of 190 volunteers, 138 (men:75, women:63) were included. The number of valves from the SF junction to 35 cm were significantly higher in upright CT than in supine CT bilaterally [upright vs. supine, Right: 4 (IQR: 3-5) vs. 2 (IQR:1-2), p < 0.0001, Left: 4 (IQR: 3-5) vs. 2 (IQR: 1-2), p < 0.0001]. The number of tributaries and vessel areas per leg were also higher for upright compared with supine CT. Upright CT enables non-invasive detection of SV valves, tributaries, and vessel size. Although not tested here, it is expected that upright CT may potentially improve graft assessment for bypass surgery.

Contemporary Treatment of Popliteal Artery Aneurysms in 14 Countries: A Vascunet Report.

OBJECTIVE: Popliteal artery aneurysm (PAA) is the second most common arterial aneurysm. Vascunet is an international collaboration of vascular registries. The aim was to study treatment and outcomes. METHODS: This was a retrospective analysis of prospectively registered population based data. Fourteen countries contributed data (Australia, Denmark, Finland, France, Hungary, Iceland, Italy, Malta, New Zealand, Norway, Portugal, Serbia, Sweden, and Switzerland). RESULTS: During 2012-2018, data from 10 764 PAA repairs were included. Mean values with between countries ranges in parenthesis are given. The incidence was 10.4 cases/million inhabitants/year (2.4-19.3). The mean age was 71.3 years (66.8-75.3). Most patients, 93.3%, were men and 40.0% were active smokers. The operations were elective in 73.2% (60.0%-85.7%). The mean pre-operative PAA diameter was 32.1 mm (27.3-38.3 mm). Open surgery dominated in both elective (79.5%) and acute (83.2%) cases. A medial surgical approach was used in 77.7%, and posterior in 22.3%. Vein grafts were used in 63.8%. Of the emergency procedures, 91% (n = 2 169, 20.2% of all) were for acute thrombosis and 9% for rupture (n = 236, 2.2% of all). Thrombosis patients had larger aneurysms, mean diameter 35.5 mm, and 46.3% were active smokers. Early amputation and death were higher after acute presentation than after elective surgery (5.0% vs. 0.7%; 1.9% vs. 0.5%). This pattern remained one year after surgery (8.5% vs. 1.0%; 6.1% vs. 1.4%). Elective open compared with endovascular surgery had similar one year amputation rates (1.2% vs. 0.2%; p = .095) but superior patency (84.0% vs. 78.4%; p = .005). Veins had higher patency and lower amputation rates, at one year compared with synthetic grafts (86.8% vs. 72.3%; 1.8% vs. 5.2%; both p < .001). The posterior open approach had a lower amputation rate (0.0% vs. 1.6%, p = .009) than the medial approach. CONCLUSION: Patients presenting with acute ischaemia had high risk of amputation. The frequent use of endovascular repair and prosthetic grafts should be reconsidered based on these results.

Editor's Choice - Sex Related Differences in Peri-operative Mortality after Elective Repair of an Asymptomatic Abdominal Aortic Aneurysm in the Netherlands: a Retrospective Analysis of 2013 to 2018.

OBJECTIVE: The aim was to compare peri-operative (30 day and/or in hospital) mortality between women and men in the Netherlands after elective repair of an asymptomatic abdominal aortic aneurysm (AAA). METHODS: This was a retrospective study using data from the Dutch Surgical Aneurysm Audit (DSAA), a mandatory nationwide registry of patients undergoing AAA repair in the Netherlands. Patients who underwent elective open surgical (OSR) or endovascular aneurysm repair (EVAR) of an asymptomatic abdominal aortic aneurysm (AAA) between 2013 and 2018 were included. Absolute risk differences (ARDs) with 95% confidence intervals (CIs) in peri-operative mortality between women and men were estimated. Logistic regression analyses were performed to estimate adjusted odds ratios (ORs) for mortality. Confounders included pre-operative cardiac and pulmonary comorbidity, serum haemoglobin, serum creatinine, type of AAA repair, and AAA diameter. RESULTS: Some 1662 women and 9637 men were included, of whom 507 (30.5%) women and 2056 (21.3%) men underwent OSR (p < .001). Crude peri-operative mortality was 3.01% in women and 1.60% in men (ARD = 1.41%, 95% CI 0.64-2.37). This significant difference was also observed for OSR (ARD = 2.63%, 95% CI 0.43-5.36), but not for EVAR (ARD = 0.36%, 95% CI -0.16 to 1.17). Female sex remained associated with peri-operative mortality after adjusting for confounders (OR = 1.79, 95% CI 1.20-2.65, p = .004), which was similarly observed for OSR (OR = 1.85, 95% CI 1.16-2.94, p = .01), but not for EVAR (OR = 1.46, 95% CI 0.72-2.95, p = .29). CONCLUSIONS: Peri-operative mortality after elective repair of an asymptomatic AAA in the Netherlands is higher in women than in men. This disparity might be explained by the higher peri-operative mortality in women undergoing OSR, because no such difference was found in patients undergoing EVAR. Yet, it is likely that there are unaccounted factors at play since female sex remained significantly associated with mortality after adjusting for type of repair.

Frailty assessment in older adults undergoing interventions for peripheral arterial disease.

OBJECTIVE: Frailty is a multidimensional syndrome that influences postoperative morbidity and mortality after vascular procedures; however, its integration in clinical practice has been limited, given the lack of consensus on how to measure it. This study sought to compare the incremental predictive value of six different nonphysical performance frailty scales to predict poor outcomes after interventions for peripheral arterial disease (PAD). METHODS: This preplanned analysis of the FRailty Assessment In Lower Extremity arterial Disease (FRAILED) prospective cohort included two centers recruiting patients between July 1, 2015, and October 1, 2016. Individuals who underwent vascular interventions for Rutherford class 3 or higher PAD were enrolled. The following scales were compared: Edmonton Frail Scale, Groningen Frailty Indicator (GFI), modified Essential Frailty Toolset (mEFT), modified Frailty Index, Multidimensional Prognostic Index, and the Risk Analysis Index-C. The primary end point was a composite of all-cause mortality and major disability at 12 months after the procedure. The secondary end point was length of stay. Logistic regression was used to determine the association of frailty with the primary end point after adjusting for confounders. To compare the incremental predictive value of each frailty scale, model performance statistics were calculated. RESULTS: The cohort was composed of 148 patients with a mean age of 70 years. Depending on the scale used, the prevalence of frailty ranged from 16% to 70%. Frailty as measured by the GFI (adjusted odds ratio, 1.76; 95% confidence interval, 1.14-2.72) and mEFT (adjusted odds ratio, 2.71; 95% confidence interval, 1.29-5.73) predicted mortality and worsening disability at 12 months after interventions for PAD. Furthermore, there was statistically significant C-statistic, Bayesian information criterion, and integrated discrimination improvement when the GFI and mEFT were added to the baseline model. Frailty was not associated with length of stay. CONCLUSIONS: Frailty is associated with mortality and worsening disability after interventions for PAD. The GFI and mEFT performed well and identified vulnerable older adults who are at risk of poor outcomes after interventions for PAD and recommended for use in this setting.

[Use of contrast-enhanced ultrasound for assessment of the state of femoropopliteal bypass graft anastomoses]. / Primenenie kontrastnoi sonografii dlia otsenki sostoianiia anastomozov bedrenno-podkolennykh shuntov.

Analysed herein is the experience of the first eight ultrasonographic studies of peripheral arteries with dynamic contrast enhancement using sulphur hexafluoride («SonoVue¼) carried out in patients after previously performed femoropopliteal bypass grafting with a synthetic prosthesis (in seven cases the distal anastomosis of the bypass graft was located below the fissure of the knee joint and in one case - above the fissure of the knee joint). Contrast-enhanced ultrasonography was performed averagely 12.5±4.0 months after the operation, according to the technique recommended by the manufacturer of the contrast agent. It was demonstrated that control ultrasonic scanning of lower-limb arteries using contrast enhancement in the remote period after bypass operations proved more informative in relation to detection of stenoses of the distal anastomosis of the femoropopliteal bypass graft, trifurcation of the popliteal artery and near-ostium segments of tibial arteries than a study with no contrast medium.

Comparison of Outcomes and Cost of Endovascular Management Versus Surgical Bypass for the Management of Lower Extremities Peripheral Arterial Disease.

The management of lower extremities peripheral arterial disease (LE-PAD) has always been debatable. We sought to explore in-hospital outcomes in hospitalizations that underwent endovascular or bypass surgery for LE-PAD from nation's largest, publicly available database. The National Inpatient Sample from 2012 to 2014 was queried to identify adult hospitalizations underwent endovascular management and bypass surgery for LE-PAD. Appropriate International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic and procedural codes were utilized to identify hospitalizations. A total of 89,256 hospitalizations were identified having endovascular management or bypass surgery for LE-PAD. More hospitalizations underwent endovascular intervention as compared with bypass surgery. Overall, hospitalizations for endovascular management had higher baseline co-morbidities and older age. A propensity score matched analysis was performed to compare in-hospital outcomes. After matching, 28,791 hospitalizations were included in each group. In-hospital mortality was significantly lower with endovascular intervention procedure as compared with surgical bypass group (1.5% vs 2.5%, p ≤0.001). All other secondary outcomes were noted lower with endovascular management except stroke and postprocedural infection. Taken together, these may account for higher discharges to home, lower length of stay, and less cost of hospitalizations associated with endovascular management. In conclusion, endovascular management is associated with lower in-hospital morbidity, mortality, length of stay, and cost when compared with bypass surgery in this study.

Organization model for allotransplantations of cryopreserved vascular grafts in Czech Republic.

The transplantation of fresh or cryopreserved vascular allografts in patients with a prosthetic graft infection or critical limb ischemia is necessary for their limb salvage and, in many cases, represents a lifesaving procedure. While transplantation of fresh allografts has a long history in the Czech Republic, the standard use of cryopreserved vascular allografts was introduced into the clinical practice in 2011 as a result of the implementation of EU Directive 2004/23/EC into national legislation (Human Cell and Tissue Act No. 296/2008 Coll.). The authors present an organizational model based on cooperation between the majority of Czech Transplant Centers with a tissue establishment licensed by the national competent authority. In various points, we are addressing individual aspects of experimental and clinical studies which affect clinical practice. Based on experimental and clinical work, the first validation of cryopreserved arterial and venous grafts for clinical use was performed between 2011 and 2013. The growing number of centers participating in this programme led to a growing number of patients who underwent transplantation of vascular allografts. In 2015 the numbers of transplanted fresh versus cryopreserved allografts in the Czech Republic were almost equal. Cooperation of the participating centers in the Czech Republic with the licensed Tissue Establishment made it possible to achieve a full compliance with the European Union Directives, and harmonized national legal norms and assured a high quality of cryopreserved vascular allografts.

Pilot Assessment of the Angiosome Concept by Intra-operative Fluorescence Angiography After Tibial Bypass Surgery.

OBJECTIVES: The "angiosome" concept as a model for decision making in revascularisation of patients with critical limb ischaemia (CLI) has been subject to lively discussion in recent years. The aim of this prospective pilot study was to use intra-operative fluorescence angiography to provide further data on the angiosome concept on the level of microcirculation after tibial bypass surgery. DESIGN, MATERIALS, AND METHODS: This was a prospective analysis of 40 patients presenting with CLI Rutherford stage IV to VI before and after tibial bypass surgery. The macrocirculation was measured by the ankle brachial index. Skin microcirculation was assessed by intra-operative fluorescence angiography. The alteration of microcirculation was compared in direct and indirect revascularised angiosomes. Clinical follow-up investigations were performed and the wound healing rate was compared between the different revascularisation methods. RESULTS: Cumulated microcirculation parameters showed a significant improvement after surgery (ingress, ingress rate p<.001). Likewise, general microcirculatory improvement was observed in each foot angiosome after revascularisation, regardless of the tibial artery revascularised. Furthermore, a comparison of the direct (DR) and the indirect revascularised (IR) angiosomes did not show a significant difference concerning the improvement of microcirculation (difference DR-IR, ingress: 1.69, 95% CI 71.73-75.11; ingress rate: 0.08, 95% CI -12.91 to 13.07). The wound healing rate was similar in both groups, although the time to wound healing was faster by on average 2.5 months in the DR group (p=.083). CONCLUSION: Microcirculatory improvement was seen over the whole foot after tibial bypass. Therefore, fluorescence angiography is a promising tool to evaluate the angiosome concept in future larger studies. Clinicaltrials.gov: NCT03012750.

Assessment of the Temporopolar Artery as a Donor Artery for Intracranial-Intracranial Bypass to the Middle Cerebral Artery: Anatomic Feasibility Study.

BACKGROUND: Intracranial-intracranial bypass is a valuable cerebral revascularization option. Despite several advantages, one of the main shortcomings of the intracranial-intracranial bypass is the possibility of ischemic complications of the donor artery. However, when sacrificed, the temporopolar artery (TPA) is not associated with major neurologic deficits. We sought to define the role of TPA as a donor for revascularization of the middle cerebral artery (MCA). METHODS: Pterional craniotomy was performed on 14 specimens. The TPA was released from arachnoid trabecula, and the small twigs to the temporal lobe were cut. The feasibility of side-to-side and end-to-side bypass to the farthest arterial targets on insular, opercular, and cortical MCA branches was assessed. The distance of the bypass point was measured in reference to limen insulae. RESULTS: A total of 15 TPAs were assessed (1 specimen had 2 TPAs). The average cisternal length of the TPA was 37.3 mm. For side-to-side bypass, the TPA was a poor candidate as an intracranial donor, except for the cortical orbitofrontal artery, which was reached in 87% of cases. However, the end-to-side bypass was successfully completed for most arteries (87%-100%) on the anterior frontal operculum and more than 50% of the cortical or opercular middle and posterior temporal arteries. There was no correlation between the TPA's cisternal length and maximum bypass reach. CONCLUSIONS: When of favorable diameter, the TPA is a competent donor for intracranial-intracranial bypass to MCA branches at the anterior insula, and anterior frontal and middle temporal opercula (arteries anterior to the precentral gyrus coronal plane).

[Assessment of surgical risk in patients with lower limb chronic critical ischaemia]. / Otsenka khirurgicheskogo riska u bol'nykh s khronicheskoi kriticheskoi ishemiei nizhnikh konechnostei.

Analysed herein are both immediate and remote results of surgical treatment of 93 patients presenting with chronic atherosclerotic occlusion of the femoral-popliteal-tibial segment in the stage of critical ischaemia. The patients were subjected to autovenous femoropopliteal bypass grafting to the isolated arterial segment or balloon angioplasty with stenting of the superficial femoral artery. While choosing the method of arterial reconstruction we assessed concomitant diseases, primarily lesions of the coronary and cerebral circulation. In order to objectively evaluate the patient state, we worked out a scale for assessing surgical risk. Survival rate without amputation after three years in patients with low risk amounted to 71.4%, in those with moderate risk to 60.0%, and in high-risk patients to 43.3%. Patients with initially high risk were found to have a high incidence rate of cardiac and cerebrovascular complications, exceeding 40%. It was shown that the worked out system of assessing the level of surgical risk objectively reflects the prognosis of patient survival following a reconstructive operation. This system of assessment may be appropriate while choosing an optimal method of arterial reconstruction (bypassing operation or endovascular intervention) in patients with atherosclerotic lesions of arteries of the femoropopliteal-tibial segment and critical ischaemia accompanied by severe concomitant pathology. Patients with high surgical risk should preferably be subjected to endovascular reconstruction, while those with low surgical risk should better undergo open shunting bypassing operation, and for those with moderate risk it is acceptable to perform both methods of arterial reconstruction.

4D flow MRI assessment of extracranial-intracranial bypass: qualitative and quantitative evaluation of the hemodynamics.

INTRODUCTION: Our aim was to assess the feasibility of using time-resolved 3D phase-contrast (4D flow) MRI to characterize extracranial-intracranial (EC-IC) bypass. METHODS: We enrolled 32 patients who underwent EC-IC bypass (15 men, 17 women; mean age 66.4 years). In all, 16 underwent radial artery graft (RAG) bypass and 16 underwent superficial temporal artery (STA) bypass. 4D flow MRI, time-of-flight (TOF) magnetic resonance angiography (MRA), and computed tomography angiography (CTA) were performed. Bypass patency, flow direction, and blood flow volume (BFV) of each artery were determined by 4D flow MRI. Arterial diameters were measured by TOF-MRA and CTA. We compared RAG and STA bypasses by evaluating the flow direction and BFV of each artery. We evaluated the correlation between arterial diameters (measured by CTA or MRA) and the BFV and the detectability of flow direction (measured by 4D flow MRI) of each artery. RESULTS: 4D flow MRI confirmed the patency of each bypass artery. Flow direction of the M1 segment of the middle cerebral artery and BFV in the bypass artery differed between RAG and STA groups (p < 0.01). BFV in the bypass slightly correlated with the diameters on CTA (p < 0.05, R (2) = 0.287). Of the 29 arteries in the circle of Willis, nine were not depicted on 4D flow MRI. Cutoff values for arterial diameters on CTA and TOF-MRA for detecting the artery on 4D flow MRI were 2.4 and 1.8 mm, respectively. CONCLUSION: 4D flow MRI provided unique information for characterizing EC-IC bypasses, although this detectability is limited when addressing small arteries with slow flow.

The assessment of collateral communication after hybrid repair for Crawford extent II thoraco-abdominal aortic aneurysms.

OBJECTIVES: The repair of extensive thoraco-abdominal aortic aneurysms (TAAAs) is invasive and carries a high risk for spinal cord injury (SCI). The aim of this study was to assess the early results and collateral circulation to the spinal cord after hybrid repair for Crawford extent II aortic aneurysms. METHODS: Between 1997 and 2013, we performed 128 thoracic endovascular aortic repair (TEVAR) procedures for TAAAs. This study reviews 12 patients who underwent hybrid TEVAR for a Crawford extent II aortic aneurysm (mean age: 56 years, 6 men, chronic dissection: 10). Aortic arch repair was performed to create a proximal landing zone and visceral debranching bypass was performed to create a distal landing zone at separate stages prior to TEVAR. Subsequently, a stent graft was deployed to cover the residual downstream aorta. TEVAR was generally performed the day after the final debranching procedure. Cerebrospinal fluid drainage was performed, and the mean blood pressure was maintained at >90 mmHg in all cases. RESULTS: The median operation time for TEVAR was 94 min (range: 71-421 min) and the mean blood loss was 300 ml (range: 130-1350 ml). No SCI or in-hospital death was observed after TEVAR. Multidetector computed tomography identified three arteries (subclavian artery, external iliac artery and internal iliac artery) providing collateral circulation to spinal segmental arteries (SAs). In all cases, mid-thoracic SAs (Th5-8) and low lumbar SAs (L2-5) were fed by the subclavian artery and the internal iliac artery, respectively. Additionally, low thoracic to high lumbar SAs (Th9-L1) communicated with the subclavian artery via the lateral thoracic wall and/or the external iliac artery via the abdominal wall. CONCLUSIONS: We achieved satisfactory early and mid-term outcomes with hybrid repair for Crawford extent II TAAAs. Furthermore, collateral circulation to SAs was maintained during and after TEVAR regardless of the extent of the aortic repair.

Three-year outcomes associated with embolic protection in saphenous vein graft intervention: results in 49 325 senior patients in the Medicare-linked National Cardiovascular Data Registry CathPCI Registry.

BACKGROUND: Information is limited on contemporary use and outcomes of embolic protection devices (EPDs) in saphenous vein graft interventions. METHODS AND RESULTS: We formed a longitudinal cohort (2005-2009; n=49 325) by linking National Cardiovascular Data Registry CathPCI Registry to Medicare claims to examine the association between EPD use and both procedural and long-term outcomes among seniors (65+ years), adjusting for clinical factors using propensity and instrumental variable methodologies. Prespecified high-risk subgroups included acute coronary syndrome and de novo or graft body lesions. EPDs were used in 21.2% of saphenous vein grafts (median age, 75; 23% women) and were more common in acute coronary syndrome (versus non-acute coronary syndrome; 22% versus 19%), de novo (versus restenotic; 22% versus 14%), and graft body lesions (versus aortic and distal anastomosis; 24% versus 20% versus 8%, respectively). EPDs were associated with a slightly higher incidence of procedural complications, including no reflow (3.9% versus 2.8%; P<0.001), vessel dissection (1.3% versus 1.1%; P=0.05), perforation (0.7% versus 0.4%; P=0.001), and periprocedural myocardial infarction (2.8% versus 1.8%; P<0.001). By 3 years, death, myocardial infarction, and repeat revascularization occurred in 25%, 15%, and 30% of cases, respectively. EPD use was associated with a similar adjusted risk of death (propensity score-matched hazard ratio, 0.96; 95% confidence interval, 0.91-1.02), myocardial infarction (propensity score-matched hazard ratio, 1.00; 95% confidence interval, 0.93-1.09), and repeat revascularization (propensity score-matched hazard ratio, 1.02; 95% confidence interval, 0.96-1.08) in the overall cohort and high-risk subgroups. CONCLUSIONS: In this contemporary cohort, EPDs were used more commonly among patients with high-risk clinical indications, yet there was no evidence of improved acute- or long-term outcomes. Further prospective studies are needed to support routine EPD use.

High pressure assessment of bilayered electrospun vascular grafts by means of an Electroforce Biodynamic System®.

INTRODUCTION: Tissue engineering offers the possibility of developing a biological substitute material in vitro with the inherent properties required in vivo. However, the inadequate performance in vascular replacement of small diameter vascular grafts (VG) reduces considerably the current alternatives in this field. In this study, a bilayered tubular VG was produced, where its mechanical response was tested at high pressure ranges and compared to a native femoral artery. MATERIALS AND METHOD: The VG was obtained using sequential electrospinning technique, by means of two blends of Poly(L-lactic acid) and segmented poly(ester urethane). Mechanical testing was performed in a biodynamic system and the pressure-strain relationship was used to determine the elastic modulus. RESULTS: Elastic modulus assessed value of femoral artery at a high pressure range (33.02×106 dyn/cm(2)) was founded to be 36% the magnitude of VG modulus (91.47×106 dyn/cm(2)) at the same interval. CONCLUSION: A new circulating mock in combination with scan laser micrometry have been employed for the mechanical evaluation of bioresorbable bilayered VGs. At same pressure levels, graft elasticity showed a purely "collagenic" behavior with respect to a femoral artery response.

Bioengineered vascular graft with autologous stem cells: first use in the clinic. Interview with Michael Olausson.

Michael Olausson talks to Regenerative Medicine about the pioneering clinical use of a bioengineered vascular graft to treat a 9-year-old girl with extrahepatic portal vein obstruction and the future potential of bioengineered vessels. Michael Olausson has been Professor of Transplantation Surgery at Gothenburg University (Gothenburg, Sweden) since 2000, and was Chairman of the Sahlgrenska Transplant Institute at Sahlgrenska University Hospital (Gothenburg, Sweden) between 1994 and June 2011. His scientific interests include transplant immunology and experimental and clinical transplantation studies. He has published over 240 original articles, reviews and book chapters in the field of transplantation. He has been invited as a speaker at several national and international meetings all over the world. He has pioneered several innovative surgical procedures in the Nordic countries, Europe and the rest of the world. Last year, he performed the first operation in the world using a stem cell-derived vein and recently he performed the two first mother-to-daughter live donor uterus transplantations in the world, together with a team from Gothenburg. In the past, he has been President of The Swedish Transplantation Society, and board member and Vice President of the European Liver and Intestinal Transplantation Association. In 2008 he received the Carl-Gustav Groth Scandinavian Transplant Prize.

Causes and implications of readmission after abdominal aortic aneurysm repair.

OBJECTIVE: To determine the frequency, causes, predictors, and consequences of 30-day readmission after abdominal aortic aneurysm (AAA) repair. BACKGROUND DATA: Centers for Medicare & Medicaid Services (CMS) will soon reduce total Medicare reimbursements for hospitals with higher-than-predicted 30-day readmission rates after vascular surgical procedures, including AAA repair. However, causes and factors leading to readmission in this population have never before been systematically analyzed. METHODS: We analyzed elective AAA repairs over a 2-year period from the CMS Chronic Conditions Warehouse, a 5% national sample of Medicare beneficiaries. RESULTS: A total of 2481 patients underwent AAA repair--1502 endovascular aneurysm repair (EVAR) and 979 open aneurysm repair. Thirty-day readmission rates were equivalent for EVAR (13.3%) and open repair (12.8%). Although wound complication was the most common reason for readmission after both procedures, the relative frequency of other causes differed-eg, bowel obstruction was common after open repair, and graft complication after EVAR. In multivariate analyses, preoperative comorbidities had a modest effect on readmission; however, postoperative factors, including serious complications leading to prolonged length of stay and discharge destination other than home, had a profound influence on the probability of readmission. The 1-year mortality in readmitted patients was 23.4% versus 4.5% in those not readmitted (P < 0.001). CONCLUSIONS: Early readmission is common after AAA repair. Adjusting for comorbidities, postoperative events predict readmission, suggesting that proactively preventing, detecting, and managing postoperative complications may provide an approach to decreasing readmissions, with the potential to reduce cost and possibly enhance long-term survival.

Changes in abdominal aortic aneurysm rupture and short-term mortality, 1995-2008: a retrospective observational study.

OBJECTIVE: To examine the modern epidemiology of abdominal aortic aneurysm (AAA) rupture and short-term AAA-related mortality after the introduction of endovascular aneurysm repair (EVAR). BACKGROUND: Previous epidemiologic studies have demonstrated stable rates of AAA repair, repair mortality, and AAA rupture. Recently, EVAR has been introduced as a less invasive treatment method, and its use has expanded to more than 75% of elective AAA repairs. METHODS: We identified Medicare beneficiaries undergoing AAA repair and those hospitalized with a ruptured AAA during the period 1995 to 2008 and calculated standardized annual rates of AAA-related deaths due to either elective repair or rupture. RESULTS: A total of 338,278 patients underwent intact AAA repair during the study period. There were 69,653 patients with AAA rupture, of whom 47,524 underwent repair. Intact repair rates increased substantially in those older than 80 years (57.7-92.3 per 100,000, P < 0.001) but decreased in those 65 to 74 years old (81.8-68.9, P < 0.001). A decline in ruptures with and without repair was seen in all age groups. By 2008, 77% of all intact repairs and 31% of all rupture repairs were performed with EVAR (P < 0.001). Operative mortality declined during the study period for both intact (4.9%-2.4%, P < 0.001) and ruptured (44.1%-36.3%, P < 0.001) AAA repair. Short-term AAA-related deaths decreased by more than half (26.1-12.1 per 100,000, P < 0.001), with the greatest decline occurring in those older than 80 years (53.7-27.3, P < 0.001). CONCLUSIONS: A recent decline in AAA rupture and short-term AAA-related mortality is demonstrated and likely related in part to the introduction and expansion of EVAR. This is due to decreased deaths from ruptures (with and without repair) and decreased mortality with intact repairs, particularly in patients older than 80 years.

The UK EndoVascular Aneurysm Repair (EVAR) trials: randomised trials of EVAR versus standard therapy.

OBJECTIVE: To assess the efficacy of endovascular aneurysm repair (EVAR) against standard alternative management in patients with large abdominal aortic aneurysm (AAA). DESIGN: Two national, multicentre randomised trials - EVAR trials 1 and 2. SETTING: Patients were recruited from 38 out of 41 eligible UK hospitals. PARTICIPANTS: Men and women aged at least 60 years, with an AAA measuring at least 5.5 cm on a computerised tomography scan that was regarded as anatomically suitable for EVAR, were assessed for fitness for open repair. Patients considered fit were randomised to EVAR or open repair in EVAR trial 1 and patients considered unfit were randomised to EVAR or no intervention in EVAR trial 2. INTERVENTIONS: EVAR, open repair or no intervention. MAIN OUTCOME MEASURES: The primary outcome was mortality (operative, all-cause and AAA related). Patients were flagged at the UK Office for National Statistics with centrally coded death certificates assessed by an Endpoints Committee. Power calculations based upon mortality indicated that 900 and 280 patients were required for EVAR trials 1 and 2, respectively. Secondary outcomes were graft-related complications and reinterventions, adverse events, renal function, health-related quality of life and costs. Cost-effectiveness analyses were performed for both trials. RESULTS: Recruitment occurred between 1 September 1999 and 31 August 2004, with targets exceeded in both trials: 1252 randomised into EVAR trial 1 (626 to EVAR) and 404 randomised into EVAR trial 2 (197 to EVAR). Follow-up closed in December 2009 with very little loss to follow-up (1%). In EVAR trial 1, 30-day operative mortalities were 1.8% and 4.3% in the EVAR and open-repair groups, respectively: adjusted odds ratio 0.39 [95% confidence interval (CI) 0.18 to 0.87], p = 0.02. During a total of 6904 person-years of follow-up, 524 deaths occurred (76 AAA related). Overall, there was no significant difference between the groups in terms of all-cause mortality: adjusted hazard ratio (HR) 1.03 (95% CI 0.86 to 1.23), p = 0.72. The EVAR group did demonstrate an early advantage in terms of AAA-related mortality, which was sustained for the first few years, but lost by the end of the study, primarily due to fatal endograft ruptures: adjusted HR 0.92 (95% CI 0.57 to 1.49), p = 0.73. The EVAR procedure was more expensive than open repair (mean difference £1177) and not found to be cost-effective, but the model was sensitive to alternative assumptions. In EVAR trial 2, during a total of 1413 person-years of follow-up, a total of 305 deaths occurred (78 AAA related). The 30-day operative mortality was 7.3% in the EVAR group. However, this group later demonstrated a significant advantage in terms of AAA-related mortality, but this became apparent only after 4 years: overall adjusted HR 0.53 (95% CI 0.32 to 0.89), p = 0.02. Sadly, this advantage did not result in any benefit in terms of all-cause mortality: adjusted HR 0.99 (95% CI 0.78 to 1.27), p = 0.97. Overall, EVAR was more expensive than no intervention (mean difference £10,222) and not found to be cost-effective. CONCLUSIONS: EVAR offers a clear operative mortality benefit over open repair in patients fit for both procedures, but this early benefit is not translated into a long-term survival advantage. Among patients unfit for open repair, EVAR is associated with a significant long-term reduction in AAA-related mortality but this does not appear to influence all-cause mortality. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 55703451. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 9. See the HTA programme website for further project information.