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The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
Midterm experience of ipsilateral axillary-axillary arteriovenous loop graft as tertiary access for haemodialysis.
Objectives. To present a series of ipsilateral axillary artery to axillary vein loop arm grafts as an alternative vascular access procedure for haemodialysis in patients with difficult access. Design. Retrospective case series. Methods. Patients who underwent an axillary loop arteriovenous graft from September 2009 to September 2012 were included. Preoperative venous imaging to exclude central venous stenosis and to image arm/axillary veins was performed. A cuffed PTFE graft was anastomosed to the distal axillary artery and axillary vein and looped on the arm. Results. 25 procedures were performed on 22 patients. Median age was 51 years, with 9 males and 13 females. Median number of previous access procedures was 3 (range 0-7). Median followup was 16.4 months (range 1-35). At 3 months and 1 year, the primary and secondary patency rates were 70% and 72% and 36% and 37%, respectively. There were 11 radiological interventions in 6 grafts including 5 angioplasties and 6 thrombectomies. There were 19 surgical procedures in 10 grafts, including thrombectomy, revision, repair for bleeding, and excision. Conclusions. Our series demonstrates that the axillary loop arm graft yields acceptable early patency rates in a complex group of patients but to maintain graft patency required high rates of surgical and radiological intervention, in particular graft thrombectomy.
Spontaneous, isolated caecal necrosis: report of a case, review of the literature, and updated classification.
Isolated necrosis of the caecum is a rare cause of abdominal pain. In the absence of occlusive vascular disease it has a number of well documented associations, the commonest of which is patients' receiving haemodialysis for endstage renal failure. It has also been associated with shock states, cardiac failure, ischaemic heart disease, diabetes and drugs such as cocaine, thiopentone and cytotoxic agents. However, there are few reported cases in the literature without the aforementioned associations and the majority of cases, regardless of aetiology, were treated with either hemicolectomy or wedge resection and ileocolic anastamosis. This report describes a case of isolated caecal necrosis, mimicking acute appendicitis, successfully treated by local excision of the necrotic segment. It also provides a systematic review of the literature and proposes an updated classification of associations in isolated caecal necrosis.
Effects of hydrogen sulphide in an experimental model of renal ischaemia-reperfusion injury.
BACKGROUND: Renal ischaemia-reperfusion injury (IRI) is a major cause of acute renal failure and renal transplant dysfunction. The aim of this study was to investigate the efficacy of the endogenous gaseous signalling molecule hydrogen sulphide in protecting against renal IRI. METHODS: Large White female pigs underwent laparotomy and cross-clamping of the left renal pedicle for 60 min. Animals were allocated randomly to treatment with either intravenous hydrogen sulphide (n = 6) or saline control (n = 6) 10 min before clamp release, and then underwent a right nephrectomy. Staff were blinded to treatment allocation and animals were recovered for 7 days. RESULTS: Hydrogen sulphide therapy resulted in a marked reduction in kidney injury with reduced serum creatinine levels on days 1-5, in a reduced area under the creatinine-time curve, and a halving of the time to achieve a creatinine level of less than 250 µmol/l, compared with the control. Hydrogen sulphide also preserved glomerular function, as shown by the urinary protein/creatinine ratio, which, compared with baseline, increased on days 1 and 3 in the control group (mean(s.e.m.) 3·22(1·43), P = 0·016 and 2·59(1·27), P = 0·031), but not in the treatment group (0·99(0·23), P = 0·190 and 1·06(0·44), P = 0·110, respectively). Mean(s.e.m.) tumour necrosis factor α levels at 6 h postreperfusion increased in the control animals (56(6) versus 115(21) pg/ml; P = 0·026), but not in the hydrogen sulphide-treated animals (61(7) versus 74(11) pg/ml; P = 0·460). Renal neutrophil infiltration at 30 min (myeloperoxidase staining) was also significantly reduced by treatment with hydrogen sulphide (P = 0·016). CONCLUSION: Hydrogen sulphide offers a promising new approach to ameliorating renal IRI with potential translation into a number of clinical settings, including renal transplantation.
Effect of season and ambient temperature on outcome of guaiac-based faecal occult blood tests performed for colorectal cancer screening.
AIM: Guaiac-based faecal occult blood tests (gFOBTs) are used in the colorectal cancer screening programme. Recent data suggested that the immunological faecal occult blood test illustrated a variation in positivity according to season and ambient temperature. Our aim was to assess the effect of season and ambient temperature on the positivity rates of the gFOBT during pilot screening for colorectal cancer. METHOD: Data from the first year of round 1 of the pilot screening programme in Coventry and Warwickshire were analysed. Patients with positive and negative gFOBT samples were included. Patients with spoilt samples or incomplete data were excluded. Of the total of 59513 patients, 30311 were men and 29202 women. Mean age was 56 years. Daily temperature data were provided by the meteorological office. RESULTS: Median exposure of the gFOBT test card was 6 days (range 1-17). Median daily maximum temperature was 14°C. Spring and summer illustrated significantly decreased positivity rates compared with autumn and winter (Pearson's chi-squared test, P<0.001). Mean daily maximum temperature for the test card exposure showed no significant difference in positivity rates (P=0.53). Subgroup analysis revealed a significant reduction in positive samples in the >25°C subgroup (P=0.045). CONCLUSIONS: There is a seasonal variation in positivity rates of gFOBTs with increased positivity in spring and summer months. There is no difference in positivity rates in relation to ambient temperature except in subgroup analysis where there is a significant reduction in positivity rates above 25°C.
Suprarenal graft fixation in endovascular abdominal aortic aneurysm repair is associated with a decrease in renal function.
INTRODUCTION: Suprarenal endograft fixation is routinely used in the endovascular repair of abdominal aortic aneurysms (EVAR) to enhance proximal endograft attachment but can be associated with an adverse outcome in renal function. This prospective study assessed the effect of suprarenal fixation on serum creatinine concentration and estimated glomerular filtration rate (eGFR), calculated by the Modified Diet in Renal Disease equation, 12 months after elective EVAR. METHODS: Patients undergoing elective EVAR were divided into suprarenal vs infrarenal fixation groups matched for age, sex, smoking, and aneurysm diameter. Serum creatinine and eGFR were measured at baseline, 6, and 12 months. RESULTS: Included were 92 patients (two women) with a mean age of 71 ± 7 years, with 46 in each group. No device-related complications were noted. Serum creatinine did not differ significantly between groups at 6 (P = .24) or 12 (P = .08) months but significantly increased in the suprarenal group at 12 months (1.08 ± 0.36 to 1.16 ± 0.36 mg/dL; P < .001) vs baseline. The eGFR (mL/min/1.73 m(2)) did not differ significantly at baseline between the suprarenal (85 ± 27) and infrarenal (80 ± 28; P = .33) groups or at 6 months (88 ± 29 vs 77 ± 24, respectively; P = .07). At 12 months, the suprarenal group had a lower eGFR (73 ± 23) than the infrarenal group (84 ± 26; P = .027). The eGFR at 12 months showed a significant decrease in the suprarenal (80 ± 28 to 73 ± 23; P < .001) but not in the infrarenal group (85 ± 27 to 84 ± 26; P = .48). The drop in eGFR differed significantly at 12 months in the infrarenal vs the suprarenal (0.82 vs -6.94; P < .001) group. No patient progressed to end-stage renal disease or disclosed a drop in eGFR > 30%. CONCLUSIONS: In contrast to previous studies, this study suggests that suprarenal endograft fixation in elective EVAR is associated with a drop in eGFR at 12 months.
Early urinary biomarkers of warm and cold ischemic injury in an experimental kidney model.
BACKGROUND: Early urinary biomarkers may be useful in determining the severity of ischemic injury in donation after circulatory death (DCD) kidneys. The aim of this study was to evaluate the efficacy of a collective series of urinary biomarkers in relation to the warm and cold ischemic intervals. METHODS: Porcine kidneys were retrieved after 0, 10, and 25 min of warm ischemia (WI), then preserved by static cold storage (CS) for period of 2 and 18 h. After preservation, kidneys were reperfused on an isolated organ perfusion system to assess renal function and injury. Levels of IL-6, TNFα, endothelin-1 (ET-1), and neutrophil gelatinase-associated lipocalin (NGAL) were measured in urine samples after 3 h of reperfusion. RESULTS: There was no significant difference in renal functional parameters or urinary biomarkers between the WI times when kidneys were stored for 2 h (P > 0.05). After 18 h CS, kidneys with 10 and 25 min of WI demonstrated a significant decline in renal function compared with kidneys without WI (P < 0.05). Levels of ET-1 and NGAL were significantly higher in kidneys with 25 min WI (25 m ET-1, 30.1 ± 21.2, versus 0 m 2.25 ± 1.5 pg/mL; P = 0.002: NGAL, 25 m 77 ± 51 versus 0 m 10 ± 0.1 pg/mL; P = 0.005). Levels of IL-6 and TNFα were significantly higher in kidneys with 10 and 25 min of WI (P = 0.001, 0.001). CONCLUSION: Early urinary biomarkers are a useful means to determine graft injury. ET-1 and NGAL are more accurate in predicting the severity of ischemic injury compared with inflammatory markers.
Anemia is associated with mortality following endovascular repair of abdominal aortic aneurysm.
AIM: The aim of this study was to compare midterm mortality between anemic and nonanemic patients undergoing endovascular repair of abdominal aortic aneurysm and to assess a correlation with markers of inflammation. METHODS: Anemia was defined as hemoglobin <13 (men) and <12 g/dL (women). The impact of anemia and inflammatory markers on mortality was assessed using Kaplan-Meier curves and Cox regression. RESULTS: A total of 224 patients (12 females [5.36%]; age: 69.73 ± 8.72 years) were included; 102 (45.53%) were anemic. Median follow-up was 17 months (interquartile range: 7-25 months). Nine patients died (1.79%; 8 anemic vs 1 nonanemic). Survival was lower for patients with anemia (log-rank, P = .01). White blood cell count and C-reactive protein (CRP) differed significantly (P < .001 and P = .01). Anemia and CRP were associated with decreased survival (Cox regression, P = .01, hazard ratio [HR]: 0.35, 95% confidence interval: 0.14-0.84 and P = .002, HR: 1.18, 95% CI: 1.06-1.31). CONCLUSION: Patients with anemia had decreased survival over the midterm; inflammatory markers were higher among this group.
Complications of Thyroid RFA
Radiofrequency ablation (RFA) has been performed internationally for over 10 years and has proven to be efficacious in the treatment of thyroid nodules. As the utilization of RFA for symptomatic nodules has increased, so has recognition of the procedural complications. The overall complication rate of patients who undergo thyroid RFA is low, reportedly up to 3.3%, with major complications occurring even more rarely. Fortunately, most complications are self-limited and resolve over time. However, a review of these complications is important for early recognition, optimal patient management, and to direct technical improvements, all of which will be discussed here.
Urine Recirculation Improves Hemodynamics and Enhances Function in Normothermic Kidney Perfusion.
UNLABELLED: The study compares urine recirculation (URC) to urine replacement (UR) with Ringer's lactate in a porcine normothermic kidney machine perfusion (NMP) model using a preclinical prototype device. METHODS: Kidney pairs were recovered uninjured (as live-donor nephrectomy) and perfused consecutively. Pig kidneys (n = 10) were allocated to either NMP with URC (n = 5) or NMP with volume replacement (n = 5). Cold ischemia time was either 2 or 27 hours for the first or second perfusion (URC or UR) of a kidney pair. An autologous blood-based perfusate, leukocyte-filtered, was used and NMP performed up to 24 hours. Perfusion parameters, biochemistry/metabolic parameters were monitored and samples collected. RESULTS: Physiological mean arterial pressures and flows were achieved in both groups but were sustainable only with URC. Significantly higher arterial flow was observed with URC (326.7 ± 1.8 versus 242.5 ± 14.3 mL/min, P = 0.001). Perfusate sodium levels were lower with URC, 129.6 ± 0.7 versus 170.3±2.7 mmol/L, P < 0.001). Stable physiological pH levels were only observed with URC. Perfusate lactate levels were lower with URC (2.2 ± 0.1 versus 7.2 ± 0.5 mmol/L, P < 0.001). Furthermore, the hourly rate of urine output was lower with URC and closer to physiological levels (150 versus 548 mL/h, P = 0.008). Normothermic kidney perfusion with URC was associated with longer achievable durations of perfusion: the objective in all experiments was a 24-hour perfusion, but this was not achieved in every case. The mean perfusions were 17.3 ± 9.2 hours with URC versus 5.3 ± 1.3 hours NMP with UR; P = 0.02. There appeared to be no differences in baseline tubular condition with and without URC. CONCLUSIONS: URC facilitates long-term kidney NMP in a porcine model. Perfusate homeostasis and stability of renal arterial flow throughout the perfusion period was only achievable with URC, independent of cold ischemia time duration.
Ex vivo delivery of Mirococept: A dose-finding study in pig kidney after showing a low dose is insufficient to reduce delayed graft function in human kidney.
The complement system plays a pivotal role in the pathogenesis of ischemia-reperfusion injury in solid organ transplantation. Mirococept is a potent membrane-localizing complement inhibitor that can be administered ex vivo to the donor kidney prior to transplantation. To evaluate the efficacy of Mirococept in reducing delayed graft function (DGF) in deceased donor renal transplantation, we undertook the efficacy of mirococept (APT070) for preventing ischaemia-reperfusion injury in the kidney allograft (EMPIRIKAL) trial (ISRCTN49958194). A dose range of 5-25 mg would be tested, starting with 10 mg in cohort 1. No significant difference between Mirococept at 10 mg and control was detected; hence the study was stopped to enable a further dose saturation study in a porcine kidney model. The optimal dose of Mirococept in pig kidney was 80 mg. This dose did not induce any additional histological damage compared to controls or after a subsequent 3 hours of normothermic machine perfusion. The amount of unbound Mirococept postperfusion was found to be within the systemic dose range considered safe in the Phase I trial. The ex vivo administration of Mirococept is a safe and feasible approach to treat DGF in deceased donor kidney transplantation. The porcine kidney study identified an optimal dose of 80 mg (equivalent to 120 mg in human kidney) that provides a basis for further clinical development.
Ischemia-Reperfusion Injuries Assessment during Pancreas Preservation.
Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of the 20th century. These perfusions led to organ oedema, hemorrhage, and venous congestion after revascularization. Despite these early hurdles, a number of factors now favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions, and the development of organ perfusion machines for the lung, heart, kidneys and liver. This has led to a resurgence of research in machine perfusion for whole organ pancreas preservation. This review highlights the ischemia-reperfusion injuries assessment during ex vivo pancreas perfusion, both for assessment in pre-clinical experimental models as well for future use in the clinic. We evaluated perfusion dynamics, oedema assessment, especially by impedance analysis and MRI, whole organ oxygen consumption, tissue oxygen tension, metabolite concentrations in tissue and perfusate, mitochondrial respiration, cell death, especially by histology, total cell free DNA, caspase activation, and exocrine and endocrine assessment.
Kidney Normothermic Machine Perfusion Can Be Used as a Preservation Technique and a Model of Reperfusion to Deliver Novel Therapies and Assess Inflammation and Immune Activation.
Ischaemia-reperfusion injury (IRI) is an inevitable process in transplantation and results in inflammation and immune system activation. Alpha-1 antitrypsin (AAT) has anti-inflammatory properties. Normothermic machine perfusion (NMP) can be used to deliver therapies and may help in assessing the effects of IRI and immunity. This study investigated the effects of AAT on IRI and inflammation in pig kidneys when administered during preservation, followed by normothermic reperfusion (NR) with autologous whole blood, as a surrogate for transplant. Two different models were used to deliver AAT or placebo to paired slaughterhouse pig kidneys: Model 1: 7-h static cold storage (SCS) + 3-h NR (n = 5 pairs), where either AAT (10 mg/ml) or placebo was delivered in the flush following retrieval; Model 2: 4-h SCS + 3-h NMP + 3-h NR (n = 5 pairs), where either AAT or placebo was delivered during NMP. Injury markers and cytokines levels were analysed in the perfusate, and heat shock protein 70 KDa (HSP-70) was analysed in biopsies. AAT delivered to kidneys showed no adverse effects on perfusion parameters. HSP-70 fold changes were significantly lower in the AAT group during NMP (P < 0.01, paired t-test) but not during NR. Interleukin-1 receptor antagonist (IL-1ra) fold changes were significantly higher in the AAT group during NR model 1 (p < 0.05, two-way ANOVA). In contrast to the AAT group, significant upregulation of interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) between t = 90 min and t = 180 min and interleukin-8 (IL-8) between baseline and t = 90 min was observed in the control group in NR model 2 (p < 0.05, Tukey's multiple comparison test). However, overall inflammatory cytokines and injury markers showed similar levels between groups. Delivery of AAT to pig kidneys was safe without any detrimental effects. NMP and NR provided excellent methods for comparison of inflammation and immune activation in the delivery of a novel therapy.
Assessment of Mitochondrial Function and Oxygen Consumption Measured During Ex Vivo Normothermic Machine Perfusion of Injured Pig Kidneys Helps to Monitor Organ Viability.
Donor kidney assessment may improve organ utilisation. Normothermic Machine Perfusion (NMP) has the potential to facilitate this advance. The mechanism of action is not yet determined and we aimed to assess mitochondrial function during NMP. Anaesthetised pigs (n = 6) had one kidney clamped for 60 min. The healthy contralateral kidney was removed and underwent NMP for 8 h (healthy control (HC), n = 6). Following 60 min warm ischaemia the injured kidney underwent HMP for 24 h, followed by NMP for 8 h (n = 6). Mitochondria were extracted from fresh tissue for analysis. Injured kidneys were analysed as two separate groups (IMa, n = 3 and IMb, n = 3). Renal resistance was higher (0.39ï, ± 0.29 vs. 1.65ï, ± 0.85; p = 0.01) and flow was lower (55ï, ± 28 vs. 7ï, ± 4; p = 0.03) during HMP in IMb than IMa. NMP blood flow was higher in IMa versus IMb (2-way ANOVA; p < 0.001) After 60 min NMP, O2 consumption was significantly lower in IMb versus IMa (p ≤ 0.002). State-3 respiration was significantly different between the groups (37ï, ± 19 vs. 24ï, ± 14 vs. 10ï, ± 8; nmolO2/min/mg; p = 0.049). Lactate levels were significantly lower in IMa versus IMb (p = 0.028). Mitochondrial respiration levels during NMP may be suggestive of kidney viability. Oxygen consumption, renal blood flow and lactate can differentiate severity of kidney injury during NMP.
Pancreas preservation: clinical practice and future developments.
PURPOSE OF REVIEW: To summarize recently published studies of preservation strategies including machine perfusion in pancreas transplantation. RECENT FINDINGS: The shortage of conventional donors is leading units to use extended criteria donors (ECDs) and donors after cardiac death (DCD). Static cold storage (SCS) is still the standard method of preservation for pancreases and University of Wisconsin remains the gold standard preservation solution. In experimental studies, oxygen delivered during preservation reduced tissue injury and improved islet cell yield and function. Hypothermic machine perfusion of discarded human pancreases has been shown to improve adenosine triphosphate levels without adversely effect histology and oedema compared with SCS. Normothermic machine perfusion of discarded human organs has so far been challenging and led to increasing injury, rather than preservation. There are currently no clinical studies in pancreas transplant with the exception of a small number of pancreases being transplanted following normothermic regional perfusion. SUMMARY: The storm of new organ preservation methods is now being more widely studied in the pancreas, with some promising results. These new strategies have the potential to allow expansion of the donor pool and greater utilization of ECD and DCD organs.
Hemodynamics and Metabolic Parameters in Normothermic Kidney Preservation Are Linked With Donor Factors, Perfusate Cells, and Cytokines.
Kidney transplantation is the best renal-replacement option for most patients with end-stage renal disease. Normothermic machine preservation (NMP) of the kidney has been studied extensively during the last two decades and implemented in clinical trials. Biomarker research led to success in identifying molecules with diagnostic, predictive and therapeutic properties in chronic kidney disease. However, perfusate biomarkers and potential predictive mechanisms in NMP have not been identified yet. Twelve discarded human kidneys (n = 7 DBD, n = 5 DCD) underwent NMP for up to 24 h. Eight were perfused applying urine recirculation (URC), four with replacement of urine (UR) using Ringer's lactate. The aim of our study was to investigate biomarkers (NGAL, KIM-1, and L-FABP), cells and cytokines in the perfusate in context with donor characteristics, perfusate hemodynamics and metabolic parameters. Cold ischemia time did not correlate with any of the markers. Perfusates of DBD kidneys had a significantly lower number of leukocytes after 6 h of NMP compared to DCD. Arterial flow, pH, NGAL and L-FABP correlated with donor creatinine and eGFR. Arterial flow was higher in kidneys with lower perfusate lactate. Perfusate TNF-α was higher in kidneys with lower arterial flow. The cytokines IL-1β and GM-CSF decreased during 6 h of NMP. Kidneys with more urine output had lower perfusate KIM-1 levels. Median and 6-h values of lactate, arterial flow, pH, NGAL, KIM-1, and L-FABP correlated with each other indicating a 6-h period being applicable for kidney viability assessment. The study results demonstrate a comparable cytokine and cell profile in perfusates with URC and UR. In conclusion, clinically available perfusate and hemodynamic parameters correlate well with donor characteristics and measured biomarkers in a discarded human NMP model.
Abdominal multiorgan procurement from slaughterhouse pigs: a bespoke model in organ donation after circulatory death for ex vivo organ perfusion compliant with the 3 Rs (Reduction, Replacement & Refinement).
BACKGROUND: Advances in organ preservation, reconditioning and assessment have been driven by the increasing necessity to utilise organs from extended criteria donors, particularly donors after circulatory death. Research efforts in this area have aided translation of machine perfusion technology into clinical practice. Pigs are anatomically and physiologically similar to humans and are an excellent model. However, conducting large animal experimental research is challenging and typically limited by ethical and economic constraints. Here we describe a reproducible, cost-effective multi-organ abdominal procurement model of porcine organs from the slaughterhouse. METHODS: Domestic pigs are electrically stunned and exsanguinated following the standard abattoir process. Via a longitudinal midline incision, the thoracoabdominal viscera are removed en bloc by incising along the anterior vertebral plane. The abdominal organs are isolated, perfused and separated preserving their respective vasculature, allowing individual organ use for specific experiments. RESULTS: The warm ischaemic time is kept between 15-30 minutes. Using this highly protocolized procurement technique we have procured 12 livers, 162 kidneys and 12 pancreata for research, the majority of which have been utilized for ex situ perfusion experiments. CONCLUSIONS: We have described a reliable and reproducible procedure for abdominal multi-organ procurement from slaughterhouse pigs.
Early Ultrasound Surveillance of Newly-Created Hemodialysis Arteriovenous Fistula.
INTRODUCTION: We assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention. METHODS: Consenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling. RESULTS: Of 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9-77.3]; elbow, 66.7% [48.9-84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan's findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data. CONCLUSION: Early ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation.
Effect of carotid endarterectomy on 20 year incidence of recorded dementia: a randomised trial
Objective Stroke and carotid atherosclerosis are associated with dementia. Carotid endarterectomy (CEA) reduces stroke risk, although its effect on later dementia is uncertain. Participants in the Asymptomatic Carotid Surgery Trial (ACST-1), randomly allocated to immediate vs. deferral of CEA (i.e., no intervention unless or until triggered by ipsilateral transient ischaemic attack or stroke), were followed, to study effects on dementia. Methods From 1993 to 2003, ACST-1 included 3 120 participants with asymptomatic tight carotid stenosis. All UK and Swedish patients (n = 1 601; 796 immediate vs. 805 deferral) were followed with trial records, national electronic health record linkage, and (UK only) by post and telephone. Cumulative incidence and competing risk analyses were used to measure the effects of risk factors and CEA on dementia risk. Intention to treat analyses yielded hazard ratios (HRs; immediate vs. deferral) of dementia. Results The median follow up was 19.4 years (interquartile range 16.9 – 21.7). Dementia was recorded in 107 immediate CEA patients and 115 allocated delayed surgery; 1 290 patients died (1 091 [538 vs. 536] before any dementia diagnosis). Dementia incidence rose with age and with female sex (men: 8.3% aged < 70 years at trial entry vs. 15.1% aged ≥ 70; women: 15.1% aged < 70 years at trial entry vs. 22.4% aged ≥ 70 years) and was higher in those with pre-existing cerebral infarction (silent or with prior symptoms; 20.2% vs. 13.6%). Dementia risk was similar in both randomised groups: 6.7% vs. 6.6% at 10 years and 14.3% vs. 15.5% at 20 years, respectively. The dementia HR was 0.98 (95% confidence interval [CI] 0.75 – 1.28; p = .89), with no heterogeneity in the neutral effect of immediate CEA on dementia related to age, carotid stenosis, blood pressure, diabetes, country of residence, or medical treatments at trial entry (heterogeneity values p > .05). Conclusion CEA was not associated with significant reductions in the long term hazards of dementia, but the CI did not exclude a proportional benefit or hazard of about 25%.