The implications of different criteria for grading carotid artery stenosis by duplex ultrasound.

PURPOSE: Duplex ultrasound is the first-line mode of investigation for carotid stenosis, whose severity could be graded according to NASCET or St. Mary's ratio criteria. The aim of this study was to compare these two methods and review the literature. METHODS: All patients who had carotid duplex ultrasound in a 1-month period were included. The reports and images were retrospectively reviewed, and the grade of carotid artery stenosis was then recalculated using the St. Mary's Ratio. RESULTS: A total of 245 (160 men) patients with a mean age 70.4 years (±11.5) were assessed, and 469 extracranial carotid systems were analyzed. Pearson's Coefficient revealed strong correlation (r = 0.79, p = 0.05) between the two methods. In 114 (24.3%) internal carotid arteries, results were different. Of these, 26 (22.8%) would have gone for surgery had they been assessed using the St. Mary's Ratio and not the NASCET grading criteria. Conversely, two internal carotid arteries (1.75%) went for surgery using the NASCET grading criteria that would not have had to should the St. Mary's Ratio been used. CONCLUSIONS: Although there is a strong level of correlation between the two criteria, choosing one or the other would have a significant impact on the patient' selection for surgery.

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

Surveillance strategies according to the rate of growth of small abdominal aortic aneurysms.

The management of small abdominal aortic aneurysms (AAA) is by ultrasound surveillance. The study aimed to calculate their growth rate, identify risk factors and determine appropriate screening intervals. The local screening programme and hospital records were used to identify patients with a small (< 5.5 cm) AAA. The dates and maximum diameter of serial scans of patients with two or more scans were obtained. Patients were subdivided by 0.5 cm increments above 3.0 cm. The rate of growth was calculated by linear regression for each patient using both the absolute measurements and logarithmically (ln) transformed measurements. The 95th centile of growth rate within each subgroup was used to estimate the minimum time to grow to 5.5 cm. A total of 252 were included. The mean (± SD) AAA size on the initial scan was 3.9 (± 0.7) cm. Statin use and initial size were predictive factors for the growth rate. The median rate of growth increased according to size from 0.075 to 0.432 cm/year for AAA < 3.5 cm and > 5.0 cm, respectively. It also steadily increased for ln measurements from 0.022 (or 2.2%/year) to 0.078 or (7.8%/year). The minimum time (months) to reach 5.5 cm was 61, 17, 11 and 5 for AAA < 3.5 cm, 3.5-3.9 cm, 4.0-4.4 cm and 4.5-4.9 cm, respectively. Based on ln measurements, the times were similar at 60, 17, 10 and 4 months. In conclusion, the rate of growth increased steadily with AAA size. An aneurysm < 3.5 cm does not require a repeat scan for 5 years, while those measuring 3.5-3.9 cm and 4.0-4.4 cm require a repeat scan after 17 and 11 months.

The impact of radiation dose exposure during endovascular aneurysm repair on patient safety.

OBJECTIVE: Endovascular aneurysm repair (EVAR) exposes patients to radiation during the procedure and in subsequent follow-up. The study goal was to calculate the radiation dose in our unit and compare it against other published data and national guidelines. METHODS: All EVAR procedures were identified from a prospectively maintained database. Radiation dose, screening time, and volume of intravenous contrast during the procedure were reviewed. Radiation exposure from subsequent computed tomography (CT) imaging was included in the overall exposure. Results are expressed as mean +/- standard deviation. RESULTS: From October 1998 to October 2008, 320 elective patients underwent EVAR. Mean screening time was 29.4 +/- 23.3 minutes, and the radiation dose was 11.7 +/- 7.1 mSv. The EVAR was an emergency in 64 patients. The mean screening time was 22.9 +/- 18.2 minutes, and the radiation dose was 13.4 +/- 8.6 mSv. During the first postoperative year, follow-up CT scans exposed the patients to 24.0 mSv, with 8.0 mSv in subsequent years. Abdominal radiographs added an additional 1.8 mSv each year. CONCLUSION: EVAR and the follow-up investigations involve substantial amounts of radiation, with well-recognized carcinogenic risks. Because patient safety is paramount, radiation exposure should be minimized. This may be possible by standardizing radiation exposure throughout the United Kingdom by implementing national guidelines and considering other imaging modalities for follow-up.

Common polymorphisms of Fibulin-5 and the risk of abdominal aortic aneurysm development.

Fibulin-5 is a crucial protein in the connective tissue structure of the aortic wall. The purpose of this study was to determine if genetic variation within the Fibulin-5 gene was associated with abdominal aortic aneurysms (AAA). AAA patients, with disease-free controls, were recruited and a past medical history questionnaire completed. Three single nucleotide polymorphisms (SNPs) in the FBLN5 gene (rs2498834, rs2430366 and rs2254320) were genotyped. The two cohorts were compared and haplotype analysis performed. A total of 230 AAA cases and 278 controls were successfully genotyped. The mean age was 71.9 years (+/- 6.8). No difference between cases and controls was found in the distribution of alleles of FBLN5 SNPs rs2498834 (p = 0.47), rs2430366 (p = 0.45) or rs2254320 (p = 0.46). Haplotype analysis did not reveal any significant difference. In conclusion, genetic variation within FBLN5 is unlikely to play any role in the development of AAA.

The effects of abdominal compartment hypertension after open and endovascular repair of a ruptured abdominal aortic aneurysm.

OBJECTIVE: This study assessed if emergency endovascular repair (eEVR) reduces the increase in intra-abdominal compartment pressure and host inflammatory response in patients with ruptured abdominal aortic aneurysm (AAA). METHODS: Thirty patients with ruptured AAA were prospectively recruited. Patients were offered eEVR or emergency conventional open repair (eOR) depending on anatomic suitability. Intra-abdominal pressure was measured postoperatively, at 2 and 6 hours, and then daily for 5 days. Organ dysfunction was assessed preoperatively by calculating the Hardman score. Multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and lung injury scores were calculated regularly postoperatively. Hematologic analyses included serum urea and electrolytes, liver function indices, and C-reactive protein. Urine was analyzed for the albumin-creatinine ratio. RESULTS: Fourteen patients (12 men; mean age, 72.2 +/- 6.2 years) underwent eEVR, and 16 (14 men; mean age, 71.4 +/- 7.0 years) had eOR. Intra-abdominal pressure was significantly higher in the eOR cohort compared with the eEVR group. The eEVR patients had significantly less blood loss (P < .001) and transfused (P < .001) and total intraoperative intravenous fluid infusion (P = .001). The eOR group demonstrated a greater risk of organ dysfunction, with a higher systemic inflammatory response syndrome score at day 5 (P = .005) and higher lung injury scores at days 1 and 3 (P = .02 and P = .02) compared with eEVR. A significant correlation was observed between intra-abdominal pressure and the volume of blood lost and transfused, amount of fluid given, systemic inflammatory response syndrome score, multiple organ dysfunction score, lung injury score, and the length of stay in the intensive care unit and hospital. CONCLUSION: These results suggest that eEVR of ruptured AAA is less stressful and is associated with less intra-abdominal hypertension and host inflammatory response compared with eOR.

The vascular and biochemical effects of cilostazol in patients with peripheral arterial disease.

OBJECTIVES: Cilostazol improves walking distance and quality of life in patients with peripheral arterial disease (PAD). This study assessed the vascular and biochemical effects of cilostazol therapy in PAD patients. METHODS: PAD patients were prospectively recruited to a randomized, double-blinded, placebo-controlled trial. Baseline clinical data were recorded. Clinical assessment included measurement of arterial compliance, transcutaneous oxygenation, ankle-brachial index (ABI), and treadmill walking distance. Blood analyses included a full blood panel, coagulation screen, urea and electrolytes, liver function tests, estimated glomerular filtration rate, and lipid profiles. Quality of life indices were recorded using validated generic and walking-specific questionnaires. All tests were performed at baseline, 6, and 24 weeks. RESULTS: Eighty patients (53 men) were recruited from December 2004 to January 2006. The cilostazol group had a significant reduction in the augmentation index compared with the placebo group at 6 weeks (19.7% vs 26.7%, P = .001) and at 24 weeks (19.7% vs 27.7%, P = .005). A paradoxic reduction in transcutaneous oxygenation levels was identified in the cilostazol group for the left foot at 6 weeks and for the right foot at both 6 and 24 weeks. The ABIs were not significantly different between treatment groups at baseline, 6 weeks, or 24 weeks for the left and right lower limbs. The mean percentage change in walking distance from baseline improved more markedly in the cilostazol compared with the placebo group for absolute claudication distance at 6 (78.6% vs 26.4%, P = .20) and 24 weeks (173.1% vs 92.1%, P = .27); however, these failed to reach significance. Significant improvements in lipid profiles were demonstrated with cilostazol therapy at 6 weeks (triglycerides, high-density lipoprotein [HDL]) and at 24 weeks (cholesterol, triglycerides, HDL, and low-density lipoprotein). The cilostazol treatment group demonstrated significant improvements in the Short Form-36 (physical functioning, physical component score), Walking Impairment (distance and speed), and Vascular Quality of Life (pain) indices at 6 and 24 weeks. Although cilostazol was associated with side effects in approximately one-third of patients, most settled within 6 weeks, facilitating the continuation of therapy in >89%. CONCLUSION: Cilostazol is a well-tolerated, safe, and efficacious treatment for PAD patients. It not only improves patients' symptomatology and quality of life but also appears to have beneficial effects on arterial compliance, possibly through its lipid-lowering property.

C-reactive protein (CRP) elevation in patients with abdominal aortic aneurysm is independent of the most important CRP genetic polymorphism.

OBJECTIVE: C-reactive protein (CRP) is a marker of cardiovascular disease. The objective was to determine if abdominal aortic aneurysm (AAA) and CRP serum concentration and its CRP gene are associated. METHODS AND RESULTS: AAA patients and AAA negative controls were recruited. CRP concentration was measured and the single nucleotide polymorphism (SNP), rs3091244, assessed. AAA cases were divided into those measuring 30-55 mm and >55 mm in diameter, to assess correlation of CRP with AAA size. A total of 248 (227 male) cases and 400 (388 male) controls were included. CRP concentration was higher in cases (385.0 microl/dL [310.4-442.8] vs 180.3 microl/dL [168.1-196.9]; P < .0001). It was higher in large aneurysms (685.7 microl/dL [511.8-1083.0] vs 291.0 microl/dL [223.6-349.6]; P < .0001), with significant correlation observed to size (r = 0.37, P < .0001). CC was the most common SNP genotype with no difference in distribution (P = .43) between cases and controls. No difference existed in CRP for each genotype in the overall cohort (P = .17), cases (P = .18) and controls (P = .19). CONCLUSION: The results demonstrate that CRP production may be related to the presence of AAA, especially in advanced disease. The serum concentration of CRP does not appear to be influenced by the functional SNP of the CRP gene, which also appears to have no association with AAA formation.

The vascular and biochemical effects of cilostazol in diabetic patients with peripheral arterial disease.

OBJECTIVES: Cilostazol improves walking in patients with peripheral arterial disease (PAD). We hypothesized that cilostazol reduces diabetic complications in PAD patients. METHODS: Diabetic PAD patients were prospectively recruited to a randomized double-blinded, placebo-controlled trial, using cilostazol 100mg twice a day. Clinical assessment included ankle-brachial index, arterial compliance, peripheral transcutaneous oxygenation, treadmill walking distance and validated quality of life (QoL) questionnaires. Biochemical analyses included glucose and lipid profiles. All tests were at baseline, 6, and 24 weeks. RESULTS: 26 diabetic PAD patients (20 men) were recruited. Cilostazol improved absolute walking distance at 6 and 24 weeks (86.4% vs. 14.1%, P = .049; 143% vs. 23.2%, P = .086). Arterial compliance and lipid profiles improved as did some QoL indices for cilostazol at 6 and 24 weeks. Blood indices were similar at baseline and at follow-up points for both treatment groups. CONCLUSIONS: Cilostazol is a well-tolerated and efficacious treatment, which improves claudication distances in diabetic PAD patients with further benefits in arterial compliance, lipid profiles, and QoL.

Interleukin-6 Receptor Signaling and Abdominal Aortic Aneurysm Growth Rates.

BACKGROUND: The Asp358Ala variant (rs2228145; A>C) in the IL (interleukin)-6 receptor ( IL6R) gene has been implicated in the development of abdominal aortic aneurysms (AAAs), but its effect on AAA growth over time is not known. We aimed to investigate the clinical association between the IL6R-Asp358Ala variant and AAA growth and to assess the effect of blocking the IL-6 signaling pathway in mouse models of aortic aneurysm rupture or dissection. METHODS: Using data from 2863 participants with AAA from 9 prospective cohorts, age- and sex-adjusted mixed-effects linear regression models were used to estimate the association between the IL6R-Asp358Ala variant and annual change in AAA diameter (mm/y). In a series of complementary randomized trials in mice, the effect of blocking the IL-6 signaling pathways was assessed on plasma biomarkers, systolic blood pressure, aneurysm diameter, and time to aortic rupture and death. RESULTS: After adjusting for age and sex, baseline aneurysm size was 0.55 mm (95% CI, 0.13-0.98 mm) smaller per copy of the minor allele [C] of the Asp358Ala variant. Change in AAA growth was -0.06 mm per year (-0.18 to 0.06) per copy of the minor allele; a result that was not statistically significant. Although all available worldwide data were used, the genetic analyses were not powered for an effect size as small as that observed. In 2 mouse models of AAA, selective blockage of the IL-6 trans-signaling pathway, but not combined blockage of both, the classical and trans-signaling pathways, was associated with improved survival ( P<0.05). CONCLUSIONS: Our proof-of-principle data are compatible with the concept that IL-6 trans-signaling is relevant to AAA growth, encouraging larger-scale evaluation of this hypothesis.

Effect of preoperative renal dysfunction on mortality and postoperative renal failure following endovascular abdominal aortic aneurysm repair.

This study was aimed to assess the effect of preoperative renal dysfunction on mortality and postoperative renal failure in patients undergoing elective endovascular repair of abdominal aortic aneurysm. A total of 155 patients with a mean age of 74.9 years (+/-6.4) were included. In all, 31 patients (20%) had a preoperative creatinine level of >1.5 mg/dL, whereas 66 patients (42.6%) had an estimated glomerular filtration rate of <60 mL/min. Perioperative mortality was 2.6% with no significant difference between those with and without abnormal renal indices. Long-term survival at 4 years was 30% in patients with creatinine >1.5 mg/dL compared to over 60% in those with normal creatinine (P < .02). The difference in long-term survival was not as significant in patients with normal or reduced glomerular filtration rate (P = .13). However, neither creatinine nor glomerular filtration rate were found to accurately predict survival even though both demonstrated strong predictivity for postoperative renal failure in patients undergoing elective endovascular repair of abdominal aortic aneurysm.

Prescribing practice of general practitioners in Northern Ireland for peripheral arterial disease.

Peripheral arterial disease is prevalent and reflects overall cardiovascular disease state. Best medical treatment is the cornerstone of management to reduce peripheral arterial disease symptoms and to minimize vascular morbidity and mortality. The aim of this study was to assess the prescription practice of general practitioners in Northern Ireland for patients with peripheral arterial disease. All general practitioners were from the Northern Ireland Professional Medical Directory, and a questionnaire was used to determine the prescribing patterns for peripheral arterial disease. In all, 468 general practitioners responded; 94% prescribed aspirin to nondiabetic patients, and 44.9% prescribed statin, with similar results for diabetic patients. Angiotensin-converting enzyme inhibitors, multivitamins, and beta-blockers were not often prescribed. Statin was prescribed to patients with diabetic peripheral arterial disease at a lower cholesterol concentration. In all, 52% would consider statin and fibrate together. Budgetary consideration influenced 6%. Northern Ireland general practitioners are reluctant to prescribe medication that is effective in the secondary prevention of vascular morbidity and mortality in high-risk patients.

Open carpal tunnel release--still a safe and effective operation.

BACKGROUND: Carpal tunnel syndrome is a common cause of neurological symptomatology. Surgical decompression remains the treatment of choice in patients not responding to conservative therapies. The aim of this study was to assess the effectiveness of standard open decompression by analysis of symptomatic and functional improvement and to assess whether a general surgeon can still perform this operation safely. PATIENTS AND METHODS: Patients undergoing standard open carpal tunnel release by a single general surgeon were recruited. A self-administered Boston questionnaire was used to assess symptom severity and functional status pre- and post-surgical intervention. RESULTS: Forty-seven patients (51 hands) underwent carpal tunnel release and 32 patients completed the questionnaire. 88% had a significant reduction in the symptom severity score, while improvement in function status score was achieved in 79% of patients. Mean symptom severity score improved from 3.41 points preoperatively to 1.85 (p < 0.0001) points at the last follow up examination, while the mean function status score improved from 2.73 to 1.99 points (p < 0.0001). Outcome was poor in six patients with slight worsening of either symptom or function status score. Three patients were treated conservatively for minor wound infection without long-term sequelae. DISCUSSION: Standard open carpal tunnel release still provides efficacious symptomatic relief with a low risk of associated complications when performed by a general surgeon.

Benefits of a supervised exercise program after lower limb bypass surgery.

This study evaluated the efficacy of an exercise program after arterial bypass surgery. Patients undergoing bypass surgery were randomized to a control group (group I), with standard preoperative and postoperative care, or the intervention group (group II) with a supervised exercise program of twice-weekly treadmill assessments from 4 to 10 weeks postoperatively. Ankle-brachial pressure indices and hemodynamic measurements were recorded before and after exercise. The mean increase of maximum walking distance was 3.8% in group I and 175.4% in group II (P = .001). There was a significant difference between group I and II in the mean ankle-brachial pressure indices increase at the second assessment (0.08 versus 0.23; P = .02). A supervised exercise program leads to better improvement after lower limb bypass surgery for ischemia, but the feasibility of a formal exercise program would be undermined by the reluctance of patients to participate, both in the short-term and long-term.

No difference in medium-term outcome between Zenith and Talent stent-grafts in endovascular aneurysm repair.

BACKGROUND: Many devices are available for endovascular aneurysm repair (EVAR). Our aim was to analyze morphological effects of the Zenith and Talent systems. METHODS: Patients included underwent EVAR from June 1999 to June 2005 using a Zenith or Talent stent-graft, with computed tomography follow-up. Aortic dimensions over time and clinical outcome were analyzed. RESULTS: Twenty-nine patients with Zenith stent-grafts and 33 with Talent devices were included. Mean preoperative age was similar (75.5+/-6.0 years vs 74.2+/-6.7 years; P=.29). Preoperative neck length was longer in the Zenith group (29.9+/-15.2 mm vs 25.5 +/- 10.8 mm; P=.10), and stent-graft oversizing was greater in the Talent patients (20.2%+/-7.9% vs 23.0% +/- 11.3%). There was proximal aortic dilatation and aneurysm sac shrinkage in each group. Complication rates were comparable, with 83% of both groups free from 10-mm migration. CONCLUSION: Although device designs differ, there is no difference in clinical outcome between Zenith and Talent stent-grafts. Migration rates were not influenced by suprarenal fixation.

Endovascular Aneurysm Repair Increases Aortic Arterial Stiffness When Compared to Open Repair of Abdominal Aortic Aneurysms.

OBJECTIVES: The initial survival advantage seen with endovascular aneurysm repair (EVAR) over open repair does not persist in the long term. Pulse wave velocity (PWV) is a measure of arterial stiffness, and increased PWV is an independent risk factor for increased cardiovascular morbidity and mortality. This prospective comparative pilot study examined the effect of implantation of an aortic graft on PWV in patients undergoing open or endovascular aortic aneurysm repair. PATIENTS AND METHODS: Thirty-four patients (15 open and 19 EVAR) were recruited. Patient demographics were similar in both the groups. Pulse wave velocity was calculated for all patients preoperatively and postoperatively using a standardized technique on a Philips IU22 Vascular Ultrasound machine and the results compared. RESULTS: An increase in mean PWV following EVAR was demonstrated. The mean postprocedure PWV of 9.7 (± 4.5) cm/sec detected in the open group was significantly lower than the elevated 12.2 (± 4.5) cm/sec detected in the EVAR group. The surgical group also demonstrated a mean decrease of 0.2 (± 4.9) cm/sec in PWV following open repair compared to a mean increase of 3.3 (± 3.7) cm/sec in the EVAR group. CONCLUSION: EVAR patients have a significantly higher postoperative PWV measurement than those undergoing open abdominal aortic aneurysm repair. Patients who have undergone EVAR may be at a higher risk of cardiovascular morbidity in the long term. A larger scale study with a longer prospective follow-up is required.

Screening for Peripheral Arterial Disease and Carotid Artery Disease in Patients With Abdominal Aortic Aneurysm.

Screening for concomitant atherosclerotic disease is important in cardiovascular risk reduction. This study assessed the prevalence of carotid artery disease (CAD) and peripheral arterial disease (PAD) in patients with known abdominal aortic aneurysms (AAAs). All patients with AAA attending the vascular laboratory between the January 1, 2007, and December 31, 2009, were eligible for a carotid ultrasound and measurement of ankle brachial indices. A total of 389 (305 males) patients were identified on the AAA surveillance program with a mean (±standard deviation) age of 76 (±8) years. The mean age of the males was 75.4 (±7.8) years, and the mean age of the females was 77 (±11) years. A total of 332 patients were assessed for CAD, and 101 (30.4%) of those were found to have significant disease. A total of 289 patients were assessed for PAD of which 131 (45.3%) were found to have PAD at rest, and 289 patients were assessed for both and 59 (20.4%) patients had significant CAD + PAD. Patients with AAAs are at high risk of other atherosclerotic disorders, and, therefore, they should receive intensive medical optimization.

PET-CT as a predictor of outcome in resectable colorectal liver metastases.

INTRODUCTION: PET-computed tomography (PET-CT) is a useful staging imaging modality in colorectal liver metastases (CRLM). This study aimed to determine whether PET-CT parameters, standardized uptake value (SUV) and reconstructed tumour volume (RTV), are predictors of prognosis and survival. METHODS: A study of all resectable CRLM patients in the regional HPB unit from 2007-2009 was performed. Preoperative PET-CT scans were retrospectively reviewed; SUV, diameter and RTV for each lesion was recorded. Correlation analysis was performed with other pathological and biochemical parameters, by Pearson's correlation analysis. Survival analysis was performed using Cox regression hazard model. A P value of less than 0.05 was considered statistically significant. RESULTS: A total of 79 patients were included. SUV moderately correlated with tumour diameter, both PET-CT (r=0.4927; P<0.0001) and histology (r=0.4513; P=0.0003); RTV (r=0.4489; P<0.001), preoperative carcinoembryonic antigen (CEA) (r=0.4977; P=0.0001), and postoperative CEA (r=0.3727; P=0.004). Multivariate analysis found that an independent predictor of SUVmax was preoperative CEA (P=0.03). RTV strongly correlated with preoperative CEA (r=0.9389; P<0.0001). SUV and RTV had a negative effect on survival. CONCLUSION: PET-CT, in the setting of CRLM, may have a prognostic role in assessing survival. Although no definite conclusions can be drawn regarding the prognostic role of SUV and RTV, it acts to reinforce the need for further prospective studies to validate these findings.

Modulation of gut barrier function in patients with obstructive jaundice using probiotic LP299v.

OBJECTIVES: This study aimed to determine the effect of LP229v on intestinal permeability and tumour necrosis factor (TNF) p55 receptor concentrations in patients with obstructive jaundice undergoing biliary drainage. PATIENTS AND METHODS: Patients undergoing biliary drainage were recruited and randomized into three groups to receive Lactobacillus plantarum 299v (LP299v), inactivated LP299v (placebo) or water. These were administered daily at noon until 7 days after biliary drainage. Intestinal permeability was measured using the lactulose/mannitol (L/M) dual sugar absorption test on admission, the day before biliary drainage and on days 1 and 7 after biliary drainage. Blood and urine were collected to determine the L/M ratio and the TNF p55 receptor levels at each time point. RESULTS: A total of 25 patients were recruited; 12 had choledocholithiasis and nine had a periampullary tumour. Open surgical biliary drainage was performed in nine patients, endoscopic retrograde cholangiopancreatography in 12 and percutaneous transhepatic cholangiography in two. Five patients received LP299v, five received placebo and seven, water. The median L/M ratio was 0.035 (0.018-0.065) at baseline. No difference existed between the groups on admission, before drainage and on day 7 after drainage (P=0.59, 0.175 and 0.61, respectively). The L/M ratio was lower in the LP299v group on day 1 after drainage [0.01 (0.01) vs. 0.18 (0.03-0.3) and 0.11 (0.07-0.14); P=0.37]. Although the TNF p55 receptor levels were lower on day 1 after drainage in the LP299v group (15.3 vs. 30.9 vs. 82.7 ng/ml; P=0.43), the concentration at the four time points was similar (P=0.24, 0.96, 0.43 and 0.68). CONCLUSION: Pretreatment with probiotic LP299v improves intestinal permeability after biliary drainage and attenuates the inflammatory response. However, a larger multicentre trial is required to determine the effect on clinical outcome.

A variant in LDLR is associated with abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a common cardiovascular disease among older people and demonstrates significant heritability. In contrast to similar complex diseases, relatively few genetic associations with AAA have been confirmed. We reanalyzed our genome-wide study and carried through to replication suggestive discovery associations at a lower level of significance. METHODS AND RESULTS: A genome-wide association study was conducted using 1830 cases from the United Kingdom, New Zealand, and Australia with infrarenal aorta diameter≥30 mm or ruptured AAA and 5435 unscreened controls from the 1958 Birth Cohort and National Blood Service cohort from the Wellcome Trust Case Control Consortium. Eight suggestive associations with P<1×10(-4) were carried through to in silico replication in 1292 AAA cases and 30,503 controls. One single-nucleotide polymorphism associated with P<0.05 after Bonferroni correction in the in silico study underwent further replication (706 AAA cases and 1063 controls from the United Kingdom, 507 AAA cases and 199 controls from Denmark, and 885 AAA cases and 1000 controls from New Zealand). Low-density lipoprotein receptor (LDLR) rs6511720 A was significantly associated overall and in 3 of 5 individual replication studies. The full study showed an association that reached genome-wide significance (odds ratio, 0.76; 95% confidence interval, 0.70-0.83; P=2.08×10(-10)). CONCLUSIONS: LDLR rs6511720 is associated with AAA. This finding is consistent with established effects of this variant on coronary artery disease. Shared causal pathways with other cardiovascular diseases may present novel opportunities for preventative and therapeutic strategies for AAA.