Editor's Choice - Comparison of Outcomes for Major Contemporary Endograft Devices Used for Endovascular Repair of Intact Abdominal Aortic Aneurysms.

OBJECTIVE: To compare rates of mortality, rupture, and secondary intervention following endovascular repair (EVAR) of intact abdominal aortic aneurysms (AAA) using contemporary endograft devices from three major manufacturers. METHODS: This was a retrospective cohort study using linked clinical registry (Australasian Vascular Audit) and all payer administrative data. Patients undergoing EVAR for intact AAA between 2010 and 2019 in New South Wales, Australia were identified. Rates of all cause death, secondary rupture, and secondary intervention (subsequent aneurysm repair; other secondary aortic intervention) were compared for patients treated with Cook, Medtronic, and Gore standard devices. Inverse probability of treatment weighted proportional hazards and competing risk regression were used to adjust for patient, clinical, and aneurysm characteristics, using Cook as the referent device. RESULTS: This study identified 2 874 eligible EVAR patients, with a median follow up of 4.1 (maximum 9.5) years. Mortality rates were similar for patients receiving different devices (ranging between 7.0 and 7.3 per 100 person years). There was no statistically significant difference between devices in secondary rupture rates, which ranged between 0.4 and 0.5 per 100 person years. Patients receiving Medtronic and Gore devices tended to have higher crude rates of subsequent aneurysm repair (1.5 per 100 person years) than patients receiving Cook devices (0.8 per 100 person years). This finding remained in the adjusted analysis, but was only statistically significant for Medtronic devices (HR 1.57, 95% CI 1.02 - 2.47; HR 1.73, 95% CI 0.94 - 3.18, respectively). CONCLUSION: Major endograft devices have similar overall long term safety profiles. However, there may be differences in rates of secondary intervention for some devices. This may reflect endograft durability, or patient selection for different devices based on aneurysm anatomy. Continuous comparative assessments are needed to guide evidence for treatment decisions across the range of available devices.

Long-Term Outcomes Following Elective Repair of Intact Abdominal Aortic Aneurysms: A Comparison Between Open Surgical and Endovascular Repair Using Linked Administrative and Clinical Registry Data.

OBJECTIVE: Compare long-term mortality, secondary intervention and secondary rupture following elective endovascular aneurysm repair (EVAR) and open surgical repair (OSR). BACKGROUND: EVAR has surpassed OSR as the most common procedure used to repair abdominal aortic aneurysm (AAA), but evidence regarding long-term outcomes is inconclusive. METHODS: We included patients in linked clinical registry and administrative data undergoing EVAR or OSR for intact AAA between January 2010 and June 2019. We used an inverse probability of treatment-weighted survival analysis to compare all-cause mortality, cause-specific mortality, secondary interventions and secondary rupture, and evaluate the impact of secondary interventions and secondary rupture on all-cause mortality. RESULTS: The study included 3460 EVAR and 427 OSR patients. Compared to OSR, the EVAR all-cause mortality rate was lower in the first 30 days [adjusted hazard ratio (HR) = 0.22, 95% confidence interval (CI) 0.140.33], but higher between 1 and 4 years (HR = 1.29, 95% CI 1.12-1.48) and after 4years (HR = 1.41, 95% CI 1.23-1.63). Secondary intervention rates were higher over the first 30 days (HR = 2.26, 95% CI 1.11-4.59), but lower between 1 and 4years (HR = 0.59, 95% CI 0.48-0.74). Secondary aortic intervention rates were higher across the entire follow-up period (HR = 2.52, 95% CI 2.06-3.07). Secondary rupture rates did not differ significantly (HR = 1.06, 95% CI 0.73-1.55). All-cause mortality beyond 1 year remained significantly higher for EVAR after adjusting for any secondary interventions, or secendary rupture. CONCLUSIONS: EVAR has an early survival benefit compared to OSR. However, elevated long-term mortality and higher rates of secondary aortic interventions and subsequent aneurysm repair suggest that EVAR may be a less durable method of aortic aneurysm exclusion.

Multicentre Covariate Adjustment Analysis of Short-Term and 5-Year Outcomes after Endovascular Repair according to Sex.

BACKGROUND: Several studies have reported worse outcomes in women compared to men after endovascular aneurysm repair (EVAR). This study aimed to evaluate sex-specific short-term and 5-year outcomes after EVAR. METHODS: A total of 409 consecutive patients underwent elective EVAR from 2004 to 2017 at two tertiary hospitals in Western Australia. Baseline, intraoperative, and postoperative variables were examined retrospectively according to sex. The primary outcome was 30-day mortality (death within 30 days after EVAR). Secondary outcomes were 30-day composite endpoint, length of stay after EVAR, 5-year survival, freedom from reintervention, residual aneurysm size after EVAR, and major adverse event rate at 5-year follow-up. RESULTS: A cohort of 409 patients, comprising 57 women (14%) and 352 men (86%), was analysed. Female patients were older (median age, 76.8 versus 73.5 years, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%, p=0.017). Male patients were more likely to be past smokers (40.9% versus 22.8%. CONCLUSION: This study found no significant differences in 30-day and 5-year outcomes between female and male patients treated with EVAR, implying that EVAR remains a safe treatment choice for female patients.

A Binational Need Assessment to Define the Level of Endovascular Expertise Required by Vascular Surgical Trainees.

BACKGROUND: There has been a shift toward competency-based surgical education programs to improve trainee performance and achieve better patient outcomes. Endovascular procedures comprise a significant volume of vascular surgery, but the current methods for assessing the endovascular competence of vascular trainees in Australia and New Zealand are suboptimal. The objective of this study was to perform a need assessment to define the scope of endovascular expertise required by vascular surgical trainees to later aid in the development of novel surgical training assessment tools. METHODS: A modified Delphi method was used to achieve expert consensus. Fifty-three key stakeholders in vascular surgical education and training (SET) in Australia and New Zealand were invited to take part in the 2-stage survey. Experts were asked which procedures they considered to be requisite for vascular surgery trainees and at which SET level competence should be achieved. The results were reiterated to the expert panel in the second stage, and consensus considered achieved if over 75% of experts were in agreement. RESULTS: In the first stage 25 experts reached consensus that competence in 18 of the 26 procedures should be requisite for SET trainees. Twenty-two experts responded to the second stage and consensus was achieved for 12 out of 14 of the procedural items with mean percentage of experts in agreement being 90%. CONCLUSIONS: A need assessment using a modified Delphi method has achieved consensus among experts in vascular surgery regarding the endovascular procedures considered to be requisite for vascular surgery trainees in Australia and New Zealand.

A secure semi-field system for the study of Aedes aegypti.

BACKGROUND: New contained semi-field cages are being developed and used to test novel vector control strategies of dengue and malaria vectors. We herein describe a new Quarantine Insectary Level-2 (QIC-2) laboratory and field cages (James Cook University Mosquito Research Facility Semi-Field System; MRF SFS) that are being used to measure the impact of the endosymbiont Wolbachia pipientis on populations of Aedes aegypti in Cairns Australia. METHODOLOGY/PRINCIPAL FINDINGS: The MRF consists of a single QIC-2 laboratory/insectary that connects through a central corridor to two identical QIC-2 semi-field cages. The semi-field cages are constructed of two layers of 0.25 mm stainless steel wire mesh to prevent escape of mosquitoes and ingress of other insects. The cages are covered by an aluminum security mesh to prevent penetration of the cages by branches and other missiles in the advent of a tropical cyclone. Parts of the cage are protected from UV light and rainfall by 90% shade cloth and a vinyl cover. A wooden structure simulating the understory of a Queenslander-style house is also situated at one end of each cage. The remainder of the internal aspect of the cage is covered with mulch and potted plants to emulate a typical yard. An air conditioning system comprised of two external ACs that feed cooled, moistened air into the cage units. The air is released from the central ceiling beam from a long cloth tube that disperses the airflow and also prevents mosquitoes from escaping the cage via the AC system. Sensors located inside and outside the cage monitor ambient temperature and relative humidity, with AC controlled to match ambient conditions. Data loggers set in the cages and outside found a <2 °C temperature difference. Additional security features include air curtains over exit doors, sticky traps to monitor for escaping mosquitoes between layers of the mesh, a lockable vestibule leading from the connecting corridor to the cage and from inside to outside of the insectary, and screened (0.25 mm mesh) drains within the insectary and the cage. A set of standard operating procedures (SOP) has been developed to ensure that security is maintained and for enhanced surveillance for escaping mosquitoes on the JCU campus where the MRF is located. A cohort of male and female Aedes aegypti mosquitoes were released in the cage and sampled every 3-4 days to determine daily survival within the cage; log linear regression from BG-sentinel trapping collections produced an estimated daily survival of 0.93 and 0.78 for females and males, respectively. CONCLUSIONS/SIGNIFICANCE: The MRF SFS allows us to test novel control strategies within a secure, contained environment. The air-conditioning system maintains conditions within the MRF cages comparable to outside ambient conditions. This cage provides a realistic transitional platform between the laboratory and the field in which to test novel control measures on quarantine level insects.

Surgical practice to reduce dialysis access insufficiency.

BACKGROUND: Patients who are dependant on a percutaneous central venous catheter for dialysis have an excess morbidity and mortality compared with patients with an autologous arteriovenous fistula. METHODS: In an effort to improve outcomes related to episodes of permanent access insufficiency, defined as a patient requiring a venous catheter for haemodialysis, a 12-month prospective audit of surgery carried out to establish and maintain dialysis access was carried out at our institution. RESULTS: Effective measures that reduced the period of time that patients required a venous catheter for dialysis included regular communication between dialysis staff, the surgical service and patients attending for treatment in the dialysis unit, liberal use of duplex ultrasound imaging, pursuing autologous access in the majority of patients, early intervention to correct failing vascular access before conduit thrombosis, using both traditional open surgical and endovascular solutions in establishing and maintaining vascular access, using peritoneal dialysis as a long-term or temporary alternative to haemodialysis and, in cases of arteriovenous polytetrafluoroethylene graft occlusion, early thrombectomy and mandatory revision to provide a conduit immediately available for effective dialysis. CONCLUSION: Conducting an audit of surgical practice contributed to an improvement in outcomes for dialysis-dependant patients. Establishing an arteriovenous fistula in a greater proportion of cases before initiating renal replacement therapy may further address the problem of dialysis access insufficiency.

Damage control surgery and angiography in cases of acute mesenteric ischaemia.

BACKGROUND: Acute mesenteric arterial occlusion typically presents late and has an estimated mortality of 60-80%. This report examines the evolution of a novel management approach to this difficult surgical problem at a teaching hospital in rural Australia. METHODS: A retrospective review of 20 consecutive cases that presented to Lismore Base Hospital, Lismore, New South Wales, between 1995 and 2003 was performed. RESULTS: Of the 16 patients who were actively treated, 10 survived. Mortality was associated with attempting an emergency operative revascularisation and not performing a second-look laparotomy. All three patients who had a damage control approach at the initial operation survived and in four cases endovascular intervention successfully achieved reperfusion of acutely ischaemic bowel. CONCLUSIONS: Evidence from the series of patients described suggests that damage control surgery and early angiography improve survival in patients suffering acute mesenteric ischaemia. A damage control approach involves emergency resection of ischaemic bowel with no attempt to restore gastrointestinal continuity and formation of a laparostomy. Patients are stabilised in the intensive care unit (ICU) and angiography can be arranged to either plan a definitive bypass procedure or alternatively endovascular therapies can be carried out in an attempt to arrest gastrointestinal infarction. Definitive surgery is then considered after 2-3 days. This approach is particularly attractive if immediate specialist vascular expertise is not available.

Prevalence of production of virus-specific interferon-gamma among seronegative hepatitis C-resistant subjects reporting injection drug use.

This report describes subjects who were highly likely to have been repeatedly exposed to hepatitis C virus (HCV) through injection drug use and who remained negative for anti-HCV antibody. Production of virus-specific interferon- gamma by peripheral blood mononuclear cells was seen in the majority of subjects (72%) and was associated with higher-risk behavior. For 92% of the subjects, results of recombinant immunoblot assays demonstrated faint bands against nonstructural proteins. The immune responses described are likely to have been primed and maintained by episodes of subclinical infection without classic seroconversion and may indicate a hepatitis C-resistant phenotype. Vaccine strategies to mimic this response may provide protection against persistent HCV infection.

Clearance of hepatitis C viremia associated with cellular immunity in the absence of seroconversion in the hepatitis C incidence and transmission in prisons study cohort.

Understanding the earliest virological and immunological events in acute hepatitis C virus (HCV) infection may provide insight into the determinants of protective immunity. Four cases of HCV viremia with subsequent viral clearance, but without biochemical hepatitis or anti-HCV seroconversion, are reported from a prospective cohort study of prison inmates. Two of the subjects who developed sustained viremia were assessed for production of interferon (IFN)- gamma, by use of the enzyme-linked immunospot (ELISPOT) method and by assessment of HCV cytotoxic T lymphocyte (CTL) activity, CD4 lymphocyte proliferative responses, HCV load, and genotype. After 2-6 months of viremia, all 4 subjects cleared serum HCV RNA. Specific cellular responses were detected in both of the subjects who were assessed, and production of IFN- gamma was demonstrated in one subject. All subjects had weak, but consistent, serological reactivity against HCV nonstructural proteins on immunoblot testing, despite repeatedly nonreactive HCV ELISA tests. These cases highlight the potential for cellular immune responses against HCV to facilitate viral clearance, responses that may model those required for effective HCV vaccination.

Natural history models for hepatitis C-related liver disease: different disease progression parameters for different settings.

An understanding of the natural history of hepatitis C virus (HCV) infection has improved in recent years. Estimates of liver disease progression among people with chronic hepatitis C have been developed from various study populations, including liver clinics, post-transfusion hepatitis C cohorts and community-based cohorts. These estimates can be used in hepatitis C natural history models; however, they need to be matched to differing requirements. Estimation and projection of liver disease burden at the population level requires estimates of HCV prevalence and incidence, and disease progression among all people with chronic hepatitis C. Liver disease progression based on community cohorts would appear the most appropriate for a population level model. In contrast, models that examine the cost-effectiveness of antiviral therapy for people with chronic hepatitis C require disease progression estimates from the treatment setting. Further models are required to determine individual prognosis and should be based on an assessment of cofactors for liver disease progression.

Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation.

The factors influencing lymphocyte trafficking to the liver lobule during chronic hepaititis C virus (HCV) infection are currently not well defined. Interferon-gamma-inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection. This study sought to define the cellular source of IP-10 in the liver by immunohistochemistry, to examine the expression of its receptor, CXCR3, on T lymphocytes isolated from blood and liver tissue, and to correlate IP-10 expression with the histological markers of inflammation and fibrosis. IP-10 was expressed by hepatocytes but not by other cell types within the liver, and the most intense immunoreactivity was evident in the areas of lobular inflammation. The IP-10 receptor was expressed on a significantly higher proportion of T lymphocytes in the liver compared with blood. CD8 T lymphocytes, which predominate in the liver lobule, were almost uniformly CXCR3-positive. The expression of IP-10 mRNA correlated with lobular necroinflammatory activity but not with inflammation or fibrosis in the portal tracts. These findings suggest that IP-10 may be induced by HCV within hepatocytes and may be important in the pathogenesis of chronic HCV infection, as recruitment of inflammatory cells into the lobule is an important predictor of disease progression.

The presence of an intrahepatic cytotoxic T lymphocyte response is associated with low viral load in patients with chronic hepatitis C virus infection.

BACKGROUND/AIMS: The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. METHODS: Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. RESULTS: A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P=0.004). Hepatic lobular infiltration by CD8(+)T cells correlated weakly with serum alanine aminotransferase levels (r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. CONCLUSIONS: HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection.

Quantification of hepatitis C virus in human liver and serum samples by using LightCycler reverse transcriptase PCR.

A highly sensitive, non-probe-based, real-time quantitative reverse transcriptase PCR was developed for viral load measurements in both serum and liver samples from patients with hepatitis C virus (HCV) infection. With synthetic RNA, the linearity of the approach was conserved over a wide range of HCV copy numbers. There was a strong correlation between hepatic and serum viral load measurements (r = 0.689, P = 0.004, n = 15), indicating that the level of viremia reflected the amount of virus present in the liver.

Is severe liver disease a common outcome for people with chronic hepatitis C?

For people with chronic hepatitis C, an assessment of their risk of progression to advanced liver disease is a major priority. Early studies of the natural history of chronic hepatitis C suggested that development of cirrhosis was a relatively common outcome, even in the first 20 years of infection. These studies were either cross-sectional liver clinic series of people referred for assessment to specialist clinics, or longitudinal cohorts of people with post-transfusion hepatitis. More recent studies (particularly longitudinal community-based cohorts) indicate that liver disease progression is generally slow, and that a minority of people with chronic hepatitis C will develop advanced liver disease. Based on an extensive review of studies reporting on chronic hepatitis C natural history, we have developed a Markov model of liver disease progression. This model estimates that the risk of progression to cirrhosis is 7% and 20% after 20 and 40 years of infection, respectively. Corresponding estimates for hepatitis C-related mortality are 1% and 4%. However, liver disease progression is highly variable, and certain subgroups of people with chronic hepatitis C are at increased risk of advanced liver disease. Those groups include people with a heavy alcohol intake, those who have coinfection with HIV or HBV, and those who have already progressed to moderate to severe hepatic fibrosis.