Selective Intra-procedural AAA sac Embolization During EVAR Reduces the Rate of Type II Endoleak.

OBJECTIVE: The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) <40% are considered to be positive predictive factors for persistent type II endoleak (ELIIp). The aim of the present study was to evaluate the effectiveness of sac embolization during EVAR in patients with pre-operative morphological risk factors (p-MRF) for ELIIp. METHODS: Patients undergoing EVAR and intra-procedural AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra-procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months. RESULTS: Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p < .001) at discharge, and this was confirmed at 6-12 months (7/26 vs. 30/44 respectively, p = .001, and 5/25 vs. 32/44, respectively, p < .001). On multivariate analysis, intra-procedural AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p = .007) and 12 months (OR 0.098, 95% CI 0.02-0.35; p < .001). No differences in median AAA sac diameter shrinkage were detected between the two groups at 6-12 months (p = .42 and p = .58, respectively). Freedom from ELIIp related and embolization related re-interventions was 100% in both groups, at 6 and 12 months. CONCLUSION: Selective intra-procedural AAA sac embolization in patients with p-MRF is safe and could be an effective method to reduce ELIIp. Further studies are mandatory to support these results at long-term follow up.

Could four-dimensional contrast-enhanced ultrasound replace computed tomography angiography during follow up of fenestrated endografts? Results of a preliminary experience.

OBJECTIVE: To evaluate four-dimensional contrast-enhanced ultrasound (4D-CEUS) as an alternative imaging method to computed tomography angiography (CTA) during follow up of fenestrated endovascular aneurysm repair (FEVAR) for juxta- and para-renal abdominal aortic aneurysms (AAA). METHODS: Between October 2011 and March 2012, all consecutive patients who underwent FEVAR follow up were included in the study and evaluated with both 4D-CEUS and CTA. The interval between the two examinations was always ≤ 30 days. Endpoints were the comparison of postoperative AAA diameter, AAA volume, presence of endoleaks, revascularized visceral vessel (RVV) visualization, and patency. Comparative analysis was performed using Bland-Altman plots and McNemar's Chi-square test. RESULTS: Twenty-two patients (96% male, 4% female; mean age 74 ± 7 years; American Society of Anesthesiologists grade III/IV 82%/18%) were enrolled. Seventy-eight RVV (fenestrations: 60; scallops: 17; branches: 1) were analyzed. The mean AAA diameter evaluated by 4D-CEUS and CTA was 45 ± 10 mm (range 30-69 mm) and 48 ± 9 mm (range 32-70 mm), respectively. The mean difference was 3 ± 3 mm. The mean AAA volume evaluated by 4D-CEUS and CTA was 150 ± 7 cc (range 88-300 cc) and 159 ± 68 cc (range 80-310 cc), respectively. The mean difference was 7 ± 4 cc; a Bland-Altman plot revealed agreement in AAA diameter and volume evaluation (p < .01) between 4D-CEUS and CTA. The observed agreement for the detection of endoleaks was 95%. McNemar's Chi-square test confirmed that 4D-CEUS and CTA were equivalent (p > .05) at detecting endoleaks. The first segment of six (8%) RVVs (four renal and two superior mesenteric arteries) was not directly visualized by 4D-CEUS owing to obesity, but the contrast enhancement into the distal part of vessel or into the relative parenchyma gave indirect information about their patency. McNemar's Chi-square test demonstrated the superiority of CTA (p = .031) in visualizing RVVs. The patency of 77/78 RVVs was confirmed with both techniques. McNemar's Chi-square test confirmed that 4D-CEUS and CTA were equivalent in their ability to detect visceral vessel patency. CONCLUSIONS: The data suggest that 4D-CEUS is as accurate as CTA in the evaluation of postoperative AAA diameter and volume, endoleak detection, and RVV patency after FEVAR. Four-dimensional CEUS could provide hemodynamic information regarding RVVs, and reduce radiation exposure and renal impairment during follow up. Obesity limits the diagnostic accuracy of 4D-CEUS.

Proximal aortic neck angle does not affect early and late EVAR outcomes: an AnacondaTM Italian Registry analysis.

AIM: The aim of this paper was to evaluate early and 3-year results of the endovascular repair (EVAR) for abdominal aortic aneurysm (AAA) using the AnacondaTM endograft in patients with severe proximal aortic neck angle. METHODS: A retrospective analysis of the AnacondaTM Italian Registry was carried out. Two groups of patients were identified according to the presence of a severe (Group A, GA: ≥ 60°) or an absent (Group B, GB: <45°) proximal aortic neck angle. Preoperative, procedural and follow-up data were evaluated. Mortality, proximal type I endoleak, freedom from iliac leg thrombosis and conversion to open repair were analyzed at 30-day and 3-year follow-up. The results of GA and GB were compared. RESULTS: From 2005 to 2012, 1030 patients were enrolled in the Registry. Sixty-five patients (6.3%) were included in GA and 737 (71.5%) in GB. The mean age and AAA diameter were respectively 76.8 years and 62.7 mm in GA and 77.2 years and 56.5 mm in GB (P=NS). The ASA ≥ 3 was reported in the 95.3% of GA vs. 81% of GB (P=0.005). The endograft main-body was repositioned in 35% of cases in GA and 20.7% in GB (P=0.008); there were no differences in the main-body ballooning and proximal aortic cuff placement. There were no statistical differences in 30-day mortality (GA 1.5% vs. GB 1.3%), proximal type I endoleaks (GA 1.5% vs. GB 0.8%), iliac leg thrombosis (GA 1.5% vs. GB 1.4%) and conversion to open repair (GA 3% vs. GB 0.6%). The 3-year survival was 95.4% in GA and 94.7% in GB (P=NS). Freedom from proximal type I endoleak, iliac leg thrombosis and conversion to open repair were respectively 98.5%, 95.4%, and 95.4% in GA and 97.8%, 96.9%, and 98.5% in GB (P=NS). CONCLUSION: The AnacondaTM Italian Registry reports good results in terms of clinical success at 3-year follow-up. AAA with severe proximal aortic neck can be treated with similar outcomes to AAA with favorable neck anatomy. The endograft repositionability is a benefit in cases with severe neck angle.

Betamethasone, progesterone and RU-486 (mifepristone) exert similar effects on connexin expression in trophoblast-derived HTR-8/SVneo cells.

Connexins (Cx) are membrane proteins able to influence cell trophoblast responses, such as proliferation, differentiation, migration and invasiveness. Likewise, glucocorticoids are also known to modulate many factors involved in implantation, including trophoblast gap-junction intercellular communication, although their influence on pregnancy is controversial. In order to investigate the effects of betamethasone, a synthetic glucocorticoid, on Cx and glucocorticoid receptor (GR) expression and localisation, as well as on cell proliferation, the extravillous trophoblast-derived HTR-8/SVneo cell line was used as a model. The results, confirmed by means of immunofluorescence, demonstrate that betamethasone selectively modifies GR and Cx expression, enhancing the GRα isoform without affecting GRß, and inhibiting Cx40 expression whilst increasing that of Cx43 and Cx45. Furthermore, betamethasone was shown to exert an inhibitory action on cell proliferation. In this model the abortion drug RU-486 (mifepristone), reported to be a GR antagonist, did not counteract this effect of betamethasone. On the contrary, it induced responses similar to those of the hormone. Knowing that RU-486 is also a potent progesterone-receptor antagonist, the effect of progesterone alone and in combination with the drug on Cx expression and cell proliferation was then tested. Progesterone showed the same effect as betamethasone on Cx expression, but it did not affect proliferation. Based on these results, neither the abortion effects of RU-486 nor the protective action of betamethasone and progesterone are exerted by modulation of Cx. RU-486 did not antagonise the progesterone effect, suggesting that its abortive action does not involve alteration of trophoblast Cx expression.

Evaluation of papain/chymopapain cross allergenicity.

Recent clinical evidence suggests that papain and chymopapain may share common allergenicity. Patients that become sensitized to papain may subsequently experience an allergic reaction when they are exposed to chymopapain. This study demonstrates a cross antigenicity between the proteolytic enzyme preparations papain and chymopapain. Serum samples from six patients who demonstrated 4+ skin reactions to papain also revealed positive RAST ratios to both papain and chymopapain. In addition, serum samples from 12 clinically nonreactive patients who had discolysis with chymopapain demonstrated positive RAST results to papain as well as to chymopapain.

Pretreatment serum levels of IgE to chymopapain in reactive patients.

Discolysis (chemonucleolysis) with chymopapain, the proteolytic enzyme, is currently being used in the treatment of herniated lumbar discs. Of the patients receiving treatment, approximately 1% experience an anaphylactic reaction. This reaction is thought to be mediated by IgE antibodies to chymopapain. Because of this, it may be possible to predict potential reactors using in vitro testing. In the current study, five out of seven patients who experienced allergic anaphylaxis during discolysis demonstrated high IgE serum levels to chymopapain before treatment.

Reactivity of IgE and IgG serum levels to chymopapain after chemonucleolysis.

Patients suffering from herniated lumbar intervertebral disks can currently be treated by chemonucleolysis. This procedure involves reducing the nucleus pulposus by injecting chymopapain into the affected intervertebral disk. A small percentage of the patients who undergo this treatment experience an immediate hypersensitivity reaction. In this study the IgE and IgG specific for sensitivity to chymopapain of 21 patients receiving chymopapain (Discase for injection) was monitored over a 6-month period after injection. This study demonstrates that serum levels of IgE and IgG to chymopapain increase after chemonucleolysis.

Further studies on the neonatal ferret model of infection and immunity to and attenuation of human parainfluenza viruses.

Earlier we reported on the susceptibility via the intranasal route of inoculation of newborn ferrets to infection by wild and serially egg passaged parainfluenza type 3 virus. The wild type consistently induced fatal infection whereas with serial egg passage, mortality rate decreased while the degree of infectivity remained the same. This attenuation was accompanied by a change in capacity to induce interferon and decreased growth in human and primate cell cultures. The present work reports, similarly, on the susceptibility of newborn ferrets to wild and serially egg passaged parainfluenza types 1 and 2. Wild type infections caused significantly greater mortality than did egg passaged materials, although infectivity rates were approximately the same. Wild and egg passaged strains produced silent infections in adult ferrets and induced specific circulating hemagglutinin inhibiting antibodies. Newborn offspring of dams inoculated with wild or egg passaged viruses resisted challenge with wild virus. The apparent attenuation of the wild type virus with serial egg passage viruses resisted challenge with wild virus. The apparent attenuation of the wild type virus with serial egg passage was correlated with alteration in cell culture host range and capacity to induce interferon. The low and mid level passages of types 1 and 3 were the subject of clinical vaccination trials in man in four age groups: 18-35 years, 14-16 years and 6-12 years. The clinical and serologic results of these studies will be reported elsewhere.

An animal model for studying infection and immunity to and attenuation of human parainfluenza viruses.

Neonatal ferrets were found to be highly via the intranasal route of inoculation to infection with wild type isolates of parainfluenza viruses. Wild type infection consistently resulted in deaths of these animals in 48 to 72 hours. Autopsy and histopathological findings in lung tissue were consistent with those of viral infection. Virus could consistently be isolated from lung tissues. Using wild green monkey kidney grown viruses and selected passage levels of egg adapted viruses, virus attenuation markers were observed by comparing infectivity in neonatal ferrets, propagation in cell cultures of human, primate, rabbit and chick embryo tissues, and in chick embryos and interferon induction. Adult pregant dams could be immunized (silently infected) and circulating hemagglutinin-inhibiting antibody could be detected within two weeks of intranasal instillation of wild and low egg passage types of virus. The animal model described could be valuable in studying immunity to parainfluenza virus infections.