Editor's Choice - Relevance of Infarct Size, Timing of Surgery, and Peri-operative Management for Non-ischaemic Cerebral Complications After Carotid Endarterectomy.

OBJECTIVE: To assess the incidence of post-operative non-ischaemic cerebral complications as a pivotal outcome parameter with respect to size of cerebral infarction, timing of surgery, and peri-operative management in patients with symptomatic carotid stenosis who underwent carotid endarterectomy (CEA). METHODS: Retrospective analysis of prospectively collected single centre CEA registry data. Consecutive patients with symptomatic carotid stenosis were subjected to standard patch endarterectomy. Brain infarct size was measured from the axial slice of pre-operative computed tomography/magnetic resonance imaging demonstrating the largest infarct dimension and was categorised as large (> 4 cm2), small (≤ 4 cm2), or absent. CEA was performed early (within 14 days) or delayed (15 - 180 days) after the ischaemic event. Peri-operative antiplatelet regimen (none, single, dual) and mean arterial blood pressure during surgery and at post-operative stroke unit monitoring were registered. Non-ischaemic post-operative cerebral complications were recorded comprising haemorrhagic stroke and encephalopathy, i.e., prolonged unconsciousness, delirium, epileptic seizure, or headache. RESULTS: 646 symptomatic patients were enrolled of whom 340 (52.6%) underwent early CEA; 367 patients (56.8%) demonstrated brain infarction corresponding to stenosis induced symptoms which was small in 266 (41.2%) and large in 101 (15.6%). Post-operative non-ischaemic cerebral complications occurred in 12 patients (1.9%; 10 encephalopathies, two haemorrhagic strokes) and were independently associated with large infarcts (adjusted odds ratio [OR] 6.839; 95% confidence interval [CI] 1.699 - 27.534) and median intra-operative mean arterial blood pressure in the upper quartile, i.e., above 120 mmHg (adjusted OR 13.318; 95% CI 2.749 - 64.519). Timing of CEA after the ischaemic event, pre-operative antiplatelet regimen, and post-operative blood pressure were not associated with non-ischaemic cerebral complications. CONCLUSION: Infarct size and unintended high peri-operative blood pressure may increase the risk of non-ischaemic complications at CEA independently of whether performed early or delayed.

Effects Of Gelatine-Coated Vascular Grafts On Human Neutrophils.

UNLABELLED: The aim of the study was to investigate the immune-modulatory potential of commercially available PTFE and polyester vascular grafts with and without gelatine-coating. The biomaterial-cell-interaction was characterized by changes of established parameters such as PMN-related receptors/mediators, phagocytosis potential and capacity as well as the effect of an additional plasma-dependent modulation. MATERIAL AND METHODS: By means of a standardized experimental in vitro model, various vascular graft material (PTFE/polyester/uncoated/gelatine-coated) was used for incubation with or without plasma and co-culturing with human neutrophile granulocytes (PMN) followed by analysis of representative receptors and mediators (CD62L, CD11b, CXCR2, fMLP-R, IL-8, Elastase, LTB4). Oxidative burst assessed phagocytosis capacity. RESULTS: Comparing the vascular grafts, un-coated PTFE induced the lowest magnitude of cell stimulation whereas in case of gelatine-coating, cell response exceeded those of the other vascular grafts. This was also found comparing the polyester-based prosthetic material. Gelatine-coated polyester led to a more pronounced release of elastase than gelatine-coated PTFE and the uncoated materials. The results of oxidative burst indicated a reduced phagocytosis capacity in case of gelatine-coated polyester. Plasma incubation did also provide an impact on the cellular response. While in case of gelatine-coating, PMN-related receptor stimulation became lower, it increased by native polyester. The latter one did also induce more mediators such as IL-8 and LTB4 than gelatine-coated material. CONCLUSIONS: There have been no extensive data on cell-cell interactions, cytokines and general histo-/hemocompatibility of human cells by the new generation of vascular grafts. It remains still open whether healing process and infectious resistance can be compromised by material-dependent over-stimulation or reduced phagocytosis potential of the immune cells of the primary unspecific immune response induced by gelatine-coated materials.

First-in-man results of a novel vascular graft coated with resorbable polymer for aortic reconstructions--a multicenter, non-randomized safety study.

OBJECTIVES: The purpose of this "first-in-man" study was to investigate the safety of a novel vascular polyester prosthesis coated with a resorbable polymer and free of any animal-based coating agents such as gelatin or collagen. METHODS: In a nonrandomized first-in-man multicenter safety study, the frequency of perigraft seroma (PGS) as the primary endpoint was studied in consecutive patients undergoing aortic reconstructions. The follow-up control to study the primary endpoint was intended at 3 months under routine clinical conditions. Pre- and postoperative white blood cell counts (WBC), C-reactive protein (CRP), and liver enzyme levels to characterize the systemic inflammation response and possible metabolic consequences were determined at different postoperative time points (secondary endpoints). Additionally, the primary unassisted patency rate, perioperative complications and serious adverse events, as well as intraoperative handling properties of the graft based on a semiquantitative scale were assessed. Magnetic resonance angiography (MRA) follow-up investigations were scheduled postoperatively at 3 months to determine graft tissue integration and the presence of PGS. RESULTS: A total of 24 patients with comorbidities such as coronary artery disease (8.3 %, 2/24), chronic occlusive pulmonary disease (COPD, 8.3 %, 2/24), Fontaine III/IV (20.8 %, 5/24), and diabetes (20.8 %, 5/24) were enrolled from June 2011 to September 2012. Due to two early nongraft-related deaths, there were 22 patients that had a follow-up. In these 22 patients, the freedom from PGS was 90.9 % (20/22) suggesting that the graft/tissue integration was comparable to other vascular grafts described in the relevant literature. WBC counts were not significantly different (pre (8.67 ± 2.98 1/nl) vs. follow-up (7.97 ± 2.24 1/nlI, p = 0.203). Likewise, preoperative CRP serum levels (6.47 ± 11.59 mg/l) were not different from those at follow-up (7.87 ± 12.81 mg/l, p = 0.769). There were two patients with a documented coagulation disorder and two premature deaths (cardiac failure, cerebral bleeding). The primary unassisted patency at follow-up was 77.3 % (17/22) in all patients who reached the follow-up (85.0 % or 17/20 if two cases with documented coagulation disorders are excluded). The reasons for occlusions were technical/surgical difficulties (2/5) and documented coagulation disorders (2/5). In one occlusion, the cause was unknown. There were no graft infections. Intraoperative graft handling properties were evaluated less favorable as compared to the routinely used gelatin- or collagen-coated polyester grafts in each investigator's clinical practice. CONCLUSIONS: Our results suggest that Uni-Graft® Synthetic is a promising prosthetic vascular graft to reduce PGS. Our findings should be interpreted with caution noting the limitation of the lack of a control group.

Interactions of neutrophils with silver-coated vascular polyester grafts.

BACKGROUND: In reconstructive vascular surgery, infection is one of the most feared complications because of the high mortality. While the antimicrobial effect of a silver-coated endoprosthesis has been proven in experimental trials, there are no reports on its interactions with granulocytes, the first effector cells in general inflammation and in infection. MATERIALS AND METHODS: Therefore, we investigated whether silver coating of vascular polyester grafts affects receptor expression, mediator release, and functions of human neutrophils relevant for microbicidal activity and the wound-healing process. Naïve neutrophils were analyzed for their cellular receptors such as cluster of differentiation (CD)62L, CD11b, CXCR2, and fMLP-R, the mediators interleukin 8, granulocyte elastase (human neutrophil elastase), and leukotriene B4 (LTB4) as well as for microbicidal capacity (oxidative burst) in vitro. In addition, the role of plasma coating for receptor expression was addressed. RESULTS: There was both a decrease of CD62L and CXCR2 expression and an increase of CD11b, fMLP-R expression, elastase release, and LTB4 generation, which were statistically significant (p = 0.04; p = 0.01; p = 0.0; p = 0.0; p = 0.01; p = 0.02, respectively) in the presence of the silver-coated graft compared with non-silver-coated vascular grafts. In addition, microbicidal activity was significantly (p = 0.0) impaired by the silver-coated graft. Coating of the vascular grafts with plasma did not alter the former observations significantly. CONCLUSION: The results may indicate that silver-coated vascular polyester grafts activate neutrophils chronically which may favor tissue destruction and impaired antimicrobial effects.

The influence of polymorbidity, revascularization, and wound therapy on the healing of arterial ulceration.

OBJECTIVE: An ulcer categorized as Fontaine's stage IV represents a chronic wound, risk factor of arteriosclerosis, and co-morbidities which disturb wound healing. Our objective was to analyze wound healing and to assess potential factors affecting the healing process. METHODS: 199 patients were included in this 5-year study. The significance levels were determined by chi-squared and log-rank tests. The calculation of patency rate followed the Kaplan-Meier method. RESULTS: Mean age and co-morbidities did not differ from those in current epidemiological studies. Of the patients with ulcer latency of more than 13 weeks (up to one year), 40% required vascular surgery. Vascular surgery was not possible for 53 patients and they were treated conservatively. The amputation rate in the conservatively treated group was 37%, whereas in the revascularizated group it was only 16%. Ulcers in patients with revascularization healed in 92% of cases after 24 weeks. In contrast, we found a healing rate of only 40% in the conservatively treated group (p<0.001). Revascularization appeared more often in diabetic patients (n=110; p<0.01) and the wound size and number of infections were elevated (p=0.03). Among those treated conservatively, wound healing was decelerated (p=0.01/0.02; chi(2) test). CONCLUSIONS: The success of revascularization, presence of diabetes mellitus, and wound treatment proved to be prognostic factors for wound healing in arterial ulcers.

Inadvertend catch of a factor VIII rich thrombus with a femoral sheath during cardiac catheterization.

The role of elevated factor VIII as a risk factor for thromboembolic events during atrial fibrillation (AF) has not been explored. Here, we present a case of a white Caucasian male with paroxysmal AF suffering from thromboembolic complications in the presence of persistently increased factor VIII levels. Immunohistological examination revealed a granulocyte-rich cardiac embolus with large deposits of factor VIII. The association between elevated factor VIII levels and thromboembolic events, especially in AF patients without classical thromboembolic risk factors, merits further investigation.

Effect of intraperitoneal application of an endotoxin inhibitor on survival time in a laparoscopic model of peritonitis in rats.

Gram-negative sepsis due to fecal peritonitis is a hazardous disease with a high percentage having a lethal course. The inflammatory effects are induced by endotoxin release. We performed this study to evaluate the potential of direct intraperitoneal application of an endotoxin inhibitor in a laparoscopic peritonitis model in rats. The human feces specimen was prepared, and a standard fecal specimen (0.5 ml/kg b.w.) was applied via minilaparotomy. The rats were randomized to two studies. First, rats were randomized to three groups to define the survival time: (1) rats without further manipulation; (2) rats with laparoscopic lavage using NaCl; (3) rats with laparoscopic lavage using endotoxin inhibitor. Second, rats underwent the same procedure used in the first part of the study and an additional group with only NaCl lavage without peritonitis was randomized. To evaluate the immunologic or biochemical effects, animals were killed at a standard time of 20 hours until the postmortem examination was established. Interleukins 6 and 10 (IL-6, IL-10), malondialdehyde, and protein carbonyl group levels in plasma and particularly in peritoneal fluid were assayed. The first part of the experiment showed significantly increased survival after endotoxin inhibitor lavage. In the second part, administration of endotoxin inhibitor intraperitoneally caused a significant reduction of IL-6 in the peritoneal fluid, in contrast to that in the other groups. Laparoscopic application of endotoxin inhibitor intraperitoneally thus produced a beneficial effect on survival and reduction of IL-6 in peritoneal fluid. Hence, it is possible to influence the inflammation cascade by causing intraperitoneal endotoxin inhibition.

Vascular graft infections: in vitro and in vivo investigations of a new vascular graft with long-term protection.

We investigated a polyester vascular prosthesis (PET) coated with elemental silver (SC). Measurement of silver release over a period of 52 weeks by means of inductively coupled plasma atomic emission spectrometry of PET with (PET-G) and without (PET-N) gelatine impregnation revealed a silver release on the first day of 1.2 +/- 0.2 microg (PET-N) and 1.2 +/- 0.1 microg (PET-G) (calculated for 1 g of prosthesis); from the 90th day onward, it was between 0.22 +/- 0.14 microg (PET-N) and 0.18 +/- 0.12 microg (PET-G) per day. The prostheses were incubated with Staphylococcus aureus (S.a.), Staphylococcus epidermidis (S.e.), or Escherichia coli (E.c.) to investigate in vitro antibacterial efficacy. After 6 h of incubation, no colony-forming units were to be seen for any of the bacterial suspensions for PET with SC (p < 0.001). To investigate in vivo antibacterial efficacy, PET-G rings with and without SC contaminated with S.a., S.e., or E.c. were implanted in 18 albino rabbits and examined 7 days after agar culture for 48 h. The silver coating was associated with a significant reduction in bacterial growth (S.a., p = 0.001; S.e., p < 0.005; E.c., p < 0.001). The silver-coated prosthesis, with and without gelatine impregnation, had a significantly antibacterial effect with continuous release of silver.

Comparison of the ovine and porcine animal models for biocompatibility testing of vascular prostheses.

OBJECTIVE: Evaluation of the pig and sheep models for biocompatibility investigations of vascular prostheses (VP). DESIGN: Comparative analysis of animal experimental investigations involving two different animal models. MATERIALS AND METHODS: Commercially available polyester vascular prostheses (PET-VP) were implanted into two different animal models (infrarenal porcine aorta and ovine carotid artery). The costs, surgical handling, patency rate, and healing on the basis of macroscopic, microscopic, and immunohistochemical criteria were analyzed over a period of 3 months. RESULTS: Handling and operating times (63 +/- 10 versus 76 +/- 16 min; P = 0.125) did not differ significantly. The cost of the two animal models was comparable. Integration of the VP was complete in the sheep model, but varied in the pig model (two complete, four incomplete). Complete endothelialization of all VPs was observed in the pig, which contrasted with the sheep with complete (circular) endothelialization only in the region of the anastomosis. The thickness of neointima in the region of the anastomosis differed insignificantly; immunohistochemically, only periprosthetic Ki67 was significantly reduced (28.7 +/- 9.9 versus 6 +/- 0.9%; P = 0.002) in the sheep. CONCLUSIONS: In the porcine model, extremely good endothelialization of the VP was observed, with formation of a rapid neointimal hyperplasia. The ovine model was characterized by the fact that postoperative follow-up investigations were easy to perform. Complete endothelialization was not observed.