A Comparison of Surgical Techniques and Outcomes for Primary Infected Abdominal Aortic Aneurysms.

BACKGROUND: Primary infected abdominal aortic aneurysms (PIAAAs) are associated with high morbidity and mortality. Three repair approaches include open in-situ repair (OIR), extra-anatomic repair (EAR), and endovascular abdominal aortic aneurysm repair (EVAR). This study is one of the largest single-center case series comparing the outcomes of the different surgical approaches for PIAAA. METHODS: This is a retrospective cohort study of all patients treated surgically for PIAAA between 2000 and 2021. PIAAA diagnosis was defined as the presence of an abdominal aortic aneurysm with evidence of infection on clinical presentation, laboratory markers, radiology, or surgically. Patients with prior aortic surgery were excluded from this study. Basic demographics were compared across the 3 surgical groups using standard statistical methods. Our primary outcomes included mortality at 1 and 5 years. Kaplan-Meier curves were generated and compared using log-rank testing. Multivariate Cox proportional hazards models were created to assess determinants of mortality. RESULTS: A total of 43 patients were included in the full cohort. Patients undergoing EVAR more often had diabetes, end-stage renal disease, and coronary artery disease. EVAR was also more often done in patients with a saccular aneurysm rather than fusiform. (93% vs. 70% in EAR and 42% in OIR; P = 0.015). All-cause mortality rates at 1 year were not significantly different between the 3 groups. Survival at 5 years did show a significant benefit of OIR over EVAR and EAR: OIR had an 8% mortality rate with EAR having a 53% rate and EVAR having the highest (72%) mortality rate at 5 years (P = 0.03). Multivariable Cox regression analysis showed that EVAR (aHR 12.1, (95% CI 1.42 to 103.9), P = 0.02) and EAR (aHR 15.1, (95% CI 1.59 to 143.3), P = 0.0.02) had an increased 5-year mortality risk when compared to OIR. CONCLUSIONS: Repair of primary infected aortic aneurysm is associated with high complication and mortality rates regardless of the approach. In our studied sample, OIR offered an improved long-term survival without added benefits in terms of complication rates. In infected AAA, EVAR should be considered bridging stage between the urgent situation and eventual open repair.

Maturation of arteriovenous fistulas in patients with ventricular assist devices.

OBJECTIVE: Postoperative renal dysfunction necessitating hemodialysis after implantation of ventricular assist devices presents a challenge with respect to establishment of hemodialysis access. Lack of pulsatile flow has led to concerns that arteriovenous fistulas will not mature. This study aims to evaluate arteriovenous fistula as a method of hemodialysis. METHODS: Consecutive patients who underwent implantation of a ventricular assist device between 1988 and 2016 with a subsequent need for hemodialysis were identified. Retrospective data were collected for patients requiring hemodialysis through an arteriovenous fistula or arteriovenous graft. Access flow rates and duration of patency are reported. RESULTS: Sixty-four patients were identified (10 required long-term hemodialysis, 5 via arteriovenous fistula, 1 via arteriovenous graft). All six patients receiving long-term hemodialysis access were on continuous-flow ventricular assist devices. Brachiocephalic arteriovenous fistulas were performed in all arteriovenous fistula patients, and the average preoperative vein diameter was 4.1 ± 0.9 mm. On 30-day follow-up, the average flow rate was 1262 ± 643 mL/min (880-2220). In arteriovenous fistula patients, one died at 30 days, one arteriovenous fistula required ligation for steal syndrome at 5 months, and one was abandoned after 10.7 months for low flow. Of remaining fistulas, one was converted to an arteriovenous graft at 1.7 years for malfunction (with 5.3 month patency), and one remains open at 4.0 years. CONCLUSION: Arteriovenous fistulas should be considered in selected patients with ventricular assist devices as a means of long-term hemodialysis access to avoid use of catheters. Maturation and usage of primary arteriovenous fistulas is possible despite lack of pulsatile flow.

Contemporary outcomes of intact and ruptured visceral artery aneurysms.

OBJECTIVE: The treatment outcomes of ruptured visceral artery aneurysms (rVAAs) have been sparsely characterized, with no clear comparison between different treatment modalities. The purpose of this paper was to review the perioperative and long-term outcomes of open and endovascular interventions for intact visceral artery aneurysms (iVAAs) and rVAAs. METHODS: This was a retrospective review of all treated VAAs at one institution from 2003 to 2013. Patient demographics, aneurysm characteristics, management, and subsequent outcomes (technical success, mortality, reintervention) and complications were recorded. RESULTS: The study identified 261 patients; 181 patients were repaired (77 ruptured, 104 intact). Pseudoaneurysms were more common in rVAAs (81.8% vs 35.3% for iVAAs; P < .001). The rVAAs were smaller than the iVAAs (20.7 mm vs 27.5 mm; P = .018), and their most common presentation was abdominal pain; 29.7% were hemodynamically unstable. Endovascular intervention was the initial treatment modality for 67.4% (75.3% for rVAAs, 61.5% for iVAAs). The perioperative complication rate was higher for rVAAs (13.7% vs 1% for iVAAs; P = .003), as was mortality at 30 days (13% vs 0% for iVAAs; P = .001), 1 year (32.5% for rVAAs vs 4.1% for iVAAs; P < .001), and 3 years (36.4% for rVAAs vs 8.3% for iVAAs; P < .001). Lower 30-day mortality was noted with endovascular repair for rVAAs (7.4% vs 28.6% open; P = .025). Predictors of mortality for rVAAs included age (odds ratio, 1.04; P = .002), whereas endovascular repair was protective (odds ratio, 0.43; P = .037). Mean follow-up was 26.2 months, and Kaplan-Meier estimates of survival were higher for iVAAs at 3 years (88% vs 62% for rVAAs; P = .045). The 30-day reintervention rate was higher for rVAAs (7.7% vs 19.5% for iVAAs; P = .019) but was similar between open and endovascular repair (8.2% vs 15%; P = NS). CONCLUSIONS: rVAAs have significant mortality. Open and endovascular interventions are equally durable for elective repair of VAAs, but endovascular interventions for rVAAs result in lower morbidity and mortality. Aggressive treatment of pseudoaneurysms is electively recommended at diagnosis regardless of size.

Prevalence of incidental or unexpected findings on low-dose CT performed during routine SPECT/CT nuclear medicine studies.

INTRODUCTION: In nuclear medicine, single-photon-emission computed tomography (SPECT) is often combined with 'simultaneous' low-dose CT (LDCT) to provide complementary anatomical and functional correlation. As a consequence, numerous incidental and unexpected findings may be detected on LDCT. Recognition of these findings and appropriate determination of their relevance can add to the utility of SPECT/CT. We aimed to evaluate the prevalence and categorise the relevance of incidental and unexpected findings on LDCT scans performed as part of routine SPECT/CT studies. METHODS: All available LDCT scans performed as part of SPECT/CT studies at St. Vincent's Hospital Melbourne in the year 2013 were retrospectively reviewed. Two qualified radiologists independently reviewed the studies and any previous available imaging and categorised any detected incidental findings. RESULTS: A total of 2447 LDCT studies were reviewed. The relevance of the findings was classified according to a modified version of a scale used in the Colonography Reporting and Data System: E1 = normal or normal variant (28.0%); E2 = clinically unimportant (63.5%); E3 = likely unimportant or incompletely characterised (6.2%); E4 = potentially important (2.5%). CONCLUSION: Imaging specialists need to be cognisant of incidental and unexpected findings present on LDCT studies performed as part of SPECT/CT. Appropriate categorisation of findings and communication of potentially important findings to referring clinicians should form part of routine practice. The overall prevalence of potentially significant incidental and unexpected findings in our series was 8.7% (E3, 6.2%; E4, 2.5%) and was comparable to rates in other published imaging series.

Endoscopic versus open saphenous vein graft harvest for lower extremity bypass in critical limb ischemia.

OBJECTIVE: Endoscopic vein harvest (EVH) has been demonstrated to improve early morbidity when compared with conventional open vein harvest (OVH) technique for infrainguinal bypass surgery. However, recent literature suggests conflicting results regarding mid- and long-term patency with EVH. The purpose of this study is to compare graft patency between harvest techniques specifically in patients with critical limb ischemia. METHODS: This retrospective study compared two groups of patients (EVH = 39 and OVH = 49) undergoing lower extremity revascularization from January 2009 to December 2011. Outcome measures included patency rates, postoperative complications, and wound infection. Graft patency was assessed using Kaplan-Meier curves. RESULTS: Both groups were matched for demographics and indications for bypass (critical limb ischemia). Median follow-up was 22 months. There was a significant reduction in the incidence of wound infection at the vein harvest site in the EVH group (OVH = 20%; EVH = 0%; P < .001), nevertheless, the difference was not significant when only the anastomotic sites were included (OVH = 12.2%; EVH = 15.4%; P = .43). The hospital length of stay was comparable between the two groups (EVH = 8.73 ± 9.69; OVH = 6.35 ± 3.28; P = .26) with no significant difference in the recovery time. Primary graft patency rate was 43.2% in the EVH group and 69.4% in the OVH group (P = .007) at 3 years. The most common reason for loss of primary patency was graft occlusion (61.5%) in the OVH group and vein graft stenosis (54.5%) in the EVH group. The average number of vascular reinterventions per bypass graft was significantly lower in the OVH group compared with the EVH group (OVH = 0.37; EVH = 1.28; P < .001). CONCLUSIONS: Our findings demonstrate inferior primary patency when using the technique of EVH. Additionally, we identified a significantly higher rate of reintervention in the EVH cohort as well as a higher rate of vein graft body stenosis. However, EVH was associated with a decreased rate of wound complications with similar limb salvage and secondary patency rates when compared to OVH. EVH should therefore be selectively utilized in patients at high risk for wound complications.

Cellular-specific role of toll-like receptor 4 in hepatic ischemia-reperfusion injury in mice.

UNLABELLED: Ischemia-reperfusion (I/R) injury is a process whereby an initial hypoxic insult and subsequent return of blood flow leads to the propagation of innate immune responses and organ injury. The necessity of the pattern recognition receptor, Toll-like receptor (TLR)4, for this innate immune response has been previously shown. However, TLR4 is present on various cell types of the liver, both immune and nonimmune cells. Therefore, we sought to determine the role of TLR4 in individual cell populations, specifically, parenchymal hepatocytes (HCs), myeloid cells, including Kupffer cells, and dendritic cells (DCs) subsequent to hepatic I/R. When HC-specific (Alb-TLR4(-/-) ) and myeloid-cell-specific (Lyz-TLR4(-/-) ) TLR4 knockout (KO) mice were subjected to warm hepatic ischemia, there was significant protection in these mice, compared to wild type (WT). However, the protection afforded in these two strains was significantly less than global TLR4 KO (TLR4(-/-) ) mice. DC-specific TLR4(-/-) (CD11c-TLR4(-/-) ) mice had significantly increased hepatocellular damage, compared to WT mice. Circulating levels of high-mobility group box 1 (HMGB1) were significantly reduced in Alb-TLR4(-/-) mice, compared to WT, Lyz-TLR4(-/-) , CD11c-TLR4(-/-) mice and equivalent to global TLR4(-/-) mice, suggesting that TLR4-mediated HMGB1 release from HCs may be a source of HMGB1 after I/R. HCs exposed to hypoxia responded by rapidly phosphorylating the mitogen-activated protein kinases, c-Jun-N-terminal kinase (JNK) and p38, in a TLR4-dependent manner; inhibition of JNK decreased release of HMGB1 after both hypoxia in vitro and I/R in vivo. CONCLUSION: These results provide insight into the individual cellular response of TLR4. The parenchymal HC is an active participant in sterile inflammatory response after I/R through TLR4-mediated activation of proinflammatory signaling and release of danger signals, such as HMGB1.

Delayed open conversions after endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Secondary interventions after endovascular aneurysm repair (EVAR) remain a concern. Most are simple catheter-based procedures, but in some instances, open conversions (OCs) are required and carry a worse outcome. We reviewed our experience to characterize these OCs. METHODS: A retrospective review was conducted of all patients who underwent an OC after a previous EVAR for an aneurysm-related indication from 2001 to 2010. Clinical outcomes are reported. RESULTS: Data were reviewed for 44 patients (77% men) with a mean age of 74 years (range, 55-90 years). The average time from EVAR to the first OC was 45 months (range, 2-190 months). In six patients (14%), the initial EVAR was at another institution. The endografts used were Ancure in 16, Excluder in 13, AneuRx in eight, Zenith in three, Lifepath in one, Renu in one, and undetermined in two. Twenty-two patients had previously undergone a total of 32 endovascular reinterventions before their index OC. Indications for OC were aneurysm expansion in 28 (64%), rupture in 12 (27%), and infection in four (9%). The endograft was preserved in situ in 10 patients (23%). Explantation was partial in 18 (41%) or complete in 16 (36%). Endograft preservation was used for type II endoleak in all but one patient by selective ligation of the culprit arteries (lumbar in four, inferior mesenteric artery in five, and middle sacral in one). Proximal neck banding was performed in one type Ia endoleak. Overall morbidity was 55%, and mortality was 18%. No deaths occurred in a subgroup of patients who underwent endograft preservation with selective ligation of culprit vessels for type II endoleak. Intraoperative complications included bowel injury in two, bleeding in two, splenectomy in one, and ureteral injury in one. At a mean follow-up of 20 months, two patients underwent additional procedures after the index OC: one after endograft preservation and one after partial explantation. None of the patients who underwent elective OC with endograft preservation required subsequent endograft explantation. CONCLUSIONS: Most OCs after EVAR are associated with significant morbidity and mortality, except when electively treating an isolated type II endoleak with ligation of branches and preservation of the endograft.

Dendritic cells and damage-associated molecular patterns: endogenous danger signals linking innate and adaptive immunity.

Dendritic cells (DCs) are potent antigen-presenting cells critical in regulating the adaptive immune response. The role of DCs is dichotomous; they may both present antigens and the appropriate stimulatory molecules to initiate an adaptive immune response, or they may induce tolerance and release anti-inflammatory signals. The activation of immature DCs, required for the expression of the necessary costimulatory T cell molecules, is dependent on pattern recognition receptors. In addition to the pathogen-derived ligands of pattern recognition receptors, several damage-associated molecular patterns (DAMPs) have recently been shown to interact with DCs and dramatically affect their ultimate function. The complex interplay of DAMPs on DCs is clinically important, with implications for transplantation, tumor immunity, autoimmunity, chronic inflammation and other conditions of sterile inflammation such as ischemia reperfusion injury. In this review, we will focus on the role of DAMPs in DC function.

Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells.

BACKGROUND: Atherosclerosis is an inflammatory disease in which interferon (IFN)-gamma, the signature cytokine of Th1 cells, plays a central role. We investigated whether interleukin (IL)-17, the signature cytokine of Th17 cells, is also associated with human coronary atherosclerosis. METHODS AND RESULTS: Circulating IL-17 and IFN-gamma were detected in a subset of patients with coronary atherosclerosis and in referent outpatients of similar age without cardiac disease but not in young healthy individuals. IL-17 plasma levels correlated closely with those of the IL-12/IFN-gamma/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1beta, IL-6, and IL-23. Both IL-17 and IFN-gamma were produced at higher levels by T cells within cultured atherosclerotic coronary arteries after polyclonal activation than within nondiseased vessels. Combinations of proinflammatory cytokines induced IFN-gamma but not IL-17 secretion. Blockade of IFN-gamma signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN-gamma synthesis; production of both cytokines was inhibited by transforming growth factor-beta1. Approximately 10-fold fewer coronary artery-infiltrating T helper cells were IL-17 producers than IFN-gamma producers, and unexpectedly, IL-17/IFN-gamma double producers were readily detectable within the artery wall. Although IL-17 did not modulate the growth or survival of cultured vascular smooth muscle cells, IL-17 interacted cooperatively with IFN-gamma to enhance IL-6, CXCL8, and CXCL10 secretion. CONCLUSIONS: Our findings demonstrate that IL-17 is produced concomitantly with IFN-gamma by coronary artery-infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.

Interleukin (IL)-1 promotes allogeneic T cell intimal infiltration and IL-17 production in a model of human artery rejection.

Interleukin (IL) 1alpha produced by human endothelial cells (ECs), in response to tumor necrosis factor (TNF) or to co-culture with allogeneic T cells in a TNF-dependent manner, can augment the release of cytokines from alloreactive memory T cells in vitro. In a human-mouse chimeric model of artery allograft rejection, ECs lining the transplanted human arteries express IL-1alpha, and blocking IL-1 reduces the extent of human T cell infiltration into the artery intima and selectively inhibits IL-17 production by infiltrating T cells. In human skin grafts implanted on immunodeficient mice, administration of IL-17 is sufficient to induce mild inflammation. In cultured cells, IL-17 acts preferentially on vascular smooth muscle cells rather than ECs to enhance production of proinflammatory mediators, including IL-6, CXCL8, and CCL20. Neutralization of IL-17 does not reduce T cell infiltration into allogeneic human artery grafts, but markedly reduces IL-6, CXCL8, and CCL20 expression and selectively inhibits CCR6(+) T cell accumulation in rejecting arteries. We conclude that graft-derived IL-1 can promote T cell intimal recruitment and IL-17 production during human artery allograft rejection, and suggest that targeting IL-1 in the perioperative transplant period may modulate host alloreactivity.

Induction of indoleamine 2,3-dioxygenase in vascular smooth muscle cells by interferon-gamma contributes to medial immunoprivilege.

Atherosclerosis and graft arteriosclerosis are characterized by leukocytic infiltration of the vessel wall that spares the media. The mechanism(s) for medial immunoprivilege is unknown. In a chimeric humanized mouse model of allograft rejection, medial immunoprivilege was associated with expression of IDO by vascular smooth muscle cells (VSMCs) of rejecting human coronary artery grafts. Inhibition of IDO by 1-methyl-tryptophan (1-MT) increased medial infiltration by allogeneic T cells and increased VSMC loss. IFN-gamma-induced IDO expression and activity in cultured human VSMCs was considerably greater than in endothelial cells (ECs) or T cells. IFN-gamma-treated VSMCs, but not untreated VSMCs nor ECs with or without IFN-gamma pretreatment, inhibited memory Th cell alloresponses across a semipermeable membrane in vitro. This effect was reversed by 1-MT treatment or tryptophan supplementation and replicated by the absence of tryptophan, but not by addition of tryptophan metabolites. However, IFN-gamma-treated VSMCs did not activate allogeneic memory Th cells, even after addition of 1-MT or tryptophan. Our work extends the concept of medial immunoprivilege to include immune regulation, establishes the compartmentalization of immune responses within the vessel wall due to distinct microenvironments, and demonstrates a duality of stimulatory EC signals versus inhibitory VSMC signals to artery-infiltrating T cells that may contribute to the chronicity of arteriosclerotic diseases.

An inflammatory pathway of IFN-gamma production in coronary atherosclerosis.

Inflammation is associated with the pathogenesis of coronary atherosclerosis, although the mechanisms remain unclear. We investigated whether cytokine secretion by innate immune responses could contribute to the production of proarteriosclerotic Th1-type cytokines in human coronary atherosclerosis. Cytokines were measured by ELISA in the plasma of patients with coronary atherosclerosis undergoing cardiac catheterization. IL-18 was detected in all subjects, whereas a subset of patients demonstrated a coordinated induction of other IFN-gamma-related cytokines. Specifically, elevated plasma levels of IL-12 correlated with that of IFN-gamma and IFN-gamma-inducible chemokines, defining an IFN-gamma axis that was activated independently of IL-6 or C-reactive protein. Systemic inflammation triggered by cardiopulmonary bypass increased plasma levels of the IFN-gamma axis, but not that of IL-18. Activation of the IFN-gamma axis was not associated with acute coronary syndromes, but portended increased morbidity and mortality after 1-year follow-up. IL-12 and IL-18, but not other monokines, elicited secretion of IFN-gamma and IFN-gamma-inducible chemokines in human atherosclerotic coronary arteries maintained in organ culture. T cells were the principal source of IFN-gamma in response to IL-12/IL-18 within the arterial wall. This inflammatory response did not require, but was synergistic with and primed for TCR signals. IL-12/IL-18-stimulated T cells displayed a cytokine-producing, nonproliferating, and noncytolytic phenotype, consistent with previous descriptions of lymphocytes in stable plaques. In contrast to cognate stimuli, IL-12/IL-18-dependent IFN-gamma secretion was prevented by a p38 MAPK inhibitor and not by cyclosporine. In conclusion, circulating IL-12 may provide a mechanistic link between inflammation and Th1-type cytokine production in coronary atherosclerosis.

The consanguinity effect on QF-PCR diagnosis of autosomal anomalies.

OBJECTIVES: Quantitative Fluorescent PCR (QF-PCR) is a simpler and faster method of detecting common chromosomal abnormalities when compared to cytogenetic analysis. The aim of our study is to investigate the applicability of this methodology in a population where consanguineous marriages are common and to estimate the heterozygous frequency of the PCR markers used. METHODS: Four hundred and twenty-three DNA samples were extracted from uncultured amniocytes and amplified with 18 short tandem repeats (STR) markers specific to chromosomes 13, 18 and 21. Amplification products were analyzed using the GeneScan software. RESULTS: QF-PCR correctly identified all the numerical abnormalities related to chromosomes 13, 18 and 21. A total of 24 autosomal trisomies (5.7%) were detected. The markers D21S1432 and D21S11 were the most consistent in providing unequivocal positive results for chromosome 21 and the heterozygosity percentages of the markers used were lower than the values reported in Western populations. CONCLUSION: QF-PCR is reliable for the prenatal diagnosis of numerical anomalies of the chromosomes 13, 18 and 21 in our study population. The absence of STR heterozygosity data from Lebanon and surrounding countries makes our study very useful for the development of a reliable QF-PCR trisomy detection test.