Is elevated creatinine level a contraindication to endovascular aneurysm repair?

AbstractPurposeIt is widely believed that chronic renal insufficiency (CRI) greatly increases the risk associated with endovascular abdominal aortic aneurysm repair (EVAR) and is a relative contraindication to the procedure and to the use of intra-arterial contrast agents (IACA). We reviewed a 5-year EVAR experience to determine whether the procedure and use of IACA have an important deleterious effect on renal function in patients with and without pre-existing CRI.MethodsEndovascular aneurysm repair (EVAR) was performed in 200 patients with a variety of endografts, with intra-arterial contrast agents. The patients were retrospectively assigned to three groups on the basis of preoperative serum creatinine concentration (Cr): group 1 (n = 108), Cr less than 1.5 mg/dL (normal range); group 2 (n = 65), Cr 1.5 to 2.0 mg/dL; group 3 (n = 27), Cr 2.1 to 3.5 mg/dL. No patients had undergone hemodialysis. In groups 2 and 3, patients received hydration perioperatively, and received mannitol intraoperatively; no nephrotoxic drugs were administered during the procedure, other than nonionic contrast agent (Omnipaque 350).ResultsThe incidence of postoperative complications between the three study groups was not statistically different. In group 1 a transient increase in serum Cr (>30% over baseline and >1.4 mg/dL) was noted in three patients (2.7%), two of whom (1.9%) required temporary hemodialysis and one (0.9%) who died of renal failure. In group 2 a transient increase in serum Cr was noted in two patients (3.1%); both patients (3.1%) required temporary hemodialysis, and one patient (1.5%) died of renal failure. In group 3 a transient increase in serum Cr was noted in two patients (7.4%); one patient (3.7%) required temporary hemodialysis, and one patient (3.7%) died of renal failure. Perioperative hypotension significantly increased the risk for elevated serum Cr and death (P < .05), and larger contrast volume was associated with an increase in serum Cr (P < .05) during the postoperative period.ConclusionsEVAR with intra-arterial contrast agents can be accomplished in patients with chronic renal insufficiency who do not require dialysis, with limited and acceptable morbidity and mortality, similar to that observed with open aneurysm repair. Contrary to other reports in which perioperative precautions were not used, our study shows that with EVAR the risk for worsening renal failure, dialysis, and death is only slightly, and not significantly, greater in patients with preoperative chronic renal insufficiency compared with patients with normal renal function. Perioperative hypotension and increased contrast volume are significant risk factors for postoperative increase in serum Cr and death. With appropriate precautions such as averting perioperative hypotension and limiting the volume of nonionic contrast agents, elevated Cr need not be a contraindication to EVAR with intra-arterial contrast agents

Early carotid endarterectomy after acute stroke

AbstractPurposeCarotid endarterectomy (CEA) after acute stroke is generally delayed 6 to 8 weeks because of fear of stroke progression. This delay can result in an interval stroke rate of 9% to 15%. We analyzed our results with CEA performed within 1 to 4 weeks of stroke.MethodsRecords for all patients undergoing CEA after stroke between 1980 and 2001 were analyzed. Perioperative evaluation included carotid duplex scanning or angiography, and head computed tomography or magnetic resonance imaging. All patients with nonworsening neurologic status, additional brain territory at risk for recurrent stroke, and severe ipsilateral carotid stenosis underwent CEA. Patients were grouped according to time of CEA after stroke: group 1, first week; group 2, second week; group 3, third week; group 4, fourth week. Statistical analysis was performed with the χ2 test, logistic regression, and analysis of variance.ResultsTwo hundred twenty-eight patients underwent CEA within 1 to 4 weeks of stroke. Perioperative permanent neurologic deficits occurred in 2.8% of patients in group 1 (72 procedures), 3.4% of patients in group 2 (59 procedures), 3.4% of patients in group 3 (29 procedures), and 2.6% of patients in group 4 (78 procedures). There was no relationship between location or size of preoperative infarct and time of surgery. Only preoperative infarct size correlated with probability of neurologic deficit after CEA (P < .05).ConclusionIncidence of postoperative stroke exacerbation is similar at all intervals. The results are within acceptable limits for treatment of symptomatic carotid stenosis. CEA may be performed within 1 month of stroke with similar results at all intervals during this period

Ligation of Macrophage Fcγ Receptors Recapitulates the Gene Expression Pattern of Vulnerable Human Carotid Plaques

Stroke is a leading cause of death in the United States. As ∼60% of strokes result from carotid plaque rupture, elucidating the mechanisms that underlie vulnerability is critical for therapeutic intervention. We tested the hypothesis that stable and vulnerable human plaques differentially express genes associated with matrix degradation. Examination established that femoral, and the distal region of carotid, plaques were histologically stable while the proximal carotid plaque regions were vulnerable. Quantitative RT-PCR was used to compare expression of 22 genes among these tissues. Distal carotid and femoral gene expression was not significantly different, permitting the distal carotid segments to be used as a paired control for their corresponding proximal regions. Analysis of the paired plaques revealed differences in 16 genes that impact plaque stability: matrix metalloproteinases (MMP, higher in vulnerable), MMP modulators (inhibitors: lower, activators: higher in vulnerable), activating Fc receptors (FcγR, higher in vulnerable) and FcγR signaling molecules (higher in vulnerable). Surprisingly, the relative expression of smooth muscle cell and macrophage markers in the three plaque types was not significantly different, suggesting that macrophage distribution and/or activation state correlates with (in)stability. Immunohistochemistry revealed that macrophages and smooth muscle cells localize to distinct and non-overlapping regions in all plaques. MMP protein localized to macrophage-rich regions. In vitro, treatment of macrophages with immune complexes, but not oxidized low density lipoprotein, C-reactive protein, or TNF-α, induced a gene expression profile similar to that of the vulnerable plaques. That ligation of FcγR recapitulates the pattern of gene expression in vulnerable plaques suggests that the FcγR → macrophage activation pathway may play a greater role in human plaque vulnerability than previously appreciated

Two Distinct Modes of Hypoosmotic Medium-Induced Release of Excitatory Amino Acids and Taurine in the Rat Brain In Vivo

A variety of physiological and pathological factors induce cellular swelling in the brain. Changes in cell volume activate several types of ion channels, which mediate the release of inorganic and organic osmolytes and allow for compensatory cell volume decrease. Volume-regulated anion channels (VRAC) are thought to be responsible for the release of some of organic osmolytes, including the excitatory neurotransmitters glutamate and aspartate. In the present study, we compared the in vivo properties of the swelling-activated release of glutamate, aspartate, and another major brain osmolyte taurine. Cell swelling was induced by perfusion of hypoosmotic (low [NaCl]) medium via a microdialysis probe placed in the rat cortex. The hypoosmotic medium produced several-fold increases in the extracellular levels of glutamate, aspartate and taurine. However, the release of the excitatory amino acids differed from the release of taurine in several respects including: (i) kinetic properties, (ii) sensitivity to isoosmotic changes in [NaCl], and (iii) sensitivity to hydrogen peroxide, which is known to modulate VRAC. Consistent with the involvement of VRAC, hypoosmotic medium-induced release of the excitatory amino acids was inhibited by the anion channel blocker DNDS, but not by the glutamate transporter inhibitor TBOA or Cd2+, which inhibits exocytosis. In order to elucidate the mechanisms contributing to taurine release, we studied its release properties in cultured astrocytes and cortical synaptosomes. Similarities between the results obtained in vivo and in synaptosomes suggest that the swelling-activated release of taurine in vivo may be of neuronal origin. Taken together, our findings indicate that different transport mechanisms and/or distinct cellular sources mediate hypoosmotic medium-induced release of the excitatory amino acids and taurine in vivo

Host-Adaptation of Francisella tularensis Alters the Bacterium's Surface-Carbohydrates to Hinder Effectors of Innate and Adaptive Immunity

The gram-negative bacterium Francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. The presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. Previously we reported in vitro culture conditions for this bacterium which, in contrast to typical methods, yielded a bacterial phenotype that mimics that of the bacterium's mammalian, extracellular phase.SDS-PAGE and carbohydrate analysis of differentially-cultivated F. tularensis LVS revealed that bacteria displaying the host-adapted phenotype produce both longer polymers of LPS O-antigen (OAg) and additional HMW carbohydrates/glycoproteins that are reduced/absent in non-host-adapted bacteria. Analysis of wildtype and OAg-mutant bacteria indicated that the induced changes in surface carbohydrates involved both OAg and non-OAg species. To assess the impact of these HMW carbohydrates on the access of outer membrane constituents to antibody we used differentially-cultivated bacteria in vitro to immunoprecipitate antibodies directed against outer membrane moieties. We observed that the surface-carbohydrates induced during host-adaptation shield many outer membrane antigens from binding by antibody. Similar assays with normal mouse serum indicate that the induced HMW carbohydrates also impede complement deposition. Using an in vitro macrophage infection assay, we find that the bacterial HMW carbohydrate impedes TLR2-dependent, pro-inflammatory cytokine production by macrophages. Lastly we show that upon host-adaptation, the human-virulent strain, F. tularensis SchuS4 also induces capsule production with the effect of reducing macrophage-activation and accelerating tularemia pathogenesis in mice.F. tularensis undergoes host-adaptation which includes production of multiple capsular materials. These capsules impede recognition of bacterial outer membrane constituents by antibody, complement, and Toll-Like Receptor 2. These changes in the host-pathogen interface have profound implications for pathogenesis and vaccine development