Nancy L. Harthun

Subintimal Arterial Flossing with Antegrade–Retrograde Intervention (SAFARI) for Subintimal Recanalization to Treat Chronic Critical Limb Ischemia

PURPOSEnTo describe the technique of subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) to improve technical success for the performance of subintimal recanalization when there is failure to reenter the distal true lumen or when there is a limited segment of patent distal target artery available for reentry.nnnMATERIALS AND METHODSnSubintimal recanalization was attempted in an antegrade direction in all patients. If reentry into the distal true lumen was unsuccessful or a short segment of target artery was present, retrograde access was obtained in the distal target artery (popliteal, anterior tibial/dorsalis pedis, or posterior tibial) and a retrograde subintimal channel was created. A guide wire was used to connect the retrograde and antegrade subintimal channels simultaneously to create a flossing guide wire. The subintimal tract was dilated with balloon angioplasty with or without stent implantation. Limb salvage, amputation-free survival, and survival rates over time were determined.nnnRESULTSnThe SAFARI technique resulted in successful subintimal recanalization creating straight-line flow to the foot in all 21 limbs in 20 patients in which the technique was attempted. Antegrade-retrograde access was performed with the femoral artery and the following vessels: popliteal, n = 11; anterior tibial/dorsalis pedis, n = 10; and posterior tibial, n = 2 (two limbs involved multiple accesses). All procedures were successful. The limb salvage rate with SAFARI was 90% (95% CI, 74%-100%) at 6 months.nnnCONCLUSIONSnThe SAFARI technique can be useful for completing subintimal recanalization when there is failure to reenter the distal true lumen from an antegrade approach or when there is limited distal target artery available for reentry. The SAFARI technique improves technical success in the performance of subintimal recanalization. Limb salvage rates are comparable to those with antegrade subintimal recanalization.

Melanomas with concordant loss of multiple melanocytic differentiation proteins : immune escape that may be overcome by targeting unique or undefined antigens

Abstract Melanoma-reactive HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) lines generated inu2009vitro lyse autologous and HLA-matched allogeneic melanoma cells and recognize multiple shared peptide antigens from tyrosinase, MART-1, and Pmel17/gp100. However, a subset of melanomas fail to be lysed by these T cells. In the present report, four different HLA-A*0201+ melanoma cell lines not lysed by melanoma-reactive allogeneic CTL have been evaluated in detail. All four are deficient in expression of the melanocytic differentiation proteins (MDP) tyrosinase, Pmel17/gp100, gp75/trp-1, and MART-1/Melan-A. This concordant loss of multiple MDP explains their resistance to lysis by melanoma-reactive allogeneic CTL and confirms that a subset of melanomas may be resistant to tumor vaccines directed against multiple MDP-derived epitopes. All four melanoma lines expressed normal levels of HLA-A*0201, and all were susceptible to lysis by xenoreactive-peptide-dependent HLA-A*0201-specific CTL clones, indicating that none had identifiable defects in antigen-processing pathways. Despite the lack of shared MDP-derived antigens, one of these MDP-negative melanomas, DM331, stimulated an effective autologous CTL response inu2009vitro, which was restricted to autologous tumor reactivity. MHC-associated peptides isolated by immunoaffinity chromatography from HLA-A1 and HLA-A2 molecules of DM331 tumor cells included at least three peptide epitopes recognized by DM331 CTL and restricted by HLA-A1 or by HLA-A*0201. Recognition of these CTL epitopes cannot be explained by defined, shared melanoma antigens; instead, unique or undefined antigens must be responsible for the autologous-cell-specific anti-melanoma response. These findings suggest that immunotherapy directed against shared melanoma antigens should be supplemented with immunotherapy directed against unique antigens or other undefined antigens, especially in patients whose tumors do not express MDP.

Limb Stress-Rest Perfusion Imaging With Contrast Ultrasound for the Assessment of Peripheral Arterial Disease Severity

OBJECTIVESnWe hypothesized that stress-rest perfusion imaging of skeletal muscle in the lower extremity with contrast-enhanced ultrasound (CEU) could evaluate the severity of peripheral arterial disease (PAD).nnnBACKGROUNDnPerfusion imaging may provide valuable quantitative information on PAD, particularly in patients with diabetes in whom microvascular functional abnormalities are common.nnnMETHODSnStudy subjects included 26 control subjects and 39 patients with symptomatic PAD, 19 of whom had type 2 diabetes mellitus. A modified treadmill exercise test was performed to determine exercise time to development of claudication. Multilevel pulse-volume recordings and ankle-brachial index (ABI) at rest and post-exercise ABI were measured in both extremities. Microvascular blood flow in the gastrocnemius and soleus muscles was measured at rest and after 2 min of calibrated plantar-flexion exercise.nnnRESULTSnDuring exercise, claudication did not occur in normal subjects and occurred earlier in PAD patients with diabetes than without (median time 1.2 min [95% confidence interval (CI) 0.6 to 2.5] vs. 3.0 min [95% CI 2.1 to 6.0], p < 0.01). Compared to control subjects, patients with PAD had lower skeletal muscle blood flow during plantar-flexion exercise and lower flow reserve on CEU. After adjusting for diabetes, the only diagnostic tests that predicted severity of disease by claudication threshold were CEU exercise blood flow and flow reserve (odds ratios 0.67 [95% CI 0.51 to 0.88; p = 0.003] and 0.64 [95% CI 0.46 to 0.89, p = 0.008], respectively). A quasi-likelihood information analysis incorporating all non-invasive diagnostic tests indicated that the best models for predicting severity of disease were the combination of diabetes and either exercise blood flow or flow-reserve on CEU.nnnCONCLUSIONSnPerfusion imaging of limb skeletal during exercise and measurement of absolute flow reserve can provide valuable information on the severity PAD. This strategy may be useful for evaluating the total impact of disease in patients with complex disease or those with coexisting functional abnormalities of flow regulation.

CTA and MRA in Mesenteric Ischemia: Part 2, Normal Findings and Complications After Surgical and Endovascular Treatment

OBJECTIVEnA number of surgical and endovascular options exist for the treatment of acute and chronic mesenteric ischemia. Both surgical and endovascular treatments necessitate close clinical and imaging follow-up because the consequences of acute occlusions can be catastrophic. MDCT angiography (CTA) and contrast-enhanced MR angiography (MRA) are the preferred imaging techniques in this setting.nnnCONCLUSIONnWe review the appearance of the normal and complicated surgical and endovascular treatment on CTA and MRA.

The plasma microparticle proteome.

All cell types shed ectosomes and exosomes, collectively known as microparticles (MP; 0.1 to 1.5 μm in diameter), when activated or stressed; normal human plasma contains ~2 μg MP protein/mL. The cellular composition of plasma MP is altered in many diseases, including acute coronary syndrome, diabetes mellitus, sepsis, and sickle cell disease. We measured the plasma MP protein composition of 42 patients (median age 69.5 years, most with cardiovascular disease) by label-free liquid chromatography coupled to tandem mass spectrometry. Among 458 proteins detected with high confidence (identified by at least two unique peptides with SEQUEST XCor (Thermo Electron Corp., San Jose, CA) ≥ 2.0, 2.2, and 3.3 for charge states +1, +2, and +3, respectively), 130 were present in most patients, representing a core set of plasma MP proteins. This core is enriched in cytoskeletal, integrin complex, and hemostasis proteins, and spectral counts of several proteins correlate with patient age and gender. We conclude that the MP proteome may be a useful and reliable source of biologically relevant disease biomarkers.

Safety and efficacy of the supraclavicular approach to thoracic outlet decompression

BACKGROUNDnThoracic outlet syndrome (TOS) is a clinical diagnosis encountered by both thoracic and vascular surgeons. The goal of surgical therapy involves relieving compression of the neurovascular structures at the superior thoracic aperture. The traditional approach to thoracic outlet decompression has been transaxillary; however more centers are moving toward a more tailored approach through a supraclavicular incision.nnnMETHODSnThe medical records of 67 patients who underwent surgical decompression between 1993 and 2001 for TOS were retrospectively reviewed. Patient demographics and early outcome were assessed through clinic follow-up.nnnRESULTSnSeventy-two thoracic outlet decompressions were performed on 67 patients with the diagnosis of TOS. Five patients underwent bilateral thoracic outlet decompression. All operations in this time period were safely accomplished through a supraclavicular approach. The syndromes associated with thoracic outlet compression were neurogenic (n = 59), venous (n = 10), and arterial (n = 3). Forty-six of 72 (63.9%) operations resulted in complete resolution of symptoms, 17 cases (23.6%) had partial resolution, and 9 patients (12.5%) had no resolution. There were no deaths and morbidity was minimal with 6 complications (8.3%).nnnCONCLUSIONSnThe supraclavicular approach is a safe and effective technique in managing all forms of thoracic outlet compression.

Current issues in the treatment of women with abdominal aortic aneurysm.

BACKGROUNDnAbdominal aortic aneurysm (AAA) accounts for approximately 45,000 deaths per year in the United States. Despite a striking male predominance of AAA (4:1 male to female), mortality from this disease is almost as high in women (20th leading killer of women and 15th leading killer of men in this country).nnnOBJECTIVEnThe purpose of this review is to highlight the differences in diagnosis, treatment, and treatment outcomes for women with AAA to determine avenues of potential improvement in their care.nnnMETHODSnPublished articles relevant to this review were determined by the experience of the author, by PubMed and MEDLINE searches, and by reviewing the references cited in the reports identified by the first 2 methods. The database searches were performed using the following terms: abdominal aorta, aneurysm, gender, endovascular, and outcomes. Reports were limited to the English language and publication since 1995.nnnRESULTSnCompared with men, women are older when their AAA is diagnosed and treated. Women have higher mortality than do men while undergoing elective open and endovascular repairs, and emergency surgery for ruptured AAAs. Owing to the anatomic complexity of their arterial anatomy, women are less frequently candidates for endovascular repair. Women receive treatment for rupture of AAA less frequently than do men. On Medicare induction, both men and women are eligible for a one-time screening for AAA; however, women qualify for this exam only if they have a family history of AAA.nnnCONCLUSIONSnOpportunities to advance the care of women with AAA include improving screening techniques to find AAA prior to rupture and when women are younger and more likely to be candidates for repair. Current clinical practice should focus on decreasing mortality for open surgical repair and developing better endovascular devices so that anatomic obstacles can be overcome and more women can be candidates for this technology. In addition, furthering the understanding of gender differences in the pathophysiology of AAA disease may provide insights into treatments that could prevent the formation of aneurysms.

Thoracic aortic endografting is the treatment of choice for elderly patients with thoracic aortic disease

Objective:To assess the effect of age on outcomes following thoracic aortic endografting. Summary Background Data:Endograft therapy for thoracic aortic disease is rapidly evolving. This therapy is less invasive, and elderly patients with significant medical comorbidities are more frequently referred for endografting. We hypothesized that elderly patients over the age of 75 have worse outcomes after thoracic endografting than patients under the age of 75. Methods:We retrospectively reviewed the charts of the first 42 patients who underwent endografting for thoracic aortic pathology. Charts were reviewed for demographics, comorbid conditions, perioperative complications and death, endoleaks, and results at 3, 6, and 12 months. Preexisting medical conditions were also evaluated to determine if any patient characteristics were associated with adverse outcomes. Perioperative morbidity included cardiac, pulmonary, renal, hemorrhagic, and neurologic (stroke and spinal cord injury) complications. Results:Twenty-four patients were under the age of 75, and 18 patients were 75 or older. Baseline demographics and comorbidities were similar between the 2 groups. There were no differences in operative time, length of stay, perioperative mortality, or the incidence of significant complications between the 2 age groups. Gender, however, was associated with a statistically significant difference between the occurrence of complications, with more women experiencing complications than men (P = 0.026, relative risk = 2.36). One patient (age >75 years) in the entire cohort of 42 (2.4%) suffered a spinal cord injury. At 3 months, endoleaks were more common in the older age group (P = 0.059). Conclusion:Endograft therapy for thoracic aortic disease can be performed safely in elderly patients with no significant increase in perioperative morbidity or mortality compared with younger patients. Female gender is associated with a higher likelihood of perioperative complications, regardless of age. The overall incidence of spinal cord injury is very low. Endograft therapy, when anatomically possible, is the treatment of choice for thoracic aortic disease in elderly patients.

Activated α2-macroglobulin reverses the immunosuppressive activity in human breast cancer cell-conditioned medium by selectively neutralizing transforming growth factor-β in the presence of interleukin-2.

The immunosuppressive activity of tumor cells may be mediated by tumor-derived cytokines such as transforming growth factor-β (TGF-β) and interleukin-10 (EL-10). A human breast cancer celt line derived from malignant ascites (BRC 173) secreted TGF-β, but not IL-10, into tissue culture supernatant (TCS). BRC 173 TCS suppressed natural killer (NK) and lymphokine-activated killer (LAK) cell activity and also blocked the generation of HLA-A*0201-restricted tumor-reactive cytotoxic T-lymphocyte (CTL) lines in vitro. Human α2-macroglobulin (α2M), a plasma protein and cytokine carrier that binds isoforms in the TGF-β family, was tested for its ability to neutralize the immunosuppressive activity in BRC 173 TCS. α2M was converted to its activated conformation by reaction with methylamine (α2M-MA) and then incubated with normal human peripheral blood lymphocytes (PBL) in the presence of IL-2 and BRC 173 TCS. Lysis of NK targets (K562) and LAK cell targets (DM6 melanoma) by the PBL was examined after 6 days of culture. PBL cultured in IL-2, without TCS or α2M-MA, were lytic for both target cells. BRC 173 TCS substantially suppressed the lytic activity of the PBL in the presence of IL-2. When TGF-β-neutralizing antibody was added to the PBL culture medium with IL-2 and TCS, a majority of the lytic activity was restored. α2M-MA (280 nM) neutralized almost all of the immunosuppressive activity in the TCS, restoring 80–100% of the lytic activity without any apparent effect on the activity of IL-2. The ability of α2M-MA to counteract immunosuppressive cytokines in breast cancer TCS was evident in serum-containing and serum-free medium. These studies demonstrate that activated α2M can function as a selective cytokine neutralizer to thereby promote the activation of NK, LAK, and tumor-specific CTL responses.

Metachronous Bilateral Posterior Tibial Artery Aneurysms in Ehlers-Danlos Syndrome Type IV

Ehlers-Danlos syndrome type IV is a life-threatening genetic connective tissue disorder. We report a 24-year-old woman with EDS-IV who presented with metachronous bilateral aneurysms/pseudoaneurysms of the posterior tibial arteries 15xa0months apart. Both were treated successfully with transarterial coil embolization from a distal posterior tibial approach.