Do Women Have Worse Amputation-Free Survival Than Men Following Endovascular Procedures for Peripheral Arterial Disease? An Evaluation of the California State-Wide Database.

OBJECTIVES: Female gender has been shown to negatively affect the outcomes of surgical bypass for peripheral arterial disease (PAD). We examined gender-related disparities in outcomes of endovascular PAD procedures in a large population-based study. METHODS: We used discharge data from California hospitals to identify patients who had PAD interventions during 2005 to 2009. Logistic regression was used for 12-month reintervention, and Cox proportional hazard regression was used for amputation-free survival comparisons. RESULTS: A total of 25 635 patients had endovascular procedures (11 389 [44.4%] women). Women were more likely than men (34.5% vs 30.1%, P < .0001) to have critical limb ischemia (CLI). Twelve-month reintervention rate in women was similar to men. Amputation-free survival was better among women than men (hazard ratio 0.84, 95% confidence interval [CI] 0.76-0.93, P = .0006). CONCLUSION: Despite presenting more frequently with CLI, women had better amputation-free survival than men following endovascular procedures. Future research should determine whether findings favor one type of PAD treatment modality over another for women.

Technical and early outcomes using ultrasound-guided reentry for chronic total occlusions.

BACKGROUND: Subintimal angioplasty is a common treatment for chronic total occlusions (CTOs) in the iliac and infrainguinal arteries. Although technical success has been described using intravascular ultrasound-guided reentry devices (IVUS-RED), outcomes are still not well defined. This report describes the technical aspects and longitudinal follow-up after intravascular ultrasound-guided reentry of iliac and infrainguinal CTOs. METHODS: A retrospective review was performed of 20 patients with lower extremity CTO treated with IVUS-RED from 2011 to 2013. A matched cohort of patients who underwent lower extremity interventions without the use of IVUS-RED was also identified. Procedural success, patency estimates, ankle-brachial indices (ABIs), complications, and limb salvage were analyzed. RESULTS: Twenty patients (mean age, 69 ± 13 years), including 11 men and 9 women, underwent attempted IVUS-RED-guided recanalization. Median follow-up was 4.3 months (range, 0.4-24). Eleven patients presented with critical limb ischemia (CLI), and 9 presented with claudication. Technical success was achieved in 18 (90%) patients. Ten common iliac arteries, 3 external iliac arteries, and 5 superficial femoral arteries (SFA) were treated. No intraoperative complications resulted from device use. After procedure, ABIs significantly increased (0.5-0.9; P < 0.01) in the 13 patients with follow-up. Primary patency for the entire cohort was 62% at 12 months. No patient treated for claudication required reintervention, whereas 3 (27%) of those treated for CLI required repeat interventions. During follow-up, 2 patients died unrelated to the procedure, 1 patient required an amputation, and 1 patient eventually required open revascularization. When the IVUS-RED group was compared with a cohort matched on Trans-Atlantic Inter-Society Consensus and age, no difference was found in runoff scores and patency between the 2 groups during follow-up (P > 0.05). CONCLUSIONS: Recanalization of CTO using IVUS-RED is safe and effective. Use of IVUS-RED does not adversely impact outcomes in conjunction with other endovascular techniques. Early follow-up demonstrates acceptable patency, especially in patients with claudication, and freedom from reintervention.

Repair of aberrant right subclavian artery entirely via a supraclavicular approach.

An aberrant right subclavian artery is a known arch variant with surgical intervention reserved for those patients presenting symptomatically, those with aneurysmal degeneration particularly of a Kommerell diverticulum, or those with adjacent aortic pathology. Varied surgical approaches have been described, often involving a supraclavicular approach in conjunction with a thoracotomy, or more recently, hybrid endovascular techniques. In the absence of aneurysmal degeneration or associated aortic pathology, surgical repair can be performed safely through a single supraclavicular incision. We present a case of a patient repaired in this fashion.

Single nucleotide polymorphisms and type of steroid impact the functional response of the human glucocorticoid receptor.

BACKGROUND: Clinical trials evaluating the use of steroids in septic shock have shown variable outcomes. Our previous studies have implicated human glucocorticoid receptor (hGR) polymorphisms as a possible cause of altered steroid response. To further evaluate this variability, we hypothesized that hGR polymorphisms along with type of steroid influence the functional response. METHODS: Total RNA was isolated from healthy human blood samples and surveyed for the hGR gene. The National Center for Biotechnology Information hGRα sequence was used as a reference, and two unique single nucleotide polymorphisms (SNPs) (A214G and T962C) were selected for evaluation. Functional response was measured using a luciferase reporting assay after transfecting hGR isoforms into tsA201 cells and stimulation with graded concentrations of hydrocortisone (HYD), methylprednisolone (MPS), and dexamethasone (DEX). RESULTS: Each isoform had a unique dose-response curve with the optimal activity depending on concentration and type of steroid. The presence of either SNP A214G or T962C resulted in a decreased response when compared with hGRα when stimulated with HYD (P < 0.01). The same decreased response occurred for the SNPs with DEX stimulation, but at a much lower concentration range than HYD (P < 0.01). However, in the presence of MPS, SNP A214G resulted in greater activity when compared with hGRα (P < 0.01), whereas the presence of T962C resulted in activity equivalent to hGRα. CONCLUSIONS: SNPs, type of steroid, and concentration range impact the functional response of the hGR. A greater understanding of hGR polymorphisms and steroid response may further elucidate mechanisms explaining the variable response seen with patient treatment.

Using NNAPPS (Nighttime Nurse and Physician Paging System) to Maximize Resident Call Efficiency within 2011 Accreditation Council for Graduate Medical Education (ACGME) work hour restrictions.

OBJECTIVES: To assess if implementing Nighttime Nurse and Physician Paging System (NNAPPS) would improve nurse and physician communication as well as reduce the number of nonurgent pages to residents taking overnight call. DESIGN: NNAPPS was implemented on the busiest General Surgery and Transplant wards at our University Hospital. We conducted 2 prospective studies that logged pages received by on call surgery residents for 2-month blocks. The logs captured time, source, reason, and action resulting from pages. Independent reviewers determined urgency of the pages. Primary outcome measures were comparison of average nonurgent pages, total pages and total pages per patient during a night shift between the NNAPPS ward and all other wards that care for surgical patients. SETTING: University teaching hospital. PARTICIPANTS: General surgery residents working overnight call shifts on nine surgical services. RESULTS: In both studies combined, there were a total of 107 night shifts during which 771 pages were received. Total census was 1179 patients. Nurses initiated most pages (67%). Eight percent of pages interrupted patient care, while 40% of pages interrupted resident sleep. Most pages resulted in either a "new order" (39%) or "patient assessment" (22%), while 36% resulted in "no action." Most pages (56%) were "urgent," 25% "nonurgent," and 19% "unable to determine urgency." Regarding the Transplant ward, significant differences (p < 0.05) existed between average nonurgent pages (0.46 vs 2.14), total pages (3.69 vs 6.14) and total pages/patient during a shift (0.38 vs 0.68) when comparing pre- and post-NNAPPS data. CONCLUSIONS: NNAPPS significantly reduced nonurgent pages, total pages and pages per patient during a night shift compared to services with conventional systems. Streamlined paging systems lead to more efficient communication between providers and decrease the nonurgent pages to residents. NNAPPS continued high standards of patient care and improved sleep patterns for residents.

Application of duplex ultrasound imaging in determining in-stent stenosis during surveillance after mesenteric artery revascularization.

OBJECTIVE: Currently, there are no well-established duplex ultrasound (DUS) criteria for the evaluation of the mesenteric arteries after stenting for occlusive disease. Previous studies suggested DUS velocity criteria in the native superior mesenteric artery (SMA) overestimate stenosis in stented arteries, but most studies have not evaluated DUS imaging after SMA stenting longitudinally. This study was undertaken to determine the accuracy of DUS after mesenteric artery revascularization and, in particular, to evaluate the utility of DUS imaging for the detection of in-stent stenosis (ISS) of the SMA. METHODS: A retrospective record review was performed for all patients who underwent SMA stenting for chronic mesenteric ischemia at a single institution from January 2004 to May 2011. RESULTS: Mesenteric artery occlusive disease resulted in 24 patients undergoing mesenteric stenting of the SMA alone (n = 20) or the SMA and celiac artery simultaneously (n = 3). The mean ± standard deviation peak systolic velocity (PSV) in 13 prestent DUS images of the SMA was 464 ± 130 cm/s. Prestenting angiography revealed an average SMA stenosis of 79% ± 14%. After stenting, completion angiography in each case revealed <20% residual stenosis. No significant correlation was identified between SMA PSV and angiographic stenosis before and after stenting (P > .05). Follow-up SMA DUS imaging showed an average PSV of 335 ± 138 cm/s at 0.9 ± 1.5 months, 360 ± 143 cm/s at 4.8 ±2.6 months, and 389 ± 95 cm/s at 14.4 ± 5.1 months. A significant difference existed between the prestent and the first poststent mean SMA PSV (P < .05), but no significant difference existed between each poststenting interval. Eight reinterventions for SMA ISS were performed, with a mean elevated in-stent SMA PSV of 505 ± 74 vs 341 ± 145 cm/s in patients who did not undergo reintervention. Angiography before the eight reinterventions demonstrated an average SMA ISS of 53% ± 25%. In-stent SMA PSV decreased from 505 ± 74 to 398 ± 108 cm/s after the reintervention (P < .05). CONCLUSIONS: Consistent with other reports, our data demonstrate the PSV in successfully stented SMAs remains higher than the PSV threshold of 275 cm/s used for the diagnosis of high-grade native SMA stenosis. In addition, in-stent SMA PSVs did not significantly change over DUS surveillance for patients who did not undergo reintervention. Thus, obtaining a baseline DUS early after mesenteric stenting should be considered to compare future surveillance DUS. An increase above this baseline or an in-stent SMA PSV approaching 500 cm/s should be considered suspicious for ISS, but larger prospective studies will be required to validate these preliminary findings.

Enhanced steroid response of a human glucocorticoid receptor splice variant.

Glucocorticoids remain a recommended therapy in advanced septic shock despite the often unpredictable response, and our understanding of the mechanisms regulating the steroid and stress response remains limited. Since the initial sequencing of the human glucocorticoid receptor α and ß gene (hGRα and hGRß), only three additional splice variants have been identified--all of which have been postulated to contribute to steroid resistance. During a survey of 97 healthy humans' blood, we identified two novel hGR splice isoforms (hGR-S1 and hGR-S1(-349A) retaining intron H between exons 8 and 9. Human GR-S1(-349A) contained a base deletion causing an early termination and a truncated protein of 118 amino acids, whereas hGR-S1 had an early termination occurring within intron H and resulted in a 745-amino acid protein. Both isoforms had decreased transactivation potentials compared with hGRα when tested in the absence of exogenous steroids. However, after treating with exogenous steroids, dose-response studies showed hGR-S1(-349A) had a substantial augmentation in activity at higher concentrations of hydrocortisone and methylprednisolone when compared with hGRα, whereas hGR-S1 did not. Removal of the 3' untranslated region (3'UTR) of the hGR-S1(-349A) mRNA sequence resulted in a loss of the augmented response. The isoform hGR-S1(-349A) augments the response to steroids, and this significant response appears to be critically regulated by the 3'UTR. The identification and evaluation of these unique hGR isoforms helps further the understanding of the complex genetic regulation of the stress and steroid response.

Novel hyperactive glucocorticoid receptor isoform identified within a human population.

Glucocorticoids serve as important therapeutic agents in diseases of inflammation, but clinical use, especially in advanced septic shock, remains controversial because of the unpredictable response. Prior studies correlate human glucocorticoid receptor (hGR) isoforms with a decreased response to steroid therapy. Further analysis of additional hGR isoforms may improve the understanding of the steroid response. Ninety-seven human volunteers' blood samples were surveyed for hGR isoforms. An isoform matching National Center for Biotechnology Informatics (NCBI) hGRα (hGR NCBI) served as a reference. Two isoforms were of particular interest-one isoform had three nonsynonymous single-nucleotide polymorphisms (SNPs) (hGR NS-1), and the second had a single-nucleotide deletion (hGR DL-1) resulting in a truncated protein. Transactivation potentials were measured using a luciferase reporter assay. Human glucocorticoid receptor NS-1 had activity more than twice of hGR NCBI, whereas hGR DL-1 demonstrated less than 10% of the activity of hGR NCBI. Cotransfection of two isoforms revealed that the presence of hGR NS-1 increased transactivation potential, whereas hGR DL-1 decreased activity. Synthetic constructs isolating individual and paired SNPs of hGR NS-1 were created to identify the SNP responsible for hyperactivity. Transactivation studies revealed a SNP within the ligand-binding domain exerted the greatest influence over hyperactivity. In evaluating the response to hydrocortisone, hGR NCBI and hGR NS-1 displayed an increased dose-dependent response, but hGR NS-1 had a response more than twice hGR NCBI. Characterization of the novel hyperactive hGR NS-1 provides insight into a possible mechanism underlying the unpredictable response to steroid treatment.

Pretransplant free fatty acids (FFA) and allograft survival in renal transplantation.

BACKGROUND: Fatty acids and their eicosanoid metabolites have been shown to be important mediators of the immune response in transplantation. We hypothesize that elevated pretransplant free fatty acids (FFA) levels may be associated with prolonged survival of kidney transplants. METHODS: Archived pretransplant sera of 130 patients who received a kidney transplant from 1991 to 1997 were analyzed by gas liquid chromatography for a comprehensive FFA profile. FFA levels were categorized by quartiles, and the association between quartiles of the levels for each free-fatty acid and graft survival was initially screened by serial univariate analyses (Kaplan-Meier). All significant variables (FFAs and transplant-specific risk factors) were entered into a multivariable (Cox regression) model. RESULTS: With > 10 y of follow-up, 68 kidney allografts were lost. Factors associated with decreased graft survival by univariate analysis included delayed graft function (DGF), acute rejection (AR), and cold ischemic time (CIT) > 24 h. High levels of arachidonic and γ-linolenic FFA were associated with higher graft survival rates. By multivariate analysis, only DGF, AR, CIT, and arachidonic acid levels were significant. The odds ratios for graft failure for the highest, third, and second quartiles of the pretransplant level of arachidonic acid, compared with the lowest quartile, were 0.18, 0.32, and 0.64, respectively (P = 0.050, log-rank test). For arachidonic acid the survival benefit appeared to be graded with the highest quartile associated with a greater than 80% reduction of risk of kidney graft failure. CONCLUSION: Pretransplant level of arachidonic acid was independently associated with higher kidney graft survival rates. Further studies are necessary to identify the underlying mechanisms and to determine whether interventions aimed at increasing pretransplant arachidonic acid levels might prove beneficial for renal transplant outcomes.

Management of a chronic carotid artery pseudoaneurysm.

An 82-year-old female with a history of right carotid endarterectomy with patch closure 12 years prior presents with a pulsatile right neck mass with skin erosion and bleeding. The patient had been previously evaluated but refused the surgical intervention because a median sternotomy was recommended to obtain adequate proximal control. Her aneurysm was successfully repaired using a combination of open and endovascular method. The repair was performed through a right-hand side anterior sternocleidomastoid neck incision, and proximal vascular control was obtained with an 8.5-mm balloon positioned under fluoroscopic guidance via a femoral puncture.