Trends, factors, and disparities associated with length of stay after lower extremity bypass for tissue loss.

OBJECTIVE: The objective of this study was to determine predictors of increased length of stay (LOS) in patients who underwent lower extremity bypass for tissue loss. METHODS: Using 2011 to 2016 National Surgical Quality Improvement Program vascular targeted databases, we compared demographics, comorbidities, procedural characteristics, and 30-day outcomes of patients who had expected LOS vs extended LOS (>75th percentile, 9 days) after nonemergent lower extremity bypass for tissue loss. We also compared factors associated with short LOS (<25th percentile, 4 days) and extended LOS (>75th percentile, 9 days) vs the interquartile range of LOS (4-9 days). Yearly trends and independent predictors were determined by linear and logistic regression. This study was exempt from Institutional Review Board approval. RESULTS: In 4964 analyzed patients, there were no significant yearly trends or changes in LOS in the recent 5 years (P > .05). Overall 30-day mortality, major amputation, and reintervention rates were 1.6%, 4.5%, and 4.8%, respectively, also with no significant yearly trends (all P > .05). On univariate analysis, nonwhite race, dependent functional status, transfers, dialysis, congestive heart failure, hypertension, beta blockers, distal bypass targets, and extended operative time were associated with extended LOS (P < .05). Extended LOS was also associated with higher rates of 30-day major adverse limb and cardiac events, additional procedures related to wound care, deep venous thrombosis, complications (pulmonary, renal, septic, bleeding, and wound), and discharge to facility but lower 30-day readmission rates. After adjustment for covariates, the independent factors for extended LOS included dialysis, beta blockers, prolonged operative time, reintervention, major amputation, additional procedures related to wound care, deep venous thrombosis, complications (pulmonary, renal, septic, bleeding, and wound), and discharge to facility (P < .05). On the other hand, multivariable analysis showed that patients with expected LOS were significantly more likely to have been of white race or readmitted postoperatively (P < .05). CONCLUSIONS: From 2011 to 2016, there were no significant changes in LOS. Efforts to decrease LOS without increasing readmission rates while focusing on some of the identified factors, including preventable postoperative complications and pre-existing socioeconomic factors, may improve the overall vascular care of these challenging patients.

Neutrophil-to-Lymphocyte Ratio Associated With Adverse Events After Endovascular Aneurysm Repair (EVAR).

BACKGROUND: The blood neutrophil-to-lymphocyte ratio (NLR) is a surrogate biomarker of systemic inflammation with important prognostic significance in multiple disease processes, including cardiovascular diseases. It is inexpensive, widely available, and may be related to the outcomes of patients after surgery. We aimed to investigate the possible association of NLR with the outcomes of patients following endovascular aneurysm repair (EVAR). METHODS: This single-center, retrospective study of a prospectively maintained database evaluated 777 patients with a diagnosed abdominal aortic aneurysm (AAA) who underwent EVAR and were longitudinally followed between 2001 and 2017. NLR was defined as the ratio of absolute neutrophil count to absolute lymphocyte count. The mortality and reinterventions were used to evaluate outcomes using the appropriate univariate models, and the effect of clinical variables on NLR was further investigated using multivariate modelling. RESULTS: The median NLR for all patients was 3 IQR [2.2 - 4.6]. A cut-off point of 3.6 was uncovered in a training set of 388 patients using the maximally ranked statistic method. Patients with NLR < 3.6 had significantly improved mortality rates (P< 0.0001) in the training set, and results were internally validated in a testing set of 389 patients (P = 0.042). Multivariate analysis revealed that high NLR (HR 1.4 95% CI [1.0 - 2.0]; P< 0.05) remained an independent predictor of mortality in a multivariate analysis controlling for characteristics such as comorbidities, age, and maximal aortic diameter. 5-year mortality and 30-day, 1-year and 5-year reinterventions were all higher in the high NLR group. CONCLUSION: High NLR was significantly associated with higher rates of death at 5 years as well as higher rates of reinterventions at 30 days, 1 year and 5 years. We also suggest that an internally validated cut-off point of NLR >3.6 may be clinically important to help segregate patients into high and low NLR categories. It remains unclear whether NLR is directly linked to adverse events post-EVAR or whether it is a surrogate for an inflammatory state that predisposes patients to higher risk of death or reinterventions.

Iliac Remote Endarterectomy to Restore Circulation in a Patient with Infected Aorto-Femoral and Axillo-Bifemoral Bypasses.

We report a case of a patient who underwent a 2-stage operation that included a right obturator bypass with left iliac remote endarterectomy followed by removal of an infected, previously failed aorto-right-femoral and right axillo-bifemoral bypass reconstructions.

Preoperative inflammatory status as a predictor of primary patency after femoropopliteal stent implantation.

OBJECTIVE: The purpose of this study was to evaluate the impact of preoperative inflammatory status, as determined by complete blood count test parameters, on 12- and 24-month patency of femoropopliteal stenting for peripheral arterial disease. METHODS: We retrospectively analyzed baseline clinical and angiographic data among 138 patients (median age, 73 years; 46% female) from 2005 to 2014 at our institution with preoperative complete blood count test values and information of patency for at least 12 months after first-time femoropopliteal stenting. Patients were stratified into tertiles on the basis of preoperative blood counts to evaluate associations with in-stent restenosis (ISR) leading to loss of primary patency, defined by a Doppler velocity ratio ≥2.5:1, computed tomography angiography demonstrating ≥50% luminal narrowing within the stent, or reintervention. RESULTS: Univariate analysis determined that the 81 patients (59%) who experienced ISR within 12 months had significantly higher preoperative white blood cell (WBC), platelet, neutrophil, and lymphocyte counts than the 57 patients (41%) whose stents remained patent for longer than 12 months (8.7 vs 6.7 [P < .001], 246 vs 184 [P < .001], 5.7 vs 4.7 [P = .001], and 1.8 vs 1.2 [P = .004], respectively). Compared with patients in the lower WBC tertile (n = 45) who had a median patency of 19.4 months, those in the upper WBC tertile (n = 44) had a median patency of only 7.0 months and a 3.3-fold increased risk for ISR after adjusting for age, sex, lesion type, TransAtlantic Inter-Society Consensus II score, tibial vessel runoff, antiplatelet therapy, presence of diabetes, critical limb ischemia, adjunct procedures, hyperlipidemia, and end-stage renal disease in multivariate analysis (P < .001). Compared with patients in the lower platelet tertile (n = 45) who had a median patency of 16.9 months, those in the upper platelet tertile (n = 47) had a median patency of 7.1 months and a 2.7-fold increased adjusted risk (P = .001). Compared with patients in the lower neutrophil tertile (n = 33) who had a median patency of 14.3 months, those in the upper neutrophil tertile (n = 33) had a median patency of 6.2 months and a 3.2-fold increased adjusted risk (P = .001). After adjusting for covariates, patients divided into tertiles by lymphocyte counts exhibited no significant differences for ISR. CONCLUSIONS: Routine preoperative tests that determine baseline inflammatory status may provide strong clinical utility in assessing potential risk stratification of patients for ISR after femoropopliteal stenting. Circulating WBCs, platelets, and neutrophils may be important inflammatory mediators of ISR.

The Impact of Surgical Care Improvement Project Measures on In-Hospital Outcomes following Elective Vascular Procedures.

BACKGROUND: As part of the Surgical Care Improvement Project (SCIP), a national quality partnership of organizations including the Centers for Medicare and Medicaid Services and the Centers for Disease Control and Prevention implemented several perioperative guidelines regarding antibiotic, venous thromboembolism (VTE), and beta-blocker prophylaxis for surgical patients. We evaluated the effect of SCIP on in-hospital surgical site infections (SSI), graft infections, VTE, myocardial infarctions (MIs), cardiac complications, mortality, and length of stay following elective major vascular surgery. METHODS: Using International Classification of Diseases, Ninth Revision (ICD-9) diagnostic and procedure codes, we identified elective open abdominal aneurysm repair (OAR), endovascular aneurysm repair (EVAR), carotid endarterectomy (CEA), major lower extremity amputation, and lower extremity bypass (LEB) procedures in the National Inpatient Sample from 2000 to 2012. Logistic regression and generalized linear models controlling for covariates were used to compare postoperative in-hospital outcomes before and after SCIP implementation (pre-SCIP era 2000-2005 versus post-SCIP era 2009-2012). RESULTS: In the post-SCIP era, the rate of in-hospital SSI following OAR increased from 1.0% to 1.6% (P < 0.05). Nonetheless, there were improvements in in-hospital SSI (in EVAR and CEA), graft infections (in OAR, EVAR, and LEB for tissue loss), VTE (in CEA), MI (in EVAR and LEB for tissue loss), cardiac complication (in all procedures except OAR), mortality (in EVAR, CEA, major lower extremity amputation, and LEB for tissue loss), and length of stay (in all procedures except OAR) (all P < 0.05). However after adjusting for covariates, SCIP was only associated with reducing SSI in CEA and major lower extremity amputation, graft infections in OAR and LEB for tissue loss, VTE in LEB for claudication or rest pain, mortality in OAR, and length of stay in all procedures except EVAR and CEA. CONCLUSIONS: Implementation of SCIP measures was associated with slight improvements in a few in-hospital outcomes following vascular procedures. Additional measures that are more specific to the clinical and technical challenges of treating vascular disease may be more effective for improving the management of vascular patents.

Spontaneous recanalization of a total occlusion of an infrarenal abdominal aorta after left axillary-bifemoral bypass.

Acute aortic occlusion is an infrequent clinical event with high morbidity and mortality. Management is determined by the cause of the occlusion, with thromboembolectomy used for embolic events and bypass for thrombotic events. After bypass, recanalization of a total aortic occlusion has been sparsely reported. We present a case of a total occlusion of an infrarenal abdominal aorta that was managed surgically with a left axillary-bifemoral bypass. Imaging performed 6 months postoperatively revealed a spontaneously recanalized aorta and occluded bypass graft.

Bilateral May-Thurner syndrome refractory to iliac aneurysm repair.

Venous complications of iliac artery aneurysms are rare. We report the case of bilateral iliac aneurysms that resulted in iliac vein outflow obstruction despite endovascular aneurysm repair. In our patient, bilateral iliac vein stenting resulted in symptom resolution.

Trends in vena cava filter insertions and "prophylactic" use.

BACKGROUND: Prophylactic vena cava filter (VCF) use in patients without venous thromboembolism is common practice despite ongoing controversy. Thorough analysis of the evolution of this practice is lacking. We describe trends in VCF use and identify events associated with changes in practice. METHODS: Using the National Inpatient Sample, we conducted a retrospective observational study of U.S. adult hospitalizations from 2000 to 2014. Trends in prophylactic VCF insertion were analyzed both across the entire study population and within subgroups according to trauma status and type of concurrent surgery. Annual percentage change (APC) was calculated, and trends were analyzed using Poisson regression. RESULTS: Among 461,904,314 adult inpatients (median [interquartile range] age, 58.1 [38.5-74.3] years; 39.6% male), the incidence of VCF insertion increased rapidly at first (from 0.19% to 0.35%; APC, 11.2%; 95% confidence interval [CI], 10.3%-12.2%; P < .001), then at a slower rate after the publication of the Prévention du Risque d'Embolie Pulmonaire par Interruption Cave 2 (PREPIC2) trial in 2005 (from 0.35% to 0.42%; APC, 4.4%; 95% CI, 2.8%-6.0%; P < .001), and it began decreasing after the 2010 Food and Drug Administration (FDA) safety alert (from 0.42% to 0.32%; APC, -5.5%; 95% CI, -6.5% to -4.6%; P < .001). The percentage of total VCFs that had a prophylactic indication increased quickly before publication of the PREPIC2 trial (APC, 19.5%; 95% CI, 17.9%-21.0%; P < .001), increased at a slower rate after publication in 2005 (APC, 4.4%; 95% CI, 2.6%-6.2%; P < .001), and dropped after the FDA safety alert, stabilizing at 18.5% for the last 3 years (APC, -0.3%; 95% CI, -2.2% to 1.7%; P = .8). Subgroups most associated with prophylactic VCF insertion were operative trauma (odds ratio [OR], 10.9; 95% CI, 10.2-11.7), orthopedic surgery (OR, 4.7; 95% CI, 4.3-5.2), and neurosurgical procedures (OR, 3.9; 95% CI, 3.6-4.2). All groups except orthopedic surgery experienced a deceleration in prophylactic VCF growth after the publication of PREPIC2. Meanwhile, the FDA safety alert was associated with a decrease in prophylactic VCF insertions for all groups except other major surgery. CONCLUSIONS: Whereas publication of the PREPIC2 trial led to a deceleration in prophylactic VCF insertion growth, the FDA alert had a bigger impact, leading to declining rates of prophylactic VCF use. Further investigations of prophylactic insertion of VCF in trauma, orthopedic, and neurosurgical patients are needed to determine whether current levels of use are justified.

Accumulation and localization of macrophage phenotypes with human intervertebral disc degeneration.

BACKGROUND CONTEXT: Chronic inflammation is an important component of intervertebral disc (IVD) degeneration, but there is limited knowledge about the identity and source of inflammatory cells involved with the degenerative processes. Macrophages can exhibit multiple phenotypes and are known inflammatory regulators in many tissues, but their phenotypes have not been characterized in IVD degeneration. PURPOSE: We aimed to characterize accumulation and localization of macrophages in IVD degeneration. STUDY DESIGN/SETTING: This is an exploratory study to characterize macrophage phenotypes in human cadaver IVDs and the effects of injury and degeneration using multiple immunohistochemistry methods. OUTCOME MEASURES: Percent positivity of immunohistochemical markers specific for CCR7, CD163, and CD206, and qualitative assessments of dual immunofluorescence and immunostaining localization were the outcome measures. METHODS: Macrophages were identified in human cadaveric IVDs with immunohistochemistry using cell surface markers CCR7, CD163, and CD206, which are associated with proinflammatory M1, remodeling M2c, and anti-inflammatory M2a phenotypes, respectively. Variations in the accumulation and localization of macrophage markers with degenerative grade across subjects and within donors are described. RESULTS: Cells expressing all three macrophage markers were found in all degenerative IVDs, but not in the healthiest IVDs. Cells expressing CCR7 and CD163, but not CD206, significantly increased with degenerative grade. Many cells also co-expressed multiple macrophage markers. Across all degenerative grades, CCR7+ and CD163+ were significantly more present in unhealthy nucleus pulposus (NP), annulus fibrosus (AF), and end plate (EP) regions exhibiting structural irregularities and defects. Positively stained cells in the NP and AF closely resembled resident IVD cells, suggesting that IVD cells can express macrophage cell surface markers. In the EP, there were increasing trends of positively stained cells with atypical morphology and distribution, suggesting a source for exogenous macrophage infiltration into the IVD. CONCLUSIONS: Chronic inflammatory conditions of IVD degeneration appear to involve macrophages or macrophage-like cells, as expression of multiple macrophage markers increased with degeneration, especially around unhealthy regions with defects and the EP. Knowledge of macrophage phenotypes and their localization better elucidates the complex injury and repair processes in IVDs and may eventually lead to novel treatments.

Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds.

In normal tissue repair, macrophages exhibit a pro-inflammatory phenotype (M1) at early stages and a pro-healing phenotype (M2) at later stages. We have previously shown that M1 macrophages initiate angiogenesis while M2 macrophages promote vessel maturation. Therefore, we reasoned that scaffolds that promote sequential M1 and M2 polarization of infiltrating macrophages should result in enhanced angiogenesis and healing. To this end, we first analyzed the in vitro kinetics of macrophage phenotype switch using flow cytometry, gene expression, and cytokine secretion analysis. Then, we designed scaffolds for bone regeneration based on modifications of decellularized bone for a short release of interferon-gamma (IFNg) to promote the M1 phenotype, followed by a more sustained release of interleukin-4 (IL4) to promote the M2 phenotype. To achieve this sequential release profile, IFNg was physically adsorbed onto the scaffolds, while IL4 was attached via biotin-streptavidin binding. Interestingly, despite the strong interactions between biotin and streptavidin, release studies showed that biotinylated IL4 was released over 6 days. These scaffolds promoted sequential M1 and M2 polarization of primary human macrophages as measured by gene expression of ten M1 and M2 markers and secretion of four cytokines, although the overlapping phases of IFNg and IL4 release tempered polarization to some extent. Murine subcutaneous implantation model showed increased vascularization in scaffolds releasing IFNg compared to controls. This study demonstrates that scaffolds for tissue engineering can be designed to harness the angiogenic behavior of host macrophages towards scaffold vascularization.

The role of macrophage phenotype in vascularization of tissue engineering scaffolds.

Angiogenesis is crucial for the success of most tissue engineering strategies. The natural inflammatory response is a major regulator of vascularization, through the activity of different types of macrophages and the cytokines they secrete. Macrophages exist on a spectrum of diverse phenotypes, from "classically activated" M1 to "alternatively activated" M2 macrophages. M2 macrophages, including the subsets M2a and M2c, are typically considered to promote angiogenesis and tissue regeneration, while M1 macrophages are considered to be anti-angiogenic, although these classifications are controversial. Here we show that in contrast to this traditional paradigm, primary human M1 macrophages secrete the highest levels of potent angiogenic stimulators including VEGF; M2a macrophages secrete the highest levels of PDGF-BB, a chemoattractant for stabilizing pericytes, and also promote anastomosis of sprouting endothelial cells in vitro; and M2c macrophages secrete the highest levels of MMP9, an important protease involved in vascular remodeling. In a murine subcutaneous implantation model, porous collagen scaffolds were surrounded by a fibrous capsule, coincident with high expression of M2 macrophage markers, while scaffolds coated with the bacterial lipopolysaccharide were degraded by inflammatory macrophages, and glutaraldehyde-crosslinked scaffolds were infiltrated by substantial numbers of blood vessels, accompanied by high levels of M1 and M2 macrophages. These results suggest that coordinated efforts by both M1 and M2 macrophages are required for angiogenesis and scaffold vascularization, which may explain some of the controversy over which phenotype is the angiogenic phenotype.