A Retrospective Cohort Study to Evaluate Adding Biomarkers to the Risk Analysis Index of Frailty.

INTRODUCTION: The Risk Analysis Index (RAI) is a frailty assessment tool associated with adverse postoperative outcomes including 180 and 365-d mortality. However, the RAI has been criticized for only containing subjective inputs rather than including more objective components such as biomarkers. METHODS: We conducted a retrospective cohort study to assess the benefit of adding common biomarkers to the RAI using the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database. RAI plus body mass index (BMI), creatinine, hematocrit, and albumin were evaluated as individual and composite variables on 180-d postoperative mortality. RESULTS: Among 480,731 noncardiac cases in VASQIP from 2010 to 2014, 324,320 (67%) met our inclusion criteria. Frail patients (RAI ≥30) made up to 13.0% of the sample. RAI demonstrated strong discrimination for 180-d mortality (c = 0.839 [0.836-0.843]). Discrimination significantly improved with the addition of Hematocrit (c = 0.862 [0.859-0.865]) and albumin (c = 0.870 [0.866-0.873]), but not for body mass index (BMI) or creatinine. However, calibration plots demonstrate that the improvement was primarily at high RAI values where the model overpredicts observed mortality. CONCLUSIONS: While RAI's ability to predict the risk of 180-d postoperative mortality improves with the addition of certain biomarkers, this only observed in patients classified as very frail (RAI >49). Because very frail patients have significantly elevated observed and predicted mortality, the improved discrimination is likely of limited clinical utility for a frailty screening tool.

A biomechanical perspective on walking in patients with peripheral artery disease.

The most common symptom of peripheral artery disease (PAD) is intermittent claudication, which consists of debilitating leg pain during walking. In clinical settings, the presence of PAD is often noninvasively evaluated using the ankle-brachial index and imaging of the arterial supply. Furthermore, various questionnaires and functional tests are commonly used to measure the severity and negative effect of PAD on quality of life. However, these evaluations only provide information on vascular insufficiency and severity of the disease, but not regarding the complex mechanisms underlying walking impairments in patients with PAD. Biomechanical analyses using motion capture and ground reaction force measurements can provide insight into the underlying mechanisms to walking impairments in PAD. This review analyzes the application of biomechanics tools to identify gait impairments and their clinical implications on rehabilitation of patients with PAD. A total of 18 published journal articles focused on gait biomechanics in patients with PAD were studied. This narriative review shows that the gait of patients with PAD is impaired from the first steps that a patient takes and deteriorates further after the onset of claudication leg pain. These results point toward impaired muscle function across the ankle, knee, and hip joints during walking. Gait analysis helps understand the mechanisms operating in PAD and could also facilitate earlier diagnosis, better treatment, and slower progression of PAD.

Patient Compliance With Wearing Lower Limb Assistive Devices: A Scoping Review.

OBJECTIVE: The aim of this scoping review was to identify information on compliance with wearing orthoses and other supportive devices, to discuss the barriers to adherence, and to suggest strategies for improvement based on these findings. METHODS: Online databases of PubMed, Web of Science, and the Cochrane Library were searched for articles about patients' compliance with regard to lower limb assistive devices. In addition, a methodological quality control process was conducted. Studies were included if in the English language and related to compliance and adherence to the lower limb assistive device. Exclusion was based on first reading the abstract and then the full manuscript confirming content was not related to orthotic devices and compliance. RESULTS: Twelve studies were included. The data revealed between 6% and 80% of patients were not using a prescribed device. Barriers to the use of the orthotic device included medical, functional, device properties and lack of proper fit. Strategies for improved compliance included better communication between patient and clinician, patient education, and improved comfort and device esthetics. CONCLUSIONS: Individualized orthotic adjustments, rehabilitation, and patient education were promising for increasing adherence. Despite positive aspects of improvements in gait, balance in elderly, and a sense of security produced by using assistive devices, compliance remains less than ideal due to barriers. As compliance in recent studies has not improved, continued work in this area is essential to realize the benefits of technological advances in orthotic and assistive devices.

Clinical Utility of the Risk Analysis Index as a Prospective Frailty Screening Tool within a Multi-practice, Multi-hospital Integrated Healthcare System.

OBJECTIVE: The goal of this project was to first address barriers to implementation of the Risk Analysis Index (RAI) within a large, multi-hospital, integrated healthcare delivery system, and to subsequently demonstrate its utility for identifying at-risk surgical patients. BACKGROUND: Prior studies demonstrate the validity of the RAI for evaluating preoperative frailty, but they have not demonstrated the feasibility of its implementation within routine clinical practice. METHODS: Implementation of the RAI as a frailty screening instrument began as a quality improvement initiative at the University of Pittsburgh Medical Center in July 2016. RAI scores were collected within a REDCap survey instrument integrated into the outpatient electronic health record and then linked to information from additional clinical datasets. NSQIP-eligible procedures were queried within 90 days following the RAI, and the association between RAI and postoperative mortality was evaluated using logistic regression and Cox proportional hazards models. Secondary outcomes such as inpatient length of stay and readmissions were also assessed. RESULTS: RAI assessments were completed on 36,261 unique patients presenting to surgical clinics across five hospitals from July 1 to December 31, 2016, and 8,172 of these underwent NSQIP-eligible surgical procedures. The mean RAI score was 23.6 (SD 11.2), the overall 30-day and 180-day mortality after surgery was 0.7% and 2.6%, respectively, and the median time required to collect the RAI was 33 [IQR 23-53] seconds. Overall clinic compliance with the recommendation for RAI assessment increased from 58% in the first month of the study period to 84% in the sixth and final month. RAI score was significantly associated with risk of death (HR=1.099 [95% C.I.: 1.091 - 1.106], p < 0.001). At an RAI cutoff of ≥37, the positive predictive values for 30- and 90-day readmission were 14.8% and 26.2%, respectively, and negative predictive values were 91.6% and 86.4%, respectively. CONCLUSIONS: The RAI frailty screening tool can be efficiently implemented within multi-specialty, multi-hospital healthcare systems. In the context of our findings and given the value of the RAI in predicting adverse postoperative outcomes, health systems should consider implementing frailty screening within surgical clinics.

Claudicating patients with peripheral artery disease have meaningful improvement in walking speed after supervised exercise therapy.

OBJECTIVE: Supervised exercise therapy (SET) is a first-line treatment for patients with peripheral artery disease (PAD). The efficacy of SET is most commonly expressed by significant statistical improvement of parameters that do not clarify how each individual patient will benefit from SET. This study examined the minimal clinically important difference (MCID) in walking speed in claudicating patients with PAD after SET. METHODS: A total of 63 patients with PAD-related claudication (Fontaine stage II PAD) participated in a 6-month SET program. Self-selected walking speed was measured before and after SET. Distribution and anchor-based approaches were used to estimate the MCID for small and substantial improvement. The ability to walk one block and the ability to climb one flight of stairs questions were chosen as anchor questions from the Medical Outcomes Study 36-item Short Form questionnaire. Receiver operating characteristics curve analyses were performed to detect the threshold for MCID in walking speed after treatment. RESULTS: The distribution-based method estimated 0.03 m/s as a small improvement and 0.08 m/s as a substantial improvement after SET. Small and substantial improvements according to the anchor question walking one block were 0.05 m/s and 0.15 m/s, respectively. For the climbing one flight of stairs anchor question, 0.10 m/s was a small improvement. Receiver operating characteristics curve analyses identified an increase of 0.04 m/s and 0.03 m/s for improvement based on walking one block and climbing one flight of stairs, respectively. CONCLUSIONS: We report our findings for the MCID for walking speed among claudicating patients receiving SET. Claudicating patients who increase walking speed of 0.03 m/s or greater are more likely to experience a meaningful improvement in walking impairment than those who do not. The MCID reported in this study can serve as a benchmark for clinicians to develop goals and interpret clinically meaningful progress in the care of claudicating patients with PAD.

Recalibration and External Validation of the Risk Analysis Index: A Surgical Frailty Assessment Tool.

OBJECTIVE AND BACKGROUND: The Risk Analysis Index (RAI) predicts 30-, 180-, and 365-day mortality based on variables constitutive of frailty. Initially validated, in a single-center Veteran hospital, we sought to improve model performance by recalibrating the RAI in a large, veteran surgical registry, and to externally validate it in both a national surgical registry and a cohort of surgical patients for whom RAI was measured prospectively before surgery. METHODS: The RAI was recalibrated among development and confirmation samples within the Veterans Affairs Surgical Quality Improvement Program (VASQIP; 2010-2014; N = 480,731) including major, elective noncardiac surgery patients to create the revised RAI (RAI-rev), comparing discrimination and calibration. The model was tested externally in the American College of Surgeons National Surgical Quality Improvement Program dataset (NSQIP; 2005-2014; N = 1,391,785), and in a prospectively collected cohort from the Nebraska Western Iowa Health Care System VA (NWIHCS; N = 6,856). RESULTS: Recalibrating the RAI significantly improved discrimination for 30-day [c = 0.84-0.86], 180-day [c = 0.81-0.84], and 365-day mortality [c = 0.78-0.82] (P < 0.001 for all) in VASQIP. The RAI-rev also had markedly better calibration (median absolute difference between observed and predicted 180-day mortality: decreased from 8.45% to 1.23%). RAI-rev was highly predictive of 30-day mortality (c = 0.87) in external validation with excellent calibration (median absolute difference between observed and predicted 30-day mortality: 0.6%). The discrimination was highly robust in men (c = 0.85) and women (c = 0.89). Discrimination also improved in the prospectively measured cohort from NWIHCS for 180-day mortality [c = 0.77 to 0.80] (P < 0.001). CONCLUSIONS: The RAI-rev has improved discrimination and calibration as a frailty-screening tool in surgical patients. It has robust external validity in men and women across a wide range of surgical settings and available for immediate implementation for risk assessment and counseling in preoperative patients.

Frailty as measured by the Risk Analysis Index is associated with long-term death after carotid endarterectomy.

OBJECTIVE: The role of carotid endarterectomy (CEA) continues to be debated in the age of optimal medical therapy, particularly for patients with limited life expectancy. The Risk Analysis Index (RAI) measures frailty, a syndrome of decreased physiologic reserve, which increases vulnerability to adverse outcomes. The RAI better predicts surgical complications, nonhome discharge, and death than age or comorbidities alone. We sought to measure the association of frailty, as measured by the RAI, with postoperative in-hospital stroke, long-term stroke, and long-term survival after CEA. We also sought to determine how postoperative stroke interacts with frailty to alter survival trajectory after CEA. METHODS: We queried the Vascular Quality Initiative CEA procedure and long-term data sets (2003-2017) for elective CEAs with complete RAI case information. For all analyses, the cohort was divided into asymptomatic and symptomatic carotid stenosis. Scoring was defined as not frail (RAI <30), frail (RAI 30-34), and very frail (RAI ≥35). Mortality information through December 2017 was obtained from the Social Security Death Index. Multivariable models (logistic and Cox proportional hazards regressions) were used to study the association of frail and very frail patients with the outcomes of interest. In a post hoc analysis, we created Kaplan-Meier curves to analyze patient mortality after CEA as well as after postoperative stroke. RESULTS: Of the 42,869 included patients, 17,092 (39.9%) were female, and 38,395 (89.6%) were white. There were 25,673 (59.9%) patients assigned to the asymptomatic stenosis group and 17,196 (40.1%) patients in the symptomatic stenosis group. Frailty was not associated with perioperative or long-term postoperative stroke. The risk of long-term mortality was significantly higher for frail (hazard ratio, 1.9 [1.7-2.3]) and very frail (hazard ratio, 3.1 [2.6-3.7]) asymptomatic patients; symptomatic frail and very frail patients also had a two to three times increased risk of long-term mortality. Frail and very frail patients had two to three times the risk for long-term mortality compared with patients who were not frail. Postoperative stroke negatively affected the mortality trajectory for all patients in the cohort, regardless of frailty status. CONCLUSIONS: RAI score is not associated with postoperative stroke; however, frail and very frail status is associated with decreased long-term survival in an incremental fashion based on increasing RAI. RAI assessment should be considered in the preoperative decision-making for patients undergoing CEA to ensure long-term survival and optimal surgical outcomes vs medical management.

Supervised walking exercise therapy improves gait biomechanics in patients with peripheral artery disease.

OBJECTIVE: In patients with peripheral artery disease (PAD), supervised exercise therapy is a first line of treatment because it increases maximum walking distances comparable with surgical revascularization therapy. Little is known regarding gait biomechanics after supervised exercise therapy. This study characterized the effects of supervised exercise therapy on gait biomechanics and walking distances in claudicating patients with PAD. METHODS: Forty-seven claudicating patients with PAD underwent gait analysis before and immediately after 6 months of supervised exercise therapy. Exercise sessions consisted of a 5-minute warmup of mild walking and stretching of upper and lower leg muscles, 50 minutes of intermittent treadmill walking, and 5 minutes of cooldown (similar to warmup) three times per week. Measurements included self-perceived ambulatory limitations measured by questionnaire, the ankle-brachial index (ABI), walking distance measures, maximal plantar flexor strength measured by isometric dynamometry, and overground gait biomechanics trials performed before and after the onset of claudication pain. Paired t-tests were used to test for differences in quality of life, walking distances, ABI, and maximal strength. A two-factor repeated measures analysis of variance determined differences for intervention and condition for gait biomechanics dependent variables. RESULTS: After supervised exercise therapy, quality of life, walking distances, and maximal plantar flexor strength improved, although the ABI did not significantly change. Several gait biomechanics parameters improved after the intervention, including torque and power generation at the ankle and hip. Similar to previous studies, the onset of claudication pain led to a worsening gait or a gait that was less like healthy individuals with a pain-free gait. CONCLUSIONS: Six months of supervised exercise therapy produced increases in walking distances and quality of life that are consistent with concurrent improvements in muscle strength and gait biomechanics. These improvements occurred even though the ABI did not improve. Future work should examine the benefits of supervised exercise therapy used in combination with other available treatments for PAD.

Assessment of the Risk Analysis Index for Prediction of Mortality, Major Complications, and Length of Stay in Patients who Underwent Vascular Surgery.

BACKGROUND: Frailty is a risk factor for adverse postoperative outcomes. We aimed to test the performance of a prospectively validated frailty measure, the Risk Analysis Index (RAI) in patients who underwent vascular surgery and delineate the additive impact of procedure complexity on surgical outcomes. METHODS: We queried the 2007-2013 American College of Surgeons National Surgical Quality Improvement Program database to identify 6 major elective vascular procedure categories (carotid revascularization, abdominal aortic aneurysm [AAA] repair, suprainguinal revascularization, infrainguinal revascularization, thoracic aortic aneurysm [TAA] repair, and thoracoabdominal aortic aneurysm [TAAA] repair). We trained and tested logistic regression models for 30-day mortality, major complications, and prolonged length of stay (LOS). The first model, "RAI," used the RAI alone; "RAI-Procedure (RAI-P)" included procedure category (e.g., AAA repair) and procedure approach (e.g., endovascular); "RAI-Procedure Complexity (RAI-PC)" added outpatient versus inpatient surgery, general anesthesia use, work relative value units (RVUs), and operative time. RESULTS: The RAI model was a good predictor of mortality for vascular procedures overall (C-statistic: 0.72). The C-statistic increased with the RAI-P (0.78), which further improved minimally, with the RAI-PC (0.79). When stratified by procedure category, the RAI predicted mortality well for infrainguinal (0.79) and suprainguinal (0.74) procedures, moderately well for AAA repairs (0.69) and carotid revascularizations (0.70), and poorly for TAAs (0.62) and TAAAs (0.54). For carotid, infrainguinal, and suprainguinal procedures, procedure complexity (RAI-PC) had little impact on model discrimination for mortality, did improve discrimination for AAAs (0.84), TAAs (0.73), and TAAAs (0.80). Although the RAI model was not a good predictor for major complications or LOS, discrimination improved for both with the RAI-PC model. CONCLUSIONS: Frailty as measured by the RAI was a good predictor of mortality overall after vascular surgery procedures. Although the RAI was not a strong predictor of major complications or prolonged LOS, the models improved with the addition of procedure characteristics like procedure category and approach.

Gait Mechanics Differences Between Healthy Controls and Patients With Peripheral Artery Disease After Adjusting for Gait Velocity Stride Length and Step Width.

Patients with peripheral artery disease (PAD) experience significant leg dysfunction. The effects of PAD on gait include shortened steps, slower walking velocity, and altered gait kinematics and kinetics, which may confound joint torques and power measurements. Spatiotemporal parameters, joint torques and powers were calculated and compared between 20 patients with PAD and 20 healthy controls using independent t-tests. Separate ANCOVA models were used to evaluate group differences after independently adjusting for gait velocity, stride length and step width. Compared to healthy controls, patients with PAD exhibited reduced peak extensor and flexor torques at the knee, and hip. After adjusting for all covariates combined, differences between groups remained for ankle power generation in late stance, and knee flexor torque. Reduced walking velocity observed in subjects affected by PAD was closely connected with reductions in joint torques and powers during gait. Gait differences remained, at the knee and ankle, after adjusting for the combined effect of spatiotemporal parameters. Improving muscle function through exercise or with the use of assistive devices needs to be a key tool in the development of interventions that aim to enhance the ability of PAD patients to restore spatiotemporal gait parameters.

Muscle strength and control characteristics are altered by peripheral artery disease.

OBJECTIVE: Peripheral artery disease (PAD), a common manifestation of atherosclerosis, is characterized by lower leg ischemia and myopathy in association with leg dysfunction. Patients with PAD have impaired gait from the first step they take with consistent defects in the movement around the ankle joint, especially in plantar flexion. Our goal was to develop muscle strength profiles to better understand the problems in motor control responsible for the walking impairment in patients with PAD. METHODS: Ninety-four claudicating PAD patients performed maximal isometric plantar flexion contractions lasting 10 seconds in two conditions: pain free (patient is well rested and has no claudication symptoms) and pain induced (patient has walked and has claudication symptoms). Sixteen matched healthy controls performed the pain-free condition only. Torque curves were analyzed for dependent variables of muscle strength and motor control. Independent t-tests were used to compare variables between groups, and dependent t-tests determined differences between conditions. RESULTS: Patients with PAD had significantly reduced peak torque and area under the curve compared with controls. Measures of control differed between PAD conditions only. Load rate and linear region duration were greater in the pain condition. Time to peak torque was shorter in the pain condition. CONCLUSIONS: This study conclusively demonstrates that the plantar flexor muscles of the PAD patient at baseline and without pain are weaker in patients with PAD compared with controls. With the onset of claudication pain, patients with PAD exhibit altered muscle control strategies and further strength deficits are manifest compared to baseline levels. The myopathy of PAD legs appears to have a central role in the functional deterioration of the calf muscles, as it is evident both before and after onset of ischemic pain.

Preoperative frailty predicts postoperative complications and mortality in urology patients.

PURPOSE: Our objective was to determine the impact of preoperative frailty, as measured by validated Risk Analysis Index (RAI), on the occurrence of postoperative complications after urologic surgeries in a national database comprised of diverse practice groups and cases. STUDY DESIGN: The National Surgical Quality Improvement Program (NSQIP) database was queried from 2005 to 2011 for a list of abdominal, vaginal, transurethral and scrotal urological surgeries using Current Procedural Terminology codes. The study population was subdivided into two groups based on the nature of procedures performed: complex procedures (inpatient) and simple procedures (outpatient). Risk Analysis Index score was calculated using preoperative NSQIP variables to determine preoperative frailty. Major postoperative morbidities (pulmonary, cardiovascular, renal and infectious), mortality, return to operating room, discharge destination and readmission to the hospital were examined. RESULTS: The study identified 42,715 patients who underwent urological procedures, 25,693 complex and 17,022 simple procedures. Mean RAI score (range) was 7.75 (0-53). The majority of patients scored low on the RAI (90.57 % with RAI < 10). As the RAI score increased, there was a significant increase in postoperative complication and mortality rate (both p < 0.0001). Similarly, the rate of return to operating room and hospital readmission rate increased as RAI increased (both p < 0.0001). Additionally, rate of discharge to home decreased. Interestingly, mortality rate in patients with high RAI did not differ comparing simple to complex procedures (p = 0.90), whereas complications were significantly greater in the complex operation (p = 0.01). CONCLUSIONS: Increase in frailty, as measured by RAI score, is associated with increased postoperative complications and mortality. RAI may allow for rapid identification and counseling of patients who are at high risk of adverse perioperative outcomes.

Contained Rupture of an Abdominal Aortic Aneurysm With Extensive Vertebral Body and Retroperitoneal Space Destruction.

Chronic contained rupture of an abdominal aortic aneurysm with vertebral body erosion most commonly presents with symptoms of low back pain. Although not well known, vertebral body erosion or destruction may be seen in up to 25% of patients with sealed or contained rupture of an abdominal aortic aneurysm. This appearance on cross-sectional imaging may mimic a malignant or infectious process. Although these cases can present a diagnostic challenge, published cases of chronic contained rupture of an abdominal aortic aneurysm with vertebral body erosion demonstrate clinical and imaging similarities that, when recognized, can assist in diagnosis.

Preoperative Frailty Increases Risk of Nonhome Discharge after Elective Vascular Surgery in Home-Dwelling Patients.

BACKGROUND: Patient-centered quality outcomes such as disposition after surgery are increasingly being scrutinized. Preoperative factors predictive of nonhome discharge (DC) may identify at-risk patients for targeted interventions. This study examines the association among preoperative risk factors, frailty, and nonhome DC after elective vascular surgery procedures in patients living at home. METHODS: The 2011-2012 National Surgical Quality Improvement Project database was queried to identify all home-dwelling patients who underwent elective vascular procedures (endovascular and open aortic aneurysm repair, suprainguinal and infrainguinal bypasses, peripheral endovascular interventions, carotid endarterectomy, and stent). Preoperative frailty was measured using the modified frailty index (mFI; derived from Canadian Study of Health and Aging). Univariate and multivariate logistic regression analysis was performed to examine the association of frailty and nonhome DC. RESULTS: Of 15,843 home-dwelling patients, 1,177 patients (7.4%) did not return home postoperatively. Frailty (mFI > 0.25) conferred a significantly increased 2-fold risk of nonhome DC disposition for each procedure type. Frailty, female gender, open procedures, increasing age, end-stage renal disease, and occurrence of any postoperative complication were associated with increased risk of nonhome DC. On multivariate logistic regression analysis, frailty increased the odds of nonhome DC by 60% (odds ratio 1.6, 95% confidence interval 1.4-1.8) after adjusting for other covariates. In the presence of complications, the risk of nonhome DC was 27.5% in frail versus 16.5% in nonfrail patients (P < 0.001). In the absence of complications, although absolute risk was lower, frail patients were nearly twice as likely to not return home (frail 5.5% vs. nonfrail 2.75%, P < 0.001). CONCLUSIONS: Frail home-dwelling patients undergoing elective vascular procedures are at high risk of not returning home after surgery. Preoperative frailty assessment appears to hold potential for counseling regarding postsurgery disposition and DC planning.

Preoperative frailty Risk Analysis Index to stratify patients undergoing carotid endarterectomy.

OBJECTIVE: Rapid and objective preoperative assessment of patients undergoing carotid endarterectomy (CEA) remains problematic. Preoperative variables correlate with increased morbidity and mortality, yet no easily implemented tool exists to stratify patients. We determined the relationship between our fully implemented frailty-based bedside Risk Analysis Index (RAI) and complications after CEA. METHODS: Patients undergoing CEA in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2005 to 2011 were included. Variables of frailty RAI were matched to preoperative NSQIP variables, and outcomes including stroke, mortality, myocardial infarction (MI), and length of stay were analyzed. We further analyzed patients who were symptomatic and asymptomatic before CEA. RESULTS: With use of the NSQIP database, 44,832 patients undergoing CEA were analyzed (17,696 [39.5%] symptomatic; 27,136 [60.5%] asymptomatic). Increasing frailty RAI score correlated with increasing stroke, death, and MI (P < .0001) as well as with length of stay. RAI demonstrated increasing risk of stroke and death on the basis of risk stratification (low risk [0-10], 2.1%; high risk [>10], 5.0%). Among patients undergoing CEA, 88% scored low (<10) on the RAI. In symptomatic patients, the risk of stroke and death for patients with a score of ≤10 is 2.9%, whereas if the RAI score is 11 to 15, it is 5.0%; 16 to 20, 6.9%; and >21, 8.6%. In asymptomatic patients, the risk of stroke and death for patients with a score of ≤10 is 1.6%, whereas if the RAI score is 11 to 15, it is 2.9%; 16 to 20, 5.2%; and >21, 6.2%. CONCLUSIONS: Frailty is a predictor of increased stroke, mortality, MI, and length of stay after CEA. An easily implemented RAI holds the potential to identify a limited subset of patients who are at higher risk for postoperative complications and may not benefit from CEA.

Abnormal myofiber morphology and limb dysfunction in claudication.

BACKGROUND: Peripheral artery disease (PAD), which affects an estimated 27 million people in Europe and North America, is caused by atherosclerotic plaques that limit blood flow to the legs. Chronic, repeated ischemia in the lower leg muscles of PAD patients is associated with loss of normal myofiber morphology and myofiber degradation. In this study, we tested the hypothesis that myofiber morphometrics of PAD calf muscle are significantly different from normal calf muscle and correlate with reduced calf muscle strength and walking performance. METHODS: Gastrocnemius biopsies were collected from 154 PAD patients (Fontaine stage II) and 85 control subjects. Morphometric parameters of gastrocnemius fibers were determined and evaluated for associations with walking distances and calf muscle strength. RESULTS: Compared with control myofibers, PAD myofiber cross-sectional area, major and minor axes, equivalent diameter, perimeter, solidity, and density were significantly decreased (P < 0.005), whereas roundness was significantly increased (P < 0.005). Myofiber morphometric parameters correlated with walking distances and calf muscle strength. Multiple regression analyses demonstrated myofiber cross-sectional area, roundness, and solidity as the best predictors of calf muscle strength and 6-min walking distance, whereas cross-sectional area was the main predictor of maximum walking distance. CONCLUSIONS: Myofiber morphometrics of PAD gastrocnemius differ significantly from those of control muscle and predict calf muscle strength and walking distances of the PAD patients. Morphometric parameters of gastrocnemius myofibers may serve as objective criteria for diagnosis, staging, and treatment of PAD.

A totally recombinant human fibrin sealant.

BACKGROUND: Applications of plasma-derived human fibrin sealants (pdhFS) have been limited because of cost, limited supply of pathogen-screened plasma, the need for bioengineering improvements, and regulatory issues associated with federal approval. We describe a totally recombinant human fibrin sealant (rhFS), which may engender an abundant, safe, and cost-effective supply of efficacious fibrin sealant. MATERIALS AND METHODS: A first-generation rhFS made from recombinant human fibrinogen (rhFI; produced in the milk of transgenic cows), activated recombinant human factor XIII (rhFXIIIa; produced in yeast), and recombinant human thrombin (rhFIIa; purchased, made in animal cell culture) was formulated using thromboelastography (TEG). The hemostatic efficacy of rhFS versus commercial pdhFS was compared in a nonlethal porcine hepatic wedge excision model. RESULTS: The maximal clot strength of rhFS measured in vitro by TEG was not statistically different than that of pdhFS. TEG analysis also showed that the rhFS gained strength more quickly as reflected by a steeper α angle; however, the rhFS achieved this clot strength with a 5-fold lower factor I content than the pdhFS. When these fibrin sealants were studied in a porcine hepatic wedge excision model, the hemostatic scores of the rhFS were equivalent or better than that of the pdhFS. CONCLUSIONS: The bioengineered rhFS had equivalent or better hemostatic efficacy than the pdhFS in a nonlethal hemorrhage model, despite the factor I concentration in the rhFS being about one-fifth that in the pdhFS. Because the rhFS is amenable to large-scale production, the rhFS has the potential to be more economical and abundant than the pdhFS, while having a decreased risk of blood-borne pathogen transmission.

Peripheral artery disease causes consistent gait irregularities regardless of the location of leg claudication pain.

BACKGROUND: The most common symptom of peripheral artery disease (PAD) is intermittent claudication that involves the calf, thigh, and/or buttock muscles. How the specific location of this leg pain is related to altered gait, however, is unknown. OBJECTIVES: We hypothesized that because the location of claudication symptoms uniquely affects different leg muscle groups in people with PAD, this would produce distinctive walking patterns. METHODS: A total of 105 participants with PAD and 35 age-matched older volunteers without PAD (CTRL) were recruited. Participants completed walking impairment questionnaires (WIQ), Gardner-Skinner progressive treadmill tests, the six-minute walk test, and we performed an advanced evaluation of the biomechanics of their overground walking. Participants with PAD were categorized into 4 groups according to their stated pain location(s): calf only (C, n = 43); thigh and calf (TC, n = 18); buttock and calf (BC, n = 15); or buttock, thigh, and calf (BTC, n = 29). Outcomes were compared between CTRL, C, TC, BC and BTC groups using a one-way ANOVA with post-hoc comparisons to identify and assess statistically significant differences. RESULTS: There were no significant differences between CTRL, C, TC, BC and BTC groups in distances walked or walking speed when either pain-free or experiencing claudication pain. Each participant with PAD had significantly dysfunctional biomechanical gait parameters, even when pain-free, when compared to CTRL (pain-free) walking data. During pain-free walking, out of the 18 gait parameters evaluated, we only identified significant differences in hip power generation during push-off (in C and TC groups) and in knee power absorption during weight acceptance (in TC and BC groups). There were no between-group differences in gait parameters while people with PAD were walking with claudication pain. CONCLUSIONS: Our data demonstrate that PAD affects the ischemic lower extremities in a diffuse manner irrespective of the location of claudication symptoms. DATABASE REGISTRATION: ClinicalTrials.gov NCT01970332.

Preoperative anemia is an independent predictor of postoperative mortality and adverse cardiac events in elderly patients undergoing elective vascular operations.

OBJECTIVE: The objective of this study was to assess the impact of preoperative anemia (hematocrit <39%) on postoperative 30-day mortality and adverse cardiac events in patients 65 years or older undergoing elective vascular procedures. BACKGROUND: Preoperative anemia is associated with adverse outcomes after cardiac surgery, but its association with postoperative outcomes after open and endovascular procedures is not well established. Elderly patients have a decreased tolerance to anemia and are at high risk for complications after vascular procedures. METHODS: Patients (N = 31,857) were identified from the American College of Surgeons' 2007-2009 National Surgical Quality Improvement Program-a prospective, multicenter (>250) database maintained across the United States. The primary and secondary outcomes of interest were 30-day mortality and a composite end point of death or cardiac event (cardiac arrest or myocardial infarction), respectively. RESULTS: Forty-seven percent of the study population was anemic. Anemic patients had a postoperative mortality and cardiac event rate of 2.4% and 2.3% in contrast to the 1.2% and 1.2%, respectively, in patients with hematocrit within the normal range (P < 0.0001). On multivariate analysis, we found a 4.2% (95% confidence interval, 1.9-6.5) increase in the adjusted risk of 30-day postoperative mortality for every percentage point of hematocrit decrease from the normal range. CONCLUSIONS: The presence and degree of preoperative anemia are independently associated with 30-day death and adverse cardiac events in patients 65 years or older undergoing elective open and endovascular procedures. Identification and treatment of anemia should be important components of preoperative care for patients undergoing vascular operations.

Oxidative damage and myofiber degeneration in the gastrocnemius of patients with peripheral arterial disease.

Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis that produces blockages in arteries supplying the legs, affects an estimated 27 million people in Europe and North America. Increased production of reactive oxygen species by dysfunctional mitochondria in leg muscles of PAD patients is viewed as a key mechanism of initiation and progression of the disease. Previous studies demonstrated increased oxidative damage in homogenates of biopsy specimens from PAD gastrocnemius compared to controls, but did not address myofiber-specific damage. In this study, we investigated oxidative damage to myofibers as a possible cause of the myopathy of PAD. To achieve this, we developed and validated fluorescence microscopy procedures for quantitative analysis of carbonyl groups and 4-hydroxy-2-nonenal (HNE) adducts in myofibers of biopsy specimens from human gastrocnemius. PAD and control specimens were evaluated for differences in 1) myofiber content of these two forms of oxidative damage and 2) myofiber cross-sectional area. Furthermore, oxidative damage to PAD myofibers was tested for associations with clinical stage of disease, degree of ischemia in the affected leg, and myofiber cross-sectional area. Carbonyl groups and HNE adducts were increased 30% (p < 0.0001) and 40% (p < 0.0001), respectively, in the myofibers of PAD (N = 34) compared to control (N = 21) patients. Mean cross-sectional area of PAD myofibers was reduced 29.3% compared to controls (p < 0.0003). Both forms of oxidative damage increased with clinical stage of disease, blood flow limitation in the ischemic leg, and reduced myofiber cross-sectional area. The data establish oxidative damage to myofibers as a possible cause of PAD myopathy.