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Purpose: To evaluate effectiveness of chairside yoga therapy on perceptions of fatigue, pain, nausea, anxiety, and distress among oncology patients concurrently receiving outpatient cancer infusion therapy. Design: This prospective pilot study used pre-/post-survey design in convenience sample of cancer patients in outpatient setting. Methods: Researchers developed and administered the Outpatient Cancer Symptom Assessment Scale (OCSAS) comprised of cancer- or treatment-related symptoms commonly reported in the oncology population (nausea, pain, fatigue, anxiety, and distress). Following IRB approval, symptoms were rated using Likert scale of 0 (not present) to 10 (severe) before and after chairside yoga therapy delivered concurrently with outpatient infusions. Qualitative data was collected related to patients' overall infusion experience. Findings: Participants ( n  = 82) reported positive patient experiences and statistically less pain ( p  < 0.001), fatigue ( p  < 0.001), anxiety ( p  < 0.001), and distress ( p  < 0.001) following the yoga intervention compared to baseline. Nausea was not significantly impacted by the yoga intervention. Conclusions: Yoga therapy received concurrently during outpatient cancer infusion is consistent with a holistic and integrative approach to care for the oncology population. Yoga therapy offers promise for reducing symptoms which negatively impact quality of life, including pain, fatigue, anxiety, and distress. Qualitative data suggests patients' overall infusion experience was enhanced with yoga therapy.

The use of a concise standardized spiritual screening process to identify spiritual practices and needs of patients is essential for holistic nursing care. This interprofessional initiative resulted in the development of a spiritual screening tool that substantially increased Pastoral Services referrals to the patients who needed them and represents a significant opportunity in the delivery of holistic nursing care. Acute care settings may benefit from the adoption of a standardized chaplain referral process housed in the EMR and completed on the frontlines by trusted nursing staff providing patient and family centered care. This standardized spiritual screening process not only triggered essential services of Pastoral Services, but also helped identify and address important spiritual needs of hospitalized patients.The ability to design a tool responsive to the evolving, spiritual needs of patients can be challenging. Through collaboration with chaplains, nurses can be instrumental in creating instruments informed by available evidence in the empirical literature. Furthermore, engaging patients as a source of data during instrument design helps to ensure the content validity and practical usefulness of an instrument. Healthcare organizations might choose to implement and further evaluate/refine the new Spiritual Screening Tool and referral process developed as a result of this initiative.

Objective: Inferior survival outcomes have historically been reported for African Americans with cardiovascular disease, and poorer outcomes have been presumed for peripheral arterial disease (PAD) as well. The current study evaluates the effect of race and ethnicity on survival of patients undergoing open or endovascular interventions for lower extremity PAD., Methods: Data of patients from the Society for Vascular Surgery Vascular Quality Initiative database were obtained for patients undergoing open infrainguinal (INFRA) or suprainguinal (SUPRA) bypass, peripheral vascular intervention (PVI), and amputation (AMP). Patients were further stratified as suprainguinal (SupraPVI) if any of the first three interventions listed included the aorta or iliac vessels or infrainguinal (InfraPVI) if not. The primary outcome was the patient's death (overall mortality) as recorded in the database or determined by cross-reference with the Social Security Death Index (SSDI). The secondary outcome consisted of perioperative mortality during the index hospitalization. Generalized linear modeling provided multivariate analysis, with entry of variables dependent on results of univariate analysis., Results: From January 2003 through September 2015, a total of 24,241 INFRA bypass, 8028 SUPRA bypass, 48,048 InfraPVI, 21,196 SupraPVI, and 3423 AMP patients met criteria for analysis, with a median follow-up of 18 (interquartile range, 8-33) months. Combining all procedures, overall mortality was lower among African Americans than among white Americans (12.4% vs 14.2%; P < .0001) but not death in the periprocedural period (1.1% vs 1.2%; P = .26). To account for differences in length of follow-up, Cox proportional hazards analysis confirmed that the African American race was independently associated with a significantly lower occurrence of overall mortality after INFRA bypass (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.70-0.88; P < .0009), InfraPVI (HR, 0.72; 95% CI, 0.67-0.78; P < .0001), and SupraPVI (HR, 0.77; 95% CI, 0.66-0.90; P = .0009) interventions but not after SUPRA bypass or AMP. Similarly, by Cox proportional hazards, Hispanic/Latino ethnicity was also independently associated with lower overall mortality after INFRA bypass (HR, 0.75; 95% CI, 0.62-0.91; P = .0030), InfraPVI (HR, 0.69; 95% CI, 0.62-0.78; P < .0001), and SupraPVI (HR, 0.68; 95% CI, 0.52-0.89; P = .0045) but not after SUPRA bypass or AMP., Conclusions: Contrary to the published data for other forms of cardiovascular disease, African American patients as well as patients identified with Hispanic/Latino ethnicity with PAD included in the Society for Vascular Surgery Vascular Quality Initiative undergoing INFRA revascularization for lower extremity PAD experienced better overall survival compared with white Americans., (Published by Elsevier Inc.)

Background: Patients with cancer commonly experience disease or treatment side effects, including pain, fatigue, nausea, and anxiety. An expanding body of literature supports the use of therapeutic massage (TM) as an adjunct to conventional therapies to manage these side effects., Objectives: This article describes patients' perceptions of pain, fatigue, nausea, and anxiety and their overall satisfaction with TM provided concurrently with chemotherapy and/or biotherapy., Methods: In an academic outpatient comprehensive cancer center, consenting patients were asked to identify massage site preference (hands and/or feet). The licensed massage therapist delivered TM for 20 minutes to patients concurrently receiving chemotherapy and/or biotherapy. Patients rated their pain, fatigue, nausea, and anxiety pre- and post-TM using a Likert-type scale. Qualitative and quantitative data related to patients' perceived value of TM were obtained postintervention., Findings: Participants (N = 58) reported a statistically significant reduction in each of the following variables.

Objective: The outcomes of open surgical or endovascular intervention for limb-threatening ischemia (LTI) involving the infrapopliteal vessels are dependent on complex anatomic, demographic, and disease factors. To assist in decision-making, we used the Vascular Quality Initiative (VQI) to derive a model using only preoperatively available factors to predict important outcomes for open or endovascular revascularization., Methods: National VQI data for the infrainguinal bypass and peripheral vascular intervention (PVI) modules were reviewed in a blinded fashion for patients who underwent intervention for LTI of the infrapopliteal vessels. Primary outcomes consisted of major adverse limb event (MALE) and amputation-free survival (AFS). Generalized linear modeling was used for the multivariate analyses, with entry of variables dependent on results of univariate analysis., Results: From January 2003 through August 2014 a total of 19,053 infrainguinal open bypass and 48,739 PVI procedures were identified, among which 5264 and 5252, respectively, represented infrapopliteal (tibial-peroneal-pedal) revascularization for LTI. From these, 3036 infrapopliteal open bypass patients and 1319 infrapopliteal PVI patients had sufficient follow-up data for study inclusion. For open surgery, the reduced generalized linear model revealed that American Society of Anesthesiologists class 4 or 5, previous major amputation, living at home, and female sex had the greatest adverse effect on MALE, and dialysis dependence, low body mass index, and lack of great saphenous vein as a conduit had the greatest negative effect on AFS. For PVI, lesion length from 10 to 15 cm, treatment of three or more arteries, and classification other than A on the Trans-Atlantic Inter-Society Consensus demonstrated the largest adverse effects on MALE, and dialysis dependence, low body mass index, and congestive heart failure most negatively affected AFS., Conclusions: This study on a cross-section of patients selected for intervention in academic and community hospitals offers a "real world" glimpse of factors predictive of outcome. The VQI can be used to derive models that predict the outcomes of open surgical bypass or PVI for LTI involving the infrapopliteal vessels., (Published by Elsevier Inc.)

Objective: To examine the role of polysomnography (PSG) in helping determine readiness of tracheostomized patients for decannulation., Study Design: Case series with chart review of pediatric patients who underwent PSG with tracheostomy tube in place with the goal of decannulation., Setting: Tertiary care pediatric center., Subjects and Methods: Twenty-eight tracheostomized patients who underwent PSG from January 2006 to March 2012 were included. Outcome measures were successful decannulation, PSG results, surgical procedures, and medical comorbidities., Results: Of the 28 patients, 20 (71.4%) were decannulated and 8 (28.6%) were not. One (3.6%) patient failed long-term decannulation. The average apnea-hypopnea index (AHI) with a capped tracheostomy for those successfully decannulated was 2.75 (range, 0.6-7.6), while the AHI for those not decannulated was 15.99 (range, 3.2-62). Factors associated with success or failure to decannulate were assessed, and an algorithm was developed to plan for successful decannulation. Laryngotracheal reconstruction was a significant factor in those successfully decannulated. Those who were not decannulated had multiple medical comorbidities, multilevel airway obstruction, need for additional surgery, or chronic need for pulmonary toilet., Conclusions: Polysomnography may be a useful adjunctive study in the process of determining a patient's readiness for decannulation. Our current algorithm for decannulation includes upper airway endoscopy with identification of levels of obstruction, followed by surgical correction of those obstructions; capped PSG to determine patency of the airway and help assess lung function; and overnight intensive care unit admission for capping trial, with decannulation the following day if well tolerated., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)

Objective: To determine the efficacy and safety of acetaminophen plus ibuprofen in treatment of post-tonsillectomy pain compared to acetaminophen plus opioids in children., Study Design: Retrospective medical record review., Setting: Tertiary-care children's hospital between September 2012 and March 2013., Subjects and Methods: All children undergoing total tonsillectomy (n=1065). Analysis included descriptive analysis, chi-square testing, and logistic regression controlling for age, diagnosis, trainee involvement, concurrent surgical procedures, and Coblator use for differences of outcomes: (1) post-operative bleeding, (2) emergency department (ED) visits for pain, dehydration, or bleeding, and (3) nurse phone calls from families., Results: All patients received acetaminophen. Seventy-four percent received ibuprofen (n=783) and 26.5% did not receive ibuprofen (n=282). In the ibuprofen group, 32.2% received opioids (n=252). Over eight percent of children had post-operative hemorrhage of any amount reported (n=89). Forty-eight percent of these required operative intervention (n=43). Ibuprofen prescription did not impact post-operative bleeding; operative intervention for bleeding, ED visits, or nurse phone calls either on chi-squared or logistic regression testing. Increasing age was found to increase bleeding risk as well as the likelihood of visiting the ED or calling the clinic nurses. All patients with multiple bleeding episodes were in the ibuprofen group., Conclusion: Prescription of ibuprofen did not increase the risk of bleeding and did not increase the likelihood of a post-operative ED visit or nurse phone call. Ibuprofen prescription may possibly increase the risk of multiple bleeding episodes, but further prospective studies are needed. Increased age increases the risk of bleeding, ED visits, and nurse phone calls., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Microstomia is the term used to describe a reduction in the size of the oral aperture that is severe enough to compromise quality of life, nutrition, and cosmesis. Few cases of congenital microstomia have been reported as most microstomia cases are due to burn injuries. We are presenting a case of a neonate who was found to be in respiratory distress with severe congenital microstomia from no known cause. This case illustrates the rarity of this type of pathologic anatomy as well as the teamwork and tools necessary to treat these patients.

Calcification of the intervertebral disc is a common occurrence in the adult population, but it is rare in children. However, its radiological and clinical findings are well described in the pediatric age group, with close to 150 publications on record. In contrast, little information is available regarding the histological features of this entity, which may prove to be challenging to surgical pathologists. Here we provide a detailed description of a young patient with an inflammatory retropharyngeal mass originating in a calcified intervertebral disc. A review of the pathological features described in the literature in English, with pathogenic considerations, is presented.

Objectives/hypothesis: To investigate interventions used for treatment of obstructive sleep apnea (OSA) in infants., Study Design: Retrospective medical record review., Methods: Patients 3 to 24 months old at the time of diagnosis of OSA by polysomnography (PSG) were studied at a tertiary care children's hospital. The main outcome measures were demographic data, PSG data, intervention data, subjective results of interventions, and medical comorbidities., Results: Of the 295 patients included, 196 (66%) were males and 99 (34%) were females. The most common interventions with average age at the time of intervention were: adenotonsillectomy, 115 patients (31.8%, 22.3 months); adenoidectomy, 82 patients (22.5%, 17.7 months); observation, 76 patients (20.9%, 12.8 months); supplemental oxygen, 27 patients (7.4%, 11.7 months); continuous positive airway pressure (CPAP)/bilevel positive airway pressure (BiPAP), 18 patients (4.9%, 15.6 months); tonsillectomy, 16 patients (4.4%, 25.7 months); and tracheostomy, six patients (1.7%, 15.3 months). In the youngest patients (3-5 months of age), 89.3% of interventions were nonsurgical and 10.7% were surgical. In the oldest patients (older than 24 months), 17.5% of interventions were nonsurgical and 82.5% were surgical. Subjective improvement following intervention was highest after adenotonsillectomy. The intervention with the greatest percentage decrease in apnea-hypopnea index (objective efficacy) was tracheostomy, followed by CPAP/BiPAP. Average time from diagnosis to intervention was 35.5 days for nonsurgical interventions and 92.4 days for surgical interventions., Conclusions: Observation was the most common nonsurgical intervention and the most common intervention in patients younger than 12 months. Adenotonsillectomy was the most common surgical and overall intervention. Adenotonsillectomy had the greatest subjective efficacy, and tracheostomy had the greatest objective efficacy., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To investigate interventions used in treating obstructive sleep apnea in neonates and infants and to report their efficacies., Design: Retrospective medical record review., Setting: Tertiary care children's hospital., Patients: Neonates and infants aged 0 to 12 months at the time of obstructive sleep apnea diagnosis by polysomnography., Main Outcome Measures: Demographic data, comorbidities, polysomnography data, and intervention data., Results: In total, 126 patients (86 [68.3%] male and 40 [31.7%] female) were included in the study. The most common interventions (and the mean age at the time of intervention) were anti-gastroesophageal reflux disease treatment (88 patients [69.8%] at age 7 months), observation (33 patients [26.2%] at age 6 months), supplemental oxygen (31 patients [24.6%] at age 4 months), adenoidectomy (30 patients [23.8%] at age 15 months), other surgical (25 patients [19.8%] at age 7 months), continuous positive airway pressure/bilevel positive airway pressure (CPAP/BiPAP) (18 patients [14.3%] at age 16 months), supraglottoplasty (11 patients [8.7%] at age 6 months), tonsillectomy and adenoidectomy (9 patients [7.1%] at age 24 months), tracheostomy (7 patients [5.6%] at age 10 months), and other nonsurgical (7 patients [5.6%] at age 15 months). Among neonates and infants, nonsurgical interventions were performed in most cases, although those aged 0 to 3 months underwent more surgical interventions (19.7%) than those aged older than 3 to 9 months (11.7%). The mean objective improvement, measured as a percentage decrease in preintervention to postintervention apnea-hypopnea index, was greatest in neonates and infants receiving CPAP/BiPAP, followed by those undergoing tracheostomy., Conclusions: Anti-gastroesophageal reflux disease treatment is the most common intervention in each age group. Although adenoidectomy is the most common surgical intervention overall, the prevalence increases with age. Supraglottoplasty is the most common surgical intervention in neonates and infants aged 0 to 3 months and offers the greatest objective improvement in this age group. Overall, the use of CPAP/BiPAP is associated with the greatest objective improvement.

Objectives/hypothesis: To investigate the prevalence of eustachian tube dysfunction (ETD) in infants with obstructive sleep apnea (OSA)., Study Design: Retrospective medical record review of infants (3-24 months old) diagnosed with OSA and ETD., Methods: There were 94 infants diagnosed with OSA by polysomnography and ETD as determined by performance of myringotomy and ventilation tube placement (MT). The main outcome measures were demographic data, apnea-hypopnea index, dates and number of MTs, interventions for treatment of OSA, and medical comorbidities., Results: Of 295 infants diagnosed with OSA, 94 (31.9%) had concomitant ETD. A total of 135 MT procedures were performed, with 30 (31.9%) patients undergoing two or more procedures. The average age of first MT was 16.3 months for those undergoing MT only once, and 11.1 months for those undergoing at least two MT procedures. There was no difference in average age of first MT when analyzed by OSA severity (15.6 months, 14.2 months, and 14.6 months for mild, moderate, and severe OSA, respectively). The first MT procedure was performed before or concurrent with the first treatment for OSA in 75 (80%) patients. Of the 137 interventions for treatment of OSA, 10 (45.5%) nonsurgical and 75 (65.2%) surgical interventions did not require further MT procedures afterward., Conclusions: The ETD prevalence of 32% in infants with OSA is increased compared to the general pediatric prevalence of 4% to 7%. Patients presenting for evaluation of OSA should also be evaluated for ETD. Surgical interventions for treatment of OSA led to decreased need for further MT procedures., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objective: To evaluate the prevalence of sleep-disordered breathing (SDB) and/or obstructive sleep apnea (OSA) in the population with nonsyndromic cleft palate., Design: Retrospective medical record review of symptoms of SDB and/or OSA and results of polysomnography (PSG) studies., Setting: The craniofacial clinic of a tertiary pediatric hospital., Patients: A total of 459 patients, with an additional 48 patients with Pierre Robin syndrome, met inclusion criteria., Main Outcome Measures: Medical records from January 1, 2005, through July 31, 2009, were reviewed for demographic data, SDB symptoms, surgical procedures, and PSG results., Results: Of the 459 patients, 172 (37.5%) had symptoms of SDB and 39 (8.5%) had PSG-diagnosed OSA. Forty-six patients underwent 1 or more PSGs, with results of 49 of the 59 studies (83.1%) being positive for OSA. Surgical procedures to address SDB and/or OSA were undertaken in 89 patients (51.7%), with combined tonsillectomy and adenoidectomy the most common procedure (44.9%). An additional 48 patients who met the inclusion criteria with a diagnosis of Pierre Robin syndrome were also identified. In this population, 35 patients (72.9%) had symptoms of SDB and/or OSA., Conclusions: An increased prevalence of SDB and/or OSA exists in the population with cleft palate, with an even greater prevalence in patients with Pierre Robin syndrome. Definitive diagnosis of OSA by PSG is underused. We suggest that surgical management of SDB and/or OSA be followed by PSG to demonstrate resolution or persistence of symptoms to ensure appropriate further management.

Background: It remains controversial whether patients with concomitant carotid and coronary disease should undergo operative repair separately or in combination., Methods: Patients with documented cerebrovascular disease undergoing coronary artery bypass grafting (CABG) alone were matched by propensity scoring with patients undergoing combined carotid endarterectomy (CEA)/CABG procedures and compared for the occurrence of stroke, myocardial infarction (MI), and mortality., Results: Of the 4943 patients undergoing CABG, 908 had known cerebrovascular disease. Among these, 134 underwent concomitant CEA, and these were propensity matched with 134 patients undergoing CABG only. No differences were observed in the perioperative risks of stroke (4% vs 3%, odds ratio [OR] 1.5, 95% confidence interval [CI] 0.4-5.5), MI (0.7% vs 0.7%, not significant [NS]), or combined cardiovascular events (6% vs 10%, OR 0.5, 95% CI [0.2-1.3]), although mortality (1% vs 8%, OR 0.2, 95% CI [0.04-0.8] was higher with CABG only., Discussion: Addition of CEA to CABG did not significantly alter the risk of perioperative stroke relative to propensity-matched patients undergoing CABG alone.

Objective: Arteriovenous fistulas (AVF) constructed before and after initiating the kidney disease outcomes and quality initiative (KDOQI) guidelines were reviewed at a single academic center to identify decreased patency with use of potentially inferior vein conduits., Methods: Primary access procedures performed pre- and post-adoption of KDOQI guidelines were compared for the primary outcomes of maturation rate and primary patency and the secondary outcome of access utilization., Results: The proportion of autologous AVFs created was higher post-KDOQI (73% vs 35%, P < .001), and an increased use of the basilic vein was observed (20% vs 2%, P < .05). The failure rate of fistula maturation was reduced post-KDOQI (24% vs 38%, P < .05); however, access utilization was also decreased (59% vs 75%, P < .001)., Conclusions: Adherence to KDOQI guidelines for AVFs does not compromise fistula patency and increased use of the basilic vein may lead to superior fistula maturation rates. Early referral may result in lower fistula utilization rates, however.

Objective: To determine the prevalence of hoarseness in the cleft palate population., Design: Retrospective chart review from a tertiary pediatric hospital's craniofacial clinic., Patients: Nonsyndromic patients with cleft palate who had undergone cleft palate repair were eligible for inclusion. Patients were excluded if they had previously undergone a tracheostomy or if they had significant hearing loss. A total of 487 patients met the inclusion criteria., Main Outcome Measures: Medical records were reviewed for demographic data, presence of hoarseness, velopharyngeal insufficiency, symptoms of gastroesophageal reflux disease, and laryngoscopic findings., Results: Of the 487 patients, 27 (5.5%) had complaints of hoarseness: 13 boys and 14 girls. The average age at initial complaint was 4.6 years, with slight differences according to sex: 4.2 years for boys and 5.0 years for girls. Of those with hoarseness, 19 (70%) had velopharyngeal insufficiency, and 8 (30%) had concomitant symptoms of possible gastroesophageal reflux disease. Eleven patients underwent either direct or flexible laryngoscopy: 9 (33%) had vocal fold nodules, and 2 (7%) had edema and/or mucosal thickening of the vocal folds., Conclusions: The 5.5% prevalence of hoarseness in this study is similar to the reported prevalence of 6% to 34% in the normal pediatric population. These results suggest that there is no difference in the cleft palate population and that hoarseness is either underrecognized and/or underreported. More studies are needed to fully elucidate the true prevalence of hoarseness in the cleft palate population and any correlation of hoarseness with velopharyngeal insufficiency and/or gastroesophageal reflux disease.

Rhinitis medicamentosa occurs with repeated and prolonged use of topical decongestants. The resultant reduced ability to respond to decongestants mediated via enlarged capillary endothelial gaps can lead to profuse bleeding during turbinate surgery. We recommend that patients with rhinitis medicamentosa be weaned off topical decongestants prior to elective turbinate surgery to minimize this complication. The management of rhinitis medicamentosa and a case of intraoperative hemorrhage are presented.

Background: Some patients require major leg amputation after lower-extremity prosthetic bypass for graft occlusion or failure of wound healing, despite a patent graft. Amputation above or below the knee was hypothesized to increase susceptibility to prosthetic graft infection in the ipsilateral extremity., Study Design: All patients undergoing implantation of prosthetic infrainguinal arterial bypass grafts identified from a vascular surgical registry during a 12-year period were reviewed. Patient demographic data, comorbid conditions, and operative details were evaluated as risk factors, with graft infection among the primary outcomes of interest., Results: Prosthetic graft infection occurred in 25 of 141 (18%) infrainguinal grafts and occurred most frequently after major amputation (41% versus 6%; odds ratio [OR] = 12; 95% CI, 4.1 to 34) or early reoperation after initial grafting (70% versus 16%; OR = 11; 95% CI, 1.9 to 63). Risk was highest after amputation within 4 weeks of bypass (70% versus 32%; OR = 5.0; 95% CI, 1.1 to 23). Graft thrombosis (84% versus 39%; OR = 8.3; 95% CI, 2.7 to 26) and presence of gangrene (52% versus 23%; OR = 3.6; 95% CI, 1.5 to 8.7) also increased infection risk. Independent predictors for development of graft infection were identified by stepwise regression analysis to be amputation (p < 0.001), early reoperation (p = 0.002), and absence of renal failure (p = 0.038) but not gangrene (p = 0.090). Amputations performed within 6 months of the initial bypass operation were more likely to be associated with prosthetic graft infection than those performed later than 6 months (52% versus 17%; OR = 5.3; 95% CI, 1.3 to 22)., Conclusions: Amputation increases risk of prosthetic graft infection, especially when performed early or after failed revascularization. Consideration should be given to partial or complete removal of a prosthetic graft above the level of the amputation under these conditions.

In response to DNA damage, cells activate a complex protein network designed to sustain genomic integrity. Many of the proteins involved in the network form discrete repair foci, the composition of which is determined by the specific type of damage. Replication protein A (RPA) and the Mre11/Rad50/Nbs1 (MRN) complex both participate in foci and co-localize at certain types of lesions. Following etoposide (ETOP) treatment, cells form foci containing either RPA or the MRN complex, but not both. To investigate this preferential foci formation, we used cell cycle synchronization experimentation. We demonstrate that cells in S phase contain RPA foci but lack phospho-Nbs1 foci. This is consistent with RPA's role in homologous recombination repair of DNA double-strand breaks (DSBs), the predominant form of repair during S phase. Cells synchronized at G0/G1 phase contain phospho-Nbs1 foci, consistent with the MRN complex involvement in non-homologous end joining, the predominant form of repair in G1 phase. Treatment of cells with the proteasome inhibitor MG132 dramatically reduced the percentage of cells forming phospho-Nbs1 foci but did not alter the percentage of cells containing RPA or phospho-RPA foci. ETOP induced similar amounts of damage in all phases of the cell cycle as measured by the comet assay. These data suggest that in response to DNA DSBs, cell cycle-preferred repair pathways differentially engage RPA and the MRN complex in repair foci.

The presence of DNA damage activates a specific response cascade culminating in DNA repair activity and cell cycle checkpoints. Although the type of lesion dictates what proteins are involved in the response, replication protein A (RPA) and the Mre11/ Rad50/Nbs1 complex (MRN) respond to most types of lesions. To examine the relationship of RPA and the MRN complex in DNA damage responses, we used siRNA-mediated protein depletion of RPA-p70 and Mre11. Depletion of RPA-p70 decreased the ability of cells to form phospho-Nbs1 foci and increased levels of DNA double-strand breaks (DSBs) following treatment with etoposide (ETOP). In contrast, depletion of Mre11 led to increased levels of RPA-p34 foci formation, but abrogated phospho-RPA-p34 foci formation. These data support a role for RPA as an initial signal/sensor for DNA damage that facilitates recruitment of MRN and ATM/ATR to sites of damage, where they then work together to fully activate the DNA damage response.

Objective: Decision making for peripheral vascular disease can be quite complex as a result of pre-existing compromise of patient functional status, anatomic considerations, uncertainty of favorable outcome, medical comorbidities, and limitations in life expectancy. The ability of prospective decision-analysis models to predict individual quality of life in patients with lower extremity arterial occlusive disease was tested., Methods: This was a prospective cohort study. The settings were university and Veterans Administration vascular surgery practices. All 214 patients referred with symptomatic lower extremity arterial disease of any severity over a 2-year period were screened, and 206 were enrolled. A Markov model was compared with standard clinical decision-making. Utility assessment and generalized (Short Form-36; SF-36) and disease-specific (Walking Impairment Questionnaire; WIQ) quality of life were derived before treatment. Estimates of treatment outcome probabilities and intended and actual treatment plans were provided by attending vascular surgeons. The main outcome measures were generalized (SF-36) and disease-specific (WIQ) variables at study entry and at 4 and 12 months., Results: Primary intervention consisted of amputation for 9, bypass for 42, angioplasty for 8, and medical treatment for 147 patients. Considering all patients, no improvement in mean overall patient quality of life measured by the SF-36 Physical Component Score (27 +/- 8 vs 28 +/- 8; P = .87) or WIQ (39 +/- 22 vs 39 +/- 23; P = .13) was noted 12 months after counseling and treatment by the vascular surgeons. Individually considered SF-36 categories were improved only for Bodily Pain (40 +/- 23 vs 49 +/- 25; P = .03), with the most significant improvement observed among patients with the most severe pain (68 +/- 25 vs 37 +/- 23; P = .02) and among those undergoing bypass (60 +/- 29 vs 31 +/- 22; P = .02). It is noteworthy that when the treatment chosen was incongruent with the Markov model, patients were more likely to report a poorer quality of life at 1 year (Physical Component Score, 25 +/- 8 vs 29 +/- 8; P < .001). The quality of life predicted at baseline by the Markov model correlated positively with the Physical Component Score (r = 0.23), Bodily Pain (r = 0.33), and Fatigue (r = 0.44) and negatively with WIQ (r = -0.08) observed 1 year later., Conclusions: Prospective application of an individualized decision Markov model in patients with vascular disease was predictive of patient quality of life at 1 year. The patient's outcome was worse when the treatment received did not follow the model's recommendation. This decision analysis model may be useful to identify patients at risk for poor outcomes with standard clinical decision making.

We report a case of combined colon cancer and Clostridium septicum aortitis involving the suprarenal abdominal aorta with rupture. An 82-year-old male presented with fever, abdominal pain, and back pain associated with constipation. He was successfully treated by in situ aortic graft placement with polytetrafluroethylene and concomitant colon resection. Only 20 other cases of C. septicum mycotic aneurysm, aortitis, or aortic dissection have been reported. Concomitant surgical treatment for Clostridium aortitis or mycotic abdominal aortic aneurysm and colon cancer can be accomplished successfully in selected cases when the diagnosis of both conditions is made preoperatively.

Background: Minimal incision techniques for vein harvest may lessen wound complications after lower extremity revascularization, but long-term patency and limb salvage data are limited., Methods: This retrospective case-control study used a computerized vascular registry set in an academic vascular surgical practice. All patients undergoing lower extremity revascularization using autogenous reversed great saphenous vein by a single vascular surgeon in a 10-year period were reviewed. Harvest of great saphenous vein via long single incision (SI) in 133 patients was compared with minimal incisions with endoscopy (MIE) in 85, or MI without endoscopy in 106. The main outcome measures were primary and secondary graft patency by Kaplan-Meier life-table analysis and cumulative sum failure (CUSUM). Secondary outcomes of interest were limb salvage and wound complications., Results: No differences were observed between MIE, MI, and SI patients for demographic data, risk factors, or primary indications, including claudication, rest pain, ischemic ulcer, and gangrene. Endoscopic vein harvest patients were significantly more likely than MI or SI to be women and more likely to use tobacco. Primary patency at 5 years was better after SI vein harvest (59%) than with either MI (33%, P = .004) or MIE (44%, P = .045) techniques, although both MI groups had a higher proportion of bypass grafts to the popliteal artery. Similarly, cumulative secondary patency was better after SI (66%) than with MI (47%, P = .045), but not MIE (58%, P = .45). Differences in limb salvage at 5 years in SI (73%) were not statistically superior to either MI (59%, P = .24) or MIE (58%, P = .13). No learning curve for MI or MIE vein grafts was evident by CUSUM for primary patency at 12 months. No differences in wound complication rates were observed for SI (9%), MI (10%), or MIE (6%) grafts (P = .54)., Conclusions: Graft patency and limb salvage deteriorated during the time when MI or MIE techniques of great saphenous vein harvest were adopted. This observation raises concern about the advisability of limiting the extent of the incision at the potential cost of compromised outcomes without an obvious advantage in limiting wound complications.

Replication protein A (RPA) is the predominant eukaryotic single-stranded DNA binding protein composed of 70, 34, and 14 kDa subunits. RPA plays central roles in the processes of DNA replication, repair, and recombination, and the p34 subunit of RPA is phosphorylated in a cell-cycle-dependent fashion and is hyperphosphorylated in response to DNA damage. We have developed an in vitro procedure for the preparation of hyperphosphorylated RPA and characterized a series of novel sites of phosphorylation using a combination of in gel tryptic digestion, SDS-PAGE and HPLC, MALDI-TOF MS analysis, 2D gel electrophoresis, and phosphospecific antibodies. We have mapped five phosphorylation sites on the RPA p34 subunit and five sites of phosphorylation on the RPA p70 subunit. No modification of the 14 kDa subunit was observed. Using the procedures developed with in vitro phosphorylated RPA, we confirmed a series of phosphorylation events on RPA from HeLa cells that was hyperphosphorylated in vivo in response to the DNA damaging agents, aphidicolin and hydroxyurea.

The DNA damage response, triggered by DNA replication stress or DNA damage, involves the activation of DNA repair and cell cycle regulatory proteins including the MRN (Mre11, Rad50, and Nbs1) complex and replication protein A (RPA). The induction of replication stress by hydroxyurea (HU) or DNA damage by camptothecin (CAMPT), etoposide (ETOP), or mitomycin C (MMC) led to the formation of nuclear foci containing phosphorylated Nbs1. HU and CAMPT treatment also led to the formation of RPA foci that co-localized with phospho-Nbs1 foci. After ETOP treatment, phospho-Nbs1 and RPA foci were detected but not within the same cell. MMC treatment resulted in phospho-Nbs1 foci formation in the absence of RPA foci. Consistent with the presence or absence of RPA foci, RPA hyperphosphorylation was present following HU, CAMPT, and ETOP treatment but absent following MMC treatment. The lack of co-localization of phospho-Nbs1 and RPA foci may be due to relatively shorter stretches of single-stranded DNA generated following ETOP and MMC treatment. These data suggest that, even though the MRN complex and RPA can interact, their interaction may be limited to responses to specific types of lesions, particularly those that have longer stretches of single-stranded DNA. In addition, the consistent formation of phospho-Nbs1 foci in all of the treatment groups suggests that the MRN complex may play a more universal role in the recognition and response to DNA lesions of all types, whereas the role of RPA may be limited to certain subsets of lesions.

In response to replicative stress, cells relocate and activate DNA repair and cell cycle arrest proteins such as replication protein A (RPA, a three subunit protein complex required for DNA replication and DNA repair) and the MRN complex (consisting of Mre11, Rad50, and Nbs1; involved in DNA double-strand break repair). There is increasing evidence that both of these complexes play a central role in DNA damage recognition, activation of cell cycle checkpoints, and DNA repair pathways. Here we demonstrate that RPA and the MRN complex co-localize to discrete foci and interact in response to DNA replication fork blockage induced by hydroxyurea (HU) or ultraviolet light (UV). Members of both RPA and the MRN complexes become phosphorylated during S-phase and in response to replication fork blockage. Analysis of RPA and Mre11 in fractionated lysates (cytoplasmic/nucleoplasmic, chromatin-bound, and nuclear matrix fractions) showed increased hyperphosphorylated-RPA and phosphorylated-Mre11 in the chromatin-bound fractions. HU and UV treatment also led to co-localization of hyperphosphorylated RPA and Mre11 to discrete detergent-resistant nuclear foci. An interaction between RPA and Mre11 was demonstrated by co-immunoprecipitation of both protein complexes with anti-Mre11, anti-Rad50, anti-NBS1, or anti-RPA antibodies. Phosphatase treatment with calf intestinal phosphatase or lambda-phosphatase not only de-phosphorylated RPA and Mre11 but also abrogated the ability of RPA and the MRN complex to co-immunoprecipitate. Together, these data demonstrate that RPA and the MRN complex co-localize and interact after HU- or UV-induced replication stress and suggest that protein phosphorylation may play a role in this interaction.

Background: Applied prospectively to patients with peripheral arterial disease, individualized decision analysis has the potential to improve the surgeon's ability to optimize patient outcome., Methods: A prospective, randomized trial comparing Markov surgical decision analysis to standard decision-making was performed in 206 patients with symptomatic lower extremity arterial disease. Utility assessment and quality of life were determined from individual patients prior to treatment. Vascular surgeons provided estimates of probability of treatment outcome, intended and actual treatment plans, and assessment of comfort with the decision (PDPI). Treatment plans and PDPI evaluations were repeated after each surgeon was made aware of model predictions for half of the patients in a randomized manner., Results: Optimal treatments predicted by decision analysis differed significantly from the surgeon's initial plan and consisted of bypass for 30 versus 29%, respectively, angioplasty for 28 versus 11%, amputation for 31 versus 6%, and medical management for 34 versus 54% (agreement 50%, kappa 0.28). Surgeon awareness of the decision model results did not alter the verbalized final plan, but did trend toward less frequent use of bypass. Patients for whom the model agreed with the surgeon's initial plan were less likely to undergo bypass (13 versus 30%, P < 0.01). Greater surgeon comfort was present when the initial plan and model agreed (PDPI score 47.5 versus 45.6, P < 0.005)., Conclusions: Individualized application of a decision model to patients with peripheral arterial disease suggests that arterial bypass is frequently recommended even when it may not maximize patient expected utility.

Background: Surgical treatment of the morbidly obese has assumed an increasingly important role in both the academic and community setting, while postoperative pulmonary embolism remains a devastating complication. Since the overall incidence remains low, the role for vena cava filter placement in this group is not yet well defined. In addition, the technical challenges and techniques for insertion have not been well-described. We present our experience with filter placement among patients with gastric bypass and the evolution of technique to facilitate safe placement in this group., Methods: From 1995 to August 2003, 586 patients underwent gastric bypass for morbid obesity. Review of registries and records from this period was accomplished to identify patients at MUSC who underwent both the gastric bypass and placement of an inferior vena cava filter. 12 patients were identified by this method., Results: Technical challenges with venous access and imaging are described. 6 patients were identified as potential high risk for thromboembolic complications and had a filter placed preoperatively with a mean postoperative stay of 5.3 days. The 6 patients who required filter placement in the postoperative period as part of the management of postoperative complications had a mean hospital stay of 24.5 days. There were no long-term complications associated with filter placement at a mean follow-up interval of 19 months., Conclusion: Inferior vena cava filter placement is not only feasible and safe for the morbidly obese individual undergoing gastric bypass, but should be strongly considered for patients with risk factors for thromboembolic complications or who experience postoperative complications requiring ICU stay or prolonged immobility.

A 77-year-old man had clinical and radiologic signs of graft infection develop 1 year after stent grafting for abdominal aortic aneurysm. Blood cultures grew Bacteroides fragilis, and cultures of the aneurysm sac grew Enterococcus. The patient's condition was successfully managed with staged extraanatomic revascularization followed by graft excision. Although stent graft infection to date is extremely rare, some aspects peculiar to the placement of these devices potentially could increase their susceptibility to infection. Recognition and standard techniques in management can lead to successful outcome.

In this study, we demonstrate that electromagnetic field (EMF) exposure results in protection from heat induced apoptosis in human cancer cell lines in a time dependent manner. Apoptosis protection was determined by growing HL-60, HL-60R, and Raji cell lines in a 0.15 mT 60 Hz sinusoidal EMF for time periods between 4 and 24 h. After induction of apoptosis, cells were analyzed by the neutral comet assay to determine the percentage of apoptotic cells. To discover the duration of this protection, cells were grown in the EMF for 24 h and then removed for 24 to 48 h before heat shock and neutral comet assays were performed. Our results demonstrate that EMF exposure offers significant protection from apoptosis (P<.0001 for HL-60 and HL-60R, P<.005 for Raji) after 12 h of exposure and that protection can last up to 48 h after removal from the EMF. In this study we further demonstrate the effect of the EMF on DNA repair rates. DNA repair data were gathered by exposing the same cell lines to the EMF for 24 h before damaging the exposed cells and non-exposed cells with H2O2. Cells were allowed to repair for time periods between 0 and 15 min before analysis using the alkaline comet assay. Results showed that EMF exposure significantly decreased DNA repair rates in HL-60 and HL-60R cell lines (P<.001 and P<.01 respectively), but not in the Raji cell line. Importantly, our apoptosis results show that a minimal time exposure to an EMF is needed before observed effects. This may explain previous studies showing no change in apoptosis susceptibility and repair rates when treatments and EMF exposure were administered concurrently. More research is necessary, however, before data from this in vitro study can be applied to in vivo systems., (Copyright 2002 Wiley-Liss, Inc.)

Real-time RT-PCR is a relatively new technology that uses an online fluorescence detection system to determine gene expression levels. It has the potential to significantly improve detection of breast cancer metastasis by virtue of its exquisite sensitivity, high throughput capacity and quantitative readout system. To assess the utility of this technology in breast cancer staging, we determined the relative expression levels of 12 cancer-associated genes (mam, PIP, mamB, CEA, CK19, VEGF, erbB2, muc1, c-myc, p97, vim and Ki67) in 51 negative-control normal lymph nodes and in 17 histopathology-positive ALNs. We then performed a receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity levels of each gene. Areas under the ROC curve indicated that the most accurate diagnostic markers were mam (99.6%), PIP (93.3%), CK19 (91.0%), mamB (87.9%), muc1 (81.5%) and CEA (79.4.0%). mam was overexpressed in 16 of 17 lymph nodes known to contain metastatic breast cancer at levels ranging from 22- to 2.8 x 10(5)-fold above normal mean expression, whereas PIP was overexpressed from 30- to 2.2 x 10(6)-fold above normal in 13 lymph nodes. Real-time RT-PCR analysis of pathology-negative LN from breast cancer patients revealed evidence of overexpression of PIP (6 nodes), mam (3 nodes) and CEA (1 node) in 8 of 21 nodes (38%). Our results provide evidence that mam, PIP, CK19, mamB, muc1 and CEA can be applied as a panel for detection of metastatic and occult micrometastatic disease., (Copyright 2001 Wiley-Liss, Inc.)

This study was designed to compare outcomes following infrainguinal bypass between patients with end-stage renal disease (ESRD) and patients with normal renal function (NRF). Sixty-three patients with ESRD undergoing 78 infrainguinal bypasses from 1990 to 1999 were compared with a concurrent group of 132 age-, race-, and gender-matched patients with NRF undergoing 148 bypasses. Limb salvage and survival were calculated using Kaplan-Meier analysis. Markov decision analysis was used to calculate expected quality-adjusted life years (QALY) with intervention. Mean follow-up was 25 months (range 1-116). The results of our study show that infrainguinal bypass in patients with ESRD and tissue necrosis appears to provide a measurable, but marginal, degree of improvement in quality of life.

Previous research has shown that thymidine kinase 1 (TK1), a nucleotide salvage pathway enzyme, is an accurate prognostic and diagnostic tumor marker. However, the current radioisotope assay for TK1 is cumbersome and has hampered the clinical application of this diagnostic technique in cancer management. To overcome the problems of the current radioisotope assay, we have produced monoclonal antibodies (MAbs) using purified TK1 from Raji cell extract. Production and confirmation of their specificity was confirmed using Western blot, immunohistochemical staining, TK1 activity inhibition assays, and enzyme-linked immunoadsorbent assay (ELISA) techniques. Thus, in the future, these antibodies may aid in the early detection of cancer and more accurate prognosis, as well as allowing for an increased ability to study the function of TK1 in basic cellular processes.

Previous research indicates that thymidine kinase I (TKI) possesses value as a tool for both prognosis and diagnosis in breast cancer. However, drawbacks to the existing radioassay for thymidine kinase have frustrated its clinical use. To overcome these drawbacks, we developed a monoclonal antibody to TK1. We have assessed this antibody for a linear antibody-antigen response and for reproducibility using ELISA techniques. We also have evaluated this antibody for TKI specificity as determined by Western blot. To test the accuracy of this monoclonal antibody further, we treated human MCF-7 breast cancer cells with tamoxifen and measured decreasing TKI activity and protein levels with the radioassay and with our monoclonal antibody in an ELISA, respectively. We then used the radioassay and our monoclonal antibody to measure TK1 activity and protein levels, respectively, in 218 serum samples of postoperative breast cancer patients and found a correlation between the two assays. Our results demonstrated that the TK1 immunoassay not only had a linear, reproducible, and specific response but accurately measured TK1 levels in both MCF-7 breast cancer cells and serum. Thus, our monoclonal antibody may demonstrate potential for practical use in a clinical setting for the management of breast cancer.

Background: Doppler-based measurement of the ankle: brachial index (ABI) has long been regarded as the standard by which to objectively quantify the degree of lower extremity arterial occlusive disease, but this method fails to account for the contribution of systemic blood pressure to actual limb perfusion. We hypothesized that the absolute blood pressure would be a better predictor of the severity of symptoms of chronic occlusive disease than the ABI., Experimental Design: retrospective comparative study., Setting: university inpatient/outpatient vascular laboratory., Patients: 1396 evaluable patients out of 2436 total consecutive patients referred with suspected lower extremity arterial occlusive disease., Measures: comparison of absolute ankle and digital pressures and ABI according to severity of symptoms of chronic lower extremity ischemia using three-way analysis of variance (ANOVA), likelihood ratios, and receiver operator characteristic (ROC) curves., Results: The symptoms of tissue ulcer/gangrene, rest pain, and gangrene were characterized by differences in absolute pressures in the great toe (47 +/- 42 mmHg vs 55 +/- 40 mmHg vs 62 +/- 33 mmHg [mean +/- SD], F = 19.05, p < 0.001) and ankle (92 +/- 53 mmHg vs 98 +/- 44 mmHg vs 106 +/- 37 mmHg, F = 12.91, p < 0.001), but not by the ABI (0.71 +/- 0.33 vs 0.68 +/- 0.34 vs 0.71 +/- 0.28, F = 1.24, p > 0.05). ROC curves confirmed absolute digital pressure (area under curve [AUC] = 0.628) and absolute ankle pressure (AUC = 0.607) to be superior to ABI (AUC = 0.572)., Conclusions: The severity of symptoms for peripheral vascular disease correlate better with absolute pressure measurement than with ABI.

Concerned about the inadequacy of a centralized database and the importance of low morbidity and mortality on carotid endarterectomy efficacy, the South Carolina Vascular Surgical Society prospectively instituted a computer registry for carotid procedures performed by its members, to establish a statewide standard of practice. From January 1994 through December 1997, 23 of the 30 physician members voluntarily registered data on 1652 carotid operations at 14 hospitals into a central database. Blinded results were reviewed biannually. Complete data (1995-1997) were available for 1199 cases. The patients tended to be >64 years old (72%), male (62%), and white (93%). Carotid endarterectomy was the most frequently performed operation (90%). Perioperative complications (< or = 30 days) occurred in 173 patients (14.4%), including stroke (n = 19; 1.6%), death (n = 8; 0.7%), and stroke/death (n = 25; 2.0%). Although 23 surgeons (77% of the society) contributed some data, only 10 surgeons (33%) contributed complete data on >10 patients/year. Despite biannual efforts to boost participation, case entry remained stable (1994, 358; 1995, 347; 1996, 425; and 1997, 427), representing about one-third of the estimated carotid procedures performed in the state during that period. The cost of the registry was approximately $11,500. Audit of 8 surgeons revealed a >95 per cent match against the statewide discharge database and low error rate versus independent medical record review. This experience confirms that excellent outcomes after carotid endarterectomy are not limited to a few select centers and can be accomplished by adequately trained surgeons in a variety of institutional settings. Incomplete physician participation, however, inevitably raises questions about the utility of such efforts. Until volunteer registries induce full participation by heightening perceived physician benefit, their role will remain limited for future outcomes research.

Objective: African Americans, especially African American women, have a greater risk of lower extremity ischemia that necessitates an infrainguinal bypass graft operation and amputation. Because the prevalence of diabetes mellitus is proportionally greater in this ethnic/racial group, the relative contribution of diabetes was compared with other potential risk factors., Methods: This study was designed as a retrospective case control study at the University and Veterans Hospitals. In a 5-year period, 764 consecutive patients who required infrainguinal revascularizations were compared with a statewide population that was described by the 1995 Behavior Risk Factor Surveillance System database. The main outcome measure was the requirement for infrainguinal revascularization., Results: Diabetes mellitus was more common among African American women who underwent bypass graft operation (70%; odds ratio [OR], 24.9; 95% confidence interval [CI], 20.3 to 30.4) than African American men (46%; OR, 11.6; 95% CI, 8.9 to 15.2), white women (49%; OR, 15.9; 95% CI, 13.0 to 19.5), or white men (42%; OR, 14.8; 95% CI, 12.5 to 17.4). Overall, bypass graft operation was associated more strongly with diabetes mellitus for all groups (OR, 15.7; 95% CI, 13.5 to 18. 3) than with smoking (OR, 4.5; 95% CI, 3.8 to 5.2) or hypertension (OR, 4.6; 95% CI, 4.0 to 5.3). Life-table analysis revealed limb salvage to be worse at 3 years among African American patients (64% vs 75%; P <.005) despite similar primary and cumulative secondary graft patency rates., Conclusion: Diabetes mellitus is the dominant risk factor that contributes to the need for bypass graft operation, especially among African American women. A greater prevalence of diabetes mellitus may account for the higher incidence of tissue necrosis and the increased requirement for distal bypass grafting and may contribute to the reduction in long-term limb salvage that was observed with these women.

Intervention for vascular occlusive disease of the distal lower extremity in elderly patients will inevitably be scrutinized as medical resources decline. The authors applied surgical decision analysis to three treatment options: revascularization, amputation and expectant management. The appropriate outcome probabilities were derived from our experience with revascularization to the tibial and pedal vessels, and utility scores were obtained by formalized patient assessment. Revascularization was predicted to improve patient outcome by 1.10 quality-adjusted life-years compared with primary amputation and by 1.16 quality-adjusted life-years compared with expectant management. To gain one additional quality-adjusted life-years, revascularization would cost $5280 more than expectant management, but $33,900 less than primary amputation. Sensitivity analysis predicted revascularization to be the least costly treatment per quality-adjusted life-years as long as 1-month patency exceeds 11%. Revascularization for limb-threatening ischemia of the distal lower extremity is justified and can be performed at a reasonable cost.

Background: Axillary lymph node status in breast cancer patients remains the single most important predictor of outcomes. Current methods of histopathologic analysis may be inadequate because 30% of node-negative patients recur. The purpose of this study was to test the hypothesis that a multigene reverse transcriptase-polymerase chain reaction (RT-PCR) panel provides a more sensitive method to detect axillary lymph node metastases than routine pathologic examination., Study Design: Sixty-one consecutive breast cancer patients were evaluated, with nine normal control patients. Nodes > 1 cm were bisected for histopathologic and RT-PCR analysis. Nodal tissue was homogenized, and total RNA was converted into cDNA with reverse transcriptase. Reverse transcriptase-polymerase chain reaction analysis was performed with primers specific for keratin-19, c-myc, prolactin inducible protein (PIP), and beta-actin using ethidium bromide gel electrophoresis. Reverse transcriptase-polymerase chain reaction positive/ pathology negative axillary lymph nodes were reevaluated using step sectioning and immunohistochemical staining., Results: Thirty-seven patients had pathologically negative axillary lymph nodes, of which 15 (40%) were positive by RT-PCR analysis. Two RT-PCR negative results (one probably from tissue processing error and the other secondary to sampling error) among the 24 histologically positive specimens were detected (8%). The number of patients in each pathologic stage was 26 patients in stage I; 18, stage IIA; 7, stage IIB; 7, stage IIIA; 3, stage IIIB; and 0 patients in stage IV. By RT-PCR staging, 8 of 26 patients went from stage I to IIA (30%), and 7 of 18 from stage IIA to IIB (39%). Of the RT-PCR positive individuals who were stage I by pathologic analysis, 100% were found to be c-myc positive, 0% keratin-19 positive, and 0% PIP positive; for stage IIIB patients these markers were 50%, 100%, and 100% respectively. Additionally, an increasing number of positive markers per specimen appeared to correlate with larger primary tumor size (p < 0.01) and decreased predicted 5-year survival (r = 0.950, p < 0.002)., Conclusions: Multimarker RT-PCR analysis appears to be a readily available and highly sensitive method for the detection of axillary lymph node micrometastases. Longterm followup of RT-PCR positive patients will be required to determine its clinical relevance. If validated as a predictor of disease recurrence, this method would provide a powerful complement to routine histopathologic analysis of axillary lymph nodes.

Pathologic examination of axillary lymph nodes (ALNs) may miss micrometastases in 30 per cent of breast cancer patients. We have developed a multimarker reverse transcriptase-polymerase chain reaction (RT-PCR)-based screening method that detects histopathologically positive ALNs with a 5 per cent false-negative rate. The purpose of this study was to compare this RT-PCR methodology with histopathology with regard to sensitivity and cost. Pathologically negative ALNs from 35 breast cancer patients were re-evaluated by a single pathologist in a blinded fashion using serial sectioning with immunohistochemical staining. Histopathologic results were then compared with those of RT-PCR. Cost analysis was performed based on standard charges for these methods. RT-PCR identified micrometastases in 14 of 35 pathologically negative nodes. Serial sectioning and immunohistochemical staining identified micrometastases in two cases, with RT-PCR positive for one of these. The charge per specimen for performing routine histopathologic examination was $380, serial sectioning and immunohistochemical staining $787, and RT-PCR $125. RT-PCR appears to be more sensitive at detecting ALN micrometastasis than histopathologic examination even with serial sectioning and immunohistochemical staining. If micrometastatic breast cancer detected by RT-PCR proves to be clinically relevant, it could be a more effective screening methodology with significant cost savings as compared to currently available pathologic examinations.

Objective: Correlate graft patency and limb salvage outcomes following popliteal aneurysm repair with the extent of tibial occlusive disease., Experimental Design: Retrospective study with a mean follow-up of 36 months (range, 2-96 months)., Setting: Institutional teaching hospital., Patients: Of 20 popliteal aneurysms among 16 patients undergoing repair, 75% were associated with preoperative tibial vessel occlusion. Normal, three vessel infrapopliteal runoff was present in 5 patients, two vessels in 7 patients, and one or no vessels in 8 patients. Fifty percent of limbs were asymptomatic, while the remainder suffered from a variety of ischemic symptoms., Interventions: Eighteen of the 20 aneurysms were repaired with femoropopliteal bypass grafts, and two femoral-tibial bypasses were performed. Autogenous saphenous vein was used in 18 cases (10 in situ, 8 reversed) and PTFE in two short segment femoral-popliteal bypasses., Measures: Graft patency was determined by presence of a palpable pulse, the re-establishment of normal ankle-brachial indices, or duplex scanning. Patency and limb salvage rates were estimated using life table analysis by the Kaplan-Meier method., Results: Preoperative symptoms did not correlate with tibial runoff, except in two patients presenting with acute thrombosis and ischemia. Cumulative graft patency by life table analysis was not different for either good (2-3 vessels, N-12) or poor (0-1 vessels, N-8) runoff. Overall primary patency at 60 months was 73%, and cumulative secondary patency was 100% with no limbs lost at 60 months., Conclusions: Concomitant distal arterial occlusive disease is frequently associated with popliteal aneurysms, yet did not appear to substantially impact either long-term graft patency or limb salvage.

Purpose: This study was carried out to determine whether early failure of infrainguinal bypass grafts is associated with increased expression of platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors. A prospective correlation of preoperative platelet TXA2/PGH2 receptor-mediated activity with lower extremity graft patency was sought., Methods: Twenty-five patients who underwent infrainguinal bypass surgery for limb salvage were studied at an inpatient academic tertiary referral center and Department of Veterans Affairs Medical Center. Outcome measures were primary graft patency rate at 3 months, platelet TXA2/PGH2 receptor activity by equilibrium binding with 125I-BOP, and aggregation to the TXA2-mimetic U46619., Results: Preoperative platelet TXA2/PGH2 receptor density was higher (Bmax, 3100 +/- 1300 vs 1500 +/- 1100 sites/platelet [mean +/- SD]; p = 0.004) in the five patients who had graft thrombosis within 3 months. The EC50 for U46619 was lower (26 +/- 6 nmol/L vs 57 +/- 30 nmol/L; p < 0.05) in these patients as well, confirming the functional effect of the increased receptor density. Early graft thrombosis was more likely in patients with a platelet TXA2/PGH2 receptor density greater than 3000 sites/platelet (odds ratio, 76; 95% confidence interval, 3.9 to 1500) or an EC50 for U46619 less than 30 nmol/L (odds ratio, 16; 95% confidence interval, 1.4 to 180)., Conclusions: Elevated platelet TXA2/PGH2 receptor levels and enhanced sensitivity of platelet aggregation to TXA2 predict early arterial graft thrombosis. Specific TXA2/PGH2 receptor antagonism may prevent one of the mechanisms that contributes to early graft occlusion.

Purpose: To evaluate the treatment of abdominal aortic aneurysm (AAA) with use of the endoluminal Talent stent-graft (TSG)., Patients and Methods: In 10 men, AAA treatment was attempted with use of the TSG. All patients presented significant surgical risk, with chronic obstructive pulmonary disease and coronary arteriopathy. The mean age was 65.5 years (range, 57-82 years). The mean proximal neck diameter was 25.8 mm (range, 21.6-34 mm). Five of the TSGs were straight tubes and five were bifurcated systems. The main body of the TSG is made of a polyester graft material mounted on a self-expandable nitinol frame. The bifurcated system uses polytetrafluoroethylene (PTFE) material for the legs and extensions mounted on a self-expandable nitinol frame. The bifurcated grafts used a 22 to 27-F introducer and the extensions, a 18-F introducer through a surgical cutdown technique., Results: The TSG system was successfully implanted in nine patients and failed in one because of dislodgment after deployment, which required conversion to surgery. Four leaks occurred initially. One was sealed off with balloon dilation at the end of the procedure, one leak was treated with an additional extension, another leak disappeared spontaneously in 30 days, and the other leak required embolization 4 weeks after discharge. Seven patients were discharged on the third day after the procedure, and two patients were discharged at 1 and 2 weeks, respectively. Blood transfusion was necessary in three patients because of hematoma at the incision site in two patients, which required surgical revision for hemostasis, and because of transoperative bleeding in one patient. Follow-up time ranged from 2 to 15 months. The only death occurred 5 days postoperatively as a consequence of ischemic colitis and multisystem organ failure in the only patient who required surgery., Conclusion: Treatment of AAA with the TSG system is effective for aneurysm exclusion. This device seems to provide a good alternative to surgery in patients who are otherwise considered to be at high risk for complications after direct surgical repair, but it is not without risk of complications.

Continuous quality improvement methods are increasingly being applied to health care systems, yet demonstration of outcome and cost benefits for surgical patients remains sparse. We used continuous quality improvement principles to specifically identify potential opportunities to reduce patient charges for carotid endarterectomy in our academic vascular surgery practice without compromising results. The targeted opportunities included: 1) limitation of laboratory examination, 2) selective cardiac stress testing, 3) discharge on 1st postoperative day, and 4) substitution of outpatient carotid duplex imaging for inpatient angiography. After 1 year, reductions in the average patient charge ($7700 versus $13,900, P < 0.001) and increases in payment/charge ratio (1.2 versus 0.8; P < 0.001) were observed. These changes were primarily due to a reduction in length of stay (2.2 versus 5.7 days; P < 0.001). No significant difference in patient morbidity occurred. Reductions in charges occurred within the targeted areas of laboratory (-77%), cardiac testing (-73%), hospital room (-60%), and radiology (-81%) utilization. Attention to the four factors identified by continuous quality improvement methods significantly reduced total patient charges without detrimental effects on patient outcome.