Better survival for African and Hispanic/Latino Americans after infrainguinal revascularization in the Society for Vascular Surgery Vascular Quality 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.

Predicting outcomes for infrapopliteal limb-threatening ischemia using the Society for Vascular Surgery Vascular Quality Initiative.

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.

Role of polysomnography in the development of an algorithm for planning tracheostomy decannulation.

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.

Placement of inferior vena cava filters in bariatric surgical patients--possible indications and technical considerations.

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.

Acetaminophen plus ibuprofen versus opioids for treatment of post-tonsillectomy pain in children.

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.

Congenital microstomia in a neonate with impending respiratory compromise.

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.

Evaluating the management of obstructive sleep apnea in neonates and infants.

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.

Analysis of outcomes in treatment of obstructive sleep apnea in infants.

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.

Idiopathic intervertebral disc calcification in childhood: an atypical case of an uncommon entity for pediatric pathologists.

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.

Increased eustachian tube dysfunction in infants with obstructive sleep apnea.

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.

Increased prevalence of obstructive sleep apnea in patients with cleft palate.

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.

Prevalence of hoarseness in the cleft palate population.

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.

Increasing the proportion of autologous arteriovenous fistulas does not diminish fistula patency.

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.

Combined carotid endarterectomy and coronary artery bypass grafting versus coronary artery bypass grafting alone: a retrospective review of outcomes at our institution.

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.

Rhinitis medicamentosa as a cause of increased intraoperative bleeding.

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.

Predictors of prosthetic graft infection after infrainguinal bypass.

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.

Cell cycle-and proteasome-dependent formation of etoposide-induced replication protein A (RPA) or Mre11/Rad50/Nbs1 (MRN) complex repair foci.

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.

Replication protein A is required for etoposide-induced assembly of MRE11/RAD50/NBS1 complex 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.

Prospective decision analysis for peripheral vascular disease predicts future quality of life.

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.