Citations

The study of hemodynamic alterations following the creation of an arteriovenous fistula (AVF) is relevant to vascular adaptive responses and hemodialysis access dysfunction. This study examined such alterations in a murine AVF created by anastomosing the carotid artery to the jugular vein. AVF blood flow was markedly increased due to reduced AVF vascular resistance. Despite such markedly increased basal blood flow, AVF blood flow further increased in response to acetylcholine. This AVF model exhibited increased cardiac output and decreased systemic vascular resistance; the kidney, in contrast, exhibited decreased blood flow and increased vascular resistance. Augmentation in AVF blood flow was attended by increased arterial heme oxygenase-1 (HO-1) mRNA and protein expression, the latter localized to smooth muscle cells of the AVF artery; AVF blood flow was substantially reduced in HO-1−/− mice compared with HO-1+/+ mice. Finally, in a murine model of a representative disease known to exhibit impaired hemodynamic responses (sickle cell disease), the creation of an AVF was attended by decreased AVF flow and impaired AVF function. We conclude that this AVF model exhibits markedly increased AVF blood flow, a vasodilatory reserve capacity, increased cardiac output, decreased renal blood flow, and a dependency on intact hemodynamic responses, in general, and HO-1 expression, in particular, in achieving and maintaining AVF blood flow. We suggest that these findings support the utility of this model in investigating the basis for and the consequences of hemodynamic stress, including shear stress, and the pathobiology of hemodialysis AVF dysfunction.

Background —The Telectronics Accufix pacing leads were recalled in November 1994 after 2 deaths and 2 nonfatal injuries were reported. This multicenter clinical study (MCS) of patients with Accufix leads was designed to determine the rate of spontaneous injury related to the J retention wire and results of lead extraction. Methods and Results —The MCS included 2589 patients with Accufix atrial pacing leads that were implanted at or who were followed up at 12 medical centers. Patients underwent cinefluoroscopic imaging of their lead every 6 months. The risk of J retention wire fracture was ≈5.6%/y at 5 years and 4.7%/y at 10 years after implantation. The annual risk of protrusion was 1.5%. A total of 40 spontaneous injuries were reported to a worldwide registry (WWR) that included data from 34 672 patients (34 892 Accufix leads), including pericardial tamponade (n=19), pericardial effusion (n=5), atrial perforation (n=3), J retention wire embolization (n=4), and death (n=6). The risk of injury was 0.02%/y (95% CI, 0.0025 to 0.072) in the MCS and 0.048%/y (95% CI, 0.035 to 0.067) in the WWR. A total of 5299 leads (13%) have been extracted worldwide. After recall in the WWR, fatal extraction complications occurred in 0.4% of intravascular procedures (16 of 4023), with life-threatening complications in 0.5% (n=21). Extraction complications increased with implant duration, female sex, and J retention wire protrusion. Conclusions —Accufix pacing leads pose a low, ongoing risk of injury. Extraction is associated with substantially higher risks, and a conservative management approach is indicated for most patients.

Background— Communicating prognosis to enable shared decision-making is strongly endorsed by heart failure (HF) guidelines. Patients are concerned with both their quantity and quality of life (QoL). To facilitate the recognition of patients at high risk for unfavorable future QoL or death, we created a simple prognostic tool to estimate this combined outcome. Methods and Results— We identified factors associated with 6-month mortality or persistently unfavorable QoL, defined by Kansas City Cardiomyopathy Questionnaire (KCCQ) scores <45 at 1 and 24 weeks after hospital discharge, among 1458 patients from the Efficacy of Vasopressin Antagonism in HF Outcome Study with Tolvaptan (EVEREST). Within 24 weeks of discharge, 478 (32.8%) patients had died and 192 (13.2%) patients had serial KCCQ scores <45. After adjusting for 23 predischarge covariates, independent predictors of the combined end point included low admission KCCQ score, high B-type natriuretic peptide, hyponatremia, tachycardia, hypotension, absence of β-blocker therapy, and history of diabetes mellitus and arrhythmia. A simplified predischarge HF score for subsequent death or unfavorable QoL had moderate discrimination ( c -statistic 0.72). Predischarge clinical covariates were substantially different in predicting the QoL end point as compared with traditional death or rehospitalization end points. Conclusions— At the time of hospital discharge, readily available clinical characteristics are associated with HF patients at high risk for persistently unfavorable QoL or death over the next 6 months. Such information can target patients for whom aggressive treatment options (eg, devices or transplantation) and/or end-of-life discussions should be strongly considered before hospital discharge. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00071331.

Background Secondhand smoke exposure poses health risks to children, including increased risks for anesthesia. In adult smokers, surgery serves as a teachable moment to motivate quitting. For parents who smoke, having a child undergo surgery may also serve as a teachable moment for smoking behavioral change. This study determined if there is an association between children undergoing a surgical procedure and changes in their parents' smoking behavior. Methods Secondary analyses were performed using logistic regression analysis of 2005 survey data from the National Health Interview Survey. Analyses included 9,289 parent respondents who provided information on both themselves and their children. Results Of the sampled children, 1,112 (12.6%, 95% CI:11.7, 13.4) lived in a home with at least one person who smoked inside in a usual week. In multivariate analysis of the relationship between parent and child surgical history in the past 12 months and smoking behavior, surgery in either the parent (odds ratio 2.19, 95% CI: 1.55, 3.08) or child (odds ratio 2.61, 95% CI: 1.56, 4.35) was associated with an increased likelihood of a quit attempt by the parent. However, these attempts were more likely to be successful if the parents (odds ratio 2.35, 95% CI: 1.35, 4.07), not their child (odds ratio 0.51, 95% CI: 0.20, 1.28), had surgery within the past 12 months. Conclusions Parents who smoke were more likely to make a quit attempt within the past 12 months if their children had surgery within this time, but they were not more likely to succeed in maintaining abstinence and thus could benefit from assistance.

Background Acute lung injury (ALI) is a serious postoperative complication with limited treatment options. A preoperative risk-prediction model would assist clinicians and scientists interested in ALI. The objective of this investigation was to develop a surgical lung injury prediction (SLIP) model to predict risk of postoperative ALI based on readily available preoperative risk factors. Methods Secondary analysis of a prospective cohort investigation including adult patients undergoing high-risk surgery. Preoperative risk factors for postoperative ALI were identified and evaluated for inclusion in the SLIP model. Multivariate logistic regression was used to develop the model. Model performance was assessed with the area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test. Results Out of 4,366 patients, 113 (2.6%) developed early postoperative ALI. Predictors of postoperative ALI in multivariate analysis that were maintained in the final SLIP model included high-risk cardiac, vascular, or thoracic surgery, diabetes mellitus, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and alcohol abuse. The SLIP score distinguished patients who developed early postoperative ALI from those who did not with an area under the receiver operating characteristic curve (95% CI) of 0.82 (0.78-0.86). The model was well calibrated (Hosmer-Lemeshow, P = 0.55). Internal validation using 10-fold cross-validation noted minimal loss of diagnostic accuracy with a mean ± SD area under the receiver operating characteristic curve of 0.79 ± 0.08. Conclusions Using readily available preoperative risk factors, we developed the SLIP scoring system to predict risk of early postoperative ALI.

Abstract Purpose: p53 as a prognostic and predictive factor in early-stage breast cancer has had mixed results. We studied p53 protein expression, by immunohistochemistry, in a randomized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel [Cancer and Leukemia Group B (CALGB) 9344, INT0148]. Patients and Methods: Epithelial p53 expression was evaluated using two immunohistochemical antibodies (DO7 and 1801) in formalin-fixed, paraffin-embedded tissue from patients with node-positive breast cancer who were randomized to four cycles of cyclophosphamide and one of three doses of doxorubicin (60, 75, or 90 mg/m2; AC) and to receive four subsequent cycles of paclitaxel (T) or not. Prognostic and predictive value of p53 protein expression was assessed, independent of treatment assignment, for escalating doses of doxorubicin or addition of T with endpoints of relapse-free (RFS) and overall survival (OS). Results: Of 3,121 patients, 1,887 patient specimens treated on C9344 were obtained, passed quality control, and evaluated for p53 expression. Expression was 23% and 27% for mAbs 1801 and D07, respectively, with 92% concordance. In univariate analysis, p53 positivity was associated with worse OS with either antibody, but only p53 staining with monoclonal antibody 1801 had significantly worse RFS. In multivariate analysis, p53 was not predictive of RFS or OS from either doxorubicin dose escalation or addition of paclitaxel regardless of the antibody. Conclusion: Nuclear staining of p53 by immunohistochemistry is associated with worse prognosis in node-positive patients treated with adjuvant doxorubicin-based chemotherapy but is not a useful predictor of benefit from doxorubicin dose escalation or the addition of paclitaxel. Clin Cancer Res; 17(15); 5170–8. ©2011 AACR.

Abstract Allogeneic hematopoietic cell transplantation in multiple myeloma is limited by prior reports of high treatment-related mortality. We analyzed outcomes after allogeneic hematopoietic cell transplantation for multiple myeloma in 1207 recipients in 3 cohorts based on the year of transplantation: 1989-1994 (n = 343), 1995-2000 (n = 376), and 2001-2005 (n = 488). The most recent cohort was significantly older (53% > 50 years) and had more recipients after prior autotransplantation. Use of unrelated donors, reduced-intensity conditioning and the blood cell grafts increased over time. Rates of acute graft-versus-host (GVHD) were similar, but chronic GVHD rates were highest in the most recent cohort. Overall survival (OS) at 1-year increased over time, reflecting a decrease in treatment-related mortality, but 5-year relapse rates increased from 39% (95% confidence interval [CI], 33%-44%) in 1989-1994 to 58% (95% CI, 51%-64%; P < .001) in the 2001-2005 cohort. Projected 5-year progression-free survival and OS are 14% (95% CI, 9%-20%) and 29% (95% CI, 23%-35%), respectively, in the latest cohort. Increasing age, longer interval from diagnosis to transplantation, and unrelated donor grafts adversely affected OS in multivariate analysis. Survival at 5 years for subjects with none, 1, 2, or 3 of these risk factors were 41% (range, 36%-47%), 32% (range, 27%-37%), 25% (range, 19%-31%), and 3% (range, 0%-11%), respectively (P < .0001).

Purpose Contralateral prophylactic mastectomy (CPM) rates in women with unilateral breast cancer are increasing despite controversy regarding survival advantage. Current scrutiny of the medical costs led us to evaluate the cost-effectiveness of CPM versus routine surveillance as an alternative contralateral breast cancer (CBC) risk management strategy. Methods Using a Markov model, we simulated patients with breast cancer from mastectomy to death. Model parameters were gathered from published literature or national databases. Base-case analysis focused on patients with average-risk breast cancer, 45 years of age at treatment. Outcomes were valued in quality-adjusted life-years (QALYs). Patients' age, risk level of breast cancer, and quality of life (QOL) were varied to assess their impact on results. Results Mean costs of treatment for women age 45 years are comparable: $36,594 for the CPM and $35,182 for surveillance. CPM provides 21.22 mean QALYs compared with 20.93 for surveillance, resulting in an incremental cost-effectiveness ratio (ICER) of $4,869/QALY gained for CPM. To prevent one CBC, six CPMs would be needed. CPM is no longer cost-effective for patients older than 70 years (ICER $62,750/QALY). For BRCA-positive patients, CPM is clearly cost-effective, providing more QALYs while being less costly. In non-BRCA patients, cost-effectiveness of CPM is highly dependent on assumptions regarding QOL for CPM versus surveillance strategy. Conclusion CPM is cost-effective compared with surveillance for patients with breast cancer who are younger than 70 years. Results are sensitive to BRCA-positive status and assumptions of QOL differences between CPM and surveillance patients. This highlights the importance of tailoring treatment for individual patients.