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Huang E.X.,University of Washington | Bradley J.D.,University of Washington | El Naqa I.,University of Washington | Hope A.J.,Princess Margaret Hospital | And 6 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 * MED+1.50 * ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets. © 2012 Elsevier Inc. Source


Stewart A.,LDS Hospital
American Journal of Health-System Pharmacy | Year: 2010

Purpose. A case of warfarin-induced skin necrosis (WISN) treated with protein C concentrate (human) is reported. Summary. A 46-year-old Caucasian woman was admitted to the hospital for a herpes viral infection complicated by neutropenic fevers of unknown origin. Broad-spectrum antibiotics were initiated, as well as enoxaparin for prophylaxis of deep venous thrombosis. By hospital day 7, the patient's platelets decreased by 50%; by hospital day 8, they decreased another 50%. A test for heparin antibody was positive, and enoxaparin was stopped. Two days later, the patient developed a clot in her peripherally inserted central catheter, and warfarin and argatroban were initiated. Within 24 hours of warfarin initiation, the patient developed swelling in her feet and new lesions on her inner thigh, buttock, face, feet, fingers, and arms. She was treated with phytonadione and fresh frozen plasma, but these treatments failed to slow the progression of her lesions, which had turned to necrotic tissue. WISN was suspected, and warfarin therapy was discontinued after three doses. After a consultation with a hematologist, treatment with protein C concentrate (human) was initiated. Within 24 hours of treatment with this product, progression of necrosis stopped, and the patient's respiratory failure resolved. The patient underwent multiple skin grafts, and the lesions healed without extensive scarring. She experienced no adverse effects with the administration of protein C concentrate (human). Conclusion. A patient with WISN was treated with protein C concentrate (human) with overall good results and no adverse effects. Copyright © 2010, American Society of Health-System Pharmacists, Inc. All rights reserved. Source


John R.,University of Minnesota | Long J.W.,LDS Hospital | Massey H.T.,University of Rochester | Griffith B.P.,University of Maryland, Baltimore | And 4 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2011

Objective: The Levitronix CentriMag (Levitronix LLC, Waltham, Mass) ventricular assist system is designed for temporary left, right, or biventricular support. Advantages include ease of use, excellent reliability, and low thrombosis risk,. which may allow wider application of short-term support and improved outcomes in patients with cardiogenic shock. This multi-institutional study evaluated safety, effectiveness, and outcomes of the CentriMag in patients with cardiogenic shock. Methods: Thirty-eight patients were supported at 7 centers. Patients included 12 after cardiotomy, 14 after myocardial infarction, and 12 with right ventricular failure after implantable left ventricular assist device placement. Devices were implanted in left (n = 8), right (n = 12), or biventricular (n = 18) configuration. Support was continued until recovery, transplantation, or implantation of long-term ventricular assist device. Results: Mean support duration for the entire cohort (n = 38) was 13 days (1-60 days), with 47% of patients (18/38) surviving 30 days after device removal. Mean CentriMag biventricular support (n = 18) duration was 15 days (1-60 days), with 44% (8/18) surviving at 30 days. Mean CentriMag right ventricular support with a commercially available left ventricular assist device (n = 12) duration was 14 days (1-29 days), with 58% (7/12) surviving at 30 days. Complications included bleeding (21%), infection (5%), respiratory failure (3%), hemolysis (5%), and neurologic dysfunction (11%). There were no CentriMag or pump failures. Conclusions: In this preliminary study, the CentriMag provided short-term support for patients with cardiogenic shock with a low incidence of device-related complications and no device failures. © 2011 by The American Association for Thoracic Surgery. Source


Aarli B.B.,University of Bergen | Calverley P.M.A.,University of Liverpool | Jensen R.L.,LDS Hospital | Eagan T.M.L.,University of Bergen | And 2 more authors.
European Respiratory Journal | Year: 2015

The forced oscillation technique can identify expiratory flow limitation (EFL) when a large difference in inspiratory and expiratory reactance (ΔXrs) occurs. However, flow limitation can vary from breath to breath, and so we compared a multiple-breath ΔXrs approach to the traditional breath-by-breath assessment of EFL. We investigated the within- and between-day reproducibility and the factors that affect the size of ΔXrs when used as a continuous measurement over multiple breaths. In addition, we examined how multiple-breath ΔXrs relates to the sensation of breathlessness. 425 moderate to very severe chronic obstructive pulmonary disease (COPD) patients and 229 controls were included. Spirometry and impedance measurements were performed on a MasterScope CT Impulse Oscillation System. Median ΔXrs approached zero in healthy controls with little variation between measurements. COPD patients generally had higher ΔXrs and higher variability. The COPD patients with ΔXrs >0.1 kPa·L-1·s-1 were prone to be more breathless and had a higher modified Medical Research Council dyspnoea scale score. In controls, the 95th percentile of ΔXrs was as low as 0.07 kPa·L-1·s-1. We describe a new method to assess EFL at a patient level and propose a cut-off, mean ΔXrs >0.1 kPa·L-1·s-1, as a way to identify COPD patients who are more likely to report dyspnoea. Copyright ©ERS 2015. Source


McMasters K.M.,University of Louisville | Edwards M.J.,University of Cincinnati | Ross M.I.,University of Texas M. D. Anderson Cancer Center | Reintgen D.S.,Lakeland Regional Cancer Center | And 6 more authors.
Annals of Surgery | Year: 2010

Objective: This analysis was performed to investigate the hypothesis that ulceration predicts improved response to adjuvant interferon (IFN) therapy. Summary Background Data: Several studies have demonstrated that adjuvant therapy for high-risk melanoma patients with IFN alfa-2b improves disease-free survival (DFS), although the impact on overall survival (OS) is controversial. Recent data have suggested that IFN therapy may preferentially benefit patients with ulcerated primary melanomas. Methods: Post hoc analysis was performed by a prospective multi-institutional randomized study of observation versus adjuvant IFN therapy for melanoma. All patients underwent sentinel lymph node biopsy; completion lymphadenectomy was performed for patients with sentinel lymph node metastasis. Patients were stratified by Breslow thickness, ulceration, and nodal status. Kaplan-Meier analysis of DFS and OS was performed and included univariate and multivariate analyses. Results: A total of 1769 patients were analyzed (1311 without ulceration, 458 with ulceration) with a median follow-up of 71 months. Ulceration was associated with significantly worse DFS and OS in both node-negative and node-positive patients. Kaplan-Meier analysis of node-negative and node-positive patients by ulceration status revealed that the only significant impact of interferon was improved DFS in the ulcerated node-positive patients (P = 0.0169). IFN therapy had no significant impact on OS regardless of ulceration status, however. On multivariate analysis, IFN treatment was a significant independent predictor of DFS among ulcerated patients (odds ratio, 0.51; 95% confidence interval, 0.30-0.83; P = 0.0053), but not among patients without ulceration. Conclusions: These data support the conclusion that ulceration is a predictive marker for response to adjuvant IFN therapy. Future studies to evaluate specifically the differential effect of IFN on patients with ulcerated melanomas may allow us to focus this therapy on patients most likely to benefit from it. © 2010 by Lippincott Williams & Wilkins. Source

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