Dynamic Contrast-Enhanced MRI-Derived Intracellular Water Lifetime (τ i ): A Prognostic Marker for Patients with Head and Neck Squamous Cell Carcinomas.

BACKGROUND AND PURPOSE: Shutter-speed model analysis of dynamic contrast-enhanced MR imaging allows estimation of mean intracellular water molecule lifetime (a measure of cellular energy metabolism) and volume transfer constant (a measure of hemodynamics). The purpose of this study was to investigate the prognostic utility of pretreatment mean intracellular water molecule lifetime and volume transfer constant in predicting overall survival in patients with squamous cell carcinomas of the head and neck and to stratify p16-positive patients based upon survival outcome. MATERIALS AND METHODS: A cohort of 60 patients underwent dynamic contrast-enhanced MR imaging before treatment. Median, mean intracellular water molecule lifetime and volume transfer constant values from metastatic nodes were computed from each patient. Kaplan-Meier analyses were performed to associate mean intracellular water molecule lifetime and volume transfer constant and their combination with overall survival for the first 2 years, 5 years, and beyond (median duration, >7 years). RESULTS: By the last date of observation, 18 patients had died, and median follow-up for surviving patients (n = 42) was 8.32 years. Patients with high mean intracellular water molecule lifetime (4 deaths) had significantly (P = .01) prolonged overall survival by 5 years compared with those with low mean intracellular water molecule lifetime (13 deaths). Similarly, patients with high mean intracellular water molecule lifetime (4 deaths) had significantly (P = .006) longer overall survival at long-term duration than those with low mean intracellular water molecule lifetime (14 deaths). However, volume transfer constant was a significant predictor for only the 5-year follow-up period. There was some evidence (P < .10) to suggest that mean intracellular water molecule lifetime and volume transfer constant were associated with overall survival for the first 2 years. Patients with high mean intracellular water molecule lifetime and high volume transfer constant were associated with significantly (P < .01) longer overall survival compared with other groups for all follow-up periods. In addition, p16-positive patients with high mean intracellular water molecule lifetime and high volume transfer constant demonstrated a trend toward the longest overall survival. CONCLUSIONS: A combined analysis of mean intracellular water molecule lifetime and volume transfer constant provided the best model to predict overall survival in patients with squamous cell carcinomas of the head and neck.

Sustained Posttransplantation Diabetes Is Associated With Long-Term Major Cardiovascular Events Following Liver Transplantation.

Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long-term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow-up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20-3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.

Higher tacrolimus concentrations early after transplant reduce the risk of acute GvHD in reduced-intensity allogeneic stem cell transplantation.

There is significant variability in the serum concentrations of tacrolimus attained early post transplant due to drug interactions and genomic variation. We evaluated whether tacrolimus concentrations early post transplant correlated with incidence of acute GvHD in 120 consecutive patients allografted with a uniform reduced-intensity conditioning regimen. All patients received standard prophylaxis with oral tacrolimus and IV methotrexate. The primary variable of interest was mean weekly tacrolimus concentrations in the initial 4 weeks post transplant. In multivariate analysis, week 1 tacrolimus concentration was an independent predictor of acute grade 2-4 GvHD (hazard ratio (HR), 0.90; 95% confidence interval (CI), 0.84-0.97; P<0.01). This association was driven by a lower risk of acute grade 2-4 GvHD in patients with week 1 tacrolimus concentrations >12 ng/mL (HR, 0.47; 95% CI, 0.25-0.88; P=0.02). Week 1 tacrolimus concentrations were not associated with chronic GvHD, relapse or overall survival. Lower tacrolimus concentrations at weeks 2, 3 and 4 were not associated with a higher incidence of GvHD. In summary, we found that higher tacrolimus concentrations during the first week after allografting with a reduced-intensity conditioning regimen were associated with significantly reduced risk of acute grade 2-4 GvHD without increasing risk of relapse.

Prediction of disease-free survival in patients with squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Patients with HNSCC have a poor prognosis and development of imaging biomarkers that predict long-term outcome might aid in planning optimal treatment strategies. Therefore, the purpose of the present study was to predict disease-free survival in patients with HNSCC by using pretreatment K(trans) measured from dynamic contrast-enhanced MR imaging. MATERIALS AND METHODS: Sixty-six patients with HNSCC were recruited from January 2005 to October 2008. Three patients were excluded because they underwent upfront neck dissection, and 6 patients were excluded due to suboptimal MR imaging data or being lost to follow-up. Disease-free survival was measured in the remaining 57 patients from the end date of chemoradiation therapy. In patients who died, the end point was the date of death, while in surviving patients the date of last clinical follow-up was used as the end point. Pretreatment K(trans) and nodal volume were computed from the largest metastatic node, and median pretreatment K(trans) and volume were used to divide patients into 2 groups (at or above the threshold value [group I] and below the threshold value [group II]. Disease-free survival was analyzed by the Kaplan-Meier method, and the results were compared by using a logrank test with K(trans) and nodal volume as predictors. A P value <.05 was considered significant. RESULTS: Thirteen of 57 patients had died of HNSCC by the last follow-up period (March 31, 2009). Patients with higher pretreatment K(trans) values had prolonged disease-free survival compared with patients with lower K(trans) values (P=.029). However, there was no significant difference in disease-free survival when nodal volume was used as a predictor (P=.599). CONCLUSIONS: Pretreatment K(trans) may be a useful prognostic marker in HNSCC.

Toxicity data for preoperative concurrent chemoradiotherapy with oxaliplatin and continuous infusion 5-fluorouracil for locally advanced esophageal cancer.

The purpose of this retrospective analysis was to characterize the feasibility and tolerability of oxaliplatin/5-fluorouracil (5-FU) given concurrently with radiotherapy for patients with locally advanced esophageal cancer. Between July 2005 and March 2009, 15 patients with clinical stage T3/T4 and/or N1/M1a lower esophageal or gastroesophageal junction adenocarcinoma were treated with preoperative chemoradiotherapy using oxaliplatin every 2 weeks and continuous infusion 5-FU. The main treatment-related toxicities were oral mucositis and dysphagia. During the first 2 weeks of treatment, 20% of patients presented with grade 1-2 oral mucositis, and one patient developed grade 1 dysphagia. In weeks 3-4, 53% of the patients experienced grade 1-2 mucositis, and 40% experienced grade 1-2 dysphagia. One patient only experienced grade 3 mucositis in week 4. Three patients (20%) had grade 3-4 dysphagia in weeks 3-4 and were continued on intravenous fluids and pain medications. During the last 2 weeks of chemoradiotherapy, 53% of patients reported grade 1-2 oral mucositis, mostly grade 1 and 73% of patients experienced grade 1-2 dysphagia and 26% patients experienced grade 3-4 dysphagia. Other toxicities included fatigue, nausea, neuropathy, and diarrhea. Only one patient experienced > 10% weight loss. The whole group was treated with aggressive supportive care during radiotherapy. Five (33%) patients achieved a pathological complete response. No patients developed locoregional failure. Sixty percent of the patients developed distant metastases and the 2-year disease-free survival was 53%. The median survival was 3.2 years with the 2-year overall survival of 73%. Preoperative oxaliplatin/5-FU-based chemoradiotherapy for locally advanced esophageal cancer is feasible, but associated with substantial gastrointestinal toxicity. A careful attention to nutrition and hydration throughout the course of therapy is required.

Modelling the long-term consequences of a hypothetical dispersal of radioactivity in an urban area including remediation alternatives.

The Urban Remediation Working Group of the International Atomic Energy Agency's EMRAS (Environmental Modelling for Radiation Safety) program was organized to address issues of remediation assessment modelling for urban areas contaminated with dispersed radionuclides. The present paper describes the second of two modelling exercises. This exercise was based on a hypothetical dispersal of radioactivity in an urban area from a radiological dispersal device, with reference surface contamination at selected sites used as the primary input information. Modelling endpoints for the exercise included radionuclide concentrations and external dose rates at specified locations, contributions to the dose rates from individual surfaces, and annual and cumulative external doses to specified reference individuals. Model predictions were performed for a "no action" situation (with no remedial measures) and for selected countermeasures. The exercise provided an opportunity for comparison of three modelling approaches, as well as a comparison of the predicted effectiveness of various countermeasures in terms of their short-term and long-term effects on predicted doses to humans.

Modelling of a large-scale urban contamination situation and remediation alternatives.

The Urban Remediation Working Group of the International Atomic Energy Agency's EMRAS (Environmental Modelling for Radiation Safety) program was organized to address issues of remediation assessment modelling for urban areas contaminated with dispersed radionuclides. The present paper describes the first of two modelling exercises, which was based on Chernobyl fallout data in the town of Pripyat, Ukraine. Modelling endpoints for the exercise included radionuclide concentrations and external dose rates at specified locations, contributions to the dose rates from individual surfaces and radionuclides, and annual and cumulative external doses to specified reference individuals. Model predictions were performed for a "no action" situation (with no remedial measures) and for selected countermeasures. The exercise provided a valuable opportunity to compare modelling approaches and parameter values, as well as to compare the predicted effectiveness of various countermeasures with respect to short-term and long-term reduction of predicted doses to people.

Improvement of modelling capabilities for assessing urban contamination: the EMRAS Urban Remediation Working Group.

The Urban Remediation Working Group of the International Atomic Energy Agency's Environmental Modelling for Radiation Safety (EMRAS) programme was established to improve modelling and assessment capabilities for radioactively contaminated urban situations, including the effects of countermeasures. An example of the Working Group's activities is an exercise based on Chernobyl fallout data in Ukraine, which has provided an opportunity to compare predictions among several models and with available measurements, to discuss reasons for discrepancies, and to identify areas where additional information would be helpful.

Role of registered nurses in error prevention, discovery and correction.

BACKGROUND: Registered nurses have a vital role in discovering and correcting medical error. OBJECTIVE: To describe the type and frequency of errors detected by American critical care nurses, and to ascertain who made the errors discovered by study participants. METHODS: Daily logbooks were used to collect information about errors discovered by a random sample of 502 critical care nurses during a 28-day period. RESULTS: Although the majority of errors discovered and corrected by critical care nurses involved medications (163/367), procedural errors were common (n = 115). Charting and transcription errors were less frequently discovered. The errors discovered by participants were attributed to a wide variety of staff members including nurses, doctors, pharmacists, technicians and unit secretaries. CONCLUSIONS: Given the importance of nurses in maintaining patient safety, future studies should identify factors that enhance their effectiveness to prevent, intercept and correct healthcare errors.

Evaluation of anemia, neutropenia and skin toxicities in standard or dose-dense doxorubicin/cyclophosphamide (AC)-paclitaxel or docetaxel adjuvant chemotherapy in breast cancer.

BACKGROUND: Results of CALGB 9741 demonstrated that administering standard doxorubicin/cyclophosphamide (AC)-paclitaxel therapy for adjuvant therapy of breast cancer in a dose-dense fashion with colony-stimulating factors increases efficacy, decreases severe neutropenia, but may increase the need for blood transfusions. A chart review was performed to evaluate the rates of anemia, neutropenia and skin toxicities with dose-dense and traditional AC-taxane chemotherapy. PATIENTS AND METHODS: A total of 112 patients received one of four treatments: non-dose-dense AC-paclitaxel (NDD Pac), dose-dense AC-paclitaxel (DD Pac), non dose-dense AC-docetaxel (NDD Doc), or dose-dense AC-docetaxel (DD Doc). RESULTS: Transfusion rates were not increased in the dose-dense population; however, rates of grade 2-4 anemia (23% versus 0%, P=0.029), as well as erythropoietin use (58% versus 0%, P <0.0001), were significantly increased in the DD Pac group compared with the NDD Pac group. Grade 3 skin toxicities were significantly increased in the DD Doc group compared with the NDD Doc group (70% versus 11%, P <0.0001). CONCLUSIONS: These results demonstrate that dose-dense AC-taxane therapy may increase rates of anemia and the need for erythropoietin, and decrease rates of neutropenia. The utility of DD Doc appears limited by skin toxicities and its use outside of a clinical study should not be recommended.

Randomized trial of enhanced anticipatory guidance for injury prevention.

OBJECTIVE: To develop and evaluate an injury prevention anticipatory guidance training program for pediatric residents. DESIGN: Thirty-one residents were randomly assigned to an intervention or control group. Both groups attended a 1-hour seminar about injury prevention and the American Academy of Pediatrics TIPP (The Injury Prevention Program) materials. The intervention group also received 5 hours of experiential instruction on injury prevention content and counseling skills (SAFE Counseling Framework). Families with infants from birth to age 6 months were enrolled in the study (N = 196); they were followed up until the child was aged 12 to 18 months. Data were collected by means of baseline and follow-up interviews, audiotapes of medical visits, parent exit surveys, and home observations. SETTING: A hospital-based continuity clinic that serves families living in low-income, inner-city neighborhoods. OUTCOMES: Physician counseling and parent satisfaction, knowledge, beliefs, and behaviors. RESULTS: Parents seen by physicians in the intervention group received significantly more injury prevention counseling for 5 of the 6 safety practices, and they were significantly more satisfied with the help their physicians provided on safety topics. They were no less satisfied with their physicians' counseling on other anticipatory guidance topics. Parents' knowledge, beliefs, and home safety behaviors did not differ between the 2 groups. CONCLUSIONS: The frequency and impact of pediatric counseling can be enhanced by experiential training that targets specific injury hazards. Because low-income families face many barriers to carrying out the recommended safety practices, supplemental strategies are needed to ensure safer homes.