ABO blood type has previously been identified as a risk factor for thrombosis and pancreatic cancer (PC). The aim of the study is to demonstrate the associations between ABO blood type and other clinical factors with the risk of thromboembolism (TE) in patients with PC. We conducted a retrospective study in 670 patients with pathologically confirmed pancreatic adenocarcinoma at the University of Texas MD Anderson Cancer Center. Clinical information was retrieved from medical records. ABO blood type was determined serologically and/or genetically. Logistic regression models, Kaplan–Meier plot, log-rank test, and Cox proportional hazard regression models were employed in data analysis. The incidence of TE was 35.2% in 670 patients who did not have TE prior to cancer diagnosis. Pulmonary embolism (PE) and deep vein thrombosis (DVT) consisted 44.1% of the TE events. Non-O blood type, pancreatic body/tail tumors, previous use of antithrombotic medication, and obesity (body mass index >30 kg/m2) were significant predictors for TE in general. Blood type A and AB, low hemoglobin level (≤10 g/dL), obesity, metastatic tumor, and pancreatic body/tail tumors were significant predictors for PE and DVT. Patients with metastatic tumor or pancreatic body/tail tumors had a much higher frequency of early TE events (≤3 months after cancer diagnosis); and early TE occurrence was a significant independent predictor for increased risk of death. These observations suggest that ABO non-O blood type is an independent predictor for TE in PC. A better understanding of the risk factors for TE in PC may help to identify patients who are most likely to benefit from prophylactic anticoagulation therapy.

Over and under nutrition are associated with worse outcomes for children with leukemia and lymphoma; however, the molecular basis for this clinical observation is not well understood. Many chemotherapeutics used for leukemia treatment are known to generate oxidative stress in vitro; therefore, we evaluated redox status and diet in pediatric leukemia patients during therapy in order to ascertain relationships between nutrition and oxidative stress. Dietary intake and redox measures in peripheral blood mononuclear cells from 32 pediatric leukemia and lymphoma patients were collected over six months during treatment. Baseline measures when patients were off chemotherapy and subsequent assessments were collected after one, two and six months. Oxidative stress increased over time in all patients, consistent with chemotherapy-induced redox effects. Older and younger children showed significantly different baseline levels of reactive oxygen species, which increased over time in all age ranges. Diet was assessed at points proximal to oxidative stress measurements and revealed a novel association with consumption of animal protein, vegetable protein, and total protein intake. Our findings demonstrate that chemotherapy increases oxidative stress in pediatric leukemia patients, and raises the possibility that dietary protein or altered protein metabolism could contribute to clinical outcomes.

Background: Cerebral vasospasm remains a major cause of morbidity and mortality in patients with subarachnoid hemorrhage. Vasospasm treatment typically includes IA infusion of vasodilators; however the optimal agent/s have not been elucidated. National surveys suggest that IA treatment algorithms vary between centers and commonly involve use of a single agent. We hypothesize that IA infusion of a cocktail of multiple vasodilators is more efficacious than single agent treatment. Methods: A prospective case series of consecutive patients with cerebral vasospasm (Group 2, N=50 patients, 106 vessels) treated between 2010-13 with IA infusion of a specific cocktail of multiple agents (nitroglycerin, verapamil and nicardipine) at a tertiary center, were compared to a historic control group (Group 1, N=54 patients, 116 vessels) at the same center between 2008-10 treated with a single agent (nicardipine or verapamil). Patient demographics, age, and modified Rankin score (mRS) at discharge and 3 months were collected in the cerebrovascular database. Arterial luminal diameters were measured on cerebral angiograms both pre-infusion (PrID) and post-infusion (PoID). The Improvement Ratio (IR) = (PoID - PrID/PrID) x 100 was calculated and statistically compared between groups using the T test. Results: Group 2 demonstrated statistically significant improvement IR 45.8% (SD 36.6) than Group 1 IR 10.9% (SD 12.0), P<0.001. Multiple agent infusion resulted in an average of 34.9% greater vessel diameter improvement than single agent therapy. Comparison of IR between different single agents within group 1 (nicardipine and verapamil) demonstrated no difference in vessel diameter change. Age of the patient had no effect on efficacy in either group. Patient outcomes measured by mRS were similar at discharge and at 3 months follow-up. Discussion: Treatment of cerebral vasospasm with an IA cocktail of nitroglycerine, verapamil, and nicardipine provides significantly better angiographic improvement of vasospasm than single agent therapy. This effect appears independent of patient age. Outcomes measured by mRS at discharge and 3 months were not significantly different, however will be examined in an ongoing prospective multi-center trial.

4228 Pediatric leukemia patients undergoing treatment are often malnourished due to nausea, food aversions, and mucositis. Clinical observations suggest that poor nutrition worsens outcomes for this patient population. Oxidative stress may be a key intermediary linking nutrition and clinical outcomes. Previous reports suggest that diet may modulate the balance of cellular pro- and antioxidants and that oxidative stress may influence the efficacy of cancer treatment. Taken together, these data suggest that dietary changes might modulate oxidative stress and consequently impact the efficacy of therapies used to treat children with cancer. We hypothesize that age-appropriate nutrition may augment oxidative stress induced by chemotherapy and improve patient response to therapy. To address this hypothesis, we commenced a pilot study evaluating the interrelationship between nutrition and oxidative stress in children who are receiving therapy for leukemia. Twenty-four hour dietary recalls were completed and analyzed using the Minnesota Nutrition Data System for Research (NDSR) dietary analysis program to ascertain nutritional information, including caloric intake and dietary antioxidant consumption. Accordingly, the levels of pro- and anti-oxidants in mononuclear cells isolated from peripheral blood were quantified to measure oxidative stress. Levels of the reactive oxygen species (ROS) superoxide and hydrogen peroxide were measured with dihydroethidium (HE) and 2′,7′-dichlorofluorescin diacetate (DCF-DA) staining, respectively. As oxidative stress results from an imbalance of pro- and anti-oxidants, the quantity of the most common cellular antioxidant glutathione (GSH) was also measured by monochlorobimane staining. Assessments of nutrition and oxidative stress were completed for each patient at regularly scheduled intervals over a six month period. The first assessment occurred either before the patient received chemotherapy or during a prolonged break from chemotherapy whereas later assessments were conducted one month, two months, and six months after the patient began or resumed chemotherapy. Consequently, changes in nutrition and oxidative stress were monitored in response to treatment. To date, analyses have been completed for 12 patients. The median age of our patient population at the time of enrollment is 28.5 months. The oldest patient was 53 months at the time of enrollment and the youngest patient was 22 months. Seven patients are male and 6 are female. All subjects are receiving therapy for acute lymphoblastic leukemia (ALL); 7 have been diagnosed with standard risk ALL and 6 have been diagnosed with high risk ALL. Preliminary results show that ROS were increased in mononuclear cells isolated from the majority of subjects during the course of their treatment. An increase was defined as a two-fold or greater elevation in ROS at any subsequent visit compared to the baseline visit. An increase in superoxides was detected in 72.7% of patients (8 of 11). Also, an increase in hydrogen peroxide was detected in 50% of patients (6 of 12). Interestingly, the antioxidant GSH was decreased in mononuclear cells isolated from many of our patients during the course of their treatment. A decrease was defined as a drop in the quantity of GSH at all subsequent visits compared to the baseline visit. A decrease in GSH was seen in 50% of patients (6 of 12) and 33% (4 of 12) demonstrated a decrease in GSH coincident with an increase in both superoxides and hydrogen peroxide. This increase in ROS and decrease in GSH suggests that the majority of our patients experience oxidative stress during therapy. To investigate the impact of diet on oxidant status, NDSR software was used to compare the consumption of dietary antioxidants, such as vitamins A, B3, C, and E, selenium, and glutamic acid, to the corresponding amounts of ROS from the same visit. The strongest correlation was between vitamin C consumption and hydrogen peroxide levels. An inverse relationship between vitamin C consumption and hydrogen peroxide levels was apparent in 58.3% of patients (7 of 12). Though this data is preliminary, our hope is that the findings from this pilot study will begin to illuminate the relationship between diet and oxidative stress in pediatric leukemia patients and justify future work which will aid in devising dietary interventions that will modulate oxidant status to favor improved survival of children with leukemia. Disclosures: No relevant conflicts of interest to declare.