The United States Food and Drug Administration (FDA) approved Vemurafenib in August 2011, for treatment of melanoma with BRAF V600 mutation. It has shown improvement in the median overall survival of melanoma patients. The most common adverse effects of vermurafenib are arthralgia, rash, alopecia, photosensitivity and fatigue. Other infrequent and severe adverse reactions reported in patients include keratocanthomas, hypersensitivity, Stevens Johnson Syndrome, toxic epidermal necrolysis, uveitis, QT prolongation, and hepatotoxicity. We hereby present a case of bilateral facial palsy as an adverse effect of vemurafenib therapy, seen after six weeks of commencement of the drug. Complete resolution of the symptoms was seen when the patient was taken off vemurafenib.

Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridineinduced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.

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Background: In several recent studies of postmenopausal women, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with lower circulating estrogens. These analgesics have also been studied in association with breast cancer risks with inconsistent findings. Cross-talk between immune and endocrine factors may play important roles in the development of breast cancer. Methods: We conducted a study of postmenopausal women drawn from the Prostate, Lung, Colon and Ovarian Cancer Screening Trial cohort (PLCO). At study baseline, participants reported their frequency of use for aspirin, non-aspirin NSAIDs via questionnaire. High-performance liquid chromatography-tandem mass spectrometry was used to measure estrogens and estrogen metabolites (EM) in baseline serum samples from 354 women who went on to get breast cancer during study follow-up, and 423 women who remained healthy. All selected participants reported no use of menopausal hormones at study baseline. General linear models were used to estimate multivariable-adjusted mean EM by self-reported use of analgesics (daily, weekly, or less than weekly) in all participants, while adjusting for continuous age, baseline BMI and breast cancer outcome. Results: In comparison to women who reported that they did not use any NSAIDs on a daily basis, those reporting daily use of aspirin only, daily use of non-aspirin NSAIDs only and daily use of both aspirin and non-aspirin NSAIDs had lower multivariable adjusted serum concentrations of unconjugated estradiol (Pdiff<0.02). Greater frequency of non-aspirin NSAID use was associated with trends towards lower concentrations of total EM (Ptrend=.004), estrone (Ptrend=.004), and unconjugated estradiol (Ptrend=.04), and higher ratios of 2- and 4- hydroxylated EM to the parent estrogens (Ptrend=.02 and .04). Associations were similar in women who did and did not go on to have breast cancer. Discussion: In this sample of postmenopausal women, more frequent use of NSAIDs was associated with lower circulating estrogens and with patterns of estrogen metabolism that may be more favorable with respect to breast cancer risk. These results require independent confirmation in additional well-designed studies. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

2578 Background: Thromboprophylaxis is the top challenge to patient safety practice in hospitals. Postoperative Deep vein thrombosis (DVT) and pulmonary embolism (PE) are the major cardiovascular killers in the surgical setting. In October 2008, Medicare designated DVT and PE occurring after total knee or hip replacement as ‘never events', and indicated that they will not pay the incremental cost to manage the complication and has made the hospital acquired DVT/PE unacceptable and serious. There are however, limited data on factors contributing to DVT/PE in-patients undergoing total knee or hip replacement. Aim: To ascertain nationwide health care utilization and associated co-morbidities in Total knee replacement (TKR) recipients who do or do not develop DVT/PE. Methods: We used the year 2007, National Inpatient Sample (NIS) to analyze the post operative occurrence of DVT/PE after TKR. We used an analysis similar to AHRQ's Patient Safety Indicator number – 12 (PSI 12) which is Postoperative Pulmonary Embolism or Deep Vein Thrombosis but restricted our analysis only to TKR. We intended to capture cases of postoperative venous thromboses and embolism - specifically, pulmonary embolism and deep venous thrombosis. For our analysis we separated TKR into 2 groups; one without DVT/PE and the other with DVT/PE. We analyzed all surgical discharges age 18 years and older with an ICD-9-CM code for an operating room procedure TKR (ICD-9 8154). From this we excluded those who have principal diagnosis of DVT/PE, as these patients are likely to have had PE/DVT present on admission and not because of TKR and also where a procedure for interruption of vena cava (IVC filter) (ICD-9 387) occurs before or on the same day as the first operating room procedure as these patients likely had DVT/PE even before TKR. We then created a subset from the first group, with discharges ICD-9-CM codes for deep vein thrombosis or pulmonary embolism in any secondary diagnosis field and thus defined the group of patients who developed DVT/PE after TKR. We used the following ICD-9 codes to represent DVT (ICD-9 codes 451.11, 451.19, 451.2, 451.81, 451.9, 453.40, 453.41, 453.42, 453.8, 453.9) and PE (ICD-9 codes 415.1–415.19). IBM SPSS Statistics 18 was used for data mining and analysis. Result: In the year 2007, there were 550,770 discharges with a procedure for TKR. After excluding primary diagnosis of DVT/PE and IVC filter, we had 550228 as our working number. Of these, 5454 discharges had a secondary diagnosis of DVT/PE (Rate - 10 new cases per 1000 TKR procedures). Demographics and health care utilization between those who did or did not develop are described in Table 1. Co-morbidities associated with those who did or did not develop DVT are described in (Table 2). Conclusion: DVT & PE are major avoidable complications of Total Knee replacement and are associated with significant mortality and health care costs. These data demonstrate that there may not be any significant differences in age and associated co-morbidities between those who do or do not develop DVT/PE following total knee replacement except for UTI which can be attributed to the difference in length of stay. The absence of serious co-morbidities like AF and CHF in both groups suggest those with serious co-morbidities may not be receiving total knee replacement. That no differences were noticed in associated co-morbidities among those who did or did not develop DVT/PE following TKR provide the rationale for further study of factors contributing to this serious complication of TKR. Such studies may inform future strategies for prevention of post-operative DVT/PE. Disclosure: No relevant conflicts of interest to declare.