A Stroke Mimic: Methotrexate-induced Neurotoxicity in the Emergency Department.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia. The treatment of ALL involves multimodality therapy, and methotrexate (MTX) remains a mainstay of treatment. A complication of MTX therapy includes acute, subacute, and chronic neurotoxocity. Signs and symptoms may range from headaches, dizziness, and mood disorders to seizures and stroke-like symptoms. CASE REPORT: An 18-year-old woman with a history of ALL presented to the emergency department with acute onset of right-sided facial paralysis, right upper extremity flaccid paralysis, and right lower extremity weakness after receiving MTX therapy 3 days earlier. Diagnostic studies were unremarkable and the patient was treated with oral dextromethorphan for presumed MTX-induced neurotoxicity. The patient's symptoms began to improve within hours and she was discharged home within 48 hours with no neurologic deficits. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be aware of this complication of MTX therapy given the sensitivity in regards to time with respect to cerebral vascular accidents. An awareness of this complication in the setting of the appropriate history and physical examination can lead to an accurate diagnosis and intervention and the avoidance of administering thrombolytics.

A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer.

BACKGROUND: Preclinical models show that an antiangiogenic regimen at low-dose daily (metronomic) dosing may be effective against chemotherapy-resistant tumors. We undertook a prospective, open-label, single-arm, multi-institutional phase II study to evaluate the efficacy of a "5-drug" oral regimen in children with recurrent or progressive cancer. PROCEDURE: Patients ≤21 years old with recurrent or progressive tumors were eligible. Treatment consisted of continuous oral celecoxib, thalidomide, and fenofibrate, with alternating 21-day cycles of low-dose cyclophosphamide and etoposide. Primary endpoint was to assess, within eight disease strata, activity of the 5-drug regimen over 27 weeks. Blood and urine angiogenesis markers were assessed. RESULTS: One hundred one patients were enrolled; 97 began treatment. Median age was 10 years (range: 191 days-21 years); 47 (49%) were female. Disease strata included high-grade glioma (HGG, 21 patients), ependymoma (19), low-grade glioma (LGG, 12), bone tumors (12), medulloblastoma/primitive neuroectodermal tumor (PNET, 8), leukemia (4), neuroblastoma (3), and miscellaneous tumors (18). Treatment was generally well tolerated; most common toxicities were hematologic. Twenty-four (25%) patients completed 27 weeks therapy without progression, including HGG: 1 (5%), ependymoma: 7 (37%), LGG: 7 (58%), medulloblastoma/PNET: 1, neuroblastoma: 1, and miscellaneous tumors: 7 (39%). Best response was complete response (one patient with medulloblastoma), partial response (12), stable disease (36), progressive disease (47), and inevaluable (1). Baseline serum thrombospondin levels were significantly higher in patients successfully completing therapy than in those who progressed (P = 0.009). CONCLUSION: The 5-drug regimen was well tolerated. Clinical activity was demonstrated in some but not all tumor strata.

Impact of Required Versus Self-Directed Use of Virtual Patient Cases on Clerkship Performance: A Mixed-Methods Study.

PURPOSE: To explore how students use and benefit from virtual patient cases (VPCs). METHOD: In academic years 2013-2014 and 2014-2015, cohorts of students in pediatrics (Peds), family medicine (FM), and internal medicine (IM) clerkships were allocated to either core required use (CRU) or self-directed use (SU) of MedU VPCs. Outcomes included number and time of case review, student perception of learning from VPCs, National Board of Medical Examiners (NBME) subject examination scores, and summative clinical ratings for medical knowledge and differential diagnoses/problem solving. Focus groups were conducted each year. Mean differences were compared by t test. RESULTS: A total of 255 students participated in the study. Mean number of cases completed by the CRU group was significantly higher than that by the SU group (13.9 vs. 3.1 for FM, 16.1 vs. 3.9 for Peds, and 10.4 vs. 1.2 for IM) (P < .001). Student-perceived value ratings of VPCs were similar between groups. Students described VPCs as time consuming but useful for supplementing clinical conditions not seen in person. Mean scores on NBME subject examinations for CRU versus SU groups were not different between groups in any clerkship, nor were there significant differences in the summative clinical ratings for medical knowledge or differential diagnosis/clinical reasoning. CONCLUSIONS: Although VPCs continue to serve an important role in exposing students to clinical conditions not seen in person, the optimal employment of this technology in clerkship pedagogy requires further exploration.