Airway, breathing, computed tomographic scanning: duplicate computed tomographic imaging after transfer to trauma center.

BACKGROUND: Trauma patients imaged at community hospitals often receive duplicate computed tomographic (CT) imaging after transfer to regional trauma centers (RTCs). CT scanning is expensive, is resource intensive, and has acknowledged radiation risk to the patient. The objective of this study was to review and evaluate the frequency, indications, impact on patient management, as well as associated radiation and charges for duplicate CT imaging of trauma patients transferred to our RTC from outside hospitals (OSH). METHODS: Patients transferred to our RTC between September 2009 and August 2010 were evaluated prospectively. The OSH patients' charts and provider interviews were used to determine the reasons for repeated scans. The primary outcome was frequency of duplicate CT scan, defined as a repeated CT image of the same body part within 24 hours. The reason for duplicate imaging and impact on patient management was categorized. Radiation exposure and charges for duplicate scans were also determined. RESULTS: Of the 185 patients transferred to our facility, 177 were eligible. CT examinations at the OSH were performed on 137 patients (77%). A duplicate CT examination occurred in 38 patients (28%). The most common reason for duplicate CT scanning was lack of thin-section multiplanar data, on images sent via CD-ROM (37%). There was a change in management in 16 patients (42%). The patients with duplicate scanning received a median of 10.2 mSv (interquartile range, 6.6-15.7 mSv) of additional radiation, with a median charge of $409 (interquartile range, $307-$734). CONCLUSION: More than one third of duplicated scans performed on transferred trauma patients were potentially avoidable, primary owing to inadequate transfer of data from the OSH CT scan. The capacity of a single CD-ROM is insufficient to contain full imaging data from a trauma scan, and establishing direct links to imaging data from OSHs would decrease the number of repeated CT scans performed on transferred trauma patients. LEVEL OF EVIDENCE: Care management study, level III.

Oral RKS262 reduces tumor burden in a neuroblastoma xenograft animal model and mediates cytotoxicity through SAPK/JNK and ROS activation in vitro.

Patients diagnosed with high-risk neuroblastoma (NB), an extracranial solid tumor in children, have metastases and low survival (30%) despite aggressive multi-modal therapy. Therefore new therapies are urgently needed. We show significant in vitro and in vivo antitumor efficacy of RKS262 in NB. RKS262 showed superior cytotoxicity (IC(50) = 6-25 µM) against six representative NB cell lines compared to its parent analog Nifurtimox (currently in phase 2). Pre-formulated RKS262 (150 mg/kg/daily) pellets administered orally, suppressed tumor growth (60%, p = 0.021) in NB xenograft mice within 28 days. RKS262-treated SMSKCNR cells showed TUNEL-positive DNA nicks and activation of ROS, MAPKs (SAPK/JNK), caspase-3, and p53, along with suppression of the IGF-1R/PI3K/PKC pathway and the Bcl2 family of proteins. RKS262 caused G(2)/M-phase arrest and suppressed cdc-2, cyclin B1, p21, and cyclin D1/D4 expression. N-acetyl-cysteine (NAC; 10 mM) pre-treatment rescued cell viability of RKS262 (23 µM)-treated SMSKCNR cells, and pre-treatment with ascorbic acid (100 µM) and a MAPK inhibitor SB203580 (20 µM) reversed SAPK/JNK, caspase-3 activation, PARP-1 cleavage, and suppression of IGF-1R, PI3K, and PKC phosphorylation. Further, treatment with exogenous BDNF (50 nM) did not suppress SAPK/JNK or ROS activation due to RKS262. Rather, BDNF (50 nM), EGF (100 nM) and IGF-1 (100 nM) co-treatment with RKS262 induced a remarkable S-phase arrest rather than a G(2)/M phase arrest when RKS262 was used alone. In summary, RKS262 shows oral efficacy in NB xenograft animals, and induces apoptosis in vitro in SMSKCNR cells via cell cycle arrest, MAPK and ROS activation, and suppression of IGF-1R/PI3K/PKC and Bcl2 family proteins in a growth factor (BDNF/EGF/IGF-1)-independent fashion.

Nifurtimox induces apoptosis of neuroblastoma cells in vitro and in vivo.

Neuroblastoma is the most common extracranial solid tumor in children and, when disseminated, carries a poor prognosis. Even with aggressive combinations of chemotherapy, surgery, autologous bone marrow transplant, and radiation, long-term survival remains at 30% and new therapies are needed. Recently, a patient with neuroblastoma who acquired Chagas disease was treated with nifurtimox with subsequent reduction in tumor size. The effect of nifurtimox on the neuroblastoma cell lines CHLA-90, LA1-55n, LA-N2, SMS-KCNR, and SY5Y was examined. Nifurtimox decreased cell viability in a concentration-dependent manner. Cell morphology, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay, and caspase-3 activation indicate that cell death was primarily due to apoptosis. Nifurtimox also suppressed basal and TrkB-mediated Akt phosphorylation, and the cytotoxicity of nifurtimox was attenuated by a tyrosine hydroxylase inhibitor (alpha-methyl-tyrosine). Nifurtimox killed catecholaminergic, but not cholinergic, autonomic neurons in culture. In vivo xenograft models showed inhibition of tumor growth with a histologic decrease in proliferation and increase in apoptosis. These results suggest that nifurtimox induces cell death in neuroblastoma. Therefore, further studies are warranted to develop nifurtimox as a promising new treatment for neuroblastoma.