Whole-body edema with olanzapine: A case report and literature review.

Olanzapine is a second-generation antipsychotic (SGA) that has been shown to promote disease remission in persons with treatment-resistant depression when used in combination with fluoxetine. However, tolerability of treatment augmentation with SGAs may be limited because of common adverse effects, such as weight gain, hypertriglyceridemia, and elevated glucose. Data exist pertaining to rare localized edematous reactions or angioedema with use of SGAs, but diffuse whole-body edema has yet to be documented. A 47-year-old white female with treatment-resistant depression presented with a 5-day history of weight gain and swelling of her torso and extremities. Five days prior, she had initiated olanzapine/fluoxetine 6/50 mg daily following failure of fluoxetine 40 mg daily monotherapy. The patient was noted to have gained 3.6 kg since her last appointment and exhibited profuse pitting edema on her forearms, lower limbs, hands, and chest. Olanzapine/fluoxetine was discontinued and the patient was prescribed a 3-day course of a loop diuretic for symptomatic management. A follow-up visit 5 days later noted complete resolution of symptoms. Because of the temporal relationship of symptoms with initiation of olanzapine, we recommend monitoring for edema with initiation and/or titration of therapy.

Impact of Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy (AVATAR) on Anesthesia Use, Payer Charges, and Treatment Time in Pediatric Patients.

PURPOSE: Pediatric radiation therapy (RT) requires optimal immobilization that often necessitates daily anesthesia. To decrease anesthesia use, we implemented a novel audiovisual-assisted therapeutic ambience in RT (AVATAR) system that projects video onto a radiolucent screen within the child's line of vision to provide attentional diversion. We investigated its reduction on anesthesia use, payer charges, and treatment time, in addition to its impact on radiation delivery. METHODS AND MATERIALS: A 6-year retrospective analysis was performed among children undergoing RT (n = 224) 3 years before and 3 years after the introduction of AVATAR. The frequency of anesthesia use before and after AVATAR implementation, in addition to RT treatment times, were compared. The number of spared anesthesia treatments allowed for a charge to payer analysis. To document the lack of surface dose perturbation by AVATAR, a phantom craniospinal treatment course was delivered both with and without AVATAR. Additionally, an ion chamber course was delivered to document changes to the dose at depth. RESULTS: More children were able to avoid anesthesia use entirely in the post-AVATAR cohort compared with the pre-AVATAR cohort (73.2% vs 63.4%; P = .03), and fewer required anesthesia for each treatment (18.8% vs 33%; P = .03). AVATAR introduction reduced anesthesia use for all ages studied. Treatment time per session was reduced by 38% using AVATAR compared with anesthesia. There were 326 fewer anesthesia sessions delivered over 3 years after AVATAR was introduced, with an estimated savings of >$500,000. Optically stimulated luminescent dosimeters revealed a small increase in dose of 0.8% to 9.5% with AVATAR, whereas the use of a thermomolded face mask increased skin dose by as much as 58%. CONCLUSIONS: AVATAR introduction decreased anesthesia use in children undergoing RT. More children avoided anesthesia entirely, and fewer needed anesthesia for every treatment, resulting in a reduction in treatment time and savings of nearly $550,000 in approximately 3 years, with minimal perturbation of RT dose delivery.

A novel-integrated quality assurance phantom for radiographic and nonradiographic radiotherapy localization and positioning systems.

PURPOSE: Various localization and positioning systems utilizing radiographic or nonradiographic methods have been developed to improve the accuracy of radiation treatment. Each quality assurance (QA) procedure requires its own phantom and is independent from each other, so the deviation between each system is unavailable. The purpose of this work is to develop and evaluate a single-integrated QA phantom for different localization and positioning systems. METHODS: The integrated phantom was designed in three-dimensional (3D) CAD software and 3D printed. The phantom was designed with laser alignment marks, a raised letter "S" on the anterior surface for optical surface monitoring system registration, a core for radiofrequency (RF) tracking system alignment, eight internal fiducials for image alignment, and an isocentric bearing for Winston-Lutz test. Tilt legs and rotational stage were designed for rotational verification of optical surface mapping system and RF tracking system, respectively. The phantom was scanned using a CT scanner and a QA plan was created. This prototype phantom was evaluated against established QA techniques. RESULTS: The QA result between the proposed procedure and established QA technique are 1.12 ± 0.31 and 1.14 ± 0.31 mm, respectively, for RF tracking system and 0.18 ± 0.06 and 0.18 ± 0.05 mm for Winston-Lutz test. There is no significant difference for the QA results between the established QA and proposed procedure (P > 0.05, t test). The accuracy of rotational verification for surface mapping system and RF tracking system are less than 0.5 and 1° compared the predefined value. The isocenter deviation of each location system is around l mm. CONCLUSION: We have designed and evaluated a novel-integrated phantom for radiographic and nonradiographic localization and positioning systems for radiotherapy. With this phantom, we will reduce the variation in measurements and simplify the QA procedures.

Biological characterization of a novel in vitro cell irradiator.

To evaluate the overall robustness of a novel cellular irradiator we performed a series of well-characterized, dose-responsive assays to assess the consequences of DNA damage. We used a previously described novel irradiation system and a traditional 137Cs source to irradiate a cell line. The generation of reactive oxygen species was assessed using chloromethyl-H2DCFDA dye, the induction of DNA DSBs was observed using the comet assay, and the initiation of DNA break repair was assessed through γH2AX image cytometry. A high correlation between physical absorbed dose and biologic dose was seen for the production of intracellular reactive oxygen species, physical DNA double strand breaks, and modulation of the cellular double stand break pathway. The results compared favorably to irradiation with a traditional 137Cs source. The rapid, straightforward tests described form a reasonable approach for biologic characterization of novel irradiators. These additional testing metrics go beyond standard physics testing such as Monte Carlo simulation and thermo-luminescent dosimeter evaluation to confirm that a novel irradiator can produce the desired dose effects in vitro. Further, assessment of these biological metrics confirms that the physical handling of the cells during the irradiation process results in biologic effects that scale appropriately with dose.

Initial clinical outcomes of audiovisual-assisted therapeutic ambience in radiation therapy (AVATAR).

PURPOSE: Radiation therapy is an important component of treatment for many childhood cancers. Depending upon the age and maturity of the child, pediatric radiation therapy often requires general anesthesia for immobilization, position reproducibility, and daily treatment delivery. We designed and clinically implemented a radiation therapy-compatible audiovisual system that allows children to watch streaming video during treatment, with the goal of reducing the need for daily anesthesia through immersion in video. METHODS AND MATERIALS: We designed an audiovisual-assisted therapeutic ambience in radiation therapy (AVATAR) system using a digital media player with wireless streaming and pico projector, and a radiolucent display screen positioned within the child's field of view to him or her with sufficient entertainment and distraction for the duration of serial treatments without the need for daily anesthesia. We piloted this system in 25 pediatric patients between the ages of 3 and 12 years. We calculated the number of fractions of radiation for which this system was used successfully and anesthesia avoided and compared it with the anesthesia rates reported in the literature for children of this age. RESULTS: Twenty-three of 25 patients (92%) were able to complete the prescribed course of radiation therapy without anesthesia using the AVATAR system, with a total of 441 fractions of treatment administered when using AVATAR. The median age of patients successfully treated with this approach was 6 years. Seven of the 23 patients were initially treated with daily anesthesia and were successfully transitioned to use of the AVATAR system. Patients and families reported an improved treatment experience with the use of the AVATAR system compared with anesthesia. CONCLUSIONS: The AVATAR system enables a high proportion of children to undergo radiation therapy without anesthesia compared with reported anesthesia rates, justifying continued development and clinical investigation of this technique.

High-throughput detection of DNA double-strand breaks using image cytometry.

Assessment of γH2AX expression for studying DNA double-strand break formation is often performed by manual counting of foci using immunofluorescence microscopy, an approach that is laborious and subject to significant foci selection bias. Here we present a novel high-throughput method for detecting DNA double-strand breaks using automated image cytometry assessment of cell average γH2AX immunofluorescence. Our technique provides an expedient, high-throughput, objective, and cost-effective method for γH2AX analysis.

AXL Is a Logical Molecular Target in Head and Neck Squamous Cell Carcinoma.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) represents the eighth most common malignancy worldwide. Standard-of-care treatments for patients with HNSCC include surgery, radiation, and chemotherapy. In addition, the anti-EGFR monoclonal antibody cetuximab is often used in combination with these treatment modalities. Despite clinical success with these therapeutics, HNSCC remains a difficult malignancy to treat. Thus, identification of new molecular targets is critical. EXPERIMENTAL DESIGN: In the current study, the receptor tyrosine kinase AXL was investigated as a molecular target in HNSCC using established cell lines, HNSCC patient-derived xenografts (PDX), and human tumors. HNSCC dependency on AXL was evaluated with both anti-AXL siRNAs and the small-molecule AXL inhibitor R428. Furthermore, AXL inhibition was evaluated with standard-of-care treatment regimens used in HNSCC. RESULTS: AXL was found to be highly overexpressed in several models of HNSCC, where AXL was significantly associated with higher pathologic grade, presence of distant metastases, and shorter relapse-free survival in patients with HNSCC. Further investigations indicated that HNSCC cells were reliant on AXL for cellular proliferation, migration, and invasion. In addition, targeting AXL increased HNSCC cell line sensitivity to chemotherapy, cetuximab, and radiation. Moreover, radiation-resistant HNSCC cell line xenografts and PDXs expressed elevated levels of both total and activated AXL, indicating a role for AXL in radiation resistance. CONCLUSIONS: This study provides evidence for the role of AXL in HNSCC pathogenesis and supports further preclinical and clinical evaluation of anti-AXL therapeutics for the treatment of patients with HNSCC.

A novel high-throughput irradiator for in vitro radiation sensitivity bioassays.

This paper describes the development and characterization of a fully automated in vitro cell irradiator using an electronic brachytherapy source to perform radiation sensitivity bioassays. This novel irradiator allows complex variable dose and dose rate schemes to be delivered to multiple wells of 96-well culture plates used in standard biological assays. The Xoft Axxent® eBx™ was chosen as the x-ray source due to its ability to vary tube current up to 300 µA for a 50 kVp spectrum using clinical surface applicators. Translation of the multiwell plate across the fixed radiation field is achieved using a precision motor driven computer controlled positioning system. A series of measurements was performed to characterize dosimetric performance of the system. Measurements have shown that the radiation output measured with an end window ionization chamber is stable between operating currents of 50-300 µA. In addition, radiochromic film was used to characterize the field flatness and symmetry. The average field flatness in the in-plane and cross-plane direction was 2.9 ± 1.0% and 4.0 ± 1.7%, respectively. The average symmetry in the in-plane and cross-plane direction was 1.8 ± 0.9% and 1.6 ± 0.5%, respectively. The optimal focal spot resolution at the cellular plane was determined by measuring sequential irradiations on radiochromic film for three different well spacing schemes. It was determined that the current system can irradiate every other well with negligible impact on the radiation field characteristics. Finally, a performance comparison between this system and a common cabinet irradiator is presented.

Modeling the impact of spatial relationships on horizontal curve safety.

The curved segments of roadways are more hazardous because of the additional centripetalforces exerted on a vehicle, driver expectations, and other factors. The safety of a curve is dependent on various factors, most notably by geometric factors, but the location of a curve in relation to other curves is also thought to influence the safety of those curves because of a driver's expectation to encounter additional curves. The link between an individual curve's geometric characteristics and its safety performance has been established, but spatial considerations are typically not included in a safety analysis. The spatial considerations included in this research consisted of four components: distance to adjacent curves, direction of turn of the adjacent curves, and radius and length of the adjacent curves. The primary objective of this paper is to quantify the spatial relationship between adjacent horizontal curves and horizontal curve safety using a crash modification factor. Doing so enables a safety professional to more accurately estimate safety to allocate funding to reduce or prevent future collisions and more efficiently design new roadway sections to minimize crash risk where there will be a series of curves along a route. The most important finding from this research is the statistical significance of spatial considerations for the prediction of horizontal curve safety. The distances to adjacent curves were found to be a reliable predictor of observed collisions. This research recommends a model which utilizes spatial considerations for horizontal curve safety prediction in addition to current Highway Safety Manual prediction capabilities using individual curve geometric features.