CT-based pleural effusion volume estimation formula demonstrates low accuracy and reproducibility for traumatic hemothorax.

PURPOSE: We aimed to evaluate the accuracy and reproducibility of the CT-based volume estimation formula V = d2 * h, where d and h represent the maximum depth and height of the effusion, for acute traumatic hemothorax. MATERIALS & METHODS: Prospectively identified patients with CT showing acute traumatic hemothorax were considered. Volumes were retrospectively estimated using d2 * h, then manually measured on axial images. Subgroup analysis was performed on borderline-sized hemothorax (200-400 mL). Measurements were repeated by three non-radiologists. Bland-Altman analysis was used to assess agreement between the two methods and agreement between raters for each method. RESULTS: A total of 46 patients (median age 34; 36 men) with hemothorax volume 23-1622 mL (median 191 mL, IQR 99-324 mL) were evaluated. Limits of agreement between estimates and measured volumes were -718 - +842 mL (± 202 mL). Borderline-sized hemothorax (n = 13) limits of agreement were -300 - +121 mL (± 114 mL). Of all hemothorax, 85 % (n = 39/46) were correctly stratified as over or under 300 mL, and of borderline-sized hemothorax, 54 % (n = 7/13). Inter-rater limits of agreement were -251 - +350, -694 - +1019, and -696 - +957 for the estimation formula, respectively, and -124 - +190, -97 - +111, and -96 - +46 for the measured volume. DISCUSSION: An estimation formula varies with actual hemothorax volume by hundreds of mL. There is low accuracy in stratifying hemothorax volumes close to 300 mL. Variability between raters was substantially higher with the estimation formula than with manual measurements.

Complement-mediated release of fibroblast growth factor 2 from human RPE cells.

PURPOSE: Complement activation is associated with choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Fibroblast growth factor 2 (FGF2) and membrane attack complex (MAC) are present in eyes of patients with CNV. Herein, we investigated the effect of complement activation on FGF2 release in human retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were primed with an anti-RPE antibody and then treated with C1q-depleted human serum in the presence or absence of Tec kinases inhibitor (LFM-A13). 38 cytokines/chemokines levels were measured by Luminex technology. Secretion of FGF2 and interleukin (IL)-6 was assessed by ELISA. Tec protein was measured by Western blot. mRNA expression of FGF2, chemokine (C-X-C motif) ligand 1 (CXCL-1), and family members of Tec kinases was evaluated by qPCR. Cell viability and MAC deposition were determined by WST-1 assay and flow cytometry, respectively. RESULTS: Complement activation caused increased FGF2 and IL-6 release. FGF2 was released when C6-depleted human serum was reconstituted with C6. Anti-C5 antibody significantly attenuated complement-mediated FGF2 release, but not IL-6. FGF2 mRNA levels were not affected, while CXCL-1 mRNA levels were increased by complement activation. FGF2-containing extracellular vesicles were detected in response to complement challenge. Tec mRNA and protein were expressed in RPE cells. In the presence of LFM-A13, secretion of FGF2, but not IL-6, and MAC deposition were significantly decreased and cell viability was significantly increased in complement-treated cells when compared to controls. CONCLUSIONS: Complement plays an important role to release FGF2 from RPE cells. Tec kinase is involved in MAC formation and complement-mediated FGF2 release. This information suggests a role for complement activation to mediate neovascularization in conditions such as AMD, and may elucidate potential therapeutic targets.

Imaging Utilization in Children With Headaches: Current Status and Opportunities for Improvement.

BACKGROUND: Despite a variety of evidence-based guidelines documents, imaging is anecdotally commonly used in the setting of children with headaches, but the frequency of such imaging is unknown. We assessed the use of and estimated costs of imaging utilization in children with headaches at a pediatric hospital. MATERIALS AND METHODS: Retrospectively reviewing charts of all relevant imaging examinations in 2015, we focused on radiology reports with indications containing the terms "headache" or "migraine" and excluded patients who fulfilled evidence-based criteria in support of obtaining imaging. All radiology results were recorded and categorized as normal, likely causative, possibly causative, or unlikely causative of headache. Societal costs were estimated using allowable Medicare fees, and losses of total facility time were estimated using scheduled examination slots. RESULTS: In 2015, 4,257 imaging studies were performed for indications of headache or migraine. Of these, 3,098 (73%) met our exclusion criteria, meaning they had appropriate indications, and 1,159 (27%) were presumably imaged outside of guideline recommendations. Overall, 19.8% (230 of 1,159) had diagnoses that were likely or potentially causative of headaches, and 71.2% (825 of 1,159) were normal. The remainder had findings unlikely to cause headaches. The total estimated societal cost of imaging studies for presumed primary headache imaging at our institution in 2015 was $322,422. The loss of imaging time was 845.3 hours. CONCLUSION: Given the large number of normal examinations and the inappropriate use of radiography, imaging utilization in children with headaches can likely be improved. In addition to reducing ionizing radiation and the need for sedation, reductions in unnecessary imaging would result in societal cost savings and increase imaging capacity for other patients.

Complement-Mediated Regulation of Apolipoprotein E in Cultured Human RPE Cells.

PURPOSE: Complement activation is implicated in the pathogenesis of age-related macular degeneration (AMD). Apolipoprotein E (ApoE) and complement activation products such as membrane attack complex (MAC) are present in eyes of individuals with AMD. Herein, we investigated the effect of complement activation on induction of ApoE accumulation in human retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were primed with a complement-fixing antibody followed by treatment with C1q-depleted (C1q-Dep) human serum to elicit alternative pathway complement activation. Controls included anti-C5 antibody-treated serum and heat-inactivated C1q-Dep. Total protein was determined on RPE cell extracts, conditioned media, and extracellular matrix (ECM) by Western blot. ApoE and MAC colocalization was assessed on cultured RPE cells and human eyes by immunofluorescent stain. ApoE mRNA expression was evaluated by quantitative PCR (qPCR). RESULTS: Complement challenge upregulated cell-associated ApoE, but not apolipoprotein A1. ApoE accumulation was blocked by anti-C5 antibody and enhanced by repetitive complement challenge. ApoE mRNA levels were not affected by complement challenge. ApoE was frequently colocalized with MAC in complement-treated cells and drusen from human eyes. ApoE was released into complement-treated conditioned media after a single complement challenge and accumulated on ECM after repetitive complement challenge. CONCLUSIONS: Complement challenge induces time-dependent ApoE accumulation in RPE cells. An understanding of the mechanisms by which complement affects RPE ApoE accumulation may help to better explain drusen composition, and provide insights into potential therapeutic targets.