Person: Caruso, Paul
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Caruso
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Paul
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Caruso, Paul
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Publication Quantifying Temporomandibular Joint Synovitis in Children With Juvenile Idiopathic Arthritis(John Wiley and Sons Inc., 2016) Resnick, Cory; Vakilian, Pouya M.; Breen, Micheal; Zurakowski, David; Caruso, Paul; Henderson, Lauren; Nigrovic, Peter; Kaban, Leonard; Peacock, ZacharyObjective: Juvenile idiopathic arthritis (JIA) frequently affects the temporomandibular joints (TMJs) and is often undetected by history, examination, and plain imaging. Qualitative assessment of gadolinium‐enhanced magnetic resonance images (MRIs) is currently the standard for diagnosis of TMJ synovitis associated with JIA. The purpose of this study is to apply a quantitative analysis of synovial enhancement to MRIs of patients with and without JIA to establish a disease threshold and sensitivity and specificity for the technique. Methods: This is a retrospective case–control study of children (age ≤16 years) who had MRIs with gadolinium including the TMJs. Subjects were divided into a JIA group and a control group. From a coronal T1‐weighted image, a ratio (enhancement ratio [ER]) of the average pixel intensity within three 0.2‐mm2 regions of interest (ROIs) in the TMJ synovium to that of a 50‐mm2 ROI of the longus capitis muscle was calculated. Receiver operating characteristic curves were used to determine the sensitivity and specificity. The inter‐ and intraexaminer reliability was evaluated with Bland‐Altman plots and 2‐way mixed, absolute agreement intraclass correlation coefficients. Results: There were 187 and 142 TMJs included in the JIA and control groups, respectively. An ER threshold of 1.55 had a sensitivity and specificity for detecting synovitis of 91% and 96%, respectively. The inter‐ and intraexaminer reliability was excellent. Conclusion: Calculating a ratio of pixel intensity between the TMJ synovium and the longus capitis muscle is a reliable way to quantify synovial enhancement. An ER of 1.55 differentiates normal TMJs from those affected by inflammatory arthritis.Publication FGF23 Deficiency Leads to Mixed Hearing Loss and Middle Ear Malformation in Mice(Public Library of Science, 2014) Lysaght, Andrew C.; Yuan, Quan; Fan, Yi; Kalwani, Neil; Caruso, Paul; Cunnane, MaryBeth; Mannstadt, Beate; Stankovic, KonstantinaFibroblast growth factor 23 (FGF23) is a circulating hormone important in phosphate homeostasis. Abnormal serum levels of FGF23 result in systemic pathologies in humans and mice, including renal phosphate wasting diseases and hyperphosphatemia. We sought to uncover the role FGF23 plays in the auditory system due to shared molecular mechanisms and genetic pathways between ear and kidney development, the critical roles multiple FGFs play in auditory development and the known hearing phenotype in mice deficient in klotho (KL), a critical co-factor for FGF23 signaling. Using functional assessments of hearing, we demonstrate that Fgf mice are profoundly deaf. Fgf mice have moderate hearing loss above 20 kHz, consistent with mixed conductive and sensorineural pathology of both middle and inner ear origin. Histology and high-voltage X-ray computed tomography of Fgf mice demonstrate dysplastic bulla and ossicles; Fgf mice have near-normal morphology. The cochleae of mutant mice appear nearly normal on gross and microscopic inspection. In wild type mice, FGF23 is ubiquitously expressed throughout the cochlea. Measurements from Fgf mice do not match the auditory phenotype of Kl−/− mice, suggesting that loss of FGF23 activity impacts the auditory system via mechanisms at least partially independent of KL. Given the extensive middle ear malformations and the overlap of initiation of FGF23 activity and Eustachian tube development, this work suggests a possible role for FGF23 in otitis media.Publication Bevacizumab Treatment for Meningiomas in NF2: A Retrospective Analysis of 15 Patients(Public Library of Science (PLoS), 2013) Nunes, Fabio Pereira; Merker, Vanessa L.; Jennings, Dominique; Caruso, Paul; di Tomaso, Emmanuelle; Muzikansky, Alona; Barker, Frederick; Stemmer-Rachamimov, Anat; Plotkin, ScottBevacizumab treatment can result in tumor shrinkage of progressive vestibular schwannomas in some neurofibromatosis 2 (NF2) patients but its effect on meningiomas has not been defined. To determine the clinical activity of bevacizumab against NF2-related meningiomas, we measured changes in volume of meningiomas in NF2 patients who received bevacizumab for treatment of progressive vestibular schwannomas. A radiographic response was defined as a 20% decrease in tumor size by volumetric MRI analysis. In addition, we determined the expression pattern of growth factors associated with tumor angiogenesis in paraffin-embedded tissues from 26 unrelated meningiomas. A total of 48 meningiomas in 15 NF2 patients were included in this study with a median follow up time of 18 months. A volumetric radiographic response was seen in 29% of the meningiomas (14/48). Tumor shrinkage was not durable: the median duration of response was 3.7 months and the median time to progression was 15 months. There was no significant correlation between pre-treatment growth rate and meningioma response in regression models. Tissue analysis showed no correlation between tumor microvascular density and expression of VEGF pathway components. This data suggests that, in contrast to schwannomas, activation of VEGF pathway is not the primary driver of angiogenesis in meningiomas. Our results suggest that a minority of NF2-associated meningiomas shrink during bevacizumab therapy and that these responses were of short duration. These results are comparable to previous studies of bevacizumab in sporadic meningiomas.Publication Analysis of Criteria for MRI Diagnosis of TMJ Disc Displacement and Arthralgia(Hindawi Publishing Corporation, 2012) Shaefer, Jeffry; Riley, Cara Joy; Caruso, Paul; Keith, DavidAims. To improve diagnostic criteria for TMJ disc displacement (DD). Methods:. The standard protocol for MRI diagnosis of DD, using a 12 o'clock reference position, was compared to an alternative protocol. The alternative protocol involves the functional relationship between the condyle and articular eminence, using a line perpendicular to the posterior slope of the eminence as a reference for disc position. The disc location was examined using both protocols, and disc diagnoses were compared in their relationship with joint pain. Statistical analyses included P value, sensitivity, specificity, odds ratio, and kappa statistic. Results:. 58 MRIs were interpreted. 36 subjects reported arthralgia; 22 did not. Both protocols demonstrated significance (standard P = 0.004, alternative P < 0.001) for the ability to predict arthralgia. The odds of arthralgia increased in DD patients diagnosed by standard methods 9.71 times and in DD diagnosed by alternative means 37.15 times. The diagnostic sensitivity decreased 30% using the alternative versus the standard protocol (0.6389 versus 0.9444), while specificity increased 60% (0.9545 versus 0.3636). Conclusions:. A stronger relationship occurs between DD and arthralgia when using a function-based protocol. The alternative protocol correctly identifies subjects without arthralgia, who by standard methods would be diagnosed with DD, as having nondisplaced discs, providing a more clinically relevant assessment of TMJ disc displacement.