Aim: We aimed to identify quantitative ultrasound (QUS)-radiomic markers to predict radiotherapy response in metastatic lymph nodes of head and neck cancer. Materials & methods: Node-positive head and neck cancer patients underwent pretreatment QUS imaging of their metastatic lymph nodes. Imaging features were extracted using the QUS spectral form, and second-order texture parameters. Machine-learning classifiers were used for predictive modeling, which included a logistic regression, naive Bayes, and k-nearest neighbor classifiers. Results: There was a statistically significant difference in the pretreatment QUS-radiomic parameters between radiological complete responders versus partial responders (p < 0.05). The univariable model that demonstrated the greatest classification accuracy included: spectral intercept (SI)-contrast (area under the curve = 0.741). Multivariable models were also computed and showed that the SI-contrast + SI-homogeneity demonstrated an area under the curve = 0.870. The three-feature model demonstrated that the spectral slope-correlation + SI-contrast + SI-homogeneity-predicted response with accuracy of 87.5%. Conclusion: Multivariable QUS-radiomic features of metastatic lymph nodes can predict treatment response a priori.
Mathematical models (MMs) have been used to study the kinetics of influenza A virus infections under antiviral therapy, and to characterize the efficacy of antivirals such as neuraminidase inhibitors (NAIs). NAIs prevent viral neuraminidase from cleaving sialic acid receptors that bind virus progeny to the surface of infected cells, thereby inhibiting their release, suppressing infection spread. When used to study treatment with NAIs, MMs represent viral release implicitly as part of viral replication. Consequently, NAIs in such MMs do not act specifically and exclusively on virus release. We compared a MM with an explicit representation of viral release (i.e., distinct from virus production) to a simple MM without explicit release, and investigated whether parameter estimation and the estimation of NAI efficacy were affected by the use of a simple MM. Since the release rate of influenza A virus is not well-known, a broad range of release rates were considered. If the virus release rate is greater than ∼0.1 h−1, the simple MM provides accurate estimates of infection parameters, but underestimates NAI efficacy, which could lead to underdosing and the emergence of NAI resistance. In contrast, when release is slower than ∼0.1 h−1, the simple MM accurately estimates NAI efficacy, but it can significantly overestimate the infectious lifespan (i.e., the time a cell remains infectious and producing free virus), and it will significantly underestimate the total virus yield and thus the likelihood of resistance emergence. We discuss the properties of, and a possible lower bound for, the influenza A virus release rate.
Strontium-based medications, such as strontium ranelate, have been suggested to have therapeutic effects in patients with osteoporosis. Strontium salts available off-shelf in stores across North America are assumed to provide similar effects as strontium ranelate and thus should lead to similar distributions of elemental strontium incorporated in bone. The objective of this study was to compare the spatial distribution of strontium in animal bones following the administration of strontium ranelate and strontium citrate. Seventeen-weekold Sprague-Dawley rats were split into three groups over 10 weeks and given 625 mg/kg/day of strontium ranelate and 676 mg/kg/day of strontium citrate; the control group received no additional supplementary strontium. The humeri were collected from all animals, and strontium distribution was mapped using 2D micro-XRF and 3D dual energy K-edge subtraction (KES) imaging. 2D and 3D elemental mapping methods demonstrated that strontium delivered during treatment by both salts had the same spatial distribution. 3D elemental strontium maps of treated animal bones showed that strontium was largely observed in the trabecular regions under the epiphyseal (growth) plate.The thickness of the strontium layers in both the strontium ranelate and strontium citrate sample was not significantly different (p = .9201). 2D micro-XRF and 3D dual-energy KES images effectively elucidated the spatial distribution of elemental strontium in calcified tissue. These methods provide a novel approach to evaluating the potential efficacy of strontium supplements in the treatment of osteoporosis.
differences in presentation and outcomes for PTC with TCM in a large, single institution cohort. Materials/Methods: From an IRB approved registry, we identified all cases of PTC with TCM at our institution with patient, tumor, treatment data and outcomes from January 1997 to July 2018. Tall Cell Variant (TCV) PTC had 30% TCM while Tall Cell Features (TCF) had <30% TCM. Pts with any other coexisting aggressive morphology/histology or no surgery were excluded. Demographic & clinico-pathologic features at the time of TCM diagnosis that were potentially associated with 10-yr locoregional recurrence free survival (LRFS), distant recurrence free survival (DRFS) and overall survival (OS) were evaluated using Kaplan-Meir (KM) method and Cox proportional hazard model. Results: A total of 365 pts with TCM (32% TCV; 68% TCF) PTC were evaluable. There were 123 (34%) males and 242 (66%) females. At time of TCM diagnosis, age (mean 53 yo vs 51 yo, pZ0.13), pT3/T4 (69.7% vs 62.0%, pZ0.15), distant metastatic disease (4.1% vs 1.2%, pZ0.08), positive surgical margins (pZ0.22), and TCM (pZ0.65) were similar. Males had more pN+ disease (62.6% vs 47.5%, pZ0.006), larger primary tumor diameter (mean 2.8 cm vs 1.8 cm, p<0.001), and a higher positive lymph node count (5.7 vs 2.8, p<0.001). KM estimated 5-yr LRFS (72.9% vs 86.2%, pZ0.003), 5-yr DRFS (82.8% vs 97.4%, p<0.001), and 5-yr OS (87.1% vs 96.3%, pZ0.004) were significantly worse in males. After adjusting for clinical features, the risks of recurrence and OS were similar between male and female. Conclusion: In this large, single institution experience of PTC with TCM, males had worse outcomes than females. This difference was attributed to worse pathologic features at presentation in males. Further validation of this finding in a larger multi-institutional cohort is warranted.
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