Gliomas are one of the most common types of brain tumors. Given low survival and high treatment resistance rates, particularly for high grade gliomas, there is a need for specific biomarkers that can be used to stratify patients for therapy and monitor treatment response. Recent work has demonstrated that metabolic reprogramming, often mediated by inflammation, can lead to an upregulation of glutamine as an energy source for cancer cells. As a result, glutamine pathways are an emerging pharmacologic target. The goal of this pilot study was to characterize changes in glutamine metabolism and inflammation in human glioma samples and explore the use of glutamine as a potential biomarker. 1H high-resolution magic angle spinning nuclear magnetic resonance spectra were acquired from ex vivo glioma tissue (n = 16, grades II–IV) to quantify metabolite concentrations. Tumor inflammatory markers were quantified using electrochemiluminescence assays. Glutamate, glutathione, lactate, and alanine, as well as interleukin (IL)-1β and IL-8, increased significantly in samples from grade IV gliomas compared to grades II and III (p ≤ .05). Following dimension reduction of the inflammatory markers using probabilistic principal component analysis, we observed that glutamine, alanine, glutathione, and lactate were positively associated with the first inflammatory marker principal component. Our findings support the hypothesis that glutamine may be a key marker for glioma progression and indicate that inflammation is associated with changes in glutamine metabolism. These results motivate further in vivo investigation of glutamine as a biomarker for tumor progression and treatment response.

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Background Continuous positive airway pressure (CPAP) is a common mode of respiratory support used in neonatal intensive care units. In preterm infants, nasal CPAP (nCPAP) therapy is often delivered via soft, biocompatible nasal mask suitable for long-term direct skin contact and held firmly against the face. Limited sizes of nCPAP mask contribute to mal-fitting related complications and adverse outcomes in this fragile population. We hypothesized that custom-fit nCPAP masks will improve the fit with less skin pressure and strap tension improving efficacy and reducing complications associated with nCPAP therapy in neonates. Methods After IRB approval and informed consent, we evaluated several methods to develop 3D facial models to test custom 3D nCPAP masks. These methods included camera-based photogrammetry, laser scanning and structured light scanning using a Bellus3D Face Camera Pro and iPhone X running either Bellus3D FaceApp for iPhone, or Heges application. This data was used to provide accurate 3D neonatal facial models. Using CAD software nCPAP inserts were designed to be placed between proprietary nCPAP mask and the model infant’s face. The resulted 3D designed nCPAP mask was form fitted to the model face. Subsequently, nCPAP masks were connected to a ventilator to provide CPAP and calibrated pressure sensors and co-linear tension sensors were placed to measures skin pressure and nCPAP mask strap tension. Results Photogrammetry and laser scanning were not suited to the neonatal face. However, structured light scanning techniques produced accurate 3D neonatal facial models. Individualized nCPAP mask inserts manufactured using 3D printed molds and silicon injection were effective at decreasing surface pressure and mask strap pressure in some cases by more than 50% compared to CPAP masks without inserts. Conclusions We found that readily available structured light scanning devices such as the iPhone X are a low cost, safe, rapid, and accurate tool to develop accurate models of preterm infant facial topography. Structured light scanning developed 3D nCPAP inserts applied to commercially available CPAP masks significantly reduced skin pressure and strap tension at clinically relevant CPAP pressures when utilized on model neonatal faces. This workflow maybe useful at producing individualized nCPAP masks for neonates reducing complications due to misfit.

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