Background To evaluate and establish a digital workflow for the custom designing and 3D printing of mouth opening tongue-depressing (MOTD) stents for patients receiving radiotherapy for head and neck cancer. Methods We retrospectively identified 3 patients who received radiation therapy (RT) for primary head and neck cancers with MOTD stents. We compared two methods for obtaining the digital impressions of patients’ teeth. The first method involved segmentation from computed tomography (CT) scans, as previously established by our group, and the second method used 3D scanning of the patients’ articulated stone models that were made during the conventional stent fabrication process. Three independent observers repeated the process to obtain digital impressions which provided data to design customized MOTD stents. For each method, we evaluated the time efficiency, dice similarity coefficient (DSC) for reproducibility, and the 3D printed stents’ accuracy. For the 3D scanning method, we evaluated the registration process using manual and automatic approaches. Results For all patients, the 3D scanning method demonstrated a significant advantage over the CT scanning method in terms of time efficiency with over 60% reduction in time consumed ( p < 0.0001) and reproducibility with significantly higher DSC ( p < 0.001). The printed stents were tested over the articulated dental stone models, and the trueness of fit and accuracy of dental anatomy was found to be significantly better for MOTD stents made using the 3D scanning method. The automated registration showed higher accuracy with errors < 0.001 mm compared to manual registration. Conclusions We developed an efficient workflow for custom designing and 3D-printing MOTD radiation stents. This workflow represents a considerable improvement over the CT-derived segmentation method. The application of this rapid and efficient digital workflow into radiation oncology practices can expand the use of these toxicity sparing devices to practices that do not currently have the support to make them. Electronic supplementary material The online version of this article (10.1186/s13014-019-1357-2) contains supplementary material, which is available to authorized users.

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BackgroundOur primary aim was to assess the ability of a non-profit foundation-sponsored clinic network to facilitate access to specialized care for patients with neurofibromatoses (NF), a group of neurogenetic disorders including NF1, NF2, and schwannomatosis (SWN). Our secondary aim was to identify how our findings in NF could be applied more broadly to other rare diseases.MethodsWe retrospectively reviewed aggregate data on patient volume reported by specialty NF clinics in a nonprofit network from 2008 to 2015. We classified clinics as high or low volume for disease type (NF1 and NF2/schwannomatosis) and pediatric/adult care. We compared clinic-level data to self-reported patient-level data from a large online patient registry.ResultsBetween 2008 and 2015, the number of certified NF clinics grew from 32 to 50, and annual patient volume rose from 6776 to 10,245 patients (13% of the total estimated U.S. NF patient population). For patient registry participants (n = 4476), the median driving distance to the nearest network clinic was 51.3 miles. Driving distances to reach high-volume centers were elevated for adults compared to children (295.8 vs. 67.9 miles), and schwannomatosis and NF2 patients compared to NF1 patients (310.9 vs. 368.1 vs. 161.7 miles). Of registry participants reporting their location of care (n = 2271), only 43.2% received care in a network specialty clinic, with especially low rates of attendance in the Southwest and Far West.ConclusionsWhile the number of certified NF clinics and volume of patients seen in these clinics has increased, many NF patients still do not attend specialty clinics and/or travel a significant distance for care. Geographic access to care is more limited for adults, patients with rarer conditions, and patients in the Western U.S. Potential measures to improve access to specialty care for people living with NF and other rare diseases are discussed.

Previously, we characterized qualitative imaging-based subtypes of pancreatic ductal adenocarcinoma (PDAC) on computed tomography (CT) scans. Conspicuous (high delta) PDAC tumors are more likely to have aggressive biology and poorer clinical outcomes compared to inconspicuous (low delta) tumors. Here, we developed a quantitative classification of this imaging-based subtype (quantitative delta; q-delta). Retrospectively, baseline pancreatic protocol CT scans of three cohorts (cohort#1 = 101, cohort#2 = 90 and cohort#3 = 16 [external validation]) of patients with PDAC were qualitatively classified into high and low delta. We used a voxel-based method to volumetrically quantify tumor enhancement while referencing normal-pancreatic-parenchyma and used machine learning-based analysis to build a predictive model. In addition, we quantified the stromal content using hematoxylin- and eosin-stained treatment-naïve PDAC sections. Analyses revealed that PDAC quantitative enhancement values are predictive of the qualitative delta scoring and were used to build a classification model (q-delta). Compared to high q-delta, low q-delta tumors were associated with improved outcomes, and the q-delta class was an independent prognostic factor for survival. In addition, low q-delta tumors had higher stromal content and lower cellularity compared to high q-delta tumors. Our results suggest that q-delta classification provides a clinically and biologically relevant tool that may be integrated into ongoing and future clinical trials.

Poly(N‐isopropylacrylamide) (PNIPAAm) has been a well‐known stimuli–responsive material and has been used in multiple novel applications. One of the key attributes to make the hydrogel more attractive is to control the response time and temperature. This work focused on comparing the physical properties, such as response time, transition temperature, heat of fusion, and mechanical strength, of macroporous and microporous PNIPAAm hydrogels, respectively. It was found that the macroporous hydrogels synthesized from a low‐temperature polymerization with addition of tetramethyl orthosilicate exhibited a faster response time and superior mechanical strength. Furthermore, to modulate the transition temperature, both the macroporous and microporous hydrogels were subjected to different qualities of media by introducing a cosolvent (methanol) or an anionic surfactant (sodium dodecyl sulfate). Interestingly, addition of a cosolvent demonstrated a more pronounced effect on the macroporous hydrogel, whereas the surfactant resulted in a more pronounced effect on the microporous hydrogel. Such results revealed that based on their porosity; there were appreciable differences when the PNIPAAm hydrogels interacted with media molecules. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42776.

BackgroundPreviously, we characterized subtypes of pancreatic ductal adenocarcinoma (PDAC) on computed-tomography (CT) scans, whereby conspicuous (high delta) PDAC tumors are more likely to have aggressive biology and poorer clinical outcomes compared to inconspicuous (low delta) tumors. Here, we hypothesized that these imaging-based subtypes would exhibit different growth-rates and distinctive metabolic effects in the period prior to PDAC diagnosis.Materials and methodsRetrospectively, we evaluated 55 patients who developed PDAC as a second primary cancer and underwent serial pre-diagnostic (T0) and diagnostic (T1) CT-scans. We scored the PDAC tumors into high and low delta on T1 and, serially, obtained the biaxial measurements of the pancreatic lesions (T0-T1). We used the Gompertz-function to model the growth-kinetics and estimate the tumor growth-rate constant (α) which was used for tumor binary classification, followed by cross-validation of the classifier accuracy. We used maximum-likelihood estimation to estimate initiation-time from a single cell (10-6 mm3) to a 10 mm3 tumor mass. Finally, we serially quantified the subcutaneous-abdominal-fat (SAF), visceral-abdominal-fat (VAF), and muscles volumes (cm3) on CT-scans, and recorded the change in blood glucose (BG) levels. T-test, likelihood-ratio, Cox proportional-hazards, and Kaplan-Meier were used for statistical analysis and p-value &lt;0.05 was considered significant.ResultsCompared to high delta tumors, low delta tumors had significantly slower average growth-rate constants (0.024 month−1 vs. 0.088 month−1, p&lt;0.0001) and longer average initiation-times (14 years vs. 5 years, p&lt;0.0001). α demonstrated high accuracy (area under the curve (AUC)=0.85) in classifying the tumors into high and low delta, with an optimal cut-off of 0.034 month−1. Leave-one-out-cross-validation showed 80% accuracy in predicting the delta-class (AUC=0.84). High delta tumors exhibited accelerated SAF, VAF, and muscle wasting (p &lt;0.001), and BG disturbance (p&lt;0.01) compared to low delta tumors. Patients with low delta tumors had better PDAC-specific progression-free survival (log-rank, p&lt;0.0001), earlier stage tumors (p=0.005), and higher likelihood to receive resection after PDAC diagnosis (p=0.008), compared to those with high delta tumors.ConclusionImaging-based subtypes of PDAC exhibit distinct growth, metabolic, and clinical profiles during the pre-diagnostic period. Our results suggest that heterogeneous disease biology may be an important consideration in early detection strategies for PDAC.

INTRODUCTION: Studies have demonstrated health benefits of caffeine consumption, including decrease in cardiovascular disease, diabetes, and liver diseases. The exact mechanisms are not known. Caffeine consumption may possibly modulate the gut microbiome and therefore affect health and disease risk. We examined the association between caffeine consumption and the composition and structure of the colonic-gut microbiota. METHODS: In this study, 34 participants underwent a screening colonoscopy and had endoscopically normal colons. We obtained a total of 97 snap-frozen colonic mucosa biopsies from various segments of colon from these individuals. Microbial DNA was extracted, and subsequently amplified for the 16S rRNA gene V4 region and sequenced using the Illumina MiSeq platform. We analyzed the sequencing data using the UPARSE and SILVA database for operational taxonomic unit (OTU) classification. Self-administered BLOCK Food Frequency Questionnaire was used to ascertain daily caffeine consumption. We compared the diversity and relative abundance of bacterial taxonomies by high (≥82.9 mg) vs. low (<82.9 mg) consumption of caffeine. False discover rate (FDR) P-values were reported and <0.05 indicated statistical significance. RESULTS: The alpha diversity was the greatest in high caffeine consumers (Shannon index P < 0.0001). The beta diversity differed significantly between high vs. low caffeine drinkers (P = 0.0001). The composition of microbiomes did not differ at the phylum level based on caffeine consumption. At the genus level, high caffeine consumption was associated with increased relative abundance of Faecalibacterium (P < 0.0005) and Roseburia (P = 0.02), but decreased levels of Erysipelatoclostridium (P value <0.001) and an OTU belonging to the Lachnospiraceae family (Unc8895) (P < 0.0005). The observed association was seen regardless of age and dietary quality. Other bacteria commonly detected in gut microbiomes, including Odoribacter, Dialister, Fusicatenibactor, Alistipes, Blautia, and multiple members of Lachnospiraceae, were significantly more abundant (P < 0.05) in participants with higher caffeine consumption (Table 1). CONCLUSION: Higher caffeine consumption was associated with increased richness and evenness of the mucosa-associated gut microbiota, and higher relative abundance of anti-inflammatory bacteria, such as Faecalibacterium and Roseburia and lower levels of potentially harmful Erysipelatoclostridium.

While schwannoma is one of the most common types of benign peripheral nerve tumors in adults, a very unique and specific variant of schwannoma, the intravascular variant, is exceedingly rare. There have only been three previously published cases of intravascular schwannomas. Here we describe a fourth case of an intravascular schwannoma in a 47‐year‐old man with an enlarging subcutaneous nodule on his posterior calf. This is the second case of an intravascular schwannoma contained within a vein. Also included is an overview of intravascular schwannomas, including a description and discussion of the histopathological diagnosis, differential diagnoses, and schwannoma variants.