Dental 3D-Printing: Transferring Art from the Laboratories to the Clinics.

The rise of three-dimensional (3D) printing technology has changed the face of dentistry over the past decade. 3D printing is a versatile technique that allows the fabrication of fully automated, tailor-made treatment plans, thereby delivering personalized dental devices and aids to the patients. It is highly efficient, reproducible, and provides fast and accurate results in an affordable manner. With persistent efforts among dentists for refining their practice, dental clinics are now acclimatizing from conventional treatment methods to a fully digital workflow to treat their patients. Apart from its clinical success, 3D printing techniques are now employed in developing haptic simulators, precise models for dental education, including patient awareness. In this narrative review, we discuss the evolution and current trends in 3D printing applications among various areas of dentistry. We aim to focus on the process of the digital workflow used in the clinical diagnosis of different dental conditions and how they are transferred from laboratories to clinics. A brief outlook on the most recent manufacturing methods of 3D printed objects and their current and future implications are also discussed.

Biomimetic Aspects of Oral and Dentofacial Regeneration.

Biomimetic materials for hard and soft tissues have advanced in the fields of tissue engineering and regenerative medicine in dentistry. To examine these recent advances, we searched Medline (OVID) with the key terms "biomimetics", "biomaterials", and "biomimicry" combined with MeSH terms for "dentistry" and limited the date of publication between 2010-2020. Over 500 articles were obtained under clinical trials, randomized clinical trials, metanalysis, and systematic reviews developed in the past 10 years in three major areas of dentistry: restorative, orofacial surgery, and periodontics. Clinical studies and systematic reviews along with hand-searched preclinical studies as potential therapies have been included. They support the proof-of-concept that novel treatments are in the pipeline towards ground-breaking clinical therapies for orofacial bone regeneration, tooth regeneration, repair of the oral mucosa, periodontal tissue engineering, and dental implants. Biomimicry enhances the clinical outcomes and calls for an interdisciplinary approach integrating medicine, bioengineering, biotechnology, and computational sciences to advance the current research to clinics. We conclude that dentistry has come a long way apropos of regenerative medicine; still, there are vast avenues to endeavour, seeking inspiration from other facets in biomedical research.

What Is Known About the Psychodermatology Clinic Model of Care? A Systematic Scoping Review.

BACKGROUND: Psychodermatology focuses on the interaction between skin and mental health. Existing research discusses the recognition and treatment of these disorders. However, little is known about the operational structure of subspecialised psychodermatology clinics. OBJECTIVE: To identify literature on the structure and logistics of delivering a psychodermatology service. METHODS: A systematic search of MEDLINE, PsycINFO, Embase, and Google Scholar was performed. Articles were included if they discussed the concept and organisation of a psychodermatology practice. RESULTS: We identified 693 studies; after screening titles and abstracts, 35 full-text articles were assessed, and 17 were included in the scoping review. Most articles discussed aspects of clinic organisation in general; others discussed management of a clinic in the context of specific diseases or made recommendations on incorporating psychotherapeutic techniques in a solo practitioner setting. A weekly multidisciplinary clinic or resident teaching clinic with joint dermatologist-psychiatrist consultation is the most commonly reported model. Specifically, a stepped level of care approach is often used, where patients in increasing level of distress are stratified to the appropriate team of trained professionals. A corresponding curriculum to supplement practitioners' knowledge is recommended. CONCLUSIONS: Various clinic models have been described to provide specialised psychodermatology care in specific settings. Research is needed to assess the impact of these multidisciplinary models of care on patient outcomes and health care costs.

Comparison of the Treatment Guidelines for Actinic Keratosis: A Critical Appraisal and Review.

There are currently several reputable guidelines on the treatment of actinic keratosis (AK) from groups in Canada, the United Kingdom, and Europe. These recommendations, based on evidence or expert consensus, offer clinicians a variety of treatment options for the different clinical presentations of AKs. Although the guidelines are similar in some regards, variations exist in treatment options, duration, and strength of recommendation. Some guidelines also lack input on specific therapies and certain types of AK, such as hypertrophic or thin presentations. The purpose of this article is to review and compare guidelines published by Canadian, UK, and European groups for the management of AKs in patients.

Volume of Lytic Vertebral Body Metastatic Disease Quantified Using Computed Tomography-Based Image Segmentation Predicts Fracture Risk After Spine Stereotactic Body Radiation Therapy.

PURPOSE: To determine a threshold of vertebral body (VB) osteolytic or osteoblastic tumor involvement that would predict vertebral compression fracture (VCF) risk after stereotactic body radiation therapy (SBRT), using volumetric image-segmentation software. METHODS AND MATERIALS: A computational semiautomated skeletal metastasis segmentation process refined in our laboratory was applied to the pretreatment planning CT scan of 100 vertebral segments in 55 patients treated with spine SBRT. Each VB was segmented and the percentage of lytic and/or blastic disease by volume determined. RESULTS: The cumulative incidence of VCF at 3 and 12 months was 14.1% and 17.3%, respectively. The median follow-up was 7.3 months (range, 0.6-67.6 months). In all, 56% of segments were determined lytic, 23% blastic, and 21% mixed, according to clinical radiologic determination. Within these 3 clinical cohorts, the segmentation-determined mean percentages of lytic and blastic tumor were 8.9% and 6.0%, 0.2% and 26.9%, and 3.4% and 15.8% by volume, respectively. On the basis of the entire cohort (n=100), a significant association was observed for the osteolytic percentage measures and the occurrence of VCF (P<.001) but not for the osteoblastic measures. The most significant lytic disease threshold was observed at ≥11.6% (odds ratio 37.4, 95% confidence interval 9.4-148.9). On multivariable analysis, ≥11.6% lytic disease (P<.001), baseline VCF (P<.001), and SBRT with ≥20 Gy per fraction (P=.014) were predictive. CONCLUSIONS: Pretreatment lytic VB disease volumetric measures, independent of the blastic component, predict for SBRT-induced VCF. Larger-scale trials evaluating our software are planned to validate the results.

Synthesis and chemical reactivity of a 6-Me-3,2-hydroxypyridinone dithiazolide with primary amines: a route to new hexadentate chelators for hard metal(III) ions.

A hydroxypyridinone building block, bifunctionalized with thiazoline, has been prepared from orthogonally protected 2-(3-(benzyloxy)-4-(ethoxycarbonyl)-6-methyl-2-oxopyridin-1(2H)-yl) acetic acid. The reactivity of the dithiazolide has been explored with two primary amines, leading to the synthesis and characterization of four new hexadentate ligands. Their complexes with selected hard trivalent ions pertinent to potential molecular imaging applications have been surveyed.

The predictive capacity of apparent diffusion coefficient (ADC) in response assessment of brain metastases following radiation.

To investigate the predictive capacity of the apparent diffusion coefficient (ADC) as a biomarker of radiation response in brain metastases. Seventy brain metastases from 42 patients treated with either stereotactic radiosurgery or whole brain radiotherapy were imaged at baseline, 1 week, and 1 month post-treatment using diffusion-weighted MRI. Mean and median relative ADC for metastases was calculated by normalizing ADC measurements to baseline ADC. At 1 year post-treatment, or last available follow-up MRI, volume criteria determined final tumour response status. Uni- and multivariate analysis was used to account for factors associated with tumour response at 1 week and 1 month. A generalized estimating equations model took into consideration multiple tumours per subject. Optimal thresholds that distinguished responders from non-responders, as well as sensitivity and specificity were determined by receiver operator characteristic analysis and Youden's index. Lower relative ADC values distinguished responders from non-responders at 1 week and 1 month (P < 0.05). Optimal cut-off values for response were 1.060 at 1 week with a sensitivity and specificity of 75.0 and 56.3 %, respectively. At 1 month, the cut-off was 0.971 with a sensitivity and specificity of 70.0 and 68.8 %, respectively. A multivariate general estimating equations analysis identified no prior radiation [odds ratio (OR) 0.211 and 0.137, P = 0.033 and 0.0177], and a lower median relative ADC at 1 week and 1 month (OR 0.619 and 0.694, P = 0.0036 and 0.005), as predictors of tumour response. Lower relative ADC values at 1 week and 1 month following radiation distinguished responders from non-responders and may be a promising biomarker of early radiation response.

Quantitative evaluation of cell death response in vitro and in vivo using conventional-frequency ultrasound.

Previous studies using high-frequency ultrasound have suggested that radiofrequency (RF) spectral analysis can be used to quantify changes in cell morphology to detect cell death response to therapy non-invasively. The study here investigated this at conventional-frequencies, frequently used in clinical settings. Spectral analysis was performed using ultrasound RF data collected with a clinical ultrasound platform. Acute myeloid leukemia (AML-5) cells were exposed to cisplatinum for 0-72 hours in vitro and prepared for ultrasound data collection. Preclinical in vivo experiments were also performed on AML-5 tumour-bearing mice receiving chemotherapy. The mid-band fit (MBF) spectral parameter demonstrated an increase of 4.4 ± 1.5 dBr for in vitro samples assessed 48 hours after treatment, a statistically significant change (p < 0.05) compared to control. Further, in vitro concentration-based analysis of a mixture of apoptotic and untreated cells indicated a mean change of 10.9 ± 2.4 dBr in MBF between 0% and 40% apoptotic cell mixtures. Similar effects were reproduced in vivo with an increase of 4.6 ± 0.3 dBr in MBF compared to control, for tumours with considerable apoptotic areas within histological samples. The alterations in the size of cells and nuclei corresponded well with changes measured in the quantitative ultrasound (QUS) parameters.

Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy.

PURPOSE: It is now recognized that the tumor vasculature is in part responsible for regulating tumor responses to radiation therapy. However, the extent to which radiation-based vascular damage contributes to tumor cell death remains unknown. In this work, quantitative ultrasound spectroscopy (QUS) methods were used to investigate the acute responses of tumors to radiation-based vascular treatments. METHODS: Tumor xenografts (MDA-MB-231) were treated with single radiation doses of 2 or 8 Gy alone, or in combination with pharmacological agents that modulate vascular radiosensitivity. The midband fit, the slope, and the 0-MHz intercept QUS parameters were obtained from a linear-regression fit to the averaged power spectrum of frequency-dependent ultrasound backscatter and were used to quantify acute tumor responses following treatment administration. Power spectrums were extracted from raw volumetric radio-frequency ultrasound data obtained before and 24 h following treatment administration. These parameters have previously been correlated to tumor cell death. Staining using in situ end labeling, carbonic anhydrase 9 and cluster of differentiation 31 of tumor sections were used to assess cell death, oxygenation, and vasculature distributions, respectively. RESULTS: Results indicate a significant midband fit QUS parameter increases of 3.2 ± 0.3 dBr and 5.4 ± 0.5 dBr for tumors treated with 2 and 8 Gy radiation combined with the antiangiogenic agent Sunitinib, respectively. In contrast, tumors treated with radiation alone demonstrated a significant midband fit increase of 4.4 ± 0.3 dBr at 8 Gy only. Preadministration of basic fibroblast growth factor, an endothelial radioprotector, acted to minimize tumor response following single large doses of radiation. Immunohistochemical analysis was in general agreement with QUS findings; an R(2) of 0.9 was observed when quantified cell death was correlated with changes in midband fit. CONCLUSIONS: Results from QUS analysis presented in this study confirm that acute tumor response is linked to a vascular effect following high doses of radiation therapy. Overall, this is in agreement with previous reports suggesting that acute tumor radiation response is regulated by a vascular-driven response. Data also suggest that Sunitinib may enhance tumor radiosensitivity through a vascular remodeling process, and that QUS may be sensitive to changes in tissue properties associated with vascular remodeling. Finally, the work also demonstrates the ability of QUS methods to monitor response to radiation-based vascular strategies.

Risk of vertebral compression fracture specific to osteolytic renal cell carcinoma spinal metastases after stereotactic body radiotherapy: A multi-institutional study.

PURPOSE: Determine the risk of vertebral compression fracture (VCF) following stereotactic body radiotherapy (SBRT), specific to osteolytic renal cell carcinoma (RCC) spinal metastases, and associated predictive factors. METHODS: 187 RCC osteolytic spinal tumor segments in 116 patients obtained from a multi-institutional pooled database were reviewed. Each segment was evaluated according to the Spinal Instability Neoplastic Score (SINS). RESULTS: The median follow-up was 8.0 months. 34 VCF (34/187, 18%) were observed and median time to VCF was 2.4 months. VCF was observed in 43% (10/23), 24% (4/17) and 14% (20/147) of segments treated with 24Gy/fraction (fx), 20-23Gy/fx and ≤19Gy/fx, respectively. Multivariate analysis identified dose per fx (p=0.005), baseline VCF (p<0.001) and spinal misalignment (p=0.002) as predictors of VCF. Prior conventional radiotherapy (p=0.029) was found to be protective. CONCLUSIONS: 18% of osteolytic RCC spinal metastases fractured post-SBRT. The presence of a baseline fracture, spinal mal-alignment and treatment with ≥20Gy/fx predicted for VCF.