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Background: Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction.Methods: In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly (ε-caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses.Results: The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group.Conclusion: Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.

Abstract Exact placement of bone conduction implants requires avoidance of critical structures. Existing guidance technologies for intraoperative placement have lacked widespread adoption given accessibility challenges and significant cognitive loading. The purpose of this study is to examine the application of augmented reality (AR) guided surgery on accuracy, duration, and ease on bone conduction implantation. Five surgeons surgically implanted two different types of conduction implants on cadaveric specimens with and without AR projection. Pre- and postoperative computer tomography scans were superimposed to calculate centre-to-centre distances and angular accuracies. Wilcoxon signed-rank testing was used to compare centre-to-centre (C-C) and angular accuracies between the control and experimental arms. Additionally, projection accuracy was derived from the distance between the bony fiducials and the projected fiducials using image guidance coordinates. Both operative time (4.3 ± 1.2 min. vs. 6.6 ± 3.5 min., p = 0.030) and centre-to-centre distances surgery (1.9 ± 1.6 mm vs. 9.0 ± 5.3 mm, p

Abstract Background Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. Methods Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. Results Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 [p

Abstract Background Current sentinel lymph node biopsy (SLNB) techniques, including use of radioisotopes, have disadvantages including the use of a radioactive tracer. Indocyanine green (ICG) based near-infrared (NIR) fluorescence imaging and cone beam CT (CBCT) have advantages for intraoperative use. However, limited literature exists regarding their use in head and neck cancer SLNB. Methods This was a prospective, non-randomized study using a rabbit oral cavity VX2 squamous cell carcinoma model (n = 10) which develops lymph node metastasis. Pre-operatively, images were acquired by MicroCT. During surgery, CBCT and NIR fluorescence imaging of ICG was used to map and guide the SLNB resection. Results Intraoperative use of ICG to guide fluorescence resection resulted in identification of all lymph nodes identified by pre-operative CT. CBCT was useful for near real time intraoperative imaging and 3D reconstruction. Conclusions This pre-clinical study further demonstrates the technical feasibility, limitations and advantages of intraoperative NIR-guided ICG imaging for SLN identification as a complementary method during head and neck surgery.

ObjectiveTo report the first use of a novel projected augmented reality (AR) system in open sinonasal tumor resections in preclinical models and to compare the AR approach with an advanced intraoperative navigation (IN) system.MethodsFour tumor models were created. Five head and neck surgeons participated in the study performing virtual osteotomies. Unguided, AR, IN, and AR + IN simulations were performed. Statistical comparisons between approaches were obtained. Intratumoral cut rate was the main outcome. The groups were also compared in terms of percentage of intratumoral, close, adequate, and excessive distances from the tumor. Information on a wearable gaze tracker headset and NASA Task Load Index questionnaire results were analyzed as well.ResultsA total of 335 cuts were simulated. Intratumoral cuts were observed in 20.7%, 9.4%, 1.2,% and 0% of the unguided, AR, IN, and AR + IN simulations, respectively (p

BackgroundThe resection of advanced maxillary sinus cancers can be challenging due to the anatomical proximity to surrounding critical anatomical structures. Transnasal endoscopy can effectively aid the delineation of the posterior margin of resection. Implementation with 3D-rendered surgical navigation with virtual endoscopy (3D-SNVE) may represent a step forward. This study aimed to demonstrate and quantify the benefits of this technology.Material and MethodFour maxillary tumor models with critical posterior extension were created in four artificial skulls (Sawbones®). Images were acquired with cone-beam computed tomography and the tumor and carotid were contoured. Eight head and neck surgeons were recruited for the simulations. Surgeons delineated the posterior margin of resection through a transnasal approach and avoided the carotid while establishing an adequate resection margin with respect to tumor extirpation. Three simulations were performed: 1) unguided: based on a pre-simulation study of cross-sectional imaging; 2) tumor-guided: guided by real-time tool tracking with 3D tumor and carotid rendering; 3) carotid-guided: tumor-guided with a 2-mm alert cloud surrounding the carotid. Distances of the planes from the carotid and tumor were classified as follows and the points of the plane were classified accordingly: “red”: through the carotid artery; “orange”: 2 mm from the carotid and within the tumor or 2 mm from the carotid and 5–10 mm from the tumor; and “blue”: >2 mm from the carotid and >10 mm from the tumor. The three techniques (unguided, tumor-guided, and carotid-guided) were compared.Results3D-SNVE for the transnasal delineation of the posterior margin in maxillary tumor models significantly improved the rate of margin-negative clearance around the tumor and reduced damage to the carotid artery. “Green” cuts occurred in 52.4% in the unguided setting versus 62.1% and 64.9% in the tumor- and carotid-guided settings, respectively (p < 0.0001). “Red” cuts occurred 6.7% of the time in the unguided setting versus 0.9% and 1.0% in the tumor- and carotid-guided settings, respectively (p < 0.0001).ConclusionsThis preclinical study has demonstrated that 3D-SNVE provides a substantial improvement of the posterior margin delineation in terms of safety and oncological adequacy. Translation into the clinical setting, with a meticulous assessment of the oncological outcomes, will be the proposed next step.

Objective(s): The purpose of this study was to compare computer‐assisted mandibular plating to conventional plating using quantitative metrics. Methods: Patients scheduled to undergo mandibular reconstruction were randomized to three‐dimensional modelling for preoperative plate bending or intraoperative freehand bending. Preoperative and postoperative head and neck computed tomography scans were obtained to generate computer models of the reconstruction. The overall plate surface contact area, mean plate‐to‐bone distance, degree of conformance, and position of the condylar head within the glenoid fossa between pre‐ and post‐operative scans were calculated. Results: Twenty patients were included with a mean age of 57.8 years (standard deviation [SD] = 13.6). The mean follow‐up time was 9.8 months (range = 1.6–22.3). Reconstruction was performed with fibular (25%) or scapular free flaps (75%). The percentage of surface contact between the reconstructive plate and mandible was improved with three‐dimensional models compared to freehand bending (93.9 ± 7.7% vs. 78.0 ± 19.9%, p = 0.04). There was improved overall plate‐to‐bone distance (3D model: 0.7 ± 0.31 mm vs. conventional: 1.3 ± 0.8 mm, p = 0.06). Total intraoperative time was non‐significantly decreased with the use of a model (3D model: 726.5 ± 89.1 min vs. conventional: 757.3 ± 84.1 min, p = 0.44). There were no differences in condylar head position or postoperative complications. Conclusion: Computer‐assisted mandibular plating can be used to improve the accuracy of plate contouring. Level of Evidence: 2 Laryngoscope, 134:2182–2186, 2024 [ABSTRACT FROM AUTHOR]

The bacterium Caulobacter crescentus and related stalk bacterial species are known for their distinctive ability to live in low nutrient environments, a characteristic of most heavy metal contaminated sites. Caulobacter crescentus is a model organism for studying cell cycle regulation with well developed genetics. We have identified the pathways responding to heavy metal toxicity in C. crescentus to provide insights for possible application of Caulobacter to environmental restoration. We exposed C. crescentus cells to four heavy metals (chromium, cadmium, selenium and uranium) and analyzed genome wide transcriptional activities post exposure using a Affymetrix GeneChip microarray. C. crescentus showed surprisingly high tolerance to uranium, a possible mechanism for which may be formation of extracellular calcium-uranium-phosphate precipitates. The principal response to these metals was protection against oxidative stress (up-regulation of manganese-dependent superoxide dismutase, sodA). Glutathione S-transferase, thioredoxin, glutaredoxins and DNA repair enzymes responded most strongly to cadmium and chromate. The cadmium and chromium stress response also focused on reducing the intracellular metal concentration, with multiple efflux pumps employed to remove cadmium while a sulfate transporter was down-regulated to reduce non-specific uptake of chromium. Membrane proteins were also up-regulated in response to most of the metals tested. A two-component signal transduction system involved in the uranium response was identified. Several differentially regulated transcripts from regions previously not known to encode proteins were identified, demonstrating the advantage of evaluating the transcriptome using whole genome microarrays.

Background Existing predictive outcomes models for type 2 diabetes developed and validated in historical European populations may not be applicable for East Asian populations due to differences in the epidemiology and complications. Despite the continuum of risk across the spectrum of risk factor values, existing models are typically limited to diabetes alone and ignore the progression from prediabetes to diabetes. The objective of this study is to develop and externally validate a patient-level simulation model for prediabetes and type 2 diabetes in the East Asian population for predicting lifetime health outcomes. Methods and findings We developed a health outcomes model from a population-based cohort of individuals with prediabetes or type 2 diabetes: Hong Kong Clinical Management System (CMS, 97,628 participants) from 2006 to 2017. The Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model comprises of 13 risk equations to predict mortality, micro- and macrovascular complications, and development of diabetes. Risk equations were derived using parametric proportional hazard models. External validation of the CHIME model was assessed in the China Health and Retirement Longitudinal Study (CHARLS, 4,567 participants) from 2011 to 2018 for mortality, ischemic heart disease, cerebrovascular disease, renal failure, cataract, and development of diabetes; and against 80 observed endpoints from 9 published trials using 100,000 simulated individuals per trial. The CHIME model was compared to United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS-OM2) and Risk Equations for Complications Of type 2 Diabetes (RECODe) by assessing model discrimination (C-statistics), calibration slope/intercept, root mean square percentage error (RMSPE), and R.sup.2 . CHIME risk equations had C-statistics for discrimination from 0.636 to 0.813 internally and 0.702 to 0.770 externally for diabetes participants. Calibration slopes between deciles of expected and observed risk in CMS ranged from 0.680 to 1.333 for mortality, myocardial infarction, ischemic heart disease, retinopathy, neuropathy, ulcer of the skin, cataract, renal failure, and heart failure; 0.591 for peripheral vascular disease; 1.599 for cerebrovascular disease; and 2.247 for amputation; and in CHARLS outcomes from 0.709 to 1.035. CHIME had better discrimination and calibration than UKPDS-OM2 in CMS (C-statistics 0.548 to 0.772, slopes 0.130 to 3.846) and CHARLS (C-statistics 0.514 to 0.750, slopes -0.589 to 11.411); and small improvements in discrimination and better calibration than RECODe in CMS (C-statistics 0.615 to 0.793, slopes 0.138 to 1.514). Predictive error was smaller for CHIME in CMS (RSMPE 3.53% versus 10.82% for UKPDS-OM2 and 11.16% for RECODe) and CHARLS (RSMPE 4.49% versus 14.80% for UKPDS-OM2). Calibration performance of CHIME was generally better for trials with Asian participants (RMSPE 0.48% to 3.66%) than for non-Asian trials (RMPSE 0.81% to 8.50%). Main limitations include the limited number of outcomes recorded in the CHARLS cohort, and the generalizability of simulated cohorts derived from trial participants. Conclusions Our study shows that the CHIME model is a new validated tool for predicting progression of diabetes and its outcomes, particularly among Chinese and East Asian populations that has been lacking thus far. The CHIME model can be used by health service planners and policy makers to develop population-level strategies, for example, setting HbA1c and lipid targets, to optimize health outcomes., Author(s): Jianchao Quan 1, Carmen S. Ng 1,*, Harley H. Y. Kwok 1, Ada Zhang 2, Yuet H. Yuen 1, Cheung-Hei Choi 3, Shing-Chung Siu 4, Simon Y. Tang 5, [...]

Indocyanine green (ICG) is the only near‐infrared (NIR) dye approved for clinical use. Despite its versatility in photonic applications and potential for photothermal therapy, its photobleaching hinders its application. Here we discovered a nanostructure of dimeric ICG (Nano‐dICG) generated by using ICG to stabilize nanoemulsions, after which ICG enabled complete dimerization on the nanoemulsion shell, followed by J‐aggregation of ICG‐dimer, resulting in a narrow, red‐shifted (780 nm→894 nm) and intense (≈2‐fold) absorbance. Compared to ICG, Nano‐dICG demonstrated superior photothermal conversion (2‐fold higher), significantly reduced photodegradation (−9.6 % vs. −46.3 %), and undiminished photothermal effect (7 vs. 2 cycles) under repeated irradiations, in addition to excellent colloidal and structural stabilities. Following intravenous injection, Nano‐dICG enabled real‐time tracking of its delivery to mouse tumors within 24 h by photoacoustic imaging at NIR wavelength (890 nm) distinct from the endogenous signal to guide effective photothermal therapy. The unprecedented finding of nanostructure‐driven ICG dimerization leads to an ultra‐stable phototheranostic platform. [ABSTRACT FROM AUTHOR]