Indocyanine green fluorescence quantification during normothermic ex situ perfusion for the assessment of porcine liver grafts after circulatory death.

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.

Does Freehand, Patient-specific Instrumentation or Surgical Navigation Perform Better for Allograft Reconstruction After Tumor Resection? A Preclinical Synthetic Bone Study.

BACKGROUND: Joint-sparing resection of periarticular bone tumors can be challenging because of complex geometry. Successful reconstruction of periarticular bone defects after tumor resection is often performed with structural allografts to allow for joint preservation. However, achieving a size-matched allograft to fill the defect can be challenging because allograft sizes vary, they do not always match a patient's anatomy, and cutting the allograft to perfectly fit the defect is demanding. QUESTIONS/PURPOSES: (1) Is there a difference in mental workload among the freehand, patient-specific instrumentation, and surgical navigation approaches? (2) Is there a difference in conformance (quantitative measure of deviation from the ideal bone graft), elapsed time during reconstruction, and qualitative assessment of goodness-of-fit of the allograft reconstruction among the approaches? METHODS: Seven surgeons used three modalities in the same order (freehand, patient-specific instrumentation, and surgical navigation) to fashion synthetic bone to reconstruct a standardized bone defect. National Aeronautics and Space Administration (NASA) mental task load index questionnaires and procedure time were captured. Cone-beam CT images of the shaped allografts were used to measure conformance (quantitative measure of deviation from the ideal bone graft) to a computer-generated ideal bone graft model. Six additional (senior) surgeons blinded to modality scored the quality of fit of the allografts into the standardized tumor defect using a 10-point Likert scale. We measured conformance using the root-mean-square metric in mm and used ANOVA for multipaired comparisons (p < 0.05 was significant). RESULTS: There was no difference in mental NASA total task load scores among the freehand, patient-specific instrumentation, and surgical navigation techniques. We found no difference in conformance root-mean-square values (mean ± SD) between surgical navigation (2 ± 0 mm; mean values have been rounded to whole numbers) and patient-specific instrumentation (2 ± 1 mm), but both showed a small improvement compared with the freehand approach (3 ± 1 mm). For freehand versus surgical navigation, the mean difference was 1 mm (95% confidence interval [CI] 0.5 to 1.1; p = 0.01). For freehand versus patient-specific instrumentation, the mean difference was 1 mm (95% CI -0.1 to 0.9; p = 0.02). For patient-specific instrumentation versus surgical navigation, the mean difference was 0 mm (95% CI -0.5 to 0.2; p = 0.82). In evaluating the goodness of fit of the shaped grafts, we found no clinically important difference between surgical navigation (median [IQR] 7 [6 to 8]) and patient-specific instrumentation (median 6 [5 to 7.8]), although both techniques had higher scores than the freehand technique did (median 3 [2 to 4]). For freehand versus surgical navigation, the difference of medians was 4 (p < 0.001). For freehand versus patient-specific instrumentation, the difference of medians was 3 (p < 0.001). For patient-specific instrumentation versus surgical navigation, the difference of medians was 1 (p = 0.03). The mean ± procedural times for freehand was 16 ± 10 minutes, patient-specific instrumentation was 14 ± 9 minutes, and surgical navigation techniques was 24 ± 8 minutes. We found no differences in procedures times across three shaping modalities (freehand versus patient-specific instrumentation: mean difference 2 minutes [95% CI 0 to 7]; p = 0.92; freehand versus surgical navigation: mean difference 8 minutes [95% CI 0 to 20]; p = 0.23; patient-specific instrumentation versus surgical navigation: mean difference 10 minutes [95% CI 1 to 19]; p = 0.12). CONCLUSION: Based on surgical simulation to reconstruct a standardized periarticular bone defect after tumor resection, we found a possible small advantage to surgical navigation over patient-specific instrumentation based on qualitative fit, but both techniques provided slightly better conformance of the shaped graft for fit into the standardized post-tumor resection bone defect than the freehand technique did. To determine whether these differences are clinically meaningful requires further study. The surgical navigation system presented here is a product of laboratory research development, and although not ready to be widely deployed for clinical practice, it is currently being used in a research operating room setting for patient care. This new technology is associated with a learning curve, capital costs, and potential risk. The reported preliminary results are based on a preclinical synthetic bone tumor study, which is not as realistic as actual surgical scenarios. CLINICAL RELEVANCE: Surgical navigation systems are an emerging technology in orthopaedic and reconstruction surgery, and understanding their capabilities and limitations is paramount for clinical practice. Given our preliminary findings in a small cohort study with one scenario of standardized synthetic periarticular bone tumor defects, future investigations should include different surgical scenarios using allograft and cadaveric specimens in a more realistic surgical setting.

Nanostructure-Driven Indocyanine Green Dimerization Generates Ultra-Stable Phototheranostics Nanoparticles.

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.

Hybrid Core-Shell Polymer Scaffold for Bone Tissue Regeneration.

A great promise for tissue engineering is represented by scaffolds that host stem cells during proliferation and differentiation and simultaneously replace damaged tissue while maintaining the main vital functions. In this paper, a novel process was adopted to develop composite scaffolds with a core-shell structure for bone tissue regeneration, in which the core has the main function of temporary mechanical support, and the shell enhances biocompatibility and provides bioactive properties. An interconnected porous core was safely obtained, avoiding solvents or other chemical issues, by blending poly(lactic acid), poly(ε-caprolactone) and leachable superabsorbent polymer particles. After particle leaching in water, the core was grafted with a gelatin/chitosan hydrogel shell to create a cell-friendly bioactive environment within its pores. The physicochemical, morphological, and mechanical characterization of the hybrid structure and of its component materials was carried out by means of infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and mechanical testing under different loading conditions. These hybrid polymer devices were found to closely mimic both the morphology and the stiffness of bones. In addition, in vitro studies showed that the core-shell scaffolds are efficiently seeded by human mesenchymal stromal cells, which remain viable, proliferate, and are capable of differentiating towards the osteogenic phenotype if adequately stimulated.

Cell-free DNA and circulating tumor cell kinetics in a pre-clinical head and neck Cancer model undergoing radiation therapy.

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 < 0.05]), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation. CONCLUSION: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.

Assessment of a liposomal CT/optical contrast agent for image-guided head and neck surgery.

This study evaluates a long-acting liposomal fluorescence / CT dual-modality contrast agent (CF800) in head and neck cancer to enhance intraoperative tumor demarcation with fluorescence imaging and cone-beam computed tomography (CBCT). CF800 was administered to 12 buccal cancer-bearing rabbits. Imaging was acquired at regular time points to quantify time-dependent contrast enhancement. Surgery was performed 5-7 days after, with intraoperative near-infrared fluorescence endoscopy and CBCT, followed by histological and ex-vivo fluorescence assessment. Tumor enhancement on CT was significant at 24, 96 and 120 hours. Volumetric analysis of tumor segmentation showed high correlation between CBCT and micro-CT. Fluorescence signal was apparent in both ex-vivo and in-vivo imaging. Histological correlation showed [100%] specificity for primary tumor. Sensitivity and specificity of CF800 in detecting nodal involvement require further investigation.CF800 is long acting and has dual function for CT and fluorescence contrast, making it an excellent candidate for image-guided surgery.

Comparing Contour Restoration of Mandibular Body Defects With Fibula, Iliac Crest, and Scapular Tip Flaps: A Conformance Virtual Study.

PURPOSE: The purpose of this study was to determine which of the most commonly used flaps restore contour more accurately in mandibular body reconstructions using conformance analyses and virtual measurements. METHODS: Using normal computed tomography (CT) scans and a 3D software, mandibular body defects were virtually created. "Single shot" and osteotomized fibula flaps (SS-FF and O-FF), iliac crest flaps (ICF) and scapular tip flaps (STF) were digitally harvested and coregistered to reconstruct those defects. Conformance analyses were performed by calculating the root mean square (RMS) for overall and contour conformance. RESULTS: Ten patients normal CT scans were included. The STF demonstrated improved overall conformance compared with the ICF, the SS-FF and the O-FF (RMS = 2.03 mm vs 4.53 mm vs 2.76 vs 2.37 mm, respectively; p<.001). Similar trends were seen for contour conformance in STF compared with the ICF and the SS-FF (RMS = 2.48 mm vs 4.50 mm vs 3.28 mm, respectively), whereas the O-FF performed better than STF (RMS = 1.85 mm vs 2.48 mm; p<.001). CONCLUSIONS: The osseous component of the STF resembles the mandibular body more accurately than the one in the ICF and FF without the need for an osteotomy. Future clinical studies can help to elucidate the clinical impact of these virtual findings.

Sentinel lymph node mapping using ICG fluorescence and cone beam CT - a feasibility study in a rabbit model of oral cancer.

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.

Donor prone positioning protects lungs from injury during warm ischemia.

A large proportion of controlled donation after circulatory death (cDCD) donor lungs are declined because cardiac arrest does not occur within a suitable time after the withdrawal of life-sustaining therapy. Improved strategies to preserve lungs after asystole may allow the recovery team to arrive after death actually occurs and enable the recovery of lungs from more cDCD donors. The aim of this study was to determine the effect of donor positioning on the quality of lung preservation after cardiac arrest in a cDCD model. Cardiac arrest was induced by withdrawal of ventilation under anesthesia in pigs. After asystole, animals were divided into 2 groups based on body positioning (supine or prone). All animals were subjected to 3 hours of warm ischemia. After the observation period, donor lungs were explanted and preserved at 4°C for 6 hours, followed by 6 hours of physiologic and biological lung assessment under normothermic ex vivo lung perfusion. Donor lungs from the prone group displayed significantly greater quality as reflected by better function during ex vivo lung perfusion, less edema formation, less cell death, and decreased inflammation compared with the supine group. A simple maneuver of donor prone positioning after cardiac arrest significantly improves lung graft preservation and function.

Establishing Orbital Floor Symmetry to Support Mirror Imaging in Computer-Aided Reconstruction of the Orbital Floor.

BACKGROUND: Surgical precision in the reconstruction of the orbital floor is crucial to functional visual and aesthetic outcomes. Increasingly, computer-aided design is being utilized to aid in precise preoperative planning by using the mirror images of the unaffected side. The authors aim to use 3-dimensional (3D) quantitative analysis to establish whether the native orbital floor topography is sufficiently symmetric to support this practice. METHODS: Ten high resolution head and neck computed tomography scans of patients without periorbital pathology were obtained. These were imported into a 3D medical image processing software and segmented to isolate bilateral orbital floors. Each native orbital floor was compared to the mirror image of the contralateral side by conformance map computation. Data collection included measures of 25% and 75% quartile, median, mean, standard deviation, and root-mean-square (RMS). RESULTS: The topographic analysis demonstrated a high degree of topographic conformance with a mean RMS of 0.58 ±â€Š0.37 mm. Further volumetric analysis comparing the total orbital volume between each side also demonstrates a high degree of volumetric symmetry with a mean difference of 0.55 mL (P = 0.30). CONCLUSION: Comparison of the native orbital floor and the mirror image of the contralateral side by conformance map computation and volumetric analysis demonstrated a high degree of morphologic similarity. The native orbital floor topography provides optimal symmetry to support mirror imaging techniques used in orbital floor reconstruction.

Orbital Floor Reconstruction: 3-Dimensional Analysis Shows Comparable Morphology of Scapular and Iliac Crest Bone Grafts.

PURPOSE: Current nonvascular osseous reconstructive options for reconstruction of the orbital floor after maxillectomy include options such as scapular tip and iliac crest bone grafts. The aim of this study was to determine whether these donor sites were morphologically comparable with the orbital floor. MATERIALS AND METHODS: A retrospective cross-sectional study design was selected. By use of a pre-existing melanoma database (January 1, 2005, through September 20, 2015), computed tomography scans of the head, neck, thorax, and pelvis were obtained from patients without evidence of bony metastases. With the use of 3-dimensional software (Mimics; Materialise, Leuven, Belgium), grafts from the scapulae and iliac crests, the predictor variables, were digitally harvested, co-registered with the orbital floors bilaterally, and analyzed. The primary outcome was conformance. Data were analyzed using descriptive statistics and tests of statistical significance. The significance level was set at P<.05. RESULTS: The study sample included 10 patients (6 men and 4 women; mean age, 55 ± 18 years). Close conformance was observed when we analyzed the morphology of the orbital floor to the scapular (2.23 ± 0.31 mm) and iliac crest (2.13 ± 0.30 mm) bone grafts, with no significant difference between sites. Conformance mapping showed maximum conformance centrally (scapula, 0.001 ± 0.001 mm; iliac crest, 0.001 ± 0.001 mm), with decreased morphologic similarity peripherally (scapula, 6.09 ± 0.94 mm; iliac crest, 5.74 ± 0.88 mm). There was no significant difference in conformance between sides of graft harvest. CONCLUSIONS: When considering nonvascularized bone grafts for reconstruction of the orbital floor, both the scapula and iliac crest offer nearly complete conformance to the orbital floor structure and represent reasonable reconstructive options.

Development and face validation of a Virtual Reality Epley Maneuver System (VREMS) for home Epley treatment of benign paroxysmal positional vertigo: A randomized, controlled trial.

PURPOSE: To develop and validate a smartphone based Virtual Reality Epley Maneuver System (VREMS) for home use. METHODS: A smartphone application was designed to produce stereoscopic views of a Virtual Reality (VR) environment, which when viewed after placing a smartphone in a virtual reality headset, allowed the user to be guided step-by-step through the Epley maneuver in a VR environment. Twenty healthy participants were recruited and randomized to undergo either assisted Epleys or self-administered Epleys following reading instructions from an Instructional Handout (IH). All participants were filmed and two expert Otologists reviewed the videos, assigning each participant a score (out of 10) for performance on each step. Participants rated their perceived workload by completing a validated task-load questionnaire (NASA Task Load Index) and averages for both groups were calculated. RESULTS: Twenty participants were evaluated with average age 26.4±7.12years old in the VREMS group and 26.1±7.72 in the IH group. The VR assisted group achieved an average score of 7.78±0.99 compared to 6.65±1.72 in the IH group. This result was statistically significant with p=0.0001 and side dominance did not appear to play a factor. Analyzing each step of the Epley maneuver demonstrated that assisted Epleys were done more accurately with statically significant results in steps 2-4. Results of the NASA-TLX scores were variable with no significant findings. CONCLUSION: We have developed and demonstrated face validity for VREMS through our randomized controlled trial. The VREMS platform is promising technology, which may improve the accuracy and effectiveness of home Epley treatments. LEVEL OF EVIDENCE: N/A.

Nanoparticle-based sorting of circulating tumor cells by epithelial antigen expression during disease progression in an animal model.

Circulating tumor cells (CTCs) can be used as markers for the detection, characterization, and targeted therapeutic management of cancer. We recently developed a nanoparticle-mediated approach for capture and sorting of CTCs based on their specific epithelial phenotype. In the current study, we investigate the phenotypic transition of tumor cells in an animal model and show the correlation of this transition with tumor progression. VX2 tumor cells were injected into rabbits, and CTCs were evaluated during tumor progression and correlated with computerized tomography (CT) measurements of tumor volume. The results showed a dramatic increase of CTCs during the four weeks of tumor growth. Following resection, CTC levels dropped but then rebounded, likely due to lymph node metastases. Additionally, CTCs showed a marked loss of the epithelial cell adhesion molecule (EpCAM) relative to precursor cells. In conclusion, the device accurately traces disease progression and CTC phenotypic shift in an animal model. FROM THE CLINICAL EDITOR: The detection of circulating tumor cells (CTCs) has been used to predict disease prognosis. In this study, the authors developed a nanoparticle-mediated platform based on microfluidics to analyze the differential expressions of epithelial cell adhesion molecule (EpCAM) on CTCs in an animal model. It was found that the loss of EpCAM correlated with disease progression. Hence, the use of this platform may be further applied in other cancer models in the future.

A 3D Analysis of Plating Strategies in Mandibular Reconstruction: A Randomized Control Pilot Study.

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.

Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models.

Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumor cells by activating the cytotoxicity of photosensitizer dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitizer-containing building blocks (∼94,000 photosensitizers per particle) and capable of potent PDT. In this study, we demonstrate the selective uptake and curative tumor ablation of PS-enabled PDT in three preclinical models of oral cavity squamous cell carcinoma (OCSCC): biologically relevant subcutaneous Cal-33 (cell line) and MOC22 (syngeneic) mouse models, and an anatomically relevant orthotopic VX-2 rabbit model. Tumors selectively uptake PS (10 mg/kg, i.v.) with 6-to 40-fold greater concentration versus muscle 24 hours post-injection. Single PS nanoparticle-mediated PDT (PS-PDT) treatment (100 J/cm2, 100 mW/cm2) of Cal-33 tumors yielded significant apoptosis in 65.7% of tumor cells. Survival studies following PS-PDT treatments demonstrated 90% (36/40) overall response rate across all three tumor models. Complete tumor response was achieved in 65% of Cal-33 and 91% of MOC22 tumor mouse models 14 days after PS-PDT, and partial responses obtained in 25% and 9% of Cal-33 and MOC22 tumors, respectively. In buccal VX-2 rabbit tumors, combined surface and interstitial PS-PDT (200 J total) yielded complete responses in only 60% of rabbits 6 weeks after a single treatment whereas three repeated weekly treatments with PS-PDT (200 J/week) achieved complete ablation in 100% of tumors. PS-PDT treatments were well tolerated by animals with no treatment-associated toxicities and excellent cosmetic outcomes. SIGNIFICANCE: PS-PDT is a safe and repeatable treatment modality for OCSCC ablation. PS demonstrated tumor selective uptake and PS-PDT treatments achieved reproducible efficacy and effectiveness in multiple tumor models superior to other clinically tested photosensitizer drugs. Cosmetic and functional outcomes were excellent, and no clinically significant treatment-associated toxicities were detected. These results are enabling of window of opportunity trials for fluorescence-guided PS-PDT in patients with early-stage OCSCC scheduled for surgery.

Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects.

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.

Surgeons blinded by enhanced navigation: the effect of augmented reality on attention.

BACKGROUND: Advanced image-guidance systems allowing presentation of three-dimensional navigational data in real time are being developed enthusiastically for many medical procedures. Other industries, including aviation and the military, have noted that shifting attention toward such compelling assistance has detrimental effects. Using the detection rate of unexpected findings, we assess whether inattentional blindness is significant in a surgical context and evaluate the impact of on-screen navigational cuing with augmented reality. METHODS: Surgeons and trainees performed an endoscopic navigation exercise on a cadaveric specimen. The subjects were randomized to either a standard endoscopic view (control) or an AR view consisting of an endoscopic video fused with anatomic contours. Two unexpected findings were presented in close proximity to the target point: one critical complication and one foreign body (screw). Task completion time, accuracy, and recognition of findings were recorded. RESULTS: Detection of the complication was 0/15 in the AR group versus 7/17 in the control group (p = 0.008). Detection of the screw was 1/15 (AR) and 7/17 (control) (p = 0.041). Recognition of either finding was 12/17 for the control group and 1/15 for the AR group (p < 0.001). Accuracy was greater for the AR group than for the control group, with the median distance from the target point measuring respectively 2.10 mm (interquartile range [IQR], 1.29-2.37) and 4.13 (IQR, 3.11-7.39) (p < 0.001). CONCLUSION: Inattentional blindness was evident in both groups. Although more accurate, the AR group was less likely to identify significant unexpected findings clearly within view. Advanced navigational displays may increase precision, but strategies to mitigate attentional costs need further investigation to allow safe implementation.

Using augmented reality to guide bone conduction device implantation.

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 < 0.001) were significantly less in augmented reality guided surgery. The difference in angular accuracy, however, was not significantly different. The overall average distance between the bony fiducial markings and the AR projected fiducials was 1.7 ± 0.6 mm. With direct intraoperative reference, AR-guided surgery enhances bone conduction implant placement while reduces operative time when compared to conventional surgical planning.

Skull-Base Surgery-A Narrative Review on Current Approaches and Future Developments in Surgical Navigation.

Surgical navigation technology combines patient imaging studies with intraoperative real-time data to improve surgical precision and patient outcomes. The navigation workflow can also include preoperative planning, which can reliably simulate the intended resection and reconstruction. The advantage of this approach in skull-base surgery is that it guides access into a complex three-dimensional area and orients tumors intraoperatively with regard to critical structures, such as the orbit, carotid artery and brain. This enhances a surgeon's capabilities to preserve normal anatomy while resecting tumors with adequate margins. The aim of this narrative review is to outline the state of the art and the future directions of surgical navigation in the skull base, focusing on the advantages and pitfalls of this technique. We will also present our group experience in this field, within the frame of the current research trends.

Assessment of effectiveness and safety of thrombolytic therapy to pulmonary emboli by endobronchial ultrasound-guided transbronchial needle injection.

Objective: Endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) may effectively treat acute pulmonary embolisms (PEs). Here, we assessed the effectiveness of clot dissolution and safety of tissue plasminogen activator (t-PA) injection using EBUS-TBNI in a 1-week survival study of a porcine PE model. Methods: Six pigs with bilateral PEs were used: 3 for t-PA injection using EBUS-TBNI (TBNI group) and 3 for systemic administration of t-PA (systemic group). Once bilateral PEs were created, each 25 mg of t-PA injection using EBUS-TBNI for bilateral PEs (a total of 50 mg t-PA) and 100 mg of t-PA systemic administration was performed on day 1. Hemodynamic parameters, blood tests, and contrast-enhanced computed tomography scans were carried out at several time points. On day 7, pigs were humanely killed to evaluate the residual clot volume in the pulmonary arteries. Results: The average of percent change of residual clot volumes was significantly lower in the TBNI group than in the systemic group (%: systemic group 36.6 ± 22.6 vs TBNI group 9.6 ± 6.1, P < .01) on day 3. Considering the elapsed time, the average decrease of clot volume per hour at pre-t-PA to post t-PA was significantly greater in the TBNI group than in the systemic group (mm3/hour: systemic 68.1 ± 68.1 vs TBNI 256.8 ± 148.1, P < .05). No hemorrhage was observed intracranially, intrathoracically, or intraperitoneally on any contrast-enhanced computed tomography images. Conclusions: This study revealed that t-PA injection using EBUS-TBNI is an effective and safe way to dissolve clots.