Combined Techniques for Bilateral Maxillary and Nasal Reconstruction After Ablative Surgery for Adenoid Cystic Carcinoma

Indolent tumor growth up to large tumor masses and broad infiltration of surrounding tissue are the most typical characteristics of malignant tumors of the nasal cavity and paranasal sinuses. If surgery is a therapeutic option, extended resections and complex reconstruction modalities have to be taken into account. We present a combination of different reconstruction techniques to restore midface integrity after bilateral maxillectomy, including parts of the nasal skeleton, for adenoid cystic carcinoma. After obtaining tumor-free margins, reconstruction was performed using a microvascular double-flap technique to achieve a neo-maxilla and soft tissue lining of the oral cavity, dental implantology with prosthetic restoration and the insertion of a patient-specific implant for nasal re-shaping and stability. In cases of extended maxillary resection, a combination of different techniques can achieve sufficient functional and aesthetic rehabilitation, and restore quality of life. Further studies are warranted to evaluate the long-term stability of such complex reconstructions. However, local tumor control remains the highest priority and will be essential for years.

Allogeneic gene-edited HIV-specific CAR-T cells secreting PD-1 blocking scFv enhance anti-HIV activity in vitro

HIV-specific chimeric antigen receptor (CAR) T cells have been developed to target latently infected CD4+ T cells that express virus either spontaneously or after intentional latency reversal. However, the T-cell exhaustion and the patient-specific autologous paradigm of CAR-T hurdled the clinical application. Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells and a 3BNC117-E27 CAR (3BE CAR) construct that enables the expression of PD-1 blocking scFv E27 and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV envelope glycoprotein (Env). In comparison with T cells expressing 3BNC117-CAR alone, 3BE CAR-T cells showed greater anti-HIV potency with stronger proliferation capability, higher killing efficiency (up to ~75%) and enhanced cytokine secretion in the presence of HIV envelope glycoprotein-expressing cells. Furthermore, our approach achieved high levels (over 97%) of the TCR-deficient 3BE CAR-T cells with the functional inactivation of endogenous TCR to avoid graft-versus-host disease without compromising their antiviral activity relative to standard anti-HIV CAR-T cells. These data suggest that we have provided a feasible approach to large-scale generation of "off-the-shelf" anti-HIV CAR-T cells in combination with antibody therapy of PD-1 blockade, which can be a powerful therapeutic candidate for the functional cure of HIV.

Effect of coronal plane acetabular correction on joint contact pressure in Periacetabular osteotomy: a finite-element analysis

Background The ideal acetabular position for optimizing hip joint biomechanics in periacetabular osteotomy (PAO) remains unclear. We aimed to determine the relationship between acetabular correction in the coronal plane and joint contact pressure (CP) and identify morphological factors associated with residual abnormal CP after correction. Methods Using CT images from 44 patients with hip dysplasia, we performed three patterns of virtual PAOs on patient-specific 3D hip models; the acetabulum was rotated laterally to the lateral center-edge angles (LCEA) of 30°, 35°, and 40°. Finite-element analysis was used to calculate the CP of the acetabular cartilage during a single-leg stance. Results Coronal correction to the LCEA of 30° decreased the median maximum CP 0.5-fold compared to preoperatively (p < 0.001). Additional correction to the LCEA of 40° further decreased CP in 15 hips (34%) but conversely increased CP in 29 hips (66%). The increase in CP was associated with greater preoperative extrusion index (p = 0.030) and roundness index (p = 0.038). Overall, virtual PAO failed to normalize CP in 11 hips (25%), and a small anterior wall index (p = 0.049) and a large roundness index (p = 0.003) were associated with residual abnormal CP. Conclusions The degree of acetabular correction in the coronal plane where CP is minimized varied among patients. Coronal plane correction alone failed to normalize CP in 25% of patients in this study. In patients with an anterior acetabular deficiency (anterior wall index < 0.21) and an aspherical femoral head (roundness index > 53.2%), coronal plane correction alone may not normalize CP. Further studies are needed to clarify the effectiveness of multiplanar correction, including in the sagittal and axial planes, in optimizing the hip joint’s contact mechanics.

Artificial Intelligence-Based Solution in Personalized Computer-Aided Arthroscopy of Shoulder Prostheses

Background: Early recognition of prostheses before reoperation can reduce perioperative morbidity and mortality. Because of the intricacy of the shoulder biomechanics, accurate classification of implant models before surgery is fundamental for planning the correct medical procedure and setting apparatus for personalized medicine. Expert surgeons usually use X-ray images of prostheses to set the patient-specific apparatus. However, this subjective method is time-consuming and prone to errors. Method: As an alternative, artificial intelligence has played a vital role in orthopedic surgery and clinical decision-making for accurate prosthesis placement. In this study, three different deep learning-based frameworks are proposed to identify different types of shoulder implants in X-ray scans. We mainly propose an efficient ensemble network called the Inception Mobile Fully-Connected Convolutional Network (IMFC-Net), which is comprised of our two designed convolutional neural networks and a classifier. To evaluate the performance of the IMFC-Net and state-of-the-art models, experiments were performed with a public data set of 597 de-identified patients (597 shoulder implants). Moreover, to demonstrate the generalizability of IMFC-Net, experiments were performed with two augmentation techniques and without augmentation, in which our model ranked first, with a considerable difference from the comparison models. A gradient-weighted class activation map technique was also used to find distinct implant characteristics needed for IMFC-Net classification decisions. Results: The results confirmed that the proposed IMFC-Net model yielded an average accuracy of 89.09%, a precision rate of 89.54%, a recall rate of 86.57%, and an F1.score of 87.94%, which were higher than those of the comparison models. Conclusion: The proposed model is efficient and can minimize the revision complexities of implants.

Patient Specific Numerical Modeling for Renal Blood Monitoring Using Electrical Bio-Impedance

Knowledge of renal blood circulation is considered as an important physiological value, particularly for fast detection of acute allograft rejection as well as the management of critically ill patients with acute renal failure. The electrical impedance signal obtained from kidney with an appropriate electrode system and optimal electrode system position regarding to the kidney projection on skin surface reflects the nature of renal blood circulation and tone of renal blood vessels. This paper proposes a specific numerical modelling based on prior information from MRI-data. The numerical modelling was conducted for electrical impedance change estimation due to renal blood distribution. The proposed model takes into the account the geometrical and electrophysiological parameters of tissues around the kidney as well as the actual blood distribution within the kidney. The numerical modelling had shown that it is possible to register the electrical impedance signal caused by renal blood circulation with an electrode system commensurate with the size of kidney, which makes it possible to reduce the influence of surrounding tissues and organs. Experimental studies were obtained to prove the numerical modelling and the effectiveness of developed electrode systems based on the obtained simulation results. The obtained electrical impedance signal with the appropriate electrode system shows very good agreement with the renal blood change estimated using Doppler ultrasound. For the measured electrical impedance signal, it is possible to obtain the amplitude-time parameters, which reflect the hemodynamic characteristics of the kidneys and used in diagnostics, which is the subject of further research.

Geometrical and Hemodynamic Variables for Thrombotic Risk Stratification in Kawasaki Disease

Objectives Thrombosis is a major adverse outcome for coronary artery aneurysms (CAA) in Kawasaki disease (KD). We investigated the geometric and hemodynamic abnormalities in patients with CAA and identified the risk factors for thrombosis by computational fluid dynamics (CFD) simulation. Methods We retrospectively studied 27 KD patients with 77 CAAs, including 20 CAAs with thrombosis in 12 patients. Patient-specific anatomic models obtained from cardiac magnetic resonance imaging (CMRI) were constructed to perform a CFD simulation. From the simulation results, we produced local hemodynamic parameters comprising of time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI) and relative resident time (RRT). The CAA’s maximum diameter (Dmax) and Z-score were measured on CMRI. Results Giant CAAs tended to present with more severe hemodynamic abnormalities. Thrombosed CAAs exhibited lower TAWSS (1.551 ± 1.535 vs. 4.235 ± 4.640dynes/cm2, p = 0.002), higher Dmax (10.905 ± 4.125 vs. 5.791 ± 2.826mm, p = 0.008), Z-score (28.301 ± 13.558 vs. 13.045 ± 8.394, p = 0.002), OSI (0.129 ± 0.132 vs. 0.046 ± 0.080, p = 0.01), and RRT (16.780 ± 11.982s vs. 9.123 ± 11.770s, p = 0.399) than the non-thrombosed group. An ROC analysis for thrombotic risk proved that all of the five parameters had area under the ROC curves (AUC) above 0.7, with Dmax delineating the highest AUC (AUCDmax = 0.871) and a 90% sensitivity, followed by Z-score (AUCZ−score = 0.849). Conclusions It is reasonable to combine the geometric index with hemodynamic information to establish a severity classification for KD cases.