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Abstract Objective Duchenne muscular dystrophy (DMD) is a neuromuscular disorder in which many patients also have neurobehavioral problems. Corticosteroids, the primary pharmacological treatment for DMD, have been shown to affect brain morphology in other conditions, but data in DMD are lacking. This study aimed to investigate the impact of two corticosteroid regimens on brain volumetrics in DMD using magnetic resonance imaging (MRI). Methods In a cross‐sectional, two‐center study, T1‐weighted MRI scans were obtained from three age‐matched groups (9–18 years): DMD patients treated daily with deflazacort (DMDd, n = 20, scan site: Leuven), DMD patients treated intermittently with prednisone (DMDi, n = 20, scan site: Leiden), and healthy controls (n = 40, both scan sites). FSL was used to perform voxel‐based morphometry analyses and to calculate intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volumes. A MANCOVA was employed to compare global volumetrics between groups, with site as covariate. Results Both patient groups displayed regional differences in gray matter volumes compared to the control group. The DMDd group showed a wider extent of brain regions affected and a greater difference overall. This was substantiated by the global volume quantification: the DMDd group, but not the DMDi group, showed significant differences in gray matter, white matter, and cerebrospinal fluid volumes compared to the control group, after correction for intracranial volume. Interpretation Volumetric differences in the brain are considered part of the DMD phenotype. This study suggests an additional impact of corticosteroid treatment showing a contrast between pronounced alterations seen in patients receiving daily corticosteroid treatment and more subtle differences in those treated intermittently.

Abstract Background Response rates of immune checkpoint inhibitor (ICI) therapy for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are low. Patients and Methods This retrospective multicentre cohort study evaluates the predictive and prognostic value of weight loss and changes in body composition prior and during therapy. Patient, tumor, and treatment characteristics of 98 patients were retrieved, including neutrophil and platelet‐lymphocyte‐ratio (NLR and PLR). Programmed death‐ligand 1 (PD‐L1) expression was determined on residual material. Cachexia was defined according to Fearon et al. (2011). Skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were evaluated on computed tomography scans at the third lumbar vertebrae level. Univariable and multivariable regression analyses were performed for 6 months progression free survival (PFS6m) and overall survival (OS). Results Significant early weight loss (>2%) during the first 6 weeks of therapy was shown in 34 patients (35%). This patient subgroup had a significantly higher NLR and PLR at baseline. NLR and PLR were inversely correlated with SM and VAT index. Independent predictors of PFS6m were lower World Health Organization performance status (HR 0.16 [0.04–0.54] p = 0.003), higher baseline SAT index (HR 1.045 [1.02–1.08] p = 0.003), and weight loss 2% early weight loss remained a predictor of OS, independent of PD‐L1 expression (HR 2.09 [1.11–3.92] p = 0.02, HR 2.18 [1.13–4.21] p = 0.02). Conclusion We conclude that the combination of cachexia at baseline and weight loss during ICI therapy is associated with worse OS in R/M HNSCC patients, independent of PD‐L1 expression.

Abstract Objectives The aim of this study is to investigate the long‐term effects on jaw and femur bone induced by oncologic doses of zoledronic acid in a young rat model. Material and Methods Six 12‐week‐old male Wistar rats received zoledronic acid (0.6 mg/kg) and six control rats received saline solution in the same volume. Compounds were administered intraperitoneally in five doses every 28 days. Euthanasia was performed 150 days after therapy onset. After animal sacrifice, their mandibles and femurs were scanned ex vivo using a high‐resolution (14 μm) micro‐computed tomography. Morphometric bone parameters were calculated using CT‐Analyzer (Bruker, Belgium) between the first and second mandibular molars and in the distal femur metaphysis and epiphysis. Results The treatment group as compared to the controls showed a significantly (p

Abstract This study used a novel 3D analysis to longitudinally evaluate orthodontic tooth movement (OTM) and bone morphometry. Twelve-week-old male Wistar rats were subjected to OTM by applying a constant orthodontic force (OF) of 25cN between one of the upper first molars and a mini-screw. In vivo micro-CTs were taken before and after 10, 17, 24 and 31 days of force application, and superimposed by a novel and rigid voxel-based registration method. Then the tooth and alveolar bone segment at different time points became comparable in the same coordinate system, which facilitated the analysis of their dynamic changes in 3D. By comparison between time points and between OF and no OF sides, this study showed that the OTM rate was not constant through time, but conformed to a ‘V’ shape changing pattern. Besides, OF induced displacement of both loaded and unloaded teeth, and the latter mirrored the former in a delayed manner. In addition, bone morphometric changes synchronized with OTM rate changes, implying that a higher OTM rate was concomitant with more alveolar bone loss. The pressure and tension areas might not be in two opposite sides, but actually adjacent and connected. These findings might provide instructive evidence for both clinical, translational and basic research in orthodontics.

Abstract Aim The aim of the study was to assess the 5-year cumulative survival rate of implant-based dental rehabilitation following maxillofacial reconstruction with a vascularized bone flap and to investigate the potential risk factors which might influence the survival rate. Materials and methods A retrospective cohort study was designed. Inclusion criteria involved 18 years old or above patients with the availability of clinical and radiological data and a minimum follow-up 1 year following implant placement. The cumulative survival rate was analyzed by Kaplan–Meier curves and the influential risk factors were assessed using univariate log-rank tests and multivariable Cox-regression analysis. Results 151 implants were assessed in 40 patients with a mean age of 56.43 ± 15.28 years at the time of implantation. The mean number of implants placed per patient was 3.8 ± 1.3 with a follow-up period of 50.0 ± 32.0 months. The cumulative survival at 1-, 2- and 5-years was 96%, 87%, and 81%. Patients with systemic diseases (HR = 3.75, 95% CI 1.65–8.52; p = 0.002), irradiated flap (HR = 2.27, 95% CI 1.00–5.17; p = 0.05) and poor oral hygiene (HR = 11.67; 95% CI 4.56–29.88; p

Abstract Background Bone-to-implant contact ratio (BIC%) plays a critical role in secondary stability of osseointegrated dental implants. The aim of this study was to identify the correlation of 2D/3D micro-CT images with histology as a gold standard for evaluating BIC% and to investigate the influence of the platelet-rich plasma (PRP) and platelet-poor plasma (PPP) on 3D BIC% following delayed implant placement with delayed loading (DIP+DL). Methods Nine beagle dogs were recruited. Following bilateral extraction of mandibular 3rd premolar, 4th premolar, and 1st molar, 54 screw-type titanium implants were inserted and randomly divided into one control and two test groups based on a split-mouth design. The control group involved DIP+DL (n = 18) and both test groups included DIP+DL with local application of PRP (n = 18) and PPP (n = 18). A BIC analysis was performed utilizing 2D histomorphometry and 2D/3D micro-CT. Following identification of correlation between histology and 2D/3D micro-CT images, a 3D micro-CT assessment of the 3D BIC% at three follow-up time-points (1, 3, and 6 months) was carried out for observing the influence of PRP and PPP on BIC. Results The 2D micro-CT BIC% values revealed a strong positive correlation with histology (r = 0.98, p

The use of Ti6Al4V in bone engineering is limited, due to the biological inertia of the surface. In this study, a porous Ti6Al4V scaffold with mechanical properties similar to cancellous bone was designed and 3D-printed. Under physiological conditions, the scaffold was immersed firstly in a 5-fold-concentrated simulated body fluid, then in a supersaturated CaP solution containing BMP-2, to form a bone-like porous micro/nano structured biomimetic coating on the surface. Scaffolds were implanted in the muscle pouches created in six beagle dogs and were retrieved four weeks later for histologic and histomorphometric analysis. Results showed that BMP-2 integrated biomimetic CaP coating induced ectopic bone formation, which was absent in other two groups. Soft tissue infiltrated the scaffold's outside 1 mm layer, while the new-formed bone was evenly distributed in the longitudinal and horizontal directions within the rest of the scaffold based on BA/TA, BIC and BA measurements. In conclusion, the BMP-2 incorporated biomimetic CaP coating creates a micro/nano surface structure on the Ti6Al4V scaffold, which helps to increase biocompatibility. The integrated BMP-2 is capable of inducing ectopic bone formation in vivo. The proposed combination may have the potential for bone reconstruction, but further studies are needed to explore its clinical applicability.

BackgroundThe objective of this systematic review was to identify the different surgical treatment modalities of severe trismus after head and neck squamous cell cancer treatment.MethodsAn electronic literature database search was conducted in Medline, Embase, Cochrane, Web of Science, and OpenGrey to determine articles published up to September 2021. Two observers independently assessed the identified papers for eligibility according to PRISMA guidelines. The inclusion criteria were trismus after head and neck squamous cell cancer with consecutive treatment, detailed description of the surgical procedure for trismus release, description of the initial treatment, at least 6 months between initial cancer treatment and trismus release surgery, a minimal follow-up (FU) of 6 months, and availability of full text. The quality was evaluated using the Newcastle-Ottawa scale. A subanalysis of the maximal mouth opening (MMO) was performed using a mixed-effect model.ResultsA total of 8,607 unique articles were screened for eligibility, 69 full texts were reviewed, and 3 studies, with a total of 46 cases, were selected based on the predetermined inclusion and exclusion criteria. Three treatment strategies were identified for trismus release (1) free flap reconstruction (FFR), (2) coronoidectomy (CN), and (3) myotomy (MT). There was a clear improvement for all treatment modalities. A quantitative analysis showed a beneficial effect of CN (mean 24.02 ± 15.02 mm) in comparison with FFR (mean 19.88 ± 13.97 mm) and MT (mean 18.38 ± 13.22 mm) (P < 0.01*). An increased gain in MMO after trismus release was found if no primary resection was performed (P = 0.014*). Two studies included in the analysis had an intermediate risk of bias and one had a low risk of bias.ConclusionCurrently available reports suggest a low threshold for performing a CN compared with FFR and MT. There is a need for high-quality randomized controlled trials with carefully selected and standardized outcome measures.

ObjectiveThe treatment approach of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has long been similar for all patients. Any difference in treatment strategy was only based on existing comorbidities and on preferences of the patient and the treating oncologist. The recent advance obtained with immune therapy and more specifically immune checkpoint blockade (ICB) has been a true game changer. Today, patients and physicians have a choice to omit chemotherapy. In a small subset of patients, ICB induces a very durable disease control. The subgroup of patients in which ICB without chemotherapy would be the preferential approach is still ill-defined. Yet, this evolution marks a major step towards a more personalized medicine in R/M HNSCC.Materials and MethodsIn this paper, we present a retrospective cohort study of a patient population that was treated with ICB in a single center and we analyze potential factors that are associated with outcome and may help to select patients for treatment with ICB.Results137 consecutively treated patients were identified. Male gender and metastatic disease appeared to be associated with improved overall survival (OS). There was no correlation observed with age, number of previous treatment lines or immune target.ConclusionAlong with PD-L1 status defined by Combined Positive Score (CPS), clinical parameters such as site of recurrence and gender may help to define the optimal treatment strategy in R/M HNSCC.

Abstract Background Autologous plasma fractions, such as platelet-rich plasma (PRP) and platelet-poor plasma (PPP), contain growth factors that can enhance neural cell survival and are therefore likely to have the ability to promote nerve regeneration. The present study compared the effect of PRP and PPP application on myelinated nerve density and diameter in the peri-implant bone region. In addition, the effect of healing time on nerve regeneration was assessed. Materials and methods Nine beagle dogs randomly received 54 dental implants in the bilateral mandible according to a split-mouth design. Each implant was randomly assigned to one of three implant protocols: delayed implant placement with delayed loading (DIP + DL) with local application of PRP, DIP + DL with local application of PPP and DIP + DL without any plasma additive. The animals were euthanized at 1, 3, and 6 months after loading (3 dogs per time point). Block biopsies were prepared for histomorphometry in the peri-implant bone within 500 μm around the implants. Results Myelinated nerve fibers were identified in the trabecular bone and in the osteons near the implants surface. The nerve fibers in the PRP group (median ± IQR; 2.88 ± 1.55 μm) had a significantly (p < 0.05) greater diameter compared to the PPP (2.40 ± 0.91 μm) and control (2.11 ± 1.16 μm) group. The nerve diameter after 6 months healing (3.18 ± 1.58 μm) was significantly (p < 0.05) greater compared to 1 (2.08 ± 0.89 μm) and 3 (2.49 ± 1.22 μm) months. No significant difference was found for myelinated nerve density between groups and healing time. Conclusions The present study showed that the healing time significantly influenced the diameter of the myelinated nerve fibers in peri-implant bone. PRP exerted a significant effect on the diameter of the myelinated nerve fibers as compared to PPP. Large-scale animal studies and longer follow-up periods are needed to confirm these findings and to verify whether platelet plasma can facilitate nerve regeneration process.

Abstract Background Bovine bone grafts have been widely used in dentistry for guided tissue regeneration and can support new bone formation in direct contact with the graft. The aim of this study was to compare the morphometric and bone density changes after using two different bovine bone graft blocks in segmental osseous defects in the mandible of rabbits following different postoperative periods. Material and methods Critical size segmental defects were surgically created bilaterally in the jaw of 18 rabbits. The defects were filled with either deproteinized bovine bone mineral with 10% collagen (DBBM-C; BioOss Collagen®), lyophilized bovine medullary bone (LBMB; Orthogen®), or left untreated according to a split-mouth design. Animals were sacrificed after 3 or 6 months of healing. The hemimandibles were scanned ex vivo using a high-resolution (19 μm) microcomputed tomography. Morphometric and bone density parameters were calculated in the region of the defect using CT-Analyser (Bruker). Initial graft blocks were used as baseline. Results DBBM-C presented a denser microarchitecture, in comparison to LBMB at baseline. DBBM-C and LBMB grafted regions showed a similar progressive remodeling, with a significant decrease in structure complexity and maintenance of bone volume fraction during the postoperative follow-up periods. Both graft materials showed an enhanced bone replacement and more complex structure compared to untreated defects. The apparent fusion between the graft and host bone was observed only in the defects filled with LBMB. Conclusion LBMB grafts showed a similar behavior as DBBM-C regarding structural remodeling. In LBMB samples, apparent integration between the host bone and the graft was present.

ObjectiveTo investigate the adherence to initially planned maxillofacial reconstructions using computer-assisted surgery (CAS) and to identify the influential factors affecting its compliance for maxillofacial reconstruction.Patients and MethodsA retrospective analysis of 136 computer-assisted maxillofacial reconstructive surgeries was conducted from January 2014 to June 2020. The categorical parameters involved age, gender, disease etiology, disease site, defect size, bone flap segments, and flap type. Apart from descriptive data reporting, categorical data were related by applying the Fisher-exact test, and a p-value below 5% was considered statistically significant (P < 0.05).ResultsThe main reasons for partial or non-adherence included unfitness, patient health condition, and other subjective reasons. Out of the total patient population, 118 patients who underwent mandibular reconstruction showed higher CAS compliance (83.9%) compared to the 18 midface reconstruction (72.2%) without any statistically significant difference (p = 0.361). Based on the size of the defect, a significantly higher CAS compliance (p = 0.031) was observed with a minor defect (80.6%) compared to the large-sized ones (74.1%). The bone flaps with two or more segments were significantly (p = 0.003) prone to observe a partial (15.4%) or complete (12.8%) discard of the planned CAS compared to the bone flaps with less than two segments. The malignant tumors showed the lowest CAS compliance when compared to other disorders without any significant difference (p = 0.1).ConclusionThe maxillofacial reconstructive surgical procedures offered optimal compliance to the initially planned CAS. However, large-sized defects and multiple bone flap segments demonstrated a higher risk of partial or complete abandonment of the CAS.