CD4+ T cell activation distinguishes response to anti-PD-L1+anti-CTLA4 therapy from anti-PD-L1 monotherapy.

Cancer patients often receive a combination of antibodies targeting programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA4). We conducted a window-of-opportunity study in head and neck squamous cell carcinoma (HNSCC) to examine the contribution of anti-CTLA4 to anti-PD-L1 therapy. Single-cell profiling of on- versus pre-treatment biopsies identified T cell expansion as an early response marker. In tumors, anti-PD-L1 triggered the expansion of mostly CD8+ T cells, whereas combination therapy expanded both CD4+ and CD8+ T cells. Such CD4+ T cells exhibited an activated T helper 1 (Th1) phenotype. CD4+ and CD8+ T cells co-localized with and were surrounded by dendritic cells expressing T cell homing factors or antibody-producing plasma cells. T cell receptor tracing suggests that anti-CTLA4, but not anti-PD-L1, triggers the trafficking of CD4+ naive/central-memory T cells from tumor-draining lymph nodes (tdLNs), via blood, to the tumor wherein T cells acquire a Th1 phenotype. Thus, CD4+ T cell activation and recruitment from tdLNs are hallmarks of early response to anti-PD-L1 plus anti-CTLA4 in HNSCC.

3D quantification of in vivo orthodontic tooth movement in rats by means of micro-computed tomography.

OBJECTIVE: (1) To test the accuracy of split-mouth models in rats for the study of orthodontic tooth movement (OTM) and (2) to propose an improved 3D model for quantification of OTM in rats. METHODS: Eleven Wistar rats were split into group 1 (dental anchorage) and group 2 (skeletal anchorage). In both groups, no orthodontic force (OF) was applied on the contralateral hemi-maxilla. In vivo micro-CT images were taken before (T0) and 31 days (T1) after OF. OTM was compared between time-points and experimental sides using conventional 2D analysis and a novel 3D model. RESULTS: Using incisors as anchorage leads to their distal displacement in both OF and no OF sides. In the OF side, movement of M1 is underestimated by incisor displacement. Mesial displacement of M1 was found in the no OF side of all groups 31 days after the application of OF. CONCLUSIONS: The new 3D model yielded higher sensitivity for tooth displacement in planes other than sagittal and incisor displacement was reduced by using skeletal anchorage. CLINICAL SIGNIFICANCE: Studies following split-mouth designs in orthodontic research in rats might be systematically underestimating the effects of techniques and/or medication on OTM, since there is tooth displacement on the control side. 3D quantification of OTM with skeletal anchorage is more sensitive and avoids displacement of the dental units used as anchorage.

Dissociating brain systems that respond to contingency and valence during monetary loss avoidance in adolescence.

Negative reinforcement processes allow individuals to avoid negative and/or harmful outcomes. They depend on the brain's ability to differentiate; (i) contingency from non-contingency, separately from (ii) judgements about positive and negative valence. Thirty-three males (8-18 years) performed a cued reaction-time task during fMRI scanning to differentiate the brain's responses to contingency and valence during loss avoidance. In two conditions, cues indicated no -contingency between participants' responses and monetary loss - (1) CERTAIN LOSS (negative valence) of €0.20, €1 or €5 or (2) CERTAIN LOSS AVOIDANCE (positive valence). In a third condition, cues indicated a contingency between short reaction times and avoidance of monetary loss. As expected participants had shorter reaction times in this latter condition where CONDITIONAL LOSS AVOIDANCE cues activated salience and motor-response-preparation brain networks - independent of the relative valence of the contrast (CERTAIN LOSS or CERTAIN LOSS AVOIDANCE). Effects of valence were seen toward the session's end where CERTAIN LOSS AVOIDANCE cues activated ventral striatum, medial-orbitofrontal cortex and medial-temporal areas more than CERTAIN LOSS. CONDITIONAL LOSS AVOIDANCE trials with feedback indicating "success" activated ventral striatum more than "failure feedback". The findings support the hypothesis that brain networks controlling contingency and valence processes during negative reinforcement are dissociable.

Effect of different platelet-rich fibrin matrices for ridge preservation in multiple tooth extractions: A split-mouth randomized controlled clinical trial.

AIM: To evaluate dimensional changes in the alveolar ridge and bone structure after tooth extraction when L-PRF or A-PRF+ was used in comparison to unassisted socket healing. MATERIALS AND METHODS: Twenty patients in need of at least three tooth extractions in the aesthetic zone were included. L-PRF, A-PRF+ or control was randomly assigned, leaving one empty socket/edentulous site between conditions. CBCT scans were obtained immediately after tooth extraction and after 3 months of healing. Horizontal and vertical dimensional changes of the ridge and socket fill were calculated. Histological and micro-CT analysis of bone biopsies were used to evaluate post-surgical bone structural healing. RESULTS: Mean horizontal and vertical changes at 1-mm below the crest (buccal and palatal side) were similar for the three sites (p > 0.05). For the socket fill, L-PRF (85.2%) and A-PRF+ (83.8%) showed superior values than the control (67.9%). The histological and radiological analysis reported more newly formed bone for the PRF groups, without any significant differences between both. CONCLUSIONS: PRF matrices failed to reduce the dimensional changes after multiple tooth extractions in the premaxilla. After 3-month healing, both PRF matrices showed radiographically a significant superiority for the socket fill. Histologically, they seemed to accelerate new bone formation.

Task-related motivation and academic achievement in children and adolescents with ADHD.

Academic impairment in individuals with attention-deficit/hyperactivity disorder (ADHD) is in part due to reduced motivation for academic tasks, which is likely to vary as a function of task characteristics. The current study employed a new questionnaire-the Child and Adolescent Motivational Profile (CHAMP)-to examine; (1) which task characteristic participants with ADHD perceive as most motivating relative to typically developing peers (TDP) and (2) whether these differences mediate academic functioning. 34 participants with ADHD and 435 TDP (8-16 years) completed the CHAMP. Academic achievement (grade point average) and self-reported positive/negative classroom experiences were recorded. No task characteristics were rated higher in terms of their motivational salience in the ADHD group than in the control sample. Marked/graded, Socially evaluated, Collaborative, Requiring focus and Cognitively challenging task characteristics were rated significantly lower by the ADHD group than controls. The lower rating of Socially evaluated was explained by comorbid ODD symptoms. Cognitively challenging was rated as particularly unmotivating by individuals with ADHD. ADHD was associated with a decreased GPA and a more negative classroom experience. The associations between ADHD and GPA/negative classroom experience were both partially mediated by scores on the Cognitively Challenging scale. For children and adolescents with ADHD tasks that are cognitively challenging were not particularly motivating. To increase task motivation, and improve academic performance of individuals with ADHD, it may be important to include rewarded task elements as they are appraised as particularly motivating by these individuals and this appraisal was similar to that of TDP.

Application of Three-Dimensional Printed Customized Surgical Plates for Mandibular Reconstruction: Report of Consecutive Cases and Long-Term Postoperative Evaluation.

ABSTRACT: This study aims to evaluate the use of customized surgical plates in patients with mandibular defects concerning postoperative aesthetics and functional outcomes during the 2-year follow-up. Preoperative virtual surgical plans and patient-specific three-dimensional printed plates were tailored for consecutive patients. Preoperative preparation, surgical produces, postoperative aesthetics, and functional outcomes were described in detail. The average follow-up period was over 2 years. In the presented clinical cases, aesthetic and functional outcomes were reported to be satisfactory.

Peri-implant myelinated nerve fibers: Histological findings in dogs.

BACKGROUND AND OBJECTIVE: While osseointegration following various dental implant placement protocols has been extensively investigated, the neurohistological integration has received little attention. The primary aim of this study was to compare the myelinated nerve fibers density in peri-implant bone tissue following various implant placement protocols. The secondary aim assessed the effect of follow-up on peri-implant nerve fibers density. METHODS: Ten beagle dogs randomly received 68 commercially pure titanium implants in the mandibular premolar or molar region bilaterally following extraction utilizing one of the six treatment protocols: (a) immediate implant placement (IIP) and immediate loading (IL); (b) IIP and delayed loading (DL); (c) IIP and left unloaded (UL); (d) delayed implant placement (DIP) and IL; (e) DIP and DL; and (f) DIP and UL. Histomorphometric analysis of the peri-implant myelinated nerve fibers was performed in a 300 µm peri-implant zone at the cervical, middle, and apical level following implant placement. The follow-up assessment involved longitudinal observation at 3 months following each implant treatment protocol and at 6 months for IIP+IL and IIP+DL protocols. RESULTS: The influence of different treatment protocols, including the fixed effects of implant groups (IIP+IL, IIP+DL, IIP+UL, DIP+IL, DIP+DL, DIP+UL) and regions (cervical, middle, apical), was examined via a linear mixed model. The IIP+IL group showed a significantly higher myelinated nerve density compared to the IIP+UL and DIP+UL group. Peri-implant nerve re-innervation was significantly higher (P = .002) in the apical region compared to the cervical region. After immediate implant placement, the IL group showed a significantly (P = .03) higher density of myelinated nerve fibers compared to DL. No significant (P = .19) effect of follow-up on nerve density was observed. CONCLUSION: The immediate implant placement and loading protocol showed most beneficial effect on peri-implant innervation with highest myelinated nerve density in the apical region. A longer loading time had no influence on the peri-implant nerve density.

Bovine-derived xenograft in combination with autogenous bone chips versus xenograft alone for the augmentation of bony dehiscences around oral implants: A randomized, controlled, split-mouth clinical trial.

AIM: The aim of the study was to evaluate whether the use of a xenograft is not inferior to the use of xenograft and autogenous bone chips in treating dehiscences at implant placement. MATERIALS AND METHODS: After implant placement, leaving a dehiscence, control sites were treated using a composite graft (autogenous bone chips and xenograft) and at the test sites 100% xenograft was used. Both sites were covered with a resorbable collagen membrane. Dehiscences were measured clinically at implant placement and at re-entry. CBCT was taken immediately after implant placement and after 4 months. RESULTS: In total, 28 GBR procedures were performed in 14 patients. On average, the change in vertical defect height was 2.07 mm (46.7%-test group) and 2.28 mm (50.9%-control group) (p > .05). The horizontal defect width at the implant shoulder change on average 1.85 mm (40.5%-test group) and 1.75 mm (40.9%-control group) (p > .05). On average, a loss in augmentation thickness of 0.45 mm (68.9%-test group) and 0.64 mm (55.5% control group) between implant placement and augmentation and abutment surgery was obtained at the implant shoulder. CONCLUSION: Both treatment modalities seem to work to a certain extent. At implant shoulder level, the augmentation thickness seems to be disappeared after the healing phase. (NCT03946020).

Relationship between trabecular bone architecture and early dental implant failure in the posterior region of the mandible.

OBJECTIVE: To investigate the relationship between preoperative trabecular bone structure and implant outcome based on bone morphometric bone parameters from CBCT scans. MATERIALS AND METHODS: Twenty consecutive cases with early implant failure in the posterior region of the mandible were matched with 20 control patients with a successful implant osseointegration selected. All patients had taken a preoperative CBCT image according to a standardized acquisition protocol. On these CBCT scans, the trabecular bone of each implantation site was selected and segmented, after which 3D morphometric bone parameters were calculated and used in a cluster analysis to objectively differentiate trabecular bone patterns. Fisher's exact test was used to determine whether there is a significant association between trabecular pattern and implant outcome. RESULTS: A sparse, intermediate, and dense trabecular bone pattern was distinguished by cluster analysis. The relationship between the trabecular bone pattern and early implant failure was significant (z = 9.6; p < .05). Early implant failure was more likely to occur in the sparse bone types, while implant survival was associated with intermediate bone types. CONCLUSION: Prior to implant placement, attention should be given to extreme deviations in trabecular structure at the planned implant sites. Very sparse or very dense bone should be carefully evaluated at the potential implant site, while intermediate bone types seem favorable for implant survival.

Effect of platelet-rich plasma on peri-implant trabecular bone volume and architecture: A preclinical micro-CT study in beagle dogs.

OBJECTIVES: To evaluate the peri-implant trabecular bone volume and architecture changes with 6-month follow-up after local application of platelet-rich plasma (PRP) and platelet-poor plasma (PPP) using high-resolution micro-CT. MATERIAL AND METHODS: Seventy-two dental implants were placed into healed mandibular sites of 9 beagle dogs. Implants were randomly divided into 4 groups following a split-mouth design: control I; control II; PPP; and PRP. Primary and secondary stabilities were assessed using resonance frequency analyses. At 1, 3, and 6 months after implant loading, trabecular structural parameters were evaluated at 0.5, 1, and 1.5 mm away from implants using micro-CT (voxel = 20 µm). RESULTS: Primary and secondary stabilities were equivalent in all conditions. PPP and PRP groups showed higher bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) but lower trabecular separation (Tb.Sp) and total porosity percentage (Po (tot)) at all 3 time points. A significant decrease in BV/TV and Tb.Th was found for the control groups after 3 months of healing, while this was not observed in both the PPP and PRP groups. However, no distinct difference was found between the PRP and PPP groups over time. Moreover, as the investigated distance from the implant surface increased, BV/TV and Po (tot) within the same group and time point stayed the same, yet Tb.Th and Tb.Sp continued to increase. CONCLUSIONS: Platelet-rich plasma and PPP with conventional implant placement lead to similar primary and secondary implant stability, but improved peri-implant bone volume and structural integration. The present research does not seem to suggest a different bone remodeling pattern when using PRP or PPP.

Delay aversion in attention deficit/hyperactivity disorder is mediated by amygdala and prefrontal cortex hyper-activation.

BACKGROUND: Experimental research supports delay aversion as a motivational feature of attention deficit/hyperactivity disorder (ADHD). To investigate the neurobiology of delay aversion in ADHD, this study examined whether adolescents with ADHD display an unusually strong activation in affective brain regions in response to cues predicting forthcoming delay and whether these effects are (a) delay-dose dependent and (b) statistically mediate the association between ADHD and self-reported delay aversion. METHODS: Twenty-nine right-handed male adolescents with combined type ADHD and 32 typically developing controls (ages 10-18 years) performed a reaction time task in an MRI scanner. Pretarget cues indicated delay-related response consequences. One indicated that delay would follow the response irrespective of response speed (CERTAIN DELAY), a second that delay would only follow if the response was too slow (CONDITIONAL DELAY), and a third that no delay would follow the response whatever its speed (NO DELAY). Delay levels were 2, 6, or 14 s. Participants also rated their own delay aversion in everyday life. RESULTS: Individuals with ADHD rated themselves as more delay averse than controls. Significantly greater activation to CERTAIN DELAY cues relative to NO DELAY cues was found in participants with ADHD compared to controls (bilaterally) in amygdala, anterior insula, temporal pole, dorsolateral prefrontal cortex (DLPFC), and ventromedial prefrontal cortex. Amygdala and DLPFC activation strength were strongly and delay-dose dependently correlated with delay aversion ratings, and statistically mediated the relationship between ADHD status and delay aversion. CONCLUSIONS: When presented with cues predicting impending delay, adolescents with ADHD, relative to controls, displayed a delay-related increase in activation in amygdala and DLPFC, regions known to be implicated in the processing of aversive events. Future studies should examine the specificity of these effects to delay aversion compared to aversive events in general.

Leucocyte- and platelet-rich fibrin block for bone augmentation procedure: A proof-of-concept study.

AIM: The objective of this proof-of-concept study was to investigate the effects of a new guided bone regeneration technique with a tissue engineering approach. MATERIALS AND METHODS: This single cohort observational study evaluated the outcome of the leucocyte- and platelet-rich fibrin (L-PRF) Block for horizontal bone augmentation in the maxilla. The L-PRF Block is prepared by mixing a particulated biomaterial with chopped L-PRF membranes at a 50:50 ratio and adding liquid fibrinogen to glue all together. Horizontal augmentation was assessed linearly and volumetrically immediately after surgery and 5-8 months later by matching consecutive cone beam computed tomography (CBCTs). RESULTS: Ten patients (mean age of 50.7 years [±17.2]) representing 15 sites with horizontal alveolar deficiencies were included. Superimposition of pre-operative and posthealing CBCT scans showed an average linear horizontal bone gain of 4.6 mm (±2.3), 5.3 mm (±1.2) and 4.4 mm (±2.3), measured at 2, 6 and 10 mm from the alveolar crest, respectively. The volumetric gain was 1.05 cm3 (±0.7) on average. The resorption rate after 5-8 months was 15.6% (±6.7) on average. CONCLUSIONS: L-PRF Block may be a suitable technique to augment deficient alveolar ridges.

Zoledronic Acid Induces Site-Specific Structural Changes and Decreases Vascular Area in the Alveolar Bone.

PURPOSE: The aim was to assess the effect of a relevant regimen of zoledronic acid (ZA) treatment for the study of bisphosphonate-related osteonecrosis of the jaw on alveolar bone microstructure and vasculature. A sub-objective was to use 3-dimensional imaging to describe site-specific changes induced by ZA in the alveolar bone. MATERIALS AND METHODS: Five Wistar rats received ZA (0.6 mg/kg) and five (controls) received saline solution in the same volume. The compounds were administered intraperitoneally in 5 doses every 28 days. The rats were euthanized 150 days after therapy onset. The mandibles were scanned using high-resolution (14-µm) micro-computed tomography (micro-CT), decalcified, cut into slices for histologic analysis (5 µm), and stained with hematoxylin-eosin. Bone quality parameters were calculated using CT-Analyser software (Bruker, Kontich, Belgium) in 2 different volumes of interest (VOIs): the region between the first molar roots (VOI-1) and the periapical region under the first and second molars' apex (VOI-2). Blood vessel density and bone histomorphometric parameters were calculated only for the region between the roots of the first molar using AxioVision Imaging software (version 4.8; Carl Zeiss, Gottingen, Germany). RESULTS: ZA-treated rats showed a significant increase in percentage of bone volume and density (P < .05), with thicker and more connected trabeculae. Furthermore, the ZA group showed a significant decrease in the size of the marrow spaces and nutritive canals and in blood vessel density (P < .05). In the micro-CT evaluation, VOI-2 showed better outcomes in measuring the effect of ZA on alveolar bone. CONCLUSIONS: ZA treatment induced bone corticalization and decreased alveolar bone vascularization. VOI-2 should be preferred for micro-CT evaluation of the effect of bisphosphonates on alveolar bone. This analysis allowed the effect of ZA on alveolar bone and its vascularization to be characterized. The results of this analysis may add further knowledge to the understanding of the physiopathology of osteonecrosis of the jaw.

Volumetric changes of grafted volumes and the Schneiderian membrane after transcrestal and lateral sinus floor elevation procedures: A clinical, pilot study.

AIM: To investigate the influence of various surgical techniques for sinus augmentation on the volumetric changes of graft, membrane and the post-operative discomfort. MATERIALS AND METHODS: Eighteen patients in need of bilateral sinus floor elevation (SFE) were assigned to lateral SFE, transcrestal SFE and intralift procedures. CBCT images taken at baseline, 1 week and 6 weeks were analysed for volumetric changes in graft and Schneiderian membrane. Questionnaires were used to analyse post-op discomfort. RESULTS: The overall average graft volume obtained after 1 week was 1.87 cm3 (range 0.12-4.72 cm3 ). Volumes decreased after 6 weeks to an overall mean volume of 1.33 cm3 (range 0.10-4.29 cm3 - average decrease of 27.6%). After 6 weeks, the amount of graft volume decreased in every treatment option, ranging from -23.13% for the tSFE, over -24.55% for the lSFE, to -33.71% for the IL. Although all treatment options correspond in an increase in Schneiderian membrane volume, no statistically significant correlation between this increase and loss of graft volume could be obtained for all treatments (p = 0.97). CONCLUSION: All SFE techniques provided sufficient graft volume for implant treatment. All techniques provoke a partially transient swelling of the Schneiderian membrane. All techniques resulted in a decrease in graft volume after 6 weeks; however, no significant differences were obtained between treatments. Furthermore, no statistical significant correlation between the post-operative swelling of the Schneiderian membrane and reduction in graft volume at 6 weeks could be obtained.

A systematic review on the innervation of peri-implant tissues with special emphasis on the influence of implant placement and loading protocols.

OBJECTIVES: To systematically review the available literature on the influence of dental implant placement and loading protocols on peri-implant innervation. MATERIAL AND METHODS: The database MEDLINE, Cochrane, EMBASE, Web of Science, LILACS, OpenGrey and hand searching were used to identify the studies published up to July 2013, with a populations, exposures and outcomes (PEO) search strategy using MeSH keywords, focusing on the question: Is there, and if so, what is the effect of time between tooth extraction and implant placement or implant loading on neural fibre content in the peri-implant hard and soft tissues? RESULTS: Of 683 titles retrieved based on the standardized search strategy, only 10 articles fulfilled the inclusion criteria, five evaluating the innervation of peri-implant epithelium, five elucidating the sensory function in peri-implant bone. Three included studies were considered having a methodology of medium quality and the rest were at low quality. All those papers reported a sensory innervation around osseointegrated implants, either in the bone-implant interface or peri-implant epithelium, which expressed a particular innervation pattern. Compared to unloaded implants or extraction sites without implantation, a significant higher density of nerve fibres around loaded dental implants was confirmed. CONCLUSIONS: To date, the published literature describes peri-implant innervation with a distinct pattern in hard and soft tissues. Implant loading seems to increase the density of nerve fibres in peri-implant tissues, with insufficient evidence to distinguish between the innervation patterns following immediate and delayed implant placement and loading protocols. Variability in study design and loading protocols across the literature and a high risk of bias in the studies included may contribute to this inconsistency, revealing the need for more uniformity in reporting, randomized controlled trials, longer observation periods and standardization of protocols.

Presurgical CBCT assessment of maxillary neurovascularization in relation to maxillary sinus augmentation procedures and posterior implant placement.

PURPOSE: To provide more information to clinicians planning sinus grafting and maxillofacial surgical interventions, the present study evaluated the prevalence, diameter and location of the superior alveolar canals (SAC) using CBCT images. METHODS: The maxillary sinus CBCT scans (i-CAT Classic(®), ISI, USA) of 100 adult patients (67 women and 33 men) aged 20-79 years [mean (SD) 40 (15)] were examined. A dentomaxillofacial radiologist observed the SAC based on CBCT image data and more specifically the parasagittal views to assess SAC's diameter and location. RESULTS: The anterior and posterior SAC, double ASAC, intraosseous anastomoses and the extension of the anterior SAC to the piriform aperture were observed in 100, 73, 24.5, 38.5 and 84 % of the cases, respectively. The anastomosis was located between canine and first premolar in 43 % of the cases. The SAC diameters were in 80 % of the cases ≤1 mm, remaining canals had a diameter between 1 and 2 mm. The distance of the SAC to the alveolar crest ranged between 2.42 and 44.6 mm. The anterior SAC was more prevalent in the upper (53 %) and middle (44 %) thirds of the maxillary sinus, while the posterior SAC was more prevalent in the middle (36 %) and lower thirds (64 %). The distance was significantly bigger in men in some tooth positions. CONCLUSIONS: Based on the present findings, one-fifth of the patients may have a diameter of the SAC >1 mm, large enough to cause bleeding and/or paraesthesia. CBCT imaging may assist surgeons to plan grafting and osteotomy procedures, while avoiding these neurovascular structures.

Bridging the knowledge-Practice gap: Insights from a survey of Belgian dental professionals on diagnosis and supportive oral cancer treatment in comparison with international guidelines.

OBJECTIVE: Early detection significantly improves the prognosis of oral cancer patients, contingent upon the knowledge of dental professionals. This study aimed to assess and compare the knowledge, practices and perceptions regarding oral cancer among dental professionals in Belgium. MATERIALS AND METHODS: A cross-sectional survey was distributed via Qualtrics to general dentists, dental specialists, dental hygienists, and oral and maxillofacial surgeons. The self-administered questionnaire comprised three sections: demographics (4 questions), knowledge (9 questions) and clinical practices (19 questions) related to oral cancer detection and treatment. Descriptive statistics were employed for data analysis, with Chi-square tests assessing responses by specialization, gender, years of experience and number of oral cancer patients treated. RESULTS: A total of 262 questionnaires were completed, with the majority of respondents being general dentists (61%) followed by dental specialists (25%), oral hygienists (8%) and oral and maxillofacial surgeons (6%). 70% of the respondents reported treating fewer than four oral cancer patients throughout their careers. 5 out of the 9 knowledge questions achieved over 50% correct responses, with an average correct answer rate of 54%. Oral and maxillofacial surgeons and dental professionals who have treated more than four oral cancer patients, demonstrated significantly higher scores on multiple knowledge questions. Responses to clinically oriented questions showed less diversity across professions, and generally aligning with guidelines from professional oncological societies. CONCLUSION: This survey highlights the need for enhanced education on oral cancer among Belgian dental professionals. Knowledge levels were notably higher among more experienced respondents. The development and implementation of comprehensive guidelines tailored to dentists and oral hygienists for oral cancer prevention and patient care are warranted to optimize clinical practice standards.

Virtual reconstruction of orbital defects using Gaussian process morphable models.

PURPOSE: The conventional method to reconstruct the bone level for orbital defects, which is based on mirroring and manual adaptation, is time-consuming and the accuracy highly depends on the expertise of the clinical engineer. The aim of this study is to propose and evaluate an automated reconstruction method utilizing a Gaussian process morphable model (GPMM). METHODS: Sixty-five Computed Tomography (CT) scans of healthy midfaces were used to create a GPMM that can model shape variations of the orbital region. Parameter optimization was performed by evaluating several quantitative metrics inspired on the shape modeling literature, e.g. generalization and specificity. The reconstruction error was estimated by reconstructing artificial defects created in orbits from fifteen CT scans that were not included in the GPMM. The developed algorithms utilize the existing framework of Gaussian process morphable models, as implemented in the Scalismo software. RESULTS: By evaluating the proposed quality metrics, adequate parameters are chosen for non-rigid registration and reconstruction. The resulting median reconstruction error using the GPMM was lower (0.35 ± 0.16 mm) compared to the mirroring method (0.52 ± 0.18 mm). In addition, the GPMM-based reconstruction is automated and can be applied to large bilateral defects with a median reconstruction error of 0.39 ± 0.11 mm. CONCLUSION: The GPMM-based reconstruction proves to be less time-consuming and more accurate than reconstruction by mirroring. Further validation through clinical studies on patients with orbital defects is warranted. Nevertheless, the results underscore the potential of GPMM-based reconstruction as a promising alternative for designing patient-specific implants.

Exploring long-term responses to immune checkpoint inhibitors in recurrent and metastatic head and neck squamous cell carcinoma.

OBJECTIVES: Immune checkpoint inhibitors (ICI) have introduced a new era in the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Optimal duration for ICI therapy is still unclear and the long-term outcomes and toxicity in patients responding to these therapies warrant further exploration. This study attempts to identify the clinical and biological determinants of a durable response and evaluate outcomes following ICI treatment discontinuation. MATERIALS AND METHODS: A retrospective review of 181 patients treated with ICI for R/M HNSCC was conducted. Long-term responders were defined as patients who sustained disease control at least two years after initiating ICI therapy. We compared clinical and biological characteristics associated with these long-term responders against the broader treatment population. RESULTS: 10 % of R/M HNSCC patients treated with ICIs demonstrated a durable long-term response. Only three relapses (16 %) occurred after discontinuing ICI treatment in this subset, with a median follow-up of 52 months. Upon retreatment with ICI, two attained a documented response. Extended ICI response was observed even with < 2 years of treatment. 74 % of long-term responders experienced immune-related adverse events (irAEs), 37 % of which severe irAEs. Hypothyroidism was the most frequently reported irAEs. The predictive potential of systemic inflammation indices for clinical response appears to be limited. CONCLUSIONS: ICI present an optimistic avenue for HNSCC patients, offering substantial long-term responses. The study suggests that a two-year treatment could be optimal and irAEs, although common, are typically mild.