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.

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.

Biomechanical feasibility of non-locking system in patient-specific mandibular reconstruction using fibular free flaps.

Mandibular reconstruction with free fibular flaps is frequently used to restore segmental defects. The osteosythesis, including locking and non-locking plate/screw systems, is essential to the mandibular reconstruction. Compared with the non-locking system that requires good adaption between plate and bone, the locking system appears to present a better performance by locking the plate to fixation screws. However, it also brings about limitations on screw options, a higher risk of screw failure, and difficulties in screw placement. Furthermore, its superiority is undermined by the advancing of patient-specific implant design and additive manufacturing. A customized plate can be designed and fabricated to accurately match the mandibular contour for patient-specific mandibular reconstruction. Consequently, the non-locking system seems more practicable with such personalized plates, and its biomechanical feasibility ought to be estimated. Finite element analyses of mandibular reconstruction assemblies were conducted for four most common segmental mandibular reconstructions regarding locking and non-locking systems under incisal biting and right molars clenching, during which the influencing factor of muscles' capacity was introduced to simulate the practical loadings after mandibular resection and reconstruction surgeries. Much higher, somewhat lower, and similar maximum von Mises stresses are separately manifested by the patient-specific mandibular reconstruction plate (PSMRP), fixation screws, and reconstructed mandible with the non-locking system than those with the locking system. Equivalent maximum displacements are identified between PSMRPs, fixation screws, and reconstructed mandibles with the non-locking and locking system in all four reconstruction types during two masticatory tasks. Parallel maximum and minimum principal strain distributions are shared by the reconstructed mandibles with the non-locking and locking system in four mandibular reconstructions during both occlusions. Conclusively, it is feasible to use the non-locking system in case of patient-specific mandibular reconstruction with fibular free flaps based on the adequate safety, comparable stability, and analogous mechanobiology it presents compared with the locking system in a more manufacturable and economical way.

Comparison of two corticosteroid regimens on brain volumetrics in patients with Duchenne muscular dystrophy.

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.

The predictive and prognostic value of weight loss and body composition prior to and during immune checkpoint inhibition in recurrent or metastatic head and neck cancer patients.

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% (HR 0.85 [0.74-0.98] p = 0.03). Baseline cachexia in combination with >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.

High doses of zoledronic acid induce differential effects on femur and jawbone microstructure.

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 < .05) increased bone quantity (↑BV/TV, ↓Po[Tot], ↑Tb.Th), bone density (↑TMD, ↑BMD), and osteosclerosis of the trabecular bone (↓Tb.Sp, ↓Conn.Dn, ↓Tb.Pf, ↓SMI) in all anatomical sites. Bone remodeling suppression due to zoledronic acid treatment was more pronounced (p < .05) in the femoral metaphysis relative to the mandible and epiphysis. The exploratory linear discriminant analysis showed that for the mandible, it was mainly the bone quantity-related morphometric indices (BV/TV and Tb.Th), while for the femoral epiphysis and metaphysis, it was bone structure-related (Tb.Pf and Tb.N), which are of primary importance to study the treatment effect. CONCLUSION: High doses of bisphosphonates can differently affect the bone quantity, density, and structure in long bones and jawbones. In the metaphysis, bone changes were primarily concentrated in the region of the growth plate. Future studies may consider the use of bone morphometric indices to evaluate the effect of bisphosphonates.

Dynamic changes in tooth displacement and bone morphometry induced by orthodontic force.

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.

Biomechanical validation of structural optimized patient-specific mandibular reconstruction plate orienting additive manufacturing.

BACKGROUND AND OBJECTIVE: Owing to the unexpected in vivo fracture failure of the original design, structural optimized patient-specific mandibular reconstruction plates (PSMRPs) were created to boost the biomechanical performance of bridging segmental bony defect in the mandibular reconstruction after tumor resection. This work aimed to validate the biomechanical benefit of the structural optimized PSMRPs relative to the original design and compare the biomechanical performance between PSMRP1 with generic contour customization and PSMRP2 with a tangent arc upper margin in mandibular angle region. METHODS: Finite Element Analysis (FEA) was used to evaluate the biomechanical behavior of mandibular reconstruction assemblies (MRAs) concerning these two structural optimized PSMRPs by simulating momentary left group clenching and incisal clenching tasks. Bonded contact was set between mandibular bone and fixation screws and between PSMRP and fixation screws in the MRA, while the frictionless connection was allocated between mandibular bone and PSMRP. The loads were applied on four principal muscles, including masseter, temporalis, lateral and medial pterygoid, whose magnitudes along the three orthogonal directions. The mandibular condyles were retrained in all three directions, and either the left molars or incisors area were restrained from moving vertically. RESULTS: The peak von Mises stresses of structural optimized PSMRPs (264 MPa, 296 MPa) were way lower than that of the initial PSMRP design (393 MPa), with 33 and 25% reduction during left group clenching. The peak magnitude of von Mises stress, minimum principal stress, and maximum principal strain of PSMRP1 (264 MPa, 254 MPa; -297 MPa, -285 MPa; 0.0020, 0.0020) was lower than that of PSMRP2 (296 MPa, 286 MPa; -319 MPa, -306 MPa; 0.0022, 0.0020), while the peak maximum principal stress of PSMRP1 (275 MPa, 257 MPa) was higher than that of PSMRP2 (254 MPa, 235 MPa) during both left group clenching and incisal clenching tasks. CONCLUSIONS: The structural optimized PSMRPs reveal their biomechanical advantage compared with the original design. The PSMRP1 presents better biomechanical performance to the patient-specific mandibular reconstruction than PSMRP2 as a result of its superior safety, preferable flexibility, and comparable stability. The PSMRP2 provides biomechanical benefit in reducing the maximum tension than PSMRP1, indicated by lower peak maximum principal stress, through tangent arc upper margin in mandibular angle region.

Long-term survival of implant-based oral rehabilitation following maxillofacial reconstruction with vascularized bone flap.

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 < 0.0001) were at a significantly higher risk of implant failure. CONCLUSION: The cumulative implant survival rate was highest at 1st year followed by 2nd and 5th year, indicating that the risk of implant failure increased over time. Risk indicators that seem to be detrimental to long-term survival include poor oral hygiene, irradiated flap and systemic diseases.

A Retrospective Analysis of a Cohort of Patients Treated With Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer.

OBJECTIVE: The 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 METHODS: In 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. RESULTS: 137 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. CONCLUSION: Along 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.

Value of six comorbidity scales for predicting survival of patients with primary surgery for oral squamous cell carcinoma.

BACKGROUND: Comorbidities influence treatment outcome of oral squamous cell carcinoma (OSCC). This study compared the predictive performance of six comorbidity scales for overall survival after surgery for OSCC. METHODS: We retrospectively analyzed OSCC patients, surgically treated at an academic center in Belgium between January 01, 2000 and January 01, 2020. Validity of the scales was evaluated using the area under the curve (AUC) of receiver operating characteristic curves. RESULTS: Three hundred and twenty three patients were included. Elixhauser Comorbidity Index (AUC = 0.74, 95% CI: 0.55-0.92; AUC = 0.73, 95% CI: 0.55-0.80), modified Elixhauser Comorbidity Index (AUC = 0.72, 95% CI: 0.54-0.91; AUC = 0.69, 95% CI: 0.51-0.77), and Combined Comorbidity Index (AUC = 0.76, 95% CI: 0.58-0.84; AUC = 0.76, 95% CI: 0.59-0.84) were meaningful predictors for 2 and 5-year survival, respectively. CONCLUSION: Selected comorbidity scales were capable of predicting overall survival for OSCC patients 2 and 5 years after primary surgery.

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.

The limits of motivational influence in ADHD: no evidence for an altered reaction to negative reinforcement.

Functional magnetic resonance imaging studies have reported a diminished response in the brain's reward circuits to contingent cues predicting future monetary gain in adolescents with attention-deficit/hyperactivity disorder (ADHD). The situation with regard to monetary loss is less clear, despite recognition that both positive and negative consequences impact ADHD behaviour. Here, we employ a new Escape Monetary Loss Incentive task in an MRI scanner, which allows the differentiation of contingency and valence effects during loss avoidance, to examine ADHD-related alterations in monetary loss processing. There was no evidence of atypical processing of contingent or non-contingent monetary loss cues in ADHD - either in terms of ratings of emotional and motivational significance or brain responses. This suggests that the ability to process contingencies between performance and negative outcomes is intact in ADHD and that individuals with ADHD are no more (or less) sensitive to negative outcomes than controls. This latter finding stands in stark contrast to recent evidence from a similar task of atypical emotion network recruitment (e.g. amygdala) in ADHD individuals to cues predicting another negative event, the imposition of delay, suggesting marked specificity in the way they respond to negative events.

Preclinical study of additive manufactured plates with shortened lengths for complete mandible reconstruction: Design, biomechanics simulation, and fixation stability assessment.

BACKGROUND: A combination of short titanium plates fabricated using additive manufacturing (AM) provides multiple advantages for complete mandible reconstruction, such as the minimisation of inherent implant deformation formed during AM and the resulting clinical impact, as well as greater flexibility for surgical operation. However, the biomechanical feasibility of this strategy is still unclear, and therefore needs to be explored. METHOD: Three different combinations of short mandible reconstruction plates (MRPs) were customised considering implant deformation during the AM process. The resulting biomechanical performance was analysed by finite element analysis (FEA) and compared to a conventional single long MRP. RESULTS: The combination of a long plate and a short plate (Design 3 [LL61 mm/RL166 mm]) shows superior biomechanical properties to the conventional single long plate (Design 1 [TL246 mm]) and reveals the most reliable fixation stability among the three designs with short plates. Compared to conventional Design 1, Design 3 provides higher plate safety (maximum tensile stress on plates reduced by 6.3%), lower system fixation instability (relative total displacement reduced by 41.4%), and good bone segment stability (bone segment dislocation below 42.1 µm) under masticatory activities. CONCLUSIONS: Preclinical evidence supports the biomechanical feasibility of using short MRPs for complete mandible reconstruction. Furthermore, the results could also provide valuable information when treating other large-sized bone defects using short customised implants, expanding the potential of AM for use in implant applications.

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.

Biomechanical comparison of locking and non-locking patient-specific mandibular reconstruction plate using finite element analysis.

Patient-specific mandibular reconstruction plate (PSMRP), as one of the patient-specific implants (PSIs), offers a host of benefits to mandibular reconstruction. Due to the limitation of fabricating screw hole threads in the PSMRP, 3D printed PSMRP is applied to the non-locking system directly in the mandibular reconstruction with bone graft regardless of the locking system. Since the conventional manual-bending reconstruction plate (CMBRP) provides better fixation in the locking system, it needs to be validated whether the locking PSMRP performs better than the non-locking PSMRP in the patient-specific mandibular reconstruction. Thereupon, the purpose of this study was to compare the biomechanical behavior between the locking and non-locking PSMRP. Finite element analysis (FEA) was used to conduct the biomechanical comparison between the locking PSMRP and non-locking PSMRP by simulating the momentary incisal clenching through static structural analysis. Mandible was reconstructed through the virtual surgical planning, and subsequently a 3D model of mandibular reconstruction assembly, including reconstructed mandible, PSMRP, and fixation screws, was generated and meshed for the following FEA simulations. In the form of equivalent von Mises stress, equivalent elastic strain, and total deformation, the locking PSMRP demonstrated its higher strengths of preferable safety, desirable flexibility, and anticipated stability compared with the non-locking PSMRP, indicated by much lower maximum stress, lower maximum strain and equivalent displacement. Locking PSMRP/screw system provides a better fixation effect to the patient-specific mandibular reconstruction than the non-locking one as a result of its productive fixation nature. FEA plays a paramount role in pre-validating the design of PSMRP through the biomechanical behavior evaluation in static structural analysis.

Adherence to Computer-Assisted Surgical Planning in 136 Maxillofacial Reconstructions.

OBJECTIVE: To 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 METHODS: A 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). RESULTS: The 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). CONCLUSION: The 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.

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.