Pharmacogenetics in Oncology: A useful tool for individualizing drug therapy.

With the continuous development of genetics in healthcare, there has been a significant contribution to the development of precision medicine, which is ultimately aimed at improving the care of patients. Generally, drug treatments used in Oncology are characterized by a narrow therapeutic range and by their potential toxicity. Knowledge of pharmacogenomics and pharmacogenetics can be very useful in the area of Oncology, as they constitute additional tools that can help to individualize patients' treatment. This work includes a description of some genes that have been revealed to be useful in the field of Oncology, as they play a role in drug prescription and in the prediction of treatment response.

Patient's Perspective on Miniscrews During Orthodontic Treatment-A Systematic Review With Meta-Analysis.

During orthodontic treatment, undesirable reciprocal forces are generated during tooth movement, which explains the use of anchorage strategies to minimise their harmful effects through intra and/or extraoral appliances. Miniscrews are intraoral devices used for temporary skeletal anchorage. Miniscrews are small-sized intraoral devices used for temporary skeletal anchorage and are easy to place and remove. However, some studies refer to adverse effects such as inflammation, pain, and discomfort. This systematic review aims to synthesise the available evidence on the use of miniscrews during orthodontic treatment from the patient's perspective. The literature search was conducted using various databases MedLine through PubMed, Cochrane Library, Web of Science Core Collection, and EMBASE. A search was also carried out in the grey literature. The search terms used were "Orthodontic Anchorage Procedures," "mini-implant," "Mini Dental Implant," "Miniscrew," and "microimplant." Cochrane risk of bias tools was used to assess the quality of included studies. Patients tend to overestimate the pain inherent in this procedure. The insertion of micro implants is more accepted than the tooth extraction procedure, with less postoperative pain reported. The location, surgical technique, and type of anaesthesia used in the placement of miniscrews influence levels of discomfort. Additionally, the execution of a good surgical technique and the clinician's communication skills are factors that influence patient satisfaction and positive perception. The most frequent outcome reported is pain and discomfort, which varies depending on its location (less with mini interradicular screws than with extra-alveolar screws). Most patients are satisfied or very satisfied with this application.

Salivary counts of Streptococcus mutans and Lactobacillus in patients with and without cleft lip and/or palate undergoing orthodontic treatment: A meta-analysis.

OBJECTIVE: To conduct a systematic review with meta-analysis to assess if cleft lip and palate (CLP) patients undergoing orthodontic treatment have a higher colonization of Streptococcus mutans and Lactobacillus than patients without this condition. METHODS: Five electronic databases were searched systematically. The inclusion criteria were as follows: randomized clinical trials, non-randomized, or quasi-randomized controlled trials, prospective and retrospective studies published until March, 2021; articles that evaluated S. mutans and Lactobacillus profile in patients with and without cleft lip and palate undergoing orthodontic treatment. The random-effect model was used to perform the analysis of all the data collected. Statistic heterogeneity was evaluated with I2 test. RESULTS: In this systematic review, 2 cohort studies were included. The data analysis from 160 patients revealed that patients without cleft lip and palate had 4.5 times more predisposition to oral colonization with S. mutans than CLP patients. No statistical significant difference was found between these patients for colonization with Lactobacillus. CONCLUSIONS: Despite the limitations in the included studies, this systematic review suggested that CLP patients have a lower predisposition to oral colonization with S. mutans when compared to healthy patients.

A retrospective and tridimensional study of the maxillary sinus in patients with cleft lip and palate.

INTRODUCTION: Structural or anatomic differences may arise during the development of the maxillary sinus and the process of fusion of the palate in the presence of cleft lip and palate. The present study aimed to compare the maxillary sinus volume of patients with unilateral cleft lip and palate and a control group (noncleft patients). METHODS: In this retrospective case-control study, 160 cone-beam computed tomography images of 80 unilateral cleft lip and palate patients (41 males and 39 females; mean age, 12.7 ± 6.03 years) and 80 control patients (43 males and 37 females; mean age, 13.1 ± 6.27 years) were evaluated through the ITK-SNAP software (Cognitica, Philadelphia, Pa) to access the maxillary sinus volume. Analysis of covariance and regression analysis were used to assess the differences between the groups while considering the relationship between maxillary sinus volume, age, and sex. RESULTS: No statistically significant differences were found in the maxillary sinus volume analyzing a unilateral cleft lip and palate and a control group (P = 0.677). Considering the cleft group, there is a tendency for the maxillary sinus volume of the cleft side to be smaller than its contralateral (P < 0.001). Statistically significant differences were found in the maxillary sinus volume, regarding the age and sex of cleft and noncleft patients (P < 0.001 for age; P = 0.001 for sex). CONCLUSIONS: According to these results, the presence of unilateral cleft lip and palate did not affect the maxillary sinus volume, comparing cleft and noncleft patients. A biphasic growth pattern of the maxillary sinus and a presence of sexual dimorphism were found.

Pediatric Colorectal Cancer: A Heterogenous Entity.

INTRODUCTION: Colorectal cancer (CRC) is extremely rare in pediatric age. A poor outcome has been reported. AIMS: We aimed to characterize a group of pediatric CRC patients. MATERIALS AND METHODS: All patients with CRC below 18 years old registered in our Familial Cancer Risk Clinic (2002-2016) were included. Clinical and histologic features were evaluated. Germline mutations, microsatellite instability, and DNA mismatch repair proteins expression were analyzed. RESULTS: Five patients were included (3 males; mean age at diagnosis: 14.2 years (range, 9 to 17 y) and 4/5 had family history of cancer in second-degree relatives. With a maximum follow-up of 5.6 years, 2/5 patients died after 10 and 24 months, and 1 recurred after 15 months. All tumors were ≥pT3N2 and 3/5 presented signet ring cells/mucinous histology, corresponding to cases with stronger family history of cancer. Nevertheless, all CRCs analyzed (n=4) were microsatellite stable and/or expressed all mismatch repair proteins. Loss of heterozygosity for the 3 Bethesda dinucleotide markers was detected in 1/3 informative CRCs. A likely pathogenic germline MSH2 mutation was identified in only 1 patient. CONCLUSIONS: Pediatric CRC presented advanced disease and poor prognosis. These tumors had distinct histologic and molecular presentations, resembling features from different carcinogenic pathways, thus suggesting a heterogenous nature.

The nonsense mutation MSH2 c.2152C>T shows a founder effect in Portuguese Lynch syndrome families.

The mutational spectrum of the MMR genes is highly heterogeneous, but specific mutations are observed at high frequencies in well-defined populations or ethnic groups, due to founder effects. The MSH2 mutation c.2152C>T, p.(Gln718*), has occasionally been described in Lynch families worldwide, including in Portuguese Lynch syndrome families. During genetic testing for Lynch syndrome at the Portuguese Oncology Institutes of Porto and Lisbon, this mutation was identified in 28 seemingly unrelated families. In order to evaluate if this alteration is a founder mutation, haplotype analysis using microsatellite and SNP markers flanking the MSH2 gene was performed in the 28 probands and 87 family members. Additionally, the geographic origin of these families was evaluated and the age of the mutation estimated. Twelve different haplotypes were phased for 13 out of the 28 families and shared a conserved region of ∼3.6 Mb. Based on the mutation and recombination events observed in the microsatellite haplotypes and assuming a generation time of 25 years, the age estimate for the MSH2 mutation was 273 ± 64 years. The geographic origins of these families were mostly from the Northern region of Portugal. Concluding, these results suggest that the MSH2 c.2152C>T alteration is a founder mutation in Portugal with a relatively recent origin. Furthermore, its high proportion indicates that screening for this mutation as a first step, together with the previously reported Portuguese founder mutations, may be cost-effective in genetic testing of Lynch syndrome suspects of Portuguese ancestry.

Short-term pharyngeal airway space changes after mandibular advancement surgery in Class II patients-a two-dimensional retrospective study.

INTRODUCTION: Planning successful treatment for the correction of anatomic abnormalities of the upper airways, by surgical advancement of the mandible, depends on extensive knowledge of the pharyngeal airway space (PAS). However, there is limited scientific evidence about changes in PAS after mandibular advancement surgery. AIM: To evaluate the immediate changes in superior posterior airway space (SPAS) in Class II patients, after mandibular advancement surgery. MATERIALS AND METHODS: A cephalometric evaluation of 37 patients with skeletal Class II deformity was performed at 2 distinct time intervals: Pre-operative (T0) and immediate post-operative (T1), using Dolphin Image & Management Solutions, version 11.9, according to the method of Arnett/Gunson FAB Surgery. The differences due to the surgical intervention were assessed with Student's t test, and a Principal Component Analysis was used to evaluate the relationship between mandibular advancement and SPAS variables. Anticlockwise and clockwise rotation groups were also evaluated with Mann-Whitney tests. The statistical analysis was conducted in SPSS and R assuming a 0.05 level of significance. RESULTS: As an effect of mandibular advancement, an anteroposterior statistically significant increase in SPAS (P < 0.001) was perceived at all points measured. CONCLUSION: Our findings indicate that mandibular advancement surgery is a viable option to achieve widening of the SPAS in patients with Class II skeletal morphology.

Efficacy of Rapid Maxillary Expansion in the Treatment of Obstructive Sleep Apnea Syndrome: A Systematic Review With Meta-analysis.

OBJECTIVE: The objective of this study was to assess the efficacy of rapid maxillary expansion (RME) in the treatment of OSAS in children and adolescents. METHODS: Five electronic databases were searched systematically: PubMed, Web of Science, LILACS, Embase and Cochrane Library. SELECTION CRITERIA: Randomized controlled trials, nonrandomized controlled trials, cohort studies, and systematic reviews published in English, Spanish, or Portuguese between January 2000 and December 2016, performed on children and adolescents younger than 18 years with OSAS who underwent RME, and assessing RME efficacy as measured by the Apnea-Hypopnea Index (AHI) normalization were included. Qualitative assessment of the selected studies was performed using Critical Appraisal Skills Programme checklists. Statistical evaluation included 2 meta-analyses and was based on a random-effects model and Cochran's Q test and I2 statistics to assess heterogeneity across the publications. Electronic searches identified 84 publications. Five publications were considered valid and included in this systematic review. RESULTS: Results from the meta-analysis show an overall reduction in AHI after RME therapy. CONCLUSIONS: Increasingly the evidence indicates that RME devices reduce AHI in children with OSAS, making RME therapy an appropriate alternative treatment option for these patients.

Patient-Reported Outcomes of Maxillomandibular Surgery for Obstructive Sleep Apnea Treatment: A Scoping Review.

(1) Background: The present scoping review aims to scrutinize all existing patient-reported outcomes and assess the perspectives of obstructive sleep apnea patients after maxillomandibular surgery. (2) Methods: The review was carried out according to the extensions for scoping reviews using the PRISMA-ScR guidelines. Several databases were used to carry out the initial search. This study included randomized controlled trials, cohort studies, cross-sectional and case-control studies. The included studies considered patients with obstructive sleep apnea who were submitted to orthognathic surgery as the main subjects, and the patient's perception of quality of life, satisfaction, treatment experience and side effects were assessed. (3) Results: From 1407 examined articles, a total of 16 were included. Most of the included studies used more than one questionnaire to assess quality of life, except for five articles. The most commonly referred instruments were the Epworth Sleepiness Scale, SF-36, the Functional Outcomes of Sleep and Ottawa Sleep Apnea. The most commonly assessed outcomes were sleep quality, daytime function, facial aesthetics, dental function and emotional health. (4) Conclusions: The number of variables that can be evaluated from a patient's perspective are endless, as are the tools available to assess them. Not all of these tools, which are generally questionnaires, assess all the various outcomes, and some do not compare the pre- and post-surgical situations. Most of them are generic and lack specificity for obstructive sleep apnea.

Surface Treatment of Dental Mini-Sized Implants and Screws: A Systematic Review with Meta-Analysis.

Miniscrews are devices that allow for absolute skeletal anchorage. However, their use has a higher failure rate (10-30%) than dental implants (10%). To overcome these flaws, chemical and/or mechanical treatment of the surface of miniscrews has been suggested. There is no consensus in the current literature about which of these methods is the gold standard; thus, our objective was to carry out a systematic review and meta-analysis of the literature on surface treatments of miniscrews. The review protocol was registered (PROSPERO CRD42023408011) and is in accordance with the PRISMA guidelines. A bibliographic search was carried out on PubMed via MEDLINE, Cochrane Library, Embase and Web of Science. The initial search of the databases yielded 1684 results, with 98 studies included in the review, with one article originating from the search in the bibliographic references of the included studies. The results of this systematic review show that the protocols of miniscrew surface treatments, such as acid-etching; sandblasting, large-grit and acid-etching; photofunctionalization with ultraviolet light; and photobiomodulation, can increase stability and the success of orthodontic treatment. The meta-analysis revealed that the treatment with the highest removal torque is SLA, followed by acid-etching. On the other hand, techniques such as oxidative anodization, anodization with pre-calcification and heat treatment, as well as deposition of chemical compounds, require further investigation to confirm their effectiveness.

Comparison of in-office and at-home bleaching techniques: An umbrella review of efficacy and post-operative sensitivity.

Objectives: The objective of this umbrella review is to evaluate the efficacy and adverse effects of different teeth whitening techniques in-office (IO) and at-home (AH), regarding chromatic changes and teeth sensitivity. Materials and methods: The search was carried out from several databases. The included studies were all systematic reviews with or without meta-analysis of RCT or quasi-RCT. The participants were patients that underwent external dental bleaching in permanent vital teeth. The interventions were in-office (IO) bleaching techniques and at-home (AT) bleaching techniques with different bleaching agents and concentrations. Results: The search resulted in a total of 257 articles, and 28 SR were included in the qualitative analysis and nine in the quantitative analysis. There is no difference between in-office and at-home techniques in terms of color change (p = 0.95) and post-treatment sensitivity (p = 0.85). There is similarity risk and intensity of teeth sensitivity between AH and IO bleaching. IO bleaching with light-activated systems with low concentrations of bleaching agent showed similar results to IO bleaching techniques with high concentrated bleaching gels. With the application of the criteria of the AMSTAR 2 tool, the reviews were considered critically low to high. Conclusions: There are no significant differences in terms of color change between the different bleaching techniques compared. Teeth sensitivity is always present regardless of the technique used. The use of light activation systems did not increase the intensity and risk of post-operative sensitivity.

NSCLC presents metabolic heterogeneity, and there is still some leeway for EGF stimuli in EGFR-mutated NSCLC.

BACKGROUND: Metabolic remodeling is crucial in carcinogenesis and cancer progression. Oncogenic mutations may promote metabolic reprogramming in cancer cells to support their energy and biomass requirements. EGFR mutations are commonly found in non-small cell lung cancer (NSCLC) and may induce NSCLC metabolic rewiring. Whether EGFR-driven metabolic reprogramming triggers cell vulnerabilities with therapeutic potential remains unknown. METHODS: The role of EGFR signaling activation by EGF was investigated using NSCLC cell lines with different EGFR and KRAS status: A549 (EGFR WT and KRAS c.34G > A), H292 (EGFR WT and KRAS WT) and PC-9 (EGFR exon 19 E746-A750 deletion and KRAS WT). The effect of EGF on NSCLC cell death and cell cycle was evaluated using flow cytometry, and cell migration was assessed through wound healing. EGFR, HER2, MCT1, and MCT4 expression was analyzed through immunofluorescence or western blotting. We explored the impact of glucose and lactate bioavailability on NSCLC cells' metabolic profile using nuclear magnetic resonance (NMR) spectroscopy. Moreover, the expression of several relevant metabolic genes in NSCLC cells or patient samples was determined by RT-qPCR. RESULTS: We showed that cell lines presented different metabolic profiles, and PC-9 cells were the most responsive to EGF stimulus, as they showed higher rates of cell proliferation and migration, together with altered metabolic behavior. By inhibiting EGFR with gefitinib, a decrease in glucose consumption was observed, which may be related to the fact that despite PC-9 harbor EGFR mutation, they still express the EGFR WT allele. The analysis of NSCLC patients' RNA showed a correlation between MCT1/MCT4 and GLUT1 expression in most cases, indicating that the metabolic information can serve as a reference in patients' follow-up. CONCLUSION: Together, this study shows that NSCLC cell lines have heterogeneous metabolic profiles, which may be underlaid by different genetic profiles, revealing an opportunity to identify and stratify patients who can benefit from metabolism-targeted therapies.

Three-Dimensional Impression of Biomaterials for Alveolar Graft: Scoping Review.

Craniofacial bone defects are one of the biggest clinical challenges in regenerative medicine, with secondary autologous bone grafting being the gold-standard technique. The development of new three-dimensional matrices intends to overcome the disadvantages of the gold-standard method. The aim of this paper is to put forth an in-depth review regarding the clinical efficiency of available 3D printed biomaterials for the correction of alveolar bone defects. A survey was carried out using the following databases: PubMed via Medline, Cochrane Library, Scopus, Web of Science, EMBASE, and gray literature. The inclusion criteria applied were the following: in vitro, in vivo, ex vivo, and clinical studies; and studies that assessed bone regeneration resorting to 3D printed biomaterials. The risk of bias of the in vitro and in vivo studies was performed using the guidelines for the reporting of pre-clinical studies on dental materials by Faggion Jr and the SYRCLE risk of bias tool, respectively. In total, 92 publications were included in the final sample. The most reported three-dimensional biomaterials were the PCL matrix, ß-TCP matrix, and hydroxyapatite matrix. These biomaterials can be combined with different polymers and bioactive molecules such as rBMP-2. Most of the included studies had a high risk of bias. Despite the advances in the research on new three-dimensionally printed biomaterials in bone regeneration, the existing results are not sufficient to justify the application of these biomaterials in routine clinical practice.

Bulk-Fill Resins versus Conventional Resins: An Umbrella Review.

Currently, composite resins have become the material of choice for the restoration of posterior teeth. Although bulk-fill resins represent a tempting alternative due to their lower complexity and faster use, some dentists are reluctant to use this material. The objective is to compare the performance of bulk-fill resins and conventional resins in direct restorations of posterior teeth based on the literature. The databases that were used to carry out the research were PubMed/MEDLINE, Embase, the Cochrane Library and the WOS. This umbrella literature review complies with PRISMA standards and assesses the quality of studies using the AMSTAR 2 tool. With the application of the criteria of the AMSTAR 2 tool, the reviews were considered low to moderate. The overall meta-analysis, although without statistical significance, favours mostly the use of conventional resin, as it is about five times more likely to obtain a favourable result than bulk-fill resin. Bulk-fill resins result in a simplification of the clinical process of posterior direct restorations, which is an advantage. The performance in terms of several properties of bulk-fill resins and conventional resins showed that they present similar behaviour.

H2S-Synthesizing Enzymes Are Putative Determinants in Lung Cancer Management toward Personalized Medicine.

Lung cancer is a lethal disease with no truly efficient therapeutic management despite the progresses, and metabolic profiling can be a way of stratifying patients who may benefit from new therapies. The present study is dedicated to profiling cysteine metabolic pathways in NSCLC cell lines and tumor samples. This was carried out by analyzing hydrogen sulfide (H2S) and ATP levels, examining mRNA and protein expression patterns of cysteine catabolic enzymes and transporters, and conducting metabolomics analysis using nuclear magnetic resonance (NMR) spectroscopy. Selenium-chrysin (SeChry) was tested as a therapeutic alternative with the aim of having an effect on cysteine catabolism and showed promising results. NSCLC cell lines presented different cysteine metabolic patterns, with A549 and H292 presenting a higher reliance on cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) to maintain H2S levels, while the PC-9 cell line presented an adaptive behavior based on the use of mercaptopyruvate sulfurtransferase (MST) and cysteine dioxygenase (CDO1), both contributing to the role of cysteine as a pyruvate source. The analyses of human lung tumor samples corroborated this variability in profiles, meaning that the expression of certain genes may be informative in defining prognosis and new targets. Heterogeneity points out individual profiles, and the identification of new targets among metabolic players is a step forward in cancer management toward personalized medicine.

Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events.

Immune-checkpoint inhibitors (ICIs) are antagonists of inhibitory receptors in the immune system, such as the cytotoxic T-lymphocyte-associated antigen-4, the programmed cell death protein-1 and its ligand PD-L1, and they are increasingly used in cancer treatment. By blocking certain suppressive pathways, ICIs promote T-cell activation and antitumor activity but may induce so-called immune-related adverse events (irAEs), which mimic traditional autoimmune disorders. With the approval of more ICIs, irAE prediction has become a key factor in improving patient survival and quality of life. Several biomarkers have been described as potential irAE predictors, some of them are already available for clinical use and others are under development; examples include circulating blood cell counts and ratios, T-cell expansion and diversification, cytokines, autoantibodies and autoantigens, serum and other biological fluid proteins, human leucocyte antigen genotypes, genetic variations and gene profiles, microRNAs, and the gastrointestinal microbiome. Nevertheless, it is difficult to generalize the application of irAE biomarkers based on the current evidence because most studies have been retrospective, time-limited and restricted to a specific type of cancer, irAE or ICI. Long-term prospective cohorts and real-life studies are needed to assess the predictive capacity of different potential irAE biomarkers, regardless of the ICI type, organ involved or cancer site.

Frequency of CDH1, CTNNA1 and CTNND1 Germline Variants in Families with Diffuse and Mixed Gastric Cancer.

The most well-characterized hereditary form of gastric cancer is hereditary diffuse gastric cancer (HDGC), an autosomal dominant syndrome characterized by an increased risk of diffuse gastric and lobular breast cancer. HDGC is predominantly caused by germline pathogenic variants in the CDH1 gene, and more rarely in the CTNNA1 gene. Furthermore, the International Gastric Cancer Linkage Consortium (IGCLC) guidelines do not clarify whether or not mixed gastric cancer (with a diffuse component) should be considered in the HDGC genetic testing criteria. We aimed to evaluate the contribution of CTNNA1 and CTNND1 germline variants to HDGC. Additionally, we also intended to compare the frequencies of CDH1 and CTNNA1 (and eventually CTNND1) germline variants between patients with diffuse and mixed gastric carcinomas to evaluate if genetic testing for these genes should or should not be considered in patients with the latter. We analyzed the CDH1 gene in 67 cases affected with early-onset/familial mixed gastric carcinomas and the CTNNA1 and CTNND1 genes in 208 cases with diffuse or mixed gastric cancer who had tested negative for CDH1 pathogenic germline variants. A deleterious CTNNA1 germline variant was found in 0.7% (1/141) of diffuse gastric cancer patients meeting the 2020 IGCLC criteria, as compared to the rate of 2.8% of CDH1 deleterious variants found by us in this setting. No deleterious variants were found in CTNND1, but six variants of uncertain significance were identified in this gene. We did not find any pathogenic CDH1, CTNNA1 or CTNND1 variant in index patients with early-onset/familial mixed gastric cancer, so there is no evidence that supports including this tumor type in the testing criteria for germline variants in these genes. The role of the CTNND1 gene in inherited gastric cancer predisposition is still unclear.

Condylar Changes after Maxillary Expansion in Children with Cleft Lip and Palate-A Three-Dimensional Retrospective Study.

BACKGROUND: The presence of posterior crossbite can trigger aesthetic and functional changes as mandibular asymmetry in individuals, contributing to asymmetrical muscle function. Mandibular asymmetry and respective condyle adaptation may be an etiological factor in temporomandibular disorder. This study aims to evaluate the effects of maxillary expansion on the position and angulation of the condyles as well as the intercondylar distance in children with cleft lip and palate. METHODS: Twenty-five individuals with cleft lip and palate who underwent maxillary expansion were selected. Condylar changes were evaluated by cone beam computed tomography using the Pullinger and Hollender formula. To determine the statistically significant differences between the variables, the Student t-test and the Benjamini-Hochberg correction method for multiple comparisons were used. RESULTS: No statistically significant differences between angulation and condylar position before and after maxillary expansion were found. The intercondylar distance tended to increase in growing individuals with cleft lip and palate after maxillary expansion. CONCLUSIONS: Intercondylar distance shows a tendency to increase after expansion regardless of the cleft phenotype. No differences were found in angulation and condylar position with the changes in occlusion resulting from maxillary expansion.

Cleft Orthodontic Care in Europe: A Cross-Sectional Survey.

(1) Background: Orthodontists have an important role in cleft care. Over the two decades since the Eurocleft studies, a significant improvement in healthcare systems has been achieved but there has been no critical assessment regarding the establishment of proposed standard protocols. This study aimed to describe the current provider characteristics, orthodontic appliances, services offered, orthodontic complications, and cost analysis of cleft treatment in Europe. (2) Methods: A cross-sectional 22-question online survey, accessible from January 2021 to July 2021, was sent to 214 practitioners, pertaining to provider characteristics, orthodontic appliances, services offered, orthodontic complications, and cost analysis. Descriptive statistics were calculated for each question. Fisher's exact test was used to assess the association between categorical variables. (3) Results: A total of 79 responses from 23 European countries completed the survey (response rate = 37%), with 69 surveys being assessed after the exclusion of incomplete surveys. Rapid maxillary expansion was the preferred expansion protocol (45%). Distraction osteogenesis was the most reported alternative treatment to secondary bone grafts (19%), with private practitioners being less likely to perform these treatments (Fisher's exact test, p = 0.001). Orthodontic services offered were, however, rather similar in the various locations of provision (hospital and/or university, private). Compromised oral hygiene (77%) was the most reported orthodontic complication. The National Health Services support the majority of cleft orthodontic care (67%) in Europe. (4) Conclusion: An apparent improvement in orthodontic healthcare provision has been achieved within Europe in the last two decades, but there are several discrepancies, namely regarding treatment timing and the appliances offered.

Application of Three-Dimensional Digital Technology in Orthodontics: The State of the Art.

Three-dimensional technologies are one of the most recent and relevant advancements in the field of Dentistry. These systems, including intraoral scans, 3D imaging exams (CAT scan, CBCT and MRI), CAD/CAM 3D printing devices and 3D computer software, have enabled clinicians to greatly improve patient care along with reducing treatment planning time. The present descriptive study aims to explore possible applications of 3D technologies during the diagnosis, treatment plan, case monitoring and result assessment in orthodontics. The overall upgrade provided by these technologies can improve the clinicians' workflow and effectiveness by simplifying conventional techniques considered to be especially arduous.