Three-dimensional evaluation of the maxillary effects of two orthopaedic protocols for the treatment of Class III malocclusion: A prospective study.

OBJECTIVES: To compare the three-dimensional maxillary dentoskeletal effects of a modified alternate rapid maxillary expansion and constriction facemask protocol (Alt-RAMEC/FM) with the traditional rapid maxillary expansion facemask protocol (RME/FM) performed in deciduous or early mixed dentition Class III patients. SETTING AND SAMPLE POPULATION: Orthodontic Clinic of the Section of Dentistry of the Department of Surgery and Translational Medicine of the University of Florence. Thirty-four Class III patients were enrolled and allocated by alternating assignment to either Alt-RAMEC/FM or RME/FM therapy. MATERIALS AND METHODS: Prior to treatment, all patients were evaluated, and a cone beam computed tomography (CBCT) scan was acquired. After completion of the orthopaedic therapy (average interval 1.2 years), a follow-up CBCT scan was obtained. Anatomic landmark identification on the CBCTs and subsequent quantification of the changes were performed. The primary outcome variable was the anteroposterior displacement of the anterior nasal spine (ANS AP). The treatment groups were compared with independent samples t tests. RESULTS: The patients in the two treatment groups showed a similar degree of compliance. No statistically significant differences were recorded for any variable when comparing the Alt-RAMEC/FM and RME/FM groups. In particular, the between-group difference for ANS AP was 0.0 mm (95%CI: -0.6;0.7, P = 0.933). CONCLUSIONS: Both Alt-RAMEC/FM and RME/FM produced favourable orthopaedic changes in Class III growing patients. Neither protocol was superior to the other in terms of maxillary protraction effectiveness.

Transverse relationship of permanent molars after crossbite correction in deciduous dentition.

OBJECTIVE: To evaluate the transverse relationships of the first permanent molars after the correction of posterior crossbite performed during the deciduous dentition with two different treatment protocols. MATERIALS/METHODS: Ninety patients (40 males and 50 females) with posterior crossbite were treated during the deciduous dentition with either a removable expansion plate (RP group, 60 patients) or rapid maxillary expander (RME group, 30 patients). The dental casts before treatment (T0, mean age 5.1 ± 0.7 years) and after treatment, when the first permanent molars were fully erupted, (T1, mean age 7.7 ± 1.0 years) were analysed. The prevalence rates for posterior crossbite on the first permanent molars in the two groups were compared by means of chi-squared test with Yates correction. A logistic regression was performed to evaluate the factors that could influence the presence/absence of posterior crossbite on the first permanent molars. RESULTS: Prevalence rate of posterior crossbite on the first permanent molars at T1 was 34.4 per cent in the total sample, 28.3 per cent for the RP group and 46.6 per cent for the RME group. No significant predictors for the 'presence/absence of posterior crossbite on the first permanent molars' at T1 were found. LIMITATIONS: Retrospective study. CONCLUSIONS: After treatment of posterior crossbite during the deciduous dentition phase, the first permanent molars erupted in crossbite in the 34.4 per cent of the cases. The type of treatment is not a significant predictor for the presence of posterior crossbite on the first permanent molars.

Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study.

BACKGROUND: Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS, BRAF, NRAS and PIK3CA mutations in a large collection of CRC patients from genetically-homogeneous Sardinian population. METHODS: A total of 1284 Sardinian patients with histologically-proven diagnosis of colorectal carcinoma (CRC) and presenting with metastatic disease were included into the study. Genomic DNA was isolated from formalin-fixed, paraffin-embedded primary tumour tissue samples of CRC patients and screened for mutations in RAS and BRAF genes, using pyrosequencing assays, and in PIK3CA gene, using automated DNA sequencing assays. RESULTS: Overall, mutation rates were 35.6 % for KRAS, 4.1 % for NRAS, and 2.1 % for BRAF. Among available DNA samples, 114/796 (14.3 %) primary CRCs were found to carry a mutation in the PIK3CA gene. In this subset of patients analysed in all four genes, a pathogenetic mutation of at least one gene was discovered in about half (378/796; 47.5 %) of CRC cases. A mutated BRAF gene was found to steadily act as a negative prognostic factor for either time to progression as metastatic disease (from detection of primary CRC to diagnosis of first distant metastasis; p = 0.009) or partial survival (from diagnosis of advanced disease to the time of death or last control; p = 0.006) or overall survival (p < 0.001). No significant impact on prognosis was observed for mutated KRAS, NRAS, and PIK3CA genes or combined RAS mutations (all RAS). CONCLUSIONS: Our study defines both prevalence and prognostic role of main activated oncogenes in a population-based large collection of CRC patients.

Bonded versus banded rapid palatal expander followed by facial mask therapy: analysis on digital dental casts.

OBJECTIVES: To compare the dental effects produced by a bonded versus a banded expander combined with facial mask (FM) in patients with Class III malocclusion by means of digital dental casts. MATERIALS AND METHODS: Two groups of patients with Class III malocclusion and maxillary transverse deficiency in the deciduous or early mixed dentition were selected. The first group consisted of 25 subjects (12 females; 13 males) with a mean age of 7.4 years (SD 1.2 years) treated with a bonded expander and FM. The second group consisted of 25 subjects (13 females; 12 males) with a mean age of 8.1 years (SD 1.3 years) treated with a banded expander and FM. For each subject of the two groups, initial (pre-treatment, T1) and final (post-treatment, T2) dental casts were taken and scanned. Maxillary digital models of T1 and T2 were superimposed on the palatal rugae in order to analyse the maxillary anchorage loss. Significant between-group differences were tested with independent sample t-test (P < 0.05). RESULTS: No statistical differences were found for any of the variables observed. CONCLUSION: Orthopaedic treatment of Class III malocclusion with either a bonded or a banded expander and FM during the deciduous or early mixed dentition induced a significant expansion of the maxillary arch and a slight mesialization of the posterior anchoring teeth with no difference between the two intraoral appliance designs.

Forecasting craniofacial growth in individuals with class III malocclusion by computational modelling.

AIM: To develop a mathematical model that adequately represented the pattern of craniofacial growth in class III subject consistently, with the goal of using this information to make growth predictions that could be amenable to longitudinal verification and clinical use. MATERIALS AND METHODS: A combination of computational techniques (i.e. Fuzzy clustering and Network analysis) was applied to cephalometric data derived from 429 untreated growing female patients with class III malocclusion to visualize craniofacial growth dynamics and correlations. Four age groups of subjects were examined individually: from 7 to 9 years of age, from 10 to 12 years, from 13 to 14 years, and from 15 to 17 years. RESULTS: The connections between pathway components of class III craniofacial growth can be visualized from Network profiles. Fuzzy clustering analysis was able to define further growth patterns and coherences of the traditionally reported dentoskeletal characteristics of this structural imbalance. Craniofacial growth can be visualized as a biological, space-constraint-based optimization process; the prediction of individual growth trajectories depends on the rate of membership to a specific 'winner' cluster, i.e. on a specific individual growth strategy. The reliability of the information thus gained was tested to forecast craniofacial growth of 28 untreated female class III subjects followed longitudinally. CONCLUSION: The combination of Fuzzy clustering and Network algorithms allowed the development of principles for combining multiple auxological cephalometric features into a joint global model and to predict the individual risk of the facial pattern imbalance during growth.

Evaluation of mechanical properties of three different screws for rapid maxillary expansion.

BACKGROUND: The aim of this in vitro study was the evaluation of the mechanical properties the screws for rapid maxillary expansion (RME). METHODS: Three commercially available screws for RME were tested: Leone A2620; Dentaurum Hyrax; Forestadent Palatal Split Screw. All expansion screws were 10 mm in size. For the evaluation of mechanical properties, the screws for RME were adjusted using the same maxillary dental model. An Instron 3365 testing machine with a load cell of 5 kN recorded the forces released by the screws at different amounts of activation (1, 5, 10, 15 and 20 quarters of a turn). Each type of screw was tested 10 times. Comparisons between the forces released by the different types of screws at different amounts of activation were carried out by means of analysis of Kruskal-Wallis test with post-hoc test di Tukey (P < 0.05). RESULTS: The results of this study showed that all 3 expansion devices were able to develop forces that could produce a separation of the palatine processes. The Hyrax and A2620 expanders developed force values over 20 kg and the Palatal Split screws about 16 kg. Both the A2620 and Hyrax expanders showed significantly greater amounts of forces at all the different amounts of activations with respect to the Palatal Split screw. CONCLUSIONS: All tested devices showed the capability of developing expansion forces (16-20 kg) adequate for RME. The A2620 and Hyrax expanders showed a greater level of rigidity than the Palatal Split screw.

Treatment timing of MARA and fixed appliance therapy of Class II malocclusion.

The objective of this study is to evaluate the effect of timing on Mandibular Anterior Repositioning Appliance (MARA) and fixed appliance treatment of Class II malocclusion in a prospective clinical trial. The treated sample consisted of 51 consecutively treated patients at prepubertal (n = 21), pubertal (n = 15), and postpubertal (n = 15) stages of development. Control groups for the three treated groups were generated from growth data of untreated Class II subjects. Lateral cephalograms were digitized and superimposed via cephalometric software at T1 (pre-treatment) and T2 (after comprehensive treatment). The T1-T2 changes in the treated groups were compared to those in their corresponding control groups with Mann-Whitney tests with Bonferroni correction. Mandibular elongation was greater at the pubertal stage (Co-Gn +2.6 mm, with respect to controls). Headgear effect on the maxilla was greater in the pre-peak sample (Co-A -1.9 mm, with respect to controls). Dentoalveolar compensations (proclination of lower incisors, extrusion and mesialization of lower molars, and reduction in the overbite) were significant in the pre-peak and post-peak groups. Optimal timing for Class II treatment with MARA appliance is at the pubertal growth spurt, with enhanced mandibular skeletal changes and minimal dentoalveolar compensations.

Dental anomalies in the primary dentition and their repetition in the permanent dentition: a diagnostic performance study.

This study investigated the recurrence in the permanent dentition of dental anomalies of the primary dentition. A sample of 189 subjects (100 males, 89 females, mean age of 5 years and 7 months) with anomalies of primary teeth (tooth hypodontia, supernumerary teeth, geminated teeth, and fused teeth) was selected and re-analyzed at a mean age of 11 years and 2 months for the recurrence of the dental anomalies in the permanent dentition. As a control group, 271 subjects (123 males, 148 females) without dental anomalies in the primary dentition were selected. The recurrence in the permanent dentition of the dental anomalies in the primary dentition was evaluated by measures of diagnostic performance. The results showed high values for the repetition of hypodontia (positive likelihood ratio = 102.0); low score for the repetition of hyperdontia (positive likelihood ratio = 6.5); low positive likelihood ratio (9.1) for gemination of primary teeth resulting in supernumerary permanent teeth; high positive likelihood ratio (47.0) for fusion of primary teeth followed by missing permanent teeth. Dental anomalies in the primary dentition are associated with an increased likelihood of anomalies of the succedaneous permanent.

Oral and craniofacial findings of Binder syndrome: two case reports.

Binder syndrome is a malformative midfacial alteration, known also as maxillonasal dysplasia or maxillonasal dysostosis. In this article, two cases of affected patients are reported, and the features of the condition are reviewed. One case presents a cleft lip. Hypotheses about etiology, pathogenesis, and classification of the syndrome are illustrated. This work provides a contribution for the delineation of a differential diagnostic procedure.

Early vs late orthodontic treatment of deepbite: a prospective clinical trial in growing subjects.

INTRODUCTION: The aim of this prospective clinical trial was to compare the outcomes of prepubertal vs pubertal treatment of deepbite patients with a protocol including biteplane and fixed appliances. METHODS: A sample of 58 subjects with deepbite completed the study. A total of 34 subjects received treatment with removable biteplane appliances in the mixed dentition at a prepubertal stage of skeletal maturation (early treatment group), and 24 subjects were treated at a pubertal stage of skeletal maturation in the permanent dentition (late treatment group). All subjects of both groups were reevaluated after an average period of 15 months after the completion of fixed appliance therapy. Treatment outcomes were assessed statistically after a phase with removable biteplane appliances and at the posttreatment observation. RESULTS: Treatment duration was significantly shorter in the early treatment group than in the late treatment group. Overbite reduction was significantly greater in the late treatment group (-3.1 mm) than in the early treatment group (-1.4 mm). In the late treatment group, 92% of the patients had a corrected overbite 1 year after therapy. CONCLUSIONS: Treatment of deepbite at puberty in the permanent dentition leads to significantly more favorable outcomes than treatment before puberty in the mixed dentition.

Stability of rapid maxillary expansion and facemask therapy: a long-term controlled study.

INTRODUCTION: The aim of this prospective controlled study was to evaluate the long-term effects of rapid maxillary expansion and facemask therapy in Class III subjects. METHODS: Twenty-two subjects (9 boys, 13 girls; mean age, 9.2 years ± 1.6) with Class III disharmony were treated consecutively with rapid maxillary expansion and facemask therapy followed by fixed appliances. The patients were reevaluated at the end of the 2-phase treatment (mean age, 14.5 years ± 1.9) and then recalled about 8.5 years after the end of rapid maxillary expansion and facemask treatment (mean age, 18.7 years ± 2.1). Two groups of controls with untreated Class III malocclusion were used for statistical comparisons of the short-term and long-term intervals. Statistical comparisons were performed with the Mann-Whitney U test. RESULTS: In the long term, no significant differences in maxillary changes were recorded, whereas the treatment group showed significantly smaller increases in mandibular protrusion. The sagittal maxillomandibular skeletal variables maintained significant improvements in the treatment group vs the control groups. CONCLUSIONS: In the long term, rapid maxillary expansion and facemask therapy led to successful outcomes in about 73% of the Class III patients. Favorable skeletal changes were mainly due to significant improvements in the sagittal position of the mandible.

Orthodontic forces released by low-friction versus conventional systems during alignment of apically or buccally malposed teeth.

The aim of the present study was to analyse the forces released by passive stainless steel self-ligating brackets (SLBs) and by a non-conventional elastomeric ligature-bracket system on conventional brackets ([slide ligatures on conventional brackets (SLCB)]) when compared with conventional elastomeric ligatures on conventional brackets (CLCB) during the alignment of apically or buccally malposed teeth in the maxillary arch. An experimental model consisting of five brackets was used to assess the forces released by the three different bracket-ligature systems with 0.012-inch super-elastic (SE) nickel-titanium (NiTi) wires in the presence of different amounts of apical or buccal canine misalignment of the canine (ranging from 1.5 to 6 mm). The forces released by each wire/bracket/ligature combination with the three different amounts of apical or buccal canine misalignment were tested 20 times. Comparisons between the different types of wire/bracket/ligature systems were carried out by means of analysis of variance on ranks with Dunnett's post hoc test (P < 0.05). No difference in the amount of force released in presence of a misalignment of 1.5 mm was recorded among the three systems. At 3 mm of apical misalignment a significantly greater amount of orthodontic force was released by SLB or SLCB when compared with CLCB, while no significant differences were found among the three systems at 3 mm of buccal canine displacement. When correction of a large amount of misalignment (6 mm) was attempted, a noticeable amount of force for alignment was still generated by the passive SLB and SLCB systems while no force was released in presence of CLCB.

Management of patients with cancer during the COVID-19 pandemic: The Italian perspective on the second wave.

The novel coronavirus disease 2019 (COVID-19) pandemic has been an overwhelming challenge for worldwide health systems. Since the beginning of year 2020, COVID-19 has represented a potential harm for cancer patients and has often hindered oncology care. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. During the second wave of COVID-19 pandemic, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on oncologists' clinical activity and what changes have been made compared with the Italian situation during the first wave of the pandemic. Overall, 138 heads of medical oncology departments participated in this survey: 75 (54%) from the North, 24 (17%) from the Centre and 39 (28%) from the South of Italy and islands. This survey provides an overview of Italian oncologists facing the second wave of COVID-19 pandemic. The lesson learned during the first wave of COVID-19 pandemic has led to a better organisation of clinical activities, and regular testing among healthcare practitioners, with better chances to grant patients' protection. However, the lack of standardised informatic platforms results in serious challenges in replacing frontal visits, often making a concrete reduction of patients' hospital accesses unfeasible. Oncologists need to keep preserving the continuum of care of patients. Standardisation of safety measures, together with the implementation of informatic platforms, can significantly improve oncology pathways during this second wave of COVID-19 pandemic.

Maxillary dental anomalies in children with cleft lip and palate: a controlled study.

OBJECTIVE: To evaluate the prevalence of dental abnormalities of the primary and permanent maxillary dentitions in children affected by unilateral (UCLP) and bilateral (BCLP) cleft of the lip and palate. METHODS: One hundred and fifty-six Caucasian patients (64 females and 92 males) affected by non-syndromic UCLP or BLCP were selected. A control sample of 1000 subjects (482 males and 518 females) without CLP was selected. All comparisons were carried out by means of z-tests on proportions. RESULTS: The prevalence rate for missing primary lateral incisors in UCLP subjects was 8.1% and it was 27.9% for the permanent lateral incisors. In BLCP subjects, the prevalence rates were 17% for the primary lateral incisors and 60% for the permanent lateral incisors. The second premolar was absent in 5.4% of UCLP subjects and in 8.8% in the BCLP sample. The statistical analysis revealed significant differences for the prevalence rates of all dental anomalies compared with the control group except for second premolar agenesis. CONCLUSIONS: In both UCLP and BCLP subjects the most prevalent missing teeth were the lateral incisors. The dental anomalies occurred predominantly in the cleft area, thus suggesting that the effect of the cleft disturbance is more local than general on the dentition.

Glenoid fossa position in Class III malocclusion associated with mandibular protrusion.

INTRODUCTION: Our aim in this study was to investigate the position of the glenoid fossa in subjects with Class III malocclusion associated with mandibular protrusion to better clarify the role of this craniofacial component in Class III skeletal disharmony. METHODS: A sample of 30 subjects, aged 8 years +/- 6 months, with skeletal and dental Class III malocclusion associated with mandibular protrusion, normal skeletal vertical relationships, and normal mandibular dimensions, was compared with a control group of 33 subjects with skeletal and dental Class I relationships. The comparisons between the Class III group and the control group on the cephalometric measures for the assessment of glenoid fossa position were performed with the Mann-Whitney U test at P <0.05. RESULTS: Subjects with Class III malocclusion had a significantly more mesial position of the glenoid fossa, when compared with the control group as measured with 3 parameters. CONCLUSIONS: An anterior position of the glenoid fossa is a possible diagnostic anatomic feature of Class III malocclusion associated with mandibular protrusion. An effective measurement to evaluate glenoid fossa position in craniofacial relationships is the cephalometric distance from the glenoid fossa to the frontomaxillary-nasal suture.

Forces produced by different nonconventional bracket or ligature systems during alignment of apically displaced teeth.

OBJECTIVE: To analyze the forces released by four types of passive stainless steel self-ligating brackets (SLBs), and by two nonconventional elastomeric ligature-bracket systems when compared with conventional elastomeric ligatures on conventional stainless steel brackets during the alignment of apically displaced teeth at the maxillary arch. MATERIALS AND METHODS: An experimental model consisting of five brackets was used to assess the forces released by the seven different ligature-bracket systems with 0.012'' or 0.014'' superelastic nickel titanium wire in the presence of different amounts of apical displacement of the canine (ranging from 1.5 mm to 6 mm). Comparisons between the different types of bracket/wire/ ligature systems were carried out by means of ANOVA on ranks with Dunnett's post hoc test (P < .05). RESULTS: When correction of a misalignment greater than 3 mm is attempted, a noticeable amount of force for alignment is generated by passive SLBs and nonconventional elastomeric ligature-bracket systems, and a null amount of force is released in the presence of conventional elastomeric ligatures on conventional brackets. CONCLUSIONS: When minimal apical displacement is needed (1.5 mm), the differences in performance between low-friction and conventional systems are minimal. These differences become significant when correction of a misalignment of greater than 3.0 mm is attempted.

Morphometric investigation in the skulls of young adults. A comparative study between 19th century and modern Italian samples.

OBJECTIVE: To test the hypothesis that there are no differences in the shape of the cranial complex between two samples from the same restricted geographical area and separated by almost 150 years. MATERIALS AND METHODS: A group of 35 skulls from the 19th century were selected and compared with a modern sample composed of 43 young adult subjects by means of lateral cephalograms and using a morphometric analysis. The peculiarity of this work is the uniformity of the two samples involving adults coming from the same restricted birthplace and with homogeneity for the orthodontic classification. RESULTS: Although the time spans are short, significant differences were found between the two samples. Shape changes included maxillary elongation toward the posterior region and a marked change in shape configuration in the mandible's points that shows a posterior rotation of the mandibular body. The global result of this cranial base point's movements symbolizes a tiny tendency toward closure of the cranial base angle. CONCLUSIONS: The hypothesis is rejected. Changes were evident, and environmental influences can be responsible for these changes.

Early orthodontic treatment of skeletal open-bite malocclusion with the open-bite bionator: a cephalometric study.

INTRODUCTION: This study was designed to evaluate the effectiveness of the open-bite bionator in growing subjects with increased vertical dimensions. METHODS: The records of 20 subjects with high-angle skeletal relationships (MPA > or =25 degrees) were examined. Cephalometric measurements were compared with those obtained from 23 sets of records of an untreated group matched according to age, sex, vertical skeletal relationships, and time intervals between records. Lateral cephalograms were analyzed before the start of treatment (mean age; 8.3 years) and after therapy and retention, with a mean period of observation of 2.5 years. RESULTS: The treated group had a significantly smaller palatal plane-mandibular plane angle (-1.9 degrees) and a greater overbite (+1.5 mm) associated with a significantly smaller overjet when compared with the control group. CONCLUSIONS: Based on the analysis of this sample, early treatment of skeletal open bite with the open-bite bionator appears to produce a modest effect that mainly consists of significant improvement in intermaxillary divergence. No favorable effects on the extrusion of posterior teeth were found.

Dentoalveolar effects induced by a removable expansion plate.

OBJECTIVE: The aim of this article was to analyze the changes in the transverse dimensions of the dental arches produced by a removable expansion plate (Removable Spring Expander, RSE) in subjects with unilateral posterior crossbite. MATERIALS AND METHODS: The treated group (TG) comprised of 17 subjects (5 males and 12 female) with unilateral posterior crossbites. Dental casts were available at pre-treatment (T1) and at a post-retention observation period (T2). The mean age at T1 was 6 years +/- 1 year and 4 months, and 7 years 11 months +/- 1 year and 5 months at T2. Seventeen subjects (7 males, 10 females) with an untreated unilateral posterior crossbite were used as the control group (CG). The mean age was 5 years 11 months +/- 1 year and 2 months at T1 and 7 years 9 months +/- 1 year and 4 months at T2. Post-retention changes in the transverse dimensions of the dental arches were evaluated statistically by means of a t-test for independent samples. RESULTS: The TG showed statistically significant increments when compared with untreated controls in maxillary intermolar widths (4.5 mm), intercanine widths (3.6 mm), and there were significant improvements in the posterior transverse interarch discrepancy (4.2 mm) and in the anterior transverse interarch discrepancy (3.3 mm). No statistically significant differences were found for the mandibular intermolar and intercanine widths between TG and CG. CONCLUSIONS: The expansion plate is a simple and effective device for the expansion of the upper arch in the deciduous and early mixed dentitions.

Enamel defects and aphthous stomatitis in celiac and healthy subjects: Systematic review and meta-analysis of controlled studies.

OBJECTIVES: The aim of this systematic review was to compare the presence of enamel defects and aphthous stomatitis between celiac patients and healthy controls. DATA SOURCES: A systematic review of articles selected from MEDLINE, EMBASE and Google Scholar was performed by two independent operators. Additional studies hand-searched and found in the principal dental and gastroenterology journals were included. STUDY SELECTION: Only controlled studies on celiac patients compared to healthy subjects were included. DATA EXTRACTION: Independent extraction of articles by 2 authors using predefined data fields, including study quality indicators. DATA SYNTHESIS: In total, the celiac patients had greater frequency of enamel defects (odds ratio=5.69, 95%CI from 3.47 to 9.33, P<0.00001, I2=90%, 30 studies). Considering only the children, the odds ratio was 5.63 (95%CI from 3.95 to 8.01, P<0.00001, I2=65%, 24 studies), while in the adults the odds ratio was not significant (odds ratio=2.16, 95%CI from 0.95 to 4.88, P=0.06, I2=40%, 3 studies). In total, the celiac patients had greater frequency of aphthous stomatitis (odds ratio=3.79, 95%CI from 2.67 to 5.39, P<0.00001, I2=49%, 21 studies). Considering only the children, the odds ratio was 4.31 (95%CI from 3.03 to 6.13, P<0.00001, I2=29%, 13 studies), while in the adults the odds ratio was 47.90 (95%CI from 6.29 to 364.57, P=0.0002, 1 study). CONCLUSIONS: In children, celiac disease was associated with both enamel defects and aphthous stomatitis. The odds ratio estimates, however, should be interpreted with caution due to the high risk of bias showed by all the studies. In adults, the association between celiac disease and enamel defects or aphthous stomatitis was unclear because very few studies were performed on this population. CLINICAL SIGNIFICANCE: The presence of enamel defects and/or aphthous stomatitis in a child affected by other typical or atypical symptoms of celiac disease represents an indication for further diagnostic exams for celiac disease.