Efficacy of topical agents in oral mucositis prevention: Systematic review and network meta-analysis.

BACKGROUND: Oral mucositis (OM) is considered one of the most common side effects of patients undergoing cancer therapy. OM prevention plays a crucial role in the effectiveness of cancer treatment and the patient's quality of life. Different preventive treatments have been proposed in clinical trials, however with inconclusive results. MATERIALS AND METHODS: A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: in cancer patients, do specific topical agents compared to standard treatments or placebo reduce the onset and severity of oral mucositis? The risk of bias was assessed, and a network meta-analysis was conducted. RESULTS: Of 2913 results, 30 randomized clinical trials were considered suitable for inclusion. A total of 2564 patients were analyzed, of which 1284 belonged to the test group and 1280 belonged to the control group. Natural products were the most used, followed mainly by antimicrobial agents, coating agents, and basic oral care measures. Topical sucralfate resulted in the most powerful intervention for the OM prevention (OR = 0.04, 95%C.I. = 0.01-0.25, p-value = 0.001). CONCLUSION: Due to its cytoprotective action, low cost, ease of administration, and safety, sucralfate could become a potential ally to prevent the onset of OM during cancer therapy.

Prosthesis Emergence Angle Influences Marginal Bone Level for External Connection Implants: A Cross-Sectional Study.

PURPOSE: To retrospectively evaluate the influence of prosthetic features on marginal bone level changes around bone-level implants with an external hex connection. MATERIALS AND METHODS: A total of 100 patients with 166 implants and cemented crowns were included. Demographic and clinical data were collected. Prosthetic features were radiographically evaluated, including emergence angle (EA), emergence profile (EP), crown-implant ratio (CIR), and abutment height. Marginal bone levels were measured on intraoral radiographs taken at baseline and after at least 1 year. The correlation between prosthetic features and marginal bone loss (MBL) was then investigated. RESULTS: The mean follow-up time was 43.94 months. Implant length varied between 5 and 13 mm. The mean height of the abutments used was 1.55 mm. EA measured an average 30.62 degrees (± 13.20) mesially and 29.45 degrees (± 13.07) distally. The CIR was 0.99 (± 0.26). The mean MBL was 0.19 mm on the mesial side and 0.20 mm on distal side of the implants. Significant positive associations emerged between MBL and implant length (P < .005) and with EA (P < .05). A convex profile of the crown was shown to be associated with a higher distal MBL (P = .025) compared to concave and straight profiles.

The Potential microRNA Prognostic Signature in HNSCCs: A Systematic Review.

Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as "signature microRNA OR miR" AND "HNSCC OR LSCC OR OSCC OR oral cancer" were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.

Mesenchymal Stem Cells in Soft Tissue Regenerative Medicine: A Comprehensive Review.

Soft tissue regeneration holds significant promise for addressing various clinical challenges, ranging from craniofacial and oral tissue defects to blood vessels, muscle, and fibrous tissue regeneration. Mesenchymal stem cells (MSCs) have emerged as a promising tool in regenerative medicine due to their unique characteristics and potential to differentiate into multiple cell lineages. This comprehensive review explores the role of MSCs in different aspects of soft tissue regeneration, including their application in craniofacial and oral soft tissue regeneration, nerve regeneration, blood vessel regeneration, muscle regeneration, and fibrous tissue regeneration. By examining the latest research findings and clinical advancements, this article aims to provide insights into the current state of MSC-based therapies in soft tissue regenerative medicine.

Effect of Fabrication Technology on the Accuracy of Surgical Guides for Dental-Implant Surgery.

BACKGROUND: The accuracy of surgical guides is a relevant factor in both surgical safety and prosthetic implications. The impact of widespread fabrication technologies (milling and 3D printing) was investigated. METHODS: Surgical guides manufactured by means of two specific milling and 3D-printing systems were digitized and compared in a 3D analysis with the digital file of the designed guides. The surface mean 3D distance (at the surface where the teeth and mucosa made contact) and the axial and linear deviations of the sleeves' housings were measured by means of a metrological software program. Univariate and multivariate statistical analyses were used to investigate the effects of the fabrication technology, type of support, and arch type on the surgical guides' accuracy. RESULTS: The median deviations of the intaglio surface in contact with the mucosa were significantly (p < 0.001) lower for the milled surgical guides (0.05 mm) than for the 3D-printed guides (-0.07 mm), in comparison with the reference STL file. The generalized estimated equation models showed that the axial deviations of the sleeves' housings (a median of 0.82 degrees for the milling, and 1.37 degrees for the 3D printing) were significantly affected by the fabrication technology (p = 0.011) (the milling exhibited better results), the type of support (p < 0.001), and the combined effect of the fabrication technology and the sleeve-to-crest angle (p = 0.003). The linear deviation (medians of 0.12 mm for the milling and 0.21 mm for the 3D printing) of their center points was significantly affected by the type of support (p = 0.001), with the milling performing slightly better than the 3D printing. CONCLUSIONS: The magnitude of the difference might account for a limited clinical significance.

Early pathological changes of peri-coronal tissue in the distal area of erupted or partially impacted lower third molars.

AIM: This study was performed to histologically evaluate peri-coronal tissues of partially impacted and erupted third molars that did not exhibit pathologic peri-coronal radiolucency. MATERIALS AND METHODS: Healthy patients with erupted or partially erupted (with part or all of the dental crown present in the oral cavity) mandibular third molars (classified as IA and IIA according to the Pell and Gregory classification) and vertically positioned (according to the Winter classification or erupted third molars) associated with peri coronal radiolucency of equal to or less than 2.5 mm. Associated with third molar surgery, tissue sampling from the distal area was performed, which was subjected to an anatomopathological examination to determine the histological nature. RESULTS: One hundred teeth (100 patients) were selected, and 100 specimens were analyzed. 53% of the sample were included in the non-pathological group and 47% showed pathological changes (fibrotic tissue (n 15), periodontal cyst-like (n 9), squamous epithelial metaplasia (4 cases), islands of odontogenic epithelial residues organized micro-cyst with keratocystic/ameloblastic appearance (4 cases), granulation tissue (n 8), giant cell tumour (n 4) and lobular capillary hemangioma (n 4)). Pathological changes did not have differences in incidence between the gender (p value = 0.85) and did not show any correlation with age, (p value = 0,96). CONCLUSIONS: These findings suggest that radiographic appearance may not be a reliable indicator of the absence of disease within a dental follicle. Therefore, clinicians should pay attention to or follow up on even peri-coronal radiolucency of less than 2.5 mm.

Dental trauma and prevention guidelines: a narrative review.

Dental injuries affect different patients every day in conditions that can range from domestic, work, or road accidents. As for traumas in the age of development, the field is restricted to domestic, sports, and school environments. The purpose of this study was to clarify the current protocols in the literature to limit and manage this type of pathology. This narrative review considers the literature of the last 20 years on this topic in different ways. The literature is in agreement with dividing the treatments into primary and secondary and also according to what is the place where the trauma occurred to evaluate the type of intervention. However, all protocols are aimed at implementing efficient preventive strategies rather than having to solve a problem subsequently, certainly, new protocols and protection systems can limit this problem which leads not only to more or less complex problems related to oral health and aesthetics but also possible subsequent psychological problems.

Hepatitis-virus-positive patients management in dental office.

BACKGROUND: Hepatitis is a condition characterized by inflammation of the liver, which can be caused by several viruses including hepatitis A, B, C, D and E. This condition can affect the oral health of patients and increase the risk of complications during dental management. The clinical management of hepatitis patients in the dental setting requires a comprehensive and individualized approach to ensure safety and optimal treatment outcomes. This article aims to provide a comprehensive overview of the current literature on the dental management of patients with different forms of hepatitis. METHODS: The article focuses on the specific challenges associated with dental treatments in hepatitis patients, including increased risk of infection and bleeding. Additionally, the article provides recommendations for dental practitioners, including infection control measures, communication with medical providers, and the use of prophylactic antibiotics. RESULTS: The authors show that the dental management of patients with hepatitis requires a thorough understanding of the specific challenges associated with this condition, as well as the implementation of appropriate preventive measures to ensure the safety and well-being of these patients. CONCLUSIONS: Further research is needed to better understand the impact of hepatitis on oral health and the most effective approaches to managing dental treatments in this patient population.

Evaluation of the effectiveness of tube drain on postoperative discomfort in mandibular third molar surgery: prospective randomized split-mouth study.

INTRODUCTION: The present randomized split-mouth study aimed to investigate the clinical effectiveness of postoperative discomfort of the use of a surgical drain after lower third molar extraction. MATERIALS AND METHODS: It was conducted a prospective randomized split-mouth study involving 30 patients with bilateral symmetric lower third molar. Each patient underwent two operations for the extraction of impacted teeth: test site (tube drain) and control site (conventional total closure of surgical flap), resulting in 30 cases in the test group, and 30 cases in the control group.Pain, swelling, and mouth opening were evaluated immediately before the surgeries, after 1, 3 and 7 days postoperatively in both groups. Data were analyzed with non-parametric test (Kruskal-Wallis test and the post hoc Dun test, and Wilcoxon matched-pairs signed rank test). RESULTS: Facial swelling (p < .001) was significantly less in test group compared with the control group on all examined days. Trismus is significantly reduced only on the third day (p < .001); Pain measurements did not differ statistically significantly between the two groups on all post-operative days (p > .05). CONCLUSION: The use of the tube drain reduced facial swelling and trismus, but had no influence on the subjective perception of postoperative pain.

Adjunctive use of locally delivered host-modulators in intra-bony defects as part of step 2 periodontal therapy: systematic review, meta-analysis and trial sequential analysis.

BACKGROUND: This systematic review and meta-analysis aimed at investigate the role of locally delivered host-modulators in combination with step 2 of periodontal therapy in reducing probing pocket depth, improving clinical attachment level and reducing bone defect depth in intra-bony defects. HIGHLIGHT: RCT with at least 6 months follow-up were included in this study. Risk of bias assessment was performed with Cochrane collaboration tool and Grade GRADEpro. In addition, meta-analysis and trial sequential analysis were used to aggregate the available evidence. 22 studies met the inclusion criteria and were included in this systematic review. At 6 months locally delivered host-modulators significantly improved PD and CAL and bone defect depth. CONCLUSION: Considering the emerging role of host-inflammatory response in the treatment of periodontitis, several studies are exploring the role of locally delivered host modulators as an adjunct to step 2 of periodontal therapy.

Three Dimensional Printed Surgical Guides: Effect of Time on Dimensional Stability.

PURPOSE: To analyze, in vitro, the dimensional stability over time of 3D-printed surgical guides. MATERIALS AND METHODS: Ten surgical guides, manufactured by digital light processing 3D-printing technology, were scanned immediately after post-processing and then after 5, 10, 15, and 20 days. The corresponding standard tessellation language (STL) files were used for comparison with the reference CAD project. Mean absolute deviation (MAD) of the intaglio surface, axial, and linear deviations of the sleeves' housings were measured. Generalized estimated equations models (α = 0.05) were used to investigate the effect of time. RESULTS: MAD of the teeth intaglio surface showed less variation (minimum: 0.002, maximum: 0.014 mm) than that of the mucosa (minimum: 0.026, maximum: 0.074 mm). Axial variations of the sleeves' housings on the sagittal (minimum: -0.008°, maximum: -0.577°) and frontal plane (minimum: -0.193°, maximum: 0.525°) changed with similar patterns, but opposite trends (decreasing for the former). Linear deviations of center points of the sleeves' housings had a shifting (minimum: -0.074, maximum: 0.02 mm) pattern with a decreasing tendency. Time after processing had a significant effect, either alone or nested with guides volume, on all outcomes of interest, except for MAD of the mucosa intaglio surface (p < 0.001), which was significantly affected only by the time-volume nested effect (p = 0.012). CONCLUSIONS: Within the limitations of the experimental design, postmanufacturing dimensional variations of surgical guides were statistically significant. Although limited, they are an additional source of variability affecting the overall accuracy of computer-guided surgery. As such, they should be addressed by further research.

Surgical guides for dental implants: Measurement of the accuracy using a freeware metrology software program.

PURPOSE: Manufacturing-related inaccuracies of surgical guides for static computer-aided implant surgery may contribute to the overall potential error in the obtained implant position. Measuring such inaccuracies before surgery may provide quality control assessment and improve the safety and outcomes of guided implant surgery. This technical report demonstrates a workflow to measure the accuracy of a surgical guide (at the intaglio surface and sleeve housing) using a freeware metrology software program. METHODS: The scan of a milled surgical guide was aligned to and compared with its reference computer-aided design model using a freeware metrology software program (GOM Inspect suite; GOM GmbH). The trueness of the internal surface of the surgical guide was measured as an indicator of adaptation to the supporting tissues. Additionally, some features were constructed to extract the plane at the sleeve entrance and sleeve axis and to set a local coordinate system on them. Linear and angular deviations between the planned and obtained sleeve axes were measured using this system. Such measurements, together with additional known data (sleeve offset and the planned implant length), allowed the estimation of linear errors in implant position at both the implant platform and apex by applying common geometric formulas, based on the assumption that all other sources of error in implant position could be effectively controlled during the surgical procedure. CONCLUSIONS: The proposed digital technique is a cost-effective approach for quality control of the inaccuracies of a surgical guide and predicts the related potential error in implant position.

Pattern and localization of perineural invasion predict poor survival in oral tongue carcinoma.

BACKGROUND: Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor-Node-Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. METHODS: About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni-/multifocal and as intra-/peritumoral. Disease-Specific and Relapse-Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. RESULTS: Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph-node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p-value = 0.008). Moreover, patients exhibiting both multifocal intra- and peritumoral PNI reported poorest DSS (Hazard Ratio = 2.409, p-value = 0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. CONCLUSIONS: Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached.

A pathogenic variant in the FLCN gene presenting with pure dementia: is autophagy at the intersection between neurodegeneration and cancer?

Introduction: Folliculin, encoded by FLCN gene, plays a role in the mTORC1 autophagy cascade and its alterations are responsible for the Birt-Hogg-Dubé (BHD) syndrome, characterized by follicle hamartomas, kidney tumors and pneumothorax. Patient and results: We report a 74-years-old woman diagnosed with dementia and carrying a FLCN alteration in absence of any sign of BHD. She also carried an alteration of MAT1A gene, which is also implicated in the regulation of mTORC1. Discussion: The MAT1A variant could have prevented the development of a FLCN-related oncological phenotype. Conversely, our patient presented with dementia that, to date, has yet to be documented in BHD. Folliculin belongs to the DENN family proteins, which includes C9orf72 whose alteration has been associated to neurodegeneration. The folliculin perturbation could affect the C9orf72 activity and our patient could represent the first human model of a relationship between FLCN and C9orf72 across the path of autophagy.

Congenital Defects in a Patient Carrying a Novel Homozygous AEBP1 Variant: Further Expansion of the Phenotypic Spectrum of Ehlers-Danlos Syndrome Classical-like Type 2?

In 2018, a new clinical subtype, caused by biallelic variants in the AEBP1 gene, encoding the ACLP protein, was added to the current nosological classification of the Ehlers-Danlos Syndromes (EDS). This new phenotype, provisionally termed EDS classical-like type 2 (clEDS2), has not yet been fully characterized, as only nine cases have been reported to date. Here we describe a patient, homozygous for a novel AEBP1 pathogenic variant (NM_001129.5 c.2123_2124delTG (p.Val708AlafsTer5)), whose phenotype is reminiscent of classical EDS but also includes previously unreported multiple congenital malformations. Furthermore, we briefly summarize the current principal clinical manifestations of clEDS2 and the molecular evidence surrounding the role of AEBP1 in the context of extracellular matrix homeostasis and connective tissue development. Although a different coexisting etiology for the multiple congenital malformations of our patient cannot be formally excluded, the emerging role of ACLP in TGF-ß and WNT pathways may explain their occurrence and the phenotypical variability of clEDS2.

Elastodontic treatment with oral bio-activators in young children.

BACKGROUND: Elastodontic therapy can correct bad oral habits and malocclusions in young patients by guiding jaw growth, eliminating functional disorders, and improving tooth position. The aim of this study was to assess the effects of bio-activator therapy on the presence of atypical swallowing with tongue thrust in growing patients. METHODS: A retrospective study was conducted. Data regarding the early orthodontic treatment of 40 consecutive patients with atypical swallowing and tongue thrust (23 males and 17 females) were assembled from January 2019 to January 2020. All patients (≥7 and ≤15 years of age) were monitored for 1 year in a private practice in Isernia, Italy. RESULTS: The mean age at commencement of orthodontic treatment was 8.5 years (range=7.1-14.9 years), and the mean total duration of therapy was 1 year (range=11 months-1 year). Final lateral radiographs demonstrated a mean of improvement of 8° for upper and lower incisor proclination (I/SN) and 3.5° for incisor mandibular plane angle (IMPA) in 36 patients, and 5° of I/SN and 2° of IMPA in the remaining 4 children after 1 year of treatment. CONCLUSIONS: Bad oral habits in younger patients must not be ignored. The duration of treatment can differ depending on the severity of the open bite and the patient's cooperation. This study demonstrates the short-term efficacy of these myofunctional appliances in the treatment of atypical swallowing. In order to quickly eliminate factors which endanger healthy development of dento-skeletal structure, it is important to closely monitor patients during their development phase.

Prevalence of temporomandibular disorders in people with multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE: To explore the prevalence of temporomandibular disorders (TMD) in patients affected by multiple sclerosis (MS) and whether there is a correlation between TMD prevalence and MS severity. METHODS: PubMed, Web of Science, and Lilacs were systematically searched until July 30 2022, to identify studies presenting patients affected by MS and whether there is a correlation between TMD prevalence and MS severity. RESULTS: Out of 292 papers, 8 studies were included with 1312 study participants. Among the 8 studies, 5 had a control group; 5 used the RDC/TMD criteria, 1 used the NOT-S instrument, and 2 did not define a standardized method to define TMD symptoms. Meta-analysis revealed that the MS group had a higher rate than the control group, showing an association between MS and TMD (RR 2.10; 95% CI: 1.21-3.65). CONCLUSION: These findings show an association between TMD and MS. ABBREVIATIONS: Australian Longitudinal Study of MS (AMSLS); Computed Tomography (CT); Community Periodontal Index of Treatment Needs (CPITN); Central Nervous System (CNS); Decayed, Missing, and Filled (DMF); Decayed, Missing, or Filled Teeth Index (DMFT); Expanded Disability Status Scale (EDSS); European Academy of Craniomandibular Disorders (EACD); Healthy Controls (HC); International Prospective Register of Systematic Reviews (PROSPERO); Multiple Sclerosis (MS); Nordic Orofacial Test-Screening (NOT-S); Participants, model of Intervention, Comparison and Outcome (PICO); Preferred Reporting Items for Systematic Reviews (PRISMA); Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD); Temporomandibular Joint (TMJ); Temporomandibular Disorders (TMD); World Health Organization (WHO).

Genetic Dysruption of the Histaminergic Pathways: A Novel Deletion at the 15q21.2 locus Associated with Variable Expressivity of Neuropsychiatric Disorders.

The involvement of the Histaminergic System (HS) in neuropsychiatric disease is not well-documented, and few studies have described patients affected by different neuropsychiatric conditions harbouring disruptions in genes involved in the HS. In humans, histamine is synthetised from histidine by the histidine decarboxylase enzyme encoded by the HDC gene (OMIM*142704). This is the sole enzyme in our organism able to synthetise histamine from histidine. Histamine is also contained in many different food types. We hereby describe a twenty-one-year-old female diagnosed with a borderline intellectual disability with autistic traits and other peculiar neuropsychological features carrying a 175-Kb interstitial deletion on chromosome 15q21.2. The deletion was inherited from the mother, who was affected by a severe anxiety disorder. The deleted region contains entirely the HDC and the SLC27A2 genes and partially the ATP8B4 gene. The HDC gene has been previously associated with Tourette Syndrome (TS). Based on the functional role of the HDC, we propose this gene as the best candidate to explain many traits associated with the clinical phenotype of our patient and of her mother.

Antibiotic prophylaxis at the time of dental implant placement: a cost-effectiveness analysis.

BACKGROUND: Antibiotic prophylaxis during implant placement may improve implant short term survival. Nevertheless, use of antibiotics carries risks of adverse effects and antibiotic resistance. The aim of the present study is to compare the use of antibiotics in dental implant procedures in terms of costs and effectiveness. METHODS: A decision-tree model was developed using TreeAge Pro Healthcare software. Two strategies were compared: Antibiotics and No antibiotics in implant placement procedures. The costs were calculated considering direct costs for implant placement, antibiotic costs, and costs for implant replacement in case of failure. Effectiveness was defined in terms of General Oral Health Assessment Index. Outcomes were evaluated as Incremental Cost Effectiveness Ratio (ICER). One-way sensitivity analysis and Probabilistic Sensitivity Analysis were performed for the most influential variables to test parameter uncertainty. Patient and healthcare perspectives were considered. RESULTS: Antibiotic prophylaxis resulted to be cost-effective compared to no use of antibiotics (ICER = 14,692,64 and ICER = 3841,18, respectively for patient's and healthcare perspective). The cost of antibiotics, cost of implant replacement in case of failure and probability of adverse effects significantly influenced the results. CONCLUSIONS: From an individual patient perspective, antibiotic strategy can be considered cost-effective, even when the cost of antibiotic therapy increases. We can conclude that the administration of antibiotics in association with implant placement is recommended in clinical practice, as it increases the success rate and makes the treatment more effective. However, attention should be placed when healthcare perspective is considered, particularly in terms of antibiotic resistance that may impact public health and associated costs.