Tooth movement with dental anchorage vs. skeletal anchorage: A systematic review of clinical trials.

The aim of this study is to compare the time and movement of orthodontic treatment using dental anchorage and skeletal anchorage in adolescent and adult patients with dental malocclusions. A systematic search was conducted in the Embase, PubMed, Lilacs, Cochrane, Trip, and Scopus databases up to October 2022. All the articles were selected using title and abstract, applying the inclusion and exclusion criteria. Disagreements were resolved with a third author. Finally, a full-text selection took place. The data extraction was conducted by two authors who independently evaluated the risk of bias. The methodological quality of the randomized clinical trials was evaluated using the Cochrane tool for the evaluation of the randomized clinical trials. Six articles were included in the data analysis. There were four clinical trials and two randomized clinical trials. A total of 176 patients was obtained with an age range between 14 and 46 years. Four studies showed significant differences when comparing the two anchorages in retraction or distalization of tooth groups, and two showed no differences when using dental and skeletal anchorage for vertical movements; only the articles with vertical movements showed relapse. We can conclude that skeletal anchorage generates precise and stable horizontal movements without overloading or changing the position of the molar. Future studies must incorporate three-dimensional technology for greater clinical accuracy.

Psychopathological characteristics in ultra-high risk for psychosis with and without comorbid ADHD.

AIM: This study investigates the psychopathological characteristics of a sample of individuals at ultra-high risk for psychosis with and without comorbid attention-deficit hyperactivity disorder (ADHD). METHODS: Twenty-eight subjects (aged 13-21 years; 13 females) with attenuated psychosis syndrome (APS) were recruited in a cross-sectional study and divided into two groups, each with 14 patients, according to the presence or absence of ADHD. RESULTS: The APS group showed a significantly higher prevalence of negative symptoms than the APS + ADHD group. Other characteristics investigated (positive symptoms, aberrant salience, psychotic-like experiences and prodromal symptoms) did not differ between groups. CONCLUSIONS: The different profiles of negative symptoms in the APS with or without ADHD might suggest the presence of a specific subtype among individuals at ultra-high risk for psychosis. Longitudinal studies with larger samples will provide information about the role of negative symptoms in determining conversion to full psychosis in those people with 'pure' APS and those with APS + ADHD.

Antimicrobial Activity of Methylene Blue Associated with Photodynamic Therapy: In Vitro Study in Multi-Species Oral Biofilm.

The control of infectious diseases caused by biofilms is a continuing challenge for researchers due to the complexity of their microbial structures and therapeutic implications. Photodynamic therapy as an adjunctive anti-infective treatment has been described as a possible valid approach but has not been tested in polymicrobial biofilm models. This study evaluated the effect of photodynamic therapy in vitro with methylene blue (MB) 0.01% and red LEDs (λ = 660 nm, power density ≈ 330 mW/cm2, 2 mm distance from culture) on the metabolic activity and composition of a multispecies subgingival biofilm. Test Groups LED and MB + LED showed a more significant reduction in metabolic activity than the non-LED application group (~50 and 55%, respectively). Groups LED and MB equally affected (more than 80%) the total bacterial count in biofilms. No differences were noted in the bacterial biofilm composition between the groups. In vitro LED alone or the MB + LED combination reduced the metabolic activity of bacteria in polymicrobial biofilms and the total subgingival biofilm count.

The effectiveness of autologous platelet concentrates in prevention and treatment of medication-related osteonecrosis of the jaws: A systematic review.

The systematic review aims to answer the PICOS question: "Are the autologous platelet concentrates (APCs) an effective strategy in prevention and/or treatment of patients at risk of/affected by medication-related osteonecrosis of the jaws (MRONJ)?". A literature search was conducted via PubMed, MEDLINE, EMBASE, and CINAHL (January 2006 - September 2023). 30 articles were included, evaluating preventive (n = 8*) and treatment strategies (n = 23*). The risk of bias and quality of studies were assessed utilising ROB-2, ROBIN-1 and GRADE criteria. Meta-analysis was undertaken for eligible studies. The application of APCs demonstrated a statistically significant effectiveness in prevention of MRONJ in 86.13% (p < 0.001) but failed to achieve the same level of certainty in treatment of established MRONJ in 83.4% (p = 0.08). High levels of bias were identified; thus, the results should be interpreted with caution. More high quality prospective randomised controlled trials are needed to further evaluate the effectiveness of APCs in management of MRONJ.

Traditional and innovative interventions in the management of enuresis.

Introduction: Enuresis (NE) is a socially stigmatising and stressful condition affecting children's and parent's quality of life. The aim of this review was to evaluate and summarize the current knowledge about the pharmacological and non-pharmacological traditional and innovative treatments in children with NE. Material and methods: We examined the following bibliographic electronic databases: PubMed and the Cochrane Library, from January 2000 until July 2023. The search was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) (8) and was limited to English-language papers that focused on enuresis in patients under 18 years old. Each paper that met the eligibility criteria was reviewed and analyzed in full text by three authors and any discrepancies among them were solved by debate. Due to the heterogeneity of the articles examined, we focused on a qualitative analysis. Results: Overall, we identified 560 records through database searching. As first step, we excluded 46 articles in non-English language, 6 records whose related articles were not available, 8 articles concerning ongoing trials and 210 duplicated papers. As second step, we eliminated 215 records by evaluating only title and abstract because they did not match the inclusive criteria we mentioned before. Of the remaining 75 studies, we excluded 34 through a further discussion among authors upon the reliability of data. Thus, 41 selected articles were included in the review. Conclusions: Multiple treatment approaches, both pharmacological and non pharmacological, have been established and validated to reduce signs and symptoms of NE and improve quality of life and the social and emotional discomfort experienced by children. The aim of pediatrician is to identify the right therapy protocol for very single child, evaluating the best approach for him and the family.

Evaluation of the Microbial Profile on the Polydioxanone Membrane and the Collagen Membrane Exposed to Multi-Species Subgingival Biofilm: An In Vitro Study.

Dehiscence in surgeries involving membranes often leads to bacterial contamination, hindering the healing process. This study assessed bacterial colonization on various membrane materials. Polydioxanone (PDO) membranes, with thicknesses of 0.5 mm and 1 mm, and a collagen membrane were examined. Packages containing polystyrene pins were crafted using these membranes, attached to 24-well plates, and exposed to oral bacteria from supra and subgingival biofilm. After a week's anaerobic incubation, biofilm formation was evaluated using the DNA-DNA hybridization test. Statistical analysis employed the Kruskal-Wallis test with Dunn's post hoc test. The biofilm on the polystyrene pins covered by the 0.5 mm PDO membrane showed a higher count of certain pathogens. The collagen membrane had a greater total biofilm count on its inner surface compared to both PDO membranes. The external collagen membrane face had a higher total biofilm count than the 0.5 mm PDO membrane. Furthermore, the 1 mm PDO membrane exhibited a greater count of specific pathogens than its 0.5 mm counterpart. In conclusion, the collagen membrane presented more biofilm and pathogens both internally and on its inner surface.

Correction: "Nutripiatto": A tool for nutritional education. A survey to assess dietary habits in preschool children.

[This corrects the article DOI: 10.1371/journal.pone.0282748.].

Condylar Positional Changes in Skeletal Class II and Class III Malocclusions after Bimaxillary Orthognathic Surgery.

Orthognathic surgery is indicated to modify the position of the maxillomandibular structure; changes in the mandibular position after osteotomy can be related to changes in the position of the mandibular condyle in the articular fossa. The aim of this study was to determine changes produced in the mandibular condyle 6 months after orthognathic surgery. A cross-sectional study was conducted that included subjects who had undergone bimaxillary orthognathic surgery to treat dentofacial deformity of Angle class II (group CII) or Angle class III (group CIII). Standardized images were taken using cone-beam computed tomography 21 days before surgery and 6 months after surgery; measurement scales were used to identify the condylar position and its relations with the anterior, superior, and posterior joint spaces. The results were analyzed using the Shapiro-Wilk and Student's t-tests, while considering a value of p < 0.05 as indicating a significant difference. Fifty-two joints from 26 patients, with an average age of 27.9 years (±10.81), were analyzed. All subjects in both group CII and group CIII showed a significant change in the anterior, superior, and posterior joint spaces. However, postoperative changes in the position of the condyle in the articular fossa were not significant in the anteroposterior analysis. We conclude that orthognathic surgery causes changes in the sagittal position of the mandibular condyle in subjects with mandibular retrognathism and prognathism.

The Interplay of Raloxifene and Sonochemical Bio-Oss in Early Maxillary Sinus Bone Regeneration: A Histological and Immunohistochemical Analysis in Rabbits.

The study aimed to assess the efficacy of using Raloxifene with ultrasonic processing to enhance Bio-Oss®, a bone graft substitute, for maxillary sinus bone height reconstruction. A total of 24 rabbit maxillary sinuses were distributed into three groups, each receiving different treatments: Bio-Oss® only, sonicated Bio-Oss, and sonicated Bio-Oss® with Raloxifene. Surgical procedures and subsequent histomorphometric and immunohistochemistry analyses were conducted to evaluate the bone formation, connective tissue, and remaining biomaterial, as well as the osteoblastic differentiation and maturation of collagen fibers. Results indicated that the sonicated Bio-Oss® and Bio-Oss® groups showed similar histological behavior and bone formation, but the Raloxifene group displayed inflammatory infiltrate, low bone formation, and disorganized connective tissue. The statistical analysis confirmed significant differences between the groups in terms of bone formation, connective tissue, and remaining biomaterial. In conclusion, the study found that while sonicated Bio-Oss® performed comparably to Bio-Oss® alone, the addition of Raloxifene led to an unexpected delay in bone repair. The findings stress the importance of histological evaluation for accurate bone repair assessment and the necessity for further investigation into the local application of Raloxifene. Future research may focus on optimizing bone substitutes with growth factors to improve bone repair.

Finite element analysis of low-profile reconstruction plates for atrophic mandibles: a comparison of novel 3D grid and conventional plate designs.

OBJECTIVES: This study aimed to compare the reconstruction with type 2.4 and three-dimensional (3D) grid plates relating the areas of weakness to anatomical regions of force incidence in atrophic mandibles with and without segmentation using finite element analysis (FEA). MATERIALS AND METHODS: Strength and force quality in the mandible were also determined. The atrophic mandible models with and without segmentation were divided into four groups, and the behavior of each plate was analyzed using finite element analysis. In the atrophic mandible without segmentation using the type 2.4 reconstruction plate, the highest stress concentration in the plate was observed in the posterior region of the mandibular body and in the grid type 3D reconstruction plate was observed in the mandibular angle. RESULTS: In the segmented atrophic mandible with the 2.4 reconstruction plate, higher stress concentration was observed in the mandibular segment defect. Analysis of the 3D grid-like reconstruction plate revealed that the geometry of the plate conferred greater stiffness to the assembly, as the most significant stress concentration was observed at the mandibular angle. CONCLUSION: The width of the plate design may influence the strength, not the thickness.

Early Treatment of Unilateral Condylar Hyperplasia in Adolescents: Preliminary Results.

Facial asymmetry associated with unilateral condylar hyperplasia (UCH) is a rare disease. The aim of this study was to evaluate the clinical conditions of progressive facial asymmetry in young subjects treated with high condylectomy. A retrospective study was performed including nine subjects diagnosed with UCH type 1B and progressive facial asymmetry around 12 years old with an upper canine progressing towards dental occlusion. After an analysis and a decision of treatment, orthodontics began one to two weeks prior to the condylectomy (with a mean vertical reduction of 4.83 ± 0.44 mm). Facial and dental asymmetry, dental occlusion, TMJ status and an open/closing mouth were analyzed before surgery and in the final stage of treatment, almost 3 years after surgery. Statistical analyses were performed using the Shapiro-Wilk test and a Student's t-test considering a p value of <0.05. Comparing T1 (before surgery) and T2 (once orthodontic treatment was finalized), the operated condyle showed a similar height to that observed in stage 1 with a 0.12 mm difference in height (p = 0.8), whereas the non-operated condyle showed greater height increase with an average of 3.88 mm of vertical growth (p = 0.0001). This indicated that the non-operated condyle remained steady and that the operative condyle did not register significant growth. In terms of facial asymmetry in the preoperative stage, a chin deviation of 7.55 mm (±2.57 mm) was observed; in the final stage, there was a significant reduction in the chin deviation with an average of 1.55 mm (±1.26 mm) (p = 0.0001). Given the small number of patients in the sample, we can conclude that high condylectomy (approx. 5 mm), if performed early, especially in the mixed-dentition stage before full canine eruption, is beneficial for the early resolution of asymmetry and thus the avoidance of future orthognathic surgery. However, further follow-up until the end of facial growth is required.

Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by high heritability estimates and recurrence rates; its genetic underpinnings are very heterogeneous and include variable combinations of common and rare variants. Array-comparative genomic hybridization (aCGH) offers significant sensitivity for the identification of copy number variants (CNVs), which can act as susceptibility or causal factors for ASD. METHODS: The aim of this study was to evaluate both diagnostic yield and clinical impact of aCGH in 329 ASD patients of Italian descent. RESULTS: Pathogenic/likely pathogenic CNVs were identified in 50/329 (15.2%) patients, whereas 89/329 (27.1%) carry variants of uncertain significance. The 10 most enriched gene sets identified by Gene Ontology Enrichment Analysis are primarily involved in neuronal function and synaptic connectivity. In 13/50 (26.0%) patients with pathogenic/likely pathogenic CNVs, the outcome of array-CGH led to the request of 25 additional medical exams which would not have otherwise been prescribed, mainly including brain MRI, EEG, EKG, and/or cardiac ultrasound. A positive outcome was obtained in 12/25 (48.0%) of these additional tests. CONCLUSIONS: This study confirms the satisfactory diagnostic yield of aCGH, underscoring its potential for better, more in-depth care of children with autism when genetic results are analyzed also with a focus on patient management.

The Use of Human Amniotic Membrane (hAM) as a Treatment Strategy of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Systematic Review and Meta-Analysis of the Literature.

Background and objectives: Although it is very uncommon, medication-induced osteonecrosis of the jaw (also known as MRONJ) can have serious consequences. Traditionally, this adverse event has been recognised in patients who were treated with bisphosphonate (BP) drugs. Nevertheless, in recent years, it has been established that individuals having treatment with various types of medications, such as a receptor activator of nuclear factor kappa-Β ligand inhibitor (denosumab) and antiangiogenic agents, have had the same issue. The purpose of this research is to determine if the application of human amniotic membrane (hAM) may be used as a therapy for MRONJ. Material and Methods: A multi-source database (MEDLINE, EMBASE, AMED, and CENTRAL) systematic search was performed. The major objective of this study is to obtain an understanding of the efficacy of hAM when it is employed as a treatment modality for MRONJ. The protocol of this review was registered in the INPLASY register under the number NPLASY202330010. Results: The authors were able to include a total of five studies for the quality analysis, whereas for the quantity evaluation, only four studies were eligible. A total of 91 patients were considered for the investigation. After treatment with human amniotic membrane (hAM), a recurrence of osteonecrosis was observed in n = 6 cases (8.8%). The combined efficacy of surgical therapy and the use of hAM resulted in an overall success rate of 91.2%. Intraoperative complications were only documented in one article, and they were mostly caused by the positioning of the hAM, which led to wound breakdown at the surgical site. Conclusions: Based on the small amount of data and low-quality research included in this study, using human amniotic membranes to treat MRONJ might represent a feasible option. Nevertheless, further studies with a wider patient population are required to understand the long-term impacts.

"Nutripiatto": A tool for nutritional education. A survey to assess dietary habits in preschool children.

Childhood obesity is a global public health concern linked to metabolic and psychological comorbidities. There is growing evidence that children's lifestyle habits are shifting towards obesity, with dire consequences for their future well-being and healthcare costs. In this interventional study, we enrolled 115 children aged between 4-5 years (53% females and 47% males) and carried out nutrition education interventions to improve their dietary habits. We introduced "Nutripiatto", a visual plate icon and easy guide, which was used by the children during the study. We investigated the children's dietary habits using a Food Frequency Questionnaire at the beginning and end of the study, after one month of using "Nutripiatto". The results showed that the children significantly increased the portion sizes and frequency of vegetable consumption (P<0.001) and reduced the consumption of several junk foods such as French fries and crisps (P<0.001), reaching the recommended dietary allowances and frequency of consumption. Daily consumption of water also significantly increased, reaching the suggested amount of six glasses per day. Based on these results, "Nutripiatto" can be considered an effective visual guide and helpful tool to achieve small changes and empower families to make healthier food choices. It can also be considered an effective educational tool for nutritionists and healthcare professionals to improve children's dietary behavior.

Maternal Epigenetic Dysregulation as a Possible Risk Factor for Neurodevelopmental Disorders.

Neurodevelopmental Disorders (NDs) are a heterogeneous group of disorders and are considered multifactorial diseases with both genetic and environmental components. Epigenetic dysregulation driven by adverse environmental factors has recently been documented in neurodevelopmental disorders as the possible etiological agent for their onset. However, most studies have focused on the epigenomes of the probands rather than on a possible epigenetic dysregulation arising in their mothers and influencing neurodevelopment during pregnancy. The aim of this research was to analyze the methylation profile of four well-known genes involved in neurodevelopment (BDNF, RELN, MTHFR and HTR1A) in the mothers of forty-five age-matched AS (Asperger Syndrome), ADHD (Attention Deficit Hyperactivity Disorder) and typically developing children. We found a significant increase of methylation at the promoter of the RELN and HTR1A genes in AS mothers compared to ADHD and healthy control mothers. For the MTHFR gene, promoter methylation was significantly higher in AS mothers compared to healthy control mothers only. The observed dysregulation in AS mothers could potentially contribute to the affected condition in their children deserving further investigation.

The use of zygomatic implants in severe maxillary atrophy: a systematic and meta-analysis review of randomised clinical trials / El uso de implantes zigomáticos para atrofia maxilar severa: una revisión sistemática y meta-análisis de ensayos clínicos aleatorizados

SUMMARY: Conventional implant treatment cannot always be used to rehabilitate edentulous patients with advanced maxillary atrophic. Zygomatic dental implants have been used over the past 20 years as an alternative treatment solution to bone grafting. The purpose of this meta-analysis is to evaluate the implant and prosthetic survival rate in non-oncologic patients with a severely atrophic maxilla. This review also aims to better understand the rate of peri-operative complications in this cohort of patients. A multi-database (PubMed, MEDLINE, EMBASE, and CINAHAL) focused systematic search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Any randomised control trials studies involving human participants treated with zygomatic osseous implants were included. After eliminating duplicates, a total of 4 studies met the inclusion criteria for this meta-analysis review. With all the studies included there was a total of 174 patients treated with zygomatic osseous implants. The overall implant success rate was 98.03 %. The prosthetic success rate was 96.4 %. The most frequent peri-operative complication was sinusitis. Based on the limited data available in literature, zygomatic dental implants represent a valid alternative to bone augmenting procedure. However, they are not without risks and longer follow-ups are required to confirm the validity of the treatment in long term.

Los tratamientos convencionales con implantes no siempre pueden ser usados para rehabilitar pacientes edentulos con atrofia maxilar avanzada. Los implantes dentales zigomáticos son usados por los pasados 20 años como alternativa de tratamiento a las reconstrucciones óseas. El objetivo de este meta-análisis es evaluar la sobrevida de implantes y prótesis en pacientes no oncológicos con maxila severamente atrófica. Esta revisión también pretende entender al promedio de complicaciones peri operatorias en esta cohorte de pacientes. Una búsqueda sistemática en bases de datos múltiples (PubMed, MEDLINE, EMBASE y CINAHAL) fue desarrollada de acuerdo a recomendaciones de Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Cualquier estudio clínico aleatorizado de participantes humanos donde se utilizaron los implantes zigomáticos fueron incluidos. Después de eliminar duplicados, un total de 4 estudios cumplieron los criterios de inclusión para esta meta análisis. Con todos los estudios incluidos se obtuvieron 174 pacientes tratados con implantes zigomáticos. El promedio de éxito fue de 98,03 %. El promedio de éxito de la rehabilitación fue de 96,4 %. La complicación mas frecuente fue la sinusitis. Basados en los datos limitados en la literatura, los implantes zigomáticos representan una alternativa valida a los procedimientos de aumento óseo. Sin embargo, estos no están libres de riesgos y seguimientos de mayores periodos son necesarios para confirmar la validez de los tratamientos en el largo plazo.

Expanding the Spectrum of KDM5C Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype-Phenotype Correlations.

As a consequence of the implementation of NGS technologies, the diagnostic yield of neurodevelopmental disorders has dramatically increased during the past two decades. Among neurodevelopmental genes, transcription-related genes and chromatin remodeling genes are the most represented category of disease-causing genes. Indeed, the term "chromatinopathies" is now widely used to describe epigenetic disorders caused by mutations in these genes. We hereby describe a twenty-seven-year-old female patient diagnosed with moderate intellectual disability comorbid with other neuropsychiatric and behavioral issues carrying a de novo heterozygous stop variant in the KDM5C gene (NM_004187.5: c. 3847G>T, p.Glu1283*), encoding a histone demethylase that specifically acts on the H3K4 lysines. The gene is located on the X chromosome and has been associated with Claes-Jensen-type intellectual disability, an X-linked syndromic disorder. We discuss our case in relation to previously reported affected females harboring pathogenic mutations in the KDM5C gene with the objective of delineating genotype-phenotype correlations and further defining a common recognizable phenotype. We also highlight the importance of reverse phenotyping in relation to whole-exome sequencing results.

Does Melatonin Associated with Nanostructured Calcium Phosphate Improve Alveolar Bone Repair?

Background and objectives: Calcium phosphates have been widely used as bone substitutes, but their properties are limited to osteoconduction. The association of calcium phosphates with osteoinductive bioactive molecules has been used as a strategy in regenerative medicine. Melatonin has been studied due to its cell protection and antioxidant functions, reducing osteoclastic activity and stimulating newly formed bone. This study aimed to evaluate the effect of topical application of melatonin associated with nanostructured carbonated hydroxyapatite microspheres in the alveolar bone repair of Wistar rats through histological and histomorphometric analysis. Materials and Methods: Thirty female Wistar rats (300 g) were used, divided randomly into three experimental groups (n = 10), G1: nanostructured carbonated hydroxyapatite microspheres associated with melatonin gel (CHA-M); G2: nanostructured carbonated hydroxyapatite (CHA); G3: blood clot (without alveolar filling). The animals were euthanized after 7 and 42 days of the postoperative period and processed for histological and histomorphometric evaluation. Kruskal-Wallis and Dunn's post-test were applied to investigate statistical differences between the groups at the same time point for new bone and connective tissue variables. Mann-Whitney was used to assess statistical differences between different time points and in the biomaterial variable. Results: Results showed a greater volume of residual biomaterial in the CHA-M than the CHA group (p = 0.007), and there were no significant differences in terms of newly formed bone and connective tissue between CHA and CHA-M after 42 days. Conclusions: This study concluded that both biomaterials improved alveolar bone repair from 7 to 42 days after surgery, and the association of CHA with melatonin gel reduced the biomaterial's biodegradation at the implanted site but did not improve the alveolar bone repair.

The clinical effect of radiotherapy on pulpal microvasculature: a systematic review.

Introduction/objectives Radiotherapy (RT) has a detrimental effect on the histomorphology of oral tissues. Patients undergoing RT are at risk of developing macrovascular and microvascular changes, which can lead to significant clinical consequences. Despite advances in RT delivery systems, radiation injury remains a modern-day clinical problem. The aim of this systematic review is to investigate the available evidence regarding the impact of RT to the dental pulp and the clinical manifestations of these effects.Data and sources A multi-database search (PubMed, Medline, Embase and CINAHL) was performed to identify related papers published from inception until November 2021. An additional manual search was performed to identify further articles. The data extracted from relevant papers were analysed according to the outcomes selected in this review.Study selection The search generated seven articles eligible for analysis with a total of 2,709 teeth included. RT dose exposure ranged from 30-71.2 Gray with a common finding that RT decreases the number of teeth responding to pulp sensibility testing.Conclusions Knowledge related to the impact of RT on dental pulp is limited and based on weak evidence and a low-level quality of studies. Future studies should incorporate exact RT doses to the teeth and use replicable pulpal testing methods. Understanding the pulpal status post-RT remains an important consideration as dental extractions should be avoided in this cohort due to the risk of osteoradionecrosis.

Genetic variants determine intrafamilial variability of SARS-CoV-2 clinical outcomes in 19 Italian families.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a wide range of outcomes characterized by a high heterogeneity in both symptomatology and susceptibility to the disease. In such a perspective, COVID-19 may be considered as a multifactorial disease featured by the interaction between the environment, which is the virus itself, and the genetic profile of the host. Our analysis aimed at investigating the transmission dynamics of SARS-CoV-2 within families whose members responded in different ways to the infection, although the exposure was common to the entire group and occurred before the availability of any vaccine. The goal was to understand how the genetic background of each subject can influence the viral infection outcome and hence the above-mentioned clinical variability. We performed a segregation analysis in 19 Italian families with a designed custom panel of 42 genes involved in immunity and virus entry and which have also been shown to be related to SARS-CoV-2 host response. We carried out both a familial segregation analysis and a global statistical analysis. In the former we identified eighteen risk variants co-segregating with a COVID-positive status and six variants with a possible protective effect. In addition, sixteen variants showed a trend of association to a severe phenotype. Together with common SNPs, we detected private rare variants that may also provide insight into the observed clinical COVID-19 heterogeneity. The global statistical analysis confirmed statistically significant positive associations between SARS-CoV-2 individual response and some specific gene variants identified in familial analysis. In conclusion our data confirm that the clinical expression of COVID-19 is markedly influenced by the host genetic profile both with a mendelian transmission pattern and a polygenic architecture.