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OBJECTIVE: Given the absence of a standardized action protocol for treating patients with dental implants (DIs) who are subjected to radiotherapy (RT), we have conducted an extensive review and analysis of published literature on this subject. Our objective is to gain a comprehensive understanding of the impact of RT on the bone surrounding osseointegrated implants during and after treatment. STUDY DESIGN: We conducted a literature review using PubMed (MEDLINE) to identify studies describing the effects of RT on preexisting osseointegrated and/or loaded DIs. Articles published between January 1963 and December 2023 were considered for inclusion. RESULTS: A total of 1,126 articles were retrieved, 64 full articles were reviewed, and only 13 articles were included in this review upon meeting the criteria. A total of 667 patients and 2,409 implants were included. Osteoradionecrosis (ORN) was observed in approximately 19 implants following antineoplastic treatment. CONCLUSIONS: The interaction between DIs and RT is a complex and multifaceted issue that requires further research and clinical guidance. Although certain studies indicate a possible connection between DIs, radiation, and ORN risk, the precise relationship remains unclear. Factors such as radiation dosage, implant characteristics, material, and timing of placement significantly influence this association.
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OBJECTIVES: Electronic nicotine delivery systems (e-cigarette, pod, and vape) are currently among the tobacco consumption of adolescents and young adults. The aim is to show oral mucosa and saliva alterations related to vape. MATERIAL AND METHODS: A vape-user patient, presenting a white plaque in the posterior region of the hard palate, underwent clinical examination, sialometry, pH evaluation, and excisional biopsy of the white lesion. Molecular changes in saliva and vape liquid were analyzed by vibrational spectroscopy. RESULTS: The histopathological analyses showed hyperparakeratosis without dysplasia. Formaldehyde, ketones, and aromatic hydrocarbon species were identified in e-cig liquid by the FTIR. CONCLUSIONS: The use of vape may be related to the development of hyperkeratotic lesions in the oral mucosa as well as significantly modify the patient's salivary patterns as the vape liquid presents carcinogenic and cytotoxic components in its composition.
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Mucosa Bucal , Saliva , Humanos , Saliva/química , Mucosa Bucal/patologia , Sistemas Eletrônicos de Liberação de Nicotina , Vaping/efeitos adversos , Masculino , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Adulto , Palato Duro/patologia , Adulto Jovem , BiópsiaRESUMO
OBJECTIVES: Acute oral mucosal damage, as well as other inflammatory processes seem to be related to dysbiosis of the oral microbiome. The need to study changes in the oral microbiome led us to hypothesize what type of sample would provide the most representative picture of the entire human oral microbiome. MATERIALS AND METHODS: An observational, and cross-sectional study was carried out. Six healthy adult participants provided 3 different sample types each, that included saliva, oral rinse and mucosal biopsy tissue. We performed 16S rRNA sequencing of the V3-V4 region of the 18 samples using Illumina MiSeq technology. RESULTS: Participants were 27 ± 6,3 years old. Bacterial alpha diversity was higher in oral rinse samples compared to whole unstimulated saliva and oral mucosa tissue (p = 0,005). However, saliva specimens showed a 56 % relative abundance of identified species followed by a 30 % in oral rinse and only 1 % in tissue samples. CONCLUSIONS: This study found differences on oral microbiome composition for each type of sample. Oral rinse should be chosen when higher alpha diversity is needed, whereas whole unstimulated saliva should be more appropriate for larger amount of bacterial DNA. CLINICAL RELEVANCE: The results obtained demonstrate the importance of a correct choice of the optimal type of oral sample for microbiome studies due to the differences found in its composition.
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Background: In cancer care, the MLH1 gene is crucial for DNA mismatch repair (MMR), serving as a vital tumor suppressor. Evaluating MLH1 protein expression status, followed by analysis of MLH1 promoter methylation, has become a key diagnostic and prognostic approach. Our study investigates the complex link between MLH1 methylation and prognosis in endometrial adenocarcinoma (EA) patients. Methodology: MLH1 methylation status was accessed by a Pyrosequencing (PSQ) assay. Qualitative positivity for methylation was established if it exceeded the 11% cut-off; as well, a quantitative methylation analysis was conducted to establish correlations with clinicopathological data, relapse-free survival, and disease-free survival. Results: Our study revealed that 33.3% of patients without MLH1 methylation experienced relapses, surpassing the 23.3% in patients with methylation. Furthermore, 16.7% of patients without methylation succumbed to death, with a slightly higher rate of 17.6% in methylated patients. Qualitative comparisons highlighted that the mean methylation rate in patients experiencing relapse was 35.8%, whereas in those without relapse, it was 42.2%. This pattern persisted in disease-specific survival (DSS), where deceased patients exhibited a higher mean methylation level of 49.1% compared to living patients with 38.8%. Conclusions: Our findings emphasize the efficacy of PSQ for evaluating MLH1 methylation. While unmethylation appears to be associated with a higher relapse rate, the survival rate does not seem to be influenced by methylation. Quantitative percentages suggest that elevated MLH1 methylation is linked to relapse and mortality, though a study with a larger sample size would be essential for statistically significant results.
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One of the most promising approaches to correct periodontal bone defects and achieve periodontal regeneration is platelet-rich fibrin (PRF). This systematic review and meta-analysis aimed to evaluate the regeneration of periodontal bone defects using PRF compared to other regenerative treatments. The data search and retrieval process followed the PRISMA guidelines. An electronic search of MEDLINE, Cochrane, and PubMed databases was performed, selecting exclusively randomized clinical trials where the following were measured: probing depth reduction (PD), clinical attachment level gain (CAL), and radiographic bone fill (RBF). Out of 284 selected articles, 32 were chosen based on inclusion criteria. The use of platelet-rich fibrin (PRF) + open flap debridement (OFD), PRF + metformin, PRF + platelet-rich plasma (PRP), and PRF + OFD/bone graft (BG) significantly reduced PD and improved CAL and RBF. However, the combination of PRF + BG, PRF + metformin, and PRF + STATINS reduced CAL. The intervention of PRF combined with different treatments such as metformin, OFD, PRP, BG, and STATINS has a significant impact on improving PD and CAL. The use of PRF significantly improved the regeneration of periodontal bone defects compared to other treatments.
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AIMS: The objective of this study was to identify the presence of human herpesvirus (HHV) in the plasma and saliva of hepatic-cirrhosis patients and correlate it with clinical data and laboratory tests. This is a pilot, observational, and cross-sectional study. METHODS AND RESULTS: Specimens of plasma and saliva from 72 cirrhotic individuals were analyzed by means of polymerase chain reaction. The patient population had a mean age of 54.84 years old (SD ± 10) and was 70% males (51/72). Approximately 47% (n = 34) of the patients had leukopenia and HHV was not identified in the plasma specimens. The main species of HHV identified in the saliva were HHV-7 (n = 42, 62%) and Epstein-Barr virus (EBV) (n = 30, 41%). Moreover, there was a significant decrease in the total number of leukocytes and lymphocytes in saliva containing EBV (P = .038 and P = .047, respectively). CONCLUSION: The results show that the presence of EBV in the saliva of cirrhotic patients was correlated with their circulating immune status. It may be possible that the immune dysfunction displayed by the cirrhotic patients plays a role in the shedding of EBV into saliva.
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OBJECTIVES: The extraction of third molars is one of the most performed surgical procedures in oral and maxillofacial surgery. Pain, oedema, and trismus are the most frequently complications related in the surgical postoperative period. The literature has indicated PBM as a potential adjuvant method to reduce these complications. The aim of this review and meta-analysis is evaluate the PBM, as an optimal method to improve patient experience and minimize postoperative morbidity. Additionally, we seek to determine which wavelength, site, and frequency of application are most effective. METHODS: This review was registered in PROSPERO (CRD42023429966) and followed PRISMA guidelines. The search was carried out in the main databases, PubMed/MEDLINE, Cochrane Library, Embase, Scopus, and Lilacs, including reviews in the most important journals in the area of oral surgery and laser applied to oral surgery. In addition, all article references and also gray literature were reviewed. After the studies selection, the relevant data was collected. All the studies were randomized controlled trials and the patients were allocated into two groups: active PBM and inactive PBM. The statistical analysis was carried out using Stata v.16, and the methodological quality and risk of bias were assessed by the Jadad scale and RoB 2.0, respectively. RESULTS: Where included 22 studies and 989 subjects, to all with a minimum follow-up of 7 days. Pain and oedema showed statistically significant results in favor to the active PBM group. Especially when laser applied in infrared mode, for pain and oedema at 48 h, MDâ¯=â¯-1.80 (CI95% -2.88, -0.72) I²â¯=â¯92.13% and MDâ¯=â¯-1.45 (CI95% -2.42, -0.48) I²â¯=â¯65.01%, respectively. The same is not true for trismus at 48 h, MDâ¯=â¯0.07 (CI95% -0.06, 0.21) I²â¯=â¯3.26%. The meta-analysis also presented results in respect of laser site of application and number of PBM sessions. CONCLUSIONS: PBM with infrared laser, in a combination intraoral and extraoral application, in one session in the immediate postoperative period, has been shown to be effective to achieve the objectives of reducing pain and oedema after third molar extraction.
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Edema , Terapia com Luz de Baixa Intensidade , Dente Serotino , Dor Pós-Operatória , Complicações Pós-Operatórias , Extração Dentária , Humanos , Dente Serotino/cirurgia , Terapia com Luz de Baixa Intensidade/métodos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Edema/prevenção & controle , Edema/etiologia , Complicações Pós-Operatórias/prevenção & controle , Mandíbula/cirurgia , Trismo/prevenção & controle , Trismo/etiologiaRESUMO
PURPOSE: Human papillomavirus (HPV) is a prevalent sexually transmitted infection responsible for many anogenital and oropharyngeal cancers. Dental care providers have the potential to influence vaccine uptake, yet little is known about how patients perceive their role in HPV education and prevention. METHODS: Parents of adolescents aged 9 to 17 years (n = 375) were recruited from Valdeorras District Hospital (Galicia, Spain) to investigate parents' attitudes concerning the involvement of dental care providers in discussions related to HPV. A survey was distributed to the participants, and 343 (91.5%) were included in the analysis. RESULTS: In general, nearly half of the parents reported feeling comfortable regarding discussing HPV with their dentist. Participants described more comfort with dentists than with dental hygienists. Parents' comfort levels were influenced by various social determinants of health, including education level, marital status, geographic origin, and child vaccination status (p > 0.05). CONCLUSION: Parents reported varying comfort levels when discussing HPV and its vaccine with dental professionals, displaying a preference for dentists. Dental settings have the potential to promote vaccination, but the existence of ongoing barriers needs to be addressed.
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Vacinas contra Papillomavirus , Pais , Humanos , Adolescente , Espanha , Pais/psicologia , Vacinas contra Papillomavirus/administração & dosagem , Feminino , Masculino , Criança , Infecções por Papillomavirus/prevenção & controle , Vacinação/psicologia , Inquéritos e Questionários , Odontólogos/psicologia , AdultoRESUMO
Damage to the inferior alveolar nerve (IAN) secondary to the extraction of the lower third molar (LTM) is a relatively frequent complication (0.35-8.40%) that can cause temporary or permanent nerve damage. Coronectomy has been proposed as an alternative, which consists of sectioning the coronary portion of the LTM, and deliberately leaving the radicular portion with the pulp intact. Two clinical cases are presented in this article, in which root migration (0-0.3 mm) and a change of angulation (+2º to +9°) occurred. None of the cases developed complications during the follow-up period (12 months). Therefore, coronectomy is a procedure to be considered in selected cases as an alternative to conventional exodontia of the LTM to avoid possible damage to the IAN. Key words:Case report, third molar, mandibular third molar, coronectomy, mandibular nerve, mandibular nerve injuries, root migration.
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Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Osteonecrose , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Hospitais , Arcada Osseodentária , DifosfonatosRESUMO
The O-6-methylguanine-DNA methyltransferase (MGMT) gene is a critical guardian of genomic integrity. MGMT methylation in diffuse gliomas serves as an important determinant of patients' prognostic outcomes, more specifically in glioblastomas (GBMs). In GBMs, the absence of MGMT methylation, known as MGMT promoter unmethylation, often translates into a more challenging clinical scenario, tending to present resistance to chemotherapy and a worse prognosis. A pyrosequencing (PSQ) technique was used to analyze MGMT methylation status at different cut-offs (5%, 9%, and 11%) in a sample of 78 patients diagnosed with IDH-wildtype grade 4 GBM. A retrospective analysis was provided to collect clinicopathological and prognostic data. A statistical analysis was used to establish an association between methylation status and treatment response (TR) and disease-specific survival (DSS). The patients with methylated MGMT status experienced progressive disease rates of 84.6%, 80%, and 78.4% at the respective cut-offs of 5%, 9%, and 11%. The number was considerably higher when considering unmethylated patients, as all patients (100%), regardless of the cut-off, presented progressive disease. Regarding disease-specific survival (DSS), the Hazard Ratio (HR) was HR = 0.74 (0.45-1.24; p = 0.251); HR = 0.82 (0.51-1.33; p = 0.425); and HR = 0.79 (0.49-1.29; p = 0.350), respectively. Our study concludes that there is an association between MGMT unmethylation and worse TR and DSS. The 9% cut-off demonstrated a greater potential for patient survival as a function of time, which may shed light on the future need for standardization of MGMT methylation positivity parameters in PSQ.
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Glioblastoma , Guanina , Isocitrato Desidrogenase , Humanos , DNA , Glioblastoma/genética , Guanina/análogos & derivados , Sequenciamento de Nucleotídeos em Larga Escala , Isocitrato Desidrogenase/genética , Metilação , O(6)-Metilguanina-DNA Metiltransferase/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Mortality is linked to tumor budding (TB) in certain neoplasms. TB as a relevant histopathological feature is conditioned by tumor site, a specific study on head and neck squamous cell carcinoma (HNSCC) is needed. METHODS: A comprehensive meta-analysis was undertaken to investigate the relationship between TB and HNSCC-related outcomes. RESULTS: Overall 42 studies were included. Patients harboring high TB reported an Overall Survival (OS) Hazard Ratio (HR) of 2.63 (95% confidential interval (CI) 2.04-3.39; p-value < 0.001), Disease-free Survival (DFS) HR of 1.88 (95%CI 1.57-2.24; p-value <0.001) and Disease-specific Survival (DSS) HR of 2.14 (95%CI 1.81-2.52; p-value <0.001). Lymph Node Metastasis (LNM) studies harbored null heterogeneity and marked association with TB (Odds Ratio (OR) = 4.48, 95%CI 2.97-6.76; p-value < 0.001). Trial Sequential Analysis (TSA) supported definitive results for DSS. CONCLUSION: The study has provided compelling evidence that there is a significant association between TB and a worse prognosis for HNSCC.
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Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/diagnóstico , Prognóstico , Intervalo Livre de Doença , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy. METHODS: 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse. RESULTS: Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse. CONCLUSIONS: Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment.
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Platelet-rich fibrin (PRF) is a second-generation platelet concentrate whose use in clinical practice has been widely disseminated. This has led to the development of several commercial protocols, creating great confusion as to the terminology and implications of each of them. This integrative review aims to identify the critical factors of each of the phases of the solid-based PRF matrix protocol and their possible influence on their macro- and microscopic characteristics. An electronic search of the MEDLINE database (via PubMed), Web of Science, Scopus, LILACS, and OpenGrey was carried out. The search was temporarily restricted from 2001 to 2022. After searching, 43 studies were included that met the established criteria. There were numerous factors to consider in the PRF protocol, such as the material of the blood collection tubes, the duration of phlebotomy, the parameters related to blood centrifugation, the time from centrifugation to dehydration of the fibrin clots and their dehydration into membranes, as well as the time to clinical use. These factors influenced the macro- and microscopic characteristics of the PRF and its physical properties, so knowledge of these factors allows for the production of optimised PRF by combining the protocols and materials.
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Fibrina Rica em Plaquetas , Cirurgia Bucal , Humanos , Desidratação , Leucócitos , PlaquetasRESUMO
Introduction: Previous studies measuring intervals on the oral cancer care pathway have been heterogenous, showing mixed results with regard to patient outcomes. The aims of this research were (1) to calculate pooled meta-analytic estimates for the duration of the patient, diagnostic and treatment intervals in oral cancer, considering the income level of the country, and (2) to review the evidence on the relationship of these three intervals with tumor stage at diagnosis and survival. Materials and methods: We conducted a systematic review with meta-analysis following PRISMA 2020 guidelines (pre-registered protocol CRD42020200752). Following the Aarhus statement, studies were eligible if they reported data on the length of the patient (first symptom to first presentation to a healthcare professional), diagnostic (first presentation to diagnosis), or treatment (diagnosis to start of treatment) intervals in adult patients diagnosed with primary oral cancer. The risk of bias was assessed with the Aarhus checklist. Results: Twenty-eight studies reporting on 30,845 patients met the inclusion criteria. The pooled median duration of the patient interval was 47 days (95% CI = 31-73), k = 18, of the diagnosis interval 35 days (95% CI = 21-38), k = 11, and of the treatment interval 30 days (95% CI = 23-53), k = 19. In lower-income countries, the patient and treatment intervals were significantly longer, and longer patient intervals were related to later stage at diagnosis. In studies with a lower risk of bias from high-income countries, longer treatment intervals were associated with lower survival rates. Conclusion: Interval duration on the oral cancer care pathway is influenced by the socio-economic context and may have implications for patient outcomes.
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Procedimentos Clínicos , Neoplasias Bucais , Adulto , Humanos , Neoplasias Bucais/terapia , Lista de Checagem , Pessoal de Saúde , RendaRESUMO
Background: Burnout syndrome (BS) is composed of three interrelated dimensions (emotional exhaustion, depersonalization, and personal fulfillment), and it has been documented that it affects health professionals from an early age. Aims: Determine the prevalence of BS and associated factors in the integral clinic of the Dentistry Pilot School. Material and Methods. Two instruments were applied: (1) Maslach Burnout Inventory, which measures the degree of professional burnout through 22 items that describe the professional's attitudes and feelings toward work, as well as symptoms associated with this phenomenon; (2) the second questionnaire determines the possible symptoms of BS and consists of 14 questions that describe tiredness, sleep problems, digestive problems, respiratory problems and headaches, temporomandibular joint (TMJ), neck pain, back pain, and upper and lower extremity pain. The instruments were answered anonymously by a total of 300 students who participated in the study. Results: The emotional exhaustion of the participants was 48.3% at a higher level, the depersonalization was 46.7% at a higher level, and the low perception of personal fulfillment was 73%. In addition, it was shown that BS is significantly related to marital status (p < 0.001∗), with single people reporting being more exhausted, with the 6-month level (p = 0.011) and with the following symptoms: non-neck pain, head, TMJ, back, waist, upper and lower body pain. Conclusion: It was found that the BS had a prevalence of high levels of exhaustion and depersonalization correlated with the marital status and level of preparation (academic degree) of the person, finding a prevalence of symptoms such as pain in the neck, head, TMJ, and back.
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Introduction: Torque teno virus (TTV) has been pointed as an endogenous marker of immune function, the objective of this study was to investigate the TTV viral load in plasma and saliva of cirrhotic individuals and correlate it with clinical characteristics. Methods: Blood, saliva, clinical data from records and laboratory tests were collected from 72 cirrhotic patients. Plasma and saliva were submitted to real-time polymerase chain reaction for quantification of TTV viral load. Results: The majority of the patients presented decompensated cirrhosis (59.7%) and 47.2% had alterations in the white blood series. TTV was identified in 28 specimens of plasma (38.8%) and in 67 specimens of saliva (93.0%), with median values of TTV copies/mL of 90.6 in plasma and 245.14 in saliva. All the patients who were positive for TTV in plasma were also positive in saliva, with both fluids having a moderately positive correlation for the presence of TTV. There was no correlation between TTV viral load, either in plasma or in saliva, and any of the variables studied. Conclusion: TTV is more frequently found and in greater amount in the saliva than in the plasma of cirrhotic patients. There was no correlation between TTV viral load and clinical parameters.
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OBJECTIVE: To analyze the influence of 3-mm high abutments with different shapes (cylindrical abutment vs. wide abutment) on marginal bone-level changes (bone loss and bone remodeling). The influence of abutment shape on implant success, probing pocket depth (PPD), and bleeding on probing (BoP) was studied as secondary objectives. MATERIALS AND METHODS: Patients with a partially edentulous area requiring fixed dental prostheses by two implants in the posterior mandible or maxilla were included. The implants were 1 mm subcrestally placed, and osseointegration healing was submerged. Three-mm high abutments with two different shapes were randomly placed in second-stage surgery: cylindrical abutments (cylindrical group) and wide abutments (wide group). Marginal bone-level changes were measured using parallelized periapical radiographs at abutment placement, at definitive prosthesis placement, and at 1, 3, 6, and 12 months after loading. PPD and BoP were likewise measured at the control visits. RESULTS: Sixty-four dental implants in 25 patients were included. Statistically significant differences were found in bone-level changes. The cylindrical group exhibited less mean marginal bone remodeling (MBR) and marginal bone loss (MBL) than the wide group (p < .05). Moreover, the cylindrical group showed significantly less BoP (p < .05). CONCLUSION: Abutment shape had a significant influence upon marginal bone-level changes during the first 12 months. Cylindrical abutments caused less MBR and MBL than wide abutments. More clinical studies involving longer follow-ups and analyzing other abutment modifications are needed to improve our understanding of how abutments can affect peri-implant tissue stability.
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Perda do Osso Alveolar , Dente Suporte , Implantes Dentários , Carga Imediata em Implante Dentário , Humanos , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/etiologia , Projeto do Implante Dentário-Pivô/efeitos adversos , Implantação Dentária Endóssea/efeitos adversos , Maxila/cirurgia , OsseointegraçãoRESUMO
Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches.
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Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Proteômica , Espectrometria de Massas em Tandem , Leucoplasia Oral/diagnóstico , Leucoplasia Oral/patologia , Leucoplasia Oral/terapia , Biomarcadores , Cromatografia Líquida , Transformação Celular Neoplásica/patologiaRESUMO
BACKGROUND: Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly informative of the prognosis and subsequent malignant transformation. Prognosis is based on histological findings by grading of dysplasia. Immunohistochemical expression of p16INK4a has been investigated in different studies, with controversial results. In this scenario, we systematically revised the current evidence about p16INK4a immunohistochemical expression and the risk of malignization of OPMDs. MATERIAL AND METHODS: After a proper set of keywords combination, 5 databases were accessed and screened to select eligible studies. The protocol was previously registered on PROSPERO (Protocol ID: CRD42022355931). Data were obtained directly from the primary studies as a measure to determine the relationship between CDKN2A/P16INK4a expression and the malignant transformation of OPMDs. Heterogeneity and publication bias were investigated by different tools, such as Cochran's Q test, Galbraith plot and Egger and Begg Mazumdar's rank tests. RESULTS: Meta-analysis revealed a twofold increased risk to malignant development (RR = 2.01, 95% CI = 1.36-2.96 - I2 = 0%). Subgroup analysis did not highlight any relevant heterogeneity. Galbraith plot showed that no individual study could be considered as an important outlier. CONCLUSION: Pooled analysis showed that p16INK4a assessment may arise adjunct tool to dysplasia grading, leading to an optimized determination of the potential progression to cancer of OPMDs. The p16INK4a overexpression analysis by immunohistochemistry techniques has a multitude of virtues that may facilitate its incorporation in the day-to-day prognostic study of OPMDs.