Brazilian dental consensus on dental management in hematopoietic stem cell transplantation−Part I−pre-HSCT

ABSTRACT The oral involvement in the Hematopoietic Stem Cell Transplantation is well described in the literature. The goal of the dental treatment and management of the oral lesions related to the HSCT is to reduce the harm caused by preexisting oral infection or even the worsening of oral acute/chronic GVHD and late effects. The aim of this guideline was to discuss the dental management of patients subjected to HSCT, considering three phases of the HSCT: pre-HSCT, acute phase, and late phase. The literature published from 2010 to 2020 was reviewed in order to identify dental interventions in this patient population. The selected papers were divided into three groups: pre-HSCT, acute and late, and were reviewed by the SBTMO Dental Committee's members. When necessary, an expertise opinion was considered for better translating the guideline recommendations to our population dental characteristics. This manuscript focused on the pre-HSCT dental management. The objective of the pre-HSCT dental management is to identify possible dental situations that On behalf of the Dental Committee of the Brazilian Society of Gene Therapy and Bone Marrow Transplantation (SBTMO) can worsening during the acute phase after the HSCT. Each guideline recommendations were made considering the Dentistry Specialties. The clinical consensus on dental management prior to HSCT provides professional health caregivers with clinical setting-specific information to help with the management of dental problems in patients to be subjected to HSCT.

Queratocisto odontogênico em maxila: relato de caso

Objetivo: Relatar o processo de diagnóstico e tratamento de um queratocisto odontogênico (QO) em seio maxilar e a sua importância na investigação e diagnóstico de Síndrome de Gorlin-Goltz (SGG). Relato de caso: Paciente do gênero feminino, 20 anos, apresentou-se no serviço de odontologia encaminhada pela equipe de genética médica para investigar a presença de QO para definição de diagnóstico de SGG. Foi realizada radiografia panorâmica e verificou-se a presença de alterações no trabeculado ósseo em tuberosidade maxilar do lado esquerdo. Por isso, foi solicitada a tomografia computadorizada de seios maxilares e encontrou-se uma lesão bem delimitada, ocupando quase completamente o seio maxilar esquerdo em íntimo contato com a raiz do dente 27. Portanto, foi realizada biópsia incisional da lesão, acompanhada da aspiração do conteúdo. Na aspiração foi obtido um conteúdo de característica caseosa sugestivo de queratina. O laudo histopatológico da lesão foi de cisto odontogênico. Com isso, foram realizados os procedimentos de exodontia do dente 27 e a enucleação da lesão em seio maxilar pela equipe da odontologia e da otorrinolaringologia, respectivamente, em centro cirúrgico. O laudo histopatológico confirmou a presença de QO, assim foi possível confirmar o diagnóstico da SGG pela equipe da genética médica. A paciente não apresentou sinais de recidiva e nem de novos QO após 2 anos do procedimento. Considerações finais: A SGG requer atenção odontológica especial, visto a alta taxa de QO nos pacientes com essa síndrome. Exame odontológico minucioso envolvendo exame clínico e exames radiográficos devem ser realizado nas consultas de seguimento.

Objective: To report the process of diagnosis and treatment of an odontogenic keratocyst (OK) in the maxillary sinus and its importance in the investigation and diagnosis of Gorlin-Goltz Syndrome (GGS). Case report: A 20-year-old female patient presented at the Dentistry and Stomatology service, referred by the Medical Genetics team to investigate the presence of OK to define the diagnosis of GGS. Panoramic radiography was performed and the presence of alterations in the bone trabeculae in the maxillary tuberosity on the left side was verified. For this reason, computed tomography of the maxillary sinuses was also requested and a well-defined lesion was found, occupying almost completely the left maxillary sinus in close contact with the root of tooth 27. Therefore, an incisional biopsy of the lesion was performed, accompanied by puncture of the same. In the puncture, a characteristic caseous content suggestive of keratin was obtained. The histopathological report of the lesion was described by the pathologist as an odontogenic cyst. With this, tooth extraction procedures for tooth 27 and enucleation of the lesion in the maxillary sinus were carried out by the dentistry and otorhinolaryngology teams, respectively, in a surgical center. The histopathological report confirmed the presence of OK, so it was possible to confirm the diagnosis of GGS by the medical genetics team. The patient showed no signs of recurrence or new OK after 2 years of the procedure. Final considerations: GGS requires special dental attention, given the high rate of OK in patients with this syndrome. A thorough dental examination involving clinical examination and radiographic examinations should be performed at follow-up visits.

Brazilian dental consensus on dental management in hematopoietic stem cell transplantation - Part I - pre-HSCT.

The oral involvement in the Hematopoietic Stem Cell Transplantation is well described in the literature. The goal of the dental treatment and management of the oral lesions related to the HSCT is to reduce the harm caused by preexisting oral infection or even the worsening of oral acute/chronic GVHD and late effects. The aim of this guideline was to discuss the dental management of patients subjected to HSCT, considering three phases of the HSCT: pre-HSCT, acute phase, and late phase. The literature published from 2010 to 2020 was reviewed in order to identify dental interventions in this patient population. The selected papers were divided into three groups: pre-HSCT, acute and late, and were reviewed by the SBTMO Dental Committee's members. When necessary, an expertise opinion was considered for better translating the guideline recommendations to our population dental characteristics. This manuscript focused on the pre-HSCT dental management. The objective of the pre-HSCT dental management is to identify possible dental situations that can worsening during the acute phase after the HSCT. Each guideline recommendations were made considering the Dentistry Specialties. The clinical consensus on dental management prior to HSCT provides professional health caregivers with clinical setting-specific information to help with the management of dental problems in patients to be subjected to HSCT.

Assessment of oral health condition in recipients of allogeneic hematopoietic cell transplantation

ABSTRACT Objective: The objective of this study was to evaluate the oral health condition and dental treatments performed in patients in pre-allogeneic HCT. Method: The records of patients treated during 2018 at a Brazilian HCT service were reviewed. The following oral health data were obtained: 1. Decayed, missing and filled teeth / correlated index for primary dentition (DMFT/dmft); 2. Quality of oral hygiene and 3. Dental pathologies: 3.1 Periodontal infectious focus, 3.2 Endodontic infectious focus and 3.3 Carie incidence. All dental procedures performed were surveyed. Results: Thirty-three patients were included, with a mean age of 28.42 (±16.37), 20 male (60%) and 13 female. The average DMFT/dmft found in this study was 10.24 (± 8.37), similar to the index found in the population in southeastern Brazil. The younger study population presented a DMFT/dmft considered high, when compared to the general population. A total of 27.2% of the patients had active caries lesions, 33.3%, foci of periodontal infection, 15.1%, endodontic infectious focus and 40%, poor oral hygiene. Almost half of the patients (48.4%) had to undergo dental intervention, 24.2% needing periodontal scaling, 21.2%, fillings and 12.1%, tooth extractions. Conclusion: We conclude that the studied population had an important incidence of dental pathologies and infectious conditions that could complicate throughout HCT, especially in younger patients, therefore presenting a high demand for dental treatment in the pre-HCT. Studies that assess the impact of dental conditioning on the outcomes of HCT with an emphasis on dental infectious complications, days of hospitalization and survival are necessary."

Molecular profile of head and neck rhabdomyosarcomas: A systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values. STUDY DESIGN: An electronic search was performed using PubMed, Embase, Scopus, and Web of Science with a designed search strategy. Inclusion criteria comprised cases of primary HNRMS with an established histopathological diagnosis and molecular analysis. Forty-nine studies were included and were appraised for methodological quality using the Joanna Briggs Institute Critical Appraisal tools. Five studies were selected for meta-analysis. RESULTS: HNRMS predominantly affects pediatric patients (44.4%), and the parameningeal region (57.7%) is the most common location. The alveolar variant (43.2%) predominates over the embryonal and spindle cell/sclerosing types, followed by the epithelioid and pleomorphic variants. PAX-FOXO1 fusion was observed in 103 cases of alveolar RMS (79.8%). MYOD1 mutation was found in 39 cases of sclerosing/spindle cell RMS (53.4%). FUS/EWSR1-TFCP2 gene fusions were identified in 21 cases of RMS with epithelioid and spindle cell morphologies (95.5%). The 5-year overall survival rate of patients was 61.3%, and MYOD1 mutation correlated with significantly higher mortality. CONCLUSION: The genotypic profile of histologic variants of HNRMS is widely variable, and MYOD1 mutation could be a potential prognostic factor, but more studies are required to establish this.

Proteases and HPV-Induced Carcinogenesis.

Persistent infection with Human papillomavirus (HPV) is the main etiologic factor for pre-malignant and malignant cervical lesions. Moreover, HPV is also associated with oropharynx and other anogenital carcinomas. Cancer-causing HPV viruses classified as group 1 carcinogens include 12 HPV types, with HPV 16 and 18 being the most prevalent. High-risk HPVs express two oncoproteins, E6 and E7, the products of which are responsible for the inhibition of p53 and pRB proteins, respectively, in human keratinocytes and cellular immortalization. p53 and pRB are pleiotropic proteins that regulate the activity of several signaling pathways and gene expression. Among the important factors that are augmented in HPV-mediated carcinogenesis, proteases not only control processes involved in cellular carcinogenesis but also control the microenvironment. For instance, genetic polymorphisms of matrix metalloproteinase 1 (MMP-1) are associated with carcinoma invasiveness. Similarly, the serine protease inhibitors hepatocyte growth factor activator inhibitor-1 (HAI-1) and -2 (HAI-2) have been identified as prognostic markers for HPV-dependent cervical carcinomas. This review highlights the most crucial mechanisms involved in HPV-dependent carcinogenesis, and includes a section on the proteolytic cascades that are important for the progression of this disease and their impact on patient health, treatment, and survival.

Impact of a dental care intervention on the hospital mortality of critically ill patients admitted to intensive care units: A quasi-experimental study.

BACKGROUND: We aimed to evaluate the impact of providing dental care to critically ill patients on their risk of death and ventilator-associated pneumonia (VAP). METHODS: A quasi-experimental study was conducted in 2 intensive care units (ICU) from 2016 to 2019. The intervention consisted of implementing routine dental care, focusing on oral hygiene and periodontal treatment, at least 3 times a week, for patients admitted to the study units. In the pre-intervention period, routine oral hygiene was provided by the ICU nursing staff. The primary and secondary study outcomes were mortality, evaluated at the end of the ICU stay, and VAP incidence density, respectively. Data were analyzed using the ARIMA (autoregressive integrated moving average) time series model in R software. RESULTS: During the intervention period, 5,147 dental procedures were performed among 355 patients. The time series showed that ICU mortality was 36.11%, 32.71%, and 32.30% within the 3 years before the intervention, and 28.71% during the intervention period (P = .015). VAP incidence density did not significantly change during the study period (P = .716). CONCLUSION: A dental care intervention focused on oral hygiene and periodontal treatment regularly provided by dentists to critically ill patients may decrease their risk of dying in the ICU. Randomized clinical trials should be performed to confirm these findings. TRIAL REGISTRATION: WHO-affiliated Brazilian Clinical Trials Registry. RBR-4jmz36. Registered 7 October 2018, before first patient enrollment.

Assessment of oral health condition in recipients of allogeneic hematopoietic cell transplantation.

INTRODUCTION: The optimization of oral health before allogeneic hematopoietic cell transplantation (HCT) is important for preventing infectious complications during treatment. OBJECTIVE: The objective of this study was to evaluate the oral health condition and dental treatments performed in patients in pre-allogeneic HCT. METHOD: The records of patients treated during 2018 at a Brazilian HCT service were reviewed. The following oral health data were obtained: 1. Decayed, missing and filled teeth / correlated index for primary dentition (DMFT/dmft); 2. Quality of oral hygiene and 3. Dental pathologies: 3.1 Periodontal infectious focus, 3.2 Endodontic infectious focus and 3.3 Carie incidence. All dental procedures performed were surveyed. RESULTS: Thirty-three patients were included, with a mean age of 28.42 (±16.37), 20 male (60%) and 13 female. The average DMFT/dmft found in this study was 10.24 (± 8.37), similar to the index found in the population in southeastern Brazil. The younger study population presented a DMFT/dmft considered high, when compared to the general population. A total of 27.2% of the patients had active caries lesions, 33.3%, foci of periodontal infection, 15.1%, endodontic infectious focus and 40%, poor oral hygiene. Almost half of the patients (48.4%) had to undergo dental intervention, 24.2% needing periodontal scaling, 21.2%, fillings and 12.1%, tooth extractions. CONCLUSION: We conclude that the studied population had an important incidence of dental pathologies and infectious conditions that could complicate throughout HCT, especially in younger patients, therefore presenting a high demand for dental treatment in the pre-HCT. Studies that assess the impact of dental conditioning on the outcomes of HCT with an emphasis on dental infectious complications, days of hospitalization and survival are necessary."

Salivary BPIFA proteins are altered in patients undergoing hematopoietic cell transplantation.

OBJECTIVE: The aim of this study was to evaluate the expression of BPIFA proteins in the saliva and salivary glands of hematopoietic cell transplant (HCT) patients. MATERIAL AND METHODS: This longitudinal study included patients who had undergone autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT), and unstimulated saliva was collected at three time points, with a fourth collection at oral chronic graft-versus-host disease (cGVHD) onset. BPIFA expression was analysed by Western blotting in saliva and immunostaining in the minor salivary glands of cGVHD patients. RESULTS: Auto-HCT patients showed increased levels of BPIFA1 (p = .021) and BPIFA2 at D+7 (p = .040), whereas allo-HCT group demonstrated decreased expression of BPIFA2 at D+8 (p = .002) and at D+80 (p = .001) and a significant association between BPIFA2 low levels and hyposalivation was observed (p = .02). BPIFA2 was significantly lower in the cGVHD patients when compared to baseline (p = .04). CONCLUSIONS: The results of this study show distinct pattern of expression of BPIF proteins in both auto-HCT and allo-HCT recipients with decreased levels of BPIFA2 during hyposalivation and cGVHD. Further studies are necessary to elucidate these proteins mechanisms and their clinical implications in these groups of patients.

Kallikrein 5 Inhibition by the Lympho-Epithelial Kazal-Type Related Inhibitor Hinders Matriptase-Dependent Carcinogenesis.

Head and neck squamous cell carcinoma remains challenging to treat with no improvement in survival rates over the past 50 years. Thus, there is an urgent need to discover more reliable therapeutic targets and biomarkers for HNSCC. Matriptase, a type-II transmembrane serine protease, induces malignant transformation in epithelial stem cells through proteolytic activation of pro-HGF and PAR-2, triggering PI3K-AKT-mTOR and NFKB signaling. The serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI) inhibits the matriptase-driven proteolytic pathway, directly blocking kallikreins in epithelial differentiation. Hence, we hypothesized LEKTI could inhibit matriptase-dependent squamous cell carcinogenesis, thus implicating kallikreins in this process. Double-transgenic mice with simultaneous expression of matriptase and LEKTI under the keratin-5 promoter showed a prominent rescue of K5-Matriptase+/0 premalignant phenotype. Notably, in DMBA-induced SCC, heterotopic co-expression of LEKTI and matriptase delayed matriptase-driven tumor incidence and progression. Co-expression of LEKTI reverted altered Kallikrein-5 expression observed in the skin of K5-Matriptase+/0 mice, indicating that matriptase-dependent proteolytic pathway inhibition by LEKTI occurs through kallikreins. Moreover, we showed that Kallikrein-5 is necessary for PAR-2-mediated IL-8 release, YAP1-TAZ/TEAD activation, and matriptase-mediated oral squamous cell carcinoma migration. Collectively, our data identify a third signaling pathway for matriptase-dependent carcinogenesis in vivo. These findings are critical for the identification of more reliable biomarkers and effective therapeutic targets in Head and Neck cancer.

Oral candidiasis prevalence in human immunodeficiency virus-1 and pulmonary tuberculosis coinfection: A systematic review and meta-analysis.

BACKGROUND: Human immunodeficiency virus-1 (HIV-1) infected people are more likely to develop tuberculosis (TB), being the leading cause of death in HIV-1. Candida spp has emerged as potential pathogenic fungi in patients with HIV and bronchopulmonary diseases. This systematic review summarizes the available data on the occurrence of oral candidiasis (OC) in the HIV-1/pulmonary tuberculosis (pTB) coinfection. METHODS: Articles that reported the occurrence of OC in the HIV-1-pTB coinfection were searched in eight databases. Observational studies that evaluated the association between OC and HIV-1-pTB coinfection were selected. The risk of bias was assessed using the meta-analysis of statistics assessment and review instrument (MAStARI) checklist. RESULTS: From a total of 1858 records, after application of inclusion and exclusion criteria, six were included in the meta-analysis. Three studies were at low risk, one at moderate risk, and two at high risk of bias. Considerable heterogeneity across the studies was identified. Meta-analyses performed showed no difference in the prevalence of OC between HIV-1 patients with and without pTB coinfection (odds ratio M-H = 1.77; 95% CI = 0.69 to 4.52). CONCLUSION: There is no association between OC and HIV-1/pTB coinfection. PROSPERO REGISTRATION NUMBER: CRD42019128735.

Evaluation of the correlation between side effects to oral mucosa, salivary glands, and general health status with quality of life during intensity-modulated radiotherapy for head and neck cancer.

PURPOSE: The aim of this study was to evaluate the distribution of acute clinical complications that involve the oral cavity (oral mucositis and salivary flow), general health status (Karnofsky performance status scale (KPS) and weight), and quality of life using the worst performance throughout radiotherapy treatment by intensity-modulated radiation therapy (IMRT) in the head and neck region and to evaluate the correlation between these variables. METHODS: This prospective, longitudinal study evaluated 32 patients who were undergoing IMRT for head and neck tumors. The measures were collected weekly through standardized protocols and a quality of life questionnaire (UW-QOL version 4). RESULTS: The worst performance for all variables was concentrated in treatment weeks 2 and 5. Regarding quality of life, the emotional dimensions were the most affected (pain 62.86; activity 55; recreation 43.57; mood 49.97; shoulder 57.06; anxiety 42.91). There were a higher number of moderate mucositis correlations with quality of life (mucositis × KPS 0.002; mucositis × weight loss 0.03; mucositis × pain 0.001; mucositis × activity 0.002; mucositis × recreation 0.001; mucositis × swallowing 0.002; mucositis × saliva 0.006; mucositis × mood 0.007; mucositis × anxiety 0.002). CONCLUSIONS: IMRT treatment severely deteriorated the patients' quality of life. There were important correlations between the clinical variables and quality of life, especially mucositis.

Juvenile Spongiotic Gingival Hyperplasia: Clinicopathological Features of Eight Cases and a Literature Review.

BACKGROUND: Juvenile spongiotic gingival hyperplasia (JSGH) is a benign proliferation of non-keratinised stratified squamous epithelium with evident spongiosis, exocytosis leukocytes and dilated vessels with varying numbers of inflammatory cells. Although uncertain, it has been suggested that the epithelial proliferation is probably related to trauma and local irritants. It emerges as a painless erythematous patch or papule with an irregular surface. CASE REPORTS: We present a series of eight cases and a literature review of the clinical presentation and treatment approaches for JSGH. This series includes four females and four males with a mean age of 11.6 years, all complaining of injury to the gums. All lesions were painless and not bleeding. One patient associated the lesion with the onset of trauma and another with a previous history of an eruption cyst. Periapical radiographs of the adjacent area did not show any alteration of bone or teeth. Based on these findings, the diagnostic hypotheses were a non-neoplastic proliferative process or a factitious injury. Incisional biopsy was performed and histopathologic diagnosis was conclusive for JSGH. Surgical excision was conducted in three cases, and the other five cases were supported by clinical observation and plaque control in order to prevent gingival recession defects. After a follow-up period of 11 months (mean), no recurrence was observed for surgically treated cases and mild improvement was achieved with periodontal treatment. CONCLUSION: This case series illustrates the importance of diagnosis and follow-up of patients with JSGH. A conservative approach consisting of basic periodontal support instead of surgical excision may be indicated because of the risk of aesthetic defects at the involved areas.

Laryngeal Cancer Attributable Factors and the Influence on Survival Rates: A Single Brazilian Institution Experience

Abstract Introduction Epidemiological studies focused on prognostic factors associated with laryngeal cancer in the Brazilian population are poorly reported in the literature. Objective To evaluate the influence of certain risk factors on the survival rates of patients with squamous cell carcinoma (SCC) of the larynx. Methods This retrospective study was conducted on adult patients who were admitted to the outpatient clinic of the head and neck department in a tertiary care hospital. Evaluation of the influence of risk factors on the survival rates of patients registered in the hospital with laryngeal SCC was performed based on age, sex, initial stage, time of evolution, habits, educational levels and relapse and death. Overall survival (OS), disease-free survival (DFS) and clinical-demographic data were analyzed using the Kaplan-Meier method, Log-rank test and Cox regression. Results A total of 107 patients with a mean age of 59.8 years (range 19-81) were included in this study. Stages III and IV were associated with decreased DFS (p = 0.02) and OS (p = 0.02). Smoking patients had a greater period of disease evolution than non-smoking patients (p = 0.003). Alcohol consumption in smokers increased the risk of death by 2.8 (p = 0.002) compared with non-drinking smokers. Male patients presented lower DFS average when compared with female patients (p = 0.04). Conclusion Our study confirms that male gender, smoking habit combined with alcohol consumption, and advanced stages were strongly associated with poor prognosis.