Risk factors for medication-related osteonecrosis of the jaw and salivary IL-6 IN cancer patients / Fatores de risco para osteonecrose dos maxilares relacionada à medicação e níveis salivares de IL-6 em pacientes com câncer

Abstract Introduction Medication-related osteonecrosis of the jaws is a severe complication of the use of antiresorptive and antiangiogenic therapy, with limited treatment options and great impact on patient's quality pf life. Objective The aim of this study was to assess the risk factors associated with medication-related osteonecrosis of the jaws in oncologic patients undergoing bisphosphonate treatment. In addition, salivary levels of interleukin-6, IL-6, were measured to investigate their association with severity and risk of medication-related osteonecrosis of the jaws. Methods Case-control study with 74 patients with bone metastases from solid tumors and multiple myeloma was included. Patients were divided into three groups: 1) those undergoing bisphosphonate treatment with medication-related osteonecrosis of the jaws; 2) those undergoing bisphosphonate without medication-related osteonecrosis of the jaws; and 3) those with bisphosphonate pretreatment. The demographic and medical data of the patients were collected to assess risk. The clinical evaluation was performed to diagnose medication-related osteonecrosis of the jaws and unstimulated saliva was collected for quantification of IL-6. Results As result, it was observed that patients diagnosed with medication-related osteonecrosis of the jaws were submitted to higher number of bisphosphonate doses (p= 0.001) and monthly infusion protocol (p= 0.044; OR = 7.75). Patients who did not have routine followup with specialized dentists during therapy with bisphosphonate and smoking were associated with medication-related osteonecrosis of the jaws (p= 0.019; OR = 8.25 and p= 0.031; OR = 9.37 respectively). Group 1 had a higher frequency of treatment with chemotherapy and corticosteroids concomitant with bisphosphonate, and surgical dental procedures (p= 0.129). Salivary IL-6 levels showed no statistically significant difference between the groups (p= 0.571) or association with medication-related osteonecrosis of the jaws severity (p= 0.923). Conclusion A higher number of bisphosphonate cycles, monthly infusion protocol, no dental follow-up for oral health maintenance and smoking were associated with medication-related osteonecrosis of the jaws. Specialized dental follow up during bisphosphonate treatment has been shown to be an important factor in preventing this complication.

Resumo Introdução A osteonecrose dos maxilares relacionada à medicação é uma complicação grave da terapia antirreabsortiva e antiangiogênica, com opção de tratamento limitada e grande impacto na qualidade de vida do paciente. Objetivo Avaliar os fatores de risco associados à osteonecrose dos maxilares relacionada à medicação em pacientes oncológicos em tratamento com bifosfonato Além disso, os níveis salivares de interleucina-6 (IL-6) foram medidos para investigar sua associação com a gravidade e o risco de osteonecrose dos maxilares relacionada à medicação. Método Estudo caso-controle com 74 pacientes com metástases ósseas de tumores sólidos e mieloma múltiplo. Os pacientes foram divididos em três grupos: 1) em tratamento por bifosfonato com osteonecrose dos maxilares relacionada à medicação; 2) submetidos ao bifosfonato sem osteonecrose dos maxilares relacionada à medicação; e 3) pré-tratamento de bifosfonato. Os dados demográficos e médicos dos pacientes foram coletados para avaliar o risco. A avaliação clínica foi feita para diagnosticar osteonecrose dos maxilares relacionada à medicação e a saliva não estimulada foi coletada para quantificação da IL-6. Resultados Observou-se que os pacientes diagnosticados com osteonecrose dos maxilares relacionada à medicação foram submetidos a maior número de doses de bifosfonato (p = 0,001) e protocolo de infusão mensal (p = 0,044; OR = 7,75). Pacientes que não tiveram acompanhamento de rotina com dentistas especializados durante a terapia com bifosfonato e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação (p = 0,019; OR = 8,25 e p = 0,031; OR = 9,37, respectivamente). O grupo 1 apresentou maior frequência de tratamento com quimioterapia e corticosteroides concomitantes ao bifosfonato e procedimentos odontológicos cirúrgicos (p = 0,129). Os níveis salivares de IL-6 não apresentaram diferença estatisticamente significante entre os grupos (p = 0,571) ou associação com a gravidade do osteonecrose dos maxilares relacionada à medicação (p = 0,923). Conclusão Maior número de ciclos de bifosfonato, protocolo de infusão mensal, ausência de acompanhamento odontológico para manutenção da saúde bucal e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação. O acompanhamento odontológico especializado durante o tratamento demonstrou ser importante na prevenção dessa complicação.

SARS-CoV-2 in saliva, viremia and seroprevalence for COVID-19 surveillance at a single hematopoietic stem cell transplantation center: a prospective cohort study

ABSTRACT This prospective cohort study aims to analyze the surveillance of COVID-19 at a single hematopoietic stem cell transplantation (HSCT) center in Brazil, in 29 patients undergoing allogeneic HSCT and 57 healthcare workers (nurses and dentists), through viral shedding of SARS-CoV-2 in saliva and plasma and seroprevalence of anti-SARS-CoV-2 IgG. In addition, we report two cases with prolonged persistent detection of SARS-CoV-2 without seroconversion. The sample collection was performed seven times for patients and five times for healthcare workers. Only two patients tested positive for SARS-CoV-2 in their saliva and plasma samples (6.9%) without seroconversion. All healthcare workers were asymptomatic and none tested positive. Two patients (6.9%) and four nurses (8%) had positive serology. No dentists had positive viral detection or positive serology. Our results reflect a low prevalence of positive RT-PCR and seroprevalence of SARS-CoV-2 in patients and healthcare workers at a single HSCT center. Results have also corroborated how the rigorous protocols adopted in transplant centers were even more strengthened in this pandemic scenario.

Presence of langerhans cells, regulatory T cells (Treg) and mast cells in asymptomatic apical periodontitis

Abstract Asymptomatic Apical Periodontitis is essentially an inflammatory disease of microbial aetiology. Association and function of the cell components involved, or specific inductive factors and growth mediators associated with development, maintenance and resolution of the periapical lesions are still unknown. The objective of this study was to evaluate the concentration of Regulatory T cells (FoxP3+; Treg), Langerhans cells (CD1a+; LC) and mast cells in asymptomatic apical periodontitis. 73 cases were selected: 30 periapical granulomas, 29 radicular cysts and 14 residual cysts. All groups were submitted to morphological analysis for classification of inflammatory infiltrate and thickness of the epithelial lining as well as to immunohistochemical analysis for detection of LC and Treg cells. Toluidine blue staining was used for detecting mast cells. Analysis showed higher mean numbers of LC (8.2 cells/0.2mm2), and Treg cells in radicular cysts (5.910 cells/0.2mm2). As for mast cells, it was found that radicular cysts had a higher mean number of these cells compared to other periapical lesions (12.68 cells/0.2mm2). The association between thickness of the epithelial lining and inflammatory cells showed that the presence of hypertrophic epithelium in radicular cysts presented higher density of LC. The number of LC and Treg cells play an important role in the control of the inflammatory micro-environment in periapical granulomas and radicular cysts, respectively. The presence of mast cells in radicular cysts may be associated with progression of the lesion. Knowledge regarding the inflammatory cell profile is therefore essential for a better understanding of the pathogenesis of asymptomatic periapical periodontitis.

Recrutamento de células dendríticas imaturas e linfócitos Treguladores (T reg) em lesões associadas ao vírus Epstein-Barr (EBV): papel dacitocina MIP3a / Recruitment of immature dendritic cells and regulatory T cells (T reg) in Epstein-Barr (EBV): associated lesions role of MIP3a

O vírus Epstein-Barr infecta aproximadamente 95% da população mundial adulta,estabelecendo uma infecção latente e assintomática. Porém, é um vírus associado àneoplasias malignas, tais como carcinomas de nasofaringe, linfomas de Hodgkin,alguns casos de carcinomas gástrico, linfomas T e NK, dentre outras. O EBVtambém está implicado em doenças não neoplásicas como a leucoplasia pilosa. Ofenômeno de imunotolerância está ligado ao potencial de infecção e oncogênico doEBV. Células dendríticas imaturas e linfócitos T reguladores são importantes nessecontexto. Em situações neoplásicas, esse mecanismo impede o reconhecimento e adestruição de células tumorais. O objetivo desse trabalho foi estudar em quatrodiferentes situações de infecção pelo EBV, a saber, amigdalite crônica, linfomas deHodgkin, leucoplasia pilosa e carcinomas de nasofaringe, a presença de célulasdendríticas imaturas e linfócitos T reguladores, e também o papel da citocina MIP3αno recrutamento dessas células. Foram utilizadas as técnicas de hibridização in situpara detecção do EBV e imunoistoquímica para detecção das células dendríticas,linfócitos T reg e para análise da expressão de MIP3α. Em todos os casos delinfoma de Hodgkin, amigdalites e carcinomas de nasofaringe EBV+ observou-seuma forte concentração de células dendríticas imaturas e linfócitos T reg. Aexpressão de MIP3α mostrou-se intensa nas neoplasias EBV positivas e fraca noscasos de amigdalite crônica. Não foi observada expressão de MIP3α nos casos deleucoplasia pilosa. A concentração de células dendríticas imaturas e linfócitos T regestá intimamente ligada à presença de céulas EBV+ e pela expressão de MIP3α noslinfomas de Hodgkin associados ao EBV e carcinomas de nasofaringe, criandoassim um micro-ambiente de imunossupressão nessas lesões.

The Epstein-Barr virus infects approximately 95% of adult world-wilde population,establishing a latent and asymptomatic infection. However it is related to malignantneoplasia, such as nasopharynx carcinomas, Hodgkin disease, some gastriccarcinomas, T/NK lymphomas among others. EBV is also implicated in non-neoplasicdisease such as hairy leukoplakia. This phenomenon is associated with the EBVinfectious and oncogenic potential. Immature dendritic cells and T reg cells areimportant in this context. In neoplasic situations, this mechanism obstructsrecognition and destruction of tumoral cells. The aim of this work was study, in fourdifferent situations of EBV infection, to knowledge, chronic tonsillitis, Hodgkin’sdisease, hairy leukoplakia and nasopharynx carcinoma, the presence of immaturedendritic cells and T reg cells, and also the role of cytokine MIP3 α in the recruitmentof these cells. In situ hybridization was performed for EBV detection andimmunohistochemistry for dendritic cells and T reg cells detection and also forexpression evaluation of MIP3α cytokine. In all the cases of Hodgkin’s disease,tonsillitis and nasopharynx carcinoma EBV+, a strong concentration of immaturedendritic cells and T reg lymphocytes was observed. The MIP3α expression wasmore intense on EBV positive neoplasia and weak in cases of chronic tonsillitis. NoMIP3α expression was observed in hairy leukoplakia. The concentration of immaturedendritic cell and T reg lymphocyte is intimately connected with the presence of EBVpositive-cells and MIP3 α expression in Hodgkin disease associated to EBV andnasopharynx carcinoma, creating a microenvironment of immunosuppression inthese neoplasias.