Infrared spectroscopy as a predictive tool for the severity of COVID-19 using patient's saliva: A strategy to avoid hyperinflammation.

Discriminate the severity level of COVID-19 disease is still a challenge. Here we investigate the capability of micro-infrared absorption spectroscopy (micro-FTIR) to probe COVID-19 severity level and predict hyperinflammation, correlating the assigned vibrational data to relevant biomolecules related to the immune system. Saliva of 184 patients was analysed by ELISA assay (Hepcidin) and micro-FTIR. Vibrational bands related to IgM and IgA can discriminate healthy from Severe individuals (sensitivity ≥ 0.749, specificity ≥ 0.945) and are less effective in discriminating Mild or Moderate individuals from the Severe group (sensitivity ≥ 0.628, specificity ≥ 0.867). Analysis of the second derivative of spectra probed increased levels of IL-6 in the saliva a key additional information for the degree of severity prediction. Because the model discriminates all the groups regarding the Severe group, it predicts an intense state of inflammation based on FTIR analysis. It is a powerful tool for predicting hyperinflammation conditions related to SARS-CoV-2 infection and may be an ally in implementing drugs or therapeutic approaches to manage COVID-19 in the Severe stage in healthcare facilities.

Combination of bazedoxifene with chemotherapy and SMAC-mimetics for the treatment of colorectal cancer.

Excessive STAT3 signalling via gp130, the shared receptor subunit for IL-6 and IL-11, contributes to disease progression and poor survival outcomes in patients with colorectal cancer. Here, we provide evidence that bazedoxifene inhibits tumour growth via direct interaction with the gp130 receptor to suppress IL-6 and IL-11-mediated STAT3 signalling. Additionally, bazedoxifene combined with chemotherapy synergistically reduced cell proliferation and induced apoptosis in patient-derived colon cancer organoids. We elucidated that the primary mechanism of anti-tumour activity conferred by bazedoxifene treatment occurs via pro-apoptotic responses in tumour cells. Co-treatment with bazedoxifene and the SMAC-mimetics, LCL161 or Birinapant, that target the IAP family of proteins, demonstrated increased apoptosis and reduced proliferation in colorectal cancer cells. Our findings provide evidence that bazedoxifene treatment could be combined with SMAC-mimetics and chemotherapy to enhance tumour cell apoptosis in colorectal cancer, where gp130 receptor signalling promotes tumour growth and progression.

Investigation of Oral Shedding of Torquetenovirus (TTV) in Moderate-to-Severe COVID-19 Hospitalised Patients.

BACKGROUND: Torquetenovirus (TTV) is a small DNA virus constituting the human virome. High levels of TTV-DNA have been shown to be associated with immunosuppression and inflammatory chronic disorders. AIM: To assess the possible association between the salivary viral load of TTV-DNA in patients hospitalised due to COVID-19 and disease severity. METHODS: Saliva samples collected from 176 patients infected with SARS-CoV-2 were used to investigate the presence of SARS-CoV-2 and TTV-DNA by use of real-time RT-PCR. RESULTS: The majority of patients were male with severe COVID-19. Presence of SARS-CoV-2 was observed in the saliva of 64.77% of patients, showing TTV-DNA in 55.68% of them. Patients with impaired clinical conditions (p < 0.001), which evolved to death (p = 0.003), showed a higher prevalence of TTV-DNA. The median viral load in patients with severe condition was 4.99 log10 copies/mL, in which those who were discharged and those evolving to death had values of 3.96 log10 copies/mL and 6.27 log10 copies/mL, respectively. A statistically significant association was found between the distribution of TTV-DNA viral load in saliva samples and severity of COVID-19 (p = 0.004) and disease outcomes (p < 0.001). CONCLUSIONS: These results indicate that TTV-DNA in saliva could be a useful biomarker of COVID-19 severity and prognosis.

Unified framework for patient-derived, tumor-organoid-based predictive testing of standard-of-care therapies in metastatic colorectal cancer.

Predictive drug testing of patient-derived tumor organoids (PDTOs) holds promise for personalizing treatment of metastatic colorectal cancer (mCRC), but prospective data are limited to chemotherapy regimens with conflicting results. We describe a unified framework for PDTO-based predictive testing across standard-of-care chemotherapy and biologic and targeted therapy options. In an Australian community cohort, PDTO predictions based on treatment-naive patients (n = 56) and response rates from first-line mCRC clinical trials achieve 83% accuracy for forecasting responses in patients receiving palliative treatments (18 patients, 29 treatments). Similar assay accuracy is achieved in a prospective study of third-line or later mCRC treatment, AGITG FORECAST-1 (n = 30 patients). "Resistant" predictions are associated with inferior progression-free survival; misclassification rates are similar by regimen. Liver metastases are the optimal site for sampling, with testing achievable within 7 weeks for 68.8% cases. Our findings indicate that PDTO drug panel testing can provide predictive information for multifarious standard-of-care therapies for mCRC.

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.

Comparación entre la piezocirugía y los instrumentos rotativos convencionales en la lateralización del nervio dentario inferior / Comparison between the piezosurgery and the conventional rotary surgery in the lateralization of the inferior alveolar nerve

Introducción: la rehabilitación de pacientes desdentados mandibulares posteriores con implantes osteointegrados, se vuelve difícil cuando la cresta alveolar presenta una atrofia severa debido al recorrido superficial del canal mandibular. La lateralización del nervio dentario inferior es una alternativa terapéutica que posibilita la colocación de implantes convencionales y cortos en esta región. Objetivo: comparar la facilidad, efectividad y seguridad de la técnica quirúrgica convencional, realizada con fresas quirúrgicas, y la piezocirugía en la lateralización del nervio dentario inferior. Presentación del caso: paciente con ausencia bilateral de los molares inferiores y cresta alveolar atrófica fue tratada mediante lateralización del nervio dentario inferior y colocación simultánea de implantes. En el lado izquierdo, la lateralización fue realizada con fresas y en el lado derecho, con motor piezoeléctrico. Fue posible observar que la piezocirugía facilitó la técnica quirúrgica, y consecuentemente disminuyó el tiempo operatorio. A la vez, produjo una osteotomía más regular y con menos sangrado, lo cual mejoró la visualización del campo operatorio. Finalmente, el daño neural inmediato fue menor en el lado tratado con motor piezoeléctrico y con recuperación más rápida. Después de 3 meses de seguimiento, los implantes en ambos lados no presentaban pérdida ósea. Conclusiones: el uso del motor piezoeléctrico trajo más beneficios durante la lateralización del nervio dentario inferior, por la simplificación de la técnica quirúrgica y la reducción del sangrado y del daño neural en comparación con el uso de fresas convencionales(AU)

Introduction: the rehabilitation of edentulous posterior mandibular patients with bone-integrated implants becomes difficult when the alveolar crest presents a severe atrophy due to the superficial course of the mandibular canal. The inferior alveolar nerve lateralization is a therapeutic alternative that allows the placement of conventional and short implants in this region. Objective: to compare the easiness, effectiveness, and safety of the conventional surgical technique, performed with surgical drills, and piezosurgery in the lateralization of the inferior alveolar nerve. Case presentation: a patient with bilateral absence of the lower molars and atrophic alveolar crest was treated by lateralization of the inferior alveolar nerve and simultaneous implant placement. On the left side, the lateralization was made with drills and on the right side, with an electric piezotome. It was possible to observe that the piezosurgery facilitated the surgical technique, and consequently decreased the operative time. At the same time, it produced a more regular osteotomy and with less bleeding, which improved the visualization of the operative field. Finally, the immediate neural damage was lower on the side treated with the electric piezotome and with faster recovery. After 3 months of follow-up, the implants on both sides did not show bone loss. Conclusions: the use of the electric piezotome brought more benefits during the lateralization of the inferior alveolar nerve, by the simplification of the surgical technique and the reduction of bleeding and neural damage in comparison with the use of conventional drills(AU)

Use of a palatal pedicle flap for closure of an oroantral fistula / Fechamento de fístula bucossinusal com retalho palatino pediculado

Sinus lifting has become a routine procedure in modern implant dentistry. Despite its predictability, this type of surgery may eventually lead to serious complications and sequelae. Most of the time, such complications are due to technical failures, such as perforation of the sinus membrane during surgery, which may eventually lead to graft loss due to infection within the sinus, which finds its drainage path into the mouth and leads to an oroantral communication (OAC). Epithelization of such a draining duct characterizes an oroantral fistula (OAF). This report presents the use of a palatal pedicle flap to successfully close an OAF in a patient who had previously undergone a sinus lifting procedure. Several surgical techniques may be used in the closure of an OAF, and the choice of a particular technique is subject to the characteristics and location of the communication as well as to the preference of the surgeon. The palatal pedicle flap was successfully chosen in the present case report. The palatal pedicle flap was considered an adequate option for closure of an OAF in a single-stage surgical procedure, with no loss of either keratinized mucosa or buccal sulcus depth in the area of the fistula.

A cirurgia de elevação da mucosa do seio maxilar para enxerto ósseo e posterior colocação de implantes osseointegráveis vem se tornando um procedimento de rotina na implantodontia moderna. Embora previsível, em alguns casos, tal procedimento, pode levar a complicações e sequelas consideráveis. Na maioria das vezes, essas complicações são ocasionadas por falhas técnicas, como a perfuração da membrana sinusal no momento transcirúrgico, o que pode acarretar perda do enxerto devido a um processo infeccioso no interior do seio maxilar, cuja via de drenagem acaba provocando a comunicação com a cavidade oral. A fístula bucossinusal é caracterizada pela persistência e epitelização desse pertuito. Neste relato é apresentado um caso de fechamento de fístula bucossinusal com o uso de um retalho palatino pediculado, em um paciente que havia desenvolvido um processo infeccioso, após ter sido submetido à realização de uma cirurgia para a elevação do seio maxilar. A cirurgia para o fechamento das comunicações bucossinusais apresenta técnicas variadas, que podem ser eleitas de acordo com as preferências do operador, além da localização e características da comunicação. Para o presente relato de caso, a técnica do retalho palatino pediculado foi eleita para o tratamento cirúrgico, proporcionando a cura do paciente. A técnica do retalho palatino pediculado mostrou-se uma opção adequada para o fechamento da fístula bucossinusal em um único ato cirúrgico, sem perda de mucosa ceratinizada ou diminuição do sulco vestibular na região da fístula.

Detecção dos herpesvirus humanos na mucosa oral de pacientes irradiados para tratamento de carcinoma epidermoide em região de cabeça e pescoço / Detection of human herpesvirus in oral mucosa of patients undergoing radiotherapic treatment for head and neck squamous cell carcinoma

A radioterapia para tratamento das neoplasias malignas em região de cabeça e pescoço é acompanhada de diversas complicações, decorrentes do comprometimento dos tecidos radiossensíveis localizados próximos ao tumor. Entre essas complicações a mucosite é a que merece maior destaque. A mucosite é uma reação tóxica inflamatória da mucosa oral causada pelo tratamento citorredutivo induzido pela radioterapia (RT) ou pela quimioterapia (QT). Ela manifesta-se com sinais de edema, eritema, úlcera e formação pseudomembrana, resultando em sintomas de ardência, que pode progredir para dor intensa e consequente prejuízo na alimentação e comunicação verbal. Infecções bacterianas, fúngicas ou virais podem acometer a mucosa bucal irradiada e exacerbar a manifestação da mucosite oral por meio da ativação de fatores de transcrição da resposta inflamatória. Existem poucos dados na literatura sobre a participação dos herpesvirus humanos na mucosite oral induzida pela radioterapia. A proposta desse trabalho foi avaliar a excreção oral dos herpesvirus humanos (HSV-1, HSV-2, EBV, CMV, VZV, HHV6, HHV7 e HHV8) e sua possível associação com o desenvolvimento e agravamento da mucosite oral, em pacientes diagnosticados com carcinoma epidermoide (CEC) de boca e orofaringe, submetidos à radioterapia associado à quimioterapia. Nesse estudo foram analisadas 158 amostras de lavado bucal, de 20 pacientes, submetidos à radioterapia para CEC em região de cabeça e pescoço, coletadas semanalmente, durante todo o tratamento. Foi realizada a extração do DNA dessas amostras e em seguida sua amplificação através da PCR utilizando dois conjuntos de primers: HSVP1/P2 para os subtipos HSV-1, HSV-2, EBV, CMV e HHV-8 e o VZVP1/P2 para os subtipos VZV, HHV-6 e HHV-7

As amostras positivas foram submetidas à digestão enzimática com enzimas de restrição BamHI e BstUI para determinação específica de cada um dos oito herpesvirus. Foi também avaliada clinicamente, a mucosite oral, em cada uma das coletas, seguindo os critérios da OMS e NCIC. As análises da amostra mostraram a excreção do EBV, HHV-6 e HHV-7, em todas as semanas de tratamento radioterápico, enquanto que a excreção do HSV1 não pode ser observada no momento da triagem. Considerando-se todos os períodos em conjunto (Triagem, semanas de radioterapia e Controle), a maior frequência foi de pacientes que excretaram EBV (55,0%), seguida daqueles que excretaram HHV-7 (20,5%). A frequência de excreção de EBV foi significativamente maior do que a dos demais vírus (Teste ?2, p<0.001 para todos os cruzamentos). A frequência de excreção de HHV-7 foi significativamente maior do que a de HSV-1 (5,9%) e HHV-6 (5,5%) (Teste ?2, p=0.001 para ambos os cruzamentos). Não houve diferenças estatísticas significantes entre as frequências de HSV-1 e HHV-6. Como conclusão, verificou-se uma correlação positiva entre a excreção oral do EBV e a presença de mucosite induzida pela associação de radioterapia e quimioterapia com graus >=2, sobretudo se considerarmos as três últimas semanas de radioterapia, período este em que a severidade da mucosite foi estatisticamente maior. Esses achados nos possibilitam inferir que o ambiente inflamatório local de mucosites com grau >=2 seja mais favorável para excreção oral do EBV.

The radiotherapy (RT) treatment for head and neck tumors is accompanied by various complications resulting from the damage of the radiosensitive tissues located close to the tumor. Among these complications, mucositis is the one that deserves a special attention. Mucositis is an inflammatory toxic reaction of the oral mucosa caused by cytoreductive treatment induced by radiotherapy (RT) or chemotherapy (QT). The clinical manifestations of mucositis are: edema, erythema, ulcers and pseudo membrane formation, resulting in symptoms of burning, which may progress to severe pain and consequent loss in deglutition and verbal communication. The development of bacterial, fungal or viral infections, may affect the oral mucosa that has been irradiated, exacerbating the manifestation of oral mucositis through the activation of transcription factors of the inflammatory response. There are few data in the literature on the participation of human herpesvirus in oral mucositis caused by radiotherapy treatment. The aim of this study is to evaluate the oral excretion of human herpesvirus (HSV-1, HSV-2, EBV, CMV, VZV, HHV6, HHV7 and HHV-8) and its possible association with the development and aggravation of oral mucositis, in patients diagnosed with squamous cell carcinoma (CEC) of oral cavity and oropharynx, undergoing radiotherapy treatment associated with chemotherapy. On our study, we analyzed 158 oral rinsing samples, collected weekly, from 20 patients during the whole radiotherapy treatment for squamous cell carcinoma in head and neck. From these samples, we extracted the DNA and afterwards we amplified them with PCR using two sets of primers: HSVP1/P2 for the subtypes HSV-1, HSV-2, EBV, CMV, and HHV-8 and VZVP1/P2 for the subtypes VZV, HHV 6, and HHV-7.

The positive samples were subjected to enzymatic digestion with BamHI and BstUI restriction enzymes for specific determination of each one, of the eight's herpesvirus. It has also been clinically evaluated in each time, the oral mucositis, following the WHO and NCIC criteria. The analysis of the sample showed the excretion of EBV, HHV-6 and HHV-7, in all the weeks of radiotherapy, whereas the excretion of HSV-1 could not be observed during screening. Considering all periods together (Screening, weeks of radiotherapy and Follow up), the highest frequency was of patients with EBV excretion (55.0%), followed by those with HHV-7 excretion (20.5%).

Tratamento cirúrgico de fibroma ameloblático: relato de caso / Ameloblatic fibroma surgical treatment: case report

O Fibroma Ameloblático (FA) é um tumor odontológico benigno misto relativamente raro, cujos componentes epiteliais e ectomesenquimais são neoplásicos. O presente estudo teve como objetivo relatar um caso de FA, tratado de forma cirúrgica. Neste estudo um paciente do gênero feminino, 20 anos, foi encaminhado para avaliação de imagem radiolúcida e multilocular em região de mandíbula esquerda, com primeiro e segundo molares envolvidos na lesão. Após o diagnóstico de FA, o tratamento realizado foi a enucleação do tumor associado a uma ostectomia periférica da loja cirúrgica com broca multilaminada de grosso calibre. Após três anos de acompanhamento clínico e radiográfico não houve sinais de recidiva, obtendo-se, assim, um prognóstico favorável

Tratamento de lesões centrais de células gigantes com corticóide, calcitonina e interferon alfa-2a / Treatment of giant cell granulona with corticosteroids, calcitonin and interferon alpha-2a

O objetivo do presente trabalho foi estudar as terapêuticas não cirúrgicas para o tratamento da lesão central de células gigantes (LCCG), usando-se calcitonina sistêmica, corticóide intralesional e interferon alfa-2a. A LCCG corresponde a 7% de todos os tumores benignos dos maxilares, acometendo principalmente a região anterior de mandíbula. É uma lesão definida como intra-óssea, constituída de tecido celular fibroso contendo múltiplos focos hemorrágicos e agregados de células gigantes multinucleadas. O tratamento convencional é a terapia cirúrgica que, apesar de muitas vezes ser radical, tem um alto índice de recidiva, podendo variar de 11 a 49%, dependendo do comportamento clínico da lesão: agressivo ou não agressivo. As terapias não cirúrgicas usando-se corticóide intralesional, calcitonina sistêmica e interferon alfa-2a sistêmico têm sido uma alternativa bem sucedida de tratamento, principalmente para lesões extensas e múltiplas que, se resecadas cirurgicamente, causariam extensos defeitos estéticos e funcionais para o paciente, especialmente em crianças e jovens adultos.