Acute coronavirus infection triggers a TNF-dependent osteoporotic phenotype in mice.

AIMS: Millions of people died during the COVID-19 pandemic, but the vast majority of infected individuals survived. Now, some consequences of the disease, known as long COVID, are been revealed. Although the respiratory system is the target of Sars-CoV-2, COVID-19 can influence other parts of the body, including bone. The aim of this work was to investigate the impact of acute coronavirus infection in bone metabolism. MAIN METHODS: We evaluated RANKL/OPG levels in serum samples of patients with and without acute COVID-19. In vitro, the effects of coronavirus in osteoclasts and osteoblasts were investigated. In vivo, we evaluated the bone phenotype in a BSL2 mouse model of SARS-like disease induced by murine coronavirus (MHV-3). KEY FINDINGS: Patients with acute COVID-19 presented decreased OPG and increased RANKL/OPG ratio in the serum versus healthy individuals. In vitro, MHV-3 infected macrophages and osteoclasts, increasing their differentiation and TNF release. Oppositely, osteoblasts were not infected. In vivo, MHV-3 lung infection triggered bone resorption in the femur of mice, increasing the number of osteoclasts at 3dpi and decreasing at 5dpi. Indeed, apoptotic-caspase-3+ cells have been detected in the femur after infection as well as viral RNA. RANKL/OPG ratio and TNF levels also increased in the femur after infection. Accordingly, the bone phenotype of TNFRp55-/- mice infected with MHV-3 showed no signs of bone resorption or increase in the number of osteoclasts. SIGNIFICANCE: Coronavirus induces an osteoporotic phenotype in mice dependent on TNF and on macrophage/osteoclast infection.

Type IV hypersensitivity associated with restorative materials: Clinical report and systematic literature review.

STATEMENT OF PROBLEM: Type IV hypersensitivity reactions (Type IV HR) are immune responses mediated by antigen-specific effector T cells. PURPOSE: The purpose of this clinical report and systematic review was to report the clinicopathological features of Type IV HR in the oral mucosa and to present a systematic literature review of case reports and case series of individuals with Type IV HR in the oral mucosa related to contact with dental materials. MATERIAL AND METHODS: The presented clinical lesions were melanotic macules with burning that affected the internal labial mucosa in contact with composite resin veneer crowns. Histopathological and immunohistochemical analysis of the lesion was performed. The systematic literature review was performed based on a search in 4 electronic databases (PubMed/MEDLINE, Scopus, Web of Science, and Ovid). RESULTS: Immunohistochemistry showed positivity for CD4, CD8, CD20, CD3, tryptase, and CD117. After conservative treatment, the patient reported improvement of symptoms, and a decrease in the number of inflammatory cells was verified. Twenty-one articles were included in the review. Unlike the present patient, the authors of all the articles recommended radical treatment with the removal of the dental material. CONCLUSIONS: Type IV HR in oral mucosa is rare, and the assessment of clinical and histopathological characteristics is essential to perform an accurate diagnosis and provide appropriate treatment.

Clinical profile of idiopathic pulmonary fibrosis patients treated with nintedanib in routine clinical practice in Spain: the BROAD Study / Perfil clínico de pacientes con fibrosis pulmonar idiopática tratados con nintedanib en la práctica clínica habitual en españa: estudio broad

Background. Few data are available on the clinical profile of patients diagnosed with idiopathic pulmonary fibrosis (IPF) treated with nintedanib. The primary objective of the study was to describe, based on pulmonary function variables, disease severity in IPF patients who initiated treatment with nintedanib in routine clinical practice. The secondary objectives were to analyze their clinical characteristics and comorbidities. Methods. A multicenter, retrospective study including 173 patients from 32 Spanish hospitals. Patients were stratified by their forced vital capacity (FVC) % predicted and diffusing capacity for carbon monoxide (DLCO) % predicted. These measures were taken as a marker of IPF severity. Results. Mean age ± SD at treatment initiation was 70.1 ± 8.1, and 76.6% of patients were male. Based on FVC, 57% of patients had mild IPF (FVC ≥ 70%), 38.4% moderate IPF (FVC 50%-69%), and 4.7% severe IPF (FVC < 50%). Based on DLCO, 42.5% of patients had mild IPF (DLCO ≥ 50%), 35.5% moderate IPF (DLCO 35%-49%), and 22.2% severe IPF (DLCO < 35%). Eighty-nine percent of patients had at least one comorbid condition. The most prevalent comorbidities were high blood pressure (45.9%), dyslipidemia (42.4%), gastroesophageal reflux (25.6%), diabetes (19.8%), emphysema (15.7%), and cardiovascular diseases (15.7%). Most patients received concomitant treatment (79.7%). Conclusions. The study provides relevant information on the clinical characteristics of IPF patients who initiate nintedanib treatment. Classification of severity depends on the lung function parameter used. The proportion of patients classified as having severe IPF was up to 4 times greater when DLCO, instead of FVC, was used (AU)

Introducción. Se dispone de pocos datos sobre el perfil clínico de los pacientes diagnosticados de fibrosis pulmonar idiopática (FPI) tratados con nintedanib. El objetivo principal del estudio fue describir, basándose en variables de función pulmonar, la gravedad de la enfermedad en pacientes con FPI que iniciaron tratamiento con nintedanib en la práctica clínica habitual. Los objetivos secundarios fueron analizar sus características clínicas y comorbilidades. Métodos. Estudio retrospectivo y multicéntrico que incluyeron a 173 pacientes de 32 hospitales españoles. Los pacientes fueron estratificados por su capacidad vital forzada (CVF) % predicho y por la capacidad de difusión de monóxido de carbono (DLCO) % predicho. Estas variables se consideraron como marcadores de la gravedad de la FPI. Resultados. La edad media ± DE al inicio del tratamiento fue de 70,1 ± 8,1 y el 76,6% de los pacientes eran varones. Según la CVF, el 57% de los pacientes tenían FPI leve (CVF ≥ 70%), el 38,4% FPI moderada (CVF 50%-69%) y el 4,7% FPI grave (CVF < 50%). Según la DLCO, el 42,5% de los pacientes tenían FPI leve (DLCO ≥ 50%), el 35,5% FPI moderada (DLCO 35%-49%) y el 22,2% FPI grave (DLCO < 35%). El 89% de los pacientes tenían al menos una comorbilidad, siendo las más prevalentes la hipertensión arterial (45,9%), dislipidemia (42,4%), reflujo gastroesofágico (25,6%), diabetes (19,8%), enfisema (15,7%) y enfermedades cardiovasculares (15,7%). La mayoría de los pacientes recibieron tratamientos concomitantes (79,7%) (AU)

Direct oral anticoagulants in oral surgery: a prospective cohort.

BACKGROUND: Quantitative assessment of bleeding in dental extractions is rarely reported in the literature. The assessment of bleeding might provide additional evidence to predict and minimize postoperative outcomes. The aim of this study was to evaluate the pattern of bleeding in individuals taking direct oral anticoagulants (DOACs) submitted to dental extractions. METHODS: Intraoperative bleeding was evaluated by using total collected bleeding corrected by absorbance reading (dental bleeding score). To monitoring bleeding episodes from the day of surgery, this cohort was followed up until the seventh postoperative day. RESULTS: Forty-five procedures were performed in three comparative groups, patients under DOACs, individuals taking vitamin K antagonists (VKAs) and without anticoagulant therapy. No bleeding events were observed in procedures carried out in individuals of the DOAC group. Additional hemostatic measures were required in two procedures in the VKA group and one in the non-anticoagulated group. The dental bleeding scores obtained for the DOAC and VKA groups were similar. CONCLUSIONS: Our data suggest that the DOAC therapy did not result in increased bleeding outcomes in this sample.

Dental management for patients undergoing heart valve surgery.

This study sought to review current guidelines and the most optimal dental management for patients undergoing cardiac valve surgery.

Common in vitro substrate specificity and differential Src homology 2 domain accessibility displayed by two members of the Src family of protein-tyrosine kinases, c-Src and Hck.

Hck and Src are members of the Src family of protein- tyrosine kinases that carry out distinct and overlapping functions in vivo (Lowell, C. A., Niwa, M., Soriano, P., and Varmus, H. E. (1996) Blood 87, 1780-1792). In an attempt to understand how Hck and Src can function both independently and in concert, we have compared 1) their in vitro substrate specificity and 2) the accessibility of their Src homology 2 (SH2) domain. Using several synthetic peptides, we have demonstrated that Hck and Src recognize similar structural features in the substrate peptides, suggesting that both kinases have the intrinsic ability to carry out overlapping cellular functions by phosphorylating similar cellular proteins in vivo. Using a phosphotyrosine-containing peptide that has previously been shown to bind the SH2 domain of Src family kinases with high affinity, we found that although Src could bind to the phosphopeptide, Hck showed no interaction. The inability of Hck to bind the phosphopeptide was not a result of a stable intramolecular interaction between its SH2 domain and C-terminal regulatory phosphotyrosine residue (Tyr-520), as most Hck molecules in the purified Hck preparation were not tyrosine-phosphorylated. In contrast to intact Hck, a recombinant truncation analog of Hck was able to bind the phosphopeptide with an affinity similar to that of the Src SH2 domain, suggesting that conformational constraints are imposed on intact Hck that limit accessibility of its SH2 domain to the phosphopeptide. Furthermore, the difference in SH2 domain accessibility is a potential mechanism that enables Src and Hck to perform their respective unique functions by 1) targeting them to different subcellular compartments, whereupon they phosphorylate different cellular proteins, and/or 2) facilitating direct binding to their cellular substrates.