Combination of leukocyte and platelet–rich fibrin and demineralized bovine bone graft enhanced bone formation and healing after maxillary sinus augmentation: a randomized clinical trial

Background and objective: The resorption of alveolar ridge bone and maxillary sinus pneumatization are challenges to implant-supported prosthetic rehabilitation. Bone regeneration using bone substitutes and growth factors are alternatives for maxillary sinus augmentation (MSA). Therefore, we sought to evaluate the effects of the association between leukocyte and platelet–rich fibrin (L-PRF) and deproteinized bovine bone mineral (DBBM) in MSA procedures. Materials and methods: Thirty-six maxillary sinuses from 24 individuals were included in this randomized clinical trial. The maxillary sinuses were randomly grafted with LPRF and DBBM (test group) or grafted only with DBBM (positive control). Dental implants were installed in the test group following two periods of evaluation: after 4 (DBBM+LPRF4) and 8 (DBBM+LPFR8) months of sinus graft healing, while the control group received implants only after 8 months. Cone beam computed tomography (CBCT) was taken 1 week after surgery (T1) and before implant placement (T2). Bone samples were collected during implant placement for histomorphometric and immunohistochemical (IHC) analysis. The primary implant stability was assessed by resonance frequency analysis. Results: CBCT analysis demonstrated a significant decrease in bone volume from T1 to T2 in all groups without differences among them. Histologically, the test group showed significantly increase in bone neoformation in both periods of evaluation (LPRF+DBBM4: 44.70±14.01%; LPRF+DBBM8: 46.56±12.25%) compared to the control group (32.34±9.49%). The control group showed the highest percentage of residual graft. IHC analysis showed increased staining intensity of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and runt related transcription factor 2 (RUNX-2) in LPRF+DBBM4 group, and osteopontin (OPN) in the L-PRF+DBBM8. Primary implant stability was successfully achieved (above 60 in implant stability quotient) in all the evaluated groups. Conclusion: Combination of L-PRF and DBBM increased and accelerated new bone formation allowing early implant placement probably due to the higher protein expression of RUNX2, VEGF, OCN, and OPN. These data suggest that the use of L-PRF might be an interesting alternative to use in combination with DBBM for augment the maxillary sinuses allowing the installation of appropriate length implants in shorter period of time. Clinical relevance: This study showed improvement in bone neoformation and accelerated healing when associating L-PRF and DBBM for maxillary sinus augmentation procedures. Trial registration: This study was registered before participant recruitment in Brazilian Registry of Clinical Trials (ReBEC - RBR-95m73t).</p

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Resistin Is Increased in Periodontal Cells and Tissues: In Vitro and In Vivo Studies.

Resistin, a proinflammatory adipokine, is elevated in many inflammatory diseases. However, little is known about its performance in periodontitis. The present study is aimed at evaluating resistin expression and synthesis in periodontal cells and tissues under inflammatory/microbial stress in addition to its effects on the periodontium. In vivo, 24 male rats were randomly divided into two groups: control and ligature-induced periodontal disease. After 6 and 12 days, animals were sacrificed to analyze gene expression of adipokines, bone loss, inflammation, and resistin synthesis. In vitro, human periodontal ligament (PDL) fibroblasts were used to evaluate the expression of resistin after inflammatory stimuli. In addition, PDL fibroblasts were exposed to resistin to evaluate its role on soft and hard tissue metabolism markers. The periodontitis group demonstrated significant bone loss, an increase in the number of inflammatory cells and vascular structures, an increase in resistin expression and synthesis, and a decrease in the expression of adiponectin, leptin, and its functional receptor. PDL fibroblasts showed a significant increase in resistin expression and synthesis in response to the inflammatory stimulus by IL-1β. Resistin induced an increase in cytokine expression and a decrease in the regulation of some hard tissue and matrix formation genes in PDL fibroblasts. These data indicate that resistin is produced by periodontal cells and tissues, and this effect is enhanced by inflammatory stimuli. Moreover, resistin seems to interfere with soft and hard tissue metabolism during periodontitis by reducing markers related to matrix formation and bone tissue

CXCL5, CXCL8, and CXCL10 regulation by bacteria and mechanical forces in periodontium

Objective: The aim of the present study was to evaluate the expressions of CXCL5, CXCL8, and CXCL10 in periodontal cells and tissues in response to microbial signals and/or biomechanical forces. Methods: Human gingival biopsies from inflamed and healthy sites were used to examine the chemokine expressions and protein levels by real-time PCR and immunohistochemistry. The chemokines were also investigated in gingival biopsies from rats submitted to experimental periodontitis and/or tooth movement. Furthermore, chemokine levels were determined in human periodontal fibroblasts stimulated by the periodontopathogen Fusobacterium nucleatum and/or constant tensile forces (CTS) by real-time PCR and ELISA. Additionally, gene expressions were evaluated in periodontal fibroblasts exposed to F. nucleatum and/or CTS in the presence and absence of a MAPK inhibitor by real-time PCR. Results: Increased CXCL5, CXCL8, and CXCL10 levels were observed in human and rat gingiva from sites of inflammation as compared with periodontal health. The rat experimental periodontitis caused a significant (p < 0.05) increase in alveolar bone resorption, which was further enhanced when combined with tooth movement. In vitro, F. nucleatum caused a significant upregulation of CXCL5, CXCL8, and CXCL10 at 1 day. Once the cells were exposed simultaneously to F. nucleatum and CTS, the chemokines regulation was significantly enhanced. The transcriptional findings were also observed at protein level. Pre-incubation with the MEK1/2 inhibitor significantly (p < 0.05) inhibited the stimulatory actions of F. nucleatum either alone or in combination with CTS on the expression levels of CXCL5, CXCL8, and CXCL10 at 1 d. Conclusions: Our data provide original evidence that biomechanical strain further increases the stimulatory actions of periodontal bacteria on the expressions of these chemokines. Therefore, biomechanical loading in combination with periodontal infection may lead to stronger recruitment of immunoinflammatory cells to the periodontium, which might result in an aggravation of periodontal inflammation and destruction. (C) 2020 Elsevier GmbH. All rights reserved

CXCL5, CXCL8, and CXCL10 regulation by bacteria and mechanical forces in periodontium.

OBJECTIVE The aim of the present study was to evaluate the expressions of CXCL5, CXCL8, and CXCL10 in periodontal cells and tissues in response to microbial signals and/or biomechanical forces. METHODS Human gingival biopsies from inflamed and healthy sites were used to examine the chemokine expressions and protein levels by real-time PCR and immunohistochemistry. The chemokines were also investigated in gingival biopsies from rats submitted to experimental periodontitis and/or tooth movement. Furthermore, chemokine levels were determined in human periodontal fibroblasts stimulated by the periodontopathogen Fusobacterium nucleatum and/or constant tensile forces (CTS) by real-time PCR and ELISA. Additionally, gene expressions were evaluated in periodontal fibroblasts exposed to F. nucleatum and/or CTS in the presence and absence of a MAPK inhibitor by real-time PCR. RESULTS Increased CXCL5, CXCL8, and CXCL10 levels were observed in human and rat gingiva from sites of inflammation as compared with periodontal health. The rat experimental periodontitis caused a significant (p<0.05) increase in alveolar bone resorption, which was further enhanced when combined with tooth movement. In vitro, F. nucleatum caused a significant upregulation of CXCL5, CXCL8, and CXCL10 at 1 day. Once the cells were exposed simultaneously to F. nucleatum and CTS, the chemokines regulation was significantly enhanced. The transcriptional findings were also observed at protein level. Pre-incubation with the MEK1/2 inhibitor significantly (p<0.05) inhibited the stimulatory actions of F. nucleatum either alone or in combination with CTS on the expression levels of CXCL5, CXCL8, and CXCL10 at 1 d. CONCLUSIONS Our data provide original evidence that biomechanical strain further increases the stimulatory actions of periodontal bacteria on the expressions of these chemokines. Therefore, biomechanical loading in combination with periodontal infection may lead to stronger recruitment of immunoinflammatory cells to the periodontium, which might result in an aggravation of periodontal inflammation and destruction