Oral inflammatory load: Neutrophils as oral health biomarkers.

Periodontal diseases present a significant challenge to our healthcare system in terms of morbidity from the disease itself as well as their putative and deleterious effects on systemic health. The current method of diagnosing periodontal disease utilizes clinical criteria solely. These are imprecise and are somewhat invasive. There is thus significant benefit to creating a non-invasive test as a method of screening for and monitoring of periodontal diseases, and, in particular, chronic periodontitis. Oral polymorphonuclear neutrophil (oPMN) counts have been found to correlate with extent of oral inflammation and the presence and severity of periodontal diseases. Potentially then, quantification of oPMNs might be used to identify and measure the severity of oral inflammation (oral inflammatory load; OIL) in subjects with healthy and inflamed periodontal tissues, demonstrating a positive correlation between higher oPMN counts and the extent/severity of OIL. These findings support the development and utilization of a non-invasive chair-side test enabling rapid, accurate, and objective screening of OIL based on measurement of oPMN numbers (similar to white blood cell levels in blood as used in medicine for assessment of infection). The use of such a test before, during, and after treatment of gingivitis and periodontitis could lead to improvements in timing of intervention (ie, when inflammation is active) thereby reducing long-term morbidity.

Parsimonious Effect of Pentoxifylline on Angiogenesis: A Novel Pentoxifylline-Biased Adenosine G Protein-Coupled Receptor Signaling Platform.

Angiogenesis is the physiological process of developing new blood vessels to facilitate the delivery of oxygen and nutrients to meet the functional demands of growing tissues. It also plays a vital role in the development of neoplastic disorders. Pentoxifylline (PTX) is a vasoactive synthetic methyl xanthine derivative used for decades to manage chronic occlusive vascular disorders. Recently, it has been proposed that PTX might have an inhibitory effect on the angiogenesis process. Here, we reviewed the modulatory effects of PTX on angiogenesis and its potential benefits in the clinical setting. Twenty-two studies met the inclusion and exclusion criteria. While sixteen studies demonstrated that pentoxifylline had an antiangiogenic effect, four suggested it had a proangiogenic effect, and two other studies showed it did not affect angiogenesis. All studies were either in vivo animal studies or in vitro animal and human cell models. Our findings suggest that pentoxifylline may affect the angiogenic process in experimental models. However, there is insufficient evidence to establish its role as an anti-angiogenesis agent in the clinical setting. These gaps in our knowledge regarding how pentoxifylline is implicated in host-biased metabolically taxing angiogenic switch may be via its adenosine A2BAR G protein-coupled receptor (GPCR) mechanism. GPCR receptors reinforce the importance of research to understand the mechanistic action of these drugs on the body as promising metabolic candidates. The specific mechanisms and details of the effects of pentoxifylline on host metabolism and energy homeostasis remain to be elucidated.

The Impact Of Active Chest Tube Clearance Technology On Surgical Outcomes After Cardiac Surgery: An Updated Systematic Review And Meta-Analysis.

OBJECTIVE: Active chest tube clearance technology (ACT) systems were introduced to improve the patency of chest tubes and to reduce the potential complications associated with inadequate mediastinal blood drainage after cardiac surgical procedures. The purpose of this study is to assess the impact of ACT on the incidence of chest tube clogging, retained blood syndromes (RBS), re-exploration for bleeding, and the incidence of postoperative atrial fibrillation (POAF) after cardiac surgical procedures. METHODS: A database search was conducted using Medline, Embase, Cochrane Library, and Web of Science. Only articles comparing the use of ACT to conventional chest tube drainage after cardiac surgery were screened. Included articles were restricted to adult patients and English language only. RESULTS: Nine of the 841 articles screened were included in this review. Two studies were randomized controlled trials (RCT) and seven were observational studies. Pooled estimates showed RBS, surgical re-exploration rates, and POAF were significantly less common in the ACT group. CONCLUSION: Our meta-analysis suggests that the use of ACT may be beneficial in reducing the incidence of postoperative complications associated with inadequate drainage of mediastinal blood after cardiac surgery. However, more robust evidence is required to endorse these findings and support the routing use of ACT in clinical practice.

Long-term impact of permanent cardiac pacing after surgical aortic valve replacement: systematic review and meta-analysis.

OBJECTIVES: Permanent pacemaker (PPM) implantation after surgical aortic valve (SAVR) is associated with short- and long-term complications. However, the impact of PPM implantation on long-term mortality has not been fully established. The aim of this meta-analysis was to determine whether PPM post-SAVR increases the risk of mortality. METHODS: We searched Cochrane, MEDLINE, and EMBASE from inception to December 2020 for studies comparing mortality between patients who received PPM post-SAVR and those who did not. Random effects meta-analysis was performed to determine the effect of PPM on early and late mortality. The effect sizes were reported as hazard ratio (HR) with 95% confidence intervals. RESULTS: Three studies met criteria, which yielded a total of 9,105 patients. The most common indication was post-operative complete atrioventricular block. While there was no difference in early mortality between the PPM and no PPM groups (RR 1.19; 95%CI 0.20-7.08; I2 = 23%), PPM implantation was shown to significantly increase late mortality (RR 1.49; 95%CI 1.25-1.77; I2 = 0%). CONCLUSION: The need for permanent pacemaker after surgically isolated aortic valve replacement is associated with increased risk of long-term mortality. This warrants further exploration on the effect of PPM on long-term mortality in patients receiving sutureless prostheses or transcatheter aortic valve implants.AbbreviationsPPM Permanent PacemakerSAVR Surgical Aortic Valve Replacement.

The use of FEIBA for refractory bleeding in cardiac surgery - a systematic review.

INTRODUCTION: Significant blood loss during cardiac surgery is associated with a dramatic increase in morbidity and mortality. Factor Eight Inhibitor Bypassing Activity (FEIBA), a hemostatic bypassing agent mainly used in hemophiliac patients, has also been used for intractable bleeding during cardiac surgical procedures in non-hemophiliac patients. However, concerns exist that its use may be linked to increased incidence of perioperative adverse effects including thrombotic complications. AREAS COVERED: A systematic literature search was performed on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases for all studies that reported the administration of FEIBA for treatment of bleeding during adult cardiac surgery in non-hemophiliac patients. After selecting the title and abstracts, two authors assessed the methodological quality of the full-text articles prior to final inclusion in the manuscript. EXPERT OPINION: The safety profile of FEIBA was determined through an aggregate count of adverse events. Major complications included renal failure, re-operation for unresolved bleeding, postoperative mortality, and thromboembolic events. Overall, there is insufficient robust evidence to make a definitive conclusion about the safety or efficacy of using of FEIBA as a hemostatic agent in the setting of cardiac surgery.

Tissue-specific murine neutrophil activation states in health and inflammation.

Neutrophils are quickly recruited to tissues in response to proinflammatory cues; however, little is known about tissue neutrophil phenotypes in health. We employ a multicolor flow cytometric approach to assess surface markers of activation on neutrophils from the bone marrow, blood, peritoneum, spleen, liver, fat, colon, and oral cavity of healthy mice. Cell preparations were promptly fixed to preserve native surface marker expression levels. Peritoneal, colonic, and oral neutrophils were also assessed in the setting of pHrodo-induced peritonitis, dextran sodium sulfate-induced colitis, and ligature-induced periodontal disease, respectively. Our results demonstrate consistent detectable neutrophil populations in various sterile and nonsterile tissues of healthy mice, and these cells had tissue-specific neutrophil immunophenotypes. Neutrophils derived from biofilm-associated mucosal tissues had 2- to 3-fold higher expression of surface markers of activation, including CD66a, CD11b, and CD62L, compared to neutrophils derived from both sterile healthy tissues as well as tissues in animals treated with broad-spectrum antibiotics. Furthermore, the unique cluster of differentiation (CD) marker activation signatures of tissue-specific neutrophils from the peritoneum, colon, and oral cavity were altered to a proinflammatory immunophenotype with the presence of an inflammatory stimulus. Based on our results, we propose a model whereby a hierarchy of tissue neutrophil immunophenotypes, based on the differential expression of CD markers of activation, correlates with sterile, healthy commensal biofilm-associated and inflamed tissue states.

In Vitro Assay for Sensitive Determination of Human Blood PMN Responses.

Polymorphonuclear neutrophils (PMNs) are the most common leukocytes in the circulation and exhibit a wide range of distinct cellular phenomena as part of their microbicidal killing activities, including degranulation, phagocytosis, reactive oxygen species (ROS) production, adhesion, chemotaxis and production of PMN Extracellular Traps (NETs). As a simple in vitro test of PMN functional responses in human blood we have developed a multicolor flow cytometry-based assay of PMN cluster of differentiation (CD) surface marker expression. Short incubations of whole human blood can be performed in the presence of a wide range of agonists or inhibitors, followed by sensitive detection of changes in CD marker expression. This protocol has the advantage that small amounts of human blood are necessary and there are no PMN isolation steps, which can alter PMN activation status.