Non-targeted identification of tianeptine photodegradation products in water samples by UHPLC-QTOF MS/MS.

This study aims the characterization of several tianeptine transformation products in ultrapure water by simulated sunlight irradiation. Tianeptine was completely degraded after 106 h of exposition following pseudo-first-order kinetics (half-life time = 12.0 ± 2.4 h). Furthermore, an ultra-high-performance liquid chromatography coupled with a high-resolution quadrupole time-of-flight-mass spectrometry method was developed and fully validated taking into account different method performance parameters for the quantification of tianeptine in river water up to a concentration of 400 pg L-1. Following a non-targeted approach based on mass data-independent acquisition, eight different transformation products not previously reported in the literature were identified and accordingly elucidated, proposing a photodegradation mechanism based on the accurate tandem mass spectrometry information acquired. Irradiation experiments were replicated for a tianeptine solution prepared in a blank river water sample, resulting in the formation of the same transformation products and similar degradation kinetics. In addition, a toxicity assessment of the photoproducts was performed by in silico method, being generally all TPs of comparable toxicity to the precursor except for TP1, and showing a similar persistence in the environment except for TP2 and TP6, while TP4 was the only TP predicted as mutagenic. The developed method was applied for the analysis of four river water samples.

Peri-implant diseases and systemic inflammation: A preliminary analysis from a cross-sectional survey of patients with hypertension.

BACKGROUND: The aim of this study was to investigate the association between peri-implant diseases and systemic inflammation assessed by serum C-reactive protein (CRP) levels in a sample of patients with hypertension. METHODS: A total of 151 participants with hypertension were included in a cross-sectional study. The population was divided into six groups according to their peri-implant and periodontal status (healthy controls, mucositis, peri-implantitis, periodontitis, periodontitis and mucositis, periodontitis, and peri-implantitis). Linear, logistic regression, and correlation analyses were performed. RESULTS: CRP levels were statistically significantly higher in participants with periodontitis alone (median 3.2 mg/L, interquartile range [IQR] 1.8, p = 0.012), combined with mucositis (3.10 mg/L, IQR 2.35, p < 0.001) or peri-implantitis (2.7 mg/L, IQR 2.53, p = 0.002) when compared to the healthy controls (1 mg/L, IQR 1.2). This association was independent of age, sex, smoking status, and adiposity differences. Participants with periodontitis with and without peri-implant diseases had the greatest odds of exhibiting CRP > 3 mg/L (odds ratio = 7.3, 95% confidence interval 1.6-33.9). CONCLUSIONS: Peri-implant diseases are associated with systemic inflammation, but the nature of the association should be further investigated.

Association between peri-implantitis and systemic inflammation: a systematic review.

Background: Peri-implantitis is an infectious/inflammatory disease with similar clinical and radiographic features to periodontitis. Overwhelming evidence confirmed that periodontitis causes elevations in systemic inflammatory mediators; this is unclear for peri-implantitis. Hence, this study aimed to appraise all available evidence linking peri-implantitis with systemic inflammation. Methods: A systematic review was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eight electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Web of Science, Dentistry & Oral Sciences Source, Scopus, LILACS, and China Online), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and gray literature were searched up to February 9, 2023. Human studies of randomized controlled trials, non-randomized intervention studies, cohort studies, case-control, and cross-sectional studies were eligible for inclusion. Quantitative analyses were performed using random effects models. Results: A total of 27 full-text articles were retrieved, and 11 clinical studies were included in the final analyses. All evidence gathered demonstrated a consistent association between peri-implantitis and systemic inflammation. Patients with peri-implantitis exhibited higher levels of serum C-reactive protein (CRP) (standard mean difference (SMD): 4.68, 98.7% CI: 2.12 to 7.25), interleukin-6 (IL-6) (weighted mean difference (WMD): 6.27 pg/mL, 0% CI: 5.01 to 7.54), and white blood cell counts (WMD: 1.16 * 103/µL, 0% CI: 0.61 to 1.70) when compared to participants without peri-implantitis. Conclusion: Peri-implantitis is associated with higher systemic inflammation as assessed by serum CRP, IL-6, and white blood cell counts. Further research is needed to clarify the nature of this association. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=246837, identifier CRD42021246837.

Local delivery of nitric oxide prevents endothelial dysfunction in periodontitis.

AIMS: Increased cardiovascular disease risk underlies elevated rates of mortality in individuals with periodontitis. A key characteristic of those with increased cardiovascular risk is endothelial dysfunction, a phenomenon synonymous with deficiencies of bioavailable nitric oxide (NO), and prominently expressed in patients with periodontitis. Also, inorganic nitrate can be reduced to NO in vivo to restore NO levels, leading us to hypothesise that its use may be beneficial in reducing periodontitis-associated endothelial dysfunction. Herein we sought to determine whether inorganic nitrate improves endothelial function in the setting of periodontitis and if so to determine the mechanisms underpinning any responses seen. METHODS AND RESULTS: Periodontitis was induced in mice by placement of a ligature for 14 days around the second molar. Treatment in vivo with potassium nitrate, either prior to or following establishment of experimental periodontitis, attenuated endothelial dysfunction, as determined by assessment of acetylcholine-induced relaxation of aortic rings, compared to control (potassium chloride treatment). These beneficial effects were associated with a suppression of vascular wall inflammatory pathways (assessed by quantitative-PCR), increases in the anti-inflammatory cytokine interleukin (IL)-10 and reduced tissue oxidative stress due to attenuation of xanthine oxidoreductase-dependent superoxide generation. In patients with periodontitis, plasma nitrite levels were not associated with endothelial function indicating dysfunction. CONCLUSION: Our results suggest that inorganic nitrate protects against, and can partially reverse pre-existing, periodontitis-induced endothelial dysfunction through restoration of nitrite and thus NO levels. This research highlights the potential of dietary nitrate as adjunct therapy to target the associated negative cardiovascular outcomes in patients with periodontitis.

Association between subclinical atherosclerosis and oral inflammation: A cross-sectional study.

BACKGROUND: The aim of this cross-sectional study was to investigate the association between carotid intima-media thickness (c-IMT) values and periodontal and peri-implant diseases in a sample of patients with hypertension. METHODS: A total of 151 participants with presence of at least one dental implant in function for >5 years were recruited. Anthropometric measurements, 24-h ambulatory blood pressure monitoring, ultrasound assessment of carotid arteries (c-IMT and presence of plaque) were recorded and venous blood samples obtained. An oral examination was performed by calibrated examiners to ascertain prevalence and severity of periodontal and peri-implant diseases. Binomial logistic regression was performed to investigate the potential association between various measures of exposure of dental diseases and predictors of cardiovascular risk (c-IMT > 0.9 mm and presence of plaque or their combination). RESULTS: Diagnosis of periodontitis (OR 6.71, 95% CI: 2.68-16.76, P < 0.001), cumulative mucosal/gingival inflammation (Periodontal Screening and Recording score) (OR 1.25, 95% CI:1.12-1.41, P < 0.001), and mucositis (OR 3.34, 95% CI:1.13-9.85, P < 0.05) were associated with c-IMT > 0.9 mm and/or plaque presence independent of age, sex, smoking, 24 h systolic blood pressure and body mass index differences. No statistically significant results were noted for peri-implantitis. Linear regression models confirmed a positive association of cumulative mucosal/gingival inflammation (ß = 0.011, SE 0.002, P < 0.001), diagnosis of periodontitis (ß = 0.114, SE 0.020, P < 0.001), and peri-implant diseases (ß = 0.011, SE 0.002, P < 0.001) with increased c-IMT values. CONCLUSIONS: This study confirms a positive association between mucosal/gingival inflammation and subclinical atherosclerosis assessed by c-IMT values and the presence of carotid plaque in patients with hypertension, independent of traditional cardiovascular risk factors. Future studies are needed to further characterize this relationship.

Treatment of periodontitis and C-reactive protein: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Systemic inflammation is implicated in the onset and progression of several chronic diseases. Periodontitis is a potential trigger of systemic inflammation. PURPOSE: To comprehensively appraise all the evidence on the effects of the treatment of periodontitis on systemic inflammation assessed by serum C-reactive protein (CRP) levels. DATA SOURCES: Six electronic databases were searched up to 10 February 2022 to identify and select articles in English language only. STUDY SELECTION: Twenty-six randomized controlled clinical trials reporting changes amongst 2579 participants about CRP levels at 6 months or more after treatment. DATA EXTRACTION: Two reviewers independently extracted data and rated the quality of studies. Meta-analyses were performed using random and fixed effect models. RISK OF BIAS: Risk of bias (RoB 2.0 tool) and quality of evidence (GRADEpro GDT tool) analyses were completed. DATA SYNTHESIS: Treatment of periodontitis reduced CRP levels by 0.69 mg/L (95% confidence interval: -0.97 to -0.40) after 6 months, but limited evidence was retrieved from studies with longer follow-ups. Similar findings were observed in participants with other co-morbidities in addition to periodontitis. Greatest reductions were observed in participants with concentrations of CRP >3 mg/L at baseline. LIMITATIONS: High level of heterogeneity. CONCLUSIONS: Treatment of periodontitis reduces serum CRP levels (up to 6 months follow-up) to a degree equivalent to that observed after traditional lifestyle or drug interventions. This evidence supports a causal association between periodontitis and systemic inflammation.

Complications and treatment errors in periodontal therapy in medically compromised patients.

Patients who are medically compromised may be at an increased risk of complications and treatment errors following periodontal therapy. A review of the evidence on the topic is presented, in relation to the type of complication reported, of periodontal treatment, and of patients' medical status. Further, a framework for risk assessment and appropriate treatment modifications is introduced, with the aim of facilitating the management of patients with existing comorbidities and reducing the incidence of treatment complications.

An umbrella review of the evidence linking oral health and systemic noncommunicable diseases.

Oral diseases are highly prevalent worldwide. Recent studies have been supporting a potential bidirectional association of oral diseases with systemic noncommunicable diseases (NCDs). Available evidence supports that people with NCDs have a greater prevalence of oral diseases particularly those with limited ability of oral self-care. Regarding the reverse relationship, the lines of evidence pointing out NCDs as putative risk factors for oral diseases have increased significantly but not with a consistent agreement. This umbrella review of meta-analyses appraises the strength and validity of the evidence for the association between oral health and systemic health (registered at PROSPERO, ID: CRD42022300740). An extensive search included systematic reviews that have provided meta-analytic estimates on the association of oral diseases with NCDs. The overall strength of evidence was found to be unfavorable and with methodological inconsistencies. Twenty-eight NCDs were strongly associated with oral diseases. Among those NCDs are five types of cancer, diabetes mellitus, cardiovascular diseases, depression, neurodegenerative conditions, rheumatic diseases, inflammatory bowel disease, gastric helicobacter pylori, obesity, and asthma. According to fail-safe number statistics, the evidence levels are unlikely to change in the future, indicating a fairly robust consistency.

Cytotoxic Compounds from Alcyoniidae: An Overview of the Last 30 Years.

The octocoral family Alcyoniidae represents a rich source of bioactive substances with intriguing and unique structural features. This review aims to provide an updated overview of the compounds isolated from Alcyoniidae and displaying potential cytotoxic activity. In order to allow a better comparison among the bioactive compounds, we focused on molecules evaluated in vitro by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, by far the most widely used method to analyze cell proliferation and viability. Specifically, we surveyed the last thirty years of research, finding 153 papers reporting on 344 compounds with proven cytotoxicity. The data were organized in tables to provide a ranking of the most active compounds, to be exploited for the selection of the most promising candidates for further screening and pre-clinical evaluation as anti-cancer agents. Specifically, we found that (22S,24S)-24-methyl-22,25-epoxyfurost-5-ene-3ß,20ß-diol (16), 3ß,11-dihydroxy-24-methylene-9,11-secocholestan-5-en-9-one (23), (24S)-ergostane-3ß,5α,6ß,25 tetraol (146), sinulerectadione (227), sinulerectol C (229), and cladieunicellin I (277) exhibited stronger cytotoxicity than their respective positive control and that their mechanism of action has not yet been further investigated.

Invasive dental treatment and acute vascular events: A systematic review and meta-analysis.

BACKGROUND: Acute infection/inflammation increases the risk of acute vascular events (AVEs). Invasive dental treatments (IDTs) trigger short-term acute inflammation. PURPOSE: The aim of this work is to critically appraise the evidence linking IDTs and AVEs. DATA SOURCES: Six bibliographical databases were searched up to 31 August 2021. A systematic review following PRISMA guidelines was performed. STUDY SELECTION: Intervention and observational studies reporting any AVEs following IDT were included. DATA EXTRACTION: Two reviewers independently extracted data and rated the quality of studies. Data were pooled using fixed-effect, inverse variance weights analysis. RISK OF BIAS: Risk of bias was assessed by the Newcastle-Ottawa Quality Assessment Scale for observational studies and the Cochrane Handbook-Rob 2.0 for randomized controlled trials. DATA SYNTHESIS: In 3 out of 16 clinical studies, a total of 533,175 participants, 124,344 myocardial infarctions, and 327,804 ischaemic strokes were reported. Meta-analysis confirmed that IDT did not increase incidence ratios (IR) for combined vascular events either at 1-4 weeks (IR of 1.02, 95% CIs: 0.92 to 1.13) and at 5-8 weeks (IR of 1.04, 95% CIs: 0.97 to1.10) after treatment. LIMITATIONS: A high level of heterogeneity (study designs and time point assessments) was found. CONCLUSION: Patients who received IDT exhibited no substantial increase in vascular risk over 8 weeks post treatment.

Periodontitis and Systemic Lupus Erythematosus: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the association between periodontitis (PD) and systemic lupus erythematosus (SLE). A systematic search was conducted through the following electronic databases: Cochrane Library, MEDLINE, EMBASE, Scopus, LILACS, CINAHL and SIGLE (System for Information on Grey Literature in Europe) for relevant publications up to September 2020 with no language restriction. The association between PD and SLE was assessed by the prevalence of PD in SLE patients (both sex and females only) as the primary outcome. Secondary outcomes included differences in common gingival parameters including probing pocket depth (PPD), clinical attachment level (CAL), disease activity index (SLEDAI) scores of SLE patients with or without PD. A total of 1183 citations and 22 full text articles were screened. Eighteen articles were included in the qualitative synthesis, and 13 in the quantitative analysis. SLE diagnosis was associated with greater odds of PD (OR = 1.33, 95% Confidence Interval [CI]: 1.20-1.48), but these were non-significant when examined in females (OR = 3.20, 95%CI: 0.85-12.02). Patients with SLE exhibited no differences in PPD (SMD: -0.09 mm, 95%CI: -0.45-0.27) and CAL (SMD: 0.05 mm, 95%CI: -0.30-0.40) when compared with systemically healthy controls. PD diagnosis was, however, associated with higher SLEDAI scores in patients suffering from SLE (SMD: 0.68, 95% CI: 0.03-1.32). PD and SLE are both inflammatory diseases and their association could be bi-directional. This review suggested that the patients with SLE have greater odds of suffering with PD. Further investigations are required to assess the association between PD and SLE.

Impact of the treatment of periodontitis on systemic health and quality of life: A systematic review.

AIM: To investigate the effect of treatment of periodontitis on systemic health outcomes, pregnancy complications, and associated quality of life. MATERIALS AND METHODS: Systematic electronic searches were conducted to identify randomized controlled trials with minimum 6-month follow-up and reporting on the outcomes of interest. Qualitative and quantitative analyses were performed as deemed suitable. RESULTS: Meta-analyses confirmed reductions of high-sensitivity C-reactive protein (hs-CRP) [0.56 mg/L, 95% confidence interval (CI) (-0.88, -0.25), p < .001]; interleukin (IL)-6 [0.48 pg/ml, 95% CI (-0.88, -0.08), p = .020], and plasma glucose [1.33 mmol/l, 95% CI (-2.41, -0.24), p = .016], and increase of flow-mediated dilation (FMD) [0.31%, 95% CI (0.07, 0.55), p = .012] and diastolic blood pressure [0.29 mmHg, 95% CI (0.10, 0.49), p = .003] 6 months after the treatment of periodontitis. A significant effect on preterm deliveries (<37 weeks) was observed [0.77 risk ratio, 95% CI (0.60, 0.98), p = .036]. Limited evidence was reported on quality-of-life (QoL) outcomes in the included studies. CONCLUSIONS: Treatment of periodontitis results in systemic health improvements including improvement in cardiometabolic risk, reduction in systemic inflammation and the occurrence of preterm deliveries. Further research is however warranted to confirm whether these changes are sustained over time. Further, appropriate QoL outcomes should be included in the study designs of future clinical trials.

From the Streets to the Judicial Evidence: Determination of Traditional Illicit Substances in Drug Seizures by a Rapid and Sensitive UHPLC-MS/MS-Based Platform.

According to the 2021 World Drug Report, around 275 million people use drugs of abuse, and 36 million people suffer from addiction, fostering a thriving market for illicit substances. In Italy, 30,083 people were reported to the Judicial Authority for offenses in violation of the Italian Law D.P.R. 309/1990. These offences are sentenced after a qualitative-quantitative analysis of seized materials. Given the large quantity of seized drugs and the need to perform accurate analytical determinations, Italian forensic laboratories struggle to complete analyses in a short time, delaying the entire reporting process needed to achieve sentencing. For this purpose, an UHPLC-MS/MS-based platform was developed at the University of Milano-Bicocca to support law-enforcement authorities. Software was designed to easily manage street seizure acquisition, documentation registration, and sampling. A sensitive UHPLC-MS/MS method was fully validated for the quantification of the traditional illicit substances (cocaine, heroin, 6-MAM, morphine, amphetamine, methamphetamine, MDMA, ketamine, GHB, GBL, LSD, trans-∆9-THC, and THCA) at the ppb level. The final report is relayed to the Prefecture in 3-4 days, even within 24 h for urgent requests. The platform allows for semi-automatic data handling to minimize erroneous results for an accurate report generation by standardized procedures.

Parsimonious Optimization of Multitask Neural Network Hyperparameters.

Neural networks are rapidly gaining popularity in chemical modeling and Quantitative Structure-Activity Relationship (QSAR) thanks to their ability to handle multitask problems. However, outcomes of neural networks depend on the tuning of several hyperparameters, whose small variations can often strongly affect their performance. Hence, optimization is a fundamental step in training neural networks although, in many cases, it can be very expensive from a computational point of view. In this study, we compared four of the most widely used approaches for tuning hyperparameters, namely, grid search, random search, tree-structured Parzen estimator, and genetic algorithms on three multitask QSAR datasets. We mainly focused on parsimonious optimization and thus not only on the performance of neural networks, but also the computational time that was taken into account. Furthermore, since the optimization approaches do not directly provide information about the influence of hyperparameters, we applied experimental design strategies to determine their effects on the neural network performance. We found that genetic algorithms, tree-structured Parzen estimator, and random search require on average 0.08% of the hours required by grid search; in addition, tree-structured Parzen estimator and genetic algorithms provide better results than random search.

Serum C-Reactive Protein and Periodontitis: A Systematic Review and Meta-Analysis.

Periodontitis has been associated with low-grade inflammation as assessed by C-reactive protein (CRP) levels and its treatment can decrease CRP serum levels. The aim of this systematic review was to critically appraise the evidence comparing CRP serum levels (standard and high-sensitivity [hs]) of otherwise healthy patients suffering from periodontitis when compared to controls. The impact of intensive and non-intensive nonsurgical periodontal treatment (NSPT) on hs-CRP was also investigated. Four electronic databases (Pubmed, The Cochrane Central Register of Controlled Trials [CENTRAL], EMBASE and Web of Science) were searched up to February 2021 and the review was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No. CRD42020167454). Observational and intervention studies that: 1) evaluated CRP and hs-CRP serum levels in patients with and without periodontitis, and; 2) hs- CRP levels after NSPT were included. Following risk of bias appraisal, both qualitative and quantitative analyses were performed. Pooled estimates were rendered through ratio of means (RoM) random-effects meta-analyses. After screening 485 studies, 77 case-control studies and 67 intervention trials were included. Chronic and aggressive periodontitis diagnoses were consistently associated with higher levels of CRP and hs-CRP (p<0.001). Patients with aggressive periodontitis exhibited on average more than 50% higher levels of CRP (RoM [95% confidence interval [CI]]: 1.56 [1.15; 2.12], p=0.0039) than patients with chronic periodontitis. Intensive NSPT induced an immediate increase of hs-CRP followed by a progressive decrease whilst non-intensive NSPT consistently decreased hs-CRP after treatment up to 180 days (p<0.001). These findings provide robust evidence that periodontitis is associated with systemic inflammation as measured by serum CRP levels. Periodontitis treatment induces a short-term acute inflammatory increase when performed in an intensive session, whilst a progressive reduction up to 6 months was demonstrated when performed in multiple visits.

Remote Ischemic Preconditioning Protects Against Endothelial Dysfunction in a Human Model of Systemic Inflammation: A Randomized Clinical Trial.

OBJECTIVE: Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemiareperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammation, we investigated whether RIPC prevents endothelial dysfunction and modulates systemic levels of inflammation and oxidative stress. APPROACH AND RESULTS: Forty-nine participants with periodontitis were randomly allocated to receive either 3 cycles of ischemia-reperfusion on the upper limb (N=24, RIPC) or a sham procedure (N=25, control) before IPT. Endothelial function assessed by flow-mediated dilatation of the brachial artery, inflammatory cytokines, markers of vascular injury, and oxidative stress were evaluated at baseline, day 1, and day 7 after IPT. Twenty-four hours post-IPT, the RIPC group had lower levels of IL-10 (interleukin-10) and IL-12 (interleukin-12) compared with the control group (P<0.05). RIPC attenuated the IPTinduced increase in IL-1ß (interleukin-1ß), E-selectin, sICAM-3 (soluble intercellular adhesion molecule 3), and sTM (soluble thrombomodulin) levels between the baseline and day 1 (P for interaction <0.1). Conversely, oxidative stress was differentially increased at day1 in the RIPC group compared with the control group (P for interaction <0.1). This was accompanied by a better flow-mediated dilatation (mean difference 1.75% [95% CI, 0.428­3.07], P=0.011). After 7 days from IPT, most of the inflammatory markers, endothelial-dependent and -independent vasodilation, were similar between groups. CONCLUSIONS: RIPC prevented acute endothelial dysfunction by modulation of inflammation and oxidation processes in patients with periodontitis following exposure to an acute inflammatory stimulus. REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT03072342; Unique identifier: NCT03072342.

Association Between Periodontitis and Blood Pressure Highlighted in Systemically Healthy Individuals: Results From a Nested Case-Control Study.

[Figure: see text].

Integrated biological and chemical characterisation of a pair of leonardesque canal lock gates.

The Museo Nazionale della Scienza e della Tecnologia "Leonardo da Vinci" in Milan is exposing two pairs of canal lock gates, used to control the water flow in Milan canal system, whose design appears in the Leonardo's Codex Atlanticus. The wood present in the gates has been deeply characterised by mean of a multidisciplinary investigation involving i) DNA barcoding of wood fragments; ii) microbial community characterisation, and iii) chemical analyses. DNA barcoding revealed that two fragments of the gates belonged to wood species widely used in the middle age: Fagus sylvatica and Picea abies. The chemical characterisations were based on the use of ionic liquid as dissolving medium in order to analyse the entire cell wall material by means of Gel Permeation Chromatography (GPC) and 2D-NMR-HSQC techniques. This multidisciplinary analytical approach was able to highlight the complex nature of the degradation occurred during the gate operation (XVI-XVIII centuries): an intricate interplay between microbial populations (i.e. Shewanella), inorganic factors (i.e. iron from nails), physical factors and the lignocellulosic material.

Periodontitis and circulating blood cell profiles: a systematic review and meta-analysis.

Periodontitis is a chronic inflammatory disease with local and systemic implications. Evidence suggests consistent hematologic changes associated with periodontitis. Our aim was to critically appraise the available evidence on hemogram, leukogram, and thrombogram alterations in otherwise healthy patients suffering from periodontitis when compared with controls. For this systematic review (SR), we searched MEDLINE, Web of Science, EMBASE, and the Cochrane Library (CENTRAL) for studies published up to June 2020. Both observational and interventional studies with baseline standard hematologic levels were included. Outcomes of interest were baseline hemogram, leukogram, and thrombogram values and the impact of periodontitis treatment on these outcomes. Upon risk of bias assessment, data extraction and both qualitative and quantitative (standardized mean differences) analyses were performed. Random-effects meta-analyses were performed to provide pooled estimates. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed (PROSPERO Reg. No. CRD42020164531). A total of 45 studies, eight intervention and 37 case-control studies, were identified after the final search of 3,012 titles. Following quality assessment, 43 articles were deemed to have low risk of bias, and two articles moderate risk. Meta-analyses confirmed that periodontitis was associated with both white and red cell lineages. Severe chronic periodontitis was associated with greater white blood cell counts (mean difference [MD] = 0.53, 95% confidence interval [CI]: 0.26-0.79) when compared with controls. Periodontitis was associated with a larger number of neutrophils (MD = 7.16%, 95% CI: 5.96-8.37) and lower mean platelet volume (MD = 0.30 fL, 95% CI: 0.49 to -0.10) compared with healthy participants. Nonsurgical periodontal treatment was associated with a decrease in white blood cell (WBC) levels (MD = 0.28 109/L, 95% CI: -0.47 to -0.08) in patients with chronic periodontitis. Periodontitis is associated with hematologic changes (Strength of Recommendation Taxonomy [SORT] A recommendation). Higher WBC levels, higher neutrophil levels, higher erythrocyte sedimentation rate, and lower mean platelet volumes are the most common blood count findings. The association between periodontitis and WBC could be causal in nature. Further assessment to determine whether periodontitis causes changes in circulating blood cells and to identify the molecular mechanisms underlying these associations is warranted.

Severe Periodontitis and Biomarkers of Bacterial Burden. Results From a Case-Control and Intervention Clinical Trial.

Background and aims: Periodontitis is an inflammatory-infectious disease. Identifying markers of systemic exposure of periodontitis might be of interest to study its interaction with other conditions. Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is upregulated during bacterial infections. Our aim was therefore to investigate whether periodontitis and its treatment are associated with bacterial endotoxin and sTREM-1. Methods: Fifty patients with severe periodontitis and 50 age-matched controls were included in a case-control study (all never smokers). A secondary analysis of a previously published intervention study was performed, in which included 69 patients with severe periodontitis were randomized to receive either intensive (IPT) or control periodontal therapy (CPT) and monitored over 6 months. Serum levels of bacterial endotoxin and sTREM-1 were determined at one time point (case-control study) and at baseline, 1 day, 1 and 6 months after periodontal treatment (intervention study). Results: Severe periodontitis was associated with elevated circulating endotoxin levels when cases (22.9 ± 2.2 EU/ml) were compared to controls (3.6 ± 0.5 EU/ml, p < 0.001) and with sTREM-1 levels (1302.6 ± 47.8 vs. 870.6 ± 62.0 pg/ml, p < 0.001). A positive correlation was observed between sTREM-1 and endotoxin levels (r = 0.4, p < 0.001). At 6 months after treatment, IPT significantly decreased serum levels of sTREM-1 compared to CPT (adjusted mean difference of 500.2 pg/ml, 95% CI: 18.9-981.4; p = 0.042). No substantial differences were noted in endotoxin levels at any time point after treatment between groups. Conclusions: Severe periodontitis is linked to increased circulating endotoxin and sTREM-1 levels and following IPT a reduction in sTREM-1 levels is observed.