Considering the central role of inflammation in the pathogenesis of periodontitis, the combination of NSPT with different agents that can modulate the host immune-inflammatory response has been proposed to enhance the outcomes of NSPT. The aim of this paper is to systematically review the literature on the efficacy of systemic host modulators (HMs) as adjuncts to non-surgical periodontal therapy (NSPT) in improving pocket depth (PD) reduction and clinical attachment level (CAL) gain in healthy and systemically compromised patients. RCTs with ≥ 3 months follow-up were independently searched by two reviewers. Meta-analysis was performed when ≥ 3 studies on the same HM were identified. The quality of the evidence was rated according to the GRADE approach to rate the certainty of evidence. 38 articles were included in the qualitative assessment and 27 of them were included in the meta-analysis. There is low/very low evidence that the adjunctive use of sub-antimicrobial dose of doxycicline, melatonin and the combination of omega-3 and low dose aspirin (in type 2 diabetic patients) to NSPT would improve PD and/or CAL. Conflicting evidence is available on the efficacy of probiotics. Future studies controlling for confounding factors, using composite outcomes to define the endpoint of therapy and considering not only the patient- but also as the site-specific effect of systemic HMs are warranted. The dosage, posology and long-term effect of HMs still need to be clarified, also in association to the presence of systemic conditions potentially affecting the response to HMs administration.

Fungal infections are common on oral mucosae, but their role in other oral sites is ill defined. Over the last few decades, numerous studies have reported the presence of fungi, particularly Candida species in endodontic infections, albeit in relatively small numbers in comparison to its predominant anaerobic bacteriome. Here, we review the fungal biome of primary and secondary endodontic infections, with particular reference to the prevalence and behavior of Candida species. Meta-analysis of the available data from a total of 39 studies fitting the inclusion criteria, indicate the overall weighted mean prevalence (WMP) of fungal species in endodontic infections to be 9.11% (from a cumulative total of 2003 samples), with 9.0% in primary (n = 1341), and 9.3% in secondary infections (n = 662). Nevertheless, WMP for fungi in primary and secondary infections which were 6.3% and 7.5% for culture-based studies, increased to 12.5% and 16.0% in molecular studies, respectively. The most prevalent fungal species was Candida spp. The high heterogeneity in the reported fungal prevalence suggests the need for standardized sampling, and speciation methods. The advent of the new molecular biological analytical platforms, such as the next generation sequencing (NGS), and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF), that enables identification and quantitation of a broad spectrum of hitherto unknown organisms in endodontic infections should radically alter our understanding of the endodontic mycobiome in the future. Candida spp. appear to be co-pathogens with bacteria in approximately one in ten patients with endodontic infections. Hence, clinicians should comprehend the importance and the role of fungi in endodontic infections and be cognizant of the need to eradicate both bacteria and fungi for successful therapy.

Diabetes is an important modifying factor of periodontitis, but its association with peri-implant diseases has not been fully explored and the existing literature reports controversial results. The aim of this retrospective study was to evaluate the influence of diabetes on peri-implantitis and implant failure. Smoking status, history of periodontal disease, presence of diabetes, diabetes type, therapy and glycaemia levels were collected in a total of 204 subjects treated with 929 implants, with a mean follow-up time of 5.7 ± 3.82 years after loading. Odds ratio (OR) for diabetes as a direct cause of peri-implantitis and implant failure were calculated, adjusted for smoking status and history of periodontitis. Nineteen patients were diabetic and most of them presented a good control of the disease at the time of surgery. The overall patient-level prevalence of peri-implantitis was 11.3%. Among diabetic patients, one developed peri-implantitis, whereas one experienced multiple implant failures. The calculated ORs, adjusted for smoking status and periodontitis, were not statistically significant. The results revealed no association between diabetes and peri-implantitis or implant failure coherently with the existing scientific literature. The actual influence of hyperglycemia on implant failure is still uncertain and new studies with larger cohorts of patients are needed.

While periodontitis has been proven to have an impact on systemic conditions, such as cardiovascular diseases, pregnancy complications, or poor glycemic control in diabetic patients, the influence of peri-implantitis on systemic health has not been adequately explored in the literature as yet. The existing evidence suggests that peri-implant lesions lead to more intense inflammatory response than periodontitis. Given the analogies between periodontal diseases and peri-implantitis, the aim of the present paper was to review the scientific evidence about the potential correlation between peri-implantitis and systemic diseases and conditions. Two clinical trials on animals reported that experimental peri-implantitis determined an alteration in hematological and biological parameters. One human study explored the risk indicators for cardiovascular diseases and found that patients with peri-implantitis had significantly higher levels of triglyceride, uric acid, and white blood cells and lower levels of vitamin D. It was described in the literature that periodontitis affects cardiovascular health through a number of mechanisms, including the increase in systemic mediators of inflammation, which also has a role in the worsening of glycemic control in diabetic patients. Similarly, peri-implantitis may influence the systemic status through inflammatory cytokines such as IL-1, IL-6, and IL-10 and matrix metalloproteinases. One microbiological mechanism, based on the systemic dissemination of periodontal bacteria, has been hypothesized for cardiovascular diseases and pregnancy complications. Again, it is plausible that the same could occur in peri-implantitis. In conclusion, only few studies explored the systemic impact of peri-implantitis. Although changes in hematological parameters, biochemical parameters, and inflammatory markers have been reported in peri-implantitis, further studies are needed to investigate this correlation.

Objective: The present retrospective study investigated the effect of chronic intake of proton pump inhibitors, selective serotonin uptake inhibitors, anti‐inflammatory, and antihypertensive drugs on the survival of dental implants and on the occurrence of peri‐implantitis.Materials and methods: Survival analyses for implant failure and peri‐implantitis were performed patient level for each drug subcategory and for risk factors. The HR for each drug was calculated with adjusted models as compared with a control group made of subjects not assuming the specific drug. Multilevel logistic regression was used to explore the influence of implant‐level and patient‐level variables on the outcomes.Results: A total of 270 subjects receiving 1118 dental implants were included, with a mean follow‐up time of 5.19 ± 4.22 years. After 10 years, the survival rate was 86.9% (patient level), and according to survival analysis, 61.3% of subjects were free from peri‐implantitis. The use of anti‐inflammatory medicines produced a significant effect (p = .04) on peri‐implantitis as compared to subjects not using the drug, with a 2.7‐year drop in the mean survival time. The HR was slightly above the level of significance in a semiadjusted model (p = .058). The multilevel analysis found a significant effect on the entire sample and not when considering only subjects with implants with more than 1‐year follow‐up.Conclusions: We found a possible relationship between anti‐inflammatory drug use and the occurrence of peri‐implantitis in the examined cohort of patients, and no correlation for the other drugs.

The aim of the present systematic review of the literature and meta‐analysis was to evaluate the efficacy of different protocols of NSPT without any adjunctive therapy in subjects with type 2 diabetes, by considering clinical and patient‐centered outcomes. For the purposes of the study randomized controlled clinical trials with more than 3‐month follow‐up were searched in MEDLINE, EMBASE, and Cochrane Central. Then the articles were screened for inclusion and considered based on the protocols adopted, the outcome measure, follow‐up, and the level of glycemic control. A total of 23 articles about 22 studies were included. NSPT was more effective than just oral hygiene measures/no treatment in reducing periodontal probing depth (PPD) and clinical attachment loss (CAL) at 3 months (0.47 mm [0.29–0.65 mm] and 0.50 mm [0.24–0.76 mm], respectively) and 6 months (0.56 mm [0.28–0.84 mm] and 0.45 mm [0.13–0.77 mm], respectively for PPD and CAL) follow‐up (very low and low level of evidence). The meta‐analysis found no evidence of a difference between full‐mouth disinfection versus quadrant protocol clinical outcomes (very low level of evidence). One study found no evidence of a difference in periodontal clinical response between good versus poor glycemic control. Based on the results of the present research NSPT protocols could be considered more efficacious than others in terms of clinical outcomes in subjects with type 2 diabetes. Moreover, NSPT resulted in efficacious improvement of periodontal parameters and HbA1c levels compared to no treatment or oral hygiene instructions alone.