Mesenchymal Stromal/Stem Cell Therapy Improves Salivary Flow Rate in Radiation-Induced Salivary Gland Hypofunction in Preclinical in vivo Models: A Systematic Review and Meta-Analysis.

BACKGROUND: Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to determine the safety and effectiveness of MSC therapy on radio-induced SG damage and hypofunction in preclinical in vivo studies. METHODS: PubMed and EMBASE were systematically searched for preclinical in vivo interventional studies evaluating efficacy and safety of MSC treatment following radio-induced salivary gland damage published before 10th of January 2022. The primary endpoint was salivary flow rate (SFR) evaluated in a meta-analysis. The study protocol was published and registered on PROSPERO ( www.crd.ac.uk/prospero ), registration number CRD42021227336. RESULTS: A total of 16 preclinical in vivo studies were included for qualitative analysis (858 experimental animals) and 13 in the meta-analysis (404 experimental animals). MSCs originated from bone marrow (four studies), adipose tissue (10 studies) and salivary gland tissue (two studies) and were administered intravenously (three studies), intra-glandularly (11 studies) or subcutaneously (one study). No serious adverse events were reported. The overall effect on SFR was significantly increased with a standardized mean difference (SMD) of 6.99 (95% CI: 2.55-11.42). Studies reported improvements in acinar tissue, vascular areas and paracrine factors. CONCLUSION: In conclusion, this systematic review and meta-analysis showed a significant effect of MSC therapy for restoring SG functioning and regenerating SG tissue following radiotherapy in preclinical in vivo studies without serious adverse events. MSC therapy holds significant therapeutic potential in the treatment of radio-induced xerostomia, but comprehensive, randomized, clinical trials in humans are required to ascertain their efficacy in a clinical setting.

Mesenchymal stromal/stem cell therapy for radiation-induced salivary gland hypofunction in animal models: a protocol for a systematic review and meta-analysis.

BACKGROUND: Salivary gland (SG) hypofunction (objectively reduced saliva flow rate) and xerostomia (subjective sensation of dry mouth) are common and burdensome side effects of radiotherapy to the head and neck region. Currently, only sparse symptomatic treatment is available to ease the discomfort of xerostomia. The objective of this study is to assess the effect of mesenchymal stem cell (MSC) therapy on SG function after radiation-induced injury. METHODS: This systematic review will include animal intervention studies assessing efficacy and safety of MSCs in treating radiation-induced SG hypofunction. The primary outcome is the effect of MSC administration on salivary flow rates (SFR), by comparing treated groups to control groups when available. Secondary outcomes are morphological and immunohistochemical effects as well as safety of MSC treatment. Electronic searches in MEDLINE (PubMed) and Embase databases will be constructed and validated according to the peer review of electronic search strategies (PRESS) and assessed by two independent researchers. Data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Risk of bias will be evaluated with the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool. DISCUSSION: Thus far, critical appraisal of MSC therapy as an effective treatment for SG hypofunction caused solely by radiation injury has not been conducted. A summary of the existing literature on preclinical studies concerning this issue can provide valuable information about effectiveness, mode of action, and safety, allowing further optimization of preclinical and clinical trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021227336.

Efficacy and risks of removable partial prosthesis in periodontitis patients: A systematic review.

AIM: The aim of this systematic review was to answer the following focused question: "In partially edentulous patients with periodontitis, are removable dental prostheses (RDPs) more efficacious than no prosthetic treatment, treatment to a shortened dental arch (SDA), or tooth-supported fixed dental prostheses (FDPs)?" MATERIALS AND METHODS: A systematic literature search was performed electronically for the period 1966-2020. Two authors independently assessed the studies for eligibility according to the PRISMA guidelines. Risk assessment was performed using RoB 2.0 and the Newcastle-Ottawa Scale. RESULTS: Two retrospective studies indicated that RDPs increased the risk of tooth loss compared to FDPs in patients with a history of periodontitis. Prospective studies found that RDPs could be maintained without any significant periodontal destruction on a long-term basis. Owing to the heterogeneity of the data, no meta-analysis could be performed. Several studies indicated that RDP increased plaque accumulation. RDPs had only a limited effect on masticatory efficiency and nutritional status. RDPs may improve oral-health-related quality of life (OHRQoL), but to a lesser extent compared with that of patients treated to an SDA. CONCLUSIONS: There is no strong evidence that RDPs per se will cause periodontal destruction including tooth loss. RDPs do not inevitably improve masticatory efficiency but improve OHRQoL, although less than for patients treated with FDPs including resin-bonded FDPs.

Patient's perception of timing concepts in implant dentistry: A systematic review.

Protocols for implant dentistry, most frequently include periods until healing of the extraction sockets and osseointegration of the implant. Deductional thinking imply that patients would prefer if treatment time in implant dentistry were reduced. AIM: What is the patient perception of immediate or early implant placement or loading in comparison with traditional, delayed placement, and/or loading assessed by patient-reported outcome measures, as evidenced in randomized controlled clinical trials or prospective controlled studies? MATERIAL AND METHODS: A systematic review was performed following the PRISMA guidelines with a literature search up to June 30. All hits were imported into Rayyan online software and analyzed by two authors for eligibility. Cochrane RoB2.0 and Newcastle-Ottawa Scale were used to evaluate risk of bias in the individual studies. RESULTS: Of the initially 1439 articles, 76 underwent full-text analysis and finally 40 articles, representing 35 cohort studies, were included. The quality evaluation demonstrated some concerns among most of the studies. CONCLUSION: a) There is no strong evidence to support that the time for implant placement or loading of implant-supported single or short-span reconstructions or overdentures influence patients´ discomfort, satisfaction with function or esthetics or overall satisfaction with the implant treatment. b) There is some evidence that studies including edentulous patients rehabilitated with implant-supported full-arch FDPs demonstrate more satisfied patients with immediate than for the early or delayed loaded implant reconstructions after short time, but the difference is not clear one year after treatment.

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis.

BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04-1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS: The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure-response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure-outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.