Predicting Treatment Nonresponse in Hispanic/Latino Children Receiving Silver Diamine Fluoride for Caries Arrest: A Pilot Study Using Machine Learning

Objectives: Silver diamine fluoride (SDF) is a nonsurgical therapy for the arrest and prevention of dental caries with demonstrated clinical efficacy. Approximately 20% of children receiving SDF fail to respond to treatment. The objective of this study was to develop a predictive model of treatment non-response using machine learning.Methods: An observational pilot study (N = 20) consisting of children with and without active decay and who did and did not respond to silver diamine fluoride provided salivary samples and plaque from infected and contralateral sites. 16S rRNA genes from samples were amplified and sequenced on an Illumina Miseq and analyzed using QIIME. The association between operational taxonomic units and treatment non-response was assessed using lasso regression and artificial neural networks.Results: Bivariate group comparisons of bacterial abundance indicate a number of genera were significantly different between non-responders and those who responded to SDF therapy. No differences were found between non-responders and caries-active subjects. Prevotella pallens and Veillonella denticariosi were retained in full lasso models and combined with clinical variables in a six-input multilayer perceptron.Discussion: The acidogenic and acid-tolerant nature of retained bacterial species may overcome the antimicrobial effects of SDF. Further research to validate the model in larger external samples is needed.

Changes in clinical parameters following adjunctive local sodium hypochlorite gel in minimally invasive nonsurgical therapy (MINST) of periodontal pockets: a 6-month randomized controlled clinical trial

Background The mechanical disruption and removal of the subgingival biofilm represent the most important step in the treatment of periodontitis. However, in deep periodontal pockets, mechanical removal of the subgingival biofilm is difficult and frequently incomplete. Preliminary findings indicate that the use of amino acid buffered sodium hypochlorite (NaOCl) gel may chemically destroy the bacterial biofilm and facilitate its mechanical removal. Objectives To clinically evaluate the efficacy of minimally invasive nonsurgical therapy (MINST) of periodontal pockets with or without local application of an amino acid buffered sodium hypochlorite (NaOCl) gel. Materials and methods Forty untreated patients diagnosed with severe/advanced periodontitis (i.e. stage III/IV) with a slow/moderate rate of progression (i.e. grade A/B) were randomly allocated in two treatment groups. In the test group, the periodontal pockets were treated by means of MINST and NaOCl gel application, while in the control group, treatment consisted of MINST alone. Full-mouth plaque scores (FMPS), full-mouth bleeding scores (FMBS), probing depths (PD), clinical attachment levels (CAL) and gingival recessions (GR) were assessed at baseline and at 6 months following therapy. The primary outcome variable was PD reduction at sites with PD ≥ 5 mm at baseline. Results At 6 months, statistically significant differences between the two groups were found (p = 0.001) in terms of PD and CAL change. No statistically significant differences were found in terms of GR (p = 0.81). The number of sites with PD ≥ 5 mm and BOP (+) decreased statistically significantly (p = 0.001), i.e. from 85.3 to 2.2% in the test group and from 81.6 to 7.3% in the control group, respectively. Statistically significant differences between test and control groups were recorded at 6 months (p = 0.001). MINST + NaOCl compared to MINST alone decreased statistically significantly (p = 0.001) the probability of residual PDs ≥ 5 mm with BOP− (14.5% vs 18.3%) and BOP+ (2.2% vs. 7.2%). Conclusions Within their limits, the present results indicate that (a) the use of MINST may represent a clinically valuable approach for nonsurgical therapy and (b) the application of NaOCl gel in conjunction with MINST may additionally improve the clinical outcomes compared to the use of MINST alone. Clinical relevance In patients with untreated periodontitis, treatment of deep pockets by means of MINST in conjunction with a NaOCl gel may represent a valuable approach to additionally improve the clinical outcomes obtained with MINST alone

Effect of Locally Delivered Melatonin as an Adjunct to Nonsurgical Therapy on GCF Antioxidant Capacity and MMP-9 in Stage II Periodontitis Patients: A Randomized Controlled Clinical Trial

Objectives. Periodontitis is characterized by inflammatory destruction of periodontal tissue, loss of attachment, and bone resorption. The increase in reactive oxygen species (ROS) is responsible for the oxidative damage occurring in periodontal tissues. Melatonin has important immunomodulatory, anti-inflammatory, and powerful antioxidant functions. The current study was carried out to evaluate the effect of topical melatonin gel as an adjunct to nonsurgical periodontal therapy. Methods. This split-mouth randomized controlled clinical trial was performed on 24 patients with grade II periodontitis. Two sites in each patient were randomly assigned; test sites were treated by nonsurgical therapy followed by intrapocket application of 5% melatonin gel. Control sites were treated by nonsurgical therapy followed by intrapocket application of placebo gel. Both the melatonin and placebo gel were applied weekly once for four weeks. Assessment of clinical parameters (PD and CAL) was done at baseline and 3 months after therapy. Total antioxidative capacity (TAC) and matrix metalloproteinase-9 (MMP-9) levels in GCF were also evaluated utilizing commercially available enzyme-linked immunosorbent assay kits (ELISA) at baseline and 3 months after therapy. Results. Treatment with topical melatonin was associated with a reduction in periodontal inflammation reflected as an improvement in the clinical periodontal parameters. Melatonin-treated sites showed a more statistically significant percent reduction in PD and more statistically significant percent gain in CAL than the control site. Additionally, a significant increase in TAC and a significant decrease in MMP-9 levels in GCF were found in melatonin-treated sites in comparison to control sites. Conclusions. The adjunctive use of topical melatonin gel with nonsurgical periodontal therapy has potent anti-inflammatory and antioxidant activity in the treatment of grade II periodontitis patients.

A Possible Relationship between Peri-Implantitis, Titanium Hypersensitivity, and External Tooth Resorption: Metal-Free Alternative to Titanium Implants

Titanium dental implant surface does not remain unaltered but may corrode and release ions or particles which trigger soft and hard tissue damage. Titanium may induce clinically relevant hypersensitivity in patients chronically exposed. A 56-year-old female patient presented peri-implantitis around a single titanium implant positioned three years earlier. Despite nonsurgical therapy, a rapid bone loss associated with pain and swelling occurred, and adjacent teeth presented external resorption. Compromised teeth were removed, and three titanium implants were inserted. Six months later, the patient complained about high mucosa sensitivity and implant exposure. At clinical and radiographic examinations, tissue inflammation and vertical bone loss involved the new implants and the process of external resorption affected the teeth. The blood test confirmed titanium hypersensitivity. Titanium implants were removed, and 5 zirconia implants were placed. No sign of bone loss or tooth resorption was recorded at clinical and radiographic control during 18 months of follow-up.

Treatment nonresponse in children receiving silver diamine fluoride for caries: A pilot study

Objectives: Silver diamine fluoride (SDF) is a nonsurgical therapy for the arrest and prevention of dental caries with demonstrated clinical efficacy. Approximately 20% of children receiving SDF fail to respond to treatment. The objective of this study was to develop a predictive model of treatment nonresponse using machine learning. Methods: An observational pilot study (N=20) consisting of children with and without active decay and who did and did not respond to silver diamine fluoride provided salivary samples and plaque from infected and contralateral sites. 16S rRNA genes from samples were amplified and sequenced on an Illumina Miseq and analyzed using QIIME. The association between operational taxonomic units and treatment nonresponse was assessed using lasso regression and artificial neural networks. Results: Bivariate group comparisons of bacterial abundance indicate a number of genera were significantly different between nonresponders and those who responded to SDF therapy. No differences were found between nonresponders and caries-active subjects. Prevotella pallens and Veillonella denticariosi were retained in full lasso models and combined with clinical variables in a six-input multilayer perceptron. Discussion: The acidogenic and acid-tolerant nature of retained bacterial species may overcome the antimicrobial effects of SDF. Further research to validate the model in larger external samples is needed.

Radio-Resistance and DNA Repair in Pediatric Diffuse Midline Gliomas

Malignant gliomas (MG) are among the most prevalent and lethal primary intrinsic brain tumors. Although radiotherapy (RT) is the most effective nonsurgical therapy, recurrence is universal. Dysregulated DNA damage response pathway (DDR) signaling, rampant genomic instability, and radio-resistance are among the hallmarks of MGs, with current therapies only offering palliation. A subgroup of pediatric high-grade gliomas (pHGG) is characterized by H3K27M mutation, which drives global loss of di- and trimethylation of histone H3K27. Here, we review the most recent literature and discuss the key studies dissecting the molecular biology of H3K27M-mutated gliomas in children. We speculate that the aberrant activation and/or deactivation of some of the key components of DDR may be synthetically lethal to H3K27M mutation and thus can open novel avenues for effective therapeutic interventions for patients suffering from this deadly disease.

Preliminary Results From a US Clinical Trial of a Novel Synthetic Polymer Meniscal Implant

Background: At least 760,000 outpatient meniscectomies are performed in the United States each year, making this the most common musculoskeletal procedure. However, meniscal resection can alter the joint biomechanics and overload the articular cartilage, which may contribute to degenerative changes and the need for knee replacement. Avoiding or delaying knee replacement is particularly important in younger or more active patients. Synthetic meniscal implants have been developed in an attempt to restore the natural joint biomechanics, alleviate pain and disability, and potentially minimize degenerative changes in patients who require meniscectomy. Purpose To evaluate the preliminary results from 2 ongoing trials that are evaluating the safety and effectiveness of a synthetic polymer meniscal implant (NUsurface; Active Implants, LLC). Study Design: Cohort study; Level of evidence, 2. Methods: This was a preliminary analysis of the first 100 patients enrolled across 2 studies for 12 months: a single-arm, intervention-only study and a randomized controlled trial comparing the investigational meniscal implant with nonsurgical therapy. There were 65 patients in the implant group (30 randomized) and 35 in the control group. Outcomes included Knee injury and Osteoarthritis Outcome Score (KOOS) and adverse events (AEs) collected at baseline and follow-up visits of 6 weeks, 6 months, and 12 months. Results: No statistically significant differences were found in baseline characteristics between the implant and control groups. At 12 months, follow-up KOOS data were available for 87% of the 100 included patients. Significantly greater improvements from baseline were observed in the implant group compared with controls in all KOOS subcomponents, except for symptoms (119%-177% greater improvement at 12 months). AEs were reported at similar rates between the 2 groups, with 12 AEs among 11 patients in the implant group (16.9%) versus 5 AEs among 5 patients (14.3%) in the control group ( P = .99). Conclusion: These preliminary results suggest significant improvements in pain and function scores with the implant over nonsurgical therapy and a similar adverse event rate.