The mediating roles of the oral microbiome in saliva and subgingival sites between e-cigarette smoking and gingival inflammation.

BACKGROUND: Electronic cigarettes (ECs) have been widely used by young individuals in the U.S. while being considered less harmful than conventional tobacco cigarettes. However, ECs have increasingly been regarded as a health risk, producing detrimental chemicals that may cause, combined with poor oral hygiene, substantial inflammation in gingival and subgingival sites. In this paper, we first report that EC smoking significantly increases the odds of gingival inflammation. Then, through mediation analysis, we seek to identify and explain the mechanism that underlies the relationship between EC smoking and gingival inflammation via the oral microbiome. METHODS: We collected saliva and subgingival samples from 75 EC users and 75 non-users between 18 and 34 years in age and profiled their microbial compositions via 16S rRNA amplicon sequencing. We conducted raw sequence data processing, denoising and taxonomic annotations using QIIME2 based on the expanded human oral microbiome database (eHOMD). We then created functional annotations (i.e., KEGG pathways) using PICRUSt2. RESULTS: We found significant increases in α-diversity for EC users and disparities in ß-diversity between EC users and non-users. We also found significant disparities between EC users and non-users in the relative abundance of 36 microbial taxa in the saliva site and 71 microbial taxa in the subgingival site. Finally, we found that 1 microbial taxon in the saliva site and 18 microbial taxa in the subgingival site significantly mediated the effects of EC smoking on gingival inflammation. The mediators on the genus level, for example, include Actinomyces, Rothia, Neisseria, and Enterococcus in the subgingival site. In addition, we report significant disparities between EC users and non-users in the relative abundance of 71 KEGG pathways in the subgingival site. CONCLUSIONS: These findings reveal that continued EC use can further increase microbial dysbiosis that may lead to periodontal disease. Our findings also suggest that continued surveillance for the effect of ECs on the oral microbiome and its transmission to oral diseases is needed.

Assessing Risks of Early Childhood Caries in Primary Care Practice Using Electronic Health Records and Neighborhood Data.

CONTEXT: Early childhood caries (ECC) is a persistent public health challenge, affecting more than 56% of US toddlers and preschool-aged children. Despite this, ECC is largely preventable with routine oral hygiene practices, diet, and application of topical fluoride. OBJECTIVE: This study assessed the utilization of preventive oral health care in primary care practices and evaluated the variation in patient characteristic and geographic disparities. DESIGN: We conducted a retrospective study using electronic health records (EHRs) over a 2-year period. Patients' home addresses were geocoded and linked to census-based neighborhood statistics and fluoridated water accessibility. Multiple logistic regression modeling was used to assess the risk of ECC in patients with fluoride preventive care, controlled for demographics, comorbid conditions, and neighborhood risk factors. PARTICIPANTS: Patients aged 6 to 71 months who had primary care providers at family medicine and general pediatric clinics in a large academic medical center. MAIN OUTCOME MEASURE: The presence of dental caries based on diagnoses in EHRs. RESULTS: The study consisted of 10 836 patients: 17% treated with topical fluoride varnish (TFV), 12% prescribed oral fluoride supplement, 6.1% with both TFV and supplement, and 64% without fluoride treatment. Patients with fluoride treatment were 24% to 53% less likely to have ECC. Children living in rural and nonfluoridated water communities had 1.7 to 1.8 times greater risk of developing ECC. Minority, under/uninsured, and low-income patients also were at an increased risk of ECC. CONCLUSION: Despite continuing efforts to improve access to dental care for vulnerable populations, substantial disparities remain among socioeconomically disadvantaged children. To address dental care shortage, primary care clinicians should serve as the safety net to care for vulnerable and underserved children who have no or limited access to oral health services. Future research into the collaboration between primary care and dental providers at the level of both practice and professional education should be considered.

Length of Stay and Cost in Patients Undergoing Orthognathic Surgery: Does Surgeon Volume Matter?

PURPOSE: The relations among procedure-specific annual surgeon volume, hospital length of stay (LOS), and hospital costs for patients undergoing the 2 most common orthognathic surgical (OGS) procedures, segmental osteoplasty or osteotomy of the maxilla (SOM) or open osteoplasty or osteotomy of the mandibular ramus (SOMR), are not known. The authors hypothesized that treatment by high-volume surgeons would be associated with decreased LOS and costs. MATERIALS AND METHODS: All patients 8 to 64 years old who underwent elective SOM or SOMR were selected from the 2001 to 2009 Nationwide Inpatient Sample. Patients with missing vital status or payment mode status or who underwent more than 1 OGS procedure during the index hospitalization were excluded. Based on year- and procedure-specific annual surgeon volumes, the highest (highest quartile) and lowest (lowest quartile) procedure volume surgeon groups were compared. Multivariable logistic regression was used to study the relation between surgeon volume and extended patient LOS (defined as LOS ≥ 75th percentile). Generalized linear models with a log-link and gamma distribution were used to examine the association between surgeon volume and hospital costs. Models were adjusted for patient- and hospital-level factors and type of procedure (SOM or SOMR). Analysis was weighted to represent national-level estimates and an α value of 0.05 was used for all comparisons. RESULTS: After weighting to the population level, 8,062 patients were included for study. Most were white (80.6%), female (61.4%), and privately insured (84.6%). Mean age was 26 years (standard deviation, 0.38 yr). After adjusting for potential confounders, patients treated by high-volume surgeons showed 40% lower odds of extended LOS (odds ratio = 0.60; 95% confidence interval [CI], 0.38-0.95; P = .032) and incurred substantially lower costs (-$1,484.74; 95% CI, -2,782.76 to -185.58; P = .025) compared with patients treated by low-volume surgeons. CONCLUSION: These findings suggest that regionalization of patients to high-volume surgeons for OGS procedures could decrease LOS and incurred costs.

CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients.

Regulatory T cells (T(regs)) are key mediators of immune tolerance and feature prominently in cancer. Depletion of CD25(+) FoxP3(+) T(regs) in vivo may promote T cell cancer immunosurveillance, but no strategy to do so in humans while preserving immunity and preventing autoimmunity has been validated. We evaluated the Food and Drug Administration-approved CD25-blocking monoclonal antibody daclizumab with regard to human T(reg) survival and function. In vitro, daclizumab did not mediate antibody-dependent or complement-mediated cytotoxicity but rather resulted in the down-regulation of FoxP3 selectively among CD25(high) CD45RA(neg) T(regs). Moreover, daclizumab-treated CD45RA(neg) T(regs) lost suppressive function and regained the ability to produce interferon-γ, consistent with reprogramming. To understand the impact of daclizumab on T(regs) in vivo, we performed a clinical trial of daclizumab in combination with an experimental cancer vaccine in patients with metastatic breast cancer. Daclizumab administration led to a marked and prolonged decrease in T(regs) in patients. Robust CD8 and CD4 T cell priming and boosting to all vaccine antigens were observed in the absence of autoimmunity. We conclude that CD25 blockade depletes and selectively reprograms T(regs) in concert with active immune therapy in cancer patients. These results suggest a mechanism to target cancer-associated T(regs) while avoiding autoimmunity.