The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma (EAC) is rising in incidence, and established risk factors do not explain this trend. Esophageal microbiome alterations have been associated with Barrett's esophagus (BE) and dysplasia and EAC. The oral microbiome is tightly linked to the esophageal microbiome; this study aimed to identify salivary microbiome-related factors associated with BE, dysplasia, and EAC. METHODS: Clinical data and oral health history were collected from patients with and without BE. The salivary microbiome was characterized, assessing differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features. Microbiome metabolic modeling was used to predict metabolite production. RESULTS: A total of 244 patients (125 non-BE and 119 BE) were analyzed. Patients with high-grade dysplasia (HGD)/EAC had a significantly higher prevalence of tooth loss (P = 0.001). There were significant shifts with increased dysbiosis associated with HGD/EAC, independent of tooth loss, with the largest shifts within the genus Streptococcus. Modeling predicted significant shifts in the microbiome metabolic capacities, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production in HGD/EAC. CONCLUSIONS: Marked dysbiosis in the salivary microbiome is associated with HGD and EAC, with notable increases within the genus Streptococcus and accompanying changes in predicted metabolite production. Further work is warranted to identify the biological significance of these alterations and to validate metabolic shifts. IMPACT: There is an association between oral dysbiosis and HGD/EAC. Further work is needed to establish the diagnostic, predictive, and causal potential of this relationship.

Identifying Children in Foster Care and Improving Foster Care Documentation in Primary Care.

Background: Children and youth in foster care (CYFC) are a population with special healthcare needs, and the American Academy of Pediatrics has healthcare standards to care for this population, but implementation challenges include identifying clinic patients in foster care (FC). Documentation of FC status in the Electronic Health Record (EHR) can support the identification of CYFC to tailor care delivery. Therefore, we aimed to improve the percentage of CYFC with problem list (PL) documentation of FC status from 20% to 60% within 12 months. Methods: This study used a five-cycle plan-do-study-act quality improvement model in two co-located primary care teaching clinics. The primary outcome was the weekly percentage of patients with FC status on EHR PL. Ishikawa cause and effect analysis and resident survey identified barriers and informed interventions: education, patient list distribution, documentation training, email reminders, and clinic champion. We constructed statistical process control charts of the primary outcome to assess for improvement. Results: Mean weekly percentage of patients with FC status on PL improved from 19.8% to 60.2%. The most extensive improvements occurred after designating a clinic champion and providing email reminders with enhanced patient lists. The sustainability of PL documentation (mean = 71.7%) was demonstrated 3-4 years after the completion of plan-do-study-act cycle interventions. Conclusions: Educating providers, collaborating with child welfare to provide patient lists to providers, standardizing documentation, and designating clinic champions are promising methods of improving EHR documentation of FC status. Identifying and documenting FC status are important initial steps to optimizing care for this vulnerable population in primary care.

The Salivary Microbiome and Predicted Metabolite Production are Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is rising in incidence and associated with poor survival, and established risk factors do not explain this trend. Microbiome alterations have been associated with progression from the precursor Barrett's esophagus (BE) to EAC, yet the oral microbiome, tightly linked to the esophageal microbiome and easier to sample, has not been extensively studied in this context. We aimed to assess the relationship between the salivary microbiome and neoplastic progression in BE to identify microbiome-related factors that may drive EAC development. We collected clinical data and oral health and hygiene history and characterized the salivary microbiome from 250 patients with and without BE, including 78 with advanced neoplasia (high grade dysplasia or early adenocarcinoma). We assessed differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features and used microbiome metabolic modeling to predict metabolite production. We found significant shifts and increased dysbiosis associated with progression to advanced neoplasia, with these associations occurring independent of tooth loss, and the largest shifts were with the genus Streptococcus. Microbiome metabolic models predicted significant shifts in the metabolic capacities of the salivary microbiome in patients with advanced neoplasia, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production. Our results suggest both a mechanistic and predictive role for the oral microbiome in esophageal adenocarcinoma. Further work is warranted to identify the biological significance of these alterations, to validate metabolic shifts, and to determine whether they represent viable therapeutic targets for prevention of progression in BE.

The impact of voluntary folate fortification of corn masa flour on US pregnancies complicated by neural tube defects.

INTRODUCTION: In 1996, the US Food and Drug Administration (FDA) mandated folic acid fortification for all enriched cereal grains. This resulted in a reduction of neural tube defect (NTD)-affected pregnancies. However, Hispanic women continued to be twice as likely to give birth to a child affected by NTD compared to non-Hispanic White women. Some hypotheses explaining this difference focus on cultural variation in dietary intake of cereal grains. In 2016, the FDA approved voluntary folic acid fortification for corn masa flour products to focus on the Hispanic diet staple. This study investigates rates of NTDs in predominantly Hispanic-populated zip codes before and after the voluntary fortification of corn masa flour with folic acid. METHODS: Normal pregnancies and those complicated by NTDs between 1/1/2016 and 9/30/2020 were identified using ICD-9 and ICD-10 codes in an all-payor claims database. The post-fortification period began 12 months after the fortification recommendation. The US Census data was used to stratify pregnancies in predominantly Hispanic zip codes (≥ 75% of households) vs. non-Hispanic zip codes. The causal impact of the FDA's recommendation was assessed by means of a Bayesian structural time series model. RESULTS: A total of 2,584,366 pregnancies were identified among females aged 15-50 years. Of these, 365,983 took place in predominantly Hispanic zip codes. Mean quarterly NTDs per 100,000 pregnancies did not significantly differ between predominantly Hispanic zip codes and predominantly non-Hispanic zip codes pre-FDA recommendation (184.5 vs. 175.6; p = 0.427), nor post-recommendation (188.2 vs. 185.9; p = 0.713). Rates of NTDs predicted to occur if no FDA recommendation had been made were compared to the actual rate post-recommendation: no significant difference was observed in predominantly Hispanic zip codes (p = 0.245) or overall (p = 0.116). CONCLUSIONS: Rates of neural tube defects were not significantly reduced in predominantly Hispanic zip codes following the 2016 FDA approval of voluntary folic acid fortification of corn masa flour. Further research and implementation of comprehensive approaches to advocacy, policy, and public health are necessary to decrease preventable congenital disease rates. Mandatory rather than voluntary fortification of corn masa flour products may achieve more substantial prevention of neural tube defects in at-risk US populations.

The Impact of Social Determinants of Health in Pediatric Shunted Hydrocephalus.

BACKGROUND: Social risk factors have been shown to negatively affect health outcomes in children. However, this has not been characterized regarding pediatric shunted hydrocephalus. OBJECTIVE: To explore the impact of social risk factors on outcomes in pediatric shunted hydrocephalus with the goal of identifying specific areas of intervention that might improve the outcomes of children undergoing cerebrospinal fluid (CSF) diversion. METHODS: In an all-payer administrative database, records between January 2010 and October 2020 were analyzed to identify children undergoing CSF shunting procedures. Children with social risk factors were compared with those without regarding rates of infection, shunt-related interventions, and mortality within 5 years of their shunting procedure. RESULTS: Among the 5420 children who underwent first-time shunting procedures, 263 (4.9%) were identified to have social risk factors. Children with identified social risk factors had increased odds of central nervous system infection (odds ratio [OR] 2.06, 95% CI 1.45-2.91), revision (OR 2.43, 95% I 1.89-3.12), and mortality (OR 2.86, 95% CI 1.23-5.72). The mean numbers of computed tomography studies (14.60 ± 17.78 vs 6.34 ± 6.10), MRI studies (18.76 ± 24.37 vs 7.88 ± 24.37), and shunt series X-rays (17.22 ± 19.04 vs 7.66 ± 8.54) were increased among children with social risk factors. CONCLUSION: Children with social risk factors had increased rates of central nervous system infection, shunt-related interventions, and mortality within 5 years of CSF shunting. We underscore the importance of characterizing the impact of social risk factors in specific conditions, such as pediatric shunted hydrocephalus, and look to future directions aimed to mitigate these risk factors with coordination and direction of individualized resources, encouragement of advocacy, and community partnership.

The gut microbiome, short chain fatty acids, and related metabolites in cystic fibrosis patients with and without colonic adenomas.

BACKGROUND: Adults with cystic fibrosis (CF) are at increased risk for colon cancer. CF patients have reductions in intestinal bacteria that produce short chain fatty acids (SCFAs), although it is unclear whether this corresponds with intestinal SCFA levels and the presence of colonic neoplasia. The aim of this study was to compare gut microbiome and SCFA composition in patients with and without CF, and to assess associations with colonic adenomas. METHODS: Colonic aspirates were obtained from adults with and without CF undergoing colon cancer screening or surveillance colonoscopy. Microbiome characterization was performed by 16S rRNA V3-V4 sequencing. Targeted profiling of SCFAs and related metabolites was performed by LC-MS. RESULTS: 42 patients (21 CF, 21 control) were enrolled. CF patients had significantly reduced alpha diversity and decreased relative abundance of many SCFA-producing taxa. There were no significant differences in SCFA levels in CF patients, although there were reduced levels of branched chain fatty acids (BCFAs) and related metabolites. CF patients with adenomas, but not controls with adenomas, had significantly increased relative abundance of Bacteroides fragilis. CF microbiome composition was significantly associated with isovalerate concentration and the presence of adenomas. CONCLUSIONS: CF patients have marked disturbances in the gut microbiome, and CF patients with adenomas had notably increased relative abundance of B. fragilis, a pathogen known to promote colon cancer. Reductions in BCFAs but not SCFAs were found in CF. Further studies are warranted to evaluate the role of B. fragilis as well the biological significance of reductions in BCFAs in CF.

Minimal Associations between Short-Term Dietary Intake and Salivary Microbiome Composition.

BACKGROUND: Increasing evidence points to the esophageal microbiome as an important co-factor in esophageal neoplasia. Esophageal microbiome composition is strongly influenced by the oral microbiome. Salivary microbiome assessment has emerged as a potential non-invasive tool to identify patients at risk for esophageal cancer, but key host and environmental factors that may affect the salivary microbiome have not been well-defined. This study aimed to evaluate the impact of short-term dietary intake on salivary microbiome composition. METHODS: Saliva samples were collected from 69 subjects prior to upper endoscopy who completed the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment. Salivary microbiome composition was determined using 16S rRNA amplicon sequencing. RESULTS: There was no significant correlation between alpha diversity and primary measures of short-term dietary intake (total daily calories, fat, fiber, fruit/vegetables, red meat intake, and fasting time). There was no evidence of clustering on beta diversity analyses. Very few taxonomic alterations were found for short-term dietary intake; an increased relative abundance of Neisseria oralis and Lautropia sp. was associated with high fruit and vegetable intake, and an increased relative abundance of a taxon in the family Gemellaceae was associated with increased red meat intake. CONCLUSIONS: Short-term dietary intake was associated with only minimal salivary microbiome alterations and does not appear to have a major impact on the potential use of the salivary microbiome as a biomarker for esophageal neoplasia.

Use of the Electronic Health Record to Target Patients for Non-endoscopic Barrett's Esophagus Screening.

BACKGROUND: Clinical prediction models targeting patients for Barrett's esophagus (BE) screening include data obtained by interview, questionnaire, and body measurements. A tool based on electronic health records (EHR) data could reduce cost and enhance usability, particularly if combined with non-endoscopic BE screening methods. AIMS: To determine whether EHR-based data can identify BE patients. METHODS: We performed a retrospective review of patients ages 50-75 who underwent a first-time esophagogastroduodenoscopy. Data extracted from the EHR included demographics and BE risk factors. Endoscopy and pathology reports were reviewed for histologically confirmed BE. Screening criteria modified from clinical guidelines were assessed for association with BE. Subsequently, a score based on multivariate logistic regression was developed and assessed for its ability to identify BE subjects. RESULTS: A total of 2931 patients were assessed, and BE was found in 1.9%. Subjects who met screening criteria were more likely to have BE (3.3% vs. 1.1%, p = 0.001), and the criteria predicted BE with an AUROC of 0.65 (95% CI 0.59-0.71). A score based on logistic regression modeling included gastroesophageal reflux disease, sex, body mass index, and ever-smoker status and identified BE subjects with an AUROC of 0.71 (95% CI 0.64-0.77). Both prediction tools produced higher AUROCs in women than in men. CONCLUSIONS: EHR-based BE risk prediction tools identify BE patients with fair accuracy. While these tools may improve the efficiency of patient targeting for BE screening in the primary care setting, challenges remain to identify high-risk patients for non-invasive BE screening in clinical practice.

Racial Disparities in Heart Disease Mortality in the 50 Largest U.S. Cities.

Heart disease is not only the leading cause of death in the U.S. but also the main contributor to racial disparities in life expectancy. Despite this, heart disease mortality rates and racial disparities in these rates are not readily available at the city level where they can be the most quickly and effectively addressed. We calculated age-adjusted heart disease mortality rates and corresponding racial rate ratios (RRs) and rate differences (RDs) for the non-Hispanic Black (Black) and non-Hispanic White (White) populations for the years 1990-1994 and 2005-2009 for the U.S. and the 50 largest cities therein. We then examined relationships between the disparities and city-level population indicators. Nationally, mortality rates were significantly higher among Blacks than Whites at both time periods. Larger improvements in rates for Whites compared to Blacks resulted in a significant increase in disparities over the 20-year period for 11 cities. There were 19,448 excess Black deaths in the U.S. annually. City-level income inequality, as well as the overall city and White median household income, contributed to these disparities. By identifying city-specific disparities and trends, health care providers, public health agencies, and researchers can target the areas with the most need and can look at cities without disparities for clues on how to best advance health equity in heart disease morbidity and mortality.