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.

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.

Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome.

Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited. Previous investigations have suggested that vaginal microbes and metabolites may be implicated in sPTB. Here we performed untargeted metabolomics on 232 second-trimester vaginal samples, 80 from pregnancies ending preterm. We find multiple associations between vaginal metabolites and subsequent preterm birth, and propose that several of these metabolites, including diethanolamine and ethyl glucoside, are exogenous. We observe associations between the metabolome and microbiome profiles previously obtained using 16S ribosomal RNA amplicon sequencing, including correlations between bacteria considered suboptimal, such as Gardnerella vaginalis, and metabolites enriched in term pregnancies, such as tyramine. We investigate these associations using metabolic models. We use machine learning models to predict sPTB risk from metabolite levels, weeks to months before birth, with good accuracy (area under receiver operating characteristic curve of 0.78). These models, which we validate using two external cohorts, are more accurate than microbiome-based and maternal covariates-based models (area under receiver operating characteristic curve of 0.55-0.59). Our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.

Determinants of ureteral obstruction after percutaneous nephrolithotomy.

BACKGROUND: Ureteral obstruction after percutaneous nephrolithotomy (PCNL) may require prolonged drainage with a nephrostomy tube (NT) or ureteral stent, but it is not well understood how and why this occurs. The goal of this study was to identify risk factors associated with postoperative ureteral obstruction to help guide drainage tube selection. METHODS: Prospective data from adult patients enrolled in the Registry for Stones of the Kidney and Ureter (ReSKU) who underwent PCNL from 2016 to 2020 were used. Patients who had postoperative NTs with antegrade imaging-based flow assessment on postoperative day one (POD1) were included. Patients with transplanted kidneys or those without appropriate preoperative imaging were excluded. We assessed the association between patient demographics, stone characteristics, and intraoperative factors using POD1 antegrade flow, a proxy for ureteral patency, as the primary outcome. Stepwise selection was used to develop a multivariate logistic regression model controlling for BMI, stone location, stone burden, ipsilateral ureteroscopy (URS), access location, estimated blood loss, and operative time. RESULTS: We analyzed 241 cases for this study; 204 (84.6%) had a visual clearance of stone. Antegrade flow on POD1 was absent in 76 cases (31.5%). A multivariate logistic regression model found that stones located anywhere other than in the renal pelvis (OR 2.63, 95% CI 1.29-5.53; p = 0.01), non-lower pole access (OR 2.81, 95% CI 1.42-5.74; p < 0.01), and concurrent ipsilateral URS (OR 2.17, 95% CI 1.02-4.65; p = 0.05) increased the likelihood of obstruction. BMI, pre-operative stone burden, EBL, and operative time did not affect antegrade flow outcomes. CONCLUSION: Concurrent ipsilateral URS, absence of stones in the renal pelvis, and non-lower pole access are associated with increased likelihood of ureteral obstruction after PCNL. Access location appears to be the strongest predictor. Recognizing these risk factors can be helpful in guiding postoperative tube management.

Do no harm: the role of perioperative heparin in urethroplasty.

OBJECTIVE: To examine the safety of single modality mechanical venous thromboembolism (VTE) prophylaxis in patients undergoing urethroplasty. VTE is a perioperative complication with significant morbidity. Routine use of peri-operative VTE prophylaxis is common guideline-driven practice across multiple surgical specialties. There is a discrepancy between guideline recommendations and clinical practice in the administration of peri-operative low-dose unfractionated heparin (LDUH) for urethroplasty. METHODS: Patients were identified from an IRB-approved database of patients undergoing urethral reconstruction by a single surgeon at MedStar Washington Hospital Center from 2012 to 2020. All patients had sequential compression devices (SCD) prior to anesthesia induction. Select patients received LDUH as dual prophylaxis. Primary endpoint was perioperative VTE within 30 days. RESULTS: We identified 345 patients who met inclusion criteria. Sixty-nine patients received peri-operative LDUH. One patient had a deep vein thrombosis in the SCD only group. CONCLUSION: Routine LDUH administration likely overtreats men undergoing urethroplasty. There may be a subset of men in whom dual prophylaxis with LDUH and SCD is beneficial for prevention of VTE. Current guidelines do not offer adequate criteria to identify these men. We offer clinical considerations to help guide further study to identify these patients.

Necrotizing Fasciitis Following Routine Genitourinary Surgery in Healthy Infants.

Morbidity and mortality associated with pediatric necrotizing fasciitis are strongly dependent on early diagnosis and timely intervention. Yet, the lack of early cutaneous findings and nonspecific symptoms may result in initial delayed diagnosis or misdiagnosis. Infants may be particularly at risk of missed or delayed diagnosis due to inherent barriers in communication and rarity of the condition, especially among healthy patients. We describe 2 cases of necrotizing fasciitis following routine genitourinary surgery in healthy infants.

Prostate Cancer in Men With Treated Advanced Heart Failure: Should we Keep Screening?

OBJECTIVE: To evaluate the outcomes of men diagnosed with prostate cancer (CaP) following implanted treatments for advanced heart failure. Given the increasingly favorable 10-year life expectancy, MedStar Washington Hospital Center screens heart transplant (HT) candidates for CaP and other malignancies prior to intervention. METHODS: Men aged 18-90 with available pretransplant Prostate Specific Antigen (PSA) who underwent left ventricular assist device (LVAD) and/or HT at MedStar Washington Hospital Center from 2007 to 2018 were identified. Serum PSA, CaP diagnosis, and treatment were captured and analyzed. Survival was analyzed using Kaplan-Meier curves. RESULTS: Data were available for 34 patients. Median age was 53 [IQR = 51-58]. Median follow-up was 77 months (95% CI = 40-87 months). Six men had postimplant elevated PSA (5.3; SD = 8.5) and 4 were diagnosed with CaP. Median age of CaP diagnosis was 59 [IQR = 58.5-62). As of 2018, 31 of the 34 patients were living, and none died from CaP. Five-year survival was 96% in those without CaP and 100% in those with CaP (Figure 2). CONCLUSION: Our cohort represents the largest known cohort with heart failure treated by LVAD and/or HT and CaP. Our median age of 59 at CaP diagnosis is considerably younger than the national median of 66.1 Of the 4 individuals diagnosed with CaP, 3 had high-grade disease. Given the favorable long-term survival of these patients post-LVAD and/or HT, age-appropriate treatment for CaP should be continued postimplantation.