P-1569. Microbiome Derived Stool Metabolites Predict E. faecium Expansion in Hospitalized Patients

Open Forum Infectious Diseases · 2026-01-01

Abstract Background Vancomycin resistant Enterococcus faecium (VRE) poses a distinct threat to hospitalized patients.(CDC, 2022) Expansion of VRE within the gut microbiome is closely linked with invasive infections in multiple hosts.(Lehmann et al., 2024; Taur et al., 2012) Stool microbial metabolite measurement offers a new diagnostic avenue to rapidly identify VRE colonization. (Lehmann et al., 2024) We developed a machine learning model using stool metabolite measurements to predict E. faecium expansion in patients.Table 1.Patient Characteristics.Demographic information of the patients whose samples were utilized to train and test this model.Figure 1.Overall performance of the Elastic Net Model.A. Receiver operator characteristic plot showing true positive vs false positive rates. This demonstrates an area under the curve of 0.919. B. Table displaying a variety of model performance metrics. Notably, this model demonstrates a high F1 score of 0.935 as well as positive and negative predictive values of 0.915 and 0.804 respectively. C. Confusion Matrix of model performance on unseen test data. Methods Using qualitative stool metabolite concentrations as measured by targeted GC and LC-MS analysis paired with microbiota composition obtained via shotgun metagenomic sequencing, we generated, tuned, and evaluated an elastic net-based machine learning model to predict stool expansion of E. faecium over 30% relative abundance.(Kuhn, 2008) Collinearity and multicollinearity analysis of the metabolites was performed using Spearman’s Rank-Order method, and Variance Inflation Factors respectively. Following hyperparametric tuning of this model, test data was used to evaluate the model’s performance. The selected classification cutoff for the model maximized the F1 score based on precision and recall.Figure 2.Collinearity Assessment of Stool Metabolites.A. Top 10 pairwise Spearman Correlations are listed with both respective metabolites and the absolute value of their correlation. B. All metabolites that demonstrate high multicollinearity (VIF>10) are shown with their respective variance inflation factor. Results 2738 stool samples from 1504 patients were included from 6 observational clinical studies on liver disease, liver transplant, heart transplant, critical care, internal medicine, and leukemia patients.(Dela Cruz et al., 2023; Lehmann et al., 2024; Odenwald et al., 2023; Stutz et al., 2022) (Table 1) The model predicted E. faecium expansion with an accuracy was 0.894, sensitivity of 0.949, precision of 0.919 and AUC of 0.917. (Figure 1.) Conclusion This work provides a proof of concept that stool metabolites can identify pathogen expansion in the gut. The approach could aid in early diagnosis leading to better outcomes. It could also identify key inhibitory metabolites as future therapeutic candidates. Future work will identify the metabolites with highest predictive value and apply this method to other gut pathogens such as Klebsiella pneumonia. Disclosures Bhakti Patel, MD, CHEST: Board review course director|Merck: Wrote medical chapters

Male Breast Cancer in a Bronx Urban Population: A Single-Institution Retrospective Observational Study

Diagnostics · 2026-01-21

Background/Objectives: This study seeks to evaluate the clinical characteristics of newly diagnosed male breast cancers within the traditionally underserved Bronx population at risk for poorer health outcomes. Methods: We retrospectively searched our database for male patients who presented for mammographic evaluation between 1 January 2016 and 1 October 2024. The primary outcomes were the prevalence of biopsy-proven male breast cancer and its association with gynecomastia and TNM stage at diagnosis. Clinical data, including TNM staging, receptor status, risk factors, and patient demographics, were recorded for patients with biopsy-proven breast cancer based on biopsy results. Two dedicated breast imagers retrospectively evaluated mammograms of these patients to determine by consensus the presence of gynecomastia. Analyses were descriptive in nature. Results: During the study period, 423 screening mammograms and 1775 diagnostic mammograms were performed on male patients. Twenty-six male patients with biopsy-proven breast cancer were identified (two were bilateral and four were multifocal). In total, 69% of our male breast cancer patients (18 out of 26) demonstrated gynecomastia, which was similar across demographic groups, ranging from 63 to 75%. Out of the three patients with Stage 4 disease, two were Black and one was White. Stage 3 or higher disease was seen in 29% of our Black patients, 12% of our White patients, and 0% of our Hispanic patients. Conclusions: Male breast cancer in this Bronx population was frequently associated with gynecomastia and showed notable demographic disparities. Black patients presented with more advanced disease than other demographic groups. These descriptive findings highlight areas of further investigation and may help inform future outreach and early detection efforts in high-risk, underserved communities. This retrospective, single-institution analysis was limited by a small sample size and did not include formal statistical testing; therefore, the findings are descriptive and warrant validation with larger cohorts.

Characterizing Variation in Documented Delivery of Spontaneous Awakening Trials Across Five Health Systems

American Journal of Respiratory and Critical Care Medicine · 2025-05-01

Abstract Rationale: Daily spontaneous awakening trials (SATs) are recommended to promote timely liberation from the ventilator. However, hospital variation in SAT performance is unknown. We sought to characterize SAT practice patterns using structured documentation in flowsheets from electronic health record data across a multi-center consortium. Methods: We identified mechanically ventilated adults at 13 US hospitals across 5 health systems in the Common Longitudinal Intensive Care Unit Format (CLIF) consortium from January 1st, 2020 to December 31, 2021. Patient-level data was merged with American Hospital Association survey files to ascertain hospital characteristics. We defined eligible patient days for SAT as those with continuous sedatives and/or opiates for >=4 hours between 10 PM the previous day and 8 AM of the current day. SAT delivery was identified using structured flowsheet documentation. We report descriptive statistics as frequencies with percentages for categorical variables and median with interquartile range [IQR] for continuous variables. We calculated SAT delivery rate at the hospital level as the proportion of eligible patient days on which SAT was documented as delivered. We characterized hospital variation by plotting SAT delivery rate at each hospital across the 5 health systems. We also evaluated differences by hospital characteristics including bed size and academic (versus community) affiliation. Results: We identified 75,770 SAT eligible patient-days among 5,823 mechanically ventilated adults admitted to 13 hospitals from 5 health systems [median age: 61.4 (IQR: 50.6-70.9); 41.1% female], The median rate of SAT delivery on eligible days was 20.3% (IQR: 15.1, 31.6). SAT delivery varied from 1.61% at the lowest-performing hospitals to 67.9% at the highest-performing hospitals (Figure). SAT was delivered on a median 28.4% of eligible days (IQR: 17.5, 31.6) at hospitals with >300 beds (n=5) as compared with 18.0% (7.3, 31.5) for those with ≤300 beds (n=8); and 23.0% (IQR: 16.9, 29.5) for academic (n=4) versus 20.3% (IQR: 9.0, 31.6) for community (n=9) hospitals. Conclusion: Hospitals vary in the delivery of SATs as documented in clinician flowsheets. Factors underlying variation in documented SAT delivery and whether it reflects differences in clinician documentation or in performance of SAT needs to be investigated.

Timing of Inspiratory Effort Measurement and Its Association With Ventilator-free Days in Mechanically Ventilated Patients

American Journal of Respiratory and Critical Care Medicine · 2025-05-01

Abstract Rationale: Inspiratory effort in mechanically ventilated patients is correlated with duration of mechanical ventilation, with normal effort, similar to that of quiet breathing, associated with the shortest duration. Diaphragm thickening fraction (TF) has been used to indirectly measure effort. However, it remains unclear when TF is most prognostic, as most ventilated patients have low effort early in their course due to sedation. We aim to determine when TF should be measured for the best prognostic value. Methods: Adult patients receiving volume-controlled ventilation within 24 hours of intubation had surrogate consent obtained. Patients on mechanical ventilation for at least 72 hours were included in the analysis. Diaphragm thickness was measured by ultrasound at end of expiration (T-de) and peak inspiration (Tdi) in patients during a sedation hold. TF was defined as (Tdi -Tde)/Tde. Normal effort was defined as TF between 15% and 30%, high effort as TF > 30%, and low effort as TF < 15%. The primary outcome was ventilator-free days (VFDs), the number of days alive free of mechanical ventilation within 28 days. TF was measured on days 1-3, and the average for the first 3 days was recorded. A Kruskal-Wallis test was performed to compare VFDs across the three categories of inspiratory effort based on TF measured on days 1-3 and the average TF. Results: A cohort of 62 patients with a median age 66 [57-75] years, 53.2% female, and a median APACHE II score of 26 [22-33] were enrolled. On day 3 of mechanical ventilation, TF had a trend toward a significant association with VFDs (Table 1; p = 0.05). Based on the TF measured on day 3, 31 (50%) patients had low effort, 21 (33.3%) had normal effort, and 10 (16.1%) had high effort. Patients with normal effort on day 3 had the highest ventilator free days (23.9 days [0-25]) as compared to low (0 days [0-23.2]) and high effort (2.3 days [0-21.1]). There was no significant association between TF and VFDs for TF measured on day 1 or day 2 or the average TF over all 3 days. Conclusion: Our findings suggest inspiratory effort on the third day of mechanical ventilation was associated with ventilator free days. More patients are needed to confirm these findings. Sedation may be a confounder in the early course of ventilation, and when it is held or reduced, effort may have greater prognostic value.

Innovative fabrication of folic acid-conjugated curcumin cellulose nanofibers for targeted lung cancer therapy

Cellulose · 2025-10-12 · 1 citations

Fecal metabolite profiling identifies critically ill patients with increased 30-day mortality

Science Advances · 2025-06-06 · 5 citations

Critically ill patients admitted to the medical intensive care unit (MICU) have reduced intestinal microbiota diversity and altered microbiome-associated metabolite concentrations. Metabolites produced by the gut microbiota have been associated with survival of patients receiving complex medical treatments and thus might represent a treatable trait to improve clinical outcomes. We prospectively collected fecal specimens, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived fecal metabolites by mass spectrometry from 196 critically ill patients admitted to the MICU for non-COVID-19 respiratory failure or shock to correlate microbiota features and metabolites with 30-day mortality. Microbiota compositions of the first fecal sample after MICU admission did not independently associate with 30-day mortality. We developed a metabolic dysbiosis score (MDS) that uses fecal concentrations of 13 microbiota-derived metabolites, which predicted 30-day mortality independent of known confounders. The MDS complements existing tools to identify patients at high risk of mortality by incorporating potentially modifiable, microbiome-related, independent contributors to host resilience.

Lateral Versus Midline: A Retrospective Review of Paracentesis Site Location and Risk of Hemorrhagic Complication

Critical Care Medicine · 2025-09-26 · 1 citations

OBJECTIVES: Patients who have cirrhosis, malignancy, or heart failure frequently accumulate ascitic fluid in their peritoneal cavity. Percutaneous drainage of ascites is a common procedure to provide diagnostic and/or therapeutic benefit to the patient; however, this procedure is associated with a small but life-threatening risk of hemorrhage. Given the avascular nature of the linea alba, it was hypothesized that a midline approach would reduce the risk of hemorrhage. DATA SOURCES: Data were collected from the electronic medical record. This review was authorized by the University of Chicago, Institutional Review Board 20-0083. STUDY SELECTION: Using the electronic medical record, 1798 patients were identified using International Classification of Diseases , 9th revision and International Classification of Diseases , 10th revision codes between January 1, 2011, and January 1, 2020. DATA EXTRACTION: We conducted a retrospective chart review of 1798 patients who underwent 4563 percutaneous abdominal paracentesis events with ultrasound guidance. Four thousand five hundred thirteen of those procedures had information about procedure location. The location of catheter placement, lateral vs. midline, was recorded in conjunction with occurence rate of post-paracentesis clinically significant hemorrhage, defined as CT imaging with evidence of hemorrhage at the procedural site within 7 days of paracentesis that required either blood transfusion, angiographic intervention, or resulted in death. Baseline characteristics were also collected, including age, sex, body mass index, volume of ascites drained, baseline hemoglobin, platelet count, international normalized ratio, serum sodium, creatinine, bilirubin, albumin, and etiology of ascites. Among paracentesis events for patients with a diagnosis of cirrhosis ( n = 2497), 2206 has sufficient data to calculate a Model for End-Stage Liver Disease (MELD) 3.0 score and 2202 had sufficient data to determine Child-Pugh Classification. DATA SYNTHESIS: Among patients receiving paracentesis, the overall occurence rate of hemorrhage was 1.3% (60/4563). There was a statistically significant reduction in the occurence rate of hemorrhage among patients who underwent midline percutaneous catheter placement (0/230) compared with lateral percutaneous catheter placement (60/4283; p = 0.03). Among patients with cirrhosis, patients undergoing lateral paracentesis ( n = 2086) had a mean MELD 3.0 score of 22 ( sd , 8.46) and patients undergoing midline paracentesis ( n = 118) had a mean MELD 3.0 score of 25 ( sd , 8.13). These groups had a statistically significant difference by Mann-Whitney U test ( p ≤ 0.001) with a standardized effect size of 0.071. Logistic regression was performed to identify patient variables that correlated with hemorrhage. Among these, only serum bilirubin nearly approached significance ( p = 0.07). No baseline variable had an odds ratio that did not cross 1.0. CONCLUSIONS: These data suggest midline paracentesis may reduce the risk of post-procedural hemorrhage among patients undergoing paracentesis.

The intensive care medicine research agenda for the management of ICU acquired weakness: a multinational, interprofessional perspective

Intensive Care Medicine · 2025-11-03 · 9 citations

Enterobactin inhibits microbiota-dependent activation of AhR to promote bacterial sepsis in mice

Nature Microbiology · 2025-01-08 · 35 citations

Potato starch bioplastic films reinforced with organic and inorganic fillers: A sustainable packaging alternative

International Journal of Biological Macromolecules · 2025-03-01 · 14 citations