Department of Medicine

Objective: Bacterial resistance is known to diminish the effectiveness of antibiotics for treatment of urinary tract infections. Review of recent healthcare and antibiotic exposures, as well as prior culture results is recommended to aid in selection of empirical treatment. However, the optimal approach for assessing these data is unclear. We utilized data from the Veterans Health Administration to evaluate relationships between culture and treatment history and the subsequent probability of antibiotic-resistant bacteria identified in urine cultures to further guide clinicians in understanding these risk factors. Methods: Using the XGBoost algorithm, a retrospective cohort of outpatients with urine culture results and antibiotic prescriptions from 2017 to 2022 was used to develop models for predicting antibiotic resistance for three classes of antibiotics: cephalosporins, fluoroquinolones, and trimethoprim/sulfamethoxazole (TMP/SMX) obtained from urine cultures. Model performance was assessed using Area Under the Receiver Operating Characteristic curve (AUC) and Precision-Recall AUC (PRAUC). Results: There were 392,647 prior urine cultures identified in 214,656 patients. A history of bacterial resistance to the specific treatment was the most important predictor of subsequent resistance for positive cultures, followed by a history of specific antibiotic exposure. The models performed better than previously established risk factors alone, especially for fluoroquinolone resistance, with an AUC of .84 and PRAUC of .70. Notably, the models' performance improved markedly (AUC = .90, PRAUC = .87) when applied to cultures from patients with a known history of resistance to any of the antibiotic classes. Conclusion: These predictive models demonstrate potential in guiding antibiotic prescription and improving infection management.

BackgroundThe fecal immunochemical test (FIT) is the primary modality used by the Los Angeles County Department of Health Services (LADHS) for colorectal cancer (CRC) screening in average-risk patients. Some patients referred for FIT-positive diagnostic colonoscopy have neither adenomas nor more advanced pathology. We aimed to identify predictors of false-positive FIT (FP-FIT) results in our largely disenfranchised, low socioeconomic status population.MethodsWe conducted a retrospective study of 596 patients who underwent diagnostic colonoscopy following a positive screening FIT. Colonoscopies showing adenomas (or more advanced pathology) were considered positive. We employed multiple logistic and linear regression as well as machine learning models (MLMs) to identify clinical predictors of FP-FIT (primary outcome) and the presence of advanced adenomas (secondary outcome).ResultsOverall, 268 patients (45.0%) had a FP-FIT. Female sex and hemorrhoids (odds ratios [ORs] 1.59 and 1.89, respectively) were associated with increased odds of FP-FIT and fewer advanced adenomas (β = − 0.658 and  − 0.516, respectively). Conversely, increasing age and BMI (ORs 0.94 and 0.96, respectively) were associated with decreased odds of FP-FIT and a greater number of advanced adenomas (β = 0.073 and 0.041, respectively). MLMs predicted FP-FIT with high specificity (93.8%) and presence of advanced adenoma with high sensitivity (94.4%).ConclusionIncreasing age and BMI are associated with lower odds of FP-FIT and greater number of advanced adenomas, while female sex and hemorrhoids are associated with higher odds of FP-FIT and fewer advanced adenomas. The presence of the aforementioned predictors may inform the decision to proceed with diagnostic colonoscopy in FIT-positive patients.

Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic lesions, decades of research have now led to the recognition that the regulatory mechanisms and the biomolecules that control cardiovascular calcification overlap with those controlling skeletal mineralization. In this review, we focus on key biomolecules driving the ectopic calcification in the circulation and their regulation by metabolic, hormonal, and inflammatory stimuli. Although calcium deposits in the vessel wall introduce rupture stress at their edges facing applied tensile stress, they simultaneously reduce rupture stress at the orthogonal edges, leaving the net risk of plaque rupture and consequent cardiac events depending on local material strength. A clinically important consequence of the shared mechanisms between the vascular and bone tissues is that therapeutic agents designed to inhibit vascular calcification may adversely affect skeletal mineralization and vice versa. Thus, it is essential to consider both systems when developing therapeutic strategies.