OBJECTIVES:Urolithiasis represents a leading cause of emergency department (ED) presentation nationally, affecting approximately 10% of Americans. However, most patients require neither hospital admission nor surgical intervention. This study investigates patient and facility factors associated with potentially avoidable ED visits and their economic consequences.STUDY DESIGN:Retrospective analysis.METHODS:Patients presenting to the ED for index urolithiasis events were selected using Florida and New York all-payer data from the 2016 Healthcare Cost and Utilization Project state databases. Avoidable visits were defined as subsequent ED encounters following initial ED presentation that did not result in intervention, admission, or referral to an acute care facility. Utilizing multivariable logistic and linear regression, researchers discerned patient and facility factors predictive of avoidable ED presentations and associated costs.RESULTS:Of the 167,102 ED encounters for urolithiasis, 7.9% were potentially avoidable, totaling $94,702,972 in potential yearly cost savings. Mean encounter-level costs were higher for unavoidable vs avoidable visits ($5885 vs $2098). In contrast, mean episode-based costs were similar for avoidable and unavoidable episodes ($7200 vs $7284). Receiving care in small metropolitan (vs large metropolitan) communities was associated with potentially avoidable visits, whereas increased comorbidities and Hispanic ethnicity were protective against avoidable visits.CONCLUSIONS:The incidence of ED use for subsequent urolithiasis care reveals opportunity for enhanced outpatient availability to reduce hospital-based costs. Several nonclinical factors are associated with potentially avoidable ED visits for urolithiasis, which, if appropriately targeted, may represent an opportunity to reduce health care spending without compromising the quality of care delivery.

Calorie restriction (CR) inhibits triple-negative breast cancer (TNBC) progression in several preclinical models in association with decreased insulin-like growth factor 1 (IGF1) signaling. To investigate the impact of CR on microRNAs (miRs) that target the IGF1/IGF1R pathway, we used the spontaneous murine model of TNBC, C3(1)/SV40 T-antigen (C3-TAg). In C3-TAg mice, CR reduced body weight, IGF1 levels, and TNBC progression. We evaluated the tumoral expression of 10 miRs. CR increased the expression of miR-199a-3p, miR-199a-5p, miR-486, and miR-15b. However, only miR-15b expression correlated with tumorigenicity in the M28, M6, and M6C C3-TAg cell lines of TNBC progression. Overexpressing miR-15b reduced the proliferation of mouse (M6) and human (MDA-MB-231) cell lines. Serum restriction alone or in combination with low levels of recombinant IGF1 significantly upregulated miR-15b expression and reduced Igf1r in M6 cells. These effects were reversed by the pharmacological inhibition of IGFR with BMS754807. In silico analysis using miR web tools predicted that miR-15b targets genes associated with IGF1/mTOR pathways and the cell cycle. Our findings suggest that CR in association with reduced IGF1 levels could upregulate miR-15b to downregulate Igf1r and contribute to the anticancer effects of CR. Thus, miR-15b may be a therapeutic target for mimicking the beneficial effects of CR against TNBC.

Abstract Introduction: We evaluated clinical and sociodemographic factors that influence care pathways following acute urinary retention with attention to subsequent bladder outlet procedures. Methods: This was a retrospective cohort study examining patients who presented for emergent care with concomitant diagnoses of urinary retention and benign prostatic hyperplasia in New York and Florida in 2016. Using Healthcare Cost and Utilization Project data, patients were followed throughout a calendar year across subsequent encounters for recurrent urinary retention and bladder outlet procedures. Multivariable logistic and linear regression were utilized to identify factors associated with recurrent urinary retention, subsequent outlet procedures and the cost of retention-related encounters. Results: Among 30,827 patients, 12,286 (39.9%) were ≥80 years of age. Though 5,409 (17.5%) experienced multiple retention-related encounters, only 1,987 (6.4%) received a bladder outlet procedure within the calendar year. Covariates associated with repeat urinary retention included older age (OR 1.31, p <0.001), Black race (OR 1.18, p=0.001), Medicare insurance (OR 1.16, p=0.005) and lower education level (OR 1.13, p=0.03). Age ≥80 years (OR 0.53, p <0.001), Elixhauser Comorbidity Index score ≥3 (OR 0.31, p <0.001), Medicaid status (OR 0.52, p <0.001) and lower education level were associated with lower odds of receiving a bladder outlet procedure. Episode-based costs favored single retention encounters vs repeat encounters ($15,285.96 vs $28,451.21, p <0.001) and undergoing an outlet procedure vs foregoing one ($16,223.38 vs $17,690.54, p=0.002). Conclusions: Sociodemographic factors are associated with recurrent retention episodes and the decision to undergo a bladder outlet procedure following an episode of urinary retention. Despite the cost benefits associated with preventing repeated episodes of urinary retention, merely 6.4% of patients presenting with acute urinary retention underwent a bladder outlet procedure during the study period. Our findings suggest that early intervention among individuals experiencing urinary retention may confer cost and duration of care benefits.

Abstract Calorie restriction (CR) has an antitumorigenic effect against triple-negative breast cancer (TNBC). A key mitogenic pathway modulated by CR involves insulin-like growth factor (IGF)-1, which plays a central role in local and systemic growth and cell survival by activating the PI3K/AKT/mTOR pathway downstream of the IGF-1 receptor (IGF-1R). Although multiple miRNAs that target components of the IGF-1 signaling pathway have been identified, the impact of CR on IGF-1-related miRNA expression has not been addressed. We hypothesize that CR-induced decreases in TNBC development and progression involve miRNA's regulating IGF-1 signaling, we used C3(1)/SV40 T-antigen (C3-TAg) mice (a TNBC model), a C3-Tag progression series of cell lines (M28, M6, and M6C), and human TNBC cell line (MDA-MB-231). The expression of miRNAs previously reported to target components of the IGF-1 and/or mTOR pathways was evaluated by real-time PCR. Hormone levels were measured using the mouse Luminex Screening Assay. To mimic CR in vitro, and to test the effects of miRNA manipulation, the C3-Tag series of TNBC cell lines were treated (separately and in combination) with serum restriction, BMS754807 (inhibitor of IGF1-R), and various levels of recombinant IGF-1 as well as manipulated levels of miRNA's associated with IGF-1/mTOR signaling. We also conducted in silico analysis using Metabric, TCGA, TargetScan, and miRTarBase data sets to identify genes and pathways associated with specific miRNAs expression related to the PI3K/Akt/mTOR pathway. Our results confirm that CR maintains lower body weight, reduces circulating levels of IGF-1, and slows spontaneous TNBC development and progression in mice. CR also significantly increased the expression of miR-15b and miR-486. In vitro studies showed miR-15b and miR-486 expression decreased with increasing tumorigenicity of the C3-tag series of TNBC progression. Treatment of mouse and human TNBC cells with low IGF-1 induced miR-15b expression and inhibited proliferation. Moreover, miR-15b overexpression inhibited cell proliferation and decreased IGF-1R expression (mRNA and protein). Consistent with these results, the in silico analysis shows that the amplification of miR-15b correlates with downregulation of pathways involved in tumor growth and IGF1-R signaling. Together these findings suggest that reduced circulating IGF-1 levels in response to CR leads to the upregulation of miR-15b, which correspondingly targets and downregulates IGF-1R, both at the mRNA and protein levels. This combination of reduced IGF-1 ligand and miR-15b-induced IGF-1R downregulation contributes to the potent anticancer effects of CR and reveals potential targets for pharmacologically mimicking those effects. This research is supported by R35CA197627. Citation Format: Ximena Minerva Bustamante-Marin, Kaylyn L. Devlin, Om Dave, Jenna L. Merlino, Shannon B. McDonell, Michael F. Coleman, Stephen D. Hursting. Anticancer effects of calorie restriction in a murine C3-TAg model of triple-negative breast cancer: the role of miR-15b [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2357.