Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many cancers where it acts to promote tumor progression. A STAT3-specific transcription factor decoy has been developed to suppress STAT3 downstream signaling, but a delivery strategy is needed to improve clinical translation. Ultrasound-targeted microbubble destruction (UTMD) has been shown to enhance image-guided local delivery of molecular therapeutics to a target site. The objective of this study was to deliver STAT3 decoy to squamous cell carcinoma (SCC) tumors using UTMD to disrupt STAT3 signaling and inhibit tumor growth. Studies performed demonstrated that UTMD treatment with STAT3 decoy-loaded microbubbles inhibited STAT3 signaling in SCC cells in vitro. Studies performed in vivo demonstrated that UTMD treatment with STAT3 decoy-loaded microbubbles induced significant tumor growth inhibition (31-51% reduced tumor volume vs. controls, p < 0.05) in mice bearing SCC tumors. Furthermore, expression of STAT3 downstream target genes (Bcl-xL and cyclin D1) was significantly reduced (34-39%, p < 0.05) in tumors receiving UTMD treatment with STAT3 decoy-loaded microbubbles compared to controls. In addition, the quantity of radiolabeled STAT3 decoy detected in tumors eight hours after treatment was significantly higher with UTMD treatment compared to controls (70-150%, p < 0.05). This study demonstrates that UTMD can increase delivery of a transcription factor decoy to tumors in vivo and that the decoy can inhibit STAT3 signaling and tumor growth. These results suggest that UTMD treatment holds potential for clinical use to increase the concentration of a transcription factor signaling inhibitor in the tumor.

Background: To provide a descriptive analysis of scrotal and testicular trauma in the USA. Additionally, we hypothesized that motorcycle collision would have a higher association with scrotal or testicular trauma and subsequent scrotal or testicular operation, compared to a bicycle collision. Methods: The National Trauma Data Bank (2007–2015) was queried to identify adult male patients with scrotal or testicular trauma. A multivariable logistic regression analysis was performed. Results: A total of 8,030 patients (0.23%) had scrotal/testicular injury, with 44.6% involved in blunt trauma. A penetrating mechanism occurred in 50.5% of cases, with assault by firearm (75.8%) being the most common. The median age of the patients was 31 years and the median injury severity score was 8. Most had isolated scrotal or testicular trauma (74.5%), with 48.3% requiring scrotal or testicular operation, most commonly repair of laceration (37.3%). Patients involved in a motorcycle collision had higher risk for scrotal/testicular trauma (OR=5.40, CI=4.40–6.61, p=0.0004) and subsequent scrotal/testicular surgery (OR=4.93, CI=3.82–6.36, p=0.0005), compared to bicycle collision. Conclusion: Scrotal or testicular trauma is rare but occurs most commonly after assault by firearm. Most patients only have isolated scrotal or testicular trauma, but nearly half require subsequent scrotal or testicular operation. Trauma patients presenting after a motorcycle collision have a higher association of scrotal or testicular trauma and subsequent surgery when compared to those involved in a bicycle collision.

Social determinants of health (SDOH) are important predictors of poor clinical outcomes in chronic diseases, but their associations among the general cirrhosis population and liver transplantation (LT) are limited. We conducted a retrospective, multiinstitutional analysis of adult (≥18-years-old) patients with cirrhosis in metropolitan Chicago to determine the associations of poor neighborhood-level SDOH on decompensation complications, mortality, and LT waitlisting. Area deprivation index and covariates extracted from the American Census Survey were aspects of SDOH that were investigated. Among 15 101 patients with cirrhosis, the mean age was 57.2 years; 6414 (42.5%) were women, 6589 (43.6%) were non-Hispanic White, 3652 (24.2%) were non-Hispanic Black, and 2662 (17.6%) were Hispanic. Each quintile increase in area deprivation was associated with poor outcomes in decompensation (sHR [subdistribution hazard ratio] 1.07; 95% CI 1.05-1.10; P < .001), waitlisting (sHR 0.72; 95% CI 0.67-0.76; P < .001), and all-cause mortality (sHR 1.09; 95% CI 1.06-1.12; P < .001). Domains of SDOH associated with a lower likelihood of waitlisting and survival included low income, low education, poor household conditions, and social support (P < .001). Overall, patients with cirrhosis residing in poor neighborhood-level SDOH had higher decompensation, and mortality, and were less likely to be waitlisted for LT. Further exploration of structural barriers toward LT or optimizing health outcomes is warranted.

INTRODUCTION: Social determinants of health (SDOH) may impact chronic liver disease (CLD) outcomes but are not clearly understood. We conducted a systematic review to describe the associations of SDOH with mortality, hospitalizations, and readmissions among patients with CLD. METHODS: This review was registered (PROSPERO ID: CRD42022346654) and identified articles through MEDLINE, Embase, Cochrane Library, and Scopus databases. The review included studies that reported SDOH characteristics within the domains of economic stability, healthcare access, education, social and community context, and the neighborhood-built environment. Associated outcomes of interest were mortality, hospitalizations, or readmissions. The Cochrane Risk of Bias in Nonrandomized Studies for Exposure was used to assess study quality and risk of bias. RESULTS: A total of 5,205 abstracts were screened, 60 articles underwent full-text review, and 27 articles were included in the final review. Poor economic stability, healthcare access, social support, and household/environmental conditions were associated with higher mortality and hospital readmissions among patients with CLD. Increasing distance (≥25 miles away) from a liver transplantation center was associated with higher mortality, despite increasing access to the liver transplantation waitlist. When assessing the overall risk of bias among included studies, most had “some concern” (N = 13, 48.1%) or “high risk” (N = 11, 40.7%), whereas a minority had “very high risk” (N = 3, 11.1%). No studies were categorized as “low risk.” DISCUSSION: Unfavorable SDOH were associated with increased mortality and hospital readmissions among patients with CLD. Rigorous empirical research is needed to identify evidence-based strategies that aim to mitigate disparities among vulnerable populations.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Educational interventions may alleviate the burden of TBI for patients and their families. Interactive modalities that involve engagement with the educational material may enhance patient knowledge acquisition when compared to static text-based educational material. OBJECTIVE: To determine the effects of educational interventions in the outpatient setting on self-reported patient knowledge, with a focus on iPad-based (Apple, Cupertino, California) interactive modules. METHODS: Patients and family members presenting to a NeuroTrauma clinic at a tertiary care academic medical center completed a presurvey assessing baseline knowledge of TBI or concussion, depending on the diagnosis. Subjects then received either an interactive iBook (Apple) on TBI or concussion, or an informative pamphlet with identical information in text format. Subjects then completed a postsurvey prior to seeing the neurosurgeon. RESULTS: All subjects (n = 152) significantly improved on self-reported knowledge measures following administration of either an iBook (Apple) or pamphlet (P < .01, 95% confidence interval [CI]). Subjects receiving the iBook (n = 122) performed significantly better on the postsurvey (P < .01, 95% CI), despite equivalent presurvey scores, when compared to those receiving pamphlets (n = 30). Lastly, patients preferred the iBook to pamphlets (P < .01, 95% CI). CONCLUSION: Educational interventions in the outpatient NeuroTrauma setting led to significant improvement in self-reported measures of patient and family knowledge. This improved understanding may increase compliance with the neurosurgeon's recommendations and may help reduce the potential anxiety and complications that arise following a TBI.