University of Colorado Denver

Diabetes mellitus is one of the fastest-growing chronic medical conditions worldwide. It disproportionately affects some minoritized populations, including certain racial and ethnic groups, migrant populations, and rural communities. Disparities in diabetes mellitus prevalence, morbidity and mortality in minoritized populations are related to longstanding structural and social inequities and are closely tied to social factors. However, current interventions to improve diabetes mellitus outcomes among people from minoritized populations have primarily focused on trying to change individual behaviour, without sufficiently addressing the root structural barriers that drive disparities. Here, we aim to describe the structural inequities in the diagnosis, management and outcomes of minoritized people with diabetes mellitus and to discuss practical measures that can ensure equitable care for people in minoritized groups who have diabetes mellitus. Using a framework to examine diabetes mellitus disparities, we will consider interventions at system levels, including public health approaches, the endocrine healthcare workforce, care quality standards, access to high-quality care (including advanced technologies) and involvement in research. We will also discuss strategies to address intermediate factors, including food insecurity and literacy, and to improve diabetes mellitus care services among migrant and refugee populations and racial and/or ethnic minority communities.

Growing evidence supports the addition of fresh frozen plasma (FFP) to a standardized crystalloid-based burn resuscitation. Fresh frozen plasma is thought to mitigate endotheliopathy, decrease total fluids and improve outcomes; however, when and how much FFP to give remains controversial. Here, we assessed the safety and efficacy of adding a non-titratable, 8-hr FFP infusion of 0.5mL/kg/% total body surface area (TBSA) to a burn resuscitation. We performed an unmatched retrospective cohort review on all patients with burn injuries aged > 18years old with > 20% TBSA burns who underwent our nursing-driven resuscitation protocol that included this early, standardized FFP infusion, from November 2016 to May 2020. Fifty-three patients received FFP and met inclusion criteria. Patients were primarily male (85%), with a median age of 36years and a TBSA burn of 39% (range 24.5%-94%). Median time to FFP administration was 7h from injury with a median of 1517mL infused. Median input/output (I/O) ratio improved from 0.8 at FFP initiation to 0.4 at 3h post-FFP, P < .001. Median urine output (UOP) improved from 0.19mL/kg/h prior to FFP administration to 0.52mL/kg/h at 3h post-FFP, P < .001. No complications related to resuscitation such as abdominal compartment syndrome, acute respiratory distress syndrome, or transfusion reactions occurred. Therefore, adding a low-dose, standardized FFP infusion to burn resuscitations significantly improved UOP, normalized I/O ratios, and did not cause any known complications. Standardizing a safe, effective, non-titratable FFP infusion provides the framework to systematically test how colloids can be optimized during burn resuscitations in the future.

Left ventricular (LV) dysfunction is a potential cardioembolic source of ischemic stroke, but its role in recurrent stroke risk and treatment response remains unclear. We explore whether LV injury associates with the risk of recurrent stroke and modifies the association between anticoagulation and stroke recurrence using real-world data. We performed a multicenter, retrospective study of Cardiac Abnormalities in Stroke Prevention and Recurrence cohort across 27 US sites. Patients with LV ejection fraction ≥20% were included. LV injury, defined as LV ejection fraction 20% to 40% and wall motion abnormality, was the primary exposure and treatment effect modifier. The treatment of interest was anticoagulant versus antiplatelet therapy. The composite outcome included recurrent stroke, major bleeding, or death. Outcomes were evaluated using unadjusted and inverse probability weighting adjusted Cox proportional hazards models, with treatment effect modification tested by LV injury status. Among 2685 patients enrolled, 2328 with complete data were analyzed (median age, 65 years; 49.8% female; median follow-up, 1.6 years). LV injury was present in 310 patients (13.3%). Overall, 535 events occurred: 258 recurrent ischemic strokes, 28 hemorrhagic strokes, 67 major hemorrhages, and 256 deaths. LV injury was associated with a higher unadjusted risk of the primary outcome (hazard ratio [HR], 1.51 [95% CI, 1.21-1.87]), though nonsignificant after inverse probability weighting adjustment (adjusted HR, 1.29 [95% CI, 0.97-1.70]). In the LV injury subgroup, anticoagulation versus antiplatelet therapy was associated with a lower risk of the primary outcome (adjusted HR, 0.24 [95% CI, 0.10-0.59]), relative to the non-LV injury subgroup (adjusted HR, 1.28 [95% CI, 0.83-1.95]; p[LV-interaction], 0.001). Similar interactions were seen for EF 20% to 40% (versus >40%; adjusted HR, 0.19 [95% CI, 0.04-0.86]; p[LV-interaction], 0.001) and wall motion abnormality (versus no wall motion abnormality; adjusted HR, 0.33 [95% CI, 0.15-0.73]). After cryptogenic stroke, anticoagulation in those with LV injury was associated with lower rates of recurrent stroke, major bleeding, and death. These findings warrant confirmation in a dedicated randomized controlled trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06398366.

RET fusions appear in 1%-2% of non-small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET-altered NSCLC and RET fusion-positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion-positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion-positive NSCLCs, confirming previous findings with longer follow-up.

The study goal was to evaluate the outcomes associated with albumin use in children with sepsis and shock compared with those without shock, using causal inference analysis in a multicenter cohort. This was a secondary analysis of electronic health record data collected from 13 U.S. PICUs between 2012 and 2018, consisting of children younger than 18 years who met Phoenix sepsis criteria within the first 24 hours of PICU admission. Covariate-balancing propensity score weighting was applied to adjust for indication bias in the albumin use. Patients receiving at least 0.5 g/kg albumin within 24 hours of PICU admission were assigned to the albumin group; others to the control. Only 24-hour survivors were included to address immortal time bias. Overall, 17,307 children with sepsis survived at least 24 hours. Of these, 1,344 patients (7.8%) who received albumin within the first 24 hours, and 9,678 (55.9%) met the criteria for septic shock. A significant interaction between albumin use and shock status was observed (interaction: -0.353, p = 0.007), with albumin administration in pediatric septic shock patients associated with lower in-hospital mortality: odds ratio equals to 0.698 (95% CI, 0.629-0.774), risk ratio equals to 0.746 (95% CI, 0.625-0.891), and hazard ratio equals to 0.688 (95% CI, 0.558-0.848). In contrast, there was no difference in outcomes between the albumin and control groups in the non-shock group. Early albumin administration was associated with improved outcomes in children with septic shock, but not in those without shock. These results highlight the importance of considering clinical heterogeneity, such as the presence of shock, in identifying treatment-responsive subgroups and enabling more targeted interventions in pediatric sepsis. Further prospective validation is warranted.

Our previous preclinical studies demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and naproxen significantly inhibited prostate tumorigenesis in a TMPRSS2-ERG fusion-driven model compared to non-fusion models. Since TMPRSS2-ERG fusion-positive tumors display heightened inflammatory signaling and substantial immune infiltration, we hypothesized that the differential efficacy of NSAIDs may arise from their ability to remodel the tumor immune microenvironment. Accordingly, in the present study, we systematically profiled innate and adaptive immune-cell populations: F4/80⁺ macrophages, mast cells, neutrophils, CD3⁺ T cells, CD8⁺ cytotoxic T cells, FoxP3⁺ regulatory T cells, CD20⁺ B cells, IgKC⁺ plasma cells, and Granzyme B⁺ effector cells in highly infiltrated dorso-lateral prostate regions of TMPRSS2-ERG fusion-driven and non-fusion PCa models, with and without NSAID intervention. Our analyses revealed pronounced macrophage infiltration in TMPRSS2-ERG. Ptenflox/flox and Hi-Myc+/ - model, which was further augmented by NSAIDs. Importantly, NSAID intervention shifted macrophage polarization toward an M1-like, pro-inflammatory state, contrasting with the M2-dominant phenotype characteristic of untreated tumors. NSAID treatment reduced mast cell density within the stromal compartment, suggesting suppression of mast cell-mediated tumor-promoting signals. In the fusion model, infiltration of total T cells and CD8⁺ cytotoxic T cells decreased following NSAID exposure, whereas FoxP3⁺ Tregs remained largely unaffected. Both models showed increased B-cell infiltration independent of NSAID efficacy, and no clear correlation was observed between plasma-cell presence and treatment response. Collectively, our findings offer new insight into NSAID-mediated immunomodulation in TMPRSS2-ERG fusion-driven PCa; however, further in-depth immune subtyping and spatial mapping could fully delineate the immunological mechanisms driving NSAID responsiveness.

To provide recommendations for the most appropriate endovascular intervention of femoropopliteal (FP) arterial disease based on plaque characterization. A panel of 22 physicians from multiple disciplines participated in a modified Delphi consensus, leveraging the RAND/UCLA Appropriateness Method. Panelists engaged in 2 rounds of voting, following a literature review, with an in-person discussion prior to the second round of voting. A rigorous statistical approach was used to analyze the points of agreement and disagreement. Consensus-based recommendations on the most appropriate endovascular approaches for treating patients with FP lesions, stratified by lesion morphology, were generated. Overall, 490 individual items were included in the voting, 458 (93%) of which achieved consensus and 32 (7%) were nonconsensus items, based on a priori criteria under the following categories: (a) recommendations on method for determining plaque morphology, (b) preferred endovascular devices for vessel preparation and definitive treatment stratified by (i) plaque morphology and (ii) Tosaka classification of in-stent restenosis, and (c) vessel preparation device safety-related considerations. This international, multidisciplinary consensus provides evidence- and expert-informed recommendations for vessel preparation and definitive treatment of FP arterial disease, tailored to plaque morphology. These consensus recommendations aim to support clinical decision making and promote best interventional practices by serving as an expert opinion supplement to existing guideline-based care pathways.