Background

Although significant racial disparities in the surgical management of lower extremity critical limb threatening ischemia have been previously reported, data on disparities in lower extremity acute limb ischemia are lacking.

Methods

The 2012-2018 National Inpatient Sample was queried for all adult hospitalizations for acute limb ischemia (N = 225,180). Hospital-specific observed-to-expected rates of major lower extremity amputation were tabulated. Multivariable logistic and linear models were developed to assess the impact of race on amputation and revascularization.

Results

Nonwhite race was associated with significantly increased odds of overall (adjusted odds ratio: 1.16, 95% confidence interval 1.06-1.28) and primary (adjusted odds ratio: 1.34, 95% confidence interval 1.17-1.53) major amputation, decreased odds of revascularization (adjusted odds ratio 0.79, 95% confidence interval 0.73-0.85), but decreased in-hospital mortality (adjusted odds ratio: 0.86, 95% confidence interval 0.74-0.99). The nonwhite group incurred increased adjusted index hospitalization costs (β: +$4,810, 95% confidence interval 3,280-6,350), length of stay (β: + 1.09 days, 95% confidence interval 0.70-1.48), and nonhome discharge (adjusted odds ratio: 1.15, 95% confidence interval 1.06-1.26).

Conclusion

Significant racial disparities exist in the management of and outcomes of lower extremity acute limb ischemia despite correction for variations in hospital amputation practices and other relevant hospital and patient characteristics. Whether the etiology lies primarily in patient, institution, or healthcare provider-specific factors has not yet been determined. Further studies of race-based disparities in management and outcomes of acute limb ischemia are warranted to provide effective and equitable care to all.

BACKGROUND: Antiplatelet agents are central in the management of vascular disease. The use of dual antiplatelet therapy (DAPT) for the management of thromboembolic complications must be weighed against bleeding risk in the perioperative setting. This balance is critical in patients undergoing cardiac or non-cardiac surgery. The management of patients on DAPT for any indication (including stents) is not clear and there is limited evidence to guide decision-making. This review summarizes current evidence since 2015 regarding the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. METHODS: A research librarian searched PubMed and Cochrane from November 30, 2015 to May 17, 2022, for relevant terms regarding adult patients on DAPT for any reason undergoing surgery, with a perioperative variation in DAPT strategy. Outcomes of interest included the occurrence of major adverse cardiac events, major adverse limb events, all-cause death, major bleeding, and reoperation. We considered withdrawal or discontinuation of DAPT as stopping either aspirin or a P2Y12 inhibitor or both agents; continuation of DAPT indicates that both drugs were given in the specified timeframe. RESULTS: Eighteen observational studies met the inclusion criteria. No RCTs were identified, and no studies were judged to be at low risk of bias. Twelve studies reported on CABG. Withholding DAPT therapy for more than 2 days was associated with less blood loss and a slight trend favoring less transfusion and surgical re-exploration. Among five observational CABG studies, there were no statistically significant differences in patient death across DAPT management strategies. Few studies reported cardiac outcomes. The remaining studies, which were about procedures other than exclusively CABG, demonstrated mixed findings with respect to DAPT strategy, bleeding, and ischemic outcomes. CONCLUSION: The evidence base on the benefits and risks of different perioperative DAPT strategies for patients with stents is extremely limited. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for greater than 2 days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations. Different DAPT strategies association with other outcomes of interest, such as MACE, remains uncertain. SYSTEMATIC REVIEW REGISTRATION: A preregistered protocol for this review can be found on the PROSPERO International Prospective Register of systematic reviews ( http://www.crd.york.ac.uk/PROSPERO/ ; registration number: CRD42022371032).

PURPOSE: Stimulator of interferon genes (STING) agonists are currently in development for treatment of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Response rates to STING agonists alone have been promising yet modest, and combination therapies will likely be required to elicit their full potency. We sought to identify combination therapies and mechanisms that augment the tumor cell-intrinsic effect of therapeutically relevant STING agonists apart from their known effects on tumor immunity. EXPERIMENTAL DESIGN: We screened 430 kinase inhibitors to identify synergistic effectors of tumor cell death with diABZI, an intravenously administered and systemically available STING agonist. We deciphered the mechanisms of synergy with STING agonism that cause tumor cell death in vitro and tumor regression in vivo. RESULTS: We found that MEK inhibitors caused the greatest synergy with diABZI and that this effect was most pronounced in cells with high STING expression. MEK inhibition enhanced the ability of STING agonism to induce type I IFN-dependent cell death in vitro and tumor regression in vivo. We parsed NFκB-dependent and NFκB-independent mechanisms that mediate STING-driven type I IFN production and show that MEK signaling inhibits this effect by suppressing NFκB activation. CONCLUSIONS: Our results highlight the cytotoxic effects of STING agonism on PDAC cells that are independent of tumor immunity and that these therapeutic benefits of STING agonism can be synergistically enhanced by MEK inhibition.

Here, we present a protocol to generate a murine model of liver metastasis by directly injecting tumor cells into the portal vein under ultrasound guidance. We describe steps for animal and cell preparation and two techniques for injecting tumor cells. One technique is freehand, while the other technique is device-assisted using a 3D-printed prototype device. Finally, we describe tumor surveillance with bioluminescent imaging.