St. Margaret Memorial Hospital

Introduction: The American Diabetes Association recommends use of glucagon-like-peptide-1 receptor agonists (GLP-1RAs) by patients with peripheral arterial disease (PAD) despite limited information regarding the impact of GLP-1RAs in these patients. Hypothesis: Patients using GLP-1RAs have lower rates of adverse events following revascularization. Methods: Our retrospective cohort (18-hospital, unified health care system; 2016-2024) included diabetic adults undergoing an index PAD revascularization, stratified by GLP-1RAs prescription. The primary outcome was overall mortality. Secondary outcomes included major adverse limb events (MALE), major adverse cardiac events (MACE), major amputation, and acute coronary syndromes (ACS). Outcomes were compared via Kaplan Meier analysis and entropy-balanced Cox regression using demographic, medical, healthy user parameters, intervention, and facility factors generating adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: We included 5,008 patients (age 69±11 years; 1,858 [37.1%] females; 4,400 [87.8%] White; 1,766 [35.2%] open interventions) of which 468 (9.3%) were prescribed GLP-1RAs. On unadjusted analysis, GLP-1RAs prescriptions were correlated with lower mortality rates (60 [13%] vs 1,649 [36%], p<0.001) (Figure 1) and ACS events (42 [9%] vs 642 [14%], p=0.04). However, MALE (123 [26%] vs 1,306 [29%], p=0.45), MACE (81 [17%] vs1,048 [23%], p=0.18), and major amputation (38 [8%] vs 498 [11%], p=0.12) differences were non-significant. After entropy-balance, covariates were well balanced with all standardized mean differences <0.1. Entropy-balance and multivariable regression noted GLP-1RA prescriptions were associated with a reduced risk of mortality (aHR [95%CI]: 0.65 [0.44-0.96]), ACS (aHR [95%CI]: 0.61 [0.37-0.99]), and major amputation (aHR [95%CI]: 0.45 [0.28-0.73]) (Figure 2) but failed to reach significance for MALE (aHR [95%CI]: 0.76 [0.56-1.03]) and MACE (aHR [95%CI]: 0.89 [0.61-1.30]). Conclusions: GLP-1RAs use in diabetic patients undergoing revascularization for PAD was associated with significantly decreased rates of postoperative mortality, major amputation, and ACS events after lower extremity revascularization. These findings support the benefit of these medications in the diabetic PAD population and warrant further investigation to understand mechanism of protection of these medications and the potential expanded use in nondiabetic patients with PAD.

Introduction/Background: Ventricular Septal Defect (VSD) is a well-known and often fatal complication of myocardial infarction (MI), particularly when presentation is delayed. The mortality of patients treated with medical therapy alone approaches 100%. Intra-aortic balloon pump (IABP) remains first-line temporary mechanical circulatory support (tMCS) as bridge therapy for surgical repair. However, at times counter pulsation alone does not provide adequate hemodynamic support. We present a single center experience using Impella 5.5 as a bridge to delayed surgical repair. Research Hypothesis: Impella 5.5 can be effective bridge therapy for delayed VSD repair in patients inadequately supported by other tMCS. Methods: We performed a retrospective chart review of all patients with post-MI VSD implanted with Impella 5.5 from 2021-2025. We evaluated demographic data, type and duration of tMCS support, development of refractory hypoxemia, survival, and complications related to tMCS. Results: Seven patients with post MI VSD were reviewed, mean age was 63.9, six patients were male, one patient was female, five patients had RCA infarct, and two patients had LAD infarct. Two of the seven patients were deemed poor surgical candidates due to stroke following impella 5.5 placement and mitral valve endocarditis, these patients died shortly after Impella 5.5 support was weaned. (Figure 1, Patients 1 and 2 respectively). The remaining five patients (Figure 1, Patients A-E) had stability or improvement in their hemometabolic profiles following placement of Impella 5.5 and underwent repair of VSD with bovine patch. For patients A-E, the average time on tMCS was 15 +/- 8.1 days and the average time on Impella 5.5 was 11 +/- 7.2 days. Known survival in post-operative group is 100% to date (Table 1). Conclusion: Standard of care for post-MI VSD involves immediate hemodynamic and hemometabolic resuscitation, and delayed surgical repair to optimize operative success. While IABP is standard of care, patients may require expedited surgery due to hemodynamic or hemometabolic instability, which results in unfavorable conditions for patch durability. Despite small case series, guidelines for IMPELLA 5.5 state post-MI VSD as a contraindication for Impella placement as it could cause worsening right to left shunting. Notably, no patients experienced refractory hypoxemia. This case series suggests Impella 5.5. may be the optimal strategy for bridging to delayed surgical repair in post-MI VSD.

ObjectiveThis study aims to evaluate whether perioperative care improves postoperative outcomes for head and neck reconstruction patients with preexisting health conditions.Study DesignRetrospective cohort study.SettingSingle tertiary academic center between 2013 and 2021.MethodsThis study included adult patients who underwent free‐flap reconstruction for head and neck cancer. Patients who received perioperative care were compared with patients who received our institution's standard of care. Comorbid health conditions were measured using the Charlson comorbidity index (CCI) excluding solid tumors. Primary outcomes were major and minor complications, length of hospital stay (LOS), days in intensive care unit (ICU), discharge to acute/subacute facility, hospital‐free days, and overall survival (OS). Interaction models were specified to evaluate the impact of preoperative care with respect to CCI.ResultsOf the 148 patients included, 83 received perioperative care and 65 received institutional standard of care (mean [SD]: age, 62.1 [10.8]; male, 100 [67.6%]; CCI ≥ 4, 43 [29.1%]). Patients with higher CCI who received perioperative care spent fewer days in the hospital (CCI 3: coefficient [β], −5.50; P = .012 and CCI ≥ 4: β, −6.41; P = .022) and ICU (CCI 3: β, −2.90; P = .002 and CCI ≥ 4: β, −6.54; P = .001), gained more hospital‐free days (CCI ≥ 4: β, 17.00; P = .002), and had improved OS (CCI ≥ 4: adjusted hazard ratio [aHR], 0.14; P = .023). Perioperative care was not significantly associated with lower rates of major and minor complications or placement at a facility.ConclusionPerioperative care provides a robust benefit for patients with medical comorbidities undergoing head and neck reconstruction, but this effect incrementally decreases for healthier patients.

BackgroundIschemic heart disease (IHD) remains one of the leading causes of morbidity and mortality across the globe, and disparities exist based on sex and geographic region.ObjectivesThis study investigates global trends in IHD mortality and examines disparities based on sex and geographic regions.MethodsIHD mortality data from 105 countries were obtained from the World Health Organization Mortality Database. Crude mortality rates (CMRs) and age-standardized mortality rates (ASMRs) per 100,000 individuals were calculated, with average annual percentage change (AAPC) analyzed using joinpoint regression. Regional and sex-specific trends were assessed using stratified analyses of CMR and ASMR.ResultsGlobally, CMR declined from 138 per 100,000 (95% CI: 131-145) in 2000 to 106 per 100,000 (95% CI: 102-114) in 2019 (AAPC: −1.79, 95% CI: −1.93 to −1.66). Similarly, ASMR declined from 104 per 100,000 (95% CI: 99-108) to 65.5 (95% CI: 62-69) in 2019 per 100,000 (AAPC: −2.16, 95% CI: −2.13 to −2.20). Regionally, CMRs decreased in Oceania, Europe, and North America, while they rose in Asia, Africa, and Central and South America. ASMRs declined worldwide except in Africa (AAPC: 1.33, 95% CI: 1.30-1.36). Males showed higher mortality than females, but both sexes demonstrated decreasing trends, with males having a steeper decline. In age groups across all regions, Africa showed an upward trend, while other regions demonstrated declines.ConclusionsWhile global IHD mortality has declined from 2000 to 2019, disparities by geographic region and sex persist. Implementing targeted health awareness programs and collaborative global health efforts are crucial for addressing these inequalities.

Abstract Rationale: There is increasing evidence that Alveolar Type II (ATII) progenitor-cell dysfunction and senescence plays a role in emphysema pathogenesis. The WNT pathway plays a key role in ATII stem-cell niche homeostasis/activation and is dysregulated in chronic lung disease (including COPD). We therefore sought to identify potential culprit mediators of this pathway in the failed alveolar regeneration seen in emphysematous tissue of patients with COPD. Methods: We interrogated a large human ATII-enriched scRNA sequencing dataset (Hu, 2024) for WNT pathway proteins differentially expressed in COPD patient vs. healthy donor ATIIs. The WNT antagonist, WNT Inhibitory Factor-1 (WIF1) was significantly upregulated in COPD ATIIs. We confirmed this difference and co-localization with HTII-280 (ATII marker) in situ with IF staining of human COPD and healthy tissue (n=5 each group). We tested activity of recombinant WIF1 by WNT reporter cell line. We isolated ATII cells (HTII-280+ enriched) and fibroblasts from explanted lungs of COPD and healthy donors for individual testing and study in an alveolar organoid model (as previously described Katsura, 2020). Results: We confirmed significantly upregulated WIF1 expression in COPD vs. healthy donors via qPCR in isolated primary cells enriched for ATIIs. Given WIF1 overexpression is known to induce senescence in non-epithelial cell lines, we also quantified expression of p16 and p21 and found these are also significantly upregulated in COPD. We did find a moderate association by linear regression between fold-increase in senescence marker and WIF1 expression within patient samples with an R2 of.498 and.435 for p16 and p21, respectively. To study the effect on primary human ATIIs, we treated alveolar organoids with 100ng/mL WIF1 (dosing per WNT-reporter testing) for 14D. We found a small decrease in organoid forming capacity (progenitor cell capacity marker) after 14D treatment WIF1 (pilot data n=3 donors, Figure1a). We stimulated primary human fibroblasts isolated from COPD patients and healthy donors (n=2) with Wnt3a (canonical Wnt activator) and treated with WIF1 for 72hrs and found a significant increase in p21 expression in WIF1 treated fibroblasts (Figure1b). Conclusions: We demonstrate a novel potential mediator of ATII progenitor cell dysfunction in COPD associated emphysema, the WNT pathway antagonist – WIF1. We demonstrate this ATII cell derived antagonist is associated with increased markers of senescence in these ATIIs of patients with COPD. Furthermore, we show that this association may be driven by a paracrine signaling mechanism between source ATIIs and neighboring fibroblasts in which senescence is induced.