Assessment of revascularization impact on microvascular oxygenation and perfusion using spatial frequency domain imaging.

The microvasculature (with vessels <100 µm in diameter) plays a crucial role in tissue oxygenation, perfusion and wound healing in the lower limb. While this holds clinical significance, microvasculature evaluation in the limbs is not a standard practice. Surgical interventions focus on reestablishing blood flow in larger vessels affected by the peripheral artery disease (PAD). Nevertheless, the impact of revascularization on tissue oxygenation and perfusion in severe microvascular disease (MVD) is still unknown. We present the cases of two patients who underwent surgical revascularization for peripheral blood flow with different outcomes. Patient A had PAD, while B had PAD, severe MVD and a non-healing wound. Although both showed improvements in ankle-brachial index post-op, spatial frequency domain imaging metrics (which measure microvascular oxygenation and perfusion) remained unchanged in B, indicating a potential gap in assessing the surgical efficacy in MVD using ankle brachial index and emphasizing microcirculation evaluation in optimizing wound healing outcomes.

Association between race/ethnicity and the risk of amputation of lower extremities among medicare beneficiaries with diabetic foot ulcers and diabetic foot infections.

INTRODUCTION: This study aimed to examine the association of race and ethnicity on the risk of lower extremity amputations among Medicare beneficiaries with diabetic foot ulcers (DFUs) and diabetic foot infections (DFIs). RESEARCH DESIGN AND METHODS: A retrospective study included 2011-2015 data of a 5% sample of fee-for-service Medicare beneficiaries with a newly diagnosed DFU and/or DFI. The primary outcome was the time to the first major amputation episode after a DFU and/or DFI were identified using the diagnosis and procedure codes. We used multivariable Cox proportional hazards models to estimate the risk of time to the first major amputation across races, adjusting for sociodemographic and health status factors. Adjusted hazard ratios (aHRs) with a 95% CI were reported. RESULTS: Among 92 929 Medicare beneficiaries newly diagnosed with DFUs and/or DFIs, 77% were whites, 14.3% African Americans (AAs), 3.3% Hispanics, 0.7% Native Americans (NAs), and 4.0% were other races. The incidence rates of major amputation were 0.02 person-years for NAs, 0.02 person-years for AAs, 0.01 person-years for Hispanics, 0.01 person-years for other races, and 0.01 person-years for whites (p<0.05). Multivariable analysis showed that AAs (aHR=1.9, 95% CI 1.7 to 2.2, p<0.0001) and NAs (aHR=1.8, 95% CI 1.3 to 2.6, p=0.001) were associated with an increased risk of major amputation compared with whites. Beneficiaries with DFUs and/or DFIs diagnosed by a podiatrist or primary care physician (aHR=0.7, 95% CI 0.6 to 0.8, p<0.0001, specialists as reference) or at an outpatient visit (aHR=0.3, 95% CI 0.3 to 0.3, p<0.0001, inpatient stay as reference) were associated with a decreased risk of major amputation. CONCLUSIONS: Racial and ethnic disparities in the risk of lower extremity amputations appear to exist among fee-for-service Medicare beneficiaries with diabetic foot problems. AAs and NAs with DFUs and/or DFIs were associated with an increased risk of major amputations compared with white Medicare beneficiaries.

Correction: Disparities in outcomes of patients admitted with diabetic foot infections.

[This corrects the article DOI: 10.1371/journal.pone.0211481.].

Disparities in outcomes of patients admitted with diabetic foot infections.

OBJECTIVE: The purpose of this study was to evaluate the disparities in the outcomes of White, African American (AA) and non-AA minority (Hispanics and Native Americans (NA)), patients admitted in the hospitals with diabetic foot infections (DFIs). RESEARCH DESIGN AND METHODS: The HCUP-Nationwide Inpatient Sample (2002 to 2015) was queried to identify patients who were admitted to the hospital for management of DFI using ICD-9 codes. Outcomes evaluated included minor and major amputations, open or endovascular revascularization, and hospital length of stay (LOS). Incidence for amputation and open or endovascular revascularization were evaluated over the study period. Multivariable regression analyses were performed to assess the association between race/ethnicity and outcomes. RESULTS: There were 150,701 admissions for DFI, including 98,361 Whites, 24,583 AAs, 24,472 Hispanics, and 1,654 Native Americans (NAs) in the study cohort. Overall, 45,278 (30%) underwent a minor amputation, 9,039 (6%) underwent a major amputation, 3,151 underwent an open bypass, and 8,689 had an endovascular procedure. There was a decreasing incidence in major amputations and an increasing incidence of minor amputations over the study period (P < .05). The risks for major amputation were significantly higher (all p<0.05) for AA (OR 1.4, 95%CI 1.4,1.5), Hispanic (OR 1.3, 95%CI 1.3,1.4), and NA (OR 1.5, 95%CI 1.2,1.8) patients with DFIs compared to White patients. Hispanics (OR 1.3, 95%CI 1.2,1.5) and AAs (OR 1.2, 95%CI 1.1,1.4) were more likely to receive endovascular intervention or open bypass than Whites (all p<0.05). NA patients with DFI were less likely to receive a revascularization procedure (OR 0.6, 95%CI 0.3, 0.9, p = 0.03) than Whites. The mean hospital length of stay (LOS) was significantly longer for AAs (9.2 days) and Hispanics (8.6 days) with DFIs compared to Whites (8.1 days, p<0.001). CONCLUSION: Despite a consistent incidence reduction of amputation over the past decade, racial and ethnic minorities including African American, Hispanic, and Native American patients admitted to hospitals with DFIs have a consistently significantly higher risk of major amputation and longer hospital length of stay than their White counterparts. Native Americans were less likely to receive revascularization procedures compared to other minorities despite exhibiting an elevated risk of an amputation. Further study is required to address and limit racial and ethnic disparities and to further promote equity in the treatment and outcomes of these at-risk patients.

Endothelial vascular cell adhesion molecule 1 is a marker for high-risk carotid plaques and target for ultrasound molecular imaging.

BACKGROUND: Molecular imaging of carotid plaque vulnerability to atheroembolic events is likely to lead to improvements in selection of patients for carotid endarterectomy (CEA). The aims of this study were to assess the relative value of endothelial inflammatory markers for this application and to develop molecular ultrasound contrast agents for their imaging. METHODS: Human CEA specimens were obtained prospectively from asymptomatic (30) and symptomatic (30) patients. Plaques were assessed by semiquantitative immunohistochemistry for vascular cell adhesion molecule 1 (VCAM-1), lectin-like oxidized low-density lipoprotein receptor 1, P-selectin, and von Willebrand factor. Established small peptide ligands to each of these targets were then synthesized and covalently conjugated to the surface of lipid-shelled microbubble ultrasound contrast agents, which were then evaluated in a flow chamber for binding kinetics to activated human aortic endothelial cells under variable shear conditions. RESULTS: Expression of VCAM-1 on the endothelium of CEA specimens from symptomatic patients was 2.4-fold greater than that from asymptomatic patients (P < .01). Expression was not significantly different between groups for P-selectin (P = .43), von Willebrand factor (P = .59), or lectin-like oxidized low-density lipoprotein receptor 1 (P = .99). Although most plaques from asymptomatic patients displayed low VCAM-1 expression, approximately one in five expressed high VCAM-1 similar to plaques from symptomatic patients. In vitro flow chamber experiments demonstrated that VCAM-1-targeted microbubbles bind cells that express VCAM-1, even under high-shear conditions that approximate those found in human carotid arteries, whereas binding efficiency was lower for the other agents. CONCLUSIONS: VCAM-1 displays significantly higher expression on high-risk (symptomatic) vs low-risk (asymptomatic) carotid plaques. Ultrasound contrast agents bearing ligands for VCAM-1 can sustain high-shear attachment and may be useful for identifying patients in whom more aggressive treatment is warranted.

RhoGEF and positioning of rappaport-like furrows in the early Drosophila embryo.

Early Drosophila embryogenesis is characterized by shifting from astral microtubule-based to central spindle-based positioning of cleavage furrows. Before cellularization, astral microtubules determine metaphase furrow position by producing Rappaport-like furrows, which encompass rather than bisect the spindle. Their positioning is explained by our finding that the conserved central spindle components centralspindlin (mKLP1 and RacGAP50C), Polo, and Fascetto (Prc1) localize to the astral microtubule overlap region. These components and the chromosomal passenger complex localize to the central spindle, though no furrow forms there. We identify the maternally supplied RhoGEF2 as a key factor in metaphase furrow positioning. Unlike the zygotic, central spindle-localized RhoGEF (Pebble), RhoGEF2 localizes to metaphase furrows, a function distinct from RhoGEF/Pebble and likely due to the absence of a RacGAP50C binding domain. Accordingly, we find that ectopic activation of Rho GTPase generates furrows perpendicular to the central spindle during syncytial divisions. Whereas metaphase furrow formation is myosin independent, these ectopic furrows, like conventional furrows, require myosin as well as microtubules. These studies demonstrate that early Drosophila embryogenesis is primed to form furrows at either overlapping astral microtubules or the central spindle. We propose that the shift to the latter is driven by a corresponding shift from RhoGEF2 to Pebble in controlling furrow formation.