Artificial intelligence of arterial Doppler waveforms to predict major adverse outcomes among patients with diabetes mellitus.

OBJECTIVE: Patients with diabetes mellitus (DM) are at increased risk for peripheral artery disease (PAD) and its complications. Arterial calcification and non-compressibility may limit test interpretation in this population. Developing tools capable of identifying PAD and predicting major adverse cardiac event (MACE) and limb event (MALE) outcomes among patients with DM would be clinically useful. Deep neural network analysis of resting Doppler arterial waveforms was used to detect PAD among patients with DM and to identify those at greatest risk for major adverse outcome events. METHODS: Consecutive patients with DM undergoing lower limb arterial testing (April 1, 2015-December 30, 2020) were randomly allocated to training, validation, and testing subsets (60%, 20%, and 20%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict all-cause mortality, MACE, and MALE at 5 years using quartiles based on the distribution of the prediction score. RESULTS: Among 11,384 total patients, 4211 patients with DM met study criteria (mean age, 68.6 ± 11.9 years; 32.0% female). After allocating the training and validation subsets, the final test subset included 856 patients. During follow-up, there were 262 deaths, 319 MACE, and 99 MALE. Patients in the upper quartile of prediction based on deep neural network analysis of the posterior tibial artery waveform provided independent prediction of death (hazard ratio [HR], 3.58; 95% confidence interval [CI], 2.31-5.56), MACE (HR, 2.06; 95% CI, 1.49-2.91), and MALE (HR, 13.50; 95% CI, 5.83-31.27). CONCLUSIONS: An artificial intelligence enabled analysis of a resting Doppler arterial waveform permits identification of major adverse outcomes including all-cause mortality, MACE, and MALE among patients with DM.

Assessment of Tissue Viability Following Amputation Surgery Using Near-Infrared Fluorescence Imaging With Indocyanine Green.

BACKGROUND: Patients with chronic limb threatening ischemia have a risk of undergoing a major amputation within 1 year of nearly 30% with a substantial risk of re-amputation since wound healing is often impaired. Quantitative assessment of regional tissue viability following amputation surgery can identify patients at risk for impaired wound healing. In quantification of regional tissue perfusion, near-infrared (NIR) fluorescence imaging using Indocyanine Green (ICG) seems promising. METHODS: This pilot study included adult patients undergoing lower extremity amputation surgery due to peripheral artery disease or diabetes mellitus. ICG NIR fluorescence imaging was performed within 5 days following amputation surgery using the Quest Spectrum PlatformⓇ. Following intravenous administration of ICG, the NIR fluorescence intensity of the amputation wound was recorded for 10 minutes. The NIR fluorescence intensity videos were analyzed and if a fluorescence deficit was observed, this region was marked as "low fluorescence." All other regions were marked as "normal fluorescence." RESULTS: Successful ICG NIR fluorescence imaging was performed in 10 patients undergoing a total of 15 amputations. No "low fluorescence" regions were observed in 11 out of 15 amputation wounds. In 10 out of these 11 amputations, no wound healing problems occurred during follow-up. Regions with "low fluorescence" were observed in 4 amputation wounds. Impaired wound healing corresponding to these regions was observed in all wounds and a re-amputation was necessary in 3 out of 4. When observing time-related parameters, regions with low fluorescence had a significantly longer time to maximum intensity (113 seconds vs. 32 seconds, P = 0.003) and a significantly lesser decline in outflow after five minutes (80.3% vs. 57.0%, P = 0.003). CONCLUSIONS: ICG NIR fluorescence imaging was able to predict postoperative skin necrosis in all four cases. Quantitative assessment of regional perfusion remains challenging due toinfluencing factors on the NIR fluorescence intensity signal, including camera angle, camera distance and ICG dosage. This was also observed in this study, contributing to a large variety in fluorescence intensity parameters among patients. To provide surgeons with reliable NIR fluorescence cut-off values for prediction of wound healing, prospective studies on the intra-operative use of this technique are required. The potential prediction of wound healing using ICG NIR fluorescence imaging will have a huge impact on patient mortality, morbidity as well as the burden of amputation surgery on health care.

The Global Anatomic Staging System Does Not Predict Limb Based Patency of Tibial Endovascular Interventions.

OBJECTIVE: Anatomic grading systems have historically been poor predictors of patency after endovascular tibial interventions. The Global Vascular Guidelines proposed a new Global Anatomic Staging System (GLASS) to estimate one-year limb-based patency (LBP). The purpose of this study was to determine the association of GLASS with LBP following endovascular tibial interventions. METHODS: We included all patients presenting to our multidisciplinary diabetic limb preservation service between 01/2012 and 8/2020 who underwent first-time endovascular tibial revascularization for chronic limb-threatening ischemia. Diagnostic angiograms were reviewed to define the preferred target artery pathway and assign a GLASS stage to each treated limb. One-year LBP was calculated and compared across GLASS stages using Kaplan-Meier curves with log-rank tests and Cox proportional hazards models. RESULTS: We performed tibial revascularization in 96 limbs (5.2% rest pain, 56.3% ulcer, 37.5% gangrene), including isolated tibial interventions in 61.5% and tibial + femoropopliteal interventions in 38.5%. 15.6% of limbs were GLASS stage 1, 28.1% were GLASS stage 2, and 56.3% were GLASS stage 3. Overall, one-year LBP was 43.2 ± 6.3%, and did not differ significantly across GLASS stages (P = 0.42). The hazard ratio for failed LBP was 1.94 (95% CI 0.70-5.41) for GLASS stage 2 and 1.49 (95% CI 0.56-3.94) for GLASS stage 3 limbs (versus GLASS stage 1). When analyzed excluding the calcium modifier, LBP remained similar across GLASS stages (P = 0.72). Major amputation was uncommon, occurring in 9.3 ± 3.4% of limbs at one year, and did not significantly differ by GLASS stage (P = 0.98). CONCLUSION: The Global Anatomic Staging System did not predict limb-based patency following tibial endovascular interventions. Given the low major amputation rates in this cohort, anatomic complexity should not preclude endovascular limb salvage efforts below the knee.

An Extension of the Bollinger Scoring System to Analyse the Distribution of Macrovascular Disease of the Lower Limb in Diabetes.

OBJECTIVE: While it is generally considered that patients with diabetes mellitus (DM) have more distal peripheral arterial disease (PAD), there is little information on how individual vessels are affected. The aim of this study was to adapt Bollinger's scoring system for lower limb angiograms (DSAs) to include the distal and planter vessels. The reliability of this extension was tested and was used to compare the distribution of disease in two cohorts of patients with and without DM. METHODS: Patients who had undergone DSA ± angioplasty for PAD at a single centre between September 2010 and April 2014 were identified. Twenty-five patients' images were reviewed by four clinicians and scored using an extended version of the Bollinger score. A total of 153 patients with DM were matched, for age, sex, ethnicity, smoking, and hypertension, with 153 patients without DM. The infrainguinal vessels were divided into 16 arterial segments, including plantar vessels, and scored using the Bollinger score. The score ranges from 0 to 15. Fifteen represents an arterial segment with more than 50% of its length occluded. Interobserver reliability was tested using interclass correlation (ICC) and Cohen's kappa coefficient. RESULTS: The ICC demonstrated good agreement between observers (0.76 [0.72-0.79]) with good internal consistency (Cronbach's alpha 0.93). When the Bollinger scores were categorised, the results were weaker, Cohen's kappa ranged from 0.39 (standard error 0.033) to 0.54 (0.030). Patients with DM had a higher burden of disease in the anterior tibial and posterior tibial arteries with relative sparing of the peroneal artery and no difference in the plantar vessels. CONCLUSION: It has been demonstrated that the Bollinger score can be extended to include the distal vessels. This amended scoring system can be used to compare the burden of distal disease in patients with PAD. How the score relates to clinical presentation and outcomes needs further investigation.

Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study.

BACKGROUND: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. METHODS: Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. RESULTS: At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (ß coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00-1.04, p < 0.001), triglycerides (0.11, 0.03-0.20, p = 0.007), log(RANKL) (0.07, 0.02-0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15-0.57, p = 0.001), statin use (0.39, 0.06-0.72, p = 0.023) and duration of follow up (0.04, 0.01-0.06, p = 0.004). CONCLUSION: In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy. Trial registration NCT02431234.

Risks and Risk Factors for Ipsilateral Re-Amputation in the First Year Following First Major Unilateral Dysvascular Amputation.

OBJECTIVE: To identify timing, incidence, and risk factors for ipsilateral re-amputation within 12 months of first dysvascular amputation and to determine specific subgroups of patients at each amputation level that are at increased risk. METHODS: A retrospective cohort study evaluating 7187 patients with first unilateral transmetatarsal (TM), transtibial (TT), or transfemoral (TF) amputation secondary to diabetes and/or peripheral artery disease (PAD) were identified in the VA Surgical Quality Improvement Program database between 2004 and 2014. Re-amputation was defined as any subsequent ipsilateral soft tissue/bony revision or amputation to a higher level. Twenty-three potential pre-operative risk factors (and nine potential interactions) were identified. A backward stepwise Cox regression was used to identify risk factors. Incidence rates and hazard ratios (HR) with 95% confidence intervals (CI) were computed. RESULTS: The median time to highest level of re-amputation in the first year was 33 (interquartile range, 13-73) days. Risk of requiring at least one re-amputation was 41% (TM), 25% (TT), and 9% (TF). Risk factors associated with requiring re-amputation included chronic obstructive pulmonary disease, elevated white blood cell count, abnormal ankle brachial index (ABI), history of revascularisation, and alcohol misuse. TM patients who had diabetes only (HR 1.9; 95% CI 1.4-2.5), diabetes with an abnormal ankle brachial index (ABI) score (HR 2.4; 95% CI 1.8-3.2), and kidney failure (HR 1.7; 95% CI 1.3-2.1) were at the greatest risk of re-amputation. TT amputees who were smokers were also at an increased risk (HR 1.4; 95% CI 1.2-1.6). CONCLUSION: This research identified important risk factors for failure of primary healing and need for re-amputation at the TM and TT level. If considering a TM amputation, caution should be exercised in patients with diabetes, in particular those with an abnormal ABI and/or renal failure. At the TT level, caution should be exercised in those who smoke.

Association of Serum Adiponectin with Intima Media Thickness of Dorsalis Pedis Artery and Macroangiopathy in Type 2 Diabetes.

OBJECTIVE: To investigate the association of the serum adiponectin level with the intima media thickness of the dorsalis pedis artery (D-IMT) and macroangiopathy in type 2 diabetes (T2DM). METHODS: We recruited 173 patients with T2DM, of whom 83 had macroangiopathy (MA group) and 90 did not have macroangiopathy (NM group), and 40 normal control subjects (NC group). We measured D-IMT using color B-mode Doppler ultrasonography. Serum adiponectin, blood glucose, lipids, and other clinical characteristics were analyzed. Participants were divided into three subgroups according to serum adiponectin level (high, moderate, and low). RESULTS: Compared with the NM and NC groups, serum adiponectin levels were significantly decreased in the MA group after adjusting for sex and body mass index. Compared with the NM and NC groups, D-IMT was significantly increased in the MA group. Compared with the moderate- and high-adiponectin subgroups, D-IMT was significantly increased in the low-adiponectin subgroup. The prevalence of diabetic macroangiopathy increased gradually with decreasing adiponectin levels. After controlling for age, sex, smoking, and alcohol drinking, partial correlation analysis showed that adiponectin was negatively correlated with D-IMT. Elevated serum adiponectin was independently associated with a decreased risk for diabetic macroangiopathy by logistic regression analysis. Multiple linear regression analysis revealed that adiponectin was an independent factor of D-IMT. In receiver operating characteristic analyses, the area under the curve for traditional risk factors plus adiponectin for prediction of macroangiopathy was 0.984, while that of traditional risk factors alone was 0.972. CONCLUSIONS: Adiponectin is lower in patients with T2DM with macroangiopathy. We suggest that D-IMT could represent a noninvasive indicator of diabetic macroangiopathy. Decrease of adiponectin as an independent risk factor for both macroangiopathy and D-IMT among Chinese patients with T2DM suggests that adiponectin might have clinical utility in the prediction of diabetic macroangiopathy. This clinical trial is registered in the "Chinese Clinical Trial Registry." The registration number is ChiCTR-ROC-17011731.

Critical analysis and limitations of resting ankle-brachial index in the diagnosis of symptomatic peripheral arterial disease patients and the role of diabetes mellitus and chronic kidney disease.

BACKGROUND: The ankle-brachial index (ABI) may underestimate the severity of peripheral arterial disease (PAD) in patients with noncompressible vessels. This study analyzed limitations of the ABI and toe-brachial index (TBI), if done alone, in patients with symptomatic PAD, diagnosed by duplex ultrasound (DUS) examination, particularly in patients with diabetes and chronic kidney disease (CKD). METHODS: This is a retrospective review of prospectively collected data. All patients underwent resting ABIs, TBI, and/or DUS. An ABIs of 0.90 or less in either leg was considered abnormal, and the term inconclusive ABIs (noncompressibility) was used if the ABI was 1.3 or greater. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy (OA) of ABIs in detecting 50% or greater stenosis of any arterial segment based on DUS were determined. A TBI of less than 0.7 was considered abnormal. RESULTS: We included 2226 ABIs and 1383 DUS examinations: 46% of patients had diabetes, 16% had CKD, and 39% had coronary artery disease. Fifty-three percent of the ABIs were normal, 34% were abnormal, and 13% were inconclusive. For patients with limb-threatening ischemia, 40% had normal ABIs, 40% abnormal ABIs, and 20% were inconclusive. The sensitivity and OA for ABIs in detecting 50% or greater stenosis in the whole series were 57% (95% confidence interval [CI], 53.7-61.2) and 74% (95% CI, 71.9-76.6); for diabetics 51% (95% CI, 46.1-56.3) and 66% (95% CI, 62.3-69.8); nondiabetics 66% (95% CI, 59.9-70.9) and 81% (95% CI, 78.2-83.9). For patients with CKD, the sensitivity and OA for ABIs in detecting 50% or greater stenosis was 43% (95% CI, 34.3-52.7) and 67% (95% CI, 60.2-73.0) versus patients with no CKD 60% (95% CI, 56.3-64.6) and 76% (95% CI, 73.1-78.1). If patients with inconclusive ABIs were excluded, these values were 69% (95% CI, 65.2-72.9) and 80% (95% CI, 77.2-81.9) in the whole series; 67% (95% CI, 61.6-72.7) and 75% (95% CI, 70.5-78.4) for diabetics; and 63% (95% CI, 51.3-73.0) and 78% (95% CI, 70.6-83.9) for patients with CKD. Thirty-three percent of TBIs were normal and 67% were abnormal. The sensitivity and OA for abnormal TBI in detecting 50% or greater stenosis were 85% (95% CI, 78.9-90.0) and 75% (95% CI, 70.1-80.2) in the whole series; 84% (95% CI, 76.0-90.3) and 74% (95% CI, 67.1-80.2) for diabetics; and 77% (95% CI, 61.4-88.2) and 72% (95% CI, 59.9-82.3) for patients with CKD. For those with inconclusive ABIs, these values for TBI were 75% and 69%. CONCLUSIONS: Of symptomatic patients with PAD with 50% or greater stenosis on DUS examination, 43% had normal/inconclusive resting ABIs (49% in diabetics and 57% in CKD). TBI may help in patients with inconclusive ABIs. These patients should undergo further imaging to determine proper treatment.

Screening mammography beyond breast cancer: breast arterial calcifications as a sex-specific biomarker of cardiovascular risk.

PURPOSE: To highlight the importance of quantitative breast arterial calcifications (BAC) assessment for an effective stratification of cardiovascular (CV) risk in women, for whom current preventive strategies are inadequate. BAC, easily detectable on mammograms, are associated with CV disease and represent a potential imaging biomarker for CV disease prevention in women. METHOD: We summarized the available evidence on this topic. RESULTS: Age, parity, diabetes, and hyperlipidemia were found to positively correlate with BAC. Women with BAC have a higher CV risk than those without BAC: the relative risk was reported to be 1.4 for transient ischemic attack/stroke, 1.5 for thrombosis, 1.8 for myocardial infarction; the reported hazard ratio was 1.32 for coronary artery disease (CAD), 1.52 for heart failure, 1.29 for CV death, 1.44 for death from CAD. However, BAC do not alarm radiologists; when reported, they are commonly mentioned as "present", not impacting on CV decision-making. Of 18 published studies, 9 reported only presence/absence of BAC, 4 used a semi-quantitative scale, and 5 a continuous scale (with manual, automatic or semiautomatic segmentation). Various appearance, topological complexity, and vessels overlap make BAC quantification difficult to standardize. Nevertheless, machine learning approaches showed promising results in BAC quantification on mammograms. CONCLUSIONS: There is a strong rationale for mammography to become a dual test for breast cancer screening and CV disease prevention. However, robust and automated quantification methods are needed for a deeper insight on the association between BAC and CV disease, to stratifying CV risk and define personalized preventive actions.

The role of coronary artery bypass surgery versus percutaneous intervention in patients with diabetes and coronary artery disease.

Patients with diabetes mellitus (DM) often exhibit a complex coronary anatomy, making coronary revascularization challenging. Coronary artery bypass grafting surgery (CABG) is currently considered the preferred revascularization method in patients with DM and multivessel disease. Percutaneous coronary intervention (PCI) has advanced with new stent generations having been developed in the recent years, but they have not yet been adequately compared against CABG in the population with DM. Comorbidities, such as renal disease and heart failure, lead to worse prognosis following a revascularization procedure and require especial consideration when choosing between CABG versus PCI. The presence of significant left main disease may also impose additional challenges to coronary revascularization, particularly when accompanied by the involvement of multivessel disease. Most of the evidence regarding revascularization in patients with DM is compiled from studies enrolling patients with stable ischemic heart disease, and trials with patients in the acute coronary syndrome setting are lacking.

Long-term Outcomes of an Endovascular-First Approach for Diabetic Patients With Predominantly Tibial Disease Treated in a Multidisciplinary Setting.

BACKGROUND: Randomized studies suggest that open lower extremity revascularization procedures are associated with improved outcomes compared with endovascular peripheral vascular interventions (PVIs). However, advances in endovascular technologies and treatment by multidisciplinary limb preservation teams have shown improved outcomes. The aim of our study was to compare perioperative and long-term outcomes after open versus PVI procedures in diabetic patients with chronic limb-threatening ischemia (CLTI) treated in a multidisciplinary setting. METHODS: All patients presenting to our multidisciplinary diabetic limb-preservation service from 6/2012 to 07/2018 were enrolled in a prospective database. Patients who underwent either an open lower extremity bypass (LEB) or a PVI for CLTI were included in the analysis. Perioperative (30-day) complications and 4-year patency and limb salvage rates were compared between PVI and LEB using chi-squared tests, Kaplan-Meier curve analyses, and stepwise multivariable Cox proportional hazards models. RESULTS: A total of 195 lower extremity revascularization procedures were performed in 120 patients (mean age: 65.0 ± 1.0 years, 61.7% male, 63.3% black), including 53 (27.2%) open procedures and 142 (72.8%) PVIs. Nearly two-thirds of procedures (65.6%) treated multilevel diseases, while 27.2% treated isolated tibial disease and 7.2% treated isolated femoropopliteal disease. More than half of the procedures (53.3%) were performed for Wound, Ischemia, and foot Infection (WIfI) classification stage 4 limbs, 25.1% for stage 3, and 21.6% for stage 1/2. In the LEB group, 67.9% of targets were infrapopliteal. In the PVI group, 63.4% of procedures were isolated tibial interventions or were multilevel interventions including the tibial segment. Perioperative complications occurred in 52.8% of LEB versus 12.0% of PVI (P < 0.001). At 4 years postoperatively, there was no significant difference in crude (unadjusted) primary patency for PVI versus LEB (34.5 ± 6.6% vs. 49.6 ± 8.1, P = 0.89). Secondary patency was better for the LEB group (50.3 ± 7.4% vs. 55.4 ± 7.5%; P = 0.04), but amputation-free survival was similar (65.1 ± 6.7% vs. 60.9 ± 9.7%; P = 0.79). After adjusting for baseline differences between groups, primary patency (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.34 to 1.10) and amputation-free survival (HR: 1.51; 95% CI: 0.71 to 2.34) remained similar for PVI versus LEB, but secondary patency was persistently lower for PVI (HR: 0.35; 95% CI: 0.14 to 0.90). CONCLUSIONS: In this cohort of diabetic patients with CLTI undergoing predominantly tibial interventions, open revascularization was associated with a higher risk of perioperative complications than PVIs. While secondary patency rates were better after LEBs, our data suggest that an endovascular-first approach results in equivalent long-term amputation-free survival for diabetic patients treated in a multidisciplinary setting.

Treatment of symptomatic coral reef aorta by a nitinol self-expanding stent.

Coral reef aorta (CRA) is a rare condition, characterised by rock-hard calcification of the juxta-renal and supra-renal aorta with luminal encroachment causing significant stenosis of the aorta and its branches. It usually presents as resistant hypertension, renal dysfunction, mesenteric ischaemia, limb claudication or embolic manifestations. Although surgical thrombo-endarterectomy along with bypass graft to the affected visceral arteries remains the cornerstone of treatment, it is associated with considerable mortality and morbidity, especially in patients with pre-existing comorbidities. Here we report an elderly female of resistant hypertension, who had successful endovascular aortic stenting using a non-graft self-expanding stent. Her blood pressure dramatically improved following endovascular management. In comparison to the conventional surgical approach, endovascular stenting can be an alternative, less invasive approach in selected CRA patients.

Plantar Acceleration Time: A Novel Technique to Evaluate Arterial Flow to the Foot.

BACKGROUND: Arterial duplex ultrasound (DUS) and ankle-brachial indices (ABIs) are accepted methods for assessing lower limb arterial perfusion. However, in a significant number of diabetic patients, medial wall calcification often precludes an ABI measurement. Direct, noninvasive duplex imaging of the pedal arch in the setting of peripheral arterial disease (PAD) has not been well evaluated. Although plantar arch interrogation is new to vascular ultrasound, imaging the plantar arteries appears to be a reliable angiographic technique for critical limb ischemia. We sought to define the utility of Plantar Acceleration Time as a surrogate for ABIs. METHODS: Patients undergoing DUS including Plantar Acceleration Time for suspicion of PAD were retrospectively reviewed in a prospective database over a 1-year period. Two hundred fifty nondiabetic patients (499 limbs) with documented ABI were studied. Plantar Acceleration Time was calculated (milliseconds [msec]) in each limb in the lateral plantar artery. Statistical analyses were performed using linear regression and analysis of variance testing using Microsoft Excel database (version 2016; Microsoft Corp, Redmond, WA). Patients were then grouped into 4 classes based on their clinical symptoms and ABI. Plantar Acceleration Time was similarly grouped into 4 distinct classes and correlated with the clinical and ABI classes. RESULTS: Plantar Acceleration Time correlated significantly with ABI (P < 0.001). There were significant differences in Plantar Acceleration Times between each class based on ABI and clinical presentation (P < 0.001 for each): Class 1 Plantar Acceleration Times 89.9 ± 15.5 msec; Class 2, 152.3 ± 28.4 msec; Class 3, 209.8 ± 25.5 msec, and Class 4, 270.2 ± 35.3 msec. CONCLUSIONS: Plantar Acceleration Time demonstrates a high correlation with ABI in patients with compressible arteries. Based on our results we propose the following categories of Plantar Acceleration Time, which appear to correlate with both clinical and ABI findings. ABI of 0.90-1.3 correlates with a Plantar Acceleration Time of 0-120 msec, ABI of 0.69-0.89 correlates with a Plantar Acceleration Time of 121-180 msec, ABI of 0.40-0.68 correlates with a Plantar Acceleration Time of 181-224 msec, and an ABI of 0.00-0.39 correlates with a Plantar Acceleration Time of greater than 225 msec. Further studies are ongoing to confirm whether Plantar Acceleration Time may be a suitable substitute to ABIs in patients with noncompressible arteries that preclude meaningful ABIs and gives more information regarding targeted angiosome perfusion to the foot.

Brachial intima-media thickness is associated with coronary artery atherosclerosis in patients with diabetes mellitus.

Coronary artery calcification (CAC) as measured by computed tomography is a strong predictor of coronary artery disease. The brachial intima-media thickness (IMT) was recently reported to be associated with cardiovascular risk factors. This study investigated the association of brachial IMT with CAC, which is a marker of coronary artery atherosclerosis, in patients with diabetes. We enrolled 292 patients with diabetes (mean age, 65 ± 12 years; 59% men) who underwent both endothelial function testing and computed tomography for risk assessment of coronary artery disease. Flow-mediated dilation (FMD) and IMT in the brachial artery were measured with a specialized machine. FMD was lower and brachial IMT was thicker in patients with than without CAC. The CAC score was significantly correlated with both brachial IMT and FMD, while the multivariate logistic analysis demonstrated that brachial IMT (> 0.32 mm) but not FMD (< 5.1%) was significantly associated with the presence of CAC (odds ratio, 2.03; 95% confidence interval, 1.10-3.77; p = 0.02). The receiver operating characteristic curve analysis showed that the area under the curve for discriminating patients with CAC was 0.67 for IMT (p < 0.001) and 0.62 for FMD (p < 0.001). When patients were classified into four groups based on brachial IMT and FMD, the CAC score was higher in patients with thicker brachial IMT and lower FMD than in patients of the other groups (p < 0.001). Measurement of brachial IMT could be useful for the risk assessment of patients with diabetes.

The impact of autoimmune thyroiditis on skin microcirculation in children with non-complicated type 1 diabetes mellitus.

BACKGROUND: The impairment of endothelial function in type 1 diabetes mellitus (DM1) is considered as the basis of microvascular complications. In DM1 patients autoimmune thyroiditis is a frequent comorbidity which may be responsible for further deterioration of microcirculation function. In studies investigating the relationship between cardiovascular risk factors and microvascular function, skin microcirculation is widely used. The aim of our study was to evaluate the impact of coexisting autoimmune thyroiditis on skin microcirculation in children with type I diabetes mellitus. SUBJECTS: The study group consisted of 25 pediatric DM1 patients, 25 pediatric patients with type 1 diabetes and autoimmune thyroiditis (DM1 + AIT) and 29 control subjects matched for age and gender. The DM1 and DM1 + AIT patients were also matched for age at onset of DM and diabetes duration. METHODS: Performed capillaroscopy studies employed non-selective stimuli such as post-occlusive reactive hyperemia (PORH) and venous occlusion (VO) tests. The relative area covered by capillaries (coverage) and the distance between capillaries were assessed. These measurements were performed before tests as well as after PORH and VO. RESULTS: Coverage at baseline, after PORH and VO and distance after VO differ significantly between control subjects and the group DM1 + AIT. The coverage at baseline, after PORH and VO were significantly smaller in DM1 + AIT compared with the control group. Post-hoc analysis after controlling for lipids levels showed that differences between the DM1 + AIT and control group were remained only for coverage at baseline and after VO. Significant differences between DM1 + AIT and DM1 and control group for coverage after VO were also presented. CONCLUSIONS: Coexisting autoimmune thyroiditis significantly deteriorates skin microcirculation function in pediatric non-complicated type 1 diabetic patients. This process is independent of patient age, diabetes duration and age of diabetes onset.

Microsurgical Reconstruction of the Plantar Foot: Long-Term Functional Outcomes and Quality of Life.

BACKGROUND: When faced with plantar defects, reconstruction of the weight-bearing areas presents unique surgical challenges. Several free flap modalities have been described in this respect, but there remains debate regarding the best-suited flap modality. Aim of this study was to compare free muscle and non-neurotized fasciocutaneous flaps for plantar reconstruction with respect to long-term functional outcomes. METHODS: Overall, 89 patients received 100 free flaps (anterolateral thigh [ALT] n = 46; gracilis n = 54) for plantar reconstruction. The data were screened for patients' demographics, as well as perioperative details. Postoperative complications were accounted for and the two groups compared accordingly. All patients were contacted for a long-term follow-up examination. RESULTS: There were no significant differences between the two groups regarding major (24 vs. 17%; p = 0.366) and minor surgical complications (61 vs. 70%; p = 0.318). However, the ALT group showed a significantly higher need for secondary surgeries (39 vs. 19%; p = 0.022). Sixty-eight patients (76%) returned for long-term follow-up evaluation (mean: 51.2 months, range: 13-71 months). The ALT group showed significantly less pain at the recipient (p = 0.0004) and donor (p = 0.010) sites, and scar assessment revealed significantly better results (p < 0.001). Additionally, the ALT group showed better depth (p = 0.017) and superficial (p = 0.007) sensation and enabled better shoe provision (p = 0.014). CONCLUSION: Both the free ALT and gracilis flaps are well suited for plantar reconstruction, yielding overall similar functional outcomes. However, the ALT flap produces less scarring and pain, while showing better recovery of sensation and enabling better shoe provision. The ALT flap thus presents our preferred option.

Evaluation of Vascular Remodeling in Carotid Atherosclerosis Among Type 2 Diabetes Mellitus Patients Using High-Frequency Ultrasonography Combined with Serum Resistin.

Diabetes remains a long standing public health issue among the Chinese population, with an incidence of up to 11.6%, of which type 2 diabetes mellitus (T2DM) accounts for 85%-95%. During this study, we aimed to elucidate the value of high-frequency ultrasonography (HFUS) combined with serum resistin on vascular remodeling (VR) in carotid atherosclerosis (CA) among patients suffering from T2DM. A total of 432 T2DM were recruited and assigned into the short T2DM duration group (<5 years), middle T2DM duration group (5~10 years) and long T2DM duration group (>10 years), while another 172 healthy cases were recruited as the control group. The intima-media thickness (IMT) as well as plaque score, detection rate and type were detected by the HFUS. The respective blood pressure readings were measured and pulse pressure was calculated accordingly. The serum resistin level, remodeling incidence and type, levels of total cholesterol (TC), fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), high-density liproprotein cholesterol (HDL-C), and triglyceride (TG) were measured. The correlation between IMT, the plaque detection rate and blood pressure were analyzed. A receiver operating characteristic (ROC) curve was constructed in order to evaluate the impact of VR in CA on T2DM patients who were solely using HFUS and serum resistin respectively, as well as a combination of HFUS with serum resistin. As In comparison with the control group, the short, middle and long T2DM duration groups all displayed increased IMT, plaque score and detection rate, serum resistin level and VR incidence, especially for the long T2DM duration group. Levels of TC, TG, FBG and LDL-C were much higher while HDL-C was lower among patients with T2DM than those in the control group. A positive correlation was detected between the disease course and IMT. The detection rate of plaque with thickening IMT exhibited upregulated levels when compared to those with normal IMT. The HFUS, serum resistin and HFUS combined with serum resistin respective areas under the ROC curve were 0.873, 0.867 and 0.923, respectively, suggesting that the combination of HFUS and serum resistin was superior to that of individual HFUS or individual serum resistin in regard to the impact of VR in CA on T2DM patients. The results of this study revealed that the combination of HFUS and serum resistin was superior to individual HFUS or individual serum resistin in relation to its ability to evaluate the impact of VR in CA in patients with T2DM.

Near-instant noninvasive optical imaging of tissue perfusion for vascular assessment.

BACKGROUND: Noninvasive vascular tests are critical for identifying patients who may benefit from surgical revascularization, but current tests have significant limitations in people with diabetes. This study aimed to evaluate the ability of spatial frequency domain imaging (SFDI), an optical imaging method capable of measuring tissue oxygen saturation (StO2) and tissue hemoglobin, to assess lower extremity blood supply. METHODS: Ankle-brachial index, toe-brachial index, pedal Doppler waveforms, and SFDI images were prospectively evaluated in 47 consecutive patients with and without diabetes in whom there was concern for peripheral artery disease (PAD). SFDI is a noncontact optical imaging technology that uses structured illumination to quantify subsurface (2-3 mm in depth) StO2 and tissue hemoglobin in the dermal microcirculation (HbT1) and macrocirculation (HbT2) over a large field of view (15 × 20 cm) within 10 seconds. RESULTS: This demonstrates the ability of SFDI to capture reliable clinical measurements of perfusion in plantar aspects of the feet. SFDI StO2 values differentiate nondiabetic patients with and without arterial disease, defined as ankle-brachial index <0.9 (P = .06), but are limited in those with diabetes (P = .43). An elevated StO2 and reduced HbT1 are observed in people with diabetes compared with nondiabetic patients (P < .05). An SFDI-derived HbT2/HbT1 index differentiates diabetics with PAD vs no PAD (P < .01) using toe-brachial index <0.7 as a cutoff for PAD in diabetes. CONCLUSIONS: SFDI is a feasible, rapid, and easy to use widefield measurement of perfusion in a clinical setting. This first-of-use study suggests that the technology has potential to evaluate lower extremity perfusion in people with and without diabetes. Further studies with increased numbers of patients and end points including wound healing will need to be designed to fully evaluate the applicability of this new technology.

Modified VEGF-A mRNA induces sustained multifaceted microvascular response and accelerates diabetic wound healing.

Capable of mediating efficient transfection and protein production without eliciting innate immune responses, chemically modified mRNA holds great potential to produce paracrine factors at a physiologically beneficial level, in a spatiotemporally controlled manner, and with low toxicity. Although highly promising in cardiovascular medicine and wound healing, effects of this emerging therapeutic on the microvasculature and its bioactivity in disease settings remain poorly understood. Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo. Using multi-parametric photoacoustic microscopy, we show that intradermal injection of AZD8601 formulated in a biocompatible vehicle results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, we evaluate the bioactivity of AZD8601 in a mouse model of diabetic wound healing in vivo. Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing.