The Prostacyclin Analogue Iloprost as an Early Predictor of Successful Revascularization in Diabetic Patients Affected by Critical Limb Ischemia and Foot Ulcers

Abstract Purpose The aim of this study is to evaluate the role of Iloprost as an early predictor of successful revascularization in patients affected by ischemic diabetic foot ulcers (DFUs). Methods Consecutive patients with ischemic DFUs with persistent low TcPO2 ( All patients underwent Iloprost infusion and TcPO2 has been recorded at days 3, 14 and 30. According to the TcPO2 reported at day 3, patients were divided into two groups: group A (patients with TcPO2 ≥30mmHg) and group B (patients with TcPO2  Results Twenty-five patients have been included, 12/25 (48%) in Group A and 13/25 (52%) in Group B. There were no significant differences at the baseline and one day after PTA between the two groups while TcPO2 values recorded in Group A at days 3, 14 and 30 after Iloprost infusion were significant higher in comparison to the Group B (χ = 0.005). The rate of re-PTA were respectively 33,3% (Group A) and 53,8% (Group B) (p = 0.03). Conclusions Iloprost may be an early predictor of successful revascularization in patients affected by critical limb ischemia (CLI) and DFUs

Diabetic Foot Infections:The Diagnostic Challenges

Diabetic foot infections (DFIs) are severe complications of long-standing diabetes, and they represent a diagnostic challenge, since the differentiation between osteomyelitis (OM), soft tissue infection (STI), and Charcot's osteoarthropathy is very difficult to achieve. Nevertheless, such differential diagnosis is mandatory in order to plan the most appropriate treatment for the patient. The isolation of the pathogen from bone or soft tissues is still the gold standard for diagnosis; however, it would be desirable to have a non-invasive test that is able to detect, localize, and evaluate the extent of the infection with high accuracy. A multidisciplinary approach is the key for the correct management of diabetic patients dealing with infective complications, but at the moment, no definite diagnostic flow charts still exist. This review aims at providing an overview on multimodality imaging for the diagnosis of DFI and to address evidence-based answers to the clinicians when they appeal to radiologists or nuclear medicine (NM) physicians for studying their patients

Results of a prospective observational study of autologous peripheral blood mononuclear cell therapy for no-option critical limb-threatening ischemia and severe diabetic foot ulcers

Cell therapy with autologous peripheral blood mononuclear cells (PB-MNCs) may help restore limb perfusion in patients with diabetes mellitus and critical limb-threatening ischemia (CLTI) deemed not eligible for revascularization procedures and consequently at risk for major amputation (no-option). Fundamental is to establish its clinical value and to identify candidates with a greater benefit over time. Assessing the frequency of PB circulating angiogenic cells and extracellular vesicles (EVs) may help in guiding candidate selection

Below-the-ankle arterial disease: a new marker of coronary artery disease in patients with diabetes and foot ulcers

Aim The aim of the current study is to evaluate the association between below-the-ankle (BTA) arterial disease and coronary artery disease (CAD) in patients with diabetic foot ulcers (DFUs). Methods The study group was composed of patients with an active neuro-ischaemic DFUs managed in a tertiary care diabetic foot clinic. All patients received a pre-set limb salvage protocol including lower limb revascularization. By a retrospective analysis of individual angiograms, patients were divided in two groups: below-the-ankle (BTA) and above-the-ankle (ATA) arterial disease groups. The rate of CAD at baseline assessment and the new events of acute myocardial ischaemia (AMI) during 1-year of follow-up were evaluated and compared between the two groups. Results Two hundreds seventy-two (272) patients were included, 120 (44.1%) showed BTA arterial disease while 152 (55.9%) ATA arterial disease. The mean age was 68.9 +/- 9.6 years, 198 (72.8%) were male, 246 (90.4%) had type 2 diabetes, the mean diabetes duration was 20.7 +/- 11.6 years, the mean HbA1c was 7.8 +/- 4.2% (62 +/- 22 mmmol/mol). The whole population reported CAD in 172 cases (63.4%), and the rate in the BTA group was significantly higher than in ATA group, respectively, 90 (75.4%) vs 82 (54.1%), p < 0.0001. During the follow-up, BTA group had 5% of new cases of AMI in comparison to 1.3% in ATA group (p < 0.001). At the multivariate analysis BTA resulted an independent marker of CAD [OR 1.9 CI 9 5% (1.3-4.5) p = 0.0001]. Conclusion The current study shows a significant association between BTA arterial disease and CAD. A close cardiovascular screen should be required in patients with DFUs

The Immune-Centric Revolution in the Diabetic Foot: Monocytes and Lymphocytes Role in Wound Healing and Tissue Regeneration—A Narrative Review

Monocytes and lymphocytes play a key role in physiologic wound healing and might be involved in the impaired mechanisms observed in diabetes. Skin wound macrophages are represented by tissue resident macrophages and infiltrating peripheral blood recruited monocytes which play a leading role during the inflammatory phase of wound repair. The impaired transition of diabetic wound macrophages from pro-inflammatory M1 phenotypes to anti-inflammatory pro-regenerative M2 phenotypes might represent a key issue for impaired diabetic wound healing. This review will focus on the role of immune system cells in normal skin and diabetic wound repair. Furthermore, it will give an insight into therapy able to immuno-modulate wound healing processes toward to a regenerative anti-inflammatory fashion. Different approaches, such as cell therapy, exosome, and dermal substitute able to promote the M1 to M2 switch and able to positively influence healing processes in chronic wounds will be discussed

Interactions of imidazoline ligands with the active site of purified monoamine oxidase A.

The two forms of monoamine oxidase, monoamine oxidase A and monoamine oxidase B, have been associated with imidazoline-binding sites (type 2). Imidazoline ligands saturate the imidazoline-binding sites at nanomolar concentrations, but inhibit monoamine oxidase activity only at micromolar concentrations, suggesting two different binding sites [Ozaita A, Olmos G, Boronat MA, Lizcano JM, Unzeta M &amp; Garcia-Sevilla JA (1997) Br J Pharmacol121, 901-912]. When purified human monoamine oxidase A was used to examine the interaction with the active site, inhibition by guanabenz, 2-(2-benzofuranyl)-2-imidazoline and idazoxan was competitive with kynuramine as substrate, giving K-i values of 3 mu m, 26 mu m and 125 mu m, respectively. Titration of monoamine oxidase A with imidazoline ligands induced spectral changes that were used to measure the binding affinities for guanabenz (19.3 +/- 3.9 mu m) and 2-(2-benzofuranyl)-2-imidazoline (49 +/- 8 mu m). Only one type of binding site was detected. Agmatine, a putative endogenous ligand for some imidazoline sites, reduced monoamine oxidase A under anaerobic conditions, indicating that it binds close to the flavin in the active site. Flexible docking studies revealed multiple orientations within the large active site, including orientations close to the flavin that would allow oxidation of agmatine.</p

Survival and factors predicting mortality after major and minor lower-extremity amputations among patients with diabetes: a population-based study using health information systems

Introduction The aim of the study was to identify the sociodemographic and clinical factors associated with death after the first lower-extremity amputation (LEA), minor and major separately, using data from regional health administrative databases.Research design and methods We carried out a population-based cohort study including patients with diabetes residing in the Lazio region and undergoing a primary amputation in the period 2012–2015. Each individual was followed up for at least 2 years. Kaplan-Meier analysis was used to evaluate long-term survival; Cox proportional regression models were applied to identify factors associated with all-cause mortality.Results The cohort included 1053 patients, 72% were male, 63% aged ≥65 years, and 519 (49%) died by the end of follow-up. Mortality rates at 1 and 4 years were, respectively, 33% and 65% for major LEA and 18% and 45% for minor LEA. Significant risk factors for mortality were age ≥65, diabetes-related cardiovascular complications, and chronic renal disease for patients with minor LEA, and age ≥75 years, chronic renal disease and antidepressant drug consumption for subjects with major LEA.Conclusions The present study confirms the high mortality rates described in patients with diabetes after non-traumatic LEA. It shows differences between minor and major LEA in terms of mortality rates and related risk factors. The study highlights the role of depression as specific risk factor for death in patients with diabetes after major LEA and suggests including its definition and management in strategies to reduce the high mortality rate observed in this group of patients