Organelle-Specific Initiation of Autophagy.

Autophagy constitutes a prominent mechanism through which eukaryotic cells preserve homeostasis in baseline conditions and in response to perturbations of the intracellular or extracellular microenvironment. Autophagic responses can be relatively non-selective or target a specific subcellular compartment. At least in part, this depends on the balance between the availability of autophagic substrates ("offer") and the cellular need of autophagic products or functions for adaptation ("demand"). Irrespective of cargo specificity, adaptive autophagy relies on a panel of sensors that detect potentially dangerous cues and convert them into signals that are ultimately relayed to the autophagic machinery. Here, we summarize the molecular systems through which specific subcellular compartments-including the nucleus, mitochondria, plasma membrane, reticular apparatus, and cytosol-convert homeostatic perturbations into an increased offer of autophagic substrates or an accrued cellular demand for autophagic products or functions.

Clinical scoring systems for the risk of cardiovascular autonomic neuropathy in type 1 and type 2 diabetes: A simple tool.

This study was aimed at developing a clinical risk score for cardiovascular autonomic neuropathy (CAN) for type 1 and type 2 diabetes. In a retrospective cross-sectional one-centre study in an unselected population, 115 participants with type 1 diabetes (age 41.1 ± 12.2 years) and 161 with type 2 diabetes (age 63.1 ± 8.9 years), well-characterized for clinical variables, underwent standard cardiovascular reflex tests (CARTs). Strength of associations of confirmed CAN (based on 2 abnormal CARTs) with clinical variables was used to build a CAN risk score. CAN risk score was based on resting heart rate, HbA1c, retinopathy, nephropathy, cardiovascular disease in both type 1 and type 2 diabetes, and on HDL cholesterol, systolic blood pressure, and smoking in type 1 diabetes or insulin treatment and physical activity in type 2 diabetes (range 0-10). In type 1 diabetes, CAN risk score showed an area under the ROC curve (AUC) of 0.890 ± 0.034, and at cut-off of 4 sensitivity of 88%, specificity of 74.4%, and negative predictive value (NPV) of 95.7% for confirmed CAN. In type 2 diabetes, CAN risk score showed an AUC of 0.830 ± 0.051 and at the cut-off of 4 sensitivity and specificity of 78.6% and 73.5%, respectively, and NPV of 97.3% for confirmed CAN. These newly developed CAN risk scores are accessible in clinical practice and, if confirmed in a validation study, they might identify asymptomatic individuals with diabetes at greater risk of CAN to be referred to CARTs, thus limiting the burden of a universal screening.

Peripheral arterial disease in patients with renal-diabetic foot ulcers.

OBJECTIVE: To describe the angiographic characteristics of peripheral arterial disease (PAD) in persons with diabetic foot ulcers (DFUs) on dialysis treatment. METHOD: The study is a retrospective analysis of patients with DFUs and PAD who had been referred to our diabetic foot clinic. All patients had been managed by a pre-set limb salvage protocol including revascularisation of the affected limb. Arterial lesions (stenosis between 50-99% and occlusions) were retrospectively evaluated through angiogram analysis. According to the presence or not of dialysis, patients were divided into two patient groups: renal-diabetic foot (RDF) and diabetic foot (DF). Distribution of PAD and immediate revascularisation outcome (technical revascularisation outcome) for RDF and DF were separately reported and compared. RESULTS: The sample included 239 patients: mean age was 71.8 years; 72.4% were male; 87.4% had type 2 diabetes; mean diabetes duration was 21.4 years; and the mean HbA1c was 63±22mmol/mol. The RDF group compared with the DF group reported higher numbers of vessels affected (n=5±1.6 versus 3.9±1.5, respectively, p<0.0001), greater involvement of the superficial femoral artery (90.2% versus 75.8%, respectively, p=0.003), the tibial-peroneal trunk (53.7% versus 25.5%, respectively, p=0.01), the anterior tibial artery (93.9% versus 80.9%, respectively, p=0.03) and below-the-ankle (BTA) arteries (70.7% versus 35.7%, respectively, p=0.0001). The RDF group showed a higher rate of revascularisation failure in comparison to DF patients (43.9% versus 15.3%, respectively, p<0.0001). BTA arterial disease (odds ratio 9.5; 95% Confidence Interval: 3.5-25.4; p=0.0001) resulted as the only independent predictor of revascularisation failure. CONCLUSION: In this study, RDF patients showed a widespread distribution of arterial lesions with a higher involvement of foot arteries in comparison with DF patients. BTA arterial disease was found to be an independent predictor of revascularisation failure.

The diagnostic usefulness of the combined COMPASS 31 questionnaire and electrochemical skin conductance for diabetic cardiovascular autonomic neuropathy and diabetic polyneuropathy.

The study investigated the diagnostic performance for diabetic cardiovascular autonomic neuropathy (CAN) and diabetic polyneuropathy (DPN) of the combined use of composite autonomic symptom score (COMPASS) 31, validated questionnaire for autonomic symptoms of CAN, and electrochemical skin conductance (ESC), proposed for detecting DPN and CAN. One-hundred and two participants with diabetes (age 57 ± 14 years, duration 17 ± 13 years) completed the COMPASS 31 before assessing cardiovascular reflex tests (CARTs), neuropathic symptoms, signs, vibratory perception threshold (VPT), thermal thresholds (TT), and ESC using Sudoscan. Two patterns were evaluated: (a) the combined abnormalities in both tests (COMPASS 31+ESC), and (b) the abnormality in COMPASS 31 and/or ESC (COMPASS 31 and/or ESC). CAN (≥1 abnormal CART) and confirmed CAN (≥2 abnormal CARTs) were present in 28.1% and 12.5%, DPN (two abnormalities among symptoms, signs, VPT, and TT) in 52%, abnormal COMPASS 31 (total weighted score >16.44) in 48% and abnormal ESC (hands ESC <50 µS and/or feet ESC <70 µS) in 47.4%. Both the patterns-COMPASS 31+ESC and COMPASS 31 and/or ESC-were associated with CAN and DPN (P < .01). COMPASS 31 and ESC reached a sensitivity of 75% and 83% for confirmed CAN, and a specificity of 65% and 67% for DPN. When combining the tests, the sensitivity for CAN rose by up to 100% for CAN and the specificity up to 89% for DPN. The combination of the tests can allow a stepwise screening strategy for CAN, by suggesting CAN absence with combined normality, and prompting to CARTs with combined abnormality.

Unsaturated fatty acids induce non-canonical autophagy.

To obtain mechanistic insights into the cross talk between lipolysis and autophagy, two key metabolic responses to starvation, we screened the autophagy-inducing potential of a panel of fatty acids in human cancer cells. Both saturated and unsaturated fatty acids such as palmitate and oleate, respectively, triggered autophagy, but the underlying molecular mechanisms differed. Oleate, but not palmitate, stimulated an autophagic response that required an intact Golgi apparatus. Conversely, autophagy triggered by palmitate, but not oleate, required AMPK, PKR and JNK1 and involved the activation of the BECN1/PIK3C3 lipid kinase complex. Accordingly, the downregulation of BECN1 and PIK3C3 abolished palmitate-induced, but not oleate-induced, autophagy in human cancer cells. Moreover, Becn1(+/-) mice as well as yeast cells and nematodes lacking the ortholog of human BECN1 mounted an autophagic response to oleate, but not palmitate. Thus, unsaturated fatty acids induce a non-canonical, phylogenetically conserved, autophagic response that in mammalian cells relies on the Golgi apparatus.

Quiescence Preconditioned Human Multipotent Stromal Cells Adopt a Metabolic Profile Favorable for Enhanced Survival under Ischemia.

A major impediment to the development of therapies with mesenchymal stem cells/multipotent stromal cells (MSC) is the poor survival and engraftment of MSCs at the site of injury. We hypothesized that lowering the energetic demand of MSCs by driving them into a quiescent state would enhance their survival under ischemic conditions. Human MSCs (hMSCs) were induced into quiescence by serum deprivation (SD) for 48 hours. Such preconditioned cells (SD-hMSCs) exhibited reduced nucleotide and protein syntheses compared to unpreconditioned hMSCs. SD-hMSCs sustained their viability and their ATP levels upon exposure to severe, continuous, near-anoxia (0.1% O2 ) and total glucose depletion for up to 14 consecutive days in vitro, as they maintained their hMSC multipotential capabilities upon reperfusion. Most importantly, SD-hMSCs showed enhanced viability in vivo for the first week postimplantation in mice. Quiescence preconditioning modified the energy-metabolic profile of hMSCs: it suppressed energy-sensing mTOR signaling, stimulated autophagy, promoted a shift in bioenergetic metabolism from oxidative phosphorylation to glycolysis and upregulated the expression of gluconeogenic enzymes, such as PEPCK. Since the presence of pyruvate in cell culture media was critical for SD-hMSC survival under ischemic conditions, we speculate that these cells may utilize some steps of gluconeogenesis to overcome metabolic stress. These findings support that SD preconditioning causes a protective metabolic adaptation that might be taken advantage of to improve hMSC survival in ischemic environments. Stem Cells 2017;35:181-196.

Risk of contrast induced nephropathy in diabetic patients affected by critical limb ischemia and diabetic foot ulcers treated by percutaneous transluminal angioplasty of lower limbs.

BACKGROUND: The aim of this study is to evaluate the risk of contrast induced nephropathy (CIN) in diabetic patients with critical limb ischemia (CLI) and foot ulcers (FUs) treated by percutaneous transluminal angioplasty of lower limbs. METHODS: The study group was composed of 145 diabetic patients who underwent a limb salvage protocol because of CLI and FUs between 2012 and 2015. All patients received a prophylactic strategy against the administration of contrast medium. Serum creatinine (SCr) levels were evaluated the day of procedure and for 3 days after. CIN was considered in case of increase of 25% of SCr in comparison to baseline value or an absolute increase of at least 0.5 mg/dl without other interfering factors. RESULTS: CIN occurred in 9% (14/145) of the cases. In the 1-year follow-up SCr returned to baseline values in 10 patients (71 %), 3 patients died (21%), and 1 patient had a major cardiovascular event (7%). No patients required dialysis. The risk was independent of chronic kidney disease stage. The rate of contrast nephropathy in each stage (X = 0.27) was as follows: 3/20 (15%) in stage 2; 3/66 (4.6%) in stage 3, 7/51 (13.7%) in stage 4; and 1/8 (12.5%) in stage 5. At the univariate analysis factors predicting this risk were anemia (HR 95% 2.5 [CI 1.8-4.2] P = .039) and heart failure (HR 95% 2.6 [CI 2.1-4.6] P = .038), while any significant variable was found at multivariate analysis. CONCLUSIONS: Peripheral percutaneous transluminal angioplasty in diabetic patients with CLI and FUs can be performed with a good safety factor and a low risk of contrast medium toxicity.

Non-healing foot ulcers in diabetic patients: general and local interfering conditions and management options with advanced wound dressings.

Medical knowledge about wound management has improved as recent studies have investigated the healing process and its biochemical background. Despite this, foot ulcers remain an important clinical problem, often resulting in costly, prolonged treatment. A non-healing ulcer is also a strong risk factor for major amputation. Many factors can interfere with wound healing, including the patient's general health status (i.e., nutritional condition indicated by albumin levels) or drugs such as steroids that can interfere with normal healing. Diabetic complications (i.e., renal insufficiency) may delay healing and account for higher amputation rates observed in diabetic patients under dialysis treatment. Wound environment (e.g., presence of neuropathy, ischaemia, and infection) may significantly influence healing by interfering with the physiological healing cascade and adding local release of factors that may worsen the wound. The timely and well-orchestrated release of factors regulating the healing process, observed in acute wounds, is impaired in non-healing wounds that are blocked in a chronic inflammatory phase without progressing to healing. This chronic phase is characterised by elevated protease activity (EPA) of metalloproteinases (MMPs) and serine proteases (e.g., human neutrophil elastase) that interfere with collagen synthesis, as well as growth factor release and action. EPA (mainly MMP 9, MMP-8 and elastase) and inflammatory factors present in the wound bed (such as IL-1, IL-6, and TNFa) account for the catabolic state of non-healing ulcers. The availability of wound dressings that modulate EPA has added new therapeutic options for treating non-healing ulcers. The literature confirms advantages obtained by reducing protease activity in the wound bed, with better outcomes achieved by using these dressings compared with traditional ones. New technologies also allow a physician to know the status of the wound bed environment, particularly EPA, in a clinical setting. These may be helpful in guiding a clinician's options in treating very difficult-to-heal ulcers.

Regulation of autophagy by stress-responsive transcription factors.

Autophagy is an evolutionarily conserved process that promotes the lysosomal degradation of intracellular components including organelles and portions of the cytoplasm. Besides operating as a quality control mechanism in steady-state conditions, autophagy is upregulated in response to a variety of homeostatic perturbations. In this setting, autophagy mediates prominent cytoprotective effects as it sustains energetic homeostasis and contributes to the removal of cytotoxic stimuli, thus orchestrating a cell-wide, multipronged adaptive response to stress. In line with the critical role of autophagy in health and disease, defects in the autophagic machinery as well as in autophagy-regulatory signaling pathways have been associated with multiple human pathologies, including neurodegenerative disorders, autoimmune conditions and cancer. Accumulating evidence indicates that the autophagic response to stress may proceed in two phases. Thus, a rapid increase in the autophagic flux, which occurs within minutes or hours of exposure to stressful conditions and is entirely mediated by post-translational protein modifications, is generally followed by a delayed and protracted autophagic response that relies on the activation of specific transcriptional programs. Stress-responsive transcription factors including p53, NF-κB and STAT3 have recently been shown to play a major role in the regulation of both these phases of the autophagic response. Here, we will discuss the molecular mechanisms whereby autophagy is orchestrated by stress-responsive transcription factors.

Potential celiac children: 9-year follow-up on a gluten-containing diet.

OBJECTIVES: Potential celiac disease (CD) is defined by the presence of serum anti-tissue-transglutaminase (anti-TG2) antibodies and normal duodenal mucosa. The major clinical problem is the management of asymptomatic patients and how to predict the development of villous atrophy. This prospective longitudinal cohort study describes the natural history of potential CD up to 9 years and explores risk factors associated with the development of mucosal damage. METHODS: Two hundred and ten potential CD children were eligible for the study; 175/210 asymptomatic children were left on a gluten-containing diet. Antibodies and clinical symptoms were checked every 6 months, and a small bowel biopsy was taken every 2 years to evaluate histological, immunohistochemical, and anti-TG2 deposits. Patients were genotyped for HLA and a set of non-HLA CD-associated genes. RESULTS: Forty-three percent of patients showed persistently elevated anti-TG2 level, 20% became negative during follow-up, and 37% showed a fluctuant anti-TG2 course with transiently negative values. At 3 years of follow-up, 86% of cases remained potential; 73 and 67% still had normal duodenal architecture at 6 and 9 years, respectively. Male sex, slight mucosal inflammation at time 0, and a peculiar genetic profile delineate a cohort of individuals who were prone to develop mucosal damage during time. CONCLUSIONS: A sizeable proportion of asymptomatic potential celiac patients showed fluctuation or negativization of antibody production, and many of these, with persistently positive anti-TG2, did not develop mucosal damage after 9 years of follow-up. Celiac population is a multivariate aggregate of individuals with different genetic and phenotypic profiles. Caution is required before prescribing a gluten-free diet for life to asymptomatic individuals with potential CD.

Regenerative surgery of the complications with Morton's neuroma surgery: use of platelet rich plasma and hyaluronic acid.

Morton's neuroma is an entrapment neuropathy of the plantar digital nerve. We treated five patients with wound dehiscence and tendon exposure, after Morton's neuroma surgery excision using a dorsal approach. In this article we describe our technique. From July 2010 to August 2011, at the Department of Plastic and Reconstructive Surgery, University of Rome 'Tor Vergata', five patients (four females and one male), with ages ranging between 35 and 52 years, were treated with a combination of PRP (platelet rich plasma) and HA (hyaluronic acid). Thirty days following surgery, all patients showed a complete healing of the wound. The use of this technique for the treatment of postoperative wound dehiscence and tendon exposure has proven as satisfactory.

Validation of the Fast-Track Model: A Simple Tool to Assess the Severity of Diabetic Foot Ulcers.

This study aimed to validate the association between the grades of severity of diabetic foot ulcers (DFUs) identified by the fast-tack model and specific outcomes. Three hundred and sixty-seven patients with new DFUs who were referred to a tertiary level diabetic foot service serving Rome, Italy, were included. The fast-track model identifies three levels of DFUs' severity: uncomplicated DFUs, including superficial wounds, not-infected wounds, and not-ischemic wounds; complicated DFUs, including ischemic wounds, infected wounds, and deep ulcers involving the muscles, tendons, or bones, and any kind of ulcers in patients on dialysis and/or with heart failure; and severely complicated DFUs, including abscesses, wet gangrene, necrotizing fasciitis, fever, or clinical signs of sepsis. Healing, minor and major amputation, hospitalization, and survival after 24 weeks of follow-up were considered. Among the included patients, 35 (9.6%) had uncomplicated DFUs, 210 (57.2%) had complicated DFUs, and 122 (33.2%) had severely complicated DFUs. The outcomes for patients with uncomplicated, complicated, and severely complicated DFUs were as follows, respectively: healing, 97.1%, 86.2%, and 69.8%; minor amputation, 2.9%, 20%, and 66.4%; major amputation, 0%, 2.9%, and 16.4%; hospitalization, 14.3%, 55.7%, and 89.3%; survival, 100%, 96.7%, and 89.3%. DFU severity was an independent predictor of healing, amputation, hospitalization, and survival. The current study shows an association between the grade of severity of DFUs identified by the fast-track model and the considered outcomes. The fast-track model may be a useful tool for assessing the severity and prognosis of DFUs.

Skin necrosis of scrotum due to endovascular embolisation: a case report.

The aim of our case report was to analyse the results obtained with the Matriderm® system and autologous skin grafting for the surgical treatment of skin necrosis of scrotum as a result of endovascular embolisation. We recruited one patient with scrotum skin necrosis as a result of endovascular embolisation admitted at the department of Plastic and Reconstructive Surgery, University of Rome 'Tor Vergata'. The patient underwent Matriderm® system and autologous skin grafting for skin necrosis treatment. After a single treatment, reduction of the skin necrosis was obtained, after 30 days from the surgical treatment. Patient experienced a reduction in pain and a complete restoration of the loss in volume and quality of skin was noticed. Matriderm® system and autologous skin grafting is a simple, safe and feasible technique. When comparing this treatment with others, Matriderm® is a simpler, more economic and less time-consuming method, and does not require sophisticated laboratory facilities.

Macrophage Activation and M2 Polarization in Wound Bed of Diabetic Patients Treated by Dermal/Epidermal Substitute Nevelia.

Clinical evidences have shown good results using dermal/epidermal substitutes (DESs) to treat diabetic foot ulcers. Recent studies suggest that, in addition to their scaffold action, DESs may favor wound healing by influencing wound bed inflammatory cells. This study aims to investigate whether DES may influence the inflammatory infiltrate and macrophages polarization toward a reparative phenotype. Fifteen diabetic patients with chronic foot ulcers have been randomly enrolled: 5 treated only by standard of care, served as control group (CG), and 10 treated with DES composed of type 1 bovin collagen (Nevelia, SYMATESE) considered as test group (TG). A biopsy was taken at baseline (T0) and after 30 days (T1). From bioptic paraffin specimen histological, immunohistochemical, and immunofluorescence analysis was performed. Immunohistochemistry reactions evaluated the number of M1 macrophage (CD38+) and M2 macrophage (CD163+). TG patients displayed general macrophage activation and their greater polarization toward M2 subpopulation 30 days after DES implant, compared with CG. From T0 to T1 there was a significant decrease of CD38+ (230 ± 42 and 135 ± 48 mm2, respectively; P < .001) and significant increase of CD163+ (102 ± 21 positive cells/mm2 and 366 ± 42 positive cells/mm2, respectively; P < .001). Confocal microscopy confirmed an increase of M2 cells as expressed by the reduced CD68+/CD163+ ratio. After 6 months of observation 6 patients (60%) of the TG completely healed, while only 1 patient (20%) healed in the CG (P < .01). The tested DES makes possible to treat diabetic foot ulcers inducing tissue reparative processes through macrophage activation and M2 reparative polarization.

Effectiveness of fast-track pathway for diabetic foot ulcerations.

AIM: To investigate the effectiveness of fast-track pathway (FTP) in the management of diabetic foot ulceration (DFU) after 2 years of implementation. METHODS: The study group was composed of patients who referred to a specialized DF centre due to DFUs. Those were divided in two groups: early referral (ER) and late referral (LR) patients. According to FTP, ER were considered patients who referred after 2 weeks in the case of uncomplicated non-healing ulcers (superficial, not infected, not ischemic), within 4 days in the case of complicated ulcers (ischemic, deep, mild infection) and within 24 h in the case of severely complicated ulcers (abscess, wet gangrene, fever). Healing, healing time, minor and major amputation, hospitalization, and survival were evaluated. The follow-up was 6 months. RESULTS: Two hundred patients were recruited. The mean age was 70 ± 13 years, 62.5% were male, 91% were affected by type 2 diabetes with a mean duration of 18 ± 11 years. Within the group, 79.5% had ER while 20.5% had LR. ER patients showed increased rates of healing (89.9 vs. 41.5%, p = 0.001), reduced healing time (10 vs. 16 weeks, p = 0.0002), lower rates of minor (17.6 vs. 75.6%, p < 0.0001) and major amputation (0.6 vs. 36.6%, p < 0.0001), hospitalization (47.1 vs. 82.9%, p = 0.001), and mortality (4.4 vs. 19.5%, p = 0.02) in comparison to LR. At multivariate analysis, ER was an independent predictor of healing, while LR was an independent predictor for minor and major amputation and hospitalization. CONCLUSION: After the FTP implementation, less cases of LR were reported in comparison to ER. ER was an independent predictor of positive outcomes such as healing, healing time, limb salvage, hospitalization, and survival.

Use of Nevelia Dermal-Epidermal Regenerative Template in the Management of Ischemic Diabetic Foot Postsurgical Wounds.

The purpose of this cross-sectional study is evaluate the effectiveness of a dermal-epidermal substitute (DES) composed of 3-dimensional porous matrix of type 1, purified, stabilized, bovin-origin collagen (Nevelia, SYMATESE, Chaponost, France) without a subsequent skin graft in the treatment ischemic postsurgical diabetic foot ulcers. This study group was composed of a sample of consecutive diabetic patients with critical limb ischemia and postsurgical wounds. All patients received a preset limb salvage protocol including the application of the DES, but none received a skin graft. Patients were closely followed until wound healing or different outcome. The outcome measures were healing, nonhealing, major amputation, and death evaluated at 1 and 2 years of follow-up. Forty-one patients were included. The average postsurgical wound area was 69.6 ± 50 cm2. Twenty-one patients (51%) healed; 10 patients (24%) did not heal after 1 year of follow-up; however, all of them achieved a mean ulcer size reduction >50%; 7 patients (17%) were amputees; 3 patients (7.3%) died. In a later follow-up (2 years), wounds in 8 additional patients healed. Successful revascularization was an independent predictor of healing (hazard ratio = 5.1, 95% confidence interval [CI] = 2.5-14-9; P = .0001), the postsurgical ulcer size (>50 cm2) was an independent predictor of nonhealing (hazard ratio = 6.2, 95% CI = 2.1-38.4; P = .0001) while recurrence of critical limb ischemia was an independent predictor of major amputation (odds ratio = 3.4, 95% CI = 1.1-4.5; P = .002). The DES composed of type 1 bovin-origin collagen is useful in the treatment of large postsurgical diabetic foot ulcers, even when the skin graft is not a suitable therapeutic option.

Management of diabetic persons with foot ulceration during COVID-19 health care emergency: Effectiveness of a new triage pathway.

AIM: To define the outcomes of persons with diabetes and foot ulcers (DFUs) managed through a specific triage pathway during the COVID-19 crisis. METHODS: Patients who had an active DFU during the COVID-19 emergency were included. All participants were managed using a specific triage system driven both by ulcer'severity and concomitant co-diseases. Subjects with severely complicated DFUs were urgently referred to hospital regardless of the concomitant comorbidities. Subjects with complicated DFUs received outpatient evaluation (within 48-72 h) and were admitted to hospital if required (revascularization, surgical intervention, intravenous antibiotic therapy); after the first outpatient visit or hospitalization, patients were followed according to the number of comorbidities (in the case of 3 or more comorbidities patients were followed up by telemedicine). Patients with uncomplicated DFUs were managed by telemedicine after outpatient evaluation. Healing, major amputation, death and rate of COVID-19 infection were evaluated. The minimum follow-up was 1 month. RESULTS: The study group included 151 patients. The mean age was 69.9 ± 14.2 years, 58.9% were male and 91.4% had type 2 diabetes; 58.7% had severely complicated, 21% complicated and 20.3% uncomplicated DFUs. Among those, 78.8% presented with 3 or more comorbidities. One hundred and six patients had regular clinical follow-ups, while 45 were managed through telemedicine. Forty-one (27.1%) patients healed, 3 (1.9%) had major amputations and 3 (1.9%) died. One patient (0.6%) reported COVID-19 positivity due to infection acquired at home. CONCLUSION: The triage pathway adopted during the COVID-19 pandemic showed adequate management of DFUs and no cases of hospital virus exposure.

Prevalence, Clinical Aspects and Outcomes in a Large Cohort of Persons with Diabetic Foot Disease: Comparison between Neuropathic and Ischemic Ulcers.

This study aims to evaluate clinical and ulcer characteristics as well the outcomes of patients with diabetic foot ulcers (DFUs). The study group was composed of DFUs patients managed by a limb salvage protocol according to guidance. Clinical and ulcers findings were described, and 1-year outcomes defined as limb salvage, healing, healing time, major amputation and death were compared between neuropathic and ischemic DFUs. One thousand, one hundred and ninety-eight subjects were included; 386 (32.2%) neuropathic and 812 (67.8%) ischemic DFUs. Neuropathic patients were younger (69.5 ± 11.5 vs. 74.5 ± 11.5, p < 0.0001) and reported less cases of nephropathy (22.8 vs. 39.6%, p < 0.0001), ischemic heart disease (22.8 vs. 36.9, p = 0.0004), cerebrovascular disease (8.3 vs. 17.2%, p = 0.002), heart failure (10.1 vs. 24.7%, p = 0.0002) and end-stage-renal-disease (ESRD) (5.4 vs. 27%, p = 0.0001) than ischemic patients; they also showed less cases of large (>5 cm2) (10.3 vs. 22.9%, p = 0.0007), infected (40.4 vs. 55.7%, p = 0.0005) and deep to the bone (22.3 vs. 39.2, p = 0.0002) ulcers, as well less multiple ulcerations (21.8 vs. 32.8%, p = 0.006) than patients with ischemic DFUs. The outcomes for neuropathic and ischemic DFUs were limb salvage (98.4 vs. 82.3%, p < 0.0001), healing (97.3 vs. 79.6%, p < 0.0001), healing time (34.9 vs. 35.6 weeks, p = 0.8), major amputation (0.5 vs. 6.6%, p = 0.0001), death (1.1 vs. 11%, p < 0.0001) respectively. Revascularization failure and ESRD were independent predictors of major amputation, while heart failure and number of co-morbidities (³5) were independent predictors of death. Ischemic DFUs patients showed more severe clinical and ulcers features as well worse outcomes than neuropathic DFUs patients.

Limb Salvage in Diabetic Patients With Ischemic Heel Ulcers.

The purpose of this study is to investigate the outcomes of diabetic individuals with ischemic heel ulcers. The study group was composed of a consecutive sample of persons with diabetic ischemic foot ulcers managed by a preset multidisciplinary limb salvage protocol, including revascularization through endovascular technique. The outcome measures were healing, major amputation (above the ankle), and death at 1-year of follow-up. The outcomes between patients with heel ulcers (HUs) and without (NHUs) were compared. A total of 254 patients were recruited. There were 50/254 (19.7%) HUs and 204/254 (79.3%) NHUs. Overall, 190/254 (74.8%) patients healed. The rate of healing for HUs and NHUs was 30/50 (60%) and 160/204 (78.4%); P = .03, respectively. Major amputation occurred in 24/254 (9.4%) patients. The rates of major amputation for HUs and NHUs were 10/50 (20%) and 14/204 (6.9%; P = .002), respectively; 40/254 (15.7%) patients died, unhealed. The rates of mortality for HUs and NHUs were 10/50 (20%) and 30/204 (14.7%; P = .07), respectively. In HUs patients, absence of infection [95% CI = 3.1 (1.6-5.5); P = .002] and superficial ulcers [95% CI = 4.4 (2.2-9.3); P = .0001] were independent predictors of healing, whereas revascularization failure [95% CI = 8.1 (1.5.0-19.4); P = .0001], involvement of the plantar arch [95% CI = 6.3 (2.0-15.4); P = .0001], and dialysis [95% CI = 2.2 (1.3-4.5); P = .006] were independent predictors of major amputation. A multidisciplinary approach achieves good rate of limb salvage in people with diabetic ischemic heel ulcers.

Characteristics and Outcome for Persons with Diabetic Foot Ulcer and No-Option Critical Limb Ischemia.

The study aimed to evaluate clinical and vascular characteristics, as well as outcomes, for diabetic persons with foot ulceration and no-option critical limb ischemia (CLI). The study group included a sample of patients admitted to our diabetic foot unit because of a new diabetic foot ulcer and CLI. All subjects were managed using a limb salvage protocol which includes lower-limb revascularization. According to whether or not the revascularization procedure was a success, patients were respectively divided into two groups: successfully treated CLI patients (ST-CLI) and no-option CLI patients (NO-CLI). Failed revascularization was considered in the case of technical recanalization failure of occluded vessels (inability to overcome the obstruction) and/or absence of arterial flow to the foot. Limb salvage, major amputation, and death after 1 year of follow-up were evaluated and compared between the two groups. Overall, 239 patients were included, 74.9% belonging to ST-CLI and 25.1% to NO-CLI. NO-CLI patients reported more cases of ischemic heart disease (80 vs. 62.1, p = 0.008), heart failure (63.3 vs. 32.4%, p < 0.0001), and end-stage renal disease (ESRD) (60 vs. 25.7%) than ST-CLI patients. In addition, more vessels were affected in the NO-CLI group (5.2 ± 1.6 vs. 4 ± 1.5, p < 0.0001), and there was more involvement of tibio-peroneal trunk (50 vs. 30.2%, p = 0.006), anterior tibial (93.3 vs. 82.7, p = 0.03), posterior tibial (93.3 vs. 73.7%, p = 0.0005), peroneal (70 vs. 48%, p = 0.002), and below-the-ankle arteries (73.3 vs. 39.1%, p < 0.0001) than ST-CLI. The 1 year outcomes for the whole population were 69.9% limb salvage, 10.9% major amputation, and 19.2% death. The outcomes for NO-CLI and ST-CLI were, respectively, as follows: limb salvage (13.8 vs. 73.4%, p < 0.0001), amputation (30 vs. 4.5%, p = 0.0001), and mortality (50 vs. 8.9%, p < 0.0001). NO-CLI patients showed a more severe pattern of peripheral arterial disease (PAD) with distal arterial lesions and worse outcomes than ST-CLI.