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Background: Several US risk stratification score systems (RSSs) have been developed to standardize a thyroid nodule risk of malignancy. It is still a matter of debate which RSS is the most reliable. The purpose of this study is to evaluate: (1) the concordance between the American College of Radiology TI-RADS (ACR TI-RADS) and fine needle aspiration cytology (FNAC), (2) the cancer rate in the ACR TI-RADS categories, (3) the characteristics of nodules evaluated by FNAC even if not formally indicated according to ACR TI-RADS (‘not indicated FNACs”). Methods: From January 2021 to September 2022, patients attending the Endocrinology Unit of the CTO Hospital of Rome for evaluation of thyroid nodules were included. Results: 830 nodules had negative cytology, belonging to TIR2 and TIR1C. One hundred and thirteen nodules were determined to be suspicious for or consistent with malignancy belonging to TIR3B/TIR4/TIR5. Of this last group, 94% were classified as TR4/TR5 nodules. In total, 87/113 underwent surgery. Among these, 73 had histologically proven cancer, 14 turned out to be benign. “Not indicated FNACs” was 623. Among these, 42 cancers were present. Conclusions: This study confirmed the diagnostic power of ACR TI-RADS. In addition, these data suggest revising the ACR TI-RADS indication to FNAC, especially for TR4.

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).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.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].The current study shows a significant association between BTA arterial disease and CAD. A close cardiovascular screen should be required in patients with DFUs.

Objectives To investigate the outcomes of patients with calcific lesions in the common femoral artery undergoing endovascular procedures with atherectomy device and scoring balloon angioplasty combined with treatment of steno-occlusive disease of the remaining arterial districts of the lower limb. Methods Between January 2015 and December 2018, 11 diabetic patients at high risk for “major amputation”, with calcific lesions of the common femoral artery and ischemic ulcers requiring endovascular treatment were retrospectively evaluated. Technical success was defined as revascularization of the common femoral artery with a residual stenosis lower than 30%. Primary endpoints were an immediate increase of perilesional transcutaneous oxygen pressure (TCPO2) > 40 mmHg, ulcerative lesions improvement up to healing or skin flaps re-epithelialization after minor amputation, limb rescue with rejected major amputation, and resolution of rest pain if present. Results The success rate of the revascularization procedures was 100%. No patient underwent surgical conversion. One case of peri-operative bleeding at the brachial access site was observed. There were no cases of arterial dissection or undesired distal embolization. The average baseline value of perilesional TCPO2 was 21.8 ± 9.2 mmHg. The mean TCPO2 value was 57.4 ± 7.2 mmHg three days after the procedure ( P Conclusions Endovascular approach for severely calcified atherosclerotic lesions of the common femoral artery seems to represent a valid therapeutic option associated with promising results in terms of clinical outcome and low complication rates.

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 p 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.

Diabetic foot osteomyelitis (DFO) is a clinical problem with high risk of amputation. The treatment of DFO is still an unsolved challenge. Surgical therapy, antibiotic therapy or conservative treatment are still debated for the timing and the consequences. Long antibiotic therapies expose the selection of multidrug-resistant bacteria. Nowadays the use of new bone substitutes aims to support the load of the bone segments and to ensure the eradication of the infectious process after surgical treatment. A case report of digital osteomyelitis due to a multidrug resistant bacteria was treated with a conservative treatment and use of bioglass (Bonalive) that has the ability to inhibit bacterial growth. A long follow-up shows the resolution of infectious process, no ulcer recurrence and persistent recovery of its ability to walk. Our results agree with literature data and suggest that bioglass may be considered a useful option to manage DFO and achieve healing with a very conservative approach.

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.

Diabetic foot syndrome (DFS) is a complex disease. The best outcomes are reported with the multi-disciplinary team (MDT) approach, where each member works collaboratively according to his/her expertise. However, which health provider should act as the team leader (TL) has not been determined. The TL should be familiar with the management of diabetes, related complications and comorbidities. He/she should be able to diagnose and manage foot infections, including prompt surgical treatment of local lesions, such as abscesses or phlegmons, in an emergent way in the first meeting with the patient. According to the Organization for Economic Co-operation and Development (OECD) reports, Italy is one of countries with a low amputation rate in diabetic patients. Many factors might have contributed to this result, including 1)the special attention directed to diabetes by the public health system, which has defined diabetes as a "protected disease", and accordingly, offers diabetic patients, at no charge, the best specialist care, including specific devices, and 2)the presence of a network of diabetic foot (DF) clinics managed by diabetologists with medical and surgical expertise. The health care providers all share a "patient centred model" of care, for which they use their internal medicine background and skills in podiatric surgery to manage acute or chronic needs in a timely manner. Therefore, according to Italian experiences, which are fully reported in this document, we believe that only a skilled diabetologist/endocrinologist should act as a TL. Courses and university master's degree programmes focused on DF should guarantee specific training for physicians to become a TL.

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.

The study aims to evaluate the effectiveness of foot revascularization in persons with diabetic foot ulcers (DFUs) and below-the-ankle (BTA) arterial disease. Consecutive patients referred for a new active ischaemic DFU requiring lower limb revascularization were considered. Among those, only patients with a BTA arterial disease were included. Revascularization procedures were retrospectively analysed: in the case of successful foot revascularization (recanalization of pedal artery, or plantar arteries or both) or not, patients were respectively divided in two groups, successful foot perfusion (SFP) and failed foot perfusion (FFP). Healing, minor and major amputation at 12 months of follow-up were evaluated and compared. Eighty patients (80) were included. The mean age was 70.5 ± 10.9 years, 55 (68.7%) were male, 72 (90%) were affected by type 2 diabetes with a mean duration of 22.7 ± 11.3 years. Overall 45 (56.2%) patients healed, 47 (58.7%) had minor amputation and 13 (16.2%) major amputation. Outcomes for SFP and FFP were respectively: healing (89.3 vs. 9.1%, p &lt, 0.0001), minor amputation (44.7 vs. 78.8%, p = 0.0001), major amputation (2.1 vs. 36.3%, p &lt, 0.0001). Failed foot revascularization resulted an independent predictor of non-healing, minor amputation, and major amputation. Foot revascularization is mandatory to achieve healing and avoid major amputation in persons with ischaemic DFU and BTA arterial disease.

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, pConclusion: 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.

Background: International comparisons of diabetes-related lower extremity amputation rates are still hampered by different criteria used for data collection and analysis. We aimed to evaluate trends and variation of major/minor amputations, using agreed definitions adopted by the Organization for Economic Cooperation and Development in 2015. Methods: Direct age–sex standardized rates were calculated per 100,000 subjects per year between 2000 and 2013, using major/minor amputations with diabetes diagnosis as numerators and the total population or number of people with diabetes as denominators. Longitudinal trends were investigated using generalized estimating equations. Results: Twenty-one countries reported major amputations referred to the general population, showing a mean reduction from 10.8 to 7.5 per 100,000 (− 30.6%). Eleven countries also reported major amputations among people with diabetes, showing a mean reduction from 182.9 to 128.3 per 100,000 (− 29.8%). Minor amputations remained stable over the study period. Longitudinal trends showed a significant average annual decrease of − 0.19 per 100,000 in the general population (95% CI − 0.36 to − 0.02; p =.03) and − 4.52 per 100,000 among subjects with diabetes (95% CI − 6.09 to − 2.94; p

A systematic review and quality assessment was performed to assess the management of diabetic foot osteomyelitis by medical or surgical treatment. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was used. All selected studies were evaluated using the Cochrane Risk of Bias Tool to assess the risk of bias for randomized controlled trials. The literature was revised using PubMed (Medline) and Embase (Elsevier) up to September 2020 to identify clinical trials assessing medical or surgical treatment to manage diabetic foot osteomyelitis. A total of six clinical trials that met our inclusion criteria, with a total of 308 participants. Healing rate, complete closure of the wound, and type of complications were the outcomes evaluated. Risk of bias assessment showed that only two of the six clinical trials included in the systematic review had a low risk of bias. Based on our findings, we believe that the management of diabetic foot osteomyelitis remains challenging. There are few high-quality clinical trials that both stratify clinical presentations and compare these treatments. We conclude that the available evidence is insufficient to identify the best option to cure diabetic foot osteomyelitis.

Il piede diabetico rappresenta una delle complicanze più severe del Diabete Mellito (DM) oltre che la prima causa di amputazione non traumatica degli arti inferiori; si stima, infatti, che ogni anno più di un milione di persone con DM siano sottoposte a trattamento demolitivo come conseguenza di questa condizione. Nonostante l’esistenza di linee guida nazionali ed internazionali sul management del piede diabetico, per alcuni aspetti gestionali le raccomandazioni proposte non raggiungono un forte livello di evidenza. Ciò rappresenta una potenziale fonte di incertezza decisionale, ma anche uno spunto da cui partire per chiarire aspetti legati al management del piede diabetico nella realtà italiana. L’obiettivo del presente documento è, quindi, quello di riadattare le raccomandazioni internazionali sulla gestione del piede diabetico alla luce dell’opinione di esperti italiani.

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 &lt, 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 &plusmn, 1.6 vs. 4 &plusmn, 1.5, p &lt, 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 &lt, 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 &lt, 0.0001), amputation (30 vs. 4.5%, p = 0.0001), and mortality (50 vs. 8.9%, p &lt, 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.

IntroductionThe 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 methodsWe 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.ResultsThe 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.ConclusionsThe 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.

Background and Aims The diabetic foot (DF) was traditionally considered a local foot problem due to diabetes; however many observations support the concept that the DF is actually a part of a more complex diabetes related syndrome which includes several long-term complications and co-morbidities. In recent years, an increase in the incidence of ischemic diabetic foot ulcers (DFUs) amongst dialyzed subjects has been observed, going up from approximately 5-10% fifteen years ago to the current rate of approximately 30-35%. Today it is well recognized that end stage renal disease (ESRD) is an independent risk factor for non-healing ulcers and amputation in diabetic subjects. In clinical practice, the presence of foot problems in ESRD diabetic patients is identified as a specific entity termed “renal-diabetic foot”. The aim of this study is to describe the angiographic characteristics of peripheral arterial disease (PAD) in patients with DFUs receiving chronic dialysis treatment. Method The study group was composed of patients with DFUs and PAD who referred to our diabetic foot unit. All patients have been managed with a pre-set limb salvage protocol including revascularization of the affected limb. Arterial lesions (stenosis between 50-99% and occlusions) were retrospectively evaluated through angiogram analysis. According to the presence of dialytic treatment, patients were divided in two subgroups: renal-diabetic foot (RDF) and diabetic foot (DF). Patterns of PAD and immediate revascularization outcome (technical revascularization outcome) for RDF and DF were separately reported and compared Results The demographic and clinical characteristics were reported in Table 1.RDF reported greater number of affected vessels (n= 5±1.6 vs 3.9±1.5, p Conclusion It was interesting to highlight that the above mentioned findings could be specifically related to the effect of renal disease on the arteries of the lower extremity because the two groups, RDF and DF, did not report any difference in terms of other traditional cardiovascular risk factors (age, smoke, arterial hypertension, dyslipidemia, diabetes duration) which could influence the characteristics of PAD. RDF patients showed a widespread distribution of arterial lesions with a higher involvement of foot arteries in comparison to DF subjects. BTA arterial disease is an independent predictor of revascularization failure.

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.

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 &plusmn, 11.5 vs. 74.5 &plusmn, 11.5, p &lt, 0.0001) and reported less cases of nephropathy (22.8 vs. 39.6%, p &lt, 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 (&gt, 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 &lt, 0.0001), healing (97.3 vs. 79.6%, p &lt, 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 &lt, 0.0001) respectively. Revascularization failure and ESRD were independent predictors of major amputation, while heart failure and number of co-morbidities (&sup3, 5) were independent predictors of death. Ischemic DFUs patients showed more severe clinical and ulcers features as well worse outcomes than neuropathic DFUs patients.

The study aimed to evaluate the effectiveness of the use of sucrose octasulfate impregnated dressing (TLC-NOSF [Technology Lipido-Colloid-Nano-OligoSaccharide Factor]) in the management of persons with neuro-ischaemic heel diabetic foot ulcers (DFUs). Consecutive patients who referred for an active non-infected neuro-ischaemic heel DFU belonging to grade IC (superficial) or IIC (deep to tendons, muscle or capsule) according to Texas University Classification were included. All patients were managed by a pre-set limb salvage protocol in the respect of International guidelines and the TLC-NOSF dressing was used as primary and specific dressing. Patients were evaluated any 2 to 4 weeks until wound healing or different outcomes. Primary outcome was the rate of complete wound healing after 24 weeks of follow-up. The secondary outcomes assessed the healing time, the rate of wound regression, the re-ulceration in the case of complete healing and the safety. Thirty patients were included. The mean age was 67 ± 11 years, 17 (56.7%) were male, all of them were affected by type 2 diabetes with a mean duration of 18 ± 7 years. Twenty patients (66.7%) showed deep ulcers (grade 2 of Texas University Classification); the mean TcPO2 at the inclusion was 42 ± 7 mm Hg. Twenty-two patients (73.3%) healed by Week 24. The mean time of healing was 84 ± 32 days, 2 (6.7%) patients had ulcer relapse after healing, 28 (93.3%) had wound regression >50%, 2 (6.7%) had mild infection, 1 (3.3%) reported major amputation. No serious adverse events related to TLC-NOSF dressing or local reactions were reported. This current study showed the potential benefit of sucrose octasulfate for treating neuro-ischaemic heel DFUs in addition to the standard of care.

Purpose: To detail a percutaneous technique for distal plantar venous arterialization in diabetic, end-stage renal disease (ESRD) patients with no-option critical limb ischemia (CLI). Technique: After failure of standard intraluminal recanalization attempts, a subintimal approach through the posterior tibial artery (PTA) is begun using a 0.014-inch, 190- or 300-cm-long guidewire supported by a 2-×20-mm, low-profile balloon catheter positioned a short distance behind the narrow “U-shaped” loop in the guidewire. Typically, heavy calcification in the distal tortuous segment of the PTA prevents reentry to the arterial true lumen; however, an entry in the distal lateral or medial plantar vein from a subintimal channel in the plantar artery can be intentionally pursued as a bailout technique, pointing the tip of the guidewire opposite to the arterial wall calcifications. Venous access is confirmed by contrast injection through the balloon catheter. Once the guidewire is advanced in the distal lateral or medial plantar vein and a plantar arteriovenous fistula (AVF) has been created, the AV anastomosis and the occluded PTA segment are dilated with 0.014-inch balloon catheters. The technique has been attempted in 9 consecutive diabetic, ESRD patients (mean age 69 years; 5 men) with no-option CLI; an AVF was created between the PTA and plantar vein in 7 patients. The mean TcPO2 at 1 month was 30±17 mm Hg (vs 7.3±2.2 at baseline). Six ulcers healed over an average of 21±4 weeks. Three of the 9 patients had below-knee amputations. Conclusion: Although further investigations are required, distal plantar venous arterialization may represent a promising technique to improve recanalization rates and limb salvage in diabetic ESRD patients with extremely calcified PTA occlusions.

Foot infection is a well recognized risk factor for major amputation in diabetic patients. The osteomyelitis is one of the most common expression of diabetic foot infection, being present approximately in present in 10%-15% of moderate and in 50% of severe infectious process. An early and accurate diagnosis is required to ensure a targeted treatment and reduce the risk of major amputation. The aim of this review is to report a complete overview about the management of diabetic foot osteomyelitis. Epidemiology, clinical aspects, diagnosis and treatment are widely described according to scientific reccomendations and our experience.

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.

Diabetic foot is a major public health issue, driven by diabetes complications (neuropathy, peripheral vascular disease, foot deformity, and abnormal leucocyte function), which may lead to leg amputation, thus resulting in severe disability, reduced quality of life, and high health costs. The prevention of diabetes complications and the early detection and proper management of diabetic foot wounds are the milestones to avoid major amputations. Unfortunately, in many areas, the prevention of diabetic foot lesions is inadequate and wounds may proceed toward infection and chronicity, with limb- and life-threatening results. Using the Delphi method, we conducted a survey on diabetic foot among Italian experts, selected across different Italian clinical centers. This method was used to achieve a consensus on current opinion and clinical leanings on the diagnosis and management of diabetic foot ulcers. Specifically, the aim of the survey was to evaluate the current management of the diabetic foot syndrome; highlight the differences in the approach among a group of experts; evaluate the role of wound bed preparation and antisepsis; and discuss any areas of disagreement in which evidences are sparse and the clinical judgment plays a crucial role in the decision-making process.

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.

Diabetic foot infections represent a severe complication of long-standing diabetes. If not adequately recognized, the infection could spread from a foot ulcer to the bone, thus causing osteomyelitis (OM) that exposes the patients to the risk of amputation, bacteraemia/septicaemia and death. One of the most difficult aspects in the evaluation of a diabetic foot is to differentiate between OM, soft tissue infection (STI) and Charcot foot because these three conditions require very different therapeutic approaches. Despite the correct diagnosis could be achieved with the isolation of the pathogen from bone or soft tissues, it would be desirable to have non-invasive test able to diagnose and localize an infection with high accuracy. In this chapter, we examine the pros and cons of NM modalities in the approach at diabetic foot disorders.

Aim. To evaluate the prognostic role of procalcitonin (PCT) in patients with diabetic foot infection (DFI) and critical limb ischemia (CLI). Materials and Methods. The study group was composed of diabetic patients with DFI and CLI. All patients were treated according to a preset limb salvage protocol which includes revascularization, wound debridement, antibiotic therapy, and offloading. Inflammatory markers, including PCT, were evaluated at admission. Only positive values of PCT, greater than 0.5 ng/ml, were considered. Hospital outcomes were categorized as limb salvage (discharge with preserved limb), major amputation (amputation above the ankle), and mortality. Results. Eighty-six patients were included. The mean age was 67.3±11.4 years, 80.7% were male, 95.1% had type 2 diabetes, and the mean diabetes duration was 20.5±11.1 with a mean HbA1c of 67±16 mmol/mol. 66/86 (76.8%) of patients had limb salvage, 7/86 (8.1%) had major amputation, and 13/86 (15.1%) died. Patients with positive PCT baseline values in comparison to those with normal values showed a lower rate of limb salvage (30.4 versus 93.6%, p=0.0001), a higher rate of major amputation (13 versus 6.3%, p=0.3), and a higher rate of hospital mortality (56.5 versus 0%, p<0.0001). At the multivariate analysis of independent predictors found at univariate analysis, positive PCT was an independent predictor of major amputation [OR 3.3 (CI 95% 2.0-5.3), p=0.0001] and mortality [OR 4.1 (CI 95% 2.2-8.3), p<0.0001]. Discussion. Positive PCT at admission increased the risk of major amputation and mortality in hospital patients with DFI and CLI.

Hypoglycemic agents differ in mechanism, efficacy, and profile. However, there is uncertainty on their impact on myocardial perfusion. We thus aimed to investigate whether individuals with type 2 diabetes mellitus treated with different drug classes exhibit different perfusion patterns at myocardial perfusion scintigraphy (MPS).We queried our administrative database for patients with diabetes mellitus without prior or recent myocardial infarction. The primary objective was to compare the severity and extent of ischemia at MPS, distinguishing patients according to management strategy. A total of 7592 patients were included [2336 (31%) on diet, 3611 (48%) on metformin, 749 (10%) on sulfonylureas, 449 (6%) on metformin plus sulfonylureas, 447 (6%) on metformin plus insulin]. Unadjusted analyses and analyses adjusting for baseline features suggested that sulfonylureas alone or in combination were associated with more severe ischemia than nonsulfonylurea regimens (P0.05), whereas combination regimens including metformin were associated with more extensive myocardial ischemia than the other regimens (P0.05 for both). However, no significant difference disfavoring either metformin or sulfonylurea regimens persisted after multivariable adjustment for baseline, stress, and angiographic characteristics (all P0.05).Several significant differences in baseline, stress, and scintigraphic features appear evident in patients with diabetes mellitus receiving different hypoglycemic agents or regimens.

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.

To evaluate the impact of below-the-ankle (BTA) arterial disease in people with ischemic diabetic foot ulcers (DFUs).Patients with ischemic DFUs treated by a pre-set limb salvage protocol including peripheral revascularization were included. They were divided in two groups according to the involvement of BTA arteries (BTA+) or not (BTA-). Not healing, minor amputation, major amputation and mortality have been evaluated as primary outcome. Revascularization failure has been evaluated as secondary outcome.The study group was composed of 272 patients, 120 (44.1%) belonging to BTA+ group and 152 (55.9%) to BTA-. After 1 year of follow-up the outcomes for BTA+ and BTA- were respectively: not healing (40.8 vs 17.8%, p 0.0001), minor amputation (80.8 vs 20.4%, p 0.0001), major amputation (18.3 vs 6.6%, p = 0.002), mortality (16.7% vs 10.5%, p = 0.001). The rate of revascularization failure was respectively 38.3 vs 11.2%, p 0.0001. At the multivariate analysis BTA arterial disease resulted an independent predictor of not healing [OR 3.5 (CI 95% 2.3-6.1) p = 0.0001], minor amputation [OR 3.1 (1.5-5.9) p 0.0001] and revascularization failure [OR 3.5 (1.9-6.3) p = 0.0001]. BTA+ patients with successful BTA revascularization showed lower rate of not healing (37.8 vs 89.1%) p 0.0001, minor amputation (74.3 vs 91.3%) p = 0.002 and major amputation (8.1 vs 34.8%) p = 0.0003 in comparison to patients with unsuccessful BTA revascularization.BTA arterial disease severely impairs the outcomes of diabetics with ischemic foot ulcers. BTA revascularization reduces the rate of not healing, minor and major amputation.

Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders, characterized by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. Several pathways have been implicated in the pathogenesis of neuronal degeneration in HSAN, while recent observations point to an emerging role of cytoskeleton organization and function. Here, we report novel biallelic mutations in the DST gene encoding dystonin, a large cytolinker protein of the plakin family, in an adult form of HSAN type VI. Affected individuals harbored the premature termination codon variant p.(Lys4330*) in trans with the p.(Ala203Glu) change affecting a highly conserved residue in an isoform-specific N-terminal region of dystonin. Functional studies showed defects in actin cytoskeleton organization and consequent delayed cell adhesion, spreading and migration, while recombinant p.Ala203Glu dystonin loses the ability to bind actin. Our data aid in the clinical and molecular delineation of HSAN-VI and suggest a central role for cell-motility and cytoskeletal defects in its pathogenesis possibly interfering with the neuronal outgrowth and guidance processes.

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.

Objective: To establish the rate of clinical recurrence of critical limb ischemia (CLI) in diabetic patients with ischemic foot ulcers (DFUs) treated by percutaneous transluminal angioplasty (PTA). Approach: The study group was composed of 304 patients with ischemic DFUs treated by PTA. We evaluated the rate of clinical recurrence of CLI requiring a second PTA (repeated PTA [rePTA]), the factors related to CLI relapse, and the outcomes of rePTA patients. The follow-up was 12.5 ± 6.6 months. Results: Seventy-four of 304 patients (24.3%) needed rePTA. The mean time to rePTA was 3.5 ± 0.64 months. rePTA group in comparison with no rePTA group had lower rate of healing (28.5% vs. 71.9% p = 0.0001), higher rate of ulcer recurrence (20% vs. 10.3% p = 0.03), major amputation (24.3% vs. 4.3% p = 0.0005), and death (33.3% vs. 7.9% p = 0.002). Glycated hemoglobin, type A1C (HbA1c; 2.2 [1.9-2.7] p = 0.02) and dialysis (1.5 [1.4-3.6] p = 0.006) were independently associated to clinical recurrence of CLI after PTA. Innovation: To identify the outcomes of patients with clinical recurrence of CLI and the clinical factors involved to reduce the rate of restenosis after endovascular treatment and improve the rate of limb salvage. Conclusions: Clinical recurrence of CLI is associated with a high rate of nonhealing ulcer recurrence, major amputation, and death. Dialysis and impaired glycemic control were independent predictors of CLI relapse after endovascular treatment.

Summary Background Diabetic foot ulcers are serious and challenging wounds associated with high risk of infection and lower-limb amputation. Ulcers are deemed neuroischaemic if peripheral neuropathy and peripheral artery disease are both present. No satisfactory treatment for neuroischaemic ulcers currently exists, and no evidence supports one particular dressing. We aimed to assess the effect of a sucrose octasulfate dressing versus a control dressing on wound closure in patients with neuroischaemic diabetic foot ulcers. Methods We did a randomised, double-blind clinical trial (Explorer) in 43 hospitals with specialised diabetic foot clinics in France, Spain, Italy, Germany, and the UK. Eligible participants were inpatients or outpatients aged 18 years or older with diabetes and a non-infected neuroischaemic diabetic foot ulcer greater than 1 cm 2 and of grade IC or IIC (as defined by the University of Texas Diabetic Wound Classification system). We excluded patients with a severe illness that might lead to them discontinuing the trial and those who had surgical revascularisation in the month before study entry. We randomly assigned participants (1:1) via a computer-generated randomisation procedure (concealed block size two); stratified by study centre and wound area (1–5 cm 2 and 5–30 cm 2 ), to treatment with either a sucrose octasulfate wound dressing or a control dressing (the same dressing without sucrose octasulfate) for 20 weeks. Both groups otherwise received the same standard of care for a 2-week screening period before randomisation and throughout the 20-week trial. Dressings were applied by nursing staff (or by instructed relatives for some outpatients). Frequencies of dressing changes were decided by the investigator on the basis of the clinical condition of the wound. Patients were assessed 2 weeks after randomisation, then monthly until week 20 or occurrence of wound closure. The primary outcome, assessed by intention-to-treat, was proportion of patients with wound closure at week 20. This trial is registered with ClinicalTrials.gov, number NCT01717183. Findings Between March 21, 2013, and March 31, 2016, we randomly assigned 240 individuals to treatment: 126 to the sucrose octasulfate dressing and 114 to the control dressing. After 20 weeks, wound closure occurred in 60 patients (48%) in the sucrose octasulfate dressing group and 34 patients (30%) in the control dressing group (18 percentage points difference, 95% CI 5–30; adjusted odds ratio 2·60, 95% CI 1·43–4·73; p=0·002). In both groups, the most frequent adverse events were infections of the target wound: 33 wound infections in 25 (20%) patients of 126 in the sucrose octasulfate dressing group and 36 in 32 (28%) patients of 114 in the control dressing group. Minor amputations not affecting the wound site were also reported in one (1%) patient in the sucrose octasulfate dressing group and two (2%) patients in the control dressing group. Three (2%) patients assigned to the sucrose octasulfate dressing and four (4%) assigned to the control dressing died, but none of the deaths were related to treatment, procedure, wound progression, or subsequent to amputation. Interpretation A sucrose octasulfate dressing significantly improved wound closure of neuroischaemic diabetic foot ulcers without affecting safety after 20 weeks of treatment along with standard care. These findings support the use of sucrose octasulfate dressing as a local treatment for neuroischaemic diabetic foot ulcers. Funding Laboratoires Urgo Medical.

OBJECTIVE Infection commonly complicates diabetic foot ulcers and is associated with a poor outcome. In a cohort of individuals with an infected diabetic foot ulcer, we aimed to determine independent predictors of lower-extremity amputation and the predictive value for amputation of the International Working Group on the Diabetic Foot (IWGDF) classification system and to develop a risk score for predicting amputation. RESEARCH DESIGN AND METHODS We prospectively studied 575 patients with an infected diabetic foot ulcer presenting to 1 of 14 diabetic foot clinics in 10 European countries. RESULTS Among these patients, 159 (28%) underwent an amputation. Independent risk factors for amputation were as follows: periwound edema, foul smell, (non)purulent exudate, deep ulcer, positive probe-to-bone test, pretibial edema, fever, and elevated C-reactive protein. Increasing IWGDF severity of infection also independently predicted amputation. We developed a risk score for any amputation and for amputations excluding the lesser toes (including the variables sex, pain on palpation, periwound edema, ulcer size, ulcer depth, and peripheral arterial disease) that predicted amputation better than the IWGDF system (area under the ROC curves 0.80, 0.78, and 0.67, respectively). CONCLUSIONS For individuals with an infected diabetic foot ulcer, we identified independent predictors of amputation, validated the prognostic value of the IWGDF classification system, and developed a new risk score for amputation that can be readily used in daily clinical practice. Our risk score may have better prognostic accuracy than the IWGDF system, the only currently available system, but our findings need to be validated in other cohorts.

Main goal of human foot evolution was to allow safe and effective barefoot motion on natural grounds. Footwear came afterwards, to protect the foot from extreme environmental conditions, to improve walking and running performance, and to cope with challenging surfaces also including new artificial substrates. But while on the one side shoes and insoles—i.e., footwear—act beneficially on the foot, on the other side they may limit foot function and render the foot itself more fragile and less prone to adaptation. This may lead the shod foot to unnaturally concentrate peak pressures under small areas at heel, forefoot, and hallux. Such a potentially dangerous condition may likely happen in diabetic patients with long-term complications, such as peripheral neuropathy, which deeply modify foot structure, foot function, and the resulting gait. Without proper protection, such patients are made vulnerable and at risk of foot ulceration. Unsuitable footwear may precipitate this condition and may be responsible for the new appearance or the recurrence of a foot ulcer. Research efforts during the last 50 years helped to better understand the criteria to take into account when prescribing or making proper footwear and/or plantar orthoses to: prevent diabetic foot ulceration (primary prevention); manage healing of an active ulcer; and prevent ulcer recurrences (secondary prevention). However, despite these huge advances in knowledge, recent literature still claims the lack of strong evidence about clinical efficacy of diabetic footwear especially in preventing first ulcer occurrence. Main reasons for that, among which the still poor adherence to treatment, are presented and discussed in the following, together with a literature review of the most recent peer-reviewed studies and position papers, to bring attention on the main causes for the still limited success of footwear intervention in diabetes and on a desirable improvement of diabetic foot care.

Insulin autoimmune syndrome is an unusual cause of spontaneous hypoglycaemia in non-Asian populations. In the majority of cases, this syndrome appears a few weeks after the administration of drugs containing a sulfhydryl group. A strong association between this syndrome and HLA-DR4 has been shown. Only seven cases have been described in non-Asian patients. We report the first case of insulin autoimmune syndrome in an Argentine woman taking alfa-lipoic acid. She developed hypoglycaemic symptoms approximately 1 month after starting therapy. Blood sampling collected during an episode of symptomatic hypoglycaemia showed low blood glucose level (2.39 mmol/L), high level of serum insulin (1971.55 pmol/L), inappropriately high level of C-peptide (2.36 nmol/L) and high levels of insulin antibodies (274.78 IU/mL). HLA-DNA typing identified DRB1*04:03. Due to the widespread use of alfa-lipoic acid for its antioxidant properties, clinicians should be aware that it may trigger an autoimmune hypoglycaemia in people with a genetic predisposition.

Plantar pressure is critical in the onset of neuropathic foot ulcers. However, risk classifications do not consider it as a stratification parameter. Whether plantar pressure distribution affects ulcer-risk was investigated. Patients from a research study (n. 134) and from a clinical environment (n. 83) were classified into ulcer-risk groups according to the International Working Group on the Diabetic Foot guidelines. Pressure distribution was acquired during gait (Pedar-X System), and assessed for hindfoot, midfoot, forefoot and toes (1way- and 2way-ANOVAs, p0.05). Pressure distribution changed with polyneuropathy even in the low-risk groups: median p = 0.048 (0.001-0.223). Risk classification correlated poorly with pressure distribution: median p = 0.686 (0.374-0.828). BMI, age and walking speed influenced most parameters and rendered the studies almost impossible to compare (2-way ANOVA factor A0.05). Pressure-time integral, the only comparable parameter between the two studies, may increase the predictive capacity of ulcer-risk stratification models.

Aim To establish the role of heart failure (HF) and dialysis (D) in the prognosis of diabetic patients with critical limb ischemia and foot ulcers (FUs). Methods Consecutive diabetic patients with ischemic FUs who referred to our Diabetic Foot Centre were prospectively included. All patients underwent a preset limb salvage protocol including peripheral revascularization. According to the presence of HF and D, they were divided in four groups: group 1 without HF and without D defined as ischemic foot (IF); group 2 with HF and without D defined as heart ischemic foot (H-IF); group 3 without HF and with D defined as renal ischemic foot (R-IF); group 4 with HF and with dialysis defined as heart-renal foot (HR-IF). Survival with limb salvage, survival with major amputation and death were reported after 1 year of follow-up. Results 136 patient have been included: 66 with IF, 26 with H-IF, 24 with R-IF and 20 with HR-IF. The mean age was 68,9 ± 9,7 years, the diabetes duration 20,7 ± 11,6 years, the mean HbA1c 62,7 ± 22,3 mmol/mol. 103/136 (75,7%) survived with limb salvage, 10/136 (7,4%) survived with major amputation, 23/136 (16,9%) died. The outcomes for group IF patients, H-IF, R-IF and HR-IF were respectively: survival with limb salvage (92,4%, 61,5%, 79,2% and 35%), survival with major amputation (6,1%, 7,7%, 8,3% and 10%), death (1,5%, 30,8%, 12,5% and 55%) χ = 0.0001. Heart failure was an independent predictor of death. Discussion The presence of heart failure and dialysis in diabetic patients with ischemic foot ulcers was associated to high risk of amputation and mortality.