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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.

We aimed to analyze sex-related differences in clinical outcomes among patients with diabetic foot disease (DFD) managed in a third-level referral center. We retrospectively analyzed data of admissions performed in our department between 2011 and 2015 for DFD. We collected demographic and clinical data, procedures performed during the admission, and short- and long-term outcomes in terms of healing rate and healing time, major amputation, and mortality rates during the follow-up. We focused on differences between genders and tried to figure out if sex could be considered a predictive factor. We collected data from 1237 admission performed in 842 patients (615 men [73%] and 227 women [27%]; age: 68.6 ± 27.9 years; diabetes duration: 16.4 ± 13.4 years; body mass index: 28.2 ± 6.4 kg/m2; hemoglobin A1c 7.9 ± 1.9%). Men showed a higher prevalence of comorbidities and previous ulcers or revascularization procedures. Men had a significantly higher healing rate compared with women (85.4% vs 63.2%, P < .001), but a longer healing time (124 ± 27 days vs 87 ± 14 days, P = .02). Major amputation did not differ between groups, while mortality rate was significantly higher in men (24.5% vs 16.1%, P = .02). In Cox’s regression analysis, male sex was a positive predictive factor for healing and a negative one for time to heal and mortality. The difference in mortality was confirmed by a Kaplan-Meier analysis (log rank test: P = .03). DFD represents a severe disease and a strong marker of mortality affecting more severely on clinical outcomes and survival on men.

Diabetic foot ulceration (DFU) is a severe complication of diabetes mellitus associated with a high morbidity and mortality rate, whose treatment requires considerable financial costs. This paper describes a test of the efficacy of proactive screening – autonomously managed by nurses in a community setting – in detecting patients at high risk of DFU, as an integrated part of a chronic care model strategy.

To test safety and efficacy of bioactive glass, a novel material used to replace bone, able to completely bond itself to the host tissues on patients treated for osteomyelitis (OM) complicating a diabetic foot (DF). We evaluated a group of patients consecutively admitted in our department between September and December 2018, who underwent surgical DF procedures for OM and in whom the use of bioactive glass could limit the demolition phase of surgical procedure. Patients were treated with bioactive glass S53P4 on top of standard treatment directly in operating room. The patients were weekly controlled for 6 months or until complete healing. During follow-up, we analyzed primarily healing rate and secondarily time of healing, need for further debridement procedures, recurrences, and adverse or hypersensitivity reactions to study treatment. Ten DF patients were enrolled (male/female 6/4; mean age 56 ± 11 years; mean duration of diabetes 10.5 ± 4.7 years, mean hemoglobin A1c 7.2 ± 0.9%). Patients underwent surgical procedure during which, after an accurate debridement, bioactive glass was applied. A healing rate of 80% in a mean time of 34 ± 2 days, with only 1 patient who needed a second surgical look, was observed. Neither recurrences nor adverse events during follow-up were observed in treated patients. This pilot experience demonstrated that bioactive glass can be considered a useful tool for the surgical treatment of DF-related OM.

Aim To evaluate the distinct contribution of obesity and diabetes (DM) to the skin modification in metabolic diseases. Methods We analysed all patients admitted for bariatric surgery in our hospital with BMI between 38 and 47 kg/m2, with (Group 1) or without (Group 2) DM and compared them with a group of nonobese diabetic patients (Group 3) and healthy volunteers (Group 4). The following features were evaluated: hardness, temperature, hydration and thickness alongside with anthropometric measures of foot and leg. Results For the general characteristics, patients differed in age and body mass index. As predictable all circumferences (dorsal foot, sovramalleolar and under the knee) were significantly higher in obese with no differences depending on DM (all parameters: p

Objectives Revascularization according to the angiosome concept is of proven importance for limb salvage in chronic limb threatening ischaemia but it is not always practicable. Bifurcated bypasses could be considered as an option when an endovascular approach is not feasible or has already failed and a single bypass would not allow direct revascularization of the ischaemic area. Bifurcated bypasses are characterized by landing on two different arteries, the main artery (in direct continuity with the foot vessels) and the secondary one (perfusing the angiosome district). The aim of this study is to evaluate the safety and effectiveness of bifurcated bypass in chronic limb threatening ischaemia. Methods Thirty-five patients were consecutively treated with a bifurcated bypass for chronic limb threatening ischaemia from January 2014 to December 2019 in a single vascular surgery centre. Data from clinical records and operative registers were collected prospectively in an electronic database and retrospectively analysed. Primary and primary assisted bypass patency, amputation-free survival, morbidity and mortality rates at 12 and 24 months were analysed. Results Mean follow-up period was 25.1 months (range 2–72 months). Thirty-six bifurcated bypasses were performed on 35 patients (age 75.3 ± 7.2 years; 69.4% were male). According to Wound, Ischemia, foot Infection classification 22.2% belonged to stage 3 and 77.8% to stage 4 and the mean Rutherford’s class was 5.1 ± 0.7. Immediate technical success was 100%. Early mortality and morbidity rates were respectively 5.5%, and 33.3%; foot surgery was performed in 50% of cases with wound healing in all patients. Primary patency and primary assisted bypass patency were 96.7% and 100% at 6 months; 85.2% and 92% at 12 months, 59.9% and 73.4% at 24 months, respectively. Amputation-free survival at 12 and 24 months was, respectively, 95.6% and 78.8%. Overall survival rates at 12 and 24 months were respectively 94.4% and 91.6%. Conclusions Bifurcates bypass can provide good results in patients with chronic limb threatening ischaemia without endovascular option, especially in diabetic ones. Bifurcated bypass is a complex surgical solution, both to be planned and performed, and it is quite invasive for frail patients that should be accurately selected.

Objective: In March 2018, the Explorer study, an international, double-blind, randomised controlled trial (RCT), established that adding a TLC-NOSF (UrgoStart Contact, Laboratoires Urgo, France) dressing to good local standard of care (SoC) significantly and substantially increases wound closure and reduces the healing time of neuroischaemic diabetic foot ulcers (DFU). Besides the TLC-NOSF treatment, the wound duration was the only other covariate that had an influence on the wound closure rate in the regression model used in the original study. The purpose of this work was to further document the impact of wound duration on the healing outcomes of the DFUs included in the Explorer study and to discuss complementary pragmatic observations on the TLC-NOSF effect. Method: In this post-hoc analysis of the Explorer data, the wound closure rates by week 20 are reported for the global cohort (n=240, Intention-to-treat population) and for the treated (n=126) and control groups (n=114) according to DFU duration and location. Results: For the combined group, wound closure rates decreased with the increase of wound duration at baseline (from 57% in wounds ≤2 months to 19% in wounds >11 months). Whatever the wound duration subgroups analysed, higher closure rates were reported in the TLC-NOSF group than in the control group. However, the maximal difference between the two treatments was reported in wounds with a duration of ≤2 months (71% versus 41%, 30 percentage points difference, Relative Risk 1.7, 95% Confidence Interval 1.1 to 2.8). Regarding wound location subgroup analyses, the outcomes were always in favour of the TLC-NOSF treatment, with closure rates ranging between 43% and 61% within the TLC-NOSF group, and between 25% and 40% within the control group. Conclusion: This clinical evidence supports that treating DFUs with TLC-NOSF dressing and good SoC results in higher wound closure rates than with a neutral dressing and the same good standard of care, whatever the duration and the location of the treated wounds. However, the earlier the TLC-NOSF dressing is initiated in DFU treatment, the greater the benefits.

Background We evaluated whether direct or indirect endovascular revascularization based on the angiosome model affects outcomes in type 2 diabetes and critical limb ischemia. Methods From 2010 to 2015, 603 patients with type 2 diabetes were admitted for critical limb ischemia and submitted to endovascular revascularization. Among these patients, 314 (52%) underwent direct and 123 (20%) indirect revascularization, depending on whether the flow to the artery directly feeding the site of ulceration, according to the angiosome model, was successfully acquired; 166 patients (28%) were judged unable to be revascularized. Outcomes were healing, major amputation, and mortality rates. Results An overall healing rate of 62.5% was observed: patients who did not receive percutaneous transluminal angioplasty presented a healing rate of 58.4% (P < .02 versus revascularized patients). A higher healing rate was observed in the direct versus the indirect group (82.4% versus 50.4%; P < .001). The major amputation rate was significantly higher in the indirect versus the direct group (9.2% versus 3.2%; P < .05). The overall mortality rate was 21.6%, and it was higher in the indirect versus the direct group (24% versus 14%; P < .05). Conclusions These data show that direct revascularization of arteries supplying the diabetic foot ulcer site by means of the angiosome model is associated with a higher healing rate and lower risk of amputation and death compared with the indirect procedure. These results support use of the angiosome model in type 2 diabetes with critical limb ischemia.

Male patients, especially the young, are at a higher risk of recurrent venous thromboembolism (RVTE) than females. Recent scientific reports show the use of D-dimer does not help predict RVTE risk in males. In the present report, we reviewed the data obtained in the DULCIS study (main report published in Blood 2014), focusing on D-dimer results recorded in non-elderly patients of both genders included in the study, and their relationship with RVTE events occurring during follow-up. Using specifically designed cutoff values for positive/negative interpretation, serial D-dimer measurements (performed during warfarin treatment and up to 3 months after discontinuation of anticoagulation) in 475 patients (males 57.3%) aged ≤ 65 years were obtained. D-dimer resulted positive in 46.3% and 30.5% of males and females, respectively (p = 0.001). Following management procedure, anticoagulation was stopped in 53.7% of males and 69.5% of females, who had persistently negative D-dimer results. The rate of subsequent recurrent events was 1.7% (95% CI 0.5–4.5%) and 0.4% (95% CI 0–2.5%) patient-years in males and females, respectively, with upper limits of confidence intervals always below the level of risk considered acceptable by international scientific societies for stopping anticoagulation (

Ultrasound (US) is a noninvasive and versatile technology that in recent years found acceptance in almost all the medical specialties, with diagnostic and interventional applications. In the diabetic foot syndrome (DFS), US found specific indications mainly in the screening, quantification, and follow-up of the vascular component of the pathology, but also in the study of the deformities and structural modifications induced by neuropathy and in the diagnosis and surgical management of infections, especially those that induce anatomical changes, like abscesses and fasciitis. This review will summarize all these application of US, giving special attention to the vascular aspects, and on the predominant role that US gained in recent times to guide the indication to revascularization, on the new standardized approach to the study of the arterial tree of the limb and the foot, the so-called duplex ultrasound arterial mapping, which significantly increased the utilization of US to plan the revascularizations in this complex pathology. Outside the vascular fields, the diagnosis of neuropathy and infection and the intraoperative use of US in the surgical management of abscesses and fasciitis will be discussed, leaving the last part to the new and interesting applications of US in the management of DFU, a field that is still in evolution, offering new possibilities to the health care professionals involved in the management of these chronic wounds. The variety of applications both in diagnostic and operative fields makes US a rather versatile technology—a toolkit—that should have a special place among those at reach of the specialists of DFS care.

To evaluate clinical outcomes in patients who underwent diabetic foot surgery (DFS) managed directly by diabetologists in a third-level Centre over 15-year.We retrospectively evaluated 1.857 patients affected by diabetic foot (Age 67.1 ± 12.3 yrs, diabetes duration 19.2 ± 9.8 yrs, HbA1c 8.1 ± 2.0%) treated in our Department between 2001 and 2015 and divided them into 3 groups: Group 1, treated between 2001 and 2005 (448 pts), group 2, between 2006 and 2010 (540 pts) and Group 3, between 2011 and 2015 (869 pts). Main clinical outcomes [peripheral revascularization rate (PR), healing rate (HR), healing time (HT), recurrences after healing (R), major amputation (MA) and death (D) rates] were compared between groups.The overall outcomes of our cohort were: HR 81.6% (HT 143 ± 54 days), PR 84.8%, MA 4.9% and D 27.9%. There were no differences in clinical characteristics, except for age, higher (p 0.05) in Group 3 (70.6 ± 14.7 yrs) than in Groups 1 (64.4 ± 11.6 yrs) and 2 (65.1 ± 11.2 yrs). No differences emerged when comparing HR and MA; HT was shorter (p 0.05) in group 3 (104 ± 44 days) than in Group 2 (169 ± 72 days) and 1 (235 ± 67 days). D was higher (p 0.05) in Group 3 (43.8%) than in Group 1 (23.1%) and 2 (28.1%). PR was 19.4% in Group 1, 28.1% in Group 2 and 53.8% in Group 3 (p 0.05).Despite the increasing age and complexity of patients our data show improvement of outcomes throughout 15 years, probably due to better surgical techniques, more aggressive medical therapy and more effective treatment of critical limb ischemia.

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. In conjunction with advice from internal and external reviewers and expert consultants in the field, this update is based on a systematic review of the literature centred on the following: the Population (P), Intervention (I), Comparator (C) and Outcomes (O) framework; the use of the SIGN guideline/Cochrane review system; and the 21 point scoring system advocated by IWGDF/EWMA. This has resulted in 13 recommendations. The recommendation on sharp debridement and the selection of dressings remain unchanged from the last recommendations published in 2016. The recommendation to consider negative pressure wound therapy in post-surgical wounds and the judicious use of hyperbaric oxygen therapy in certain non-healing ischaemic ulcers also remains unchanged. Recommendations against the use of growth factors, autologous platelet gels, bioengineered skin products, ozone, topical carbon dioxide, nitric oxide or interventions reporting improvement of ulcer healing through an alteration of the physical environment or through other systemic medical or nutritional means also remain. New recommendations include consideration of the use of sucrose-octasulfate impregnated dressings in difficult to heal neuro-ischaemic ulcers and consideration of the use of autologous combined leucocyte, platelet and fibrin patch in ulcers that are difficult to heal, in both cases when used in addition to best standard of care. A further new recommendation is the consideration of topical placental derived products when used in addition to best standard of care.

The management of diabetic foot ulcers (DFU) remains a challenge, and there is continuing uncertainty concerning optimal approaches to wound healing. The International Working Group of the Diabetic Foot (IWGDF) working group on wound healing has previously published systematic reviews of the evidence in 2008, 2012 and 2016 to inform protocols for routine care and to highlight areas which should be considered for further study. The working group has now updated this review by considering papers on the interventions to improve the healing of DFU's published between June 2014 and August 2018. Methodological quality of selected studies was independently assessed by a minimum of two reviewers using the recently published 21-point questionnaire as recommended by IWGDF/European Wound Management Association, as well as the previously incorporated Scottish Intercollegiate Guidelines Network criteria. Of the 2275 papers identified, 97 were finally selected for grading following full text review. Overall, there has been an improvement in study design and a significant rise in the number of published studies. While previous systematic reviews did not find any evidence to justify the use of newer therapies, except for negative pressure wound therapy in post-surgical wounds, in this review we found additional evidence to support some interventions including a sucrose-octasulfate dressing, the combined leucocyte, fibrin and platelet patch as well as topical application of some placental membrane products, all when used in addition to usual best care. Nonetheless, the assessment and comparison of published trials remains difficult with marked clinical heterogeneity between studies: in patient selection, study duration, standard of usual care provision and the timing and description of the clinical endpoints.

Guillain-Barré syndrome (GBS) represents an acute inflammatory immune-mediated demyelinating polyradiculoneuropathy with an incidence of 0.6 per 100 000 people. In this article, we report the case of a 19-year-old girl affected by GBS since the age of 2 who presented at our clinic complaining for a chronic plantar hindfoot–infected ulceration. Serology showed increase of inflammatory markers and leukocytosis, and magnetic resonance imaging revealed osteomyelitis of calcaneum and soft tissue alterations with air bubbles. The patient was treated in our clinic by an integrated multidisciplinary approach consisting of immediate admission, soft tissue and bone debridement, and administration of antibiotics under the close control of infectious disease specialist. After the control of acute condition, the patient underwent negative pressure therapy associated with instillation of antiseptic solution until the restoration of bone and soft tissue loss of substance and, eventually, to the application of bioactive glass substitute until the achievement of complete wound healing.

Necrotizing fasciitis (NF) is a rapidly progressive, life-threatening infection, involving the skin, soft tissue and fascia. We evaluated outcomes of its surgical management in diabetic foot (DF) patients in a tertiary referral centre. We retrospectively searched for NF in the database of our DF Section from 2016 to 2018. All cases were treated according to a multiprofessional integrated protocol, with Prompt Identification, Surgical debridement and systemic Antibiotic therapy (P.I.S.A. Protocol). We analysed short-term evolution (surgical procedures and major amputations), and long-term outcomes (survival and healing rates). Sixty-eight patients were referred to our DF clinic for suspicion of NF. The diagnosis was confirmed in 54 (79.4%; male/female 40/14; type 1/2 diabetes 6/48; age 62.8 ± 8.1 years; duration of diabetes 13.6 ± 10.1 years). According to the microbiological results, cases were classified as Type 1 (33–61.2%), 2 (7−12.9%) and 3 (14–25.9%). No significant differences were observed. All patients underwent a decompressive fasciotomy. Six patients (11.1%) required also a forefoot amputation and 12 (22.2%) a toe or ray amputation. No major amputation was performed in the short-term period. During the follow-up (26 ± 12 months) 46 patients (85%) healed in 94 ± 11 days. Of the remaining 8: 5 (9.2%) died for other reasons before healing, 2 (3.7%) recurred and one (1.9%) required a major amputation. Our experience reveals a relatively high prevalence of NF in DF; despite this, we observed how, when promptly and aggressively treated, NF has a good prognosis and it is not associated with an excess of limb loss and deaths.

1. Introduction Since its introduction in clinical practice in the early 1990's negative pressure wounds therapy (NPWT) has become widely used in the management of complex wounds in both inpatient and outpatient care.1 NPWT has been described as a effective treatment for wounds of many different aetiologies2,3 and suggested as a gold standard for treatment of wounds such as open abdominal wounds,4–6 dehisced sternal wounds following cardiac surgery7,8 and as a valuable agent in complex non-healing wounds.9,10 Increasingly, NPWT is being applied in the primary and home-care setting, where it is described as having the potential to improve the efficacy of wound management and help reduce the reliance on hospital-based care.11 While the potential of NPWT is promising and the clinical use of the treatment is widespread, highlevel evidence of its effectiveness and economic benefits remain sparse.12–14 The ongoing controversy regarding high-level evidence in wound care in general is well known. There is a consensus that clinical practice should be evidence-based, which can be difficult to achieve due to confusion about the value of the various approaches to wound management; however, we have to rely on the best available evidence. The need to review wound strategies and treatments in order to reduce the burden of care in an efficient way is urgent. If patients at risk of delayed wound healing are identified earlier and aggressive interventions are taken before the wound deteriorates and complications occur, both patient morbidity and health-care costs can be significantly reduced. There is further a fundamental confusion over the best way to evaluate the effectiveness of interventions in this complex patient population. This is illustrated by reviews of the value of various treatment strategies for non-healing wounds, which have highlighted methodological inconsistencies in primary research. This situation is confounded by differences in the advice given by regulatory and reimbursement bodies in various countries regarding both study design and the ways in which results are interpreted. In response to this confusion, the European Wound Management Association (EWMA) has been publishing a number of interdisciplinary documents15–19 with the intention of highlighting: The nature and extent of the problem for wound management: from the clinical perspective as well as that of care givers and the patients Evidence-based practice as an integration of clinical expertise with the best available clinical evidence from systematic research The nature and extent of the problem for wound management: from the policy maker and healthcare system perspectives The controversy regarding the value of various approaches to wound management and care is illustrated by the case of NPWT, synonymous with topical negative pressure or vacuum therapy and cited as branded VAC (vacuum-assisted closure) therapy. This is a mode of therapy used to encourage wound healing. It is used as a primary treatment of chronic wounds, in complex acute wounds and as an adjunct for temporary closure and wound bed preparation preceding surgical procedures such as skin grafts and flap surgery. Aim An increasing number of papers on the effect of NPWT are being published. However, due to the low evidence level the treatment remains controversial from the policy maker and health-care system's points of view—particularly with regard to evidence-based medicine. In response EWMA has established an interdisciplinary working group to describe the present knowledge with regard to NPWT and provide overview of its implications for organisation of care, documentation, communication, patient safety, and health economic aspects. These goals will be achieved by the following: Present the rational and scientific support for each delivered statement Uncover controversies and issues related to the use of NPWT in wound management Implications of implementing NPWT as a treatment strategy in the health-care system Provide information and offer perspectives of NPWT from the viewpoints of health-care staff, policy makers, politicians, industry, patients and hospital administrators who are indirectly or directly involved in wound management.

Objective: To test the efficacy and safety of therapeutic magnetic resonance (TMR) in the management of diabetic foot ulcers (DFU), the authors designed a prospective randomised controlled trial in three highly specialised diabetic foot clinics. Method: All the patients consecutively visited in a period of 18 months were screened according to the inclusion (presence of an ulcer >1 cm2 in the foot lasting at least 6 weeks; ABPI>0.6; consent to participate in the study) and exclusion (Charcot's foot; local or systemic infections; chronic renal failure; any wearable electrically-driven life-supporting device) criteria. Patients, who were treated according to international guideline protocols, were randomised into two groups: group A received for four weeks the sham application of TMR, while group B received the active TMR for the same period. People were followed-up to 10 weeks and healing rate (HR), healing time (HT), rate of granulation tissue on wound bed (% GT), reduction of the area of the lesion (∆AL) and a score (0–3) evaluating erythema, oedema, pain and tenderness, respectively, were measured. Adverse events (AE) were registered and monitored throughout the study. Results: No differences were observed in HR, HT and ∆AL between the two groups during follow-up, while % GT and the scores for erythema, oedema and pain at 10 weeks showed significant (p0.8), ∆AL was significantly (pConclusion: Our study, despite not being able to demonstrate the effectiveness of TMR on healing rate at 10 weeks, with 4 weeks of active treatment in neuro-ischaemic DFUs, shows positive effects on clinical aspects of the DFU and is associated with a significant increase of GT in the wound bed. Declaration of interest: The study has been fully sponsored by Thereson S.p.A., manufacturer of TMR devices.

We report results from the clinical use of IDegLira compared to basal-bolus (BB) insulin regimen in T2DM patients admitted to our department because of DFU and CLI. We retrospectively identified 44 consecutive T2DM patients admitted to our diabetes ward because of DFU (M/F: 24/20; age: 67.3±9.5 years; BMI: 30.6±5.2 Kg/m2; diabetes duration (DD): 23.5±9.9 years; HbA1c 71.7±24.5 mmol/mol). During hospitalization, 28 patients (Group A: M/F: 15/13; age: 65.7±8.9 years; BMI: 32.6±4.8 Kg/m2; DD: 21.1±9.9 years; HbA1c 76.1±25.2 mmol/mol) previously on BB (63.7±33.9 U/day), were started on IDegLira (IDeg 22.8±7.8 U/day, liraglutide 0.82±0.3 mg/day) while the remaining 16 (Group B; M/F: 9/7; age: 70.4±10.1 years; BMI: 30.3±2.2 Kg/m2; DD: 27±9.2 years; HbA1c 63.9±22.0 mmol/mol; all p=NS vs. Group A) continued BB (43±18 U/day), allowing comparison over a mean follow-up period of 3 months. Patients were comparable with respect to distal lesions, pain-relieving, antibiotic therapies, revascularization procedures and surgical treatments performed. In Group A, BMI, HbA1c and LDL-C improved significantly (26.4±10.1 Kg/m2; 54±11 mmol/mol; 61.5±32 mg/dl; p Disclosure P. Falcetta: None. F.S. Indovina: None. R. Giannarelli: None. A. Piaggesi: None. G. Penno: None. R. Miccoli: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. A. Coppelli: None.

Background: Offloading interventions are commonly used in clinical practice to heal foot ulcers. The aim of this updated systematic review is to investigate the effectiveness of offloading interventions to heal diabetic foot ulcers. Methods: We updated our previous systematic review search of PubMed, EMBASE, and Cochrane databases to also include original studies published between July 29, 2014 and August 13, 2018 relating to four offloading intervention categories in populations with diabetic foot ulcers: (a) offloading devices, (b) footwear, (c) other offloading techniques, and (d) surgical offloading techniques. Outcomes included ulcer healing, plantar pressure, ambulatory activity, adherence, adverse events, patient-reported measures, and cost-effectiveness. Included controlled studies were assessed for methodological quality and had key data extracted into evidence and risk of bias tables. Included non-controlled studies were summarised on a narrative basis. Results: We identified 41 studies from our updated search for a total of 165 included studies. Six included studies were meta-analyses, 26 randomised controlled trials (RCTs), 13 other controlled studies, and 120 non-controlled studies. Five meta-analyses and 12 RCTs provided high-quality evidence for non-removable knee-high offloading devices being more effective than removable offloading devices and therapeutic footwear for healing plantar forefoot and midfoot ulcers. Total contact casts (TCCs) and non-removable knee-high walkers were shown to be equally effective. Moderate-quality evidence exists for removable knee-high and ankle-high offloading devices being equally effective in healing, but knee-high devices have a larger effect on reducing plantar pressure and ambulatory activity. Low-quality evidence exists for the use of felted foam and surgical offloading to promote healing of plantar forefoot and midfoot ulcers. Very limited evidence exists for the efficacy of any offloading intervention for healing plantar heel ulcers, non-plantar ulcers, and neuropathic ulcers with infection or ischemia. Conclusion: Strong evidence supports the use of non-removable knee-high offloading devices (either TCC or non-removable walker) as the first-choice offloading intervention for healing plantar neuropathic forefoot and midfoot ulcers. Removable offloading devices, either knee-high or ankle-high, are preferred as second choice over other offloading interventions. The evidence bases to support any other offloading intervention is still weak and more high-quality controlled studies are needed in these areas.

There are still many unmet needs in the treatment of chronic wounds, especially regarding microenvironment modulation. Nexodyn is a novel super-oxidized solution capable of contrast bacterial proliferation. We aimed to evaluate if this solution, on top of standard of care, was safe and effective in improving diabetic foot outcome. We selected 50 patients admitted in our department to be submitted to surgery for acute diabetic foot infection. All patients were left open to heal for secondary intent. We divided patients into 2 groups: Group A (n = 25, male/female = 17/8, age = 67.3 ± 12.1 years, hemoglobin A1C = 7.9 ± 1.1%), patients treated with standard of care and, on top of this, Nexodyn solution, and Group B, treated only with standard of care. After discharge, patients continued Nexodyn application. We followed up patients until complete healing or up to 6 months. No differences between groups in healing rate, while time required for complete healing was significantly shorter in Group A (64.9 ± 12.1 days vs 147.4 ± 23.1 days, P < .01). During follow-up, the group treated with Nexodyn showed a reduced rate of reinfections (12 patients in Group B vs 3 patients in Group A, P < .05) and of further debridement procedures (1 patient in Group A vs 10 patients in Group B, P < .05). Nexodyn provided effective protection against reinfections in diabetic foot patients, thus reducing the necessity for debridement procedures and their healing time and presents a safety profile similar to saline solution.

Aim The aim of this study was to evaluate the adherence to guideline recommended medical therapies in type 2 diabetic patients with chronic critical limb ischemia (CCLI). Methods We retrospectively analyzed the data of 1315 admissions performed in our Department, focusing on diabetic foot patients (842–64%) of which 603 consecutive type 2 diabetic patients with CCLI (M/F(%): 73/27; age: 70.3 ± 10.4 yrs; diabetes duration: 17.3 ± 13.7 yrs; BMI: 27.7 ± 5.3 Kg/m2; HbA1c 7.8 ± 1.8%) referred to a third-level Center from 2011 to 2015. We focused on medical therapy of diabetes, dyslipidemia, hypertension, peripheral vascular disease and smoke habits. Results In total, at admission, 66.6% of patients had HbA1c levels higher than recommended; 65.9% of patients were on statins; 81.4% on anti-hypertensive treatment and 72.4% on antiplatelet drugs. Concerning smoke habits, 27% of patients were no-smokers; 41% former smokers and 32% active smokers. Among all patients, only 24% were prescribed all five guideline recommended therapies while 32% reached four out of five of these. As for patients treated with anti-hypertensive drugs, we observed higher levels of systolic pressure (138.0 ± 29.5 vs 107.7 ± 36.6 p Conclusions In conclusion, when it comes to diabetic patients with a severe limb and life threatening clinical condition, we noticed a lower-than-expected application of international guideline-recommended medical therapies. In fact, only one out of four patients was following all the recommended therapies. Nevertheless, these patients did not reach the standard targets requested to prevent cardiovascular disease.

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: Fluorescence biomodulation (FB), a form of photobiomodulation (PBM) that is also known as low energy level light (LELL), has become an increasingly used clinical tool to induce wound healing in wounds that remain recalcitrant to treatment. In a real-life clinical setting, the aim of the EUREKA (EvalUation of Real-lifE use of Klox biophotonic system in chronic wound mAnagement) study was to confirm the efficacy and safety of LumiHeal, a system based on FB, in the treatment of chronic wounds such as venous leg ulcers (VLUs), diabetic foot ulcers (DFUs) and pressure ulcers (PUs). The effects of this FB system on the modulation of wound healing in chronic ulcers through FB induction were previously examined in an interim analysis of this study. Method: A multicenter, prospective, observational, uncontrolled trial in 12 clinical sites in Italy. The wound was cleansed with saline and a 2mm thick layer of a chromophore gel was applied to the affected area in a biweekly regimen. The area was then illuminated with the LED activator for five minutes at a distance of 5cm. Treatment was used in combination with standard of care specific to each type of chronic wound (VLU, DFU, PU). Wound area evaluation was assessed using the Silhouette Imaging System and quality of life (QoL) with the Cardiff Wound Impact Schedule (CWIS). A seven-point evaluation of the clinicans' view was also examined. Results: We enrolled 100 subjects, with the final analysis including 99 patients/ulcers consisting of 52 VLUs, 32 DFUs and 15 PUs. Total wound closure at the end of the study was achieved in 47 patients by aetiology: 26 VLUs (50% of VLUs); 16 DFUs (50% of DFUs); and five PUs (33.3% of PUs). The mean wound area regression at last study assessment was significant for VLUs (41.0%; pConclusion: The study confirmed a positive efficacy profile of the FB system in inducing the wound healing process in three different types of hard-to-heal chronic wounds. The treatment was shown to be safe and well tolerated by the patients, with a significant improvement in patient QoL. This approach offers an effective modality for the treatment of hard-to-heal chronic ulcers.

Marco Romanelli,1 Alberto Piaggesi,2 Giovanni Scapagnini,3 Valentina Dini,1 Agata Janowska,1 Elisabetta Iacopi,2 Carlotta Scarpa,4 Stéphane Fauverghe,5 Franco Bassetto4 1Wound Healing Research Unit, Division of Dermatology, School of Medicine, University of Pisa, Pisa, 2Diabetic Foot Section, Department of Medicine, University of Pisa, Pisa, 3Department of Medicine and Health Sciences, School of Medicine, University of Molise, Campobasso, 4Clinic of Plastic and Reconstructive Surgery, Padova University-Hospital, Padova, Italy; 5KLOX Technologies Inc., Laval, QC, Canada Objective: Interest has grown regarding photobiomodulation (PBM) with low-level light therapy, which has been shown to positively affect the stages of the wound healing process. In a real-life context clinical setting, the objective of the EUREKA study was to investigate efficacy, safety, and quality of life associated with the use of a BioPhotonic gel (LumiHeal™) in the treatment of chronic wounds such as venous leg ulcers (VLUs), diabetic foot ulcers (DFUs), and pressure ulcers (PUs). This BioPhotonic gel represents a new, first-in-class emission spectrum of light, including fluorescence, to induce PBM and modulate healing.Design: The multicenter, prospective, interventional, uncontrolled, open-label study enrolled 100 patients in 12 wound centers in Italy. We performed an early interim analysis based on the first 33 subjects (13 VLU, 17 DFU, 3 PU) in seven centers who completed the study.Main results: Seventeen patients (52%) achieved total wound closure (full re-epithelialization for 2 weeks) during the study period. Two patients (6%) were considered “almost closed” (decrease of the wound area of more than 90% at study end) and three others (9%) were considered “ready for skin grafting”. No related serious adverse events were observed, and the compliance was excellent. After the treatment, the average time to “pain-free” was 11.9 days in the VLU group. Quality of life was improved with overall increase of 26.4% of the total score (Cardiff Wound Impact Schedule, p=0.001).Conclusion: The study revealed a positive efficacy profile of the BioPhotonic gel in promoting wound healing and reactivating the healing process in different types of chronic, hard-to-heal wounds. The treatment was shown to be safe and well tolerated by the patients, and a reduction of pain perception was also detected during the treatment period. The improvement of the quality of life was accompanied by a high level of clinician satisfaction. Keywords: photobiomodulation, fluorescence biomodulation, biophotonics, phototherapy, light, venous leg ulcers, VLUs, pressure ulcers, PUs, diabetic foot ulcers, DFUs, hard-to-heal wounds&nbsp

The diabetic foot syndrome represents a relatively recent field of scientific interest: since the beginning the double origin of the disease has been evident: neuropathy and arteriopathy act together.

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.

A 72-year-old male was referred to our hospital for a plantar ulceration that had occurred many years earlier. The lesion, with exuberant granulation and large areas of necrosis and fibrin, had long been treated by plastic surgeons with no positive evolution. At admission in our hospital no ischemia was detected, and foot radiograph was negative for bone involvement. The patient underwent a foot magnetic resonance imaging, which showed high vascularization in the plantar region and early capture of the contrast medium. We then performed multiple biopsies of the ulceration that revealed a moderately differentiated squamous cell carcinoma. The total body computed tomography exam raised a systemic involvement. A lymph node biopsy and immunohistochemistry assay on the pleural cytological sample proved the presence of a primary squamous cell carcinoma of the foot with systemic dissemination. Although rare, squamous cell carcinoma could be associated with chronic nonhealing ulcers; therefore, when a lesion does not heal, despite adequate standard treatment, its etiopathogenesis should be challenged.

Diabetic foot ulcers (DFUs) often result in severely adverse outcomes, such as serious infections, hospitalization, and lower extremity amputations. In last few years, to improve the outcome of DFUs, clinicians and researchers put their attention on the application of low intensity pulsating electro-magnetic fields through Therapeutic Magnetic Resonance (TMR®). In our study, patients with DFUs have been divided into two groups: The Sham Group treated with non-functioning TMR® device, and the Active Group treated with a functioning device. Biopsies were recovered from ulcers before and after a 15-day treatment with both kind of TMR® device. To recognize signs of inflammation or healing process, the harvested biopsies were subjected to histological and molecular analyses. The histological analysis showed a change in cell population after treatment with TMR®: an increase of fibroblasts and endothelial cells with a reduction of inflammatory cells. After TMR® application, the gene expression profile analysis revealed an improvement in extracellular matrix components such as matrix metalloproteinases, collagens and integrins, a reduction in pro-inflammatory interleukins, and an increase in growth factors expression. In conclusion, our research has identified histological and molecular features of reduced inflammation and increased cell proliferation during the wound healing process in response to TMR® application.

Aims: Diabetic complications, and in particular diabetic foot ulcers (DFUs), are associated with low health-related quality of life (HRQoL). We evaluated whether the presence of diabetic complications also influenced the improvement of HRQoL during DFU treatment.Methods: 1088 patients presenting for DFU treatment at the centers participating in the Eurodiale study were followed prospectively up to one year. HRQoL was measured both at presentation and after healing or at end of follow up, using EQ-5D: a standardized instrument consisting of five domains and a summary index. The influence of diabetic comorbidity on the course of HRQoL was evaluated for each of the EQ-5D outcomes in multi-level linear regression analyses, adjusting for baseline characteristics.Results: HRQoL improved in all EQ-5D outcomes over the course of treatment for those DFUs that healed. The few significant differences in the development of HRQoL between patients with and without comorbidity showed a more beneficial development for patients with comorbidity in DFUs that did not heal or healed slowly.Conclusions: Comorbidity does not hamper improvement of HRQoL in DFU treatment. On the contrary, HRQoL improved sometimes more in patients with certain comorbidity with hard-to-heal ulcers. (C) 2017 Elsevier Inc. All rights reserved.

Pietro Salvo,1,2 Nicola Calisi,1 Bernardo Melai,1 Valentina Dini,3 Clara Paoletti,1 Tommaso Lomonaco,1 Andrea Pucci,1 Fabio Di Francesco,1 Alberto Piaggesi,4 Marco Romanelli3 1Department of Chemistry and Industrial Chemistry, University of Pisa, 2Institute of Clinical Physiology, National Council of Research, 3Wound Healing Research Unit, Department of Dermatology, University of Pisa, 4Diabetic Foot Section, Department of Medicine, University of Pisa, Pisa, Italy Abstract: Foot ulcers account for 15% of comorbidities associated with diabetes. Presently, no device allows the status of foot ulcers to be continuously monitored when patients are not hospitalized. In this study, we describe a temperature and a pH sensor capable of monitoring diabetic foot and venous leg ulcers developed in the frame of the seventh framework program European Union project SWAN-iCare (smart wearable and autonomous negative pressure device for wound monitoring and therapy). Temperature is measured by exploiting the variations in the electrical resistance of a nanocomposite consisting of multiwalled carbon nanotubes and poly(styrene-b-(ethylene-co-butylene)-b-styrene). The pH sensor used a graphene oxide (GO) layer that changes its electrical potential when pH changes. The temperature sensor has a sensitivity of ~85 Ω/°C in the range 25°C–50°C and a high repeatability (maximum standard deviation of 0.1% over seven repeated measurements). For a GO concentration of 4 mg/mL, the pH sensor has a sensitivity of ~42 mV/pH and high linearity (R2=0.99). Keywords: diabetic foot ulcer, wearable sensors, wound temperature, wound pH

The diabetic foot (DF) is a complex pathology involving the lower limb of 8 to 10 million people around the world, and its prevalence is rising, creating a dramatic need for effective therapeutic answers. The multidisciplinary DF clinic has been proposed as a model to fight this complication from the International Working Group on Diabetic Foot (IWGDF) inside a more articulated 3-level organization strategy. The organization and technical aspects of this strategy, together with the characteristics of each of the 3 levels have been analyzed and described in the article, together with the aims and limitations of each of the levels to cope with a 3-dimensional pathology involving systemic, local, and logistic aspects. The implementation of this model in Europe produced positive results measured so far in at least 2 nationwide experiences, in Germany and in Italy, and it should be taken in account whenever health policies apply to the DF issue.

The optimal duration of anticoagulation in patients with venous thromboembolism (VTE) is uncertain. We investigated whether persistently negative D-dimers in patients with vein recanalization or stable thrombotic burden can identify subjects at low recurrence risk. Outpatients with a first VTE (unprovoked or associated with weak risk factors) were eligible after at least 3 months (12 in those with residual thrombosis) of anticoagulation. They received serial D-dimer measurements using commercial assays with predefined age/sex-specific cutoffs and were followed for up to 2 years. Of 1010 patients, anticoagulation was stopped in 528 (52.3%) with persistently negative D-dimer who subsequently experienced 25 recurrences (3.0% pt-y; 95% confidence interval [CI], 2.0-4.4%). Of the remaining 482 patients, 373 resumed anticoagulation and 109 refused it. Recurrent VTE developed in 15 patients (8.8% pt-y; 95% CI, 5.0-14.1) of the latter group and in 4 of the former (0.7% pt-y; 95% CI, 0.2-1.7; hazard ratio = 2.92; 95% CI, 1.87-9.72; P = .0006). Major bleeding occurred in 14 patients (2.3% pt-y; 95% CI, 1.3-3.9) who resumed anticoagulation. Serial D-dimer measurement is suitable in clinical practice for the identification of VTE patients in whom anticoagulation can be safely discontinued. This study was registered at clinicaltrials.gov as #NCT00954395.

Introduction and Background: As diabetic foot (DF) care benefits from integration, monitoring geographic variations in lower limb Major Amputation rate enables to highlight potential lack of Integrated Care. In Tuscany (Italy), these DF outcomes were good on average but they varied within the region. In order to stimulate an improvement process towards integration, the project aimed to shift health professionals’ focus on the geographic variation issue, promote the Population Medicine approach, and engage professionals in a community of practice. Method: Three strategies were thus carried out: the use of a transparent performance evaluation system based on benchmarking; the use of patient stories and benchmarking analyses on outcomes, service utilization and costs that cross-checked delivery- and population-based perspectives; the establishment of a stable community of professionals to discuss data and practices. Results: The project enabled professionals to shift their focus on geographic variation and to a joint accountability on outcomes and costs for the entire patient pathways. Organizational best practices and gaps in integration were identified and improvement actions towards Integrated Care were implemented. Conclusion and Discussion: For the specific category of care pathways whose geographic variation is related to a lack of Integrated Care, a comprehensive strategy to improve outcomes and reduce equity gaps by diffusing integration should be carried out.

Background: Despite its efficacy in healing neuropathic diabetic foot ulcers (DFUs), total contact cast (TCC) is often underused because of technical limitations and poor patient acceptance. We compared TCC to irremovable and removable commercially available walking boots for DFU offloading. Methods: We prospectively studied 60 patients with DFUs, randomly assigned to 3 different offloading modalities: TCC (group A), walking boot rendered irremovable (i-RWD; group B), and removable walking boot (RWD; group C). Patients were followed up weekly for 90 days or up to complete re-epithelization; ulcer survival, healing time, and ulcer size reduction (USR) were considered for efficacy, whereas number of adverse events was considered for safety. Patients’ acceptance and costs were also evaluated. Results: Mean healing time in the 3 groups did not differ ( P = .5579), and survival analysis showed no difference between the groups (logrank test P = .8270). USR from baseline to the end of follow-up was significant ( P < .01) in all groups without differences between the groups. Seven patients in group A (35%), 2 in group B (10%), and 1 in group C (5%) (Fisher exact test P = .0436 group A vs group C) reported nonsevere adverse events. Patients’ acceptance and costs were significantly better in group C ( P < .05). Conclusions: Our results suggest that a walking boot was as effective and safe as TCC in offloading the neuropathic DFUs, irrespective of removability. The better acceptability and lesser costs of a removable device may actually extend the possibilities of providing adequate offloading. Level of Evidence: Level II, prospective comparative study.

Innovations in technology are used in managing chronic wounds. Despite the wide range of technologies available, healing of chronic wounds remains variable. In this paper, the authors offer an evidence based approach to the use of technology for diagnosis and management based on the concept of standardised care.

To evaluate the outcomes of a multidisciplinary team working on diabetic foot (DF) patients with critical limb ischemia (CLI) in a specialized center, the authors retrospectively traced all the patients admitted in their department in 3 consecutive years with a diagnosis of CLI. From January 2006 to December 2008, 245 consecutive DF patients with CLI according the TransAtlantic interSociety Consensus II criteria were included in the study. Treatment strategy was decided by a team of diabetologists, inteventional radiologists, and vascular surgeons. Technical and clinical success, mortality, and ulcer recurrence were evaluated at 6 months and at a mean follow-up of 19.5 ± 13.4 months. Percutaneous transluminal angioplasty (PTA) was performed in 189 (77%) patients, whereas medical treatment, open surgical revascularization (OSR), and primary amputation were performed in 44 (18.3%), 11 (4.3%), and 1 (0.5%) patients, respectively. Revascularization was successful in 227/233 (97.4%) patients. At follow-up, the overall clinical success rate was 60.4%; it was significantly ( P = .001) higher after revascularization (75.9%) compared with medical treatment (48.3%). During follow-up, surgical interventions in the foot were 1.5 ± 0.4 in those treated with PTA, 1.6 ± 0.5 in those treated with OSR, and 0.3 ± 0.8 in those receiving medical therapy ( P < .05 compared with the others). Ulcer recurrence occurred in 29 (11.8%) patients: 4 (1.6%) in PTA, 2 (0.8%) in OSR, and 23 (9.4%) in the medical therapy group ( P < .05). Major amputation rate was 9.3%, being significantly ( P = .04) lower after revascularization (5.2%) compared with medical therapy alone (13.8%). Cumulative mortality rate was 10.6%. In conclusion, this study confirms the positive role of a PTA-first approach for revascularizing the complex cases of DF with CLI in a teamwork management strategy.

Background Forefoot ulcers (FU) are one of the most disabling and relevant chronic complications of diabetes mellitus (DM). In recent years there is emerging awareness that a better understanding of the biomechanical factors underlying the diabetic ulcer could lead to improve the management of the disease, with significant socio-economic impacts. Our purpose was to try to detect early biomechanical factors associated with disease progression. Methods Thirty subjects (M/F: 22/8; mean age ± SD: 61,84 ± 10 years) with diagnosis of type II DM were included. The participants were divided into 3 groups (10 subjects per group) according to the stage of evolution of the disease: Group 1, subjects with newly diagnosed type II DM, without clinical or instrumental diabetic peripheral neuropathy (DPN) nor FU (group called “DM”); Group 2, with DPN but without FU (group called “DPN”); Group 3, with DPN and FU (group called “DNU”). All subjects underwent 3-D Gait Analysis during walking at self-selected speed, measuring spatio-temporal, kinematic and kinetic parameters and focusing on ankle and foot joints. The comparative analysis of values between groups was performed using 1-way ANOVA. We also investigated group to group differences with Tukey HSD test. The results taken into consideration were those with a significance of P

Samples from 1295 patients with diabetic foot infection were evaluated; 4332 samples were collected with an average of 3.3 samples per patient. Fifty-seven percent of patients had a 2B ulcer and 23% had a 3B ulcer according to Texas University Classification. In 64.2% of samples collected at first visit an etiologic agent was identified. About 40% of the positive samples were polymicrobial. Gram positive bacteria were more frequently isolated (52.6%), Staphylococcus aureus was the most frequently isolated single agent (29.9%) and MRSA was 22% of S. aureus. Enterococcus spp., mainly Enterococcus faecalis, were 9.9%, all vancomycin susceptible except 2 isolates. Streptococci were 4.6%, more than 60% Streptococcus agalactiae. Gram negative rods were 40.6%, with enterobacteria 23.5% and Pseudomonas aeruginosa 10.3%. Anaerobes were only 0.3%, probably due to culture methods applied in our laboratory. Cotrimoxazole, rifampin and doxycycline were still active against S. aureus. ESBL producers, among enterobacteria, were 10%, mainly Escherichia coli and Proteus spp. Only colistin had a rate of susceptibility against P. aeruginosa above 90%. Levofloxacin had the best clinical activity with respect to the other quinolones, but when it failed, selected more resistant strains with respect to moxifloxacin among S. aureus and with respect to ciprofloxacin among P. aeruginosa.

Objectives The incidence of minor amputation may vary significantly, and determinants of minor amputation have not been studied systematically. We evaluated minor amputation rate, the determinants of minor amputation and differences in amputation rate between European centres. Methods In the Eurodiale study, a prospective cohort study of 1232 patients (1088 followed until end-point) with a new diabetic foot ulcer were followed on a monthly basis until healing, death, major amputation or up to a maximum of 1 year. Ulcers were treated according to international guidelines. Baseline characteristics independently associated with minor amputation were examined using multiple logistic regression modelling. Based on the results of the multivariable analysis, a disease severity score was calculated for each patient. Results One hundred and ninety-four (18%) patients underwent a minor amputation. Predictors of minor amputation were depth of the ulcer (odds ratio 6.08, confidence interval 4.10-9.03), peripheral arterial disease (odds ratio 1.84, confidence interval 1.30-2.60), infection (odds ratio 1.56, confidence interval 1.05-2.30) and male sex (odds ratio 1.42, confidence interval 0.99-2.04). Minor amputation rate varied between 2.4 and 34% in the centres. Minor amputation rate in centres correlated strongly with disease severity score at the moment of presentation to the foot clinic (r = 0.75). Conclusions Minor amputation is performed frequently in diabetic foot centres throughout Europe and is determined by depth of the ulcer, peripheral arterial disease, infection and male sex. There are important differences in amputation rate between the European centres, which can be explained in part by severity of disease at presentation. This may suggest that early referral to foot clinics can prevent minor amputations.

SUMMARY Ischemia represents the most important determinant for major amputation in the diabetic foot, and is associated with a higher prevalence of foot infections, systemic comorbidity and mortality. Until recently, prognosis for these patients was very poor; however, despite solid population-based evidence not being presently available, there are still indications that the introduction of both endovascular and surgical revascularization has improved prognosis. Improvements in the materials, technology and procedures in the last 10 years, as well as increasing experience, suggest that revascularization should no longer be considered a limb-saving option, but instead, a first-line intervention with a wide range of indications in the ischemic diabetic foot. This approach, when integrated into a therapeutic strategy that includes both local surgery and systemic medical management and applied in highly specialized centers, allows high healing rates with a significant reduction of major amputations.

Aims/hypothesis Outcome data on individuals with diabetic foot ulcers are scarce, especially in those with peripheral arterial disease (PAD). We therefore examined the clinical characteristics that best predict poor outcome in a large population of diabetic foot ulcer patients and examined whether such predictors differ between patients with and without PAD. Methods Analyses were conducted within the EURODIALE Study, a prospective cohort study of 1,088 diabetic foot ulcer patients across 14 centres in Europe. Multiple logistic regression modelling was used to identify independent predictors of outcome (i.e. non-healing of the foot ulcer). Results After 1 year of follow-up, 23% of the patients had not healed. Independent baseline predictors of non-healing in the whole study population were older age, male sex, heart failure, the inability to stand or walk without help, end-stage renal disease, larger ulcer size, peripheral neuropathy and PAD. When analyses were performed according to PAD status, infection emerged as a specific predictor of non-healing in PAD patients only. Conclusions/interpretation Predictors of healing differ between patients with and without PAD, suggesting that diabetic foot ulcers with or without concomitant PAD should be defined as two separate disease states. The observed negative impact of infection on healing that was confined to patients with PAD needs further investigation.

This study evaluated the prevalence of peripheral arterial disease (PAD) in type 2 diabetes and its association with traditional and non-traditional cardiovascular (CV) risk factors.In 1610 type 2 diabetics PAD was defined as ankle-brachial pressure index (ABPI)0.9.PAD prevalence was 17%, increased with age, diabetes duration, HbA 1c levels, previous CV events. There were no significant differences in the prevalence of traditional CV risk factors between patients with and without PAD. PAD patients had higher levels of fibrinogen (10.88+/-2.32 versus 10.2+/-2.23micromol/L; p0.0001), uric acid (327.1+/-89.2 versus 315.2+/-83.3micromol/L, p0.01), pulse pressure (70+/-18 versus 60+/-16mm Hg, p0.0001), higher rate of microalbuminuria (21.3% versus 13.7%; p0.05) and lower glomerular filtration rate (GFR, 80.7+/-24 versus 89.9+/-22 ml/min/1.73 m2; p0.001) than those without. In age-gender-adjusted analysis, smoking (OR 1.5; CI: 1.07-2.2), HbA 1c (OR 1.45; CI: 1.07-2.08), high pulse pressure (OR 2.81; CI: 1.63-4.82), reduced GFR (OR 2.16; CI: 1.4-3.3), microalbuminuria (OR 1.62; CI: 1.11-2.36), high fibrinogen levels (OR 2.03; CI: 1.34-3.07) were associated with PAD. In multivariate analysis age, male sex, smoking, high pulse pressure, low GFR, high fibrinogen levels, previous CV events were independent risk factors for PAD.PAD prevalence is high in Type 2 diabetic patients. Non-traditional cardiovascular risk factors may be involved in the development of this complication.

The safety and efficacy of a novel superoxidized solution (Dermacyn™ Wound Care [DWC], Oculus Innovative Sciences, Petaluma, Calif) was evaluated for the treatment of wide postsurgical infected ulcers of the diabetic foot. A group (group A,n = 18) of patients with diabetes mellitus who had postsurgical lesions>5 cm2 without ischemia or infection were recruited consecutively and treated with DWC-saturated dressings. These dressings were renewed once daily and were compared with a group of patients that had been previously treated with diluted povidone iodine (group B,n = 15) using a quasi-experimental study design. Both sets of patients also received standard systemic antibiotic therapy, as per the practice in this center, and local surgical debridement. Patients had weekly assessments until wounds had re-epithelialized completely. Patients in group A had statistically significant shorter healing time and duration of antibiotic therapy and a higher healing rate at 6 months compared with those in group B (p < .01). Recurrence of infection, requirement for debridement procedures, and requirement for minor amputations were significantly less frequent during follow-up in group A patients (p < .05) when compared with those in group B. These preliminary data suggest that DWC used as a wound dressing together with other local and systemic therapies may have a role in reducing healing time as well as complications in patients with diabetes who have postsurgical lesions of the diabetic foot. These data propose the need for a robust controlled study of DWC-saturated dressings to explore its full potential.

OBJECTIVE—This study was designed to test the safety, effectiveness, and costs of off-loading with a novel, off-the-shelf irremovable device in the management of diabetic foot ulceration (DFU). RESEARCH DESIGN AND METHODS—We prospectively evaluated off-loading of neuropathic plantar ulcers in 40 diabetic outpatients attending our diabetic foot clinic and compared healing rates at the 12-week follow-up, number and severity of adverse events, healing time, costs and applicability of the device, and patients’ satisfaction between those randomly assigned to total contact casting (TCC; group A) or to the Optima Diab walker (group B). Deep or infected ulcers were excluded. RESULTS—No difference between groups A and B was observed in healing rates at 12 weeks (95 vs. 85%), healing time (6.5 ± 4.4 vs. 6.7 ± 3.4 weeks), and number of adverse events (six versus four). Treatment was significantly less expensive in group B, which showed a mean reduction of costs of 78% compared with group A (P < 0.001). Practicability was more favorable in group B, with a reduction of 77 and 58% of the time required for application and removal of the devices, respectively (P < 0.001). Patients’ satisfaction with the treatment was higher in group B (P < 0.01). CONCLUSIONS—The Optima Diab walker is as safe and effective as TCC in the management of DFU, but its lower costs and better applicability may be of help in spreading the practice of off-loading among the centers that manage the diabetic foot.

Necrotizing fasciitis (NF) represents a rapidly progressive, life-threatening infection involving skin, soft tissue, and deep fascia. An early diagnosis is crucial to treat NF effectively. The disease is generally due to an external trauma that occurs in predisposed patients: the most important risk factor is represented by diabetes mellitus. NF is classified into 3 different subtypes according to bacterial strains responsible: type 1 associated to polymicrobial infection, type 2 NF, generally associated to Streptococcus species, often associated to Staphylococcus aureus and, eventually, Type 3, due to Gram-negative strains, such as Clostridium difficile or Vibrio. NF is usually characterized by the presence of the classic triad of symptoms: local pain, swelling, and erythema. In daily clinical practice immune-compromised or neuropathic diabetic patients present with atypical symptomatology. This explains the high percentage of misdiagnosed cases in the emergency department and, consequently, the worse outcome presented by these patients. Prompt aggressive surgical debridement and antibiotic systemic therapy are the cornerstone of its treatment. These must be associated with an accurate systemic management, consisting in nutritional support, glycemic compensation, and hemodynamic stabilization. Innovative methods, such as negative pressure therapy, once the acute conditions have resolved, can help fasten the surgical wound closure. Prompt management can improve prognosis of patients affected from NF reducing limb loss and saving lives.

Diabetic foot ulcerations (DFU) represent a major cause of hospitalization and amputation. In people with diabetes it's not uncommon to find chronic wounds due to pathogenic mechanisms different from diabetes. Here we report the case of a foot lesion misdiagnosed as DFU but actually caused by diffuse large B-cell lymphoma.