Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update).

AIMS: Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are of utmost importance when attempting to heal a chronic diabetes-related foot ulcer. However, the rising incidence and costs of diabetes-related foot ulcer management necessitate that interventions to enhance wound healing of chronic diabetes-related foot ulcers are supported by high-quality evidence of efficacy and cost effectiveness when used in conjunction with established aspects of gold-standard multidisciplinary care. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on wound healing interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline. MATERIALS AND METHODS: We followed the GRADE approach by devising clinical questions and important outcomes in the Patient-Intervention-Control-Outcome (PICO) format, undertaking a systematic review, developing summary of judgements tables, and writing recommendations and rationale for each question. Each recommendation is based on the evidence found in the systematic review and, using the GRADE summary of judgement items, including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability, we formulated recommendations that were agreed by the authors and reviewed by independent experts and stakeholders. RESULTS: From the results of the systematic review and evidence-to-decision making process, we were able to make 29 separate recommendations. We made a number of conditional supportive recommendations for the use of interventions to improve healing of foot ulcers in people with diabetes. These include the use of sucrose octasulfate dressings, the use of negative pressure wound therapies for post-operative wounds, the use of placental-derived products, the use of the autologous leucocyte/platelet/fibrin patch, the use of topical oxygen therapy, and the use of hyperbaric oxygen. Although in all cases it was stressed that these should be used where best standard of care was not able to heal the wound alone and where resources were available for the interventions. CONCLUSIONS: These wound healing recommendations should support improved outcomes for people with diabetes and ulcers of the foot, and we hope that widescale implementation will follow. However, although the certainty of much of the evidence on which to base the recommendations is improving, it remains poor overall. We encourage not more, but better quality trials including those with a health economic analysis, into this area.

Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: A systematic review.

BACKGROUND: It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design. AIMS: Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only. MATERIALS AND METHODS: For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality. RESULTS: The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence. CONCLUSION: Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.

Bifurcated bypass in severe chronic limb threatening ischaemia.

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.

Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: a systematic review.

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.

Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update).

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.

Optimal wound closure of diabetic foot ulcers with early initiation of TLC-NOSF treatment: post-hoc analysis of Explorer.

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.

Evaluation of fluorescence biomodulation in the real-life management of chronic wounds: the EUREKA trial.

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%; p<0.001) and DFUs (52.4%; p<0.001). After four weeks of treatment, it was possible to significantly predict if the ulcer would respond (defined as a decrease of wound size) to the study treatment. Adherence was high (95.2%) and no related serious adverse events were reported during the study. QoL significantly improved, with an increase of 15.4% of the total score, using the CWIS (p<0.001). CONCLUSION: 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.

EWMA Document: Negative Pressure Wound Therapy.

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.

Quantitative assessment of early biomechanical modifications in diabetic foot patients: the role of foot kinematics and step width.

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 < 0,05. 95 % confidence interval was also calculated. RESULTS: A progressive and significant trend of reduction of ROM in flexion-extension of the metatarso-phalangeal joint (P = 0.0038) and increasing of step width (P = 0.0265) with the advance of the disease was evident, with a statistically significant difference comparing subjects with recently diagnosed diabetes mellitus and subjects with diabetic neuropathy and foot ulcer (P = 0.0048 for ROM and P = 0.0248 for step width at Tukey's test). CONCLUSIONS: The results provide evidence that foot segmental kinematics, along with step width, can be proposed as simple and clear indicators of disease progression. This can be the starting point for planning more targeted strategies to prevent the occurrence and the recurrence of a FU in diabetic subjects.

From a Spark to a Flame: The Evolution of Diabetic Foot Disease in the Last Two Decades.

Despite many improvements have been achieved, diabetic foot disease (DFD) remains a clinical, social, and economic burden. In the last years, DFD showed an evolution of its characteristics with an increase of the ischaemic/neuro-ischaemic foot in comparison to the pure neuropathic foot. Simultaneously, there was and increased incidence of concomitant cardiovascular co-morbidities, which influences the higher fragility of patients with DFS. Peripheral arterial disease (PAD) in subjects with diabetic foot seems to show a more aggressive pattern, being more distal and difficult to treat. Untreatable PAD remains the unmet need for clinicians and the main risk factor of major amputation in patients with diabetic foot ulcers. Authors aimed to describe the evolution of diabetic foot patients in the last two decades, describing also the current and future treatment which may improve outcomes in the next generations.

In blood we trust: anemia as a negative healing prognostic factor in diabetic foot patients.

AIM: Anemia has been associated with severity of diabetic foot (DF) disease. Our study aimed to evaluate whether the presence of anemia could decrease the healing chances in DF. METHODS: We retrospectively analyzed all patients admitted in our department in 2021 for DF, dividing them according to presence (Group A) or absence (Group B) of anemia. Groups were compared for clinical and demographic characteristics, procedures and outcomes: healing rate (HR) at 6 months, healing time (HT) and recurrence rate (RR) at 12 months. RESULTS: We sorted out data from 196 consecutive patients: 114 (58%) in Group A and 82 (42%) in B. Group A had a higher male prevalence and a longer duration of disease. Group A showed lower hemoglobin concentration (10.3 ± 1.3 g/dL vs 13.1 ± 1.4 g/dL, p < 0.002) and red blood cells count (3.4 ± 0.5 × 106/mL vs 4.8 ± 0.6 × 106/mL, p = 0.004). Group A presented a lower HR (55.2% vs 76.8%, p = 0.0028), no differences in HT and a higher RR (23.6% vs 17.1%, p < 0.02). Cox's logistic regression on healing confirmed the negative impact of anemia: hazard ratio 2.8 (CI 95% 1.4-5.4, p = 0.0037). CONCLUSIONS: Anemia is frequent in DF and associates to a reduction in healing chances and an increase in recurrences representing an independent predictor of healing failure.

Higher Prevalence of Cancer in Patients with Diabetic Foot Syndrome.

Background: Diabetes mellitus (DM) is associated with a higher prevalence of many forms of cancer. Diabetic foot syndrome (DFS) is associated with higher risk of lower limb amputation and mortality not all explainable with a cardiovascular profile at greater risk compared with DM patients without DFS. DFS could be associated with an increasing cancer incidence. To explore a possible link between DFS and cancer, comparing two cohorts of patients (DFS+ and DFS-) with a cohort of superimposable non-DM controls. Methods: We retrospectively analysed the databases of our department for all consecutive patients admitted between January 2019 and December 2021, selecting all DM pts, and sorting DFS+ pts, admitted for foot complications, from DFS- ones, admitted for other reasons. Cases of pancreatic cancer as well as cancer-related admissions were excluded. Patients were compared to non-DM patients admitted for non-oncological medical problems. The primary endpoint was to compare the prevalence of cancer among the groups, while the secondary endpoint was to look for predictors for cancer in the groups studied. Results: A cohort of 445 consecutive DM inpatients (222 DFS+ and 223 DFS-) and 255 controls were studied. Cancer prevalence in DFS+ group was significantly higher than in DFS- (p = 0.008) and controls (p = 0.031), while no differences were observed between DFS- and the controls. Univariate regression analysis showed a significant association between cancer and DFS (p = 0.007), age at admission (p ≤ 0.001), years of diabetes (p = 0.017) and haemoglobin concentration [Hb] (p = 0.030). In the multivariate regression analysis with DFS, age at admission and [Hb], only DFS (p = 0.021) and age at admission (p ≤ 0.001) persisted as independent factors associated with cancer. Conclusions: A higher prevalence of cancer in DFS+ patients than in DFS- patients and non-diabetic controls is reported. DFS and age can both be considered independent predictors of cancer in patients with DM.

Charcot Neuro-Osteoarthropathy With Superimposed Osteomyelitis in a Nondiabetic Patient, as a Consequence of Cancer Chemotherapy: A MR-Monitored Case Report.

Charcot neuro-osteoarthropathy (CNO) is a manifestation of peripheral neuropathy as a chronic complication of diabetes mellitus but, less frequently, can be associated to other conditions such as alcoholism or neurotoxic therapies. An increasingly emerging cause of CNO is the use of oncological drugs which can cause neuropathic damage. The use of these therapies dramatically increased in recent years. CNO leads to a progressive degeneration of the foot's joints and to bone destruction and resorption which ends in deformities. These alterations in the foot's anatomy determine a high risk of ulceration, infection, and osteomyelitis. The superimposition of osteomyelitis on CNO increases the risk of major amputation, already high in patients suffering either from only CNO or osteomyelitis alone. We report the case of a 61-year old nondiabetic woman affected by CNO as a consequence of antiblastic therapy for breast cancer and the subsequent overlap of osteomyelitis, confirmed by magnetic resonance imaging. This case underlines how it is necessary to consider CNO as a possible complication of antiblastic therapy in the view of the severe consequences of missing its diagnosis.

Predictive value of angiographic scores for the integrated management of the ischemic diabetic foot.

OBJECTIVE: To retrospectively evaluate the agreement between the angiographic scores and the clinical outcomes after endoluminal revascularization in diabetic patients with Fontaine stage IV critical limb ischemia (CLI). METHODS: Clinical and procedural data were retrospectively collected of consecutive diabetic patients with Fontaine stage IV CLI who underwent percutaneous lower limb endoluminal revascularization from January 2009 to June 2011. Pre- and postprocedural angiographic images were retrospectively reviewed to classify lower limb arterial involvement according to four systems: (1) TransAtlantic Inter-Society Consensus [TASC] I; (2) TASC II; (3) Graziani's morphologic classification; and (4) Joint Vascular Society Council calf and foot scores. Foot lesions were graded according to the University of Texas wound classification system. Clinical results (healing, nonhealing, or major amputation) were compared with baseline clinical data and angiographic results. RESULTS: In the study period, 202 percutaneous procedures were performed, with an immediate technical success rate of 94%. Preprocedurally, the mean ± standard deviation calf and foot scores were 7.8 ± 1.6 and 7.3 ± 2.3, respectively; 132 patients (65%) were in Graziani's morphologic classes from 4 to 7; in 112 (55%) cases, TASC II was considered inapplicable, for the absence of femoropopliteal lesions; and finally, 93% of limbs were classified as TASC I type D lesions. After the procedure, mean calf and foot scores were 4.8 ± 2.3 and 5.9 ± 2.6, respectively, and 87% of cases were in Graziani's classes 1 and 2; TASC II was inapplicable in all cases, whereas 80% of cases remained TASC I type D lesions. Healing rate was 67% and major amputation rate was 4%. Among all the clinical and angiographic variables included in the analysis, only pre- and postprocedural foot scores were significantly associated to the clinical outcome (P < .05). CONCLUSIONS: Endoluminal revascularization represents a valuable treatment option in diabetic patients with CLI. TASC classifications are inadequate to describe peripheral arterial involvement in the vast majority of diabetic patients with CLI. Pre- and postprocedural foot scores represent the most significant angiographic parameters to evaluate treatment success.

The Elephant in the Room.

Despite its increasing prevalence, severity, and mortality, Diabetic foot syndrome (DFS) still remains an unaddressed critical issue. The management of DFS is adequately performed only in few centers, and clinical outcomes vary, depending on the possibility of patients to access optimal standards of care. To focus on the critical aspects of the management of DFS in Italy with the purpose of suggesting arguments that might have a more general audience, to improve the quality of therapy and accessibility to optimal care, we have written this article.

The Weakness of the Strong Sex: Differences Between Men and Women Affected by Diabetic Foot Disease.

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.

Necrotizing Fasciitis and Diabetic Foot: Results of a Prompt Identification, Surgery and Antibiotic Therapy (P.I.S.A.) Protocol.

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.

Non-reversed bifurcated vein graft improves time to healing in ischemic patients undergoing lower limb distal bypass.

BACKGROUND: Bifurcated vein grafts have been described in reconstructive microsurgery. No comparative studies have been published in lower limb arterial revascularization. The aim of this study was to compare non-reversed bifurcated vs. single vein graft in patients with critical limb-threatening ischemia (CLTI) undergoing lower limb distal bypass. METHODS: Between January 2015 and December 2021 193 CLTI patients have been treated at our center with vein bypass, and distal anastomosis on infrapopliteal vessels; 137 patients (71%) received a single graft (Group SIN), and 56 patients (29%) had a bifurcated bypass (Group BIF). Primary outcomes measures were time to healing, primary patency, primary assisted patency, secondary patency, and limb salvage. Two-year outcomes according to Kaplan-Meier curves were evaluated and compared. RESULTS: Both groups were homogeneous in terms of demographic data, preoperative risk factors, and clinical presentation except for an elderly age in Group BIF (77.5 vs. 71.5 years; P<0.001). Intraoperative technical success was achieved in all patients. Overall median duration of follow-up was 19 months (interquartile range 9-36). Wound healing did not differ between the two groups (77.4% Group SIN vs. 73.2% Group BIF; P=0.33). Mean time to healing was faster in Group BIF (2.4 vs. 6.8 months; P<0.001). At 2-year follow-up there were no differences between the two groups in terms of primary patency (71.4% Group SIN vs. 54% Group BIF; P=0.10), primary assisted patency (81.7% Group SIN vs. 76.4% Group BIF; P=0.53), secondary patency (85.1% Group SIN vs. 80.9% Group BIF; P=0.79), and limb salvage (92.3% Group SIN vs. 87.2% Group BIF; P=0.64). CONCLUSIONS: Bifurcated graft improved time to healing in CLTI patients undergoing infrapopliteal non-reversed vein bypass. Two-year overall patencies and limb salvage did not differ accordingly to vein graft configuration (single vs. bifurcated).

Peripheral Interventional Strategy Assessment (PISA) for Diabetic Foot Ulcer Revascularization: Preliminary Outcomes of a Multidisciplinary Pilot Study.

BACKGROUND: Digital subtraction angiography (DSA) still represents the gold standard for anatomical arterial mapping and revascularization decision-making in patients with chronic limb-threatening ischemia (CLTI), although DUS (Doppler Ultrasound) remains a primary non-invasive examination tool. The Global Vascular Guidelines established the importance of preoperative arterial mapping to guarantee an adequate in-line flow to the foot. The aim of this study was to evaluate the accuracy of DUS in guiding therapeutic vascular treatments on the basis of Global Vascular Guidelines without the need of a second-level examination. METHODS: Between January 2022 and June 2022, all consecutive patients with CLTI to be revascularized underwent clinical examination and DUS without further diagnostic examinations. Primary outcomes assessed were technical success, and 30-day mortality. Secondary outcomes were 1-year amputation free survival, and time between evaluation and revascularization. RESULTS: Sixty-eight patients with a mean age of 73.6 ± 8.5 years underwent lower limb revascularization. Technical success was 100%, and the 30-day mortality rate was 2.9%. Mean time between evaluation and revascularization was 29 ± 17 days. One-year amputation free survival was 97.1%. CONCLUSIONS: DUS without further diagnostic examinations can accurately assess the status of the vascular tree and foot runoff, providing enough information about target vessels to guide revascularization strategies.