The Republic of Srpska (RS), as a part of the Western Balkans (WB) region, has a higher diabetes prevalence than the EU. This study aims to assess the cost-effectiveness of early treatment of high-risk patients with pre-diabetes and undiagnosed diabetes in our setting. We designed a Markov chain Monte Carlo (MCMC) model which reflects the current International Diabetes Federation (IDF) three-step plan for the prevention of T2DM in those at increased risk. The model captures the evolution of the disease in FINDRISC high-risk patients from normal glucose tolerance (NGT) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) and then to T2DM and its complications. We developed two MCMC models, in order to follow the progression of the disease in high-risk cases, ie, when early treatment is undertaken or when it is not undertaken. The health costs and quality adjusted life years (QALY) were discounted at an annual rate of 3%. The key model parameters were varied in one-way and probabilistic sensitivity analysis. Early treatment resulted in increased life expectancy, postponement of the onset of diabetes and increased QALY for all patients. The discounted incremental cost-effectiveness-ratios (ICER) in NGT, IFG, IGT, and T2DM patients were -289.9, 9724.03, -1478.59 and 4084.67 €. In high-risk IGT patients, ICER was the most favorable, being both a cost saving and QALY gaining, with the consistent results confirmed by the sensitivity analysis. The results recommend the acceptance of a new health policy of identifying IGT patients with the use of FINDRISC questionnaire and plasma glucose measurements; providing them with a lifestyle change program; and implementing intensive diabetes treatment, as their disease progresses. Our results are especially significant for the Western Balkan countries, since this was the first cost-effectiveness study of T2DM prevention in this region.

Diabetic foot ulcers (DFUs) are the leading cause of non-traumatic amputations, and its efficient management remains a clinical challenge, particularly in treating severe infections. Current treatment strategies often fail to address the multifactorial nature of DFUs. Combining antimicrobial peptides (AMPs) with the intrinsic properties of alginate hydrogels offers a promising solution for handling the complex etiology of DFUs. In this study, we designed alginate-based hydrogels for delivery of AMPs, namely the AMPs human β-defensin 2 (hBD-2) and PP4-3.1, to enhance diabetic wound healing. The hydrogels exhibited high storage modulus, low swelling ratio, and a nanometric porous structure, enabling sustained AMP release for over three days. Rheology analyses further confirmed their stability across pH 6 to 8. In vitro, hBD-2 hydrogels displayed excellent biocompatibility and promoted better cell migration than PP4-3.1 hydrogels, for up to 48 h. Thus, hBD-2 hydrogels were used in a streptozotocin-induced diabetic mouse model of wound healing. The hBD-2 hydrogels significantly accelerated wound closure and improved wound maturation, enhancing re-epithelialization and tissue remodeling, compared to controls. Furthermore, hBD-2 hydrogels reduced the microbial load from the wounds and attenuated inflammation at the wound site by decreasing the number of M1-like macrophages, M1/M2 ratio, and CD3+ cells. Lastly, a pro-reparative environment was promoted through a decrease in reactive oxygen species (ROS) levels, and an increase in neovascularization and collagen deposition. Altogether, these findings suggest that hBD-2 alginate hydrogels hold promise as a novel therapeutic option for managing DFUs, offering a combined anti-inflammatory, ROS-scavenging and tissue-regenerative effect.

In the United Kingdom, the prevalence of diabetes-related foot ulcer disease (DFUD) is 6.3%, and cardiovascular disease (CVD) is the leading cause of mortality in people with DFUD. This study aims to evaluate the effectiveness of a multifactorial intervention to reduce CVD events and mortality in adults with type 2 diabetes (T2D) and DFUD.

The MiFoot study is a multi-centre, pragmatic randomised controlled trial to test intervention effectiveness and cost-effectiveness compared to usual care that will include an internal feasibility study and a process evaluation. English-speaking adults (≥18 years; n = 392) with T2D and current/previous (within 5 years) DFUD will be recruited from multiple sites across the United Kingdom and randomised 1:1 to intervention (MiFoot multifactorial intervention plus usual care) or control (usual care), with data collected at baseline, 12- and 24-month follow-up. The MiFoot intervention comprises an individualised assessment with a healthcare practitioner to optimise treatment and assess the suitability of physical activity participation; group-based disease self management education and physical activity sessions; and a digital-based programme, consisting of cohort-relevant topics, physical activity guidance and peer support functionality. The primary outcome will be extended major adverse cardiovascular events (MACE, i.e. myocardial infarction, stroke, cardiovascular death, peripheral arterial bypass, coronary artery bypass, coronary angioplasty or peripheral artery angioplasty) at 24 months.

This study will provide evidence on the feasibility and clinical effectiveness, and cost-effectiveness of a multifactorial intervention to prevent or slow the progression of CVD-related complications in the extremely high-risk population with T2D and DFUD.

Of the roughly 38 million people diagnosed with type 2 diabetes mellitus in the United States, up to 34% will develop a diabetic foot ulcer at some point, up to 75% of those who develop an ulcer will experience recurrent ulcers, and approximately 18% of patients with a diabetic foot ulcer will undergo lower-limb amputation. The aim of this study was to determine whether depressive symptoms change after a minor, nontraumatic amputation. We conducted a multimethod study consisting of semi-structured interviews (n = 12) and a retrospective cohort (n = 20) of patients with type 2 diabetes mellitus who underwent a nontraumatic, minor amputation of a single toe (partial or total) or partial ray resection. Patient Health Questionnaire-9 (PHQ-9) scores were noted before and after surgery within 30 days of each other. The Wilcoxon matched pairs signed rank test was used to determine differences in the PHQ-9 scores before amputation and after amputation. Of the 20 patients in the retrospective cohort, 90% (18 of 20) had higher PHQ-9 scores within 30 days of amputation. Mean PHQ-9 scores were 3.65 and 12.35 before and after amputation, respectively (a difference of 8.7; P = .0001). Diabetes-related extremity amputation depression and distress is a potentially dangerous complication of diabetes mellitus. Nontraumatic amputations can be a traumatic experience for patients. Surgeons should screen their patients with type 2 diabetes mellitus before and after any (minor or major) nontraumatic amputation and make the appropriate referral, if necessary. Sufficient evidence exists in the literature to warrant the inclusion of psychiatrists and other mental health clinicians in multidisciplinary limb preservation teams.

Non-healing wounds are long-term complications of diabetes mellitus (DM) that increase mortality risk and amputation-related disability and decrease the quality of life. Nitric oxide (NO·)-based treatments (i.e., use of both systemic and topical NO· donors, NO· precursors, and NO· inducers) have received more attention as complementary approaches in treatments of DM wounds. Here, we aimed to highlight the potential benefits of NO·-based treatments on DM wounds through a literature review of experimental and clinical evidence. Various topical NO·-based treatments have been used. In rodents, topical NO·-based therapy facilitates wound healing, manifested as an increased healing rate and a decreased half-closure time. The wound healing effect of NO·-based treatments is attributed to increasing local blood flow, angiogenesis induction, collagen synthesis and deposition, re-epithelization, anti-inflammatory and anti-oxidative properties, and potent broad-spectrum antibacterial effects. The existing literature lacks human clinical evidence on the safety and efficacy of NO·-based treatments for DM wounds. Translating experimental favors of NO·-based treatments of DM wounds into human clinical practice needs conducting clinical trials with well-predefined effect sizes, i.e., wound reduction area, rate of wound healing, and hospital length of stay.

Diabetes-related foot ulceration (DFU) is associated with increased cardiovascular risk, but the mechanisms remain unclear. Inflammation and infection are mediators of CVD, which may be important in DFU.

Prospectively collected data from patients attending a multidisciplinary DFU service were analysed. A deep ulcer was defined as one that reached muscle, tendon or deeper structures. Patients were categorised into four DFU groups: not deep and no infection (D-/I-), not deep but infected (D-/I+), deep with no infection (D+/I-) or deep with infection (D+/I+). Incident major adverse cardiovascular events (MACE) were defined as hospitalisation for myocardial infarction, stroke or transient ischaemic attack, or heart failure. Survival analyses were performed using the logrank test and multivariate Cox regression.

Of 513 patients, 241 (47.0%) were in the D-/I- group, 110 (21.4%) were in the D-/I+ group, 35 (6.8%) were in the D+/I- group and 127 (24.8%) were in the D+/I+ group. MACE or all-cause mortality occurred in 75 patients (14.6%), and MACE alone occurred in 46 patients (9.0%) after median follow-up of 381 days (IQR 220-551) and 404 days (IQR 228-576), respectively. Infection was associated with significantly higher MACE or all-cause mortality (21.5% vs 8.7%; p<0.001) and MACE alone (13.5% vs 5.1%; p=0.003). MACE or all-cause mortality was significantly higher in the D+/I+ group (D-/I- 7.9%; D-/I+ 15.5%; D+/I- 14.3%; D+/I+ 26.8%; p<0.001), as was MACE alone (D-/I- 5.0%; D-/I+ 10.9%; D+/I- 5.7%; D+/I+ 15.7%; p=0.017). Infection and a deep ulcer were independent predictors of adverse outcomes.

Deep and/or infected DFUs are associated with increased cardiovascular risk compared with DFUs that are not deep or infected. These findings provide a potential mechanistic explanation that requires investigation.

Diabetes-related foot ulceration (DFU), a serious but preventable complication of diabetes, is a leading cause of hospitalisation, lower extremity amputation and disability worldwide. People with DFU have a greater burden of cardiovascular risk factors, heart failure and chronic kidney disease, resulting in over two-fold higher risk of cardiovascular death compared with people with diabetes without DFU. Here, we propose a "cardio-renal-metabolic-foot" connection in people with diabetes based on shared pathophysiological mechanisms linking DFU with cardiovascular and renal disease. Whilst these mechanistic links remain to be fully elucidated, systemic inflammation and infection in the context of DFU are postulated as key mediators in the development, and progression of, cardiovascular and renal disease. However, cardiovascular and renal disease are also implicated in the pathogenesis of DFU, highlighting the multi-directional interplay between conditions. The impact of screening, prevention, and early management of cardiovascular complications associated with DFU requires further research. Multi-modality cardiac imaging could play a role in unravelling disease mechanisms leading to novel therapeutic strategies, as well as facilitating personalised risk assessment and management. Recent clinical trials have transformed the therapeutic landscape for people with type 2 diabetes, by demonstrating that sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 agonists and non-steroidal mineralocorticoid receptor antagonists improve cardiovascular and renal outcomes. Although dedicated research in people with DFU is warranted, these therapies could target multiple facets of the "cardio-renal-metabolic-foot" connection. The holistic, person-centred approach to managing DFU should incorporate new multidisciplinary models of care focusing on the prevention and management of cardiovascular and kidney disease.

People with diabetic foot ulcers (DFUs) are at risk of major amputation, which is associated with a high mortality rate (exceeding 50% at 5 years) and reduced quality of life. The authors hypothesized that flap reconstruction of DFUs improves patient outcomes in comparison with standard treatment modalities, including major amputation.

MEDLINE, Embase, the Cochrane Library, and gray literature were searched on February 9, 2022. Comparative and single-arm studies reporting outcomes of DFUs treated with local, regional, or free flaps that included function, limb loss, mortality rates, and flap failure rates were included. Risk of bias was assessed, and meta-analysis of proportions was performed.

A total of 3878 records were retrieved, of which 45 met the inclusion criteria, including the records of 1681 patients who underwent flap reconstruction of DFUs. Free flaps were most commonly performed ( n = 1257 [72%]). Only one study used a verified functional outcome measure. At 12 months, the mortality rate was 6.35% (95% CI, 3.89% to 10.20%), the limb loss rate was 11.39% (95% CI, 7.02% to 17.96%), and the free flap failure rate was 9.95% (95% CI, 8.19% to 12.05%). All studies were at high risk of bias. A comparative meta-analysis of interventions was not performed because of study method and outcome heterogeneity.

There is short-term evidence that flap reconstruction (including microsurgical transfer) has low mortality, limb loss, and flap failure rates. However, there are limited high-quality comparative studies, and uncertainty remains regarding the outcome of DFU flap reconstruction in comparison to other treatments.

This study evaluated the efficacy of various local management strategies for diabetic foot ulcers (DFUs).

Several surgical and non-surgical local interventional approaches are available for the treatment of DFUs. The comparative effectiveness of different treatments is unknown, and it remains unclear which approach is the optimal choice for DFUs treatment due to limited direct comparisons.

We did a systematic review and meta-analysis to select the optimal approach to DFUs local management. We searched Medline, Embase, Web of Science, and ClinicalTrials.gov from inception to September 1, 2023, to identify relevant randomized controlled trials (RCTs). We analysed data by pairwise meta-analyses with a random-effects model. A network meta-analysis using the surface under the cumulative ranking curve (SUCRA) was performed to evaluate the comparative efficacy of different interventional approaches in the early (within 12 wk) and late stages (over 12 wk).

141 RCTs involving 14076 patients and exploring 14 interventional strategies were eligible for inclusion. Most studies (102/141) had at least one risk-of-bias dimension. Good consistency was observed during the analysis. Local pairwise comparisons demonstrated obvious differences in the early-stage healing rate and early- and late-stage healing times, while no significant difference in the late-stage healing rate or adverse events were noted. SUCRAs identified the standard of care (SOC) + decellularized dressing (DD), off-loading (OL), and autogenous graft (AG) as the three most effective interventions within 12 weeks for both healing rate (97%, mean rank: 1.4; 90%, mean rank: 2.3; 80.8%, mean rank: 3.5, respectively) and healing time (96.7%, mean rank: 1.4; 83.0%, mean rank: 3.0; 76.8%, mean rank: 3.8, respectively). After 12 weeks, local drug therapy (LDT) (89.5%, mean rank: 2.4) and OL (82.4%, mean rank: 3.3) ranked the highest for healing rate, and OL (100.0%, mean rank: 1.0) for healing time. With respect to adverse events, moderate and high risks were detected in the SOC + DD (53.7%, mean rank: 7.0) and OL (24.4%, mean rank: 10.8) groups, respectively.

The findings suggest that OL provided considerable benefits for DFU healing in both the early and late stages, but the high risk of adverse events warrants caution. SOC+DD may be the preferred option in the early stages, with an acceptable risk of adverse events.

Diabetic foot ulcer is one of the most devastating complications of uncontrolled diabetes. Although there have been advances in the management of diabetic foot ulcers, still diabetic foot ulcers are a major cause of many amputations in diabetic patients. Teucrium polium (T. polium) is widely used by folk medicine practitioners in Iran for the treatment of diabetic ulcers.The present study was designed to evaluate the safety and efficacy of topical T. polium ointment besides the standard treatment in diabetic foot ulcers.A total of 70 diabetic patients with foot ulcers grade 1 or 2 according to Wagner's scale were enrolled in this study. Patients were randomly divided into two groups. Patients in both groups received standard treatment for diabetic foot ulcers. In addition, group 1 received topical T. polium ointment, and group 2 received topical placebo ointment for 4 weeks. The T. polium and placebo ointments were rubbed twice daily two hours before the conventional dressing. The ulcer size, healing time, and laboratory tests were measured in both groups at baseline and end of the study after 4 weeks.Twenty-nine patients remained in the T. polium group and 26 in the placebo group until the end of the study. The mean surface area of ulcers was 3.52 ± 1.47 and 3.21 ± 1.67 cm2 in T. polium group and placebo group respectively at baseline which decrease to .717 ± .19 and 1.63 ± .72 cm2 respectively at the endpoint. The mean ulcer surface area was significantly lower in T. polium compared with the placebo group (p < .0001) at end of the study. Also, the number of patients that completely recovered in the T. polium group was significantly higher than the placebo group (p < .001) at the end of the study.The addition of topical T. polium ointment to standard treatment significantly improves the healing time of diabetic non-infected foot ulcers.

Foot complications are common in people with diabetes mellitus (DM), leading to increased health care utilization, heightened mortality risk, and notable recurrence rates even after treatment. This retrospective cohort study aimed to investigate the impact of repeated occurrence of DM-related foot complications on the risk of all-cause mortality and to identify the potential risk factors associated with repeated events.

People with DM admitted with foot complications (ulcer, skin and soft tissue infection, or osteomyelitis) from 2012 to 2014 were identified from Taiwan's National Health Insurance Research Database, with a 3-year follow-up for repeated events. We categorized the study subjects based on their cumulative number of hospital admissions with foot complications. Logistic regression was conducted to explore the potential risk factors associated with repeated diabetic foot events. Kaplan-Meier curves and Cox proportional hazard models were used to examine the associations between repeated diabetic foot events and all-cause mortality.

In this study, 28 754 eligible individuals were enrolled and classified into 3 groups: no repeated diabetic foot events (76.1%), 1 repeated event (16.0%), and 2 or more repeated events (7.9%). Logistic regression revealed that advanced age, male sex, congestive heart failure, dyslipidemia, hypertension, nephropathy, retinopathy, neuropathy, peripheral vascular disease, diabetes-related preventable hospitalizations, and outpatient visits due to diabetic foot were significantly associated with repeated events of diabetic foot complications. Compared with those with no repeated events, the adjusted hazard ratios for all-cause mortality were 1.26 (95% CI, 1.19-1.34) for 1 repeated event and 1.36 (95% CI, 1.26-1.47) for 2 or more repeated events.

The significant association between repeated diabetic foot and elevated mortality risk highlights the critical necessity for proactive and targeted patient care within clinical practice. More research to delve into the predictive factors related to the repeated occurrence of diabetic foot is needed to provide additional insights for prevention strategies.

To conduct a systematic review and meta-analysis of prevalence of cardiovascular-related morbidity and mortality in patients with diabetic foot ulcers (DFU), as well as compare risks of cardiovascular-related morbidity and mortality between diabetic patients with and without DFU.

A systematic search was conducted on Medline, Embase, and Cochrane databases for randomized controlled trials and observational studies which explored the association between DFU and cardiovascular-related morbidity & mortality, or compared differences in hazard ratios of cardiovascular diseases between diabetics with and without DFU. Frequentist, pairwise meta-analysis was performed on studies with two comparator arms, whereas single-arm studies reporting pooled incidences of cardiovascular-related mortality and morbidity were calculated based on exact binomial distributions. A random-effect meta-analysis model was used with heterogenicity of studies assessed using I2, τ2, and χ2 statistics.

10 studies were identified and included in the systematic review & meta-analysis of 8602 patients. DFU was consistently found to have significant association with cardiovascular-related morbidity and mortality, with pooled prevalences of all cause cardiovascular-related morbidity (37.1%), IHD (44.7%), CHF (25.1%), CAD (11.7%), and CVA (10.9%), and all cause cardiovascular-related mortality (14.6%), fatal IHD (6.2%), fatal CHF (3.67%), fatal CAD (7.92%), and fatal CVA (1.99%). Diabetic patients with DFU were found to have significantly increased risk of IHD (RR 1.25), CVA (RR 2.03), and all-cause cardiovascular-related mortality (RR 2.59) compared to those without DFU.

The presence of DFU is associated with major adverse cardiac events. The alarming rates of cardiovascular-related morbidity and mortality in DFU patients highlight its potential role as a marker of cardiovascular complications and should prompt early clinical investigation and management.

Diabetes-related foot ulcers (DFU) are a persistent healthcare challenge, impacting both patients and healthcare systems, with adverse effects on quality of life and productivity. Our primary aim was to examine the trends in lifetime prevalence of DFU, as well as other micro- and macrovascular complications in the Trøndelag Health Study (HUNT) in Norway.

This study consists of individuals ≥20 years with diabetes participating in the population-based cross-sectional HUNT surveys (1995-2019). Prevalence ratios, comparing the lifetime prevalence of DFU and other relevant micro- and macrovascular complications between the HUNT surveys, were calculated using Poisson regression.

The lifetime prevalence (95% confidence interval (CI)) of a DFU requiring three or more weeks to heal was 11.0% (9.5-12.7) in HUNT2, 7.5% (6.3-8.8) in HUNT3 and 5.3% (4.4-6.3) in HUNT4. The decrease in DFU prevalence from 1995 to 2019 was observed in both men and women, for all age groups, and for both type 1 and type 2 diabetes. The highest lifetime prevalence of DFU was found among those with type 1 diabetes. The decrease in HbA1c from HUNT2 to HUNT4 did not differ between those with and without a DFU. The prevalence of chronic kidney disease (eGFR <60 mL/min/1.73 m2 (eGFR categories G3-G5)) increased in both individuals with and without a DFU.

Results from the HUNT surveys show a substantial decline in the lifetime prevalence of DFU from 1995 to 2019.

The presence of a wound can be anywhere from non-problematic to life-threatening on a severity spectrum, with bacterial infection and resistance playing a major role in the development of chronicity, delaying wound healing. Wound colonization with multiple organisms and the limited number of effective antibiotics place a heavy burden on the healthcare system, with patients going through multiple surgeries during a prolonged hospitalization time. By analyzing the resistance patterns of pluri-bacterial populations and the approach used in managing complex cases, we aim to improve the protocols applied in caring for chronic wounds in our practice and share our experiences and observations.

We designed a retrospective study on 212 diabetic and non-diabetic patients, aiming to evaluate the course of chronic wound treatment in our practice. We focused on the impact that MDR bacteria and diabetes have on surgical outcomes and their role in the healing process.

Patients who received empiric antibiotic therapy before being admitted eventually presented with multiple MDR bacteria compared to those who did not receive antibiotics (p = 0.014). The presence of at least one MDR bacteria in the wound bed was associated with ulcers reaching bone (p = 0.02) and was positively correlated with the number of surgeries performed (p < 0.001). Diabetes played a significant role in surgery-related complications (p = 0.02) and hospitalization time (p < 0.001).

Proper management of chronic wounds requires a comprehensive, multidisciplinary approach and a thorough understanding of antibiotic usage. To address this need, we have developed and implemented a chronic wound treatment protocol in our clinic, with the goal of discharging patients once their ulcers have been treated and closed. A key summary of the protocol presented is to reduce the incidence of MDR bacteria and improve the patient's quality of life.

To evaluate the cost-effectiveness of dehydrated human amnion/chorion membrane (DHACM) in Medicare enrolees who developed a venous leg ulcer (VLU).

This economic evaluation used a four-state Markov model to simulate the disease progression of VLUs for patients receiving advanced treatment (AT) with DHACM or no advanced treatment (NAT) over a three-year time horizon from a US Medicare perspective. DHACM treatments were assessed when following parameters for use (FPFU), whereby applications were initiated 30-45 days after the initial VLU diagnosis claim, and reapplications occurred on a weekly to biweekly basis until completion of the treatment episode. The cohort was modelled on the claims of 530,220 Medicare enrolees who developed a VLU between 2015-2019. Direct medical costs, quality-adjusted life years (QALYs), and the net monetary benefit (NMB) at a willingness-to-pay threshold of $100,000/QALY were applied. Univariate and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty of model results.

DHACM applied FPFU dominated NAT, yielding a lower per-patient cost of $170 and an increase of 0.010 QALYs over three years. The resulting NMB was $1178 per patient in favour of DHACM FPFU over the same time horizon. The rate of VLU recurrence had a notable impact on model uncertainty. In the PSA, DHACM FPFU was cost-effective in 63.01% of simulations at the $100,000/QALY threshold.

In this analysis, DHACM FPFU was the dominant strategy compared to NAT, as it was cost-saving and generated a greater number of QALYs over three years from the US Medicare perspective. A companion VLU Medicare outcomes analysis revealed that patients who received AT with a cellular, acellular and matrix-like product (CAMP) compared to patients who received NAT had the best outcomes. Given the added clinical benefits to patients at lower cost, providers should recommend DHACM FPFU to patients with VLU who qualify. Decision-makers for public insurers (e.g., Medicare and Medicaid) and commercial payers should establish preferential formulary placement for reimbursement of DHACM to reduce budget impact and improve the long-term health of their patient populations dealing with these chronic wounds.

Support for this analysis was provided by MiMedx Group, Inc., US. JLD, and RAF are employees of MiMedx Group, Inc. WHT, BH, PS, BGC and WVP were consultants to MiMedx Group, Inc. VD, AO, MRK, JAN, NW and GAM served on the MiMedx Group, Inc. Advisory Board. MRK and JAN served on a speaker's bureau. WVP declares personal fees and equity holdings from Stage Analytics, US.

Despite the known higher risk of cardiovascular disease in individuals with type 2 diabetes, the pathophysiology and optimal management of diabetic foot ulcers (DFUs), a leading complication associated with diabetes, is complex and continues to evolve. Complications of type 2 diabetes, such as DFUs, are a major cause of morbidity and mortality and the leading cause of major lower extremity amputation in the United States. There has recently been a strong focus on the prevention and early treatment of DFUs, leading to the development of multidisciplinary diabetic wound and amputation prevention clinics across the country. Mounting evidence has shown that, despite these efforts, amputations associated with DFUs continue to increase. Furthermore, due to increasing patient complexity of management secondary to comorbid conditions, such as cardiovascular disease, the management of peripheral artery disease associated with DFUs has become increasingly difficult, and care delivery is often episodic and fragmented. Although structured, process-specific approaches exist at individual institutions for the management of DFUs in the cardiovascular patient population, there is insufficient awareness of these principles in the general medicine communities. Furthermore, there is growing interest in better understanding the mechanistic underpinnings of DFUs to better define personalized medicine to improve outcomes. The goals of this scientific statement are to provide salient background information on the complex pathogenesis and current management of DFUs in cardiovascular patients, to guide therapeutic and preventive strategies and future research directions, and to inform public policy makers on health disparities and other barriers to improving and advancing care in this expanding patient population.

Foot ulcers and/or infections are common long-term complications of diabetes and are associated with increased mortality, especially from cardiovascular disease, though only a few studies have investigated the independent contribution of these events to risk of death. This study aimed at assessing the association of history of diabetic foot with all-cause mortality in individuals with type 2 diabetes, independent of cardiovascular risk factors, other complications, and comorbidities.

This prospective cohort study enrolled 15,773 Caucasian patients in 19 Italian centers in the years 2006-2008. Prior lower extremity, coronary, and cerebrovascular events and major comorbidities were ascertained by medical records, diabetic retinopathy by fundoscopy, diabetic kidney disease by albuminuria and estimated glomerular filtration rate, cardiovascular risk factors by standard methods. All-cause mortality was retrieved for 15,656 patients on 31 October 2015.

At baseline, 892 patients (5.7%) had a history of diabetic foot, including ulcer/gangrene and/or amputation (n = 565; 3.58%), with (n = 126; 0.80%) or without (n = 439; 2.78%) lower limb revascularization, and revascularization alone (n = 330; 2.09%). History of diabetic foot was associated with all-cause death over a 7.42-year follow-up (adjusted hazard ratio, 1.502 [95% confidence interval, 1.346-1.676], p < 0.0001), independent of confounders, among which age, male sex, smoking, hemoglobin A1c, current treatments, other complications, comorbidities and, inversely, physical activity level and total and HDL cholesterol were correlated independently with mortality. Both ulcer/gangrene and amputation alone were independently associated with death, with a higher strength of association for amputation than for ulcer/gangrene (1.874 [1.144-3.070], p = 0.013 vs. 1.567 [1.353-1.814], p < 0.0001). Both ulcer/gangrene/amputation and lower limb revascularization alone were independently associated with death; mortality risk was much higher for ulcer/gangrene/amputation than for revascularization (1.641 [1.420-1.895], p < 0.0001 vs. 1.229 [1.024-1.475], p = 0.018) and further increased only slightly for combined ulcer/gangrene/amputation and revascularization (1.733 [1.368-2.196], p < 0.0001).

In patients with type 2 diabetes, an history of diabetic foot event, including ulcer/gangrene, amputation, and lower limb revascularization, was associated with a ~ 50% increased risk of subsequent death, independent of cardiovascular risk factors, other complications and severe comorbidities, which were also significantly associated with mortality. The association with mortality was greatest for amputation, whereas that for revascularization alone was relatively modest.

ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Psychological factors and psychosocial care for individuals with diabetic neuropathy (DN), a common and burdensome complication of diabetes, are important but overlooked areas. In this article we focus on common clinical manifestations of DN, unremitting neuropathic pain, postural instability, and foot complications, and their psychosocial impact, including depression, anxiety, poor sleep quality, and specific problems such as fear of falling and fear of amputation. We also summarize the evidence regarding the negative impact of psychological factors such as depression on DN, self-care tasks, and future health outcomes. The clinical problem of underdetection and undertreatment of psychological problems is described, together with the value of using brief assessments of these in clinical care. We conclude by discussing trial evidence regarding the effectiveness of current pharmacological and nonpharmacological approaches and also future directions for developing and testing new psychological treatments for DN and its clinical manifestations.

The Taiwan Society of Cardiology (TSOC) and Taiwan Society of Plastic Surgery (TSPS) have collaborated to develop a joint consensus for the management of patients with advanced vascular wounds. The taskforce comprises experts including preventive cardiologists, interventionists, and cardiovascular and plastic surgeons. The consensus focuses on addressing the challenges in diagnosing, treating, and managing complex wounds; incorporates the perfusion evaluation and the advanced vascular wound care team; and highlights the importance of cross-disciplinary teamwork. The aim of this joint consensus is to manage patients with advanced vascular wounds and encourage the adoption of these guidelines by healthcare professionals to improve patient care and outcomes. The guidelines encompass a range of topics, including the definition of advanced vascular wounds, increased awareness, team structure, epidemiology, clinical presentation, medical treatment, endovascular intervention, vascular surgery, infection control, advanced wound management, and evaluation of treatment results. It also outlines a detailed protocol for assessing patients with lower leg wounds, provides guidance on consultation and referral processes, and offers recommendations for various wound care devices, dressings, and products. The 2024 TSOC/TSPS consensus for the management of patients with advanced vascular wounds serves as a catalyst for international collaboration, promoting knowledge exchange and facilitating advancements in the field of advanced vascular wound management. By providing a comprehensive and evidence-based approach, this consensus aims to contribute to improved patient care and outcomes globally.

Diabetic foot ulcers (DFU) can be avoided if symptoms of diabetic foot complications are detected early and treated promptly. Early detection requires regular examination, which might be limited for many reasons. To identify affected or potentially affected regions in the diabetic plantar foot, the region-wise severity of the plantar foot must be known.

A novel thermal diabetic foot dataset of 104 subjects was developed that is suitable for Indian healthcare conditions. The entire plantar foot thermogram is divided into three parts, i.e., forefoot, midfoot, and hindfoot. The division of plantar foot is based on the prevalence of foot ulcers and the load on the foot. To classify the severity levels, conventional machine learning (CML) techniques like logistic regression, decision tree, KNN, SVM, random forest, etc., and convolutional neural networks (CNN), such as EfficientNetB1, VGG-16, VGG-19, AlexNet, InceptionV3, etc., were applied and compared for robust outcomes.

The study successfully developed a thermal diabetic foot dataset, allowing for effective classification of diabetic foot ulcer severity using the CML and CNN techniques. The comparison of different methods revealed variations in performance, with certain approaches outperforming others.

The region-based severity analysis offers valuable insights for targeted interventions and preventive measures, contributing to a comprehensive assessment of diabetic foot ulcer severity. Further research and development in these techniques can enhance the detection and management of diabetic foot complications, ultimately improving patient outcomes.

Diabetic foot ulcers (DFUs) represent a significant and challenging complication of diabetes mellitus, often leading to serious morbidity and a substantial burden on healthcare systems. The study was conducted with the objectives of evaluating the outcomes of DFUs.

A cohort study was conducted to evaluate the outcomes of DFUs from May 2019 to May 2020 at a tertiary care hospital located in Chennai. The study included patients aged 18 to 90 years who were diagnosed with DFUs. Individuals with diabetic foot lesions (skin lesions such as fissures, abscess, cellulites) other than ulcers or those without diabetes were excluded. The data was collected from a total of 100 diabetic patients using systematic random sampling technique.

The mean (SD) age of the study participants was 54.68 (6.72) years with males constituting 56% of the study population. Among 100 participants, 65% experienced healing while 35% did not. Logistic regression analysis showed that glycated haemoglobin (HbA1c) levels, age, and diabetes duration had significant effect on patient outcome. Logistic regression analysis showed that HbA1c levels, age, and diabetes duration had significant effect on patient outcome. Out of 12 patients with major amputation, seven (58.3%) survived, while out of 19 patients with minor amputations, 18 (94.7%) showed remarkably higher survival rate. Meanwhile, 100% survival rate was observed in patients with no amputation.

The study's comprehensive assessment of risk factors and their associations with healing outcomes provides essential knowledge for clinical practice. The study findings collectively support the optimization of interventions and strategies to prevent and manage DFUs, ultimately improving patient care and enhancing their quality of life. The study highlights the significance of glycemic control and limb preservation in DFU management.

One of the most devastating complications of diabetes is diabetes-related foot disease (DFD), which is a priority for public health systems. The 2016-2020 Catalonia Health Plan aimed to reduce the incidence of total and major lower-extremity amputations (LEAs) due to DFD by 10% in the population aged 45-74 years. The aim of the present study was to compare the incidence of LEA-DFD 5 years before and after the creation of the Diabetic Foot Multidisciplinary Unit at our Hospital.

We prospectively collected all cases of LEA-DFD performed at Vall d'Hebron University Hospital from 1 January 2016 to 31 December 2020. Cases of LEA-DFD performed from 1 January 2011 to 31 December 2015 were retrospectively reviewed. The incidence of LEA-DFD between these periods was compared.

A total of 457 LEAs due to DFD were performed in 316 patients. We observed a reduction of 27.9% [CI: 23.7-32.1%] in the incidence of total LEA in the 2016-2020 period in comparison with the period 2011-2016 (0.8 ± 0.1 vs. 1.1 ± 0.3 per 10.000 inhabitants/year, p < 0.001), as well as a reduction of 49.3% [CI: 44.6-53.9%] in the incidence of major LEA-DFD (0.15 ± 0.1 vs. 0.30 ± 0.1 per 10.000 inhabitants/year, p < 0.001).

The implementation of a Diabetic Foot Multidisciplinary Unit resulted in a significant reduction in the rate of amputations due to DFD in the population with diabetes in North Barcelona.

Lower extremity diabetic foot ulcers (DFUs) are a severe consequence of diabetes mellitus (DM). It has been estimated that people with diabetes have a 15% to 25% lifetime risk of acquiring DFUs which leads to the risk of lower limb amputations up to 85% due to poor diagnosis and treatment. Diabetic foot develops planter ulcers where thermography is used to detect the changes in the planter temperature. In this study, publicly available thermographic image data including both control group and diabetic group patients are used. Thermograms at image level as well as patch level are utilized for DFU detection. For DFU recognition, several machine-learning-based classification approaches are employed with hand-crafted features. Moreover, a couple of convolutional neural network models including ResNet50 and DenseNet121 are evaluated for DFU recognition. Finally, a CNN-based custom-developed model is proposed for the recognition task. The results are produced using image-level data, patch-level data, and image-patch combination data. The proposed CNN-based model outperformed the utilized models as well as the state-of-the-art models in terms of the AUC and accuracy. Moreover, the recognition accuracy for both the machine-learning and deep-learning approaches was higher for the image-level thermogram data in comparison to the patch-level or combination of image-patch thermograms.

Objective The prevalence of diabetes and its complications are on the rise worldwide. This is particularly prevalent in low- and middle-income countries. The Index of Multiple Deprivation (IMD) is a measure of relative social deprivation. This index classifies England into small subsets called lower layer super output areas (LSOAs) and then ranks these LSOAs into deciles from the most deprived to the least deprived area. We used this to analyse the relationship between deprivation and outcomes in diabetic foot disease (DFD). Methods We evaluated patients admitted to our multidisciplinary unit with DFD over a five-year period. Their postal codes were used to classify these patients into IMD deciles with decile 1 representing the 10% of most deprived LSOAs and decile 10 the least deprived areas in the country. We used this classification to analyse the relationship between deprivation and its influence on surgical outcomes and lower limb amputation. We specifically compared those falling in the top five against the bottom five deciles. Results Our cohort consisted of 70 patients with diabetes who had surgery on their diabetic foot. Of this cohort, 33 (47%) of these underwent amputation. The majority of these procedures were minor amputations conducted on the forefoot (75.6%) and there were no below knee amputations. Of those requiring an amputation, 27 patients (81.8%) had an IMD decile of 5 or below, and only six (18.2%) patients had above 5. Conclusion Our study shows that the likelihood of amputations related to diabetic foot disease is inversely proportional to the index of multiple deprivation.

Background. Diabetic foot osteomyelitis may precede major limb amputations and lengthy hospital admission. These complications impact patients' morbidity and mortality. Healthcare institutions with dedicated limb-preservation teams realize reduced amputation rates and improved quality of care. This study evaluates the outcomes following the implementation of a rigorous diabetic limb-preservation program at an academic institution. Methods. Patients with diabetes admitted for osteomyelitis occurring below the knee were identified by ICD-10 codes and included for retrospective review. The number and type of amputations, bone biopsies, revascularizations, and hospital length of stay (LOS) were evaluated. Outcomes were compared using the high-low (Hi-Lo) amputation ratio for the 24 months preceding and the 24 months after the integration of a diabetic limb-preservation service. Results. The authors identified and included 337 patients admitted for diabetic foot osteomyelitis. In the 24-month period prior to program implementation, 140 patients were evaluated. In the 24-month period after program implementation, 197 patients were evaluated. The overall amputation rate decreased from 67.1% (n = 94) to 59.9% (n = 118) (P = .214). Major limb amputation rates significantly decreased from 32.9% (n = 46) to 12.7% (n = 25) (P = .001). Minor amputation rates significantly increased from 34.2% (n = 48) to 47.2% (n = 93) (P = .024). The Hi-Lo amputation ratio decreased from 0.96 to 0.27 (P < .001). The rate of obtaining bone biopsies increased from 32.1% (n = 45) to 72.1% (P < .001). The rate of revascularization increased from 10.7% (n = 15) to 15.2% (n = 30) (P = .299). Average hospital LOS decreased significantly from 11.6 days to 9.8 days (P = .044). Conclusion. After the implementation of a limb-preservation team, there was a precipitous drop in major limb amputations in favor of minor amputations. The average hospital LOS decreased. These findings demonstrated improved clinical care and outcomes in patients with lower extremity osteomyelitis and reinforce the importance of a diabetic foot-preservation service within healthcare institutions.

Objective: To compare the number of ulcer-free days during 24 months in persons with diabetes and a healed foot ulcer below the ankle provided with adjusted therapeutic shoes who were given standard information and participated in participant-driven group education compared with standard information alone. Methods: A randomized controlled trial was designed to evaluate the number of ulcer-free days after participant-driven group education in addition to standard information compared with standard information alone. The number needed to treat (N = 174) was not met, as only 138 persons with diabetes and previously healed foot ulcer were recruited (age median 63 years [34-79], 101 men/37 women). Results: A total of 138 persons were recruited, of whom 107 (77.5%) completed the study, 7 (5%) dropped out, and 12 (9%) deceased. No statistically significant difference was found between the intervention group compared with the control group after 6, 18, or 24 months. After 12 months, more patients in the intervention group had developed ulcers. Seventy-seven participants (56%) developed new foot ulcers, irrespective of side and site. Development of one ulcer appeared in 36 participants, two ulcers in 19, and 22 participants developed three ulcers. Forty-eight participants remained ulcer-free (35%) during the 24-month follow-up. Median ulcer-free days until first ulceration were 368 (4-720); until second ulceration, 404 (206-631); and until third ulceration, 660 (505-701). The participants wore prescribed therapeutic shoes during 88% of the follow-up visits. Conclusions: One-third of the participants remained ulcer-free for 24 months. Patient-driven education in groups did not give better results than standard information in this underpowered study. This study illustrates the challenges to perform comparative preventive studies in this group of patients with extensive comorbidity. Further studies are needed to evaluate interventions on ulceration in persons with a healed foot ulcer.

Diabetic foot is a severe complication of diabetes, with serious consequences such as amputations and high mortality rates as well as elevated economic costs. To evaluate whether or not nursing staff follow the recommendations of national and international organizations regarding diabetic foot prevention, a cross-sectional and observational descriptive study was carried out using an ad hoc self-administered questionnaire validated by seven experts, with a Cronbach's alpha of 0.731. Of the total 164 participants, 157 met the inclusion criteria. Findings showed that 96.58% asked their patients to remove their footwear, 78.34% performed thorough examinations, and 80.25% assessed the risk of developing diabetic foot. Participants educated their patients in self-care and evaluated skills related to diabetic foot control either frequently (84.07%) or very frequently (62.42%), and only 19.11% of them carried out group activity workshops. Significant statistical differences were found in the performance of activities in the groups by participant age intervals, whether working in primary health care or a hospital, having specific training, and the participant's DM patient ratio. We obtained high percentages of compliance in the assessed activities in comparison to other studies. Nevertheless, we believe it is necessary to encourage screening in specialized care, skills testing, and the implementation of educational group activities and workshops.

Diabetic chronic wounds cause massive levels of patient suffering and economic problems worldwide. The state of chronic inflammation arises in response to a complex combination of diabetes mellitus-related pathophysiologies. Advanced treatment options are available; however, many wounds still fail to heal, exacerbating morbidity and mortality. This review describes the chronic inflammation pathophysiologies in diabetic ulcers and treatment options that may help address this dysfunction either directly or indirectly. We suggest that treatments to reduce inflammation within these complex wounds may help trigger healing.

To analyze the associations among and contributions of sociodemographic, clinical, and psychological variables to quality of life (QoL) related to diabetic foot ulcers (DFUs; DFUQoL).

The sample comprised 70 patients with DFUs who answered the following questionnaires: the Hospital Anxiety and Depression Scale, Illness Perception Questionnaire-Brief, Diabetic Foot Ulcer-Short Form, Medical Term Recognition test, and a sociodemographic and clinical questionnaire. Pearson and biserial correlation coefficients, hierarchical regressions, and moderation analyses were conducted to study the relationships among variables.

The results showed that a large DFU, threatening representations about DFU, and more psychological distress were associated with lower DFUQoL. Also, more psychological distress, more threatening DFU representations, and taking antibiotics contributed to worse DFUQoL. Clinically significant levels of psychological distress moderated the relationship between the DFU extent and negative emotions.

This study showed that QoL and its domains were associated with psychological distress and that QoL was more influenced by DFU representations than by a larger-sized wound, emphasizing the importance of psychological interventions in the treatment of patients with DFUs.

One of the most serious complications of diabetes mellitus (DM) is a diabetic foot ulcer (DFU), with lower extremity amputation (LEA).

This study aims to explore the role of anxiety and depression on mortality, reamputation and healing, after a LEA due to DFU.

A sample of 149 patients with DFU who underwent LEA answered the Hospital Anxiety and Depression Scale and a sociodemographic and clinical questionnaire. This is a longitudinal and multicenter study with four assessment moments that used Cox proportional hazards models adjusted for demographic and clinical variables.

Rate of mortality, reamputation and healing, 10 months after LEA were 9.4%, 27.5% and 61.7%, respectively. Anxiety, at baseline, was negatively associated with healing. However, depression was not an independent predictor of mortality. None of the psychological factors was associated with reamputation.

Results highlight the significant contribution of anxiety symptoms at pre-surgery, to healing after a LEA. Suggestions for psychological interventions are made.

The present study investigates whether modifiable behavioral factors of current cigarette smoking, heavy alcohol consumption, and regular exercise are associated with risk of lower extremity amputation (LEA) in diabetic patients.

A total of 2,644,440 diabetic patients (aged ≥20 years) was analyzed using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios (HRs) for the behavioral factors with risk of LEA under adjustment for potential confounders.

The risk of LEA was significantly increased by current cigarette smoking and heavy alcohol consumption (HR, 1.436; 95% confidence interval [CI], 1.367 to 1.508 and HR, 1.082; 95% CI, 1.011 to 1.158) but significantly decreased with regular exercise (HR, 0.745; 95% CI, 0.706 to 0.786) after adjusting for age, sex, smoking, alcohol consumption, exercise, low income, hypertension, dyslipidemia, body mass index, using insulin or oral antidiabetic drugs, and diabetic duration. A synergistically increased risk of LEA was observed with larger number of risky behaviors.

Modification of behaviors of current smoking, heavy alcohol intake, and exercise prevents LEA and can improve physical, emotional, and social quality of life in diabetic patients.

Motivational approaches may help target the psychological aspects of self-care, improving adherence to good practices in individuals with diabetes. The present study was designed to test the feasibility and effectiveness of a psychoeducational program for diabetic foot prevention or disease progression.

Eighty-one subjects with or at high risk of foot ulcer development entered a program consisting of six 120-min group sessions, conducted by a podiatrist and an expert in psycho-education. Occurrence/recurrence of lesions in a 3-year follow-up was compared with 172 cases with similar risk score (IWGDF score 2019), receiving education at any 6-month podiatric visit (standard-of-care). Motivation to self-care and competence were assessed by specific questionnaires. The experimental program increased adherence to follow-up. The prevalence of foot lesions was higher at baseline and was remarkably reduced at any time-point in patients attending the psychoeducational program, whereas it remained relatively stable in standard care (around 10% of cases). The cumulative incidence was lower in the psychoeducational program (13.2, 95% CI 9.2-18.0 per 100 patient-year vs. 26.1; 95% CI 22.1-30.2); time to new lesions was increased (P = 0.022). Cox proportional hazard analysis confirmed an overall reduction of lesions in the psychoeducational program (HR 0.34; 95% CI 0.18-0.66; P < 0.001), after adjustment for confounders. The program was associated with significant changes in competence and motivation to self-care.

A psychoeducational approach is both feasible and effective to support patients with diabetes at high risk of first or recurrent foot lesions, increasing their adherence to self-care practices.

Diabetes mellitus (DM) is one of the most prevalent diseases in the world, and is correlated to a high index of mortality. One of its major complications is diabetic foot, leading to plantar ulcers, amputation, and death. Several studies report that a thermogram helps to detect changes in the plantar temperature of the foot, which may lead to a higher risk of ulceration. However, in diabetic patients, the distribution of plantar temperature does not follow a standard pattern, thereby making it difficult to quantify the changes. The abnormal temperature distribution in infrared (IR) foot thermogram images can be used for the early detection of diabetic foot before ulceration to avoid complications. There is no machine learning-based technique reported in the literature to classify these thermograms based on the severity of diabetic foot complications. This paper uses an available labeled diabetic thermogram dataset and uses the k-mean clustering technique to cluster the severity risk of diabetic foot ulcers using an unsupervised approach. Using the plantar foot temperature, the new clustered dataset is verified by expert medical doctors in terms of risk for the development of foot ulcers. The newly labeled dataset is then investigated in terms of robustness to be classified by any machine learning network. Classical machine learning algorithms with feature engineering and a convolutional neural network (CNN) with image-enhancement techniques are investigated to provide the best-performing network in classifying thermograms based on severity. It is found that the popular VGG 19 CNN model shows an accuracy, precision, sensitivity, F1-score, and specificity of 95.08%, 95.08%, 95.09%, 95.08%, and 97.2%, respectively, in the stratification of severity. A stacking classifier is proposed using extracted features of the thermogram, which is created using the trained gradient boost classifier, XGBoost classifier, and random forest classifier. This provides a comparable performance of 94.47%, 94.45%, 94.47%, 94.43%, and 93.25% for accuracy, precision, sensitivity, F1-score, and specificity, respectively.

The 'Outcomes & Multi-morbidity in Type 2 Diabetes' (OMIT) is an observational registry-based cohort of Norwegian patients with type 2 diabetes (T2D) established to study high-risk groups often omitted from randomised clinical trials.

The OMIT cohort includes 57 572 patients with T2D identified via linkage of Norwegian Diabetes Register for Adults and the Rogaland-Oslo-Salten-Akershus-Hordaland study, both offering data on clinical patient characteristics and drug prescriptions. Subsequently these data are further linked to the Norwegian Prescription Database for dispensed medications, the Norwegian Population Register for data on death and migration, Statistics Norway for data on socioeconomic factors and ethnicity and the Norwegian Directorate of Health for data on the general practices and clinical procedures involved in the care of cohort patients. OMIT offers large samples for key high-risk patient groups: (1) young-onset diabetes (T2D at age <40 years) (n=6510), (2) elderly (age >75 years) (n=15 540), (3) non-Western ethnic minorities (n=9000) and (4) low socioeconomic status (n=20 500).

On average, patient age and diabetes duration is 67.4±13.2 and 12.3±8.3 years, respectively, and mean HbA_1c for the whole cohort through the study period is 7.6%±1.5% (59.4±16.3 mmol/mol), mean body mass index (BMI) and blood pressure is 30.2±5.9 kg/m² and 135±16.1/78±9.8 mm Hg, respectively. Prevalence of retinopathy, coronary heart disease and stroke is 10.1%, 21% and 6.7%, respectively.

The OMIT cohort features 5784 subjects with T2D in 2006, a number that has grown to 57 527 in 2019 and is expected to grow further via repeated linkages performed every third to fifth year. At the next wave of data collection, additional linkages to Norwegian Patient Registry and Norwegian Cause of Death Registry for data on registered diagnoses and causes of death, respectively, will be performed.