EUREKA study - The evaluation of real-life use of a biophotonic system in chronic wound management: An interim analysis

Objective: Interest has grown regarding photobiomodulation (PBM) with low-level light therapy, which has been shown to positively affect the stages of the wound healing process. In a real-life context clinical setting, the objective of the EUREKA study was to investigate efficacy, safety, and quality of life associated with the use of a BioPhotonic gel (LumiHeal\u2122) in the treatment of chronic wounds such as venous leg ulcers (VLUs), diabetic foot ulcers (DFUs), and pressure ulcers (PUs). This BioPhotonic gel represents a new, first-in-class emission spectrum of light, including fluorescence, to induce PBM and modulate healing. Design: The multicenter, prospective, interventional, uncontrolled, open-label study enrolled 100 patients in 12 wound centers in Italy. We performed an early interim analysis based on the first 33 subjects (13 VLU, 17 DFU, 3 PU) in seven centers who completed the study. Main results: Seventeen patients (52%) achieved total wound closure (full re-epithelialization for 2 weeks) during the study period. Two patients (6%) were considered \u201calmost closed\u201d (decrease of the wound area of more than 90% at study end) and three others (9%) were considered \u201cready for skin grafting\u201d. No related serious adverse events were observed, and the compliance was excellent. After the treatment, the average time to \u201cpain-free\u201d was 11.9 days in the VLU group. Quality of life was improved with overall increase of 26.4% of the total score (Cardiff Wound Impact Schedule, p=0.001). Conclusion: The study revealed a positive efficacy profile of the BioPhotonic gel in promoting wound healing and reactivating the healing process in different types of chronic, hard-to-heal wounds. The treatment was shown to be safe and well tolerated by the patients, and a reduction of pain perception was also detected during the treatment period. The improvement of the quality of life was accompanied by a high level of clinician satisfaction

Outcomes of three years of teamwork on critical limb ischemia in patients with diabetes and foot lesions

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

PERCORSI DIAGNOSTICO-TERAPEUTICI IN PAZIENTI CON SINDROME DEL PIEDE DIABETICO AFFERENTI AD UN CENTRO DI TERZO LIVELLO: REVISIONE CRITICA DI 5 ANNI DI ATTIVITA'

Il Diabete mellito rappresenta un esempio paradigmatico di patologia sistemica multifattoriale. La condizione di iperglicemia cronica, mediante molteplici vie di danno, determina lo sviluppo di complicanze croniche a carico di vari organi target. In particolare, a carico degli arti inferiori, più meccanismi etiopatogenetici concorrono: neuropatia somatica periferica, arteriopatia obliterante ed immunopatia. Ciò spiega perchè il piede diabetico vada considerato la manifestazione locale a livello di un organo – l’arto inferiore appunto – di una malattia cronica sistemica progressiva e ingravescente. Il nostro studio ha evidenziato come le complicanze a carico degli arti inferiori rappresentino la prima causa di ricovero nel soggetto diabetico. Nella nostra casistica abbiamo evidenziato un tasso di guarigione pari al 71% nel corso del periodo di follow up con un’incidenza di amputazioni maggiori analoga a quanto riportato in letteratura. Stratificando la popolazione in base alla gravità della patologia vascolare emerge chiaramente come la rivascolarizzazione, in particolare se diretta secondo la teoria degli angiosomi, rappresenti la strategia terapeutica in grado di fare la differenza sia in termini di guarigione delle lesioni (in tal senso insieme all’intervento chirurgico), che di amputazioni maggiori e di mortalità. L’analisi dei ricoveri ripetuti infine ha confermato l’elevata frequenza di recidiva nonché l’aggravamento della patologia e dello stato generale del malato ad ogni nuovo episodio

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

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

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

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

KPC-producing Klebsiella pneumoniae rectal colonization is a risk factor for mortality in patients with diabetic foot infections

To evaluate the relationship between carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) gut colonization and mortality in diabetic patients with a foot infection (DFI) we performed a single-centre, retrospective, matched case-control study. In the study period, we identified 21 patients with DFI who had KPC-Kp gut colonization and 21 controls. The 90-day mortality rate was significantly higher in patients with colonized guts (47%) than the controls (4%) (p 0.013). A multivariate analysis demonstrated that gut colonization with KPC-Kp was the only independent predictor of mortality: odds ratio 13.33, 95% CI 1.90-272.80, p 0.024. In patients with DFI, KPC-Kp gut colonization appears to be an important risk factor for mortality

Treatment of diabetic foot ulcers with therapeutic magnetic resonance (TMR®) improves the quality of granulation tissue

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