The international journal of lower extremity wounds最新文献

Plasminogen (Pg) is currently considered a master regulator of wound healing, but the molecular mechanisms of its efficacy in improving impaired closure of chronic skin ulcers in type 2 diabetes patients remain unclear. Here, we investigated wound healing effects of autologous plasma-derived Pg in diabetes patients with chronic foot ulcers and evaluated Pg-induced changes in levels of key protein markers related to wound repair. Type 2 diabetes patients with chronic wounds of lower extremities were included in the study and received topical applications of Pg in a dose of 1.0 mg/mL every 2 days during 20 days, in addition to the standard wound management treatment. Patients treated only according to conventional protocol served as a control. Wound closure rates were monitored by digital planimetry of wound areas. Plasminogen supplementary treatment significantly accelerated relative wound closure as compared with diabetes patients from the control group (24 ± 4 days vs 120 ± 17 days, respectively, P < .01). As shown by Western blot, Pg application reduced expression of protein regulators of hypoxia events, angiogenesis, and autophagy such as hypoxia-inducible factor-1α (by 6.3-folds, P < .01), angiostatins (by 2.5-folds, P < .05), and autophagy marker LC3-II/LC3-I (by 8.6-folds, P < .05), while increasing vascular endothelial growth factor level by 1.9-folds (P < .05). Gelatin zymography showed that Pg-supplemented therapy decreased activity of matrix metalloproteinase-9 (MMP-9) by 3.5-folds at the end of treatment period (P < .01). We report here for the first time that topically applied plasma-derived Pg has a pronounced beneficial effect in promoting foot ulcer healing in patients with type 2 diabetes through preventing hypoxia-induced signaling, reducing autophagy flux, diminishing excessive MMP activity, and enhancing angiogenesis.

The aim of the present study was to evaluate effects of curcumin-polyethylene glycol loaded on chitosan-gelatin nanoparticles (C-PEG-CGNPs) on healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in rat as a model study. Forty male Wistar rats were randomized into 5 groups of 8 animals each. In CNTRL group, no infected/no treated wounds were covered with sterile saline 0.9% solution (0.1 mL). In MRSA group, MRSA-infected wounds were only treated with sterile saline 0.9% solution (0.1 mL). In MRSA/CP group, 0.1 mL curcumin nanoparticles (1 mg/mL) was applied topically to treat MRSA-infected wounds. In MRSA/CG group, 0.1 mL CG (1 mg/mL) was applied topically to treat MRSA-infected wounds. In MRSA/CP-CG group, 0.1 mL CP-CG (1 mg/mL) was applied topically to treat MRSA-infected wounds. Microbiological examination; planimetric, biochemical, histological, morphometric studies, angiogenesis, hydroxyproline levels, and reverse transcription polymerase chain reaction for caspase 3, Bcl-2, and p53 showed significant difference between rats in MRSA/CP-CG group in comparison with other groups (P < .05). Accelerated and improved healing in wounds infected with MRSA were observed in animals treated with C-PEG-CGNPs. Via increasing solubility of curcumin in C-PEG-CGNP, this harmless and easily available composition could be considered to be topically applied in infected wounds.

Chronic diabetic foot ulcers pose significant challenges in wound management, often necessitating innovative therapeutic approaches to promote healing. This case report highlights the efficacy of Granulox®, a topical hemoglobin spray designed to enhance oxygen supply to chronic wounds, in conjunction with standard care. An 84-year-old male with a longstanding diabetic foot ulcer demonstrated remarkable improvement following the addition of Granulox® to his treatment regimen. Significant reduction in ulcer size, resolution of clinical signs of infection, and improvement in peri-wound skin condition were observed within weeks of initiating Granulox® therapy. The patient-reported decrease in pain severity and the ultimately complete healing of the ulcer underscore the potential of topical oxygen therapy as an adjunctive modality in wound management. This case report contributes to the growing body of evidence supporting the efficacy and ease of use of Granulox® in promoting wound healing, particularly in chronic diabetic foot ulcers.

Introduction: Refractory diabetic foot ulcer (rDFU) and osteomyelitis (diabetic foot osteomyelitis [DFO]) are a major problem in people with diabetes. Often resulting from multidrug-resistant polymicrobial infection, these may result in amputation or nonhealing ulcers. In this nonrandomized open-label study, we looked at the outcome of treatment with rifampicin in patients with nonhealing diabetic foot ulcers.

Material and methods: Patients with DFUs (n = 67, n = 55 with DFO) unresponsive to conventional antimicrobial therapy for >3 months (rDFU) were taken as the study group. All patients received rifampicin for a minimum of 3 months (maximum 6 months if DUFs did not heal after 3 months) in addition to standard antibiotics and compared with similar kind of DFUs (n = 68, n = 55 DFO) who formed the control group, treated with conventional antimicrobial therapy. Patients were followed up for 12 months. Healing of DFU at 6 months and amputation were primary endpoints of the study.

Results: In total, 43 patients (64.2%) in the rifampicin group healed at 3 months and another 4 patients healed when rifampicin was continued for 6 months (n = 47, 70.1%). In the control group, 11 patients healed at 3 months (16.2%) and 25 patients healed at 6 months (36.8%). In total, 14 patients (20.9%) in the study group and 29 patients (42.6%) in the control group had to undergo minor amputation. Comparison between the rate of healing at 3 and 6 months and minor amputation between the study group and control group showed statistically significant results (P ≤ .00001, <.00001, and .008, respectively). In total, 6 and 8 patients despite healing of the primary ulcer had a subsequent recurrence of ulcer in the rifampicin and control group, respectively.

Conclusion: Rifampicin used in conjunction with other standard poly-microbial therapy in refractory complex diabetic foot ulcer unresponsive to standard antimicrobial therapy, can significantly improve wound healing as well as decrease the need for amputation in addition to standard of care.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional, multidisciplinary team (MDT) program for patients with diabetic foot ulcers (DFU) within a healthcare cluster in Singapore. This is one of our subgroup analyses within DEFINITE Care, assessing clinical outcomes of lower extremity amputation prevention program (LEAPP), a multidisciplinary diabetic foot clinic, and non-LEAPP patients within the program. From June 2020 to June 2022, 2798 patients within the DEFINITE cohort completed a minimum of 12-month follow up. Of these patients, 20.6% were managed by LEAPP, whereas 79.4% were non-LEAPP patients. Patients in the LEAPP cohort were older with co-existing metabolic conditions and complications of diabetes. Using non-LEAPP cohort as the reference group and after adjusting for age, gender, ethnicity, comorbidities, and medications, there was a significantly lower risk of death (odds ratio [OR] 0.60, P = .001) and composite major lower extremity amputation (LEA) or death (OR 0.66, P = .002) among LEAPP patients at 1 year with longer mean days from enrollment to minor LEA, major LEA, and death. The adjusted 1-year healthcare utilization outcomes for LEAPP patients demonstrated an increase in inpatient admissions, primary care polyclinic visits, hospital specialist outpatient clinic (SOC) visits and elective day surgery procedures. Despite the increased in inpatients admissions, cumulative hospital length of stay in LEAPP patients were lower. This subgroup analysis has demonstrated that the MDT approach to caring for patients with DFU in tertiary centers not only improves mortality by 40%, but also delayed the incidence of minor LEA, major LEA, and death.

Background and aims: Charcot neuroosteoarthropathy (CN) is considered a rare complication of diabetic neuropathy. Due to its insidious mode of presentation, CN may be difficult to diagnose timely and a high index of suspicion is required from both, the diabetic patient (especially those with neuropathy) and their physicians for the early diagnosis and treatment to prevent major complications.

Methods: We planned a narrative review and searched MEDLINE database to identify evidence regarding CN incidence, treatment options, and recent guidelines. As practitioners do not commonly treat CN, a characteristic clinical case is also presented.

Results: The available evidence for diagnosis and treatment remains of low quality. On the one hand, there is an urgent need for action to increase awareness of the disease in both practitioners and people with diabetes. On the other hand, prospective nationwide registries of patients with diabetic neuropathy will help clarify the prognostic factors that may predispose to this complication, and more randomized clinical trials are needed to identify whether medical treatment may improve CN outcomes. For the time being, offloading of the foot to stop the perpetuation of trauma, and inflammation, and importantly to arrest the progression to a deformed nonfunctional foot is the cornerstone of medical therapy of CN. Multidisciplinary assessment between diabetologists and radiologists is fundamental for prompt diagnosis.

Conclusions: To avoid potentially deleterious delays in diagnosis and treatment, every physician should bear in mind that every patient with diabetic neuropathy presenting with a warm swollen foot should be treated as having CN until proven otherwise.

Charcot neuro-osteoarthropathy (CNO) is a complication of diabetes occurring in people with diabetic neuropathy with a prevalence of 0.5% to 1% that may culminate to foot deformity, amputation, and early mortality. However, it is not known why only certain patients with diabetic neuropathy develop CNO. Hence, early recognition of risk factors, timely diagnosis, and appropriate intervention of CNO is pertinent. Recent understanding of the pathophysiology of CNO has expanded to suggest the involvement of RANKL-OPG pathways. But pharmaco-therapeutic interventions targeting bone metabolism predominantly inhibiting RANKL were not found to be useful. Moreover, there are not enough markers to help identify patients with diabetes who are at a higher risk of developing CNO. Hence, we explored the literature in the present systematic review of mainly case-control studies to identify genetic factors that could help in understanding the pathophysiology and risk factors for the development of CNO. We could identify 7 relevant studies identifying single nucleotide polymorphism of OPG and RANK genes. There is an isolated study identifying alterations of micro RNA associated with RANKL-OPG pathway. Another study found epigenetic alterations by performing whole methylome sequencing in people with CNO compared to control. These genetic factors can be used as a diagnostic marker and their functional counterparts as targets for future therapeutic interventions. However, we found that literature is sparse on the genetic risk factors for CNO in people with diabetic neuropathy and there is still a lot of scope for future studies towards finding the molecular and genetic markers for CNO.