Neuropathic Diabetic Foot Ulcers Research Articles

Effect of Buerger-Allen exercise on wound healing in patients with diabetic foot ulcers: a randomised controlled trial.

A diabetic foot ulcer (DFU) is a complication of type 2 diabetes that is difficult to treat. Buerger-Allen exercise has shown effectiveness in improving foot circulation and neuropathy in several studies; however, to the best of our knowledge, no randomised controlled study has investigated its effectiveness for DFU healing. Therefore, this study aimed to assess the effects of Buerger-Allen exercise on the healing of DFUs in patients with type 2 diabetes. This is a parallel-group randomised controlled trial (RCT). Of 50 patients with neuropathic DFUs, 41 completed the study. They were assigned randomly to a study group (n=21) and a control group (n=20). Patients in the study group received the standard medical treatment and semi-supervised Buerger-Allen exercise for three sessions per week for four weeks, while patients in the control group only received the standard medical treatment. The outcome measures were: ankle-brachial pressure index (ABPI); ulcer size; ulcer depth; SINBAD score; and ulcer risk for poor outcomes (based on the SINBAD score). The study group's mean age was 49.48±6.45 years and the control group's mean age was 49.15±5.85. The study group's ABPI increased significantly compared to the baseline (1.17±0.04 versus 1.11±0.05, respectively; p<0.001) and the control group (1.17±0.04 versus 1.14±0.05, respectively; p=0.04) post-intervention. Ulcer size also reduced significantly in the study group compared to the baseline (2.63±2.0 versus 7.48±5.55cm2, respectively; p<0.001) and the control group (2.63±2.0 versus 6.43±4.45cm2, respectively; p<0.001) post-intervention. Ulcer depth decreased significantly in the study group compared to the baseline (1.71±1.05 versus 4.19±1.74mm, respectively; p<0.001) and the control group (1.71±1.05 versus 2.80±1.57mm, respectively; p=0.01) post-intervention. Furthermore, the SINBAD score in the study group decreased significantly compared to the baseline (1.38±0.86 versus 2.14±1.06, respectively; p<0.001) and the control group (1.38±0.86 versus 2.0±0.79, respectively; p=0.02) post-intervention. Moreover, the ulcer risk for poor outcomes, based on the SINBAD score, reduced significantly only in the study group, compared to the baseline (p=0.041). The control group showed non-significant changes compared to the baseline in all outcome measures (p>0.05). From the findings of this RCT, Buerger-Allen exercise, in combination with standard wound care, may help accelerate the healing of neuropathic DFUs in patients with type 2 diabetes, and could be suggested as part of the management plan for such conditions as an easy-to-perform offloading exercise intervention.

A deeper look at low-frequency contact ultrasonic debridement in the clinical management of patients with diabetic foot ulcers.

The current study aimed to evaluate the dispersal of solution and microbes (aerosol) in the clinical environment during treatment with Low-frequency contact ultrasonic debridement (LFCUD) with or without suction attachment in patients with diabetic foot ulcers (DFUs). We performed 20 treatments in 10 patients divided into two groups to receive the proposed LFCUD modalities. We measured the microbial load of the environment pre-treatment (sample M1), during treatment with each LFCUD modality (sample M2) and post-treatment (sample M3). The use of LFCUD debridement without a suction attachment results in significantly higher immediate contamination of the clinic environment than the suction attachment, particularly during the procedure (1.70 ± 0.98 log 10 CFU/mL versus 0.77 ± 0.85 log 10 CFU/mL, p = 0.035). When suction is not applied, there are statistically significant differences depending on whether the DFUs are neuropathic or neuroischemic, finding a greater number of microorganisms with high loads in neuropathic DFUs. We found a statistically significant positive correlation between wound area (r = 0.450, p = 0.047) and TBI (r = 0.651, p = 0.006) with the bacterial load during the LFCUD. Based on our results, we recommend using the personal protective equipment required to protect staff members and patients during treatment with LFCUD and using a suction attachment where clinically possible to reduce clinic environmental pollution, especially in neuropathic DFUs and those with larger areas.

Exploring barriers and enablers of self-management behaviours in patients with diabetic foot ulcers: A qualitative study from the perceptions of patients, caregivers, and healthcare professionals in primary care.

Exploring barriers and enablers of self-management behaviours in patients with diabetic foot ulcers: A qualitative study from the perceptions of patients, caregivers, and healthcare professionals in primary care.

A Feasibility and Safety Study of a Novel Human Decellularized Dermal Matrix to Accelerate Healing of Neuropathic Diabetic Foot Ulcers in People With Type 1 and Type 2 Diabetes

ObjectivesThe purpose of this study was to determine the feasibility and safety of a novel decellularized dermal matrix (DDM) for the treatment of chronic diabetic foot ulcers (DFUs). MethodsAn interventional, single-arm, prospective study of DDM for DFU treatment was conducted in 2 Canadian centres from July 1, 2016, to May 30, 2017. Individuals ≥18 years of age with an active DFU of ≥2 weeks and ulcer area ≥1 cm2 before debridement and who consented to participate were enrolled in this clinical trial. ResultsA total of 11 patients were enrolled, with 9 patients (82%) having achieved 100% closure between 2 and 8 weeks. The mean and median times to wound closure for these patients were 3.3 and 2.5 weeks, respectively. The mean and median reductions in wound area at 4 weeks posttreatment were 87% and 100%, respectively. The proportion of patients having achieved complete healing at 12 weeks was 82%. All patients received only 1 DDM application to achieve these results. There were no adverse events related to use of the product. No cases of recurrence during a 1-year follow-up after completion of the study were reported for patients who achieved wound closure. ConclusionsThese findings provide evidence that this DDM may be safe and effective for the treatment of chronic, hard-to-heal neuropathic DFUs. Specifically, DDM demonstrated the potential to accelerate healing of DFUs when compared with reported times of 8 to 12 weeks required to achieve closure using the current standard of care.

Investigation of the relationship between lower extremity selective motor control, center of pressure distribution, and gross motor function: Plot study

The purpose of this study was to investigate the feasibility and safety of a novel Decellularized Dermal Matrix (DDM) for the treatment of chronic Diabetic Foot Ulcers (DFUs).An interventional, single-arm, prospective study of DDM for DFU treatment was conducted in two Canadian from July 1st, 2016 to May 30th, 2017. Individuals 18 or older, with an active DFU for at least 2 weeks, ulcer area of ≥1 cm2 prior to debridement who consented to participate were enrolled in this clinical trial.A total of 11 patients were enrolled with 9 patients (82%) having achieved 100% closure between 2-8 weeks. The mean and median times to wound closure for these patients was 3.3 and 2.5 weeks, respectively. The mean and median reduction in wound area at 4 weeks post-treatment was 87 and 100 %, respectively. The proportion of patients having achieved complete healing at 12 weeks was 82%. All patients received only 1 application of the DDM to achieve these results. There were no adverse events related to the product. No cases of recurrence during a one-year follow-up after completion of the study have been reported for patients who achieved wound closure in the study.These findings provide evidence that this DDM may be safe and effective for the treatment of chronic, hard to heal neuropathic DFUs. Specifically, it demonstrated the potential to accelerate the healing rate of DFUs when compared with reported times of 8-12 weeks required to achieve closure using standard of care.

Early and Intensive Glycemic Control for Diabetic Foot Ulcer Healing: A Prospective Observational Nested Cohort Study.

We aimed to assess the effect of glycemic control on diabetic foot ulcer (DFU) healing. A prospective nested cohort study was employed of individuals with poorly controlled diabetes (glycated hemoglobin [HbA1c] >9%) and neuropathic DFU of >2-week duration. All individuals received standard diabetes and ulcer interventions for 12 weeks. Baseline demographic characteristics, ulcer area (automated assessment by wound zoom camera), and biochemical parameters were analyzed. The cohort was stratified into ulcer healed and unhealed groups. Ulcer area and glycemic parameters at 4 and 12 weeks on follow up were compared. Forty-three individuals (47 DFU) with baseline HbA1c 11.6% and ulcer area 9.87 cm2 were enrolled. After 12 weeks, mean HbA1c was 7.2%, 17 ulcers closed (healed group) and 30 ulcers did not close (unhealed group). The median time to ulcer healing was 10 weeks. Individuals in the healed group had lower fasting blood glucose (P = .010), postprandial blood glucose (P = .006), and HbA1c at 4 weeks (P = .001), and 12 weeks (0.018) compared to the unhealed group. Cox-regression analysis that revealed lower baseline ulcer area (P = .013) and HbA1c at 4 weeks (P = .009) significantly predicted DFU healing by 12 weeks. Baseline ulcer area of >10.58 cm2 and HbA1c at 4 weeks of >8.15% predicted delayed DFU healing. In conclusion, early and intensive glycemic control in the first 4 weeks of treatment initiation is associated with greater healing of DFU independent of initial ulcer area.

Randomized comparative study between metatarsal head resection and total contact cast in the treatment of diabetic plantar forefoot ulcer

Objective The present study assessed and compared the efficacy of metatarsal head resection (MHR) compared with total contact cast (TCC) in the treatment of neuropathic diabetic foot ulcers located at the plantar surface of metatarsal heads. Materials and methods Between January 2017 and September 2019, this prospective, randomized, comparative study was performed at Menoufia University −Hospitals. One hundred patients suffering from solitary planter forefoot neuropathic ulceration were assigned into two groups: the first group was treated by MHR and the second group was treated by TCC. Wound healing was the primary outcome while ulcer recurrence and complications were the secondary outcomes of this study. Results Baseline patient characteristics were comparable in both groups. Both intention-to-treat and per-protocol analysis were used to evaluate ulcer healing during the treatment period. Percentage of ulcers healed within 12 weeks was 82 and 58% for MHR and TCC groups, respectively (P Conclusion Being an invasive procedure, MHR offers a safe effective offloading option with higher healing potential and lower recurrence rate compared with TCC as the standard offloading modality.

A Meta-Analysis of the Outcomes of Metatarsal Head Resection for the Treatment of Neuropathic Diabetic Foot Ulcers.

Significance: Diabetic foot ulcers (DFUs) are associated with high morbidity, mortality, and health costs. Standard care (SC) associated with nonsurgical offloading is the mainstay treatment for DFUs, but it has high recurrence and infection rates. Metatarsal head resection (MHR) has been proposed as an effective surgical offloading technique for the treatment of plantar neuropathic DFUs, but with no evidence synthesis yet. Recent Advances: Based on PRISMA guidelines, a meta-analysis was conducted to assess the efficacy of MHR. Four electronic databases were searched for. Eleven studies met the inclusion criteria with a total of 477 patients (494 feet and 593 neuropathic forefoot ulcers). The studies included three retrospective comparative studies and eight case series. Critical Issues: Meta-analytical results of comparative studies on recent noninfected DFUs showed MHR having significantly better rates of healing, time to healing, ulcer recurrence, and infection than SC. Failure to heal, recurrence, and infection rates were 4 times higher in the SC group than in the MHR group, and the amputation rate was two times higher in the SC group than in the MHR group. The outcomes of the meta-analysis of case series on chronic and recalcitrant ulcers treated with MHR were similar. Future Directions: Considering the natural history of DFUs treated conservatively and the satisfactory outcomes with a significantly low complication rate of MHR, physicians should consider the use of MHR more often and include this technique in the early management of DFUs. Scope and Significance: DFU impose great public health burden around the globe. Standard of care using in-office debridement and topical agents is the usual mainstay of treatment. However, such conservative care is known to result in high rates of ulcer recurrence and complications. In this systematic review, we quantitatively investigate the outcomes of a surgical off-loading technique, the MHR in the treatment of chronic plantar neuropathic wounds. Translational Relevance: Many biochemical factors are implicated in the complex process of wound healing. In the case of diabetic neuropathic ulcers of the forefoot, additional mechanical factors induced by the presence of diabetic neuropathy lead to high pressure loads of the metatarsal heads on the plantar skin. With time, such chronic loads could favor ulcer formation. Removal of the causal mechanical factor could alleviate the pressure and allow wound healing. Clinical Relevance: Neuropathic plantar ulcers are difficult-to-heal wounds and chronicity is associated to frequent hospitalizations, higher rates of amputation, and mortality. Early removal of the indirect causal agent, the resection of the metatarsal head, after failure of a well-conducted conservative standard of care could be a needed solution for wound healing and consequently a potential for reducing complications and costs.

Studying the impact of the cost-effective Suvidha off-loading dressing in healing neuropathic ulcers in diabetic foot: a case series of 83 cases from South India

Neuropathic ulcers pose a global burden carrying a risk of amputation of 15-46 times especially in developing countries. These ulcers are mainly managed with offloading techniques. In this study we share our experience of using an easy to use, cost effective method the Suvidha offloading dressings in terms of its acceptability and effectiveness in managing these cases. A prospective case series of 83 patients with mean age 58 years, managed with Suvidha offloading dressing in our institution from 2016 till 2019, excluding patients with ABI less than 0.4 and Wagner 4 and 5. They were reviewed after 6 months/SOS. Ulcer measured 1×1 to 4×4 cm, was present most commonly in the mid foot and least commonly in the lateral aspect of the foot. 53 cases were Wagner grade 2 and 9 cases Wagner grade 3. Forty cases were initially infected, 29 cases had a deformed foot, 5 cases needed interval wound debridement. The duration of ulcer healing was 2 weeks for 1×1 cm great toe ulcer, to 12 weeks for the 4×4 cm mid foot ulcer. All 83 patients were followed up for 6 months. 5 ulcers recurred. The patient satisfaction was measured by a 5-points Likert scale with a mean value of 17.4 out of 20. The Suvidha offloading footwear is a cost effective, easily replicable and efficient dressing requiring only the readily available dressing materials, with good healing rates, good patient satisfaction and adapted for developing countries. The results are comparable with other methods of offloading practiced worldwide.

Prevalence, Clinical Aspects and Outcomes in a Large Cohort of Persons with Diabetic Foot Disease: Comparison between Neuropathic and Ischemic Ulcers.

This study aims to evaluate clinical and ulcer characteristics as well the outcomes of patients with diabetic foot ulcers (DFUs). The study group was composed of DFUs patients managed by a limb salvage protocol according to guidance. Clinical and ulcers findings were described, and 1-year outcomes defined as limb salvage, healing, healing time, major amputation and death were compared between neuropathic and ischemic DFUs. One thousand, one hundred and ninety-eight subjects were included; 386 (32.2%) neuropathic and 812 (67.8%) ischemic DFUs. Neuropathic patients were younger (69.5 ± 11.5 vs. 74.5 ± 11.5, p < 0.0001) and reported less cases of nephropathy (22.8 vs. 39.6%, p < 0.0001), ischemic heart disease (22.8 vs. 36.9, p = 0.0004), cerebrovascular disease (8.3 vs. 17.2%, p = 0.002), heart failure (10.1 vs. 24.7%, p = 0.0002) and end-stage-renal-disease (ESRD) (5.4 vs. 27%, p = 0.0001) than ischemic patients; they also showed less cases of large (>5 cm2) (10.3 vs. 22.9%, p = 0.0007), infected (40.4 vs. 55.7%, p = 0.0005) and deep to the bone (22.3 vs. 39.2, p = 0.0002) ulcers, as well less multiple ulcerations (21.8 vs. 32.8%, p = 0.006) than patients with ischemic DFUs. The outcomes for neuropathic and ischemic DFUs were limb salvage (98.4 vs. 82.3%, p < 0.0001), healing (97.3 vs. 79.6%, p < 0.0001), healing time (34.9 vs. 35.6 weeks, p = 0.8), major amputation (0.5 vs. 6.6%, p = 0.0001), death (1.1 vs. 11%, p < 0.0001) respectively. Revascularization failure and ESRD were independent predictors of major amputation, while heart failure and number of co-morbidities (≥5) were independent predictors of death. Ischemic DFUs patients showed more severe clinical and ulcers features as well worse outcomes than neuropathic DFUs patients.

Comparison of a new versus standard removable offloading device in patients with neuropathic diabetic foot ulcers: a French national, multicentre, open-label randomized, controlled trial

IntroductionThe offloading is crucial to heal neuropathic diabetic foot ulcer (DFU). Removable offloading are the most used devices. Orthèse diabète is a new customized removable knee-high offloading device immobilizing foot...

Long term outcomes after incident diabetic foot ulcer: Multicenter large cohort prospective study (EDI-FOCUS investigators) epidemiology of diabetic foot complications study: Epidemiology of diabetic foot complications study

AimsThis long-term prospective study evaluated limb amputation and mortality after the first neuropathic diabetic foot ulcer (DFU). MethodsA total of 2880 patients with neuropathic DFU (DFU group) and a similar number of patients of diabetes without DFU (nDFU) matched for age and diabetes duration were prospectively assessed at five referral-centers over 14 years. Pre-defined outcome was death during follow-up. Various diabetic co-morbidities and amputation were assessed as mortality predictors. ResultsOverall, 501 (17.4%) patients in DFU group died compared to 89 (3.1%) (p < 0.01) in nDFU group during a median follow-up of 7(1–14) years. The 5- and 10-year mortality was 22% and 71% in the DFU group with a median survival of 7.72 (7.37–8.08) years compared to 3% (p < 0.01) and 5% (p < 0.01) and survival of 12.6 (10.5–12.7) years (p < 0.001) in nDFU group. 29.3% patients had limb amputations. The mortality risk was independent of glycemic control [OR 1.03 (0.80–1.32; p = 0.83)]. However, diabetes duration > 10 years [OR 1.31(1.02–1.70, p = 0.035)], nephropathy [OR 1.47 (1.04–2.09, p < 0.030)], minor 1.85 (1.40–2.44; p < 0.001) or major amputation 2.96 (2.01–4.34, p < 0.001)] predicted mortality. ConclusionsEvery one-in-three individual with neuropathic DFU has amputation and every sixth individual has an early demise. Prevalent nephropathy and incident amputation following DFU predicts mortality.

Application of a collagen matrix dressing on a neuropathic diabetic foot ulcer: a randomised control trial.

Diabetic foot ulcers (DFU) are often hard-to-heal, despite standard care. With such a complicated healing process, any advanced wound care to aid healing is recommended. Chitosan/collagen composite hydrogel materials have the potential to promote the regenerative process. In this study, the efficacy of a new collagen matrix dressing including chitosan/collagen hydrogel was compared with a standard dressing of saline-moistened gauze for wound healing in patients with a hard-to-heal neuropathic DFU. This is an open labelled, randomised clinical trial. After conventional therapy consisting of debridement, infection control and offloading, patients were randomly allocated to receive either a collagen matrix dressing (the study group, receiving Tebaderm manufacturer) or a saline-moistened gauze dressing (control group) for wound care. The reduction in DFU size and the number of patients with complete healing were measured throughout the treatment and in follow-up. A total of 61 patients with a neuropathic DFU were recruited. Average percentage reduction in DFU size at four weeks was greater in the study group compared with the control group (54.5% versus 38.8%, respectively). Rate of complete healing rate at 20-weeks' follow-up was significantly better in the study group than the control group (60% versus 35.5%, respectively). The collagen matrix dressing used in this study accelerated the healing process of patients with a hard-to-heal DFU. Further research may suggest the used of this dressing to shorten the length of time to achieve complete healing.

Association between baseline abundance of Peptoniphilus, a Gram-positive anaerobic coccus, and wound healing outcomes of DFUs.

Diabetic foot ulcers (DFUs) lead to nearly 100,000 lower limb amputations annually in the United States. DFUs are colonized by complex microbial communities, and infection is one of the most common reasons for diabetes-related hospitalizations and amputations. In this study, we examined how DFU microbiomes respond to initial sharp debridement and offloading and how the initial composition associates with 4 week healing outcomes. We employed 16S rRNA next generation sequencing to perform microbial profiling on 50 samples collected from 10 patients with vascularized neuropathic DFUs. Debrided wound samples were obtained at initial visit and after one week from two DFU locations, wound bed and wound edge. Samples of the foot skin outside of the wounds were also collected for comparison. We showed that DFU wound beds are colonized by a greater number of distinct bacterial phylotypes compared to the wound edge or skin outside the wound. However, no significant microbiome diversity changes occurred at the wound sites after one week of standard care. Finally, increased initial abundance of Gram-positive anaerobic cocci (GPAC), especially Peptoniphilus (p < 0.05; n = 5 subjects), was associated with impaired healing; thus, GPAC’s abundance could be a predictor of the wound-healing outcome.

Efficacy and Safety of Low-Frequency, Noncontact Airborne Ultrasound Therapy (Glybetac) For Neuropathic Diabetic Foot Ulcers: A Randomized, Double-Blind, Sham-Control Study.

The diabetic foot ulcer (DFU) healing rates remain dismally low. Therefore, many adjunctive therapies have been evaluated including ultrasound therapy. The prior studies with noncontact, low-frequency ultrasound were retrospective, single arm, unblinded, or with historical controls. The aim of the present study was to compare the efficacy of noncontact, low-frequency airborne ultrasound (Glybetac) therapy with sham therapy added to standard treatment in patients with neuropathic, clinically infected, or noninfected DFU (wound size >2 cm2), Wagner grades 2 and 3. Patients received ultrasound or sham therapy for 28 days dosed daily for first 6 days followed by twice a week for next 3 weeks along with standard of care. The primary outcome was percentage of patients with at least >50% decrease in wound area at 4 week of intervention. Fifty-eight patients completed the study protocol. The duration of wound was 15.8 ± 11.2 weeks and 12.1 ± 10.9 weeks and wound area of 11.3 ± 8.2 cm2 and 14.8 ± 13.8 cm2 ( P = .507) in the ultrasound and sham groups, respectively. A >50% reduction in wound area was observed in 97.1% and 73.1% subjects ( P = .042) in ultrasound and sham groups, respectively. Wound contraction was faster in the first 2 weeks with ultrasound therapy, 5.3 cm2, compared with 3.0 cm2 ( P = .025) with sham treatment. Overall, wound area reduction of 69.4 ± 23.2% and 59.6 ± 24.9% ( P = .126) was observed at 4 weeks in the ultrasound and sham groups, respectively. We conclude that the airborne low-frequency ultrasound therapy improves and hastens the healing of chronic neuropathic DFU when combined with standard wound care.

Association of diabetic foot ulcers with chronic vascular diabetic complications in patients with type 2 diabetes

ContextDiabetes mellitus is a common disease which is prevalent globally, presenting with chronic complications and constitutes a major risk to the patient. Diabetic foot ulcers are the single biggest risk factor for non-traumatic lower limb amputations in persons with diabetes. We aimed to screen for the chronic vascular diabetic complications in patients with diabetic foot ulcers (DFUs) and to assess the association of diabetic foot ulcers with these complications in the study group. Subjects and methodsThis cross-sectional study included 180 type 2 diabetic patients (aged 30–70 years) with diabetic foot ulcers who attended the Outpatient Clinic of Diabetes in Alexandria Main University Hospital. Full diabetic foot examination was done to all study subjects. DFUs were assessed using University of Texas Diabetic Wound Classification System. HbA1c, LDL-C, serum creatinine, and urinary albumin creatinine ratio (ACR) were measured for all study subjects. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Fundus examination was done for all study subjects. ResultsThe prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) was 86.1% and 90% respectively among the study group. 86.7% of patients had neuropathic DFUs, 11.1% of them had ischemic DFUs and 2.2% had neuro-ischemic DFUs. Regarding diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) as risk factors for developing DFU, the prevalence of both of them respectively was 82% and 20% among the study group. There was statistically significant association between both DKD, DR and peripheral neuropathy. There was also statistically significant association between both DKD, DR and peripheral arterial disease (PAD). ConclusionChronic vascular diabetic complications are common among type 2 diabetic patients with diabetic foot ulcers. There is statistically significant association between these complications and diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD).

Wound exudate CXCL6: a potential biomarker for wound healing of diabetic foot ulcers.

The aim of this study was to investigate the relationship between CXCL-6 levels in wound exudates and healing of diabetic foot ulcers (DFU). One hundred patients with neuropathic DFU were recruited. Wound exudate CXCL-6 levels were measured by enzyme-linked immunosorbent assay. Patients were followed for 24weeks and divided into rapidly healing and nonhealing groups. Compared with the NH group, the mean CXCL-6 levels in the wound exudates of the rapidly healing group were significantly higher. After adjusting for traditional risk factors, wound exudate CXCL-6 levels were still significantly associated with wound healing. CXCL6 is an independent predictor of wound healing in DFU patients and may be a potentially novel therapeutic target for the treatment of DFU.

Genetic parameters of wound healing in patients with neuropatic diabetic foot ulcers

Background. Tissue repair processes are impaired in diabetic foot ulcers (DFUs). Previous research has shown that glycaemic control, cytokines and growth factors play an important role in wound healing. Emerging evidence also suggests that genes play a role via their regulation of cell proliferation, collagen synthesis and granulation tissue formation.&#x0D; Aim. To evaluate collagen genes expression in different stages of wound healing in patients with DFUs.&#x0D; Materials and methods. Prospective study included four patients with neuropathic DFUs after surgical debridement. Tissue samples were taken for morphological and genetic tests on days 0, 10 and 15 of local treatment to evaluate expression of collagen genes (i.e. COL1A1, COL1A2, COL3A1) and to perform morphological tests.&#x0D; Results. The present study confirmed that the size of wounds decreased by 8.8 7% after 10 days of local treatment and by 18.3 8% after 15 days of local treatment. According to histological examination of wound biopsies at day 10, all patients showed a tendency for lower levels of inflammatory infiltrate, increased number of fibroblast-like cells, presence of maturing granulation tissue and emergence of connective tissue fibres. After 15 days, we detected inflammatory infiltration in the wounds, despite the formation of mature granulation tissue. According to results of genetic analysis on day 10 of local wound treatment, we found a tendency for increased expression of collagen genes relative to the baseline: COL1A1 increased by 3.2 1.3 times, COL1A2 by 2.0 1.0 times and COL3A1 by 1.25 1.1 times. On day 15 of local treatment, in contrast, we found a tendency for decreased expression of COL1A1, COL1A2 and COL3A1 relative to the baseline (1.7 0.6, 2.5 2 and 20.0 3 times, respectively).&#x0D; Conclusions. The expression of collagen genes (COL1A1, COL1A2, COL3A1) is more pronounced in proliferation phase and is subsequently reduced towards the end. These data were confirmed by morphological study and clinical pictures.

Treatment of diabetic foot ulcers with dehydrated amniotic membrane allograft: a prospective case series.

A diabetic foot ulcer (DFU) is one of the many potential complications associated with diabetes. If not effectively and rapidly treated, DFUs can result in lower extremity amputations. This prospective case series aimed to assess the effectiveness of a dehydrated amniotic-derived tissue allograft (DAMA), with regards to time to wound closure and total number of applications. Patients were recruited with a neuropathic non-healing DFU(s) despite standard care for at least 4 weeks before the study. The number of DAMA applications and time between applications was based on the physician's judgment. For the majority of patients (n=13/14), offloading, usually total contact casting (TCC), was used in conjunction with DAMA. Wounds were assessed, measured, and photographed every 1-2 weeks. Cases included 14 patients (11 men, 3 women; mean age 56.7±9.1 years) with 15 non-healing neuropathic DFUs with a mean baseline wound area of 6.5±11.6cm2 (median: 2.2cm2; range: 0.1-44.2cm2) and mean volume of 4.3±10.9cm3 (median: 0.3cm3; range: 0-39.8cm3). All patients in this series achieved complete wound closure within a median time of 5 weeks (range: 1-14 weeks). Wound area was reduced by a median of 58.3% at week 1 and 74.1% at week 3, and volume by a median of 62.8% at week 1, 97.4% at week 3 and by a median of 100% at week 5 and all time points thereafter. Patients received a median of 2 DAMA applications (range: 1-11). In those that required more than 1 application (n=12), DAMA was applied at intervals of 1 week (n=3) or ≥2 weeks (n=9). Smaller wounds (areas <2.2cm2) closed rapidly (<1 month, 1-2 applications), whereas larger wounds (>2.2cm2) required >2 weekly/biweekly applications. The use of DAMA, particularly when coupled with TCC, led to wound closure of DFUs in all patients in this case series, including complex patients with DFUs of ≥1 year in duration, lack of prior response to conservative treatment measures, area >10cm2 and/or multiple comorbidities. Prospective randomised trials would help to elucidate the precise role of DAMA in these encouraging results. Derma Sciences, Inc. (Princeton, NJ) funded editorial support services.

Erratum to: Cost‐effectiveness of clostridial collagenase ointment on wound closure in patients with diabetic foot ulcers: economic analysis of results from a multicenter, randomized, open‐label trial

[This corrects the article DOI: 10.1186/s13047-015-0065-x.].