Risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis and diabetic nephropathy: A 3‐year follow‐up study

This study aimed to explore the risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis (DFO) and diabetic nephropathy (DN). This is a prospective cohort study. Between May 2018 and May 2021, we selected 120 inpatients with comorbid severe diabetic foot infection (PEDIS Grade 3 or above) and DN for inclusion in our study. All cases were followed up for 36 months. The study outcomes were whether foot ulcer recurred and the time to recurrence. The risk factors of ulcer recurrence were analysed by comparing the data of the three groups. According to the recurrence of foot ulcer, the participants were divided into three groups: Group A (no foot ulcer recurrence, n = 89), Group B (foot ulcer recurrence within 12‐36 months, n = 19) and Group C (foot ulcer recurrence within 6‐12 months, n = 12). The multivariate Cox regression analysis showed that urine albumin‐creatinine ratio (UACR) (HR: 1.008, 95% CI: 1.005‐1.011, P < .001) and vibration perception threshold (VPT) (HR: 1.064, 95% CI: 1.032‐1.096, P < .001) were identified as independent risk factors. Kaplan‐Meier curves showed a significant positive association between UACR or VPT and the risk of foot ulcer recurrence (log rank, all P < .05). Areas under the ROC curves for UACR, VPT and the combination of UACR and VPT were 0.802, 0.799 and 0.842, respectively. The best cut‐off values of UACR and VPT were 281.51 mg/g and 25.12 V, respectively. In summary, elevated UACR and VPT were independent risk factors. The best clinical cut‐off values of UACR and VPT for prediction of foot ulcer recurrence were 281.51 mg/g and 25.12 V, respectively. Besides, our results suggested that microcirculation disorders rather than macrovascular complications play a major role in the recurrence of foot ulcer in patients with comorbid DFO and DN.     

Effect of platelet‐rich plasma vs standard management for the treatment of diabetic foot ulcer wounds: A meta‐analysis

We performed a meta‐analysis to evaluate the effect of platelet‐rich plasma vs standard management for the treatment of diabetic foot ulcer wounds. A systematic literature search up to March 2022 was performed and 1435 subjects with diabetic foot ulcer wounds at the baseline of the studies; 723 of them were treated with platelet‐rich plasma, and 712 used control. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to assess the effect of platelet‐rich plasma vs standard management for the treatment of diabetic foot ulcer wounds using the dichotomous method with a random or fixed‐effect model. The use of autologous platelet‐rich plasma resulted in significantly higher complete‐healed diabetic foot ulcer wounds compared with control (OR, 1.95; 95% CI, 1.49‐2.56, P < 0.001). The use of allogeneic platelet‐rich plasma resulted in significantly higher complete‐healed diabetic foot ulcer wounds compared with control (OR, 6.19; 95% CI, 2.32‐16.56, P < 0.001). The use of autologous and allogeneic platelet‐rich plasma resulted in significantly higher complete‐healed diabetic foot ulcer wounds compared with control. Though, the analysis of outcomes should be with caution because of the low number of studies in certain comparisons, for example, allogeneic platelet‐rich plasma compared with control.     

Association between vitamin D deficiency and diabetic foot ulcer wound in diabetic subjects: A meta‐analysis

A meta‐analysis was performed to evaluate the association between vitamin D deficiency and diabetic foot ulcer wounds in diabetic subjects. A systematic literature search up to March 2022 incorporated 7586 subjects with diabetes mellitus at the beginning of the study; 1565 were using diabetic subjects with foot ulcer wounds, and 6021 were non‐ulcerated diabetic subjects. Statistical tools like the dichotomous and contentious method were used within a random or fixed‐influence model to establish the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to evaluate the influence of vitamin D deficiency in managing diabetic foot ulcer wound. Diabetic subjects with foot ulcer wounds had significantly lower vitamin D levels (MD, −6.48; 95% CI, −10.84 to −2.11, P < .004), higher prevalence of vitamin D deficiency (<50 nmoL/L) (OR, 1.82; 95% CI, 1.32‐2.52, P < .001), and higher prevalence of severe vitamin D deficiency (OR, 2.53; 95% CI, 1.65‐3.89, P < .001) compared with non‐ulcerated diabetic subjects. Diabetic subjects with foot ulcer wounds had significantly lower vitamin D levels, higher prevalence of vitamin D deficiency, and higher prevalence of severe vitamin D deficiency compared with non‐ulcerated diabetic subjects. Further studies are required to validate these findings.     

Risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis and diabetic nephropathy: A 3-year follow-up study

This study aimed to explore the risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis (DFO) and diabetic nephropathy (DN). This is a prospective cohort study. Between May 2018 and May 2021, we selected 120 inpatients with comorbid severe diabetic foot infection (PEDIS Grade 3 or above) and DN for inclusion in our study. All cases were followed up for 36 months. The study outcomes were whether foot ulcer recurred and the time to recurrence. The risk factors of ulcer recurrence were analysed by comparing the data of the three groups. According to the recurrence of foot ulcer, the participants were divided into three groups: Group A (no foot ulcer recurrence, n = 89), Group B (foot ulcer recurrence within 12-36 months, n = 19) and Group C (foot ulcer recurrence within 6-12 months, n = 12). The multivariate Cox regression analysis showed that urine albumin-creatinine ratio (UACR) (HR: 1.008, 95% CI: 1.005-1.011, P < .001) and vibration perception threshold (VPT) (HR: 1.064, 95% CI: 1.032-1.096, P < .001) were identified as independent risk factors. Kaplan-Meier curves showed a significant positive association between UACR or VPT and the risk of foot ulcer recurrence (log rank, all P < .05). Areas under the ROC curves for UACR, VPT and the combination of UACR and VPT were 0.802, 0.799 and 0.842, respectively. The best cut-off values of UACR and VPT were 281.51 mg/g and 25.12 V, respectively. In summary, elevated UACR and VPT were independent risk factors. The best clinical cut-off values of UACR and VPT for prediction of foot ulcer recurrence were 281.51 mg/g and 25.12 V, respectively. Besides, our results suggested that microcirculation disorders rather than macrovascular complications play a major role in the recurrence of foot ulcer in patients with comorbid DFO and DN.     

Analysis of routine blood markers for predicting amputation/re‐amputation risk in diabetic foot

Diabetic foot is challenging progressive disease which requires multisystemic control. Neuropathy, arteriopathy, and cellular responses should treated collaboratively. Despite all medical advances, diabetic foot can highly resulted with amputation and also re‐amputation can be required because of failed wound healing. In this study, we aimed to investigate the relation between blood parameters and amputation events. Diabetic 323 patients include to the study who referred to orthopaedic clinic for amputation. Amputation levels (amputation levels phalanx, metatarsal, lisfranc, syme, below knee, knee‐disarticulation, above‐knee amputation) and re‐amputations recorded and compared with routine blood parameters. Re‐amputation was observed at 69 patients. The significant difference detected between lower albumin, higher HbA1c, higher CRP levels (P < 0.05) in regards to gross amputation levels, and increased wound depth. Furthermore, lower albumin levels and higher levels of WBC, HbA1c, CRP, and Creatinine were detected in re‐amputation levels. Especially, HbA1c, CRP, and Creatinine levels were found as upper bound of reference line for re‐amputation. The statistically optimal HbA1c cutoff point for diabetes was ≥7.05%, with a sensitivity of 86% and a specificity of 59%. In according to our results, simple blood parameters can be useful for observing the progress of amputation in diabetic foot. Particularly, lower albumin, and higher HbA1c, CRP, and Creatinine levels detected as related with poor prognosis. Besides, screening of HbA1c level seems to be highly sensitive for detecting of re‐amputation possibility.     

Multidrug‐resistant bacteria in diabetic foot infections: Experience from a portuguese tertiary centre

In recent years, the emergence of antibiotic resistant pathogens made increasingly difficult to establish appropriate empiric antimicrobial therapy protocols for acute diabetic foot infection (DFI) treatment. Early recognition of the population at‐risk for multidrug‐resistant (MDR) bacterial infection is of paramount importance in order to decrease large‐spectrum antibiotic overuse. This study used retrospective cohort study in a multidisciplinary tertiary diabetic foot unit. Patients with severe DFI were included and divided according to their infection resistance profile (susceptible vs MDR bacteria). Data regarding their comorbidities and length of hospital stay were collected. The primary endpoint was to determine the risk factors for MDR infections and to evaluate if these were associated with an increased length of stay (LOS). A total of 112 microbial isolates were included. Predominance of Gram‐positive bacteria was observed and 22.3% of isolated bacteria were MDR. Previous hospitalisation was associated with a higher likelihood of MDR infection. MDR bacterial infection was also associated with an increased LOS (P = .0296). Our study showed a high incidence of MDR bacteria in patients with a DFI, especially in those who had a recent hospitalisation. MDR infections were associated with a prolonged LOS and represent a global public health issue for which emergent measures are needed.     

Clinical and economic outcomes of a multidisciplinary team approach in a lower extremity amputation prevention programme for diabetic foot ulcer care in an Asian population: A case‐control study

Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case‐control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow‐up (33% vs 76%, P < .001), decrease in 1‐year minor amputation rate (14% vs 3%, P = .007), and decrease in 1‐year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m.     

Transverse Tibial Bone Transport Enhances Distraction Osteogenesis and Vascularization in the Treatment of Diabetic Foot

ObjectiveTo investigate the effect of transverse tibial bone transport on the treatment of Wagner Stage 4 diabetic foot.MethodsFrom January 2017 to October 2019, a total of 19 patients with Wagner Stage 4 diabetic foot ulcers were recruited. All patients were treated with transverse tibial bone transport. A detailed follow‐up was carried out at 1 week, 1 month, 3 months, 6 months, and 1 year after surgery. The wound healing rate and the limb salvage rate at 1 year after the surgery were evaluated. Preoperative and 3‐month postoperative digital subtraction angiography (DSA) were obtained. The level of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and platelet‐derived growth factor (PDGF) before surgery and on 1st, 4th, 11th, 18th, 28^th, and 35th days after surgery were measured. Operation time, intraoperative blood loss, postoperative complications, visual analog scale (VAS) pain score, skin temperature, Semmes‐weinstein monofilament (SWM), and ankle brachial index (ABI) were also assessed.ResultsThe wound healing rate and the limb salvage rate were both 94.74% in the patients at 1 year after the surgery. DSA showed the thickening of the calf and foot arteries, clear visualization, and a rich vascular network. The levels of VEGF, bFGF, and PDGF on the 11th, 18th, 28^th, and 35th days after surgery were significantly higher than those before surgery (p < 0.05). The EGF level on the 18th, 28th, and 35th days after surgery was significantly higher than that before surgery (p < 0.05). Superficial wound complications occurred in one patient during the hospitalization. There was no movement area infection, skin flap necrosis, tibial fracture, loosening of the external fixator, or rupture in study.ConclusionTransverse tibial bone transport can improve the blood circulation of the affected limbs, promote the healing of diabetic foot wounds, and reduce the amputation rate of the affected limbs. Transverse tibial bone transport can promote the healing of Wagner Stage 4 diabetic foot.     

Transcultural adaptation and validation of Italian Selfcare diabetic foot questionnaire

The Italian Selfcare diabetic foot questionnaire, (SDFQ‐IT) is considered a diabetic foot self‐care evaluation tool with 16 questions for assessing diabetic foot health disorders. To date, SDFQ has been validated in different languages, but an Italian version was lacking. Consequently, the purpose of this study was to translate and validate the Italian version of the SDFQ‐IT (SDFQ‐IT). A suitable method was developed for the translation protocol and cross‐cultural validation from Spanish to Italian. Regarding the total marks from each sub‐scale, agreement degrees, and confidence were analysed using the Cronbach''s α and intraclass correlation coefficient (ICC), respectively. In addition, the mean ± SD differences between pre and post‐tests were calculated and completed using the Bland and Altman distribution plots. Excellent agreement between the two versions based on Cronbach''s α was demonstrated. Three sub‐scales consisting of knowledge of foot hygiene, the appropriate use of footwear and socks, and podiatric self‐care were added together to obtain the total score. Excellent retest reliability was shown for the total score. Test/retest reliability was excellent for the self‐care domain, and shock and shoe sub‐scales. There were no significant differences among any domain (P > .05). There were no statistically significant differences (P = .000) for the mean ± SDs differences between pre‐and post‐tests (92.9200 ± 12.914) [89.25‐96.59] and 92.9200 ± 13.012 [89.22‐96.62] points, respectively). Bland and Altman plots or clinically pertinent variations were not statistically significantly different. The SDFQ‐IT is considered a strong and valid questionnaire with adequate repeatability in the Italian community.     

The effect of low‐level laser therapy on diabetic foot ulcers: A meta‐analysis of randomised controlled trials

Our purpose was to perform a meta‐analysis to evaluate the effect of Low‐level laser therapy (LLLT) on diabetic foot ulcers (DFUs). The PubMed, Cochrane, Embase, Web of Science, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases were searched systematically up to August 27, 2020. Studies that met the inclusion criteria were included in the analysis. A total of 13 randomised controlled trials (RCTs) and 413 patients were analysed. Compared with the control group, LLLT significantly increased the complete healing rate (risk ratio [RR] = 2.10, 95% confidence interval [CI] 1.56‐2.83, P < .00001), reduced the ulcer area (standardised mean difference [SMD] = 3.52, 95% CI 1.65‐5.38, P = .0002), and shortened the mean healing time (SMD = −1.40, 95% CI −1.90 to −0.91, P < .00001) of patients with DFUs. The quality of the evidence was very low according to the GRADE system. LLLT is a promising and effective adjuvant treatment to accelerate the healing of DFUs. Further evidence from larger samples and higher quality RCTs is needed to prove the effect of LLLT and to determine the most appropriate parameters for the healing of DFUs.     

Relationships among social support,coping style,self‐stigma,and quality of life in patients with diabetic foot ulcer: A multicentre,cross‐sectional study

Patients with diabetic foot ulcer have a significantly lower quality of life. Quality of life could be connected to other psychological or social processes. The purpose of this study was to examine the relationships between social support, decision regret, self‐stigma, and quality of life in patients with diabetic foot ulcers. The sample of the study consisted of 229 diabetic foot ulcer patients. Data were collected from September 2019 to March 2020. The demographic and clinical information, the Stigma Scale for Chronic Illness, Medical Coping Scale, Social Support Scale, and Quality of Life scale were used to assess the quality life for diabetic foot ulcer. Pearson correlation coefficient and structural equation modelling were used for data analysis. The quality of life was negatively correlated with self‐stigma, positively correlated with social support, giving up coping, and not significantly correlated with confrontation coping and avoidance coping. Self‐stigma has significant indirect effects on quality of life through social support and coping style. Further clinical intervention strategies for decreasing self‐stigma as well as strengthening social support and positive coping styles are needed to inform diabetic foot ulcer patients, thus improving their quality of life.     

Analysis of the Effect of Antibiotic Bone Cement in the Treatment of Diabetic Foot Ulcer through Tibia Transverse Transport

ObjectiveTo explore the efficacy of antibiotic bone cement (ABC) combined with the modified tibial transverse transport (mTTT) on the treatment of severe diabetic foot with infection.MethodsA retrospective cohort study was conducted of 243 patients with TEXAS grade 3/4 stage D diabetic foot ulcers from December 2016 to December 2019. A total of 115 patients treated with mTTT were classified as the mTTT group (78 male and 37 female, mean age: 70.4 ± 6 years) and 128 patients who were treated with ABC combined with mTTT were in the ABC + mTTT group (89 male and 39 female, mean age: 68.9 ± 8 years). Follow‐up records during treatment and 6 months after surgery were collected, including the time required for white blood cells (WBC) and C‐reactive protein (CRP) to return to normal range, wound healing time, pain visual analog scale (VAS), ankle‐brachial index (ABI), foot skin temperature, transcutaneous oxygen pressure measurement (TcPO₂), complications, and other indicators. Normally distributed data were compared using the independent sample t‐test, non‐normally distributed data were analyzed by one‐way ANOVA analysis of variance.ResultsThere were 128 cases in the ABC + mTTT group (89 male and 39 female, mean age: 68.9 ± 8 years) treated with ABC and mTTT, and 115 cases in the TTT group (78 male and 37 female, mean age: 70.4 ± 6 years) treated with mTTT alone. The time required for WBC and CRP to return to the normal range and wound healing time in the ABC + mTTT group were significantly shorter than those in the mTTT group (12.9 ± 4.6 vs. 22.6 ± 1.6 days, t = 3.979, p < 0.001; 25.3 ± 1.3 vs. 31.3 ± 2.3 days, t = 4.261, p = 0.001; 11.9 ± 3.8 vs. 15.9 ± 3.9 days, t = 4.539, p < 0.001). There were no significant intergroup differences in the foot skin temperature, VAS score, ABI, and TcPO₂ (t = 0.349, 0.542, 0.765, 0.693 while all p > 0.05).ConclusionAlthough the application of ABC with mTTT for treatment of diabetic foot ulcers did not affect the wound healing time and ankle blood supply in the mid‐term, it could control ulcer infection faster and accelerate wound healing.     

The effect of continuous diffusion of oxygen treatment on cytokines,perfusion, bacterial load,and healing in patients with diabetic foot ulcers

To evaluate continuous diffusion of oxygen therapy (CDO) on cytokines, perfusion, and bacterial load in diabetic foot ulcers we evaluated 23 patients for 3 weeks. Tissues biopsies were obtained at each visit to evaluate cytokines and quantitative bacterial cultures. Perfusion was measured with hyperspectral imaging and transcutaneous oxygen. We used paired T tests to compare continuous variables and independent T tests to compare healers and nonhealers. There was an increase from baseline to week 1 in TGF‐β (P = .008), TNF‐α (P = .014), VEGF (P = .008), PDGF (P = .087), and IGF‐1 (P = .058); baseline to week 2 in TGF‐β (P = .010), VEGF (P = .051), and IL‐6 (P = .031); and baseline to week 3 with TGF‐β (P = .055) and IL‐6 (P = .054). There was a significant increase in transcutaneous oxygen after 1 week of treatment on both medial and lateral foot (P = .086 and .025). Fifty‐three percent of the patients had at least a 50% wound area reduction (healers). At baseline, there were no differences in cytokines between healers and nonhealers. However, there was an increase in CXCL8 after 1 week of treatment (P = .080) and IL‐6 after 3 weeks of treatment in nonhealers (P = .099). There were no differences in quantitative cultures in healers and nonhealers.     

Misdiagnosis of diabetic foot ulcer in patients with undiagnosed skin malignancies

A growing number of studies report dermal malignancies mimicking diabetic foot ulcers (DFUs). We reviewed clinical cases reporting malignant tumours misdiagnosed to be DFU aiming to identify factors contributing to misdiagnosis. We systematically searched in PubMed for clinical cases reporting on misdiagnosis of DFU in patients with cancer. A chi‐square analysis was conducted to show the link between the incidence of initial DFU misdiagnosis and patient age, gender and wound duration. Lesions misdiagnosed to be DFU were subsequently diagnosed as melanoma (68% of the cases), Kaposi''s sarcoma (14%), squamous cell carcinoma (11%), mantle cell lymphoma, and diffuse B‐cell lymphoma (both by 4%). Older age (≥65 years) was associated with a significantly increased risk of malignancy masked as DFU (OR: 2.452; 95% CI: 1.132 to 5.312; P value = .019). The risk of such suspicion in older patients (age ≥ 65 years) was 145% higher than in younger patients (age < 65 years). Clinicians should maintain a high level of awareness towards potentially malignant foot lesions in elderly patients with diabetes (age ≥ 65).     

Potential cost‐effectiveness of using adjunctive dehydrated human amnion/chorion membrane allograft in the management of non‐healing diabetic foot ulcers in the United Kingdom

The aim of this study was to estimate the cost‐effectiveness of using dehydrated human amnion/chorion membrane (dHACM) allografts (Epifix) as an adjunct to standard care, compared with standard care alone, to manage non‐healing diabetic foot ulcers (DFUs) in secondary care in the United Kingdom, from the perspective of the National Health Service (NHS). A Markov model was constructed to simulate the management of diabetic lower extremity ulcers over a period of 1 year. The model was used to estimate the cost‐effectiveness of using adjunctive dHACM, compared with standard care alone, to treat non‐healing DFUs in the United Kingdom, in terms of the incremental cost per quality‐adjusted life year (QALY) gained at 2019/2020 prices. The study estimated that at 12 months after the start of treatment, use of adjunctive dHACM instead of standard care alone is expected to lead to a 90% increase in the probability of healing, a 34% reduction in the probability of wound infection, a 57% reduction in the probability of wound recurrence, a 6% increase in the probability of avoiding an amputation, and 8% improvement in the number of QALYs. Additionally, if £4062 is spent on dHACM allografts per ulcer, then adjunctive use of dHACM instead of standard care alone is expected to lead to an incremental cost per QALY gain of £20 000. However, if the amount spent on dHACM allografts was ≤£3250 per ulcer, the 12‐month cost of managing an ulcer treated with adjunctive dHACM would break‐even with that of DFUs treated with standard care, and it would have a 0.95 probability of being cost‐effective at the £20 000 per QALY threshold. In conclusion, within the study''s limitations, and within a certain price range, adjunctive dHACM allografts afford the NHS a cost‐effective intervention for the treatment of non‐healing DFUs within secondary care among adult patients with type 1 or 2 diabetes mellitus in the United Kingdom.     

Lyopreserved amniotic membrane is cellularly and clinically similar to cryopreserved construct for treating foot ulcers

We compared cellular viability between cryopreserved and lyopreserved amniotic membranes and clinical outcomes of the lyopreserved construct in a prospective cohort study of 40 patients with neuropathic foot ulcers. Patients received weekly application of lyopreserved membrane for 12 weeks with standard weekly debridement and offloading. We evaluated the proportion of foot ulcers that closed, time to closure, closure trajectories, and infection during therapy. We used chi‐square tests for dichotomous variables and independent t‐tests for continuous variables with an alpha of α = .10. Cellular viability was equivalent between cryo‐ and lyopreserved amniotic tissues. Clinically, 48% of subjects'' wounds closed in an average of 40.0 days. Those that did not close were older (63 vs 59 years, P = .011) and larger ulcers at baseline (7.8 vs 1.6 cm², P = .012). Significantly more patients who achieved closure reached a 50% wound area reduction in 4 weeks compared with non‐closed wounds (73.7% vs 47.6%, P = .093). There was no difference in the slope of the wound closure trajectories between closed and non‐closed wounds (0.124 and 0.159, P = .85), indicating the rate of closure was similar. The rate of closure was 0.60 mm/day (SD = 0.47) for wounds that closed and 0.50 mm/day (SD = 0.58) for wounds that did not close (P = .89).     

The efficacy of low‐frequency ultrasound as an added treatment for chronic wounds: A meta‐analysis

We performed a meta‐analysis to evaluate the effect of low‐frequency ultrasound as an added treatment for chronic wounds. A systematic literature search up to May 2022 was performed and 838 subjects with chronic wounds at the baseline of the studies; 412 of them were using the low‐frequency ultrasound (225 low‐frequency high‐intensity contact ultrasound for diabetic foot wound ulcers, and 187 low‐frequency low‐intensity non‐contact ultrasound for a venous leg wound ulcers), and 426 were using standard care (233 sharp debridements for diabetic foot wound ulcers and 193 sham treatments for venous leg wound ulcers). Odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of low‐frequency ultrasound as an added treatment for chronic wounds using the dichotomous, and contentious methods with a random or fixed‐effect model. The low‐frequency high‐intensity contact ultrasound for diabetic foot wound ulcers had significantly lower non‐healed diabetic foot wound ulcers at ≥3 months (OR, 0.37; 95% CI, 0.24‐0.56, P < .001), a higher percentage of diabetic foot wound ulcers area reduction (MD, 17.18; 95% CI, 6.62‐27.85, P = .002) compared with sharp debridement for diabetic foot wound ulcers. The low‐frequency low‐intensity non‐contact ultrasound for a venous leg wound ulcers had a significantly lower non‐healed venous leg wound ulcers at ≥3 months (OR, 0.31; 95% CI, 0.15‐0.62, P = .001), and higher percentage venous leg wound ulcers area reduction (MD, 18.96; 95% CI, 2.36‐35.57, P = .03) compared with sham treatments for a venous leg wound ulcers. The low‐frequency ultrasound as an added treatment for diabetic foot wound ulcers and venous leg wound ulcers had significantly lower non‐healed chronic wound ulcers at ≥3 months, a higher percentage of chronic wound ulcers area reduction compared with standard care. The analysis of outcomes should be with caution because of the low sample size of all the 17 studies in the meta‐analysis and a low number of studies in certain comparisons.     

The effectiveness of a new dried human amnion derived membrane in addition to standard care in treating diabetic foot ulcers: A patient and assessor blind,randomised controlled pilot study

Recent reviews suggest that amniotic membrane products may accelerate healing of diabetic foot ulcers. A new dried human amniotic membrane (dHAM) has been used for ocular ulcers but not for diabetic foot ulcers. This was a multi‐centre, prospective, patient and observer blind, randomised controlled pilot trial, to investigate whether 2 weekly addition of the dHAM to standard care versus standard care alone increased the proportion of healed participants'' index foot ulcers within 12 weeks. Thirty‐one people (mean age 59.8 years, 81% male, 87% type 2 diabetes) were randomised (15 dHAM, 16 usual care). Within 12 weeks, healing occurred in 4 (27%) ulcers in the dHAM group versus 1 (6.3%) usual care group (P = .1). Percentage wound area reduction was higher in the dHAM versus control group. (P = .0057). There was no difference in AEs between the two groups. Six participants allocated to dHAM correctly identified their treatment group, although 5 in usual care incorrectly thought they were in the intervention arm. This pilot trial result is encouraging showing that this dHAM preparation is safe and promising treatment. These results will be used to design a statistically powered, definitive double blind randomised controlled trial.     

Changes in miroRNA‐103 expression in wound margin tissue are related to wound healing of diabetes foot ulcers

To investigate the relationship between small noncoding microRNA‐103 (miR‐103) and wound healing of diabetic foot ulcers (DFU) and the underlying molecular mechanism, forty type 2 diabetes mellitus with DFU (DFU group), and 20 patients with a chronic skin ulcer of lower limbs and normal glucose tolerance (SUC group) were included. Quantitative real‐time PCR method was used to determine miR‐103 expression levels in the wound margin tissue of subjects, and to analyse the relationship between the expression of miR‐103 and DFU wound healing. In vitro experiments were also performed to understand the effect of miR‐103 on the high glucose‐induced injury of normal human dermal fibroblasts (NHDFs) cells. The results showed that the miR‐103 expression level in the DFU group was significantly higher than that in the SUC group [5.81 (2.25–9.36) vs 2.08 (1.15–5.72)] (P < 0.05). The expression level of miR‐103 in the wound margin tissue of DFU was negatively correlated with the healing rate of foot ulcers after four weeks (P = 0.037). In vitro experiments revealed that miR‐103 could inhibit the proliferation and migration of NHDF cells and promote the apoptosis of NHDF cells by targeted regulation of regulator of calcineurin 1 (RCAN1) gene expression in a high glucose environment. Down‐regulation of miR‐103 could alleviate high glucose‐induced NHDF cell injury by promoting RCAN1 expression. Therefore, the increased expression of miR‐103 is involved in the functional damage of NHDF cells induced by high‐glucose conditions, which is related to poor wound healing of DFU. These research findings will provide potential targets for the diagnosis and treatment of chronic skin wounds in diabetes.