富血小板凝胶在糖尿病足溃疡治疗中的应用

富血小板凝胶是近年来新出现的辅助治疗糖尿病足溃疡(DFU)的方法之一.局部应用富血小板凝胶治疗DFU可有效改善DFU的难愈合性并提高溃疡愈合率,且无明显不良反应发生;也可降低截肢率,且没有增加医疗总费用.富血小板凝胶治疗DFU的作用机制可能与其中富含的生长因子、细胞因子和白细胞等有关,还可能与凝胶超微结构、溃疡中基质金属蛋白酶的变化有关.     

High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study

Aims/hypothesis Large clinical studies describing the typical clinical presentation of diabetic foot ulcers are limited and most studies were performed in single centres with the possibility of selection of specific subgroups. The aim of this study was to investigate the characteristics of diabetic patients with a foot ulcer in 14 European hospitals in ten countries. Methods The study population included 1,229 consecutive patients presenting with a new foot ulcer between 1 September 2003 and 1 October 2004. Standardised data on patient characteristics, as well as foot and ulcer characteristics, were obtained. Foot disease was categorised into four stages according to the presence or absence of peripheral arterial disease (PAD) and infection: A: PAD −, infection −; B: PAD −, infection +; C: PAD +, infection −; D: PAD +, infection +. Results PAD was diagnosed in 49% of the subjects, infection in 58%. The majority of ulcers (52%) were located on the non-plantar surface of the foot. With regard to severity, 24% had stage A, 27% had stage B, 18% had stage C and 31% had stage D foot disease. Patients in the latter group had a distinct profile: they were older, had more non-plantar ulcers, greater tissue loss and more serious comorbidity. Conclusions/interpretation According to our results in this European cohort, the severity of diabetic foot ulcers at presentation is greater than previously reported, as one-third had both PAD and infection. Non-plantar foot ulcers were more common than plantar ulcers, especially in patients with severe disease, and serious comorbidity increased significantly with increasing severity of foot disease. Further research is needed to obtain insight into the clinical outcome of these patients.     

CXC趋化因子配体16与糖尿病足的相关性探讨

目的 探讨血清CXC趋化因子配体16 (CXCL16)与糖尿病足的相关性.方法 以2013年1月至2014年12月住院的164例糖尿病患者作为受试对象,根据有无糖尿病足将其分为糖尿病足组(90例)和单纯糖尿病组(74例).采用酶联免疫吸附双抗体夹心法测定血清CXCL16的浓度.以高CXCL16浓度作为暴露因素,探讨CXCL16与糖尿病足的相关性.采用Logistic回归分析探讨糖尿病足的危险因素.结果 糖尿病足组血清CXCL16水平明显高于单纯糖尿病组(t=3.111,P =0.002).糖尿病患者血清CXCL16浓度在1.72 μg/L以上时,患糖尿病足的危险性是CXCL16在1.72μg/L以下的4.39倍.Logistw回归分析结果显示,CXCL16(OR=24.487,95％ CI:3.733 ～160.628,P=0.001)和纤维蛋白原(OR=2.994,95％ CI:1.654 ～5.419,P=0.000)是糖尿病足的危险因素.结论 血清CXCL16和纤维蛋白原是糖尿病足的危险因素.     

The potential of transdermal nitric oxide treatment for diabetic peripheral neuropathy and diabetic foot ulcers

The Center for Disease Control (CDC) estimates that 29 million Americans have diabetes, and 70% of diabetic patients develop diabetic peripheral neuropathy [1,2]. Up to 27% of the direct medical cost of diabetes may be attributed to DPN [3]. A 2013 article from the American Diabetes Association reported a $176 billion direct medical cost of diabetes in 2012 [4]. DPN patients often suffer from shooting and burning pain in their distal limbs and a severe loss of sensation. Diabetic foot ulcers, infections, and amputations may follow. Currently available treatments: tricyclic antidepressants, anticonvulsants such as gabapentin and pregabalin, serotonin and norepinephrine reuptake inhibitor, duloxetine, topical 5% lidocaine (applied to the most painful area) can manage painful symptoms but do not address the underlying pathologies of DPN and diabetic wound ulcers. A combination of pain-reducing medications can provide relief when individual medications fail, and opioids such as tramadol and oxycodone may be administered with these medications to reduce pain [5]. Due to the prevalence of diabetes, DPN, and diabetic foot ulcers, and because of the lack of available effective treatments to directly address the pathology contributing to these conditions, novel treatments are being sought. Our hypothesis is that a deficiency of nitric oxide synthase in diabetic patients leads to a lack of vascularization of the peripheral nerves, which causes DPN; and this could be treated with vasodilators such as nitric oxide. In this paper, the mechanisms of DPN are reviewed and analyzed to elucidate the potential of a transdermal nitric oxide application for the treatment of DPN and diabetic wound ulcers by increasing vasodilation.     

糖尿病足溃疡危险因素分析

观察23例糖尿病足溃疡患者的年龄、糖尿病病程、空腹血糖、血清总蛋白、血清白蛋白、血清肌酐、血清尿素氮及溃疡发生的位置,并与20例无溃疡糖尿病患者进行对比分析。结果显示：两组患者糖尿病病程、空腹血糖、血清总蛋白、血清白蛋白有显著性差异,年龄,血清肌酐、尿素氮、无显著性差异,糖尿病足溃疡患者右足溃疡发生率（86％）显著高于左足（39％）,双母趾溃疡发生率（65％）高于部位（35％）,但无显著性差异,结果提示：糖尿病程、高血糖、低蛋白血症及足部受力过多和压迫是糖尿病足溃疡发生的危险因素。     

Squamous cell carcinoma arising in a diabetic foot ulcer

Diabetic complications such as poor circulation and nerve damage can result in loss of sensation and slower wound healing in the lower extremities. The possibility of malignancy arising in association with chronic osteomyelitis in the diabetic foot should also be considered.     

Aetiology of Diabetic Foot Ulceration: A Role for the Microcirculation?

Neuropathy, mechanical stress, and macrovascular disease are involved in the pathogenesis of diabetic foot ulceration. Implicit in the development of gangrene and ulceration is the recognition that these factors interact with the microcirculation, resulting in the failure of skin capillary flow to meet nutritive requirements. There is little evidence to associate structural microangiopathy with foot microcirculatory failure. Significant functional abnormalities of the microcirculation have been defined. In accord with the haemodynamic hypothesis early hyperaemia and capillary hypertension promote more sinister late functional abnormalities with increasing duration of diabetes. These late functional abnormalities include loss of autoregulation and reduced hyperaemic responses which interact with loss of neurogenic flow regulation, disturbed endothelial function, and abnormal rheology to produce the familiar clinical picture of the diabetic foot. Ischaemia secondary to multi-segment arterial disease induces additional abnormalities of microcirculatory function which are superimposed on the pre-existing diabetic microvascular structural and functional microangiopathy.     

Complexity of factors related to outcome of neuropathic and neuroischaemic/ischaemic diabetic foot ulcers: a cohort study

Aims/hypothesis  We sought to identify factors related to short-term outcome of foot ulcers in patients with diabetes treated in a multidisciplinary system until healing was achieved. Methods  Consecutively presenting patients with diabetes and worst foot ulcer (Wagner grade 1–5, below ankle) (n = 2,511) were prospectively followed and treated according to a standardised protocol until healing was achieved or until death. The number of patients lost to dropout was 31. The characteristics of the remaining 2,480 patients were: 1,465 men, age 68 ± 15 years (range 18–96), type 1 diabetes 18%, type 2 diabetes 82% and insulin-treated 62%. Results  The healing rate without major amputation in surviving patients was 90.6% (n = 1,867). Sixty-five per cent (n = 1,617) were healed primarily, 9% (n = 250) after minor amputation and 8% after major amputation; 17% (n = 420) died unhealed. Out of 2,060 surviving patients, 1,007 were neuroischaemic (48.8%). In a multiple regression analysis, primary healing was related to co-morbidity, duration of diabetes, extent of peripheral vascular disease and type of ulcer. In neuropathic ulcers, deep foot infection, site of ulcer and co-morbidity were related to amputation. Amputation in neuroischaemic ulcers was related to co-morbidity, peripheral vascular disease and type of ulcer. Age, sex, duration of diabetes, neuropathy, deformity and duration of ulcer or site of ulcer did not have an evident influence on probability of amputation. Conclusions/interpretation  Patients with diabetic foot ulcer suffer from multi-organ disease. Factors related to outcome are correspondingly complex.     

313例糖尿病足患者临床特点及疗效分析

目的了解住院糖尿病（DM）患者糖尿病足（DF）的患病率,并分析其临床特点和治疗效果。方法调查我院1996年1月至2006年12月共313例住院DF病患者的临床资料,并比较1996年1月-2003年12月（A组）和2004年1月-2006年12月（B组）两个时间段患者的治疗效果。结果DF患者占同期住院DM总人数的2．79％,平均DM病程9．33±6．52年,DF病程8．13±17．06月。DF患者总的治愈率为28．1％,好转率为40．6％,无效率为31．3％;DF分级越高,治疗效果越差。B组治愈率（37．04％）显著高于A组（18．54％）。结论DF的发生率不断升高,多学科合作团队有利于提高DF的治愈率。     

The risk of foot ulceration in diabetic patients with high foot pressure: a prospective study

Summary Foot ulceration results in substantial morbidity amongst diabetic patients. We have studied prospectively the relationship between high foot pressures and foot ulceration using an optical pedobarograph. A series of 86 diabetic patients, mean age 53.3 (range 17–77) years, mean duration of diabetes 17.1 (range 1–36) years, were followed-up for a mean period of 30 (range 15–34) months. Clinical neuropathy was present in 58 (67%) patients at baseline examination. Mean peak foot pressure was higher at the follow-up compared to baseline (13.5 kg·cm^–2±7.1 SD vs 11.2±5.4, p<0.001) with abnormally high foot pressures (>12.3) being present in 55 patients at follow-up and 43 at the baseline visit (p=NS). Plantar foot ulcers developed in 21 feet of 15 patients (17%), all of whom had abnormally high pressures at baseline; neuropathy was present in 14 patients at baseline. Non-plantar ulcers occurred in 8 (9%) patients. Thus, plantar ulceration occurred in 35% of diabetic patients with high foot pressures but in none of those with normal pressures. We have shown for the first time in a prospective study that high plantar foot pressures in diabetic patients are strongly predictive of subsequent plantar ulceration, especially in the presence of neuropathy.     

Inter-observer reproducibility of diagnosis of diabetic foot osteomyelitis based on a combination of probe-to-bone test and simple radiography

Probe-to-bone test and simple X-rays are both standard tests for the diagnosis of diabetic foot osteomyelitis. This study demonstrates the importance of considering jointly clinical information (probe-to-bone test) and diagnostic tests (simple radiography) to increase agreement among clinicians on diagnosis of diabetic foot osteomyelitis.     

Application of tele-podiatry in diabetic foot management: A series of illustrative cases

Background and aimsTelemedicine had been proposed as a tool to manage diabetes, but its role in management of diabetic foot ulcer is still evolving. The COVID-19 pandemic and related social restrictions have necessitated the use of telemedicine in the management of diabetic foot disease (tele-podiatry), particularly of patients classified as low-risk.Materials and methodsWe present a report of three cases of varied diabetic foot problems assessed during the present pandemic using different forms of telemedicine for triaging, management of low-risk cases and for follow-up.ResultsTele-podiatry was effective in the management of low-risk subjects with diabetic foot ulcer, and also useful in referral of high-risk subjects for hospital/clinic visit, facilitating proper management. It also helped in the follow-up of the cases.ConclusionTelemedicine is a good screening tool for diagnosing and managing low-risk subjects with diabetic foot problems, and also enables a triaging system for deciding on hospital visits and hospitalization. Telemedicine offers several benefits in the management of diabetic foot disease, although it also has some limitations. Based on our experience during the pandemic, we recommend its judicious use in the triaging of patients of diabetic foot disease and management of low-risk cases. Future innovation in technology and artificial intelligence may help in better tele-podiatry care in the time to come.     

重视下肢动脉病变的诊治是降低糖尿病截肢率的重要措施

下肢动脉疾病(PAD)是常见的糖尿病并发症,具有多节段、更远端、病变更广泛等临床特点.该症起病缓慢而隐匿,临床上尚未受到足够重视,但危害性大,是糖尿病足的重要原因.该症诊断相对容易,触诊、踝肱动脉压指数测定、皮温测定、超声检查、CT或核磁共振都是有效的诊断技术,血管减数造影仍然是诊断的金标准.轻-中度病变采用药物治疗,重症患者需要外科手术治疗.介入治疗如深部球囊扩张术和血管内支架置放和干细胞移植治疗已在国内一些大医院开展并取得了相当疗效.     

糖尿病足患者血清脂联素水平变化及其生理意义

目的研究糖尿病足患者血清脂联素水平的变化及其生理意义。方法选取2008年1月至2010年12月于上海市第二人民医院内分泌科收治的糖尿病患者85例为研究对象,按照WHO糖尿病足诊断标准分为糖尿病足组（DF组）55例[其中男29例,女26例,平均年龄（68±11）岁]和糖尿病组（DM组）30例[其中男16例,女14例,平均年龄（65±11）岁]。以同期我院门诊的健康体检者30名（年龄、性别均匹配）为对照组（NC组）。测定身高、体重,计算体质指数（BMI）,测定空腹血糖（FPG）、糖化血红蛋白（HbAlc）、高密度脂蛋白胆固醇（HDL—C）、超敏c反应蛋白（hsCRP）、24h尿白蛋白排泄率（UAER）,测定肱动脉压和踝动脉压并计算踝肱指数（ABI）,彩色多普勒超声检查颈动脉内中膜厚度（IMT）及下肢动脉病变。ELISA法测定血清脂联素水平。比较DM和DF组中他汀类调脂药的应用对脂联素水平的影响。方差齐性的正态分布资料采用单因素方差分析,方差不齐或非正态分布资料采用非参数检验（KruskM—WallisH检验）,相关因素分析采用简单相关分析和逐步回归分析。结果DF组血清脂联素水平显著高于DM组,较NC组亦有升高趋势[（9．7±5．3）VS（5．4±2．8）VS（8．3±3．4）mg／L,F=8．65,P〈0．01]。在DF组中,随着UAER的增加,血清脂联素水平逐步升高[正常白蛋白尿组（6．0±1．7）mg／L,微量白蛋白尿组（9．0±3．4）mg／L,大量白蛋白尿组（11．7±4．4）mg／L;F=10．22,P〈0．01]。DF组中使用他汀类药物者血清脂联素水平较未使用者高,但差异无统计学意义[（10±6）VS（8±3）mg／L,t=-1．27,P〉0．05]。相关分析显示,糖尿病足患者血清脂联素水平与BMI、HbAlc呈显著负相关（r值分别为-0．314、-0．329,均P〈0．05）,与UAER、IMT、HDL—C呈显著正相关（r值分别为0．401、0．360、0．441,均P〈0．05）。逐步回归分析显示,HDL—C、UAER为糖尿病足患者血清脂联素的独立影响因素。结论糖尿病足患者血清脂联素水平升高,HDL-C、UAER为血清脂联素水平的独立影响因素。     

A review on diabetic foot challenges in Guyanese perspective

BackgroundDiabetes mellitus signifies a major public health threat worldwide. Type 2 diabetes has been reported as the fourth leading cause of death and has affected 15.5% of the adult population in Guyana, South America. Diabetes has also led to major lower extremity amputation at the only referral public hospital in Guyana. Diabetic foot and related complications are known to be multifactorial. Conclusion: In this review, we highlight the information on the diabetic foot and related complications with an emphasis on Guyanese background.     

Nanotherapeutic approach to treat diabetic foot ulcers using tissue-engineered nanofiber skin substitutes: A review

Background and aimsDiabetes mellitus (DM) is a chronic metabolic disease associated with long-term multisystem complications, among which nonhealing diabetic foot ulcers (DFUs) are recognized as major cause of morbidity and mortality. Treating DFUs with surgical procedures such as synthetic or biological skin grafts or skin substitutes has several limitations, where none of the currently available skin substitutes is ideal.MethodsOVID/Medline and PubMed databases were searched using the Medical Subject Heading (MeSH) or Title/Abstract words (“diabetic foot ulcers”, “skin substitutes”, and “nanofibers”), to identify published research studies on DFUs and nanofibers.ResultsElectrospinning nanotechnology is being used in the biomedical field to produce polymeric nanofibers impregnated with drugs for wound healing, burns and diabetic ulcers. Those nanofibers also enable seeding of cells into them and culturing them in vitro to synthesize tissue-like structures. Knowing the advantages of generating patient-specific induced pluripotent stem cells (iPSCs) and organoids in three-dimension (3D), including skin organoids, it is worth mingling these technologies to develop tissue-engineered biological skin substitutes.ConclusionNanofiber-skin substitutes hold promise for treatment of patients suffering from DFUs and inspire novel strategies that could be applied to other organ systems as well, introducing a new era of “regenerative and personalized medicine”.     

VEGF gene polymorphism association with diabetic foot ulcer

Objective

Functional polymorphisms within vascular endothelial growth factor (VEGF) gene have shown association with various conditions including diabetic neuropathy and retinopathy. In this study we have performed a candidate gene association study in order to examine VEGF gene polymorphism association with diabetic foot ulcer (DFU).

Methods

The study group comprised of type 2 diabetes patients with (N = 247) and without (N = 241) DFU. Healthy control subjects (N = 98) were also recruited from the same area. The ARMS-PCR technique was applied for genotyping of VEGF gene SNPs at positions −7*C/T and −2578*C/A.

Results

The frequency of genotype AA was significantly decreased in patients with DFU compared with diabetic subjects without DFU (AA vs CA + CC, p = 0.003, OR = 0.44, CI = 0.24-0.80). Also there was a significant decrease in frequency of A allele in patients with DFU compared to the controls (p = 0.02, OR = 0.68, CI = 0.48-0.96).

Conclusion

It seems that lower frequency of A allele in patients with DFU is conferring a protective effect which might be as a result of increased angiogenesis in patients carrying this allele.     

A clinico-pathological study of diabetic foot ulcers

During a 32-month period 94 foot ulcers in 54 diabetic patients aged 38-90 years (mean 64 years) were managed in a specialist foot clinic. Fifty-six percent were men, and they were significantly younger than women; 46% were taking insulin. Mean duration of diabetes was 13.4 years. Comparison with controls revealed a higher prevalence (p less than 0.01) of retinopathy (60% vs 23%), neuropathy (89% vs 31%), vasculopathy (71% vs 34%), arterial calcification (31% vs 20%) and previous lesions (54% vs 4%). There was no difference in quality of diabetic control, or smoking habit. A simple classification of lesions was used. All types yielded mixed cultures of microorganisms (average 2.1 per swab); the flora obtained was affected by systemic antibiotics. Abnormal pressure was judged to have contributed to all lesions occurring in areas of callus. In addition definable trauma precipitated the event in up to 60% of all other types. Lesions in areas of callus were more likely to have healed by the end of the study period, but average time to healing was significantly longer than other lesions. Despite intensive outpatient support, 33 patients spent a total of 1188 days in hospital during the 974 day period, an average of 36 days per patient and 1.2 beds per day. Further research is urgently required to define optimal methods of prevention and treatment of diabetic foot ulcers.     

Redefining diabetic foot disease management service during COVID-19 pandemic

Background & aimsDiabetic Foot Disease (DFD) management had to be redefined during COVID-19. We aim to evaluate the impact of this on diabetic foot care services and the strategies adopted to mitigate them.MethodsWe have performed a comprehensive review of the literature using suitable keywords on the Search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the first two weeks of May 2020. We have reviewed how the diabetic foot service in the hospital and community setting has been affected by the current Coronavirus outbreak.ResultsWe found considerable disruption in diabetic foot service provisions both in the primary care and in the hospital settings. Social distancing and shielding public health guidelines have impacted the delivery of diabetic foot services.ConclusionAs the COVID-19 pandemic spreads worldwide, health care systems are facing the tough challenges in delivering diabetic foot service to patients. Public health guidelines and the risk of virus transmission have resulted in reconfiguration of methods to support and manage diabetic foot patients including remote consultations.