Outcomes of subatmospheric pressure dressing therapy on wounds of the diabetic foot

The purpose of this retrospective study was to evaluate outcomes of people with large diabetic foot wounds treated with subatmospheric pressure dressing therapy immediately following surgical wound debridement. Data were abstracted from the medical records of 31 consecutive patients with diabetes, 77.4% male (n = 24), aged 56.1 +/- 11.7 years, presenting for care at two large multidisciplinary wound care centers. All patients received surgical debridement for indolent diabetic foot wounds and were subsequently started on a regimen of subatmospheric pressure dressing therapy delivered using a vacuum-assisted closure device for a mean of 4.7 +/- 4.2 weeks (mode = 2 weeks) using a protocol that called for cessation of therapy when the wound bed approached 100% coverage with granulation tissue with no exposed tendon, joint capsule, or bone. Outcomes evaluated included time to complete wound closure, proportion of patients achieving wound healing at the level of initial debridement, and complications associated with use of the device. The mean duration of wounds before therapy was 25.4 +/- 23.8 weeks. In patients treated with subatmospheric pressure dressing therapy, 90.3% (n = 28) of wounds healed at the level of debridement without the need for further bony resection in a mean 8.1 +/- 5.5 weeks. The remaining 9.7% (n = 3) went on to higher level amputation (below knee amputation = 3.2%, [n = 1] and transmetatarsal amputation = 6.5% [n = 2]). Complications included periwound maceration (19.4% [n = 6]), periwound cellulitis (3.2% [n = 1]), and deep space infection (3.2% [n = 1]). The authors concluded that appropriate use of subatmospheric pressure dressing therapy to achieve a rapid granular bed in diabetic foot wounds may have promise in treatment of this population at high risk for amputation and that a large, randomized trial is now indicated.     

基质金属蛋白酶及其组织抑制物在糖尿病足创面愈合中作用的研究概况

糖尿病足(diabetic foot,DF)是糖尿病最严重的并发症之一,属难治性创面。基质金属蛋白酶(matrix metalloproteinases,MMPs)具有促进细胞迁移、降解细胞外基质(extracellular matrix,ECM)等作用,参与创面愈合的每个过程。基质金属蛋白酶组织抑制剂(the tissue inhibitors of MMPs,TIMPs)是MMPs的特异性抑制剂,抑制MMPs过度表达。二者协同,在创面愈合中发挥重要作用。该文就MMPs和TIMPs在DF溃疡创面愈合中作用的研究概况进行综述。     

银离子敷料在老年糖尿病足溃疡合并感染治疗中的应用

目的探讨银离子敷料在老年糖尿病足溃疡合并感染治疗中的应用效果。 方法选取2018年1月至2021年1月云南德宏州人民医院收治的60例老年糖尿病足溃疡合并感染患者作为研究对象。其中30例给予湿疗伤口敷料治疗（对照组）,余30例给予银离子敷料治疗（观察组）。比较两组患者溃疡程度、血管内皮生长因子（VEGF）、表皮细胞生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）及C反应蛋白（CRP）水平。计量资料的比较采用t检验。 结果与治疗前比较,治疗后两组患者Wagner分级评分和CRP水平均明显下降（观察组：t=19.443、7.353,对照组：t=7.486、4.142,P<0.01）,VEGF、EGF、bFGF水平均明显提高（观察组：t=15.408、28.493、17.668,对照组：t=9.510、18.365、12.956,P<0.01）。与对照组患者比较,观察组患者治疗后Wagner分级评分和CRP水平更低（t=14.593、3.594,P<0.01）,VEGF、EGF、bFGF水平更高（t=4.382、7.922、5.641,P<0.01）。 结论银离子敷料治疗老年糖尿病足溃疡合并感染,能够减轻溃疡程度,促进相关生长因子的分泌,降低炎症水平。     

Outcomes of hyaluronan therapy in diabetic foot wounds

The purpose of this study was to evaluate outcomes of persons with neuropathic diabetic foot wounds treated with a hyaluronan-containing dressing. Data were abstracted for 36 patients with diabetes, 72.2% male, aged 60.0+/-10.7 years and a mean glycated hemoglobin (HbA(1c)) of 9.5+/-2.5% presenting for care at two large, multidisciplinary wound care centers. All patients received surgical debridement for their diabetic foot wounds and were placed on therapy consisting of hyaluronan dressing (Hyalofill, Convatec, USA) with dressing changes taking place every other day. Outcomes evaluated included time to complete wound closure and proportion of patients achieving wound closure in 20 weeks. Hyalofill therapy was used until the wound bed achieved 100% granulation tissue. Therapy was then followed by a moisture-retentive dressing until complete epithelialization. In total, 75.0% of wounds measuring a mean 2.2+/-2.2 cm(2) healed in the 20-week evaluation period. Of those that healed in this period, healing took place in a mean 10.0+/-4.8 weeks. The average duration of Hyalofill therapy in all patients was 8.6+/-4.2 weeks. Deeper (UT Grade 2A) wounds were over 15 times less likely to heal than superficial (1A) wounds (94.7 vs. 52.9%, Odds Ratio=15.9, 95% Confidence Interval=1.7-142.8, P=0.006). We conclude that a regimen consisting of moist wound healing using hyaluronan-containing dressings may be a useful adjunct to appropriate diabetic foot ulcer care. We await the completion of a multicenter randomized controlled trial in this area to either support or refute this initial assessment.     

Expression of matrix metalloproteinases in patients with Wegener's granulomatosis

BACKGROUND: Enhanced activity of matrix metalloproteinases (MMPs) has been reported to have a pathogenic role in several diseases such as cancer and cardiovascular disorders, and seems also to play a part in certain autoimmune diseases. OBJECTIVE: To examine whether enhanced MMP activity may also have a role in the pathogenesis of Wegener's granulomatosis (WG). METHODS: In a study group of 15 patients with WG and 15 controls, plasma levels and gene expression were measured in freshly isolated peripheral blood mononuclear cells (PBMCs) of several MMPs and their endogenous inhibitors (that is, tissue inhibitors of metalloproteinases (TIMPs)) by enzyme immunoassays and RNase protection assay, respectively. RESULTS: Whereas patients with WG in remission had enhanced gene expression of several MMPs and TIMPs in PBMCs, those with active disease had a selective up regulation of MMP-2 and MMP-8 compared with healthy controls, and a down regulation of TIMP-1 and TIMP-3 compared with other patients with WG. Moreover, plasma levels of TIMP-1 and MMP-8 correlated significantly with C reactive protein levels, further supporting an association between activation of the MMP/TIMP system and disease activity in WG. Finally, these changes in MMP/TIMP expression in WG were accompanied by increased total MMP activity in PBMC supernatants, particularly in those with active disease, suggesting a matrix degrading net effect. CONCLUSION: These findings suggest that disturbed MMP and TIMP activity has a role in the pathogenesis of WG.     

Expression of matrix metalloproteinases in vasculitic neuropathy

The aim of this study was to investigate the expression pattern and cellular source of matrix metalloproteinases (MMP) in vasculitic neuropathy. Matrix metalloproteinases are endopeptidases degrading components of extracellular matrix proteins, and they have been implicated in the pathogenesis of inflammatory demyelination. They are induced by cytokines, secreted by inflammatory cells, and enhance T cell migration. Vasculitic neuropathy occurs as a component of systemic vasculitis or as an isolated angiitis of the peripheral nervous system, and T cell-mediated inflammation is detected in its pathogenesis. Nerve biopsy sections of eight patients with nonsystemic vasculitic neuropathy (NSVN) and four with systemic vasculitic neuropathy were examined for the presence of CD4+, CD8+, and CD68+ cells and immunohistochemically for MMP-2 and MMP-9 expression. Nerve biopsies of eight patients with noninflammatory neuropathy were used as a control group. Semiquantitative polymerase chain reaction analysis was performed to detect MMP-2 and MMP-9 mRNA. The predominant cells were CD8+ and CD68+ T cells. Expression of MMP-9, but not MMP-2, was increased in perivascular inflammatory infiltrate in nerve tissues of vasculitic neuropathy patients. This MMP-9 expression correlated positively with immunostaining of CD8+ T cells. No difference was detected between immunostaining patterns of nonsystemic and systemic vasculitic neuropathies with the antibodies used, except in MMP-9 immunostaining, which was found to be enhanced in NSVN group. Polymerase chain reaction analysis revealed elevated mRNA levels of MMP-9 and MMP-2 compared with controls, but this did not reach statistical significance. Our results imply a pathogenic role for MMP-9 secreted from CD8+ cells in vasculitic neuropathy.     

Expression of matrix metalloproteinases in patients with acute myocardial infarction

This study investigated the clinical significance of matrix metalloproteinases (MMPs) in acute myocardial infarction (AMI) and the involvement of peripheral blood mononuclear cells (PBMCs), which are a possible source of MMPs in AMI. Forty patients with AMI were recruited. Plasma and PBMCs were isolated from peripheral blood on days 1, 7, 14 and 21 after the onset of AMI. Levels of MMP-1 and MMP-2 were measured by enzyme-linked immunosorbent assay. The MMP-1 level in the culture medium of PBMCs after incubation for 24h was designated as 'PBMC-MMP-1 level.' Plasma MMP-1 did not significantly change during the course of AMI, but the plasma MMP-2 levels increased gradually after the onset of AMI with maximum elevation on day 21 after onset. Plasma MMP-2 activity also became significantly elevated during the course of AMI. PBMC-MMP-1 levels in the patients were significantly higher than those in control subjects over the course of AMI. Significant positive correlations were observed between maximum PBMC-MMP-1 levels and maximum plasma C-reactive protein levels (r=+0.55, p<0.01) and left ventricular end-diastolic volume index (r=+0.63, p<0.001). In conclusion, plasma MMP-2 levels and activity and MMP-1 production by PBMCs are increased in patients with AMI. Inflammation after AMI may enhance production of MMP-1 by PBMCs. These changes may play an important role in the ventricular remodeling that occurs after AMI by promoting the degradation of the extracellular matrix.     

Synergistic action of protease-modulating matrix and autologous growth factors in healing of diabetic foot ulcers. A prospective randomized trial

This study tests the hypothesis that addition of a protease-modulating matrix enhances the efficacy of autologous growth factors in diabetic ulcers.

Fifty-one patients with chronic diabetic foot ulcers were managed as outpatients at the Democritus University Hospital of Alexandroupolis and followed up for 8 weeks. All target ulcers were ≥2.5 cm in any one dimension and had been previously treated only with moist gauze. Patients were randomly allocated in three groups of 17 patients each: Group A was treated only with the oxidized regenerated cellulose/collagen biomaterial (Promogran, Johnson & Johnson, New Brunswick, NJ), Group B was treated only with autologous growth factors delivered by Gravitational Platelet Separation System (GPS™, Biomet), and Group C was managed by a combination of both. All ulcers were digitally photographed at initiation of the study and then at change of dressings once weekly. Computerized planimetry (Texas Health Science Center ImageTool, Version 3.0) was used to assess ulcer dimensions that were analyzed for homogeneity and significance using the Statistical Package for Social Sciences, Version 13.0.

Post hoc analysis revealed that there was significantly greater reduction of all three dimensions of the ulcers in Group C compared to Groups A and B (all P<.001). Although reduction of ulcer dimensions was greater in Group A than in Group B, these differences did not reach statistical significance.

It is concluded that protease-modulating dressings act synergistically with autologous growth factors and enhance their efficacy in diabetic foot ulcers.     

Expression of immunoreactive matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human normal livers and primary liver tumors

Matrix metalloproteinases (MMPs) play an important role in cancer cell invasion by degrading extracellular matrix proteins. However, little is known about the in situ expression of MMP in human normal livers and primary liver tumors. In this study, we therefore examined the in situ expression of immunoreactive MMP and tissue inhibitors of MMP (TIMP) in 10 normal livers, 11 surgically resected intrahepatic cholangiocarcinomas (CCs), and 6 surgically resected hepatocellular carcinomas (HCCs). In normal livers, MMP and TIMP were infrequently and faintly expressed in bile ducts, but were not expressed in hepatocytes. In the 11 CCs, MMP-1, MMP-2, MMP3, MMP-9, TIMP-1, and TIMP-2 were expressed in tumor cells and/or tumor stroma in 11 (100%), 5 (45%), 8 (73%), 3 (27%), 9 (82%), and 9 (82%), respectively. The expression of MMP and TIMP in tumor cells was located in the cytoplasm with a diffuse or granular pattern; that in the tumor stroma was situated in fibroblasts, leukocytes, and extracellular matrix. Their expression was stronger in CC cases with severe invasion than in CC cases with mild invasion. In contrast, MMP and TIMP were not expressed in any cases of HCC. These results show that intrahepatic bile duct cells may neoexpress or overexpress MMP and TIMP after malignant transformation but that hepatocytes do not, and suggest that MMP and TIMP play an important role in CC cell invasion by degrading extracellular matrix proteins. (Hepatology 1996 Jun;23(6):1341-4)     

CD147分子和基质金属蛋白酶在类风湿关节炎滑膜中的表达

目的 探讨类风湿关节炎(RA)滑膜组织CD147的表达及其与基质金属蛋白酶(MMP)-01和MMP-2表达的相关性。方法 采用免疫组织化学SP(streptavidin／peroxidase)染色方法检测11例RA患者受损关节软骨-血管翳接合部（CPJ)滑膜组织中CD147和MMP-1及MMP-2的表达，并与3例骨关节炎（OA)患者滑膜组织CD147和MMP-1及MMP-2的检测相对照。结果 3例OA滑膜组织CD147和MMP-1及MMP-2的表达均为阴性，而11例RA滑膜组织中均有CD147和MMP-1及MMP-2的表达。其中，表达CD147的细胞为单核-巨噬细胞、淋巴细胞和滑膜成纤维样细胞，表达MMP-1及MMP-2的细胞为滑膜成纤维样细胞。统计学分析表明RA滑膜细胞CD147的表达和MMP-1及MMP-2的表达间存在显著相关性。结论 CD147在RA滑膜组织中表达增高，可能是导敏RA受损关节软骨、骨基质降解的重要因素之一。     

Expression of chemokines and matrix metalloproteinases in early rheumatoid arthritis

OBJECTIVE: To compare macrophage infiltration and expression of chemokines and matrix metalloproteinases (MMPs) in synovial tissue between patients with early and long-standing rheumatoid arthritis (RA). METHODS: Knee synovial biopsies were taken from 22 patients with early (<1 yr) and 22 patients with long-standing (>5 yr) RA and immunostained with antibodies specific for CD68; macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1; MMP-1 and -3 and the tissue inhibitors of metalloproteinases (TIMP)-l and -2. Immunostaining was quantified using a colour video image analysis system. RESULTS: CD68+ macrophage infiltration and the expression of MIP-1alpha, MCP-1, MMP-1, MMP-3, TIMP-1, and TIMP-2 were observed in synovial tissue of patients with early RA. In long-standing RA, there was a further increase in CD68+ macrophage infiltration and MIP-1alpha expression in the synovial lining layer. CD68 expression correlated with MIP-1alpha (R=0.39, P=0.01), but not with MCP-1 expression. CONCLUSION: Macrophage accumulation, and the expression of chemokines and MMPs in synovial tissue occur in early RA. Targeting chemokines which play a role in the migration of macrophages into the joints may be of therapeutic benefit in RA patients.     

Expression of matrix metalloproteinases in pigs with hyperoxia-induced acute lung injury.

The aim of this study was to determine the role of matrix metalloproteinases (MMPs) in the pathogenesis of acute lung injury induced by hyperoxia. Twenty-three pigs were exposed in sealed cages to >80% oxygen (for 24-120 h) or room air. Correlation between MMP-2/MMP-9 activity, measured by gelatin zymography in bronchoalveolar lavage fluid (BALF), and the histological findings and pathological parameters were examined in detail. Sources of these MMPs in the hyperoxic lung were analysed by immunohistochemistry. The histological progression of acute lung injury in this model ranged from the early exudative to the early proliferative phase of diffuse alveolar damage (DAD). MMP-2 and -9 activities were elevated under prolonged hyperoxic exposure. MMP-9 activity correlated significantly with the oxygen tension in arterial blood/inspiratory oxygen fraction, the lung wet-to-dry weight ratio, and the number of neutrophils in BALF, whereas MMP-2 activity did not correlate at all with these factors. MMP-9 activity correlated more closely with the pathological findings of DAD than did MMP-2 activity. Strong MMP-9 expression was observed in neutrophils, alveolar macrophages as well as alveolar lining epithelial cells. These results suggest that matrix metalloproteinase. which may derive from neutrophils recruited into airspaces, plays an important role in the pathogenesis of hyperoxic diffuse alveolar damage     

糖尿病足患者截肢的相关危险因素

糖尿病足足糖尿病的严重并发症之一,是非创伤件截肢的主要原因.神经病变、缺血、感染、营养不良、吸烟等多种因素与糖尿病足溃疡截肢有关.控制上述危险因素,可以降低糖尿病足溃疡的发病率和截肢率.     

Role of growth factors and cytokines in diabetic foot ulcer healing: A detailed review

The aim of the review is to examine the role of growth factors and cytokines in the management of Diabetic Foot Ulcers, such as platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and Insulin like growth factor (IGF). Taking this a step further, the role of Hypoxia-inducible factors (HIFs), Transforming growth factor beta 1 (TGF-β-1) and other growth factors have also been examined, with regard to the treatment of diabetic foot ulcers. The roles of these above-mentioned growth cytokines have been analyzed by studying various scholastic articles. The complete process of wound healing is implemented and regulated by numerous cytokines and human growth factors. The findings of the study indicate that wound healing of diabetic foot ulcers is a complex and extremely challenging biological and molecular process that involves coordinated efforts of multiple cell types. The therapeutic effects of various growth factors in the clinical management of wounds are chronic venous ulcers, pressure ulcers, and diabetic foot ulcers. It has been concluded that altercations of various cytokines are found in patients enduring diabetic foot ulcers. In a similar way, changes in the level of cytokines are also found in patients suffering from other diabetic complications such as diabetic nephropathy, retinopathy, and neuropathy. Subsequently, the diabetic wound healing process can be accelerated by regulating the levels of the cytokines.

     

Experiences with hydrofibres in the moist treatment of chronic wounds, in particular of diabetic foot

BACKGROUND: Chronic wounds are an everyday problem in general medicine. Likewise, their persistence, painfulness and frequency of relapse are everyday problems which strain the stamina of patients and doctors to the point of desperation. Over recent years, the moist therapy concept has proven to be a major advance in wound treatment. The introduction of innovative wound dressings in the 1990's made it possible to substantially accelerate wound healing and couple it with a simultaneous alleviation of pain. PATIENTS: In the scope of our team's experience one such product is the hydrofibre. This paper offers information on the possibilities for using this material on the basis of 135 wound situations, 44% of which are within the context of diabetes mellitus. RESULTS: There was a positive influence on wound healing in 92% of the cases. This treatment result is analysed in terms of causal, topographic and iconographic aspects. CONCLUSION: Given the main focal points of our group of patients, it may be stated that hydrofibres are suitable for diabetic wounds.     

血清基质金属蛋白酶9、糖基化终产物与糖尿病足的相关研究

比较糖尿病足患者(糖尿病足组)、2型糖尿病但非糖尿病足患者(非糖尿病足组)及健康体检者血清基质金属蛋白酶9(MMP-9)、晚期糖基化终产物(AGE)水平.糖尿病患者MMP-9、AGE水平高于健康者,糖尿病足组MMP-9高于非糖尿病足组.血清MMP-9升高似可预测糖尿病足发生及足溃疡的预后.