The International Journal of Lower Extremity Wounds

Integrin-linked kinase (ILK) mediates signal transduction between cells and the extracellular matrix, regulating cell proliferation, migration, angiogenesis, and apoptosis. However, its roles in the formation of hypertrophic scars are not yet clear. In this study, we found that ILK was predominantly expressed on the microvascular endothelial cells and the epidermal basal cells of human hypertrophic scars. The proliferation, migration and angiogenesis of primary human scar microvascular endothelial cells (HSMECs) were significantly inhibited after ILK was silenced. The ILK inhibitor QLT0267 had the same effect of impeding angiogenesis in vitro by blocking ILK activity. Both siRNA and QLT0267 markedly decreased the expression of vascular endothelial growth factor, but not its receptors, such as human vascular endothelial cell growth factor receptor 1 or kinase insert domain-containing receptor. We also showed that the expression of ILK was enhanced by inducing mild hypoxia with CoCl₂, but it was suppressed under serious hypoxia. Thus, ILK regulates HSMEC proliferation and angiogenesis and participates in the formation of hypertrophic scars, in which mild hypoxia may be the mechanism of action.

A systematic review and meta-analyses of nutritional supplementation to treat chronic lower extremity wounds was done in order to test the premise that impaired nutrition is implicated in healing. The databases of Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and EBSCO CINAHL (1972-October 2014) were searched systematically. Only randomized controlled trials in adults with chronic lower extremity wounds were included. Both topical and systemic routes of supplementing nutrition were considered. The primary outcome was wound healing. Study characteristics, outcomes, and risk of bias were extracted by trained researchers and confirmed by the principal investigator. Twenty-three of 278 (8.3%) retrieved articles met the inclusion criteria and were selected. Most of the studies were of unclear or low risk. Overall, nutritional supplementation was favorable (risk ratio [RR] = 1.44, 95% confidence interval [CI] = 1.25-1.66). The systemic route was marginally better than the topical one (RR = 1.51, 95% CI = 1.36-1.67; RR = 1.14, 95% CI = 0.96-1.36, respectively). For venous ulcers, the data showed nutritional supplementation to be significantly beneficial compared to placebo (RR = 1.44, 95% CI = 1.31-1.59). Similar data were found for diabetic foot and sickle cell ulcers (RR = 1.17, 95% CI = 0.93-1.47; RR = 1.56, 95% CI = 0.94-2.60, respectively). These data permit the inferences that nutritional supplementation in the populations studied showed significant benefits in the healing of venous ulcers and tendency (nonsignificant trends) in the healing of diabetic and sickle cell ulcers.

We sought to identify factors associated with treatment failure and leg amputations among those patients who presented with foot osteomyelitis. Characteristics, treatments, and outcomes for all patients treated for probable or definite foot osteomyelitis (per consensus definition) between January 2011 and March 2015 were reviewed. Multivariate Cox regression models were used to identify risk factors for treatment failure (unanticipated resection of additional bone or leg amputation) and of leg amputation alone. A total of 184 episodes of foot osteomyelitis met inclusion criteria. Treatment failure occurred in 53 (28.8%) and leg amputation in 21 (11.4%). Risk factors for treatment failure included severe/unaddressed peripheral artery disease, homelessness, Pseudomonas aeruginosa or Escherichia coli bone isolates, serum albumin <2.8 mg/dL, hallux involvement, insulin therapy, 60 or more pack-years smoking, and <7 days of directed antibiotic therapy for a positive bone margin. Delayed primary wound closure (ie, staged operations) had significantly lower treatment failure risk. Unanticipated resection of bone was not associated with leg amputation. Foot osteomyelitis treatment failure is common. Various factors can help identify those at risk for treatment failure and/or leg amputation, and further studies should focused whether initial management or follow-up should change when these factors are present.

Pressure ulcers are difficult to treat. Recent reports of low-temperature atmospheric-pressure plasma (LTAPP) indicated its safe and effectiveness in chronic wound care management. It has been shown both in vitro and vivo studies that LTAPP not only helps facilitate wound healing but also has antimicrobial efficacy due to its composition of ion and electron, free radicals, and ultraviolet ray. We studied the beneficial effect of LTAPP specifically on pressure ulcers. In a prospective randomized study, 50 patients with pressure ulcers were divided into 2 groups: Control group received standard wound care and the study group was treated with LTAPP once every week for 8 consecutive weeks in addition to standard wound care. We found that the group treated with LTAPP had significantly better PUSH (Pressure Ulcer Scale for Healing) scores and exudate amount after 1 week of treatment. There was also a reduction in bacterial load after 1 treatment regardless of the species of bacteria identified.

The use of a validated screening questionnaire to identify individuals with chronic leg ulcers allows large-scale population-based studies to be conducted that measure and monitor the prevalence of the disease. The aim of this study was to design and validate such a screening questionnaire to identify patients with chronic leg ulcers. A simple 3-item questionnaire was developed at the Department of Dermatology, University Hospital of Zealand, Denmark. In total, 90 patients attending the department’s outpatient clinic for dermatological diseases and chronic wounds were included in this study. All included participants completed the questionnaire and were subsequently examined by dermatologists. We found that the constructed 3-item questionnaire in this study had a sensitivity and specificity of 95% and 93% and a positive predictive value and negative predictive value of 78% and 95%, respectively. Moreover, we found that the use of the 3-item questionnaire, as compared with a single question, in which the participants were asked whether they currently have a leg ulcer, resulted in significantly higher positive predictive value (+11.6%, P = .035) and specificity (+5.6%, P = .046) of the diagnostic test. Future studies are merited to investigate the diagnostic accuracy of the questionnaire in other populations and settings.

Patients scheduled for microsurgical reconstruction of the lower leg often receive preoperative assessment of recipient vessels using angiography. However, no clear standard is available for evaluating angiographic results to predict free-flap survival outcomes. We developed angiographic criteria for predicting surgical outcome in patients with lower-extremity peripheral arterial disease based on abnormality of the anterior tibial and posterior tibial arteries. We applied the criteria to a small number of patients scheduled for microsurgical reconstruction of the lower leg. Angiographies with arterial abnormalities were classified into 3 groups: favorable free-flap survival, compromised free-flap survival, and postsurgical pedal ischemia. The study enrolled 50 patients between 2005 and 2013. In 42% of patients, arterial abnormalities were observed by angiography. Age >65 years was the strongest risk factor for development of lower-leg arterial abnormality (P < .001). The anterior tibial and peroneal arteries were significantly more stenotic than other vessels. In the favorable free-flap survival and compromised free-flap survival groups, free-flap transfers were attempted in 7 patients but intraoperatively abandoned in 2 patients, with postoperative failure in 1 patient. In the postsurgical pedal ischemia group, free-flap transfers were attempted in 10 patients but intraoperatively abandoned in 6 patients, with postoperative failure in 3.

Diabetic hindfoot ulcers, complicated by osteomyelitis, are associated with a high risk of major amputation. Partial calcanectomy, preceded by an effective management of the infection and of the eventual peripheral artery disease, can be considered as valid therapeutic option. We have evaluated a therapeutic protocol for diabetic hindfoot ulcers complicated by osteomyelitis, which, besides an adequate surgical debridement, considers a reconstructive pathway assisted by the positioning of a circular external fixator. We made a prospective study of a cohort of diabetic patients affected by heel ulcer complicated by osteomyelitis. All patients underwent open partial calcanectomy associated with the positioning of a circular external frame specifically designed for hindfoot stabilization and offloading. A reconstructive procedure was implemented starting with the application of negative pressure wound therapy and coverage with dermal substitute and split thickness skin grafting. From November 2014 to November 2015, 18 consecutive patients were enrolled. Mean follow-up period was 212.3 ± 64.0 days. Healing was achieved in 18 (100%) patients. The mean healing time was 69.0 ± 64.0 days. No major amputation had to be performed during the follow-up. Open partial calcanectomy associated with external fixation and skin reconstruction was as efficient as limb salvage in patients with infected lesions of the hindfoot complicated by calcaneal osteomyelitis.

Donor-site wound healing was tested with a silver sulfadiazine (SSD)-impregnated hydrocolloid dressing and hydrocolloid dressing applied manually by a physician on site. A total of 14 patients, 5 woman and 9 men (23-89 years old, average = 61.6 ± 18.70 years), were enrolled in this prospective controlled study. The degree of bleeding was significantly less with the SSD-impregnated than with the hydrocolloid dressing (P < .01). In the moisture meter analysis, the values of the effective contact coefficient and corneal thickness were significantly smaller with the SSD-impregnated dressing (P < .05). In the color analysis, the clarity was significantly lower with the hydrocolloid dressing after 3 months than that of intact neighboring skin (P < .01). Regarding red-green color, SSD-impregnated and hydrocolloid values were significantly greater than the intact skin value immediately after and at 3 months, and the hydrocolloid value was significantly greater than intact at 6 months (P < .01 immediately; P < .01 at 3 months and intact at 6 months) in redness. Regarding yellow-blue color, the hydrocolloid value was significantly lower than the intact skin value at 3 months (P < .05 and intact) in yellow. The extensibility was significantly lower with the hydrocolloid dressing than in intact skin immediately (P < .01), and viscoelasticity was significantly lower with the hydrocolloid dressing than in intact skin immediately and after 3 and 6 months (P < .01 immediately and at 6 months and P < .05 at 3 months). The SSD-impregnated hydrocolloid dressing led to superior wound healing, decreased the degree of bleeding, and demonstrated better corneal barrier function, clarity, color matching, and viscoelasticity in split-thickness donors.

The D+Wound Solution is a mobile phone application (app) that assists users in the assessment and treatment of the wound. The app has 6 components for assessment: need for debridement, infection control, revascularization, and exudate control; whether it is chronic; and finally, the top surface of the skin. These components are named D.I.R.E.C.T. The app makes you review these components as an algorithm to provide a reasonable solution for dressing. It is designed to understand the status of the wound and provide a practical treatment idea for wound care providers. A total of 118 nurses were divided into 2 groups, designated as experienced and less-experienced groups, and surveyed. Both groups found the app to be helpful in making a treatment plan. However, the less-experienced group found it to be significantly more useful in assessing the wound (P = .026) but difficult to understand the logic. The experienced group found the logic to be significantly easier to understand (P = .018) and had significantly higher similarities (P = .015) in treatment protocols compared with the less-experienced group. We may conclude that this app has a logical algorithm resembling experienced wound caregivers and is more useful in the less-experienced group.

Compartment syndrome (CS) is a pathological increase of the interstitial pressure within the closed osseous fascial compartments. Trauma is the most common cause, followed by embolization, burns, and iatrogenic injuries; it usually involves the limbs. The major issue when dealing with CS is the possibility to do an early diagnosis in order to intervene precociously, through a fasciotomy, reducing the risk of tissue, vascular and nervous damage. Although it is an infrequent condition, it is potentially life threatening. In our case report, we present a 59-year-old patient, smoker, affected by hypertension, dyslipidemia, chronic renal failure, and morbid obesity who came at our attention for a 6-cm abdominal aorta aneurysm, treated with an aorto-aortic graft. Within 24 hours from surgery, the patient presented acute ischemia of the right lower limb due to thrombosis of the common iliac artery and underwent the positioning of a kissing stent at the aortic bifurcation. In the immediate postoperative period, a relevant increase in serum creatinine, creatine phosphokinase, and myoglobin value was recorded, associated with clinical presentation of swelling in the right buttock with intense pain. The diagnosis of gluteal CS was confirmed by the measurement of the gluteal compartment pressure, which resulted of 110 mm Hg. The treatment of the CS consisted in gluteal dermofasciotomy, surgical debridement of the buttock, and positioning of negative pressure medication, associated with infusive therapy, avoiding hemodialysis. Because of the epidural anesthesia only later on it was possible to observe a persistent plegia of the right lower limb, which was solved within 1 month of neurological and physical therapy. With our experience, we can state that the CS is an extremely severe complication that can occur in vascular surgeries and it should therefore be kept in mind in the short-term postoperative period in order to guarantee a precocious diagnosis and immediate treatment.

Despite ongoing smoking cessation efforts and optimized perfusion, failed wound closure in the presence of peripheral arterial disease (PAD) and diabetes are common. A clinical effectiveness review was conducted in actively smoking diabetic patients diagnosed with PAD, treated with serial applications of a viable intact cryopreserved human placental membrane (vCPM) (Grafix, Osiris Therapeutics Inc, Columbia, MD) for recalcitrant lower extremity ulcerations (n = 6). More than half of the patients were not candidates for revascularization. Baseline vascular status in 5 of 6 lower-extremity wounds remained unchanged throughout the entire course of vCPM treatment. Daily cigarette consumption averaged 18 cigarettes per patient. Mean wound duration and mean surface area was 53 weeks and 4.6 cm², respectively. Mean number of vCPM applications and time to closure was 7.0 grafts in 7.8 weeks. There were no wound-related infections or amputations and no vCPM-related adverse events. All 6 wounds remained closed at the 12-month follow-up visit. In conclusion, vCPM demonstrated clinically effective outcomes in 6 previously nonhealing ulcerations despite ongoing smoking habits in the presence of PAD and diabetes.

Ischemic wounds unresponsive to standard treatment in thromboangiitis obliterans are associated with amputation, morbidity, and mortality. In this study, hyperbaric oxygen therapy was added to standard treatment of 36 patients with thromboangiitis obliterans with ischemic ulcerated wounds in the extremities. Full recovery was observed in 52.7% of cases (25% at discharge, 27.7% during follow-up). Resting pain after treatment decreased significantly compared to pretreatment levels based on visual analog scale scores (7.1 ± 1.7 vs 2.2 ± 3.0, P = .0001). Mean wound area also decreased significantly after treatment (22.6 ± 17.5 vs 13.02 ± 16.5, P = .0001). The number of patients requiring no assistance during routine daily activities increased significantly (25% vs 55.5%, P = .001). All patients were at Fontaine stage IV before hyperbaric oxygen therapy. The number of patients at stage IIB increased significantly after treatment, while that of patients at stage IV decreased significantly (0% vs 47.2%, P = .0001, and 100% vs 47.2%, P = .0001, respectively). None of our patients was able to walk without pain before treatment; however, walking distance was significantly extended in 16 patients who were capable of walking (0 vs 190.6 ± 129.4 meters, P = .0001). In addition, 11.1% of patients underwent major amputation during follow-up.

Lipodermatosclerosis may develop clinical aspects that have striking analogies with Van Gogh’s style of painting cypresses. They may reveal specific physiopathological disorders and identify a homogeneous group of patients with chronic venous insufficiency.