Efficacy of maggot debridement therapy on refractory leg ulcers of Behçet disease: an open-label study.

BACKGROUND: Cutaneous ulcers of Behçet disease (BD) are rare but have high morbidity and resistance to conventional therapies. An important and essential aspect of ulcer management is debridement. Regarding maggot therapy (MT), excretions of the green bottle fly, Lucilia sericata, have been shown to have the ability to remove necrotic debris and promote healing. AIM: To evaluate the efficacy of MT for cutaneous ulcers of BD. METHODS: In this open-label trial, patients with BD with refractory leg ulcers suitable for MT were enrolled. Maggot application was performed until complete debridement was achieved, and all patients were followed up for 12 months afterwards to assess the total healing of ulcers. RESULTS: In total, 24 patients with 32 ulcers were enrolled. Using MT, 91.6% of all ulcers were completely debrided. Mean time to debridement was 14.9 days and mean number of cycles required was 5.3. Mean ulcer size was decreased by 23% with treatment. Time to debridement was positively correlated with pretreatment ulcer size and ulcer duration (P = 0.01 and P < 0.01) but not with ulcer depth, comorbidities, smoking, age or sex (P > 0.05 for all). During follow-up, 79.1% of all ulcers healed completely. Mean time required for total healing was positively correlated with ulcer duration, pretreatment and post-treatment ulcer area, ulcer depth and mean time to total debridement (P < 0.03, P = 0.00, P = 0.04 and P < 0.01, respectively). CONCLUSIONS: To our knowledge, the findings presented in this first and unique study may provide key answers about factors affecting success rate of MT in BD cutaneous ulcers.

Free gastroepiploic lymph nodes and omentum flap for treatment of lower limb ulcers in severe lymphedema: Killing two birds with one stone.

BACKGROUND AND OBJECTIVES: In patients with lymphedema, the disruption of the lymphatic network increases skin turgor and fibrosis of subcutaneous tissue, delays wound healing, causing recurrent ulcerations and infections. In these cases, management of ulcers can be challenging. METHODS: Between January 2016 and June 2018, patients presenting with lymphedema were enrolled at our Institution. We selected patients with severe lymphedema and ulcers of lower limbs and we performed a surgical approach, involving free gastroepiploic lymph nodes and omentum flap, harvested through laparoscopy. RESULTS: We enrolled 135 patients presenting for lymphedema. Among them, 10 eligible cases underwent excision of the ulcer and reconstruction with omentum flap. Mean age was 57.8 years and average follow-up 24.1 months. Circumferences and skin tonicity significantly decreased from the preoperative period. Lymphoscintigraphy showed improvement of the lymphatic drainage and restoration of lymphatic network. No episodes of infection were recorded in the postoperative period. CONCLUSIONS: Our combined procedure merges free flap techniques and lymphedema surgery: omentum covers the defect while providing a new source of lymph nodes, improving the lymphatic networks of the affected limb. This technique can highly increase the quality of life of the patient in a single-stage operation with fast recovery and low donor site morbidity.

A Prospective, Postmarket, Compassionate Clinical Evaluation of a Novel Acellular Fish-skin Graft Which Contains Omega-3 Fatty Acids for the Closure of Hard-to-heal Lower Extremity Chronic Ulcers.

INTRODUCTION: A novel piscine acellular fish-skin graft product has 510k clearance on the US market. This product (Omega3, Kerecis, Isafjordur, Iceland) is to be used similarly to extracellular matrices (ECMs) on the market (eg, bovine and porcine) except that it contains fats, including omega-3 polyunsaturated fatty acids that have been associated with anti-inflammatory properties in many studies. While many current ECMs are effective on open wounds, studies have largely excluded application to hard-to-heal ulcers. To test this product in a real-world environment, the authors chose to look specifically at hard-to-heal ulcers based on previously defined wound and patient factors. METHODS: The primary objective was to assess the percentage of wound closure area from baseline after 5 weekly fish-skin graft applications in 18 patients with at least 1 "hard-to-heal" criteria. Patients underwent application of the fish skin for 5 sequential weeks, followed by 3 weeks of standard of care. Wound area, skin assessments, and pain were assessed weekly. RESULTS: A 40% decrease in wound surface area (P < 0.05) and a 48% decrease in wound depth was seen with 5 weekly applications of the fish-skin graft and secondary dressing (P < 0.05). Complete closure was seen in 3 of 18 patients by the end of the study phase. CONCLUSION: This fish-skin product appears to provide promise as an effective wound closing adjunctive ECM. This is true when used in this compassionate setting, where many other products fail. This study lacks a control arm and an aggressive application schedule, but the investigators believe it represents real-world practice.

Therapy with autologous adipose-derived regenerative cells for the care of chronic ulcer of lower limbs in patients with peripheral arterial disease.

BACKGROUND: An ulcer is a trophic lesion with loss of tissue that often has a multifactorial genesis. It typically diverges from the physiologic processes of regeneration because it rarely tends to heal spontaneously. In this study, we used purified adipose-derived stem and regenerative cells (ADRCs) extracted from autologous fat, for the care of chronic ulcers of the lower limbs of arteriopathic patients. The primary objective of this study was complete re-epithelization of chronic ulcers; the secondary objective was a decrease in diameter and depth. METHODS: From January 2010 to January 2012, 20 patients with peripheral arterial disease, with an ankle-brachial index between 0.30-0.40, in the age range 60-70 y (14 men and six women), with chronic ulcers of the lower limb, were involved in the study. Only 10 arteriopathic patients (seven men and three women) with chronic ulcers of the lower limb were surgically treated. Using the Celution system, we isolated a solution of ADRCs in about 150 min. The isolated cells were injected through a 10-mL syringe into the edges of the ulcer, taking care to spread it in all directions. Using a small amount of Celution extract, we performed cell characterization by flow cytometry analysis and cell viability assay. RESULTS: We monitored patients treated with ADRC or untreated at 4, 10, 20, 60, and 90 d. In all cases treated with ADRC, we found a reduction in both diameter and depth of the ulcer, which led to a decrease in pain associated with the ulcer process. In six of 10 cases there was complete healing of the ulcer. Characterization of the cells by FACS clearly showed that the ADRC cells contained adipose-derived stem cells. Viability assays demonstrated that partial or total closure of the ulcer was attributable exclusively to ADRC cells present in the Celution extract, and not to growth factors extracted during the process of purification of the Celution and injected together with the cells. CONCLUSIONS: For the first time, the Celution method has been applied for the care of chronic ulcers in the lower extremity of patients with peripheral arterial disease. Our results demonstrate that the technique is feasible for autologous cell application and is not associated with adverse events. Moreover, the transplantation of autologous stem cells extracted with Celution may represent a valuable method for the treatment of chronic ulcers in lower limbs of arteriopathic patients.

Mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs): potential role in healing cutaneous chronic wounds.

Chronic wounds remain a major challenge in modern medicine and represent a significant health care burden. Several treatments have been suggested, but without a full understanding of the exact mechanism by which chronic wound occurs. Numerous studies have shown that mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) may have therapeutic potential in healing cutaneous chronic wounds through various mechanisms. So far, a series of hypotheses have been proposed, but a holistic image of them is lacking. This review provides a systematic analysis of recent research in animal models and preclinical or clinic trails to evaluate the potential role of MSCs in chronic cutaneous wound healing. Most important, we highlight how mesenchymal stem cells could potentially revolutionize our approach to treating cutaneous chronic wounds. Special attention should be focused on ongoing research regarding the challenges in using and prospects of MSCs in clinical settings.

[Surgical approach to atypical wounds (clinical cases). Subcutaneous ischemic arteriolosclerosis (Martorell ulcer, calciphylaxis, eutrophication)]. / Kirurski pristup atipicnim ranama (klinicki primjeri) Supkutana ishemicka arterioloskleroza (Martorellov vrijed, kalcifilaksija, eutrofikacija).

Atypical wounds are probably the most delicate modern medicine topics as well as the most demanding surgical issue. Recently, we submitted an original report of two similar atypical vascular cases at our surgery department. Both presented a rare type of atypical, potentially fatal, vascular illness due to acute ischemic subcutaneous arteriolosclerosis. Because of the strikingly similar common pathophysiological features, Martorell hypertensive ischemic leg ulcer (HYTILU) and calciphylaxis require identical approach and therapy, both systemic and surgical. Even an experienced clinician can easily confuse it with other atypical wounds, namely pyoderma gangrenosum, which due to the corticosteroid induced immunodeficiency can be detrimental, since the two different approach strategies are required. Based on typical localization, necrotic painful skin necroses, progressive local deterioration, often difficult secondary infections along with long term hypertension and diabetes history could elucidate suspicion of ischemic subcutaneous arteriosclerosis. Hypertension (and often diabetes), local findings and histologically proven subcutaneous arteriolosclerosis are mandatory to make the diagnosis. Rapid local amelioration following correct treatment approach additionally confirms the presumed diagnosis. Besides the minutely repetitive surgical debridement, negative wound pressure therapy and split skin transplantation, one should consider systemic medication (analgesics, antioxidants, LMWH, sodium thiosulfate and antibiotics). Considering the cases presented, opportune decisions along with moderate aggressive and modern holistic surgical approach should inevitably resolve hard to heal atypical wounds.

Impact on wound healing and efficacy of various leg ulcer debridement techniques.

AIM: To evaluate the evidence on the impact of different debridement techniques on healing and their efficacy in the treatment of leg ulcers. METHODS: Web-based search (PubMed) for trials investigating surgical, enzymatic, autolytic, osmotic, ultrasound-assisted, and biosurgical wound debridement on leg ulcers with regard to healing and efficacy. RESULTS: Both surgical and hydrosurgical methods proved to be effective debridement techniques. For conventional surgical debridement, a significantly greater reduction of the wound surface area and a higher healing rate were reported. Studies on autolytic, osmotic, and enzymatic wound debridement showed effective debridement for krill enzymes, dextranomer and manuka honey. Only for manuka honey was there a significantly greater reduction of the wound surface area compared to standard treatment. One study comparing fibrinolysin/DNAse with placebo and one comparing autolytic with enzymatic debridement showed no significant differences between the respective techniques. Trials on ultrasound-assisted wound debridement reported a positive impact on healing. A significant wound surface area reduction was demonstrated in one of them. Maggot therapy led to effective debridement. The largest trial showed no significantly improved healing. CONCLUSIONS: Further studies are needed to strengthen the evidence for a significant impact of wound debridement on the healing of leg ulcers.

Efficacy, tolerability and patient benefit of ultrasound-assisted wound treatment versus surgical debridement: a randomized clinical study.

BACKGROUND: Low-frequency ultrasound has been shown to be an alternative to surgical wound debridement (WD) to stimulate wound healing; however, few data are available. OBJECTIVE: To compare the efficacy, tolerability and benefit of both wound treatment methods. METHODS: A monocentric prospective randomized-controlled clinical study assessing patient-reported outcomes and clinical efficacy of ultrasound-assisted wound treatment (UAW) compared to WD. RESULTS: In total, 67 patients were treated. Efficacy and tolerability were found to be good for both treatments, with 88% of UAW and 85.2% of WD patients experiencing more-than-minimal patient benefit. Quality of life improved significantly. Wound status improved and pain decreased in both groups. CONCLUSION: Compared to the gold standard (i.e. WD), UAW displays the same high efficacy, comparable patient benefit and improved quality of life. Both procedures are equally suitable for highly beneficial guideline-based treatment of chronic wounds.

The surgeon and the patient with ß-thalassaemia intermedia.

BACKGROUND: Unlike patients with ß-thalassaemia major, where lifelong transfusion and iron chelation therapy are necessary for survival, patients with ß-thalassaemia intermedia (TI) generally have a milder course and anaemia. The underlying pathophysiology of the disease still allows several complications to manifest. Surgical management during the course of the disease is common but relevant data from the literature have never been reviewed constructively. This aim of this review was to highlight this clinical entity to the surgeon, and ensure optimal and timely intervention. METHODS: The review was based on potentially relevant studies identified from an electronic search of MEDLINE and PubMed databases. There were no language or publication year restrictions. References in published articles were also reviewed. RESULTS: Surgical intervention is often essential to ensure optimal control of the associated morbidity in TI. Several general considerations are necessary before surgical intervention with regard to anaemia, cardiovascular disease, thromboembolic events and the effects of iron overload. Splenectomy, cholecystectomy, leg ulcers, fractures and extramedullary pseudotumours are the most commonly encountered surgical problems related to TI. CONCLUSION: Awareness of TI and its associated morbidity is important so that appropriate preoperative care can occur.

Atypical calciphylaxis in a patient receiving warfarin then resolving with cessation of warfarin and application of hyperbaric oxygen therapy.

UNLABELLED: Calciphylaxis is a rare, usually fatal vasculopathic disorder characterized by cutaneous ischemia and necrosis due to calcification of arterioles. Although calciphylaxis is most frequently associated with end-stage renal disease (ESRD) and secondary hyperparathyroidism, it has been reported infrequently among patients on warfarin. No standard treatment has been established for atypical calciphylaxis; however, a potentially beneficial treatment is hyperbaric oxygen therapy (HBOT). A high degree of clinical suspicion, early diagnosis, and understanding the pathophysiology of this disease promotes the optimal management of this extremely morbid and often fatal condition. CASE REPORT: We present a 63-year-old Polynesian woman with biopsy-proven calciphylaxis in the absence of ESRD or elevated serum calcium levels while taking warfarin. Therapeutic dose enoxaparin was substituted for warfarin and she received 40 sessions of HBOT during which lower extremity ulcers resolved. DISCUSSION: Warfarin has been implicated when calciphylaxis presents in an atypical fashion. No guidelines exist for treatment of atypical calciphylaxis in the setting of concomitant warfarin therapy. Up to 80% of calciphylaxis patients die within 1 year of diagnosis. Our patient was changed to low-molecular-weight heparin and received HBOT. CONCLUSION: We present what we believe is the first case of atypical calciphylaxis thought to be attributable to warfarin treated with a therapeutic substitution of anticoagulant and HBOT leading to resolution of cutaneous lesions.

A prognostic model for amputation in critical lower limb ischemia.

In a (negative) multicenter randomized trial on management for inoperable critical lower limb ischemia, comparing spinal cord stimulation and best medical treatment, a number of pre-defined factors were analyzed for prognostic value. We included a radiological arterial disease score, modified from the SVS/ISCVS runoff score. The purpose of this analysis was to evaluate clinical factors and commonly used circulatory measurements for prognostic modeling in patients with critical lower limb ischemia. We determined the incidence of amputation and its relation to various pre-defined risk factors. A total of 120 patients with critical limb ischemia were included in the study. The integrity of circulation in the affected limb was evaluated on five levels: suprainguinal, infrainguinal, popliteal, infrapopliteal and pedal. A total radiological arterial disease score was calculated from 1 (full integrity of circulation) to 20 (maximally compromised state). We used Cox regression analysis to quantify prognostic effects and differential treatment (predictive) effects. Major amputation occurred in 33% of the patients at 6 months and in 51% at 2 years. The presence of ischemic skin lesions and the radiological arterial disease score were independent prognostic factors for amputation. Patients with ulcerations or gangrene had a higher amputation risk (hazard ratio 2.38, p = 0.018 and 2.30, p = 0.036 respectively) as well as patients with a higher radiological arterial disease score (hazard ratio 1.17 per increment, p = 0.003). We did not observe significant interactions between prognostic factors and the effect of spinal cord stimulation. In conclusion, in patients with critical lower limb ischemia, the presence of ischemic skin lesions and the described radiological arterial disease score can be used to estimate amputation risk.

New method for bacterial load measurement during hydro-debridement of cutaneous ulcer.

AIM OF THE STUDY: Based on their experience using Versajet for debridement of chronic wounds, the Authors set up a study protocol to verify whether the hydro-surgical cleansing could offer the possibility of taking tissue specimens suitable for diagnostic microbiological evaluation. The aims of the study were the following: MAIN PURPOSE: To evaluate the efficacy of hydro-surgery in detecting the presence of microorganisms and measuring their load, as an alternative to conventional tissue sampling methods; SECONDARY PURPOSE: To set up an easier and less invasive diagnostic modality than surgical biopsy, even though likewise significant. RESULTS: The results of this study show that tissue specimen collection by hydro-aspiration using Versajet is comparable to biopsy sampling (and in some cases it can be even more reliable); moreover, it is not more time-consuming and is certainly less invasive. Compared to surgical biopsy, with such a method a greater amount of tissue may be collected; moreover, tissue specimens can be taken from a broader surface or, depending on the needs, from a more focused area on the margin or at the bottom of the wound.

A prospective randomised controlled clinical trial comparing hydrosurgery debridement with conventional surgical debridement in lower extremity ulcers.

Debridement of devitalised tissue is an essential component of the effective treatment of chronic wounds. The Versajet Hydrosurgery System is a new technology that simultaneously cuts and aspirates soft tissue. In this study we compared Versajet with conventional surgical techniques in the debridement of lower extremity ulcers to assess impact on time and resources for debridement. Forty-one patients with a mean age of 68 years (range 33 to 95 years) underwent surgical debridement of a lower extremity ulcer. Operating room (OR) sessions were randomised to Versajet (n= 22) or conventional debridement (n= 19) with scalpel plus pulsed lavage. Procedure time and utilisation of consumables were recorded. Wound areas were monitored for 12 weeks. There was significant evidence (P < 0.008) of a shorter debridement time (10.8 min) using Versajet over conventional debridement (17.7 min); a mean saving of 6.9 minutes (39%). In addition, a significant reduction in use of pulsed lavage and saline (P < 0.001) was observed with Versajet. Overall, clinical efficacy of the shorter debridement procedure was similar: median time to wound closure 71 days (Versajet) vs. 74 days (conventional) (P= 0.733). We found Versajet to be quicker than conventional debridement in the debridement of lower extremity ulcers without compromising wound healing. Potential cost savings were identified from the use of VERSAJET through the shorter debridement time allowing more patients to be treated in the same operating schedule.

Surgical revascularization in patients with end-stage renal disease: results using a new paradigm in outcomes assessment.

Studies evaluating the outcome of surgical revascularization (SR) for critical limb ischemia in patients who have end-stage renal disease (ESRD) have differed widely in their findings and conclusions. Differences in definitions of success are largely responsible for the varying outcomes. We developed a method of outcomes assessment that incorporates four all-inclusive endpoints to define success. These include primary graft patency to the point of wound healing, postoperative survival of at least 6 months, limb salvage of at least 1 year, and maintenance of ambulatory status of at least 6 months. The purpose of this study was to use this novel method of defining success to determine the outcome of SR in patients with ESRD. From 1998 to 2004, 40 patients (52 limbs) with ESRD and tissue loss underwent SR for limb salvage. Secondary graft patency and limb salvage rates at 36 months were 54.7 per cent and 53 per cent, respectively. When considering each of the four components used to define success separately, success encouragingly ranged between 60 per cent (patent graft until wound healing) and 87.5 per cent (survival for 6 months). However, if all parameters were combined, clinical success was achieved in only 40 per cent (16/40) of patients. Coronary artery disease was the only factor found to significantly reduce success (P = 0.04). In conclusion, using this multiparameter definition of success, which combines four rather modest outcome milestones, favorable outcome occurred in the minority of cases. This study challenges our current method of analyzing success and questions our therapeutic approach to patients with critical limb ischemia and ESRD.

Maggot debridement therapy of infected ulcers: patient and wound factors influencing outcome - a study on 101 patients with 117 wounds.

INTRODUCTION: It has been known for centuries that maggots are potent debriding agents capable of removing necrotic tissue and slough. In January 2004, the US Food and Drug Administration decided to regulate maggot debridement therapy (MDT). As it is still not clear which wounds are likely or unlikely to benefit from MDT, we performed a prospective study to gain more insight in patient and wound characteristics influencing outcome. PATIENTS AND METHODS: In the period between August 2002 and December 2005, patients with infected wounds with signs of gangrenous or necrotic tissue who seemed suited for MDT were enrolled in the present study. In total, 101 patients with 117 ulcers were treated. Most wounds were worst-case scenarios, in which maggot therapy was a treatment of last resort. RESULTS: In total, 72 patients (71%) were classified as ASA III or IV. In total, 78 of 116 wounds (67%) had a successful outcome. These wounds healed completely (n = 60), healed almost completely (n = 12) or were clean at least (n = 6) at last follow-up. These results seem to be in line with those in the literature. All wounds with a traumatic origin (n = 24) healed completely. All wounds with septic arthritis (n = 13), however, failed to heal and led in half of these cases to a major amputation. According to a multivariate analysis, chronic limb ischaemia (odds ratio [OR], 7.5), the depth of the wound (OR, 14.0), and older age (>or= 60 years; OR, 7.3) negatively influenced outcome. Outcome was not influenced by gender, obesity, diabetes mellitus, smoking, ASA-classification, location of the wound, wound size or wound duration. CONCLUSIONS: Some patient characteristics (i. e. gender, obesity, smoking behaviour, presence of diabetes mellitus and ASA-classification at presentation) and some wound characteristics (i. e. location of the wound, wound duration and size) do not seem to contra-indicate eligibility for MDT. However, older patients and patients with chronic limb ischaemia or deep wounds are less likely to benefit from MDT. Septic arthritis does not seem to be a good indication for MDT.

Skin grafting of a chronic leg ulcer with combined Versajet-V.A.C. therapy.

A new method for surgical wound debridement is the Versajet hydrosurgery technique. This technique uses a high velocity jet of sterile saline with a speed up to 1,078 km/h (670 miles/h). By using the Venturi effect (fluid speeds up in a restriction, reducing its pressure and producing a partial vacuum), a simultaneous vacuum is created across the operating window of the handpiece. The application of this high velocity fluid jet to a chronic wound enables precise debridement without collateral tissue damage. The vacuum-assisted closure (V.A.C.) therapy is used for chronic wounds to induce faster wound healing. This system creates a vacuum-induced negative pressure to a specific wound area resulting in an accelerated formation of granulation tissue in the wound bed. We present a patient who experienced rapid wound healing when both of these techniques were combined to clean the wound. After split-thickness skin grafting, V.A.C. therapy was continued. The result was excellent graft acceptance with complete wound healing. This case is unique in that a combination of both therapies resulted in complete wound healing.

[A new therapeutic approach in trophic defects of the lower extremities]. / Nový lécebný prístup u trofických defektu dolních koncetin.

The authors describe the case of a 60-year-old woman patient with a crural ulcer with a traumatic, arterial, venous and lymphatic aetiology. After three-year unsuccessful treatment by conventional methods and surgery a combination of hyperbaric oxygen therapy and plastic surgery was used. This rational therapeutic approach was very effective and the authors recommend its introduction into routine practice.

Organization and development of a university multidisciplinary wound care clinic.

BACKGROUND: A multidisciplinary wound care clinic was established to diagnose and treat patients with nonhealing ulcers of the lower extremity. METHODS: The clinic was organized under the direction of the departments of vascular surgery and dermatology with support by the departments of plastic surgery, hyperbaric medicine, orthopedic surgery, and podiatry, and a research nurse. RESULTS: In the first 4 years and 3 months, 683 patients were evaluated. One hundred seventy-one patients underwent outpatient testing in the noninvasive vascular laboratory and 30 patients underwent angiography. Causes of the ulcers were venous stasis, 280 patients (41%); diabetic neuropathy, 182 patients (27%); arterial insufficiency, 119 patients (17%); rheumatologic disorders, 38 patients (6%); trauma, 15 patients (2%); and in 49 patients (7%) a variety of other disorders. One hundred seventy-nine operations were performed including 86 operating room debridements, 48 amputations (43 toe, 4 below knee, 1 above knee), 23 arterial bypasses, 1 venous bypass, 14 skin grafts, 2 pedicle flaps, and 5 excisions of tumor. Fifty-six patients with cellulitis were admitted to the hospital for intravenous antibiotics and 12 patients were treated with hyperbaric oxygen therapy. One-hundred thirty-two patients were entered into randomized prospective trials of topical growth factors on Institutional Review Board approved protocols. CONCLUSIONS: We concluded that a multidisciplinary approach to wound care is beneficial to patients with chronic wounds and provides a mechanism for clinical investigation on the healing of problem wounds.