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Arterial leg ulcers are a debilitating sequela of chronic ischemia, and their management, particularly in the octogenarian, is an immense challenge. ALUs are frequently a manifestation of end-stage peripheral arterial disease, and their presence portends a high morbidity and mortality. Management primarily relies on restoration of flow, but in the geriatric population, interventions may carry undue risk and pathologies may not be amenable. Adjunctive therapies that improve quality of life and decrease morbidity and mortality are therefore essential, and understanding their benefits and limitations is crucial in developing a multimodal treatment algorithm of care for the uniquely challenging octogenarian population., Competing Interests: Disclosure A.L. Fierro, M Abeshouse, and T Lagziel have no commercial or financial conflicts of interest to disclose. J C. Lantis II has previously been an investigator for topical oxygen companies and currently serves as a consultant for Smith and Nephew, Organogenesis, Kerecis, and Integra. In addition, he is currently a principal investigator for MediWound, Organogenesis, and Biotissue. No grants nor payments from any company were received in regard to this academic study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cellular and matrix-like products come in many forms. Among them, powdered and micronized formulations have become increasingly available and popular owing to their unique properties and advantages. Powders have increased tissue contact which many believe can enhance granulation tissue formation, they fill irregular and deep cavities, and they can be used in concert with sheet-like products and skin grafts for improved healing. Despite their advantages, powdered products do have certain limitations that hinder their use, including poor insurance coverage and a lack of CPT coding for adequate reimbursement in an outpatient setting, making their use primarily limited to the operating room. Also, most published data on powdered products consists of smaller case studies and case series, with few reports evaluating the efficacy and utility of powdered formulations compared to their sheet-like progenitors. In this manuscript, we organize available powdered matrix products by type of substrate: xenograft, allograft, placental-based, and synthetic, and review the data in support of various products in specific wound types. This review of the supporting literature provides the current body of evidence on the utility of powdered matrices in wounds.

Autologous blood-derived therapies have emerged as a unique and promising treatment option for chronic wounds. From whole blood clots to spun-down clot constituents, these therapies are highly versatile and tend to have a lower cost profile, allow for point-of-service preparation, and inherently carry minimal to no risk of rejection or allergic reaction when compared to many alternative cellular and matrix-like products. Subsequently, a diversity of processing systems, devices, and kits have surfaced on the market for preparing autologous blood-derived products (ABDPs) and many have demonstrated preclinical and clinical efficacy in facilitating chronic wound healing. However, not all ABDPs are created equal, and the lack of standardization among product formulations and cell concentrations as well as varying complexities in preparation protocols has led to unreliable substrate viabilities and overall inconsistent conclusions on efficacy. Additionally, external factors, such as the ease of drawing blood, the health of a patient's blood, and the reimbursement landscape have dissuaded some practitioners from incorporating ABDPs into an algorithm of care for recalcitrant wounds. Here, we attempt to categorize ABDPs into "classes" and examine their efficacy, advantages, and limitations when used as both a primary therapy and an adjunct for treating chronic wounds as well as comment on some potential considerations that may help gear future product development and application.

Background: Chronic lower extremity (LE) wounds frequently require significant interventions to close. The success of any method depends on an adequately prepared wound bed, while factors including wound size, perfusion, contamination, or exposed tissue structures can thwart efforts. We propose a standardized algorithm of care utilizing an acellular dermal matrix, split-thickness skin graft (STSG), and negative pressure wound therapy (NPWT) for the treatment of LE wounds., Methods: This was a single-center, retrospective cohort study examining patients who underwent LE wound debridement, placement of fetal bovine dermis (FBD), and STSG between 2016 and 2022. The primary outcome was wound closure, while secondary outcomes were wound infection and amputation-free survival., Results: Twenty patients (mean age 59 years, M:F 12:8)-including 24 LE venous ulcers (29.4%), amputation sites (29.4%), diabetic foot ulcers (25.0%), and atypical wounds (16.7%) with an average area of 39.15 cm 2 -underwent debridement and FBD placement followed by STSG a median of 61 days thereafter. Of these patients, 83.3% received NPWT after FBD and STSG with 86% closure. There was successful engraftment in 92% of wounds whose FBD placement was within 2 months of STSG. Of wounds that had <50% engraftment, 75% had a STSG placed over 2 months after FBD placement. Of those patients with post-STSG infection, 75% had the graft placed >2 months after FBD placement, one of which required proximal amputation., Conclusions: By following a treatment plan including debridement with treatment of infection, application of FBD with placement of STSG within 2 months thereafter, and reinforcing NPWT, chronic wounds will have an increased rate of successful reepithelialization. Many cases experienced delays from FBD engraftment until STSG application due to schedule and insurance impediments, which led to less favorable outcomes. Therefore, a protocol that involves scheduling the placement of STSG 4 weeks after successful engraftment of FBD has been adopted., (© 2023 HMP Global. All Rights Reserved. Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of ePlasty or HMP Global, their employees, and affiliates.)

Since the late 1990s, a growing number of "skin substitutes" have become available to practitioners seeking to heal large surface wounds. These extracellular matrices were originally from xenograft sources, and then from very highly engineered living human cellular tissues. More recently, they consist of biosynthetic materials that are combinations of silicone, collagen and chondroitin. The list of xenograft materials as well as minimally manipulated human tissues, such as human skin-, amniotic- and placental-based products, has grown exponentially. Over the last 5 years, truly synthetic materials have become part of the armamentarium available for closing large wounds. The first notable product in this category was made of polyurethane. These purely synthetic products do not have any components made of naturally occurring structures, such as collagen. In this review, we seek to create a rudimentary framework in which to understand these synthetic products and to review the current literature that supports the use of these novel yet intriguing therapies.

Soft tissue reinforcement focuses on medical grafts that are designed to support and regenerate soft tissue under or near suture lines. Soft tissue is defined as areas of similarly specialized cells that function to connect, support, and surround other structures and organs of the body. These tissues include skin, subcutaneous tissue, fascia, ligaments, tendons, fibrous tissues, fat, synovial membranes, and muscle. Most of the implantable devices used for this purpose are made of collagen, the most abundant protein in mammals and a key component of the extracellular matrix of soft tissues that allows for tissue repair. For suture line reinforcement, exogenous collagen from various sources is implanted under or in continuity with the suture line to allow for increased strength and better healing. First introduced in the field of breast reconstruction, this practice is now also used in hernia repair, dural repair, vaginal slings, amputation reinforcement, tendon repair reinforcement, and even dental soft tissue regeneration.

In modern practice, xenografts play a crucial role in wound management due to their regenerative properties. Of the various xenografts currently available on the market, acellular fish skin (AFS) grafts have emerged as a more effective alternative to existing xenografts and other standard of care (SOC) treatments for wound healing. Since AFS grafts require minimal processing, they maintain their structural integrity and natural properties, including an abundance of Omega-3 fatty acids, which is a distinctive, pro-regenerative feature. AFS grafts are also unique in that they are not derived from mammalian tissue, so there is no risk of viral transmission and no cultural or religious barriers to use. AFS grafts have been shown to be more cost-effective in the treatment of diabetic foot ulcers (DFUs) and result in a higher percentage of healed wounds, fewer amputations, and better patient quality of life. Several studies and case reports have highlighted the versatility of AFS in not only acute and chronic wound healing, but also for burn wound skin regeneration. Additionally, AFS may have promise as an implantable biologic matrix for suture line reinforcement in hernia repairs or breast and dura reconstruction.

The ability to grow skin has long been a topic of study and therapeutic interest. Currently, the main ways of doing this are 1) by placing tissue-expansion devices in the subcutaneous space and expanding skin over time, which can then be moved to cover contiguous structures, and 2) via processes that require relatively long (30 days) incubation periods to grow the patient's autogenous skin into laminar sheets. Over the past five years, there have been significant developments in the ability to expand skin cells, either at the bedside or in the laboratory, but much more rapidly than with previous methods. We explore and discuss the current skin cell-expansion techniques, focusing on point-of-care therapeutic interventions that can be used in the burn population as well as the chronic wound population, hair follicle stem-cell incubation techniques and studies supporting this therapy, as well as micro bullae grafting, and morcellated skin cell therapy. The current data supporting these therapeutic interventions and their current direction are outlined in detail.

Preparation of the wound bed is a key step in the use of cell- and tissue-based therapy (CTP). In particular, good pre-application debridement is an essential component of CTP. However, there are many situations in which the wound bed is not adequately debrided, including trauma, burn, and in cases of chronic wounds with significant biofilm. In the setting of inadequate wound bed preparation, the use of a CTP that has either added or intrinsic antimicrobial properties is attractive. Some CTPs include added antimicrobial agents such as PHMB or silver, while others have intrinsic antimicrobial components, such as Omega 3 fatty acids. In addition, some wound-covering dressings are completely synthetic, and therefore simply do not become infected. A full understanding of the basic science and clinical data supporting the use of these therapies is important for the advanced wound care practitioner.

Over the past three decades, there has been a growing interest in the use of oxygen therapy to promote wound healing. Although the most commonly recognized oxygen therapy for the treatment of chronic wounds is hyperbaric oxygen therapy, topical oxygen therapy has a greater level of evidence supporting its use in chronic wound care. Still, it is imperative that these two treatment modalities be recognized not merely as competitors, but as distinct therapeutic entities. Through personal experience and a thorough literature review, we investigated the use of topical oxygen therapy in the management of chronic wounds. The benefits of using topical oxygen therapy have been demonstrated in patients with diabetic foot ulcers, ischemic ulcers, post-revascularization ulcers, and pressure ulcers. There are several topical oxygen devices currently on the market that are versatile, relatively low-risk, and generally well-tolerated by patients. While these devices have been used in the treatment of chronic wounds at different locations and of different etiologies, other uses of these devices are still being investigated. Topical oxygen therapy is yet another tool in our arsenal to be used in treating difficult to heal chronic wounds and could potentially be used more readily.

Intermittent pneumatic compression devices (IPC) are often used as noninvasive adjuncts in patients with lymphedema, and more recently with venous stasis disease, to promote flow and reduce the adverse effects of interstitial edema associated with both disorders. We will be focusing on lower extremity wounds associated with venous and/or lymphatic disease, the combination often referred to as "lymphophlebitic" disease, and the treatment effect of IPC on this disease process and its sequelae. The function and purpose of pneumatic compression is closely examined along with a variety of pneumatic compression devices that currently exist in the market. A thorough review of the literature was conducted to evaluate the utility of intermittent pneumatic compression in the treatment of lower extremity venous stasis ulcers. Additionally, the author describes personal experience with the use of pneumatic compression on 10 patients with venous stasis ulcers at a single center. There is significant data supporting the use of IPC in patients with lymphophlebitic disease. Overall, ideal patient selection may be crucial. Previous data has shown that patients with high body mass index (>33 kg/m2) and poor functional status (walking less than 200m a day) are related to poor ulcer healing. Therefore, a study that looks primarily at this group (as our small quality assurance [QA] project did) may show increased benefit in this population. It is clear that IPC is of benefit to some patient cohorts with lymphophlebitic disease. This advanced therapy would help patients who have failure of their calf muscle pump and an inability to improve it through other means. However, it is only part of an algorithm that includes: direct wound bed management, moisture control, possible primary venous disease intervention, physical therapy, weight loss, and improved nutrition.

In vascular surgery, bypass procedures are standard treatments for many arterial and venous diseases. The choice of conduit for the bypass operation is fundamental in planning for the appropriate intervention for each individual patient. Although an autogenous conduit is superior, this option is not available in many patients, and prosthetic grafts have been the preferred conduit in a variety of clinical situations. However, since prosthetic graft infections are seen in all realms of vascular surgery, from arteriovenous access to aortic graft infections and lower-extremity bypass infections, cryopreserved arterial and venous allografts, which are relatively resistant to infection, have become the conduit of choice. This discussion will focus on the clinical applications of cryopreserved allografts in vascular surgery, specifically lower-extremity peripheral bypass, aortic disease, and dialysis access.

There is growing evidence on an interconnection between the venous and lymphatic systems in venous leg ulceration, and the possible effects of prolonged oedema and lymphatic impairment in delayed wound healing. Compression therapy is a widely accepted treatment for venous and lymphatic disorders, as it decreases recurrence rates and prolongs the interval between recurrences. Compression bandages improve venous return, increase the volume and rate of venous flow, reduce oedema and stimulate anti-inflammatory processes. The pressure at the interface (IP) of the bandage and the skin is related to the elastic recoil of the product used and its resistance to expansion. The pressure difference between the IP in the supine and standing positions is called the static stiffness index (SSI). Elastic materials provide little resistance to muscle expansion during physical activity, resulting in small pressure differences between resting and activity, with an SSI <10mmHg. Stiff, inelastic materials with a stretch of <100% resist the increase of muscle volume during physical activity, producing higher peak pressures, an SSI of >10mmHg and a greater haemodynamic benefit than elastic systems. UrgoK2 is a novel dual-layer high-compression system consisting of an inelastic (short stretch) and elastic (long stretch) bandage, resulting in sustained tolerable resting pressure and elevated working pressures over extended wear times. It is indicated for the treatment of active venous leg ulcers and the reduction of chronic venous oedema. Each bandage layer has a visual aid to enable application at the correct pressure level. Published European studies have assessed this compression system, exploring its consistency of application, tolerability and efficacy. This article presents the first reports of health professionals' clinical experience of using the compression system in the US, where it has been recently launched. Initial feedback is promising.

An open label, multicenter 16-week trial of cryopreserved human umbilical cord (TTAX01) was previously undertaken in 32 subjects presenting with a Wagner grade 3 or 4 diabetic foot ulcer, with 16 (50%) of these having confirmed closure following a median of one product application (previous study). All but two subjects (30/32; 94%) consented to participate in this follow-up study to 1-year postexposure. No restrictions were placed on treatments for open wounds. At 8-week intervals, subjects were evaluated for adverse events (AEs) and wound status (open or closed). Average time from initial exposure to end of follow-up was 378 days (range 343-433), with 29 of 30 (97%) subjects completing a full year. AEs were all typical for the population under study, and none were attributed to prior exposure to TTAX01. One previously healed wound re-opened, one previously unconfirmed closed wound remained healed, and nine new wound closures occurred, giving 25 of 29 (86.2%) healed in the ITT population. Three of the new closures followed the use of various tissue-based products. Three subjects whose wounds were healed required subsequent minor amputations due to osteomyelitis, one of which progressed to a major amputation (1/29; 3.4%). One additional subject underwent two minor amputations prior to healing. Overall, the study found TTAX01 to be safe in long-term follow-up and associated with both a low rate of major amputation and a higher than expected rates of healing., (© 2020 The Authors. Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of by the Wound Healing Society.)

Chronic, nonhealing wounds consume a great deal of healthcare resources and are a major public health problem, associated with high morbidity and significant economic costs. Skin grafts are commonly used to facilitate wound closure. The grafts can come from the patient's own skin (autograft), a human donor (allograft), or from a different species (xenograft). A fish skin xenograft from cold-water fish (Atlantic cod, Gadus morhua) is a relatively recent option that shows promising preclinical and clinical results in wound healing. Chronic wounds vary greatly in etiology and nature, requiring large cohorts for effective comparison between therapeutic alternatives. In this study, we attempted to imitate the status of a freshly debrided chronic wound by creating acute full-thickness wounds, 4 mm in diameter, on healthy volunteers to compare two materials frequently used to treat chronic wounds: fish skin and dHACM. The purpose is to give an indication of the efficacy of the two therapeutic alternatives in the treatment of chronic wounds in a simple, standardized, randomized, controlled, double-blind study. All volunteers were given two identical punch biopsy wounds, one of which was treated with a fish skin graft and the other with dehydrated human amnion/chorion membrane allograft (dHACM). In the study, 170 wounds were treated (85 wounds per group). The primary endpoint was defined as time to heal (full epithelialization) by blinded assessment at days 14, 18, 21, 25, and 28. The superiority hypothesis was that the fish skin grafts would heal the wounds faster than the dHACM. To evaluate the superiority hypothesis, a mixed Cox proportional hazard model was used. Wounds treated with fish skin healed significantly faster (hazard ratio 2.37; 95% confidence interval: (1.75-3.22; p = 0.0014) compared with wounds treated with dHACM. The results show that acute biopsy wounds treated with fish skin grafts heal faster than wounds treated with dHACM., (© 2019 The Authors. Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of by the Wound Healing Society.)

Clinical trials of potential new therapies for diabetic foot ulcers rarely enroll patients whose wounds extend to muscle, fascia, or bone with clinical and radiographic evidence of underlying osteomyelitis. An open-label, multicenter trial of cryopreserved human umbilical cord (TTAX01) was undertaken in 32 subjects presenting with such complex wounds with a mean duration of 6.1 ± 9.0 (range: 0.2-47.1) months and wound area at screening of 3.8 ± 2.9 (range: 1.0-9.6) cm 2 . Aggressive surgical debridement at baseline resulted in 17 minor amputations and an increase in mean wound area to 7.4 ± 5.8 (range: 1.1-28.6) cm 2 . All subjects were placed on systemic antibiotics for at least 6 weeks in conjunction with baseline application of TTAX01. Repeat applications were made at no less than 4-week intervals over the 16-week trial. Initial closure occurred in 18 of 32 (56%) wounds, with 16 (50%) of these having confirmed closure in 16 weeks with a median of one-product application. Cases with biopsy confirmed osteomyelitis (n = 20) showed initial closure in 12 (60%) wounds and confirmed closure in 10 (50%) wounds. Four of the five ulcers presenting as recurrences experienced confirmed closure. Mean overall time to healing was 12.8 ± 4.3 weeks. Mean wound area reduction from baseline was 91% for all wounds. Of the 16 wounds without confirmed closure during the 16-week treatment period, five (31.3%) achieved 99-100% wound area reduction by their final visit. The product was well tolerated. Two minor amputations occurred during the study period due to recurrent or persistent osteomyelitis; however, there were no major amputations., (© 2019 The Authors. Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of by the Wound Healing Society.)

At least 15% of patients with critical limb ischemia are not candidates for standard revascularization. In this day and age, with new techniques-including retrograde access to the foot-and numerous angioplasty and atherectomy techniques available, the critical limb ischemia patient can still be faced without options. Distal bypass surgery may still remain the gold standard, and likely permits the patient to have the best options for healing, but carries significant comorbidities after undergoing the procedure. There are patients who do not have targets of interest in their foot for arterial revascularization and there are patients who have very poor conduit or are very poor candidates due to their medical comorbidities. Guidelines as to who should and should not undergo surgery-or even percutaneous revascularization-are starting to become more widely accepted. We are starting to see the tide change and there is interest in this cohort of patients. There are patients with no distal target that may benefit from an arteriovenous bypass, which is regaining popularity and can be done completely endovascularly. The patient that may be a very poor candidate for intervention may benefit from arterial counterpulsation therapy and/or topical oxygen therapy (which are commercially available). They may also benefit from placental stem cell injection, which is undergoing Phase II trial assessment. We will review the current literature as it surrounds these potential therapeutic interventions for patients with significant lower extremity ischemia who do not have standard revascularization options.

Diabetes Mellitus is a serious systemic illness that has an epidemic-like increasing prevalence in the United States, as well as the rest of the world. With the increasing number of people with diabetes comes the higher incidence of diabetes-related complications. One of these known complications, diabetic foot ulcers (DFU), has an estimated lifetime incidence of 15% in diabetics. Having a DFU increases the risk of infection, amputation, and even death, which is why prompt treatment and surveillance of such ulcers is imperative. Multiple organizations and journals have recently published best practices to heal and close DFU. Despite these guidelines, it is estimated that only 50% of all diabetic foot ulcers close within one year in the United States. To further confuse this picture, many trials include postoperative wounds that behave in a very different way than chronic wounds. The management of diabetic ulcers requires an understanding of not only the pathophysiology along with a multi-modal approach involving local wound care, pressure prevention, infection control, and, in some, revascularization, but also how care is delivered in the United States presently. In this review, we hope to elucidate the current knowledge and modalities used in ulcer management and to focus on key areas and best practices to inform the clinician, both in what they should do and what they can do.

Objective: The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials., Methods: Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm 2 to 12 cm 2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm 2 and ≤36 cm 2 with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure., Results: This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < .10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < .05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]), wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline (0.907 [0.887-0.927]), and shorter wound duration at baseline (0.971 [0.955-0.987])., Conclusions: Factors associated with VLU lesions including location, area, and duration were important predictors of healing. Women were more likely than men to achieve wound closure. Factors including body mass index, the presence of diabetes mellitus, and higher concentrations of glycated hemoglobin were not significant independent predictors of wound closure in this analysis., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Wound care dressings have evolved over time, from bandaging to the development of occlusive dressings to negative pressure wound therapy. A novel therapeutic delivery system dressing has been cleared by the United States Food and Drug Administration. This semi occlusive wound dressing has been developed to provide local, continuous delivery of aqueous topical agents, such as therapeutics (anesthetics, antiseptics, antibiotics, steroids, topical beta-blockers, immune modulatory agents, growth factors, and fibrinolytic agents, among others), at a rate of about ¾ mL per day, thus maintaining a hydrated environment and providing topical treatment. This type of system may be beneficial in situations where systemic therapies cannot be used, wounds are small and few, wounds may need frequent application of medication or moisture, or low and steady delivery of medications is needed., Objective: The authors assessed a delivery system dressing with different types of liquid medications for the management of hard-to-heal, chronic lower extremity wounds., Materials and Methods: Patients aged ≥ 18 and ≤ 90 years with stalled chronic wounds > 30 days' duration were selected for the use of a topical delivery system, which consists of a semi occlusive wound dressing and fluid delivery unit that can provide local application of small therapeutic quantities of medication directly to the wound., Results: Several successful cases with the use of this device are presented in which pain relief, enhancement of epithelial migration, inflammation reduction, bacterial control, and wound size reduction were achieved., Conclusions: This delivery system dressing is an effective and safe treatment option for wounds. Advantages include reduced potential of systemic side effects, flexibility in what can be delivered, constant rate of medication delivery, and convenience.

In 2012 we reported promising results from a phase 2 clinical trial of HP802-247, a novel spray-applied investigational treatment for chronic venous leg ulcers consisting of human, allogeneic fibroblasts and keratinocytes. We now describe phase 3 clinical testing of HP802-247, its failure to detect efficacy, and subsequent investigation into the root causes of the failure. Two randomized, controlled trials enrolled a total of 673 adult outpatients at 96 centers in North America and Europe. The primary endpoint was the proportion of ulcers with confirmed closure at the end of 12 weeks of treatment. An investigation into the root cause for the failure of HP802-247 to show efficacy in these two phase 3 trials was initiated immediately following the initial review of the North American trial results. Four hundred twenty-one patients were enrolled in the North American (HP802-247, 211; Vehicle 210) and 252 in the European (HP802-247, 131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12 was observed between treatment groups for either the North American (HP802-247, 61.1%; Vehicle 60.0%; p = 0.5896) or the European (HP802-247, 47.0%; Vehicle 50.0%; p = 0.5348) trials. Thorough investigation found no likelihood that design or execution of the trials contributed to the failure. Variability over time during the trials in the clinical response implicated the quality of the cells comprising HP802-247. Concordance between the two separate, randomized, controlled trials with distinct, nonoverlapping investigative sites and independent monitoring teams renders the possibility of a Type II error vanishingly small and provides strong credibility for the unexpected lack of efficacy observed. The most likely causative factors for the efficacy failure in phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to batch to batch variability due to the age of the cell banks., (© 2016 by the Wound Healing Society.)

Persistence of skin wounds due to underlying disease, bacterial contamination, and/or repeated trauma, causes a chronic condition where a functional extracellular matrix (ECM) cannot be established and the normal wound-healing cascade is unable to progress. These open chronic wounds leave the body susceptible to infection and present a major healthcare problem. To this end, a broad range of biologic ECM scaffolds have been developed that can provide other therapeutic options aside from traditional wound care approaches. These tissue engineered ECM scaffolds aim to facilitate the restoration of functional skin-like tissue by altering the chronic wound environment and facilitating cellular attachment, proliferation, and differentiation. This discussion will center on reviewing current ECM scaffolds and highlighting their properties and mechanism of action with respect to the clinical application in chronic, non-healing wounds.

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.

Objective: The preponderance of existing literature for the treatment of Paget-Schroetter syndrome (PSS) advocates clot lysis followed by thoracic outlet decompression (TOD). We postulate that long-term anticoagulation has equal outcomes to more invasive and costly surgical intervention, and review our experience with non-operative management of PSS., Methods: A retrospective review was conducted, examining patients between 1994-2014. Forty patients were identified with PSS, and 27 of these patients had sufficient follow-up for this analysis. Charts were reviewed for details of clinical presentation, disease course, interventions, duration of oral anticoagulation, ultrasound reports, and symptoms at long-term follow-up., Results: With a mean follow-up of 54.3 months, 23/27 patients (85%) were asymptomatic after non-operative therapy. In this cohort, 16/27 patients (59%) underwent catheter-directed thrombolysis. Average treatment course with oral anticoagulation was 8.6 months. Four patients (15%) remained symptomatic at follow-up. Two patients (7%) underwent thoracic outlet decompression at another institution, with good results. At least partial recanalization of vessels was documented in 25/27 patients (93%), although recanalization did not correlate with symptoms at long-term follow-up., Conclusions: Based upon equivalent functional results, non-operative management appears to offer similar outcomes for some patients with PSS. We propose a patient-tailored approach to the treatment of PSS, in which patients presenting acutely undergo catheter-directed thrombolysis, followed by a 6-12 month course of oral anticoagulation. Persistent symptoms, recurrent disease, lengthy duration of symptoms prior to diagnosis, and identifiable structural abnormalities may be factors predictive of poor outcomes after non-operative intervention.

Difficult-to-heal and chronic wounds affect tens of millions of people worldwide. In the U.S. alone, the direct cost for their treatment exceeds $25 billion. Yet despite advances in wound research and treatment that have markedly improved patient care, wound healing is often delayed for weeks or months. For venous and diabetic ulcers, complete wound closure is achieved in as few as 25%-50% of chronic or hard-to-heal wounds. Wound bed preparation and the consistent application of appropriate and effective debridement techniques are recommended for the optimized treatment of chronic wounds. The TIME paradigm (Tissue, Inflammation/infection, Moisture balance and Edge of wound) provides a model to remove barriers to healing and optimize the healing process. While we often think of debridement as an episodic event that occurs in specific care giver/patient interface. There is the possibility of a maintenance debridement in which the chronic application of a medication can assist in both the macroscopic and microscopic debridement of a wound. We review the various debridement therapies available to clinicians in the United States, and explore the characteristics and capabilities of clostridial collagenase ointment (CCO), a type of enzymatic debridement, that potentially allows for epithelialization while debriding. It appears that in the case of CCO it may exert this influences by removal of the necrotic plug while promoting granulation and sustaining epithelialization. It is also easily combined with other methods of debridement, is selective to necrotic tissue, and has been safely used in various populations. We review the body of evidence has indicated that this concept of maintenance debridement, especially when combined episodic debridement may add a cost an efficacious, safe and cost-effective choice for debridement of cutaneous ulcers and burn wounds and it will likely play an expanding role in all phases of wound bed preparation.

Infrapopliteal arterial disease is a challenging problem to treat. A shift toward an endovascular treatment approach over surgical bypass has occurred over recent years. Although current standard percutaneous transluminal balloon and bare metal stents are employed, their durability and outcomes are questionable. A number of endovascular advancements in the treatment of infrapopliteal (IP) arterial disease have recently been made. We review the recent literature for new atherectomy, stent, and balloon technologies.

Objective: Massive (≥100 cm(2)) venous leg ulcers (VLUs) demonstrate very low closure rates with standard compression therapy and are costly to manage. Negative-pressure wound therapy (NPWT), followed by a split-thickness skin graft (STSG), can be a cost-effective alternative to this standard care. We performed a cost analysis of these two treatments., Methods: A retrospective review was performed of 10 ulcers treated with surgical debridement, 7 days of inpatient NPWT with topical antiseptic instillation (NPWTi), and STSG, with 4 additional days of inpatient NPWT bolster over the graft. Independent medical cost estimators were used to compare the cost of this treatment protocol with standard outpatient compression therapy., Results: The average length of time ulcers were present before patients entered the study was 38 months (range, 3-120 months). Eight of 10 patients had complete VLU closure by 6 months after NPWTi with STSG. The 6-month costs of the proposed treatment protocol and standard twice-weekly compression therapy were estimated to be $27,000 and $28,000, respectively., Conclusions: NPWTi with STSG treatment is more effective for closure of massive VLUs at 6 months than that reported for standard compression therapy. Further, the cost of the proposed treatment protocol is comparable with standard compression therapy., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: While much has been written about multiple methods of neuromonitoring during carotid endarterectomy (CEA), there has been relatively little discussion of the use of triple monitoring via somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) in conjunction with electroencephalography (EEG). Our objective was to evaluate the rate of detection and prevention of neurologic events by multinerve SEP, MEP, and EEG in patients undergoing CEA while under general anesthesia., Methods: A prospective study of 181 consecutive patients undergoing CEA between June 2005 and September 2010 was reviewed. Intraoperative changes, including a 50% reduction in the amplitude of SEP waveforms, loss of MEP, and/or a 50% change in EEG frequency were noted as indications for shunting. This was correlated with the actual use of intraoperative shunting and postoperative neurologic sequelae at both 24 hours and 30 days. Median and tibial nerve SEPs and MEPs were also correlated., Results: Eleven patients (6%) experienced intraoperative monitoring changes (SEP: 11/11; MEP: 6/11). Five of 11 patients with MEP/SEP changes underwent shunting, while the other 6 had normalization with the elevation of their blood pressure. Of the 11 patients that had neurophysiologic changes, 54% (6/11) were patients with symptomatic disease. No patients had significant EEG changes. The total shunt rate was 2.7% (5/181). No postoperative neurologic sequelae were noted., Conclusion: The ratio of shunting at 2.7% is equal to the lowest rates reported in the awake patient literature. Interestingly, the predicted synergy of multimodality monitoring cannot be directly attributed to an increased specificity resulting from the addition of SEP and MEP to EEG, because no patients had EEG changes. In addition, in today's cost-conscious world of health care, our results do not justify implementing this particular technique of neuromonitoring across the board-but it is apparent that the combination of these 3 modalities is both safe and effective with potential applications in symptomatic patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: An overabundance of bacteria in the chronic wound plays a significant role in the decreased ability for primary closure. One means of decreasing the bioburden in a wound is to operatively debride the wound for wound bed optimization prior to application of other therapy, such as Negative Pressure Wound Therapy (NPWT). We undertook a prospective pilot study to assess the efficacy of wound bed preparation for a standard algorithm (sharp surgical debridement followed by NPWT) versus one employing sharp surgical debridement followed by Negative Pressure Wound Therapy with Instillation (NPWTi)., Methods: Thirteen patients, corresponding to 16 chronic lower leg and foot wounds were taken to the operating room for debridement. The patients were sequentially enrolled in 2 treatment groups: the first receiving treatment with operative debridement followed by 1 week of NPWT with the instillation of quarter strength bleach solution; the other receiving a standard algorithm consisting of operative debridement and 1 week of NPWT. Quantitative cultures were taken pre-operatively after sterile preparation and draping of the wound site (POD # 0, pre-op), post-operatively once debridement was completed (POD # 0, post-op), and on post-operative day 7 after operative debridement (POD # 7, post-op)., Results: After operative debridement (post-operative day 0) there was a mean of 3 (±1) types of bacteria per wound. The mean CFU/gram tissue culture was statistically greater - 3.7 × 10(6) (±4 × 10(6)) in the NPWTi group, while in the standard group (NPWT) the mean was 1.8 × 10(6) (±2.36 × 10(6)) CFU/gram tissue culture (p = 0.016); at the end of therapy there was no statistical difference between the two groups (p = 0.44). Wounds treated with NPWTi had a mean of 2.6 × 10(5) (±3 × 10(5)) CFU/gram of tissue culture while wounds treated with NPWT had a mean of 2.79 × 10(6) (±3.18 × 10(6)) CFU/gram of tissue culture (p = 0.43). The mean absolute reduction in bacteria for the NPWTi group was 10.6 × 10(6) bacteria per gram of tissue while there was a mean absolute increase in bacteria for the NPWT group of 28.7 × 10(6) bacteria per gram of tissue, therefore there was a statistically significant reduction in the absolute bioburden in those wounds treated with NPWTi (p = 0.016)., Conclusion: It has long been realized that NPWT does not make its greatest impact by bioburden reduction. Other work has demonstrated that debridement alone does not reduce wound bioburden by more than 1 Log. Wounds treated with NPWTi (in this case with quarter strength bleach instillation solution) had a statistically significant reduction in bioburden, while wounds treated with NPWT had an increase in bioburden over the 7 days.

Objective: To examine patient and wound variables presumed to influence healing outcomes in the context of therapeutic trials for chronic venous leg ulcers., Methods: This double-blind, vehicle-controlled study was conducted with randomized assignment to one of four cell therapy dose groups (n = 46, 43, 44, 45) or vehicle control (n = 50). A 2-week run-in period was used to exclude rapid healers and those with infection or uncontrolled edema. This was a multicenter (ambulatory, private, hospital-based and university-based practices, and wound care centers in North America) study. Adults ≥ 18 years old with chronic venous insufficiency associated with an uninfected venous leg ulcer (2-12 cm(2) area, 6-104 weeks' duration) were included in the study. Excluded were pregnant or lactating women, wounds with exposed muscle, tendon or bone, patients unable to tolerate compression bandages, or patients who had exclusionary medical conditions or exposure to certain products. Exclusion during run-in included patients with infection, uncontrolled severe edema or with healing rates ≥ 0.349 cm/2 wk. Screen fail rate was 37% (134/362), and the withdrawal rate was~10% (23 of 228). Growth-arrested neonatal dermal fibroblasts and keratinocytes were delivered via pump spray in a fibrin sealant-based matrix, plus a foam dressing and four-layer compression bandaging. Treatment continued for 12 weeks or until healed, whichever occurred first. Patient demographic and wound-related variables were evaluated for influence on complete wound healing in all patients, as well as the subsets of treated and control patients., Results: Wound duration (P = .004) and the presence of specific quantities of certain bacterial species (P < .001) affected healing in the vehicle group, while healing in the cell-treated groups was influenced by wound duration (P = .012), wound area (P = .026), wound location (P = .011), and specific quantities of certain bacterial species (P = .002). Age, sex, race, diabetes, HbA1C, peripheral neuropathy, and serum prealbumin did not significantly affect healing. Body mass index was positively associated with healing in cell-treated patients., Conclusions: Wound duration is a quantifiable surrogate for one or more undefined variables that can have a profound negative effect on venous leg ulcer healing. Although cell therapy overcame barriers to healing, the only specific barrier identified was the presence of certain bacterial species. Interventional trials of potentially effective new therapies can be most informative when patients with suspected barriers to healing are included. The specific measurement of candidate barriers such as microbial pathogens, wound inflammatory state, and fibroblast function should be considered in future randomized trials to improve our understanding of the basis for chronicity., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Few studies regarding wound treatment with topical antimicrobials evaluate change in the bacterial bioburden of the wound with treatment. This study sought out to determine the in vivo effect of cadexomer iodine antibacterial dressing on diabetic foot ulcers (DFUs) that were infected or achieved a critical level of colonisation, looking specifically at wound progression in relation to bioburden. Fifteen patients corresponding to 16 total DFUs met criteria of displaying clinical signs of infection or critical colonisation and were suitable for a topical antibacterial dressing. They underwent weekly treatment for 6 weeks. Cultures were taken at week 0, 3 and 6 as appropriate. At week 6 median log10 bacterial count reduction of 1.0 was observed from baseline (p = 0·025). At week 3- a median log10 bacterial count reduction of 0.3 was observed from baseline (p = 0·049). Over the study period there was a 53.6% median reduction of the wound surface area. There were no patients that completely healed their ulcer over the 6 week study period. There was a statistically significant median reduction in the bacterial load over the 6 week period (p = 0·025) as well as 3 weeks (p = 0·049). This was accompanied by a median reduction of 53.6% in ulcer surface area and 50% in ulcer depth from baseline to final., (© 2012 The Authors. International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.)

Objective: There are numerous dressings designed to manage the overabundance of matrix metalloproteinases, while also addressing the excessive bioburden found in chronic wounds. The authors compared the efficacy of 2 such dressings: a sodium carboxymethylcellulose/1.2% ionic silver (CMC), which theoretically reduces bacteria by providing silver ions, versus a bovine native collagen (BDC)/ionic silver dressing, which also delivers silver ions in an aqueous environment. Both dressings theoretically modulate the wound bed; CMC through moist wound care and fibrin ingrowth and BDC through matrix metalloproteinase balancing., Methods: A prospective protocol was undertaken using patients as their own controls. Ten patients with bilateral venous stasis or diabetic foot ulcers were selected. One limb was randomized to treatment by either CMC or BDC, whereas the contralateral wound was treated with the other dressing. Biopsies for quantitative cultures were taken at weeks 1 and 4. Wound area was assessed at the weekly visits., Results: The BDC wounds started with 1.0 × 10 (±1.2 × 10) bacteria, and the CMC wounds started with 1.4 × 10 (±1.3 × 10) bacteria. Over the 4-week period, the bacteria in the 3-ppm (parts per million) silver-treated wound increased 1.53 × 10, whereas in the 21-ppm silver-treated wound, the bacteria increased 1.42 × 10. The rates of closure for CMC-treated wounds was 0.79 ± 0.735 cm/wk and for BDC-treated wounds was 1.38 ± 1.44 cm/wk. Only 1 wound treated with either dressing exhibited a decrease in bacteria., Conclusion: Both CMC and BDC silver dressings appeared to have statistically similar efficacy regarding the rate of wound healing and little impact on the actual bioburden in chronic lower-extremity wounds. Interestingly, there was no correlation in the size of the wound and any effect on bioburden. Although the BDC dressing showed a higher absolute rate of wound closure, neither technology demonstrated a statistically significant difference in wound closure rate when corrected for initial wound size.

In many series of diabetic foot ulcer care, heel ulcers greater than 4 cm across have been identified as an independent predictor of limb loss. Therefore, we set out to pursue the most aggressive limb salvage algorithm in patients with heel ulcers greater than 4 cm in diameter. Over 5 years, we identified 21 patients, 39-84 years of age, all with diabetes mellitus, with heel ulcers greater than 4 cm in diameter and had magnetic resonance imaging or bone scan evidence of osteomyelitis. Seven of the 21 patients had end-stage renal disease defined as being haemodialysis dependent. All patients had ankle brachial indices <0·4 or monophasic pulse volume recordings. All patients underwent distal bypass surgery with vein. After adequate perfusion was obtained, all patients underwent partial calcanectomy and intra-operative negative pressure wound therapy (NPWT) placement. This was followed by treatment with recombinant platelet-derived growth factor (PDGF). One patient underwent amputation during the healing process secondary to ongoing sepsis. Twenty of 21 patients healed acutely (within 6 months). Three of 20 patients went on to subsequent below knee amputation within 12 months of healing primarily. At 2 years, 12 of 21 (57%) were ambulating independently, 1 of 21 was dead, 4 of 21 had undergone amputation, 4 (19%) had limbs that were intact but were not ambulating. A total limb salvage rate of 76% at 2 years mirrored the secondary patency rates, with 100% follow up. Heel ulcers require multimodality therapy if they are going to have any chance to heal. We believe the algorithm presented allows for the required revascularisation and a modulation of the heel ulcer microenvironment by augmenting the microcirculation through NPWT, and improving the proliferative capacity with PDGF., (© 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.)

Objective: To determine the in vivo effect of a sustained-release silver sulphadiazine powder foam dressing on the bacterial burden of venous leg ulcers (VLUs), with a view to correlating the wound closure rate with the degree of bioburden and to assess other markers of its progression towards healing., Method: Patients attending a tertiary care wound practice were screened for a VLU bacterial count of >105 colony forming units (cfu/g) per gram of tissue. Patients were treated with the above topical dressing plus multilayer compression bandaging for 12 weeks. Quantitative cultures were taken at weeks 0, 2, 4 and 8. Wounds were assessed at each weekly visit using photography and planimetry., Results: Twenty-four of the 33 screened patients met the inclusion criteria. The average baseline wound size was 12.3 cm². At week 8, the bioburden had reduced to < 105 cfu/g in 54.2% of patients, with 41.7% achieving this reduction by week 2. At week 8, the median reduction was 0.7 log¹⁰ (p < 0.001). The median percentage reductions in bioburden were 50.5%, 56.8% and 80.4% at weeks 2, 4 and 8 respectively. Over the study period, 79.2% of the patients had > 75% wound area reduction and 45.8% achieved ulcer closure in a median of 80.5 days., Conclusion: Although the wound size and bacterial counts reduced significantly, there was no statistical correlation between the two. Nevertheless, the in vivo data show that this active antimicrobial dressing was associated with a very high healing rate in these hard-to-heal wounds.

Background: Open venous ulcers in patients with combined arterial and venous insufficiency are notoriously hard to treat. Patients with an ankle-brachial index (ABI) of 0.5-0.8 have been shown to heal poorly. Because adequate compression therapy is contraindicated in patients with an ABI of <0.7, we decided to undertake an aggressive approach of percutaneous revascularization for these patients., Methods: A total of 27 patients with clinical and duplex scan evidence of chronic venous insufficiency, active leg ulcers, and impaired arterial perfusion (ABI: <0.7) were treated using a protocol that required performing percutaneous revascularization before ambulatory compression therapy. The patients were followed at 2-week intervals (average) before and after revascularization. Wound measurements and time to complete closure were also recorded., Results: The results of the patients were compared with their own previous wound healing trajectories. Additionally, their healing rate was compared with previously published rates of impaired arterial perfusion venous wound closure; 25% closure at 10 weeks, 50% at 19 weeks. At enrollment, the average ABI and wound sizes were 0.56 and 12 cm(2), respectively. On average, the wounds had remained open for 17 weeks. After the intervention, the average ABI was 0.97, average time taken to complete closure was 10 weeks, closure rate at 10 weeks was 75%, and absolute closure rate was 100%., Conclusion: Although previous studies have shown that closure of mixed arterial venous ulcers occur without arterial intervention, attaining a near normal ABI allows for timelier wound closure. Therefore, we advocate an aggressive approach of percutaneous revascularization in this population., (Copyright © 2011 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Patients with massive venous stasis ulcers that have very high bacterial burdens represent some of the most difficult wounds to manage. The vacuum-assisted closure (VAC) device is known to optimise wound bed preparation; however, these patients have too high a bacterial burden for simple VAC application to facilitate this function. We present the application of the VAC with instillation of dilute Dakins solution as a way of bacterial eradication in these patients. Five patients with venous stasis ulcers greater than 200 cm(2) that were colonised with greater than 10(5) bacteria were treated with the VAC instill for 10 days with 12.5% Dakins solution, instilled for 10 minutes every hour. Two patients had multi-drug-resistant pseudomonas, three with MRSA. All the five had negative quantitative cultures, prior to split thickness skin graft with 100% take and complete healing at 1 year. Adequate delivery of bactericidal agents to the infected tissue can be very difficult, especially while promoting tissue growth. By providing a single delivery system for a bactericidal agent for a short period of time followed by a growth stimulating therapy, the VAC instill provides a unique combination that appears to maximise wound bed preparation.

Introduction: The 2-year cost of a new diabetic foot ulcer (DFU) is estimated to be $27,987. These costs are thought to be secondary to hospitalization, amputation, and the duration of care. Treatments that accelerate rapid and complete healing of DFUs reduce the need for hospitalization, thus reducing the costs of care. One of the therapies previously shown to lead to more rapid and complete wound healing of DFUs is recombinant human platelet-derived growth factor (rhPDGF). Many centers, however, do not initiate rhPDGF therapy, based on patient cost issues. Therefore, many centers reserve a potentially cost-saving therapy as a second- or third-line therapy. The goal of the authors' analysis was to examine the actual cost to patients of a policy of initiating rhPDGF as the initial therapy for appropriately debrided DFUs., Methods: A 12-month retrospective analysis of all patients presenting to a tertiary care referral wound practice with the diagnosis of DFUs was performed. The algorithm the authors followed specified that all wounds of patients with an ankle brachial index of greater than 0.7 and a diagnosis of DFUs (that were not enrolled in a research protocol) were debrided widely (ie, all wounds were debrided sharply with a 45-degree bevel on the border and the bases of the wounds were sharply debrided to a clean granular base), provided off-loading, and initiated on rhPDGF at the patients' first center visit. The patient payer mix and average cost-per-patient per year were analyzed, and the average number of tubes of rhPDGF was recorded., Results: There were 121 patients with the diagnosis of DFUs, representing 766 visits. A total of 187 tubes of rhPDGF were prescribed for these 121 patients over the course of 12 months. There was an average use of 1.54 tubes per patient. The primary payer mix was Medicare, 44%; Medicaid, 27%; and private-payer mix, 29%, representing 10 companies. The average patient cost per tube was $28, the average cost for Medicare was $25 (many with secondary payers, as data predate 2006 Medicare D), Medicaid was $2, and private insurance was $71. Therefore, the average patient cost per course of therapy was $42., Discussion: The average cost to patients with prescription benefits for a course of rhPDGF therapy, over a diverse and representative patient mix, is less than $50 in an inner-city tertiary care facility. Thus, patient cost alone should not provide a barrier to initiating active therapy in the form of rhPDGF to the patient presenting with a DFU. This early initiation could potentially lead to lower overall health costs by improving wound-healing outcomes.

The purpose of this study was to assess the technical feasibility and early outcome of tibial angioplasty for a subset of patients with limb-threatening ischemia who were not candidates for bypass grafting. A retrospective analysis was conducted of 19 patients (7 male, 12 female) who underwent crural angioplasty for limb-threatening ischemia using 0.018- or 0.014 inch-based systems. Contraindications to bypass were insufficient conduit in 7 patients and severe comorbid illness in 12. Concurrent treatment of inflow lesions was performed in 12 of 20 limbs via either angioplasty alone (5) or combined with stenting (12). Outcome measures were ankle-brachial indices (ABI), relief of rest pain, and healing or healed wounds. Twenty-three vessels were treated, including 14 tibial occlusions and 9 stenoses. The average length of diseased segment was 11 cm (range, 3-25 cm). Thirteen of 14 occlusions were treated with subintimal recanalization, the remainder with laser recanalization. Technical success was achieved in 22 of 23 treated vessels. Mean preoperative ABI was 0.53 and mean postoperative ABI was 0.85. Palpable pulses were present in 11 of 20 limbs (55%). There was one perioperative mortality (5.2%). Mean follow-up was 3 months. Three failures occurred requiring amputation (15.8%). The remaining 16 patients were improved with healing (8) or healed (4) wounds and relief of rest pain (4). These results indicate that technical success may be achieved with outflow lesion angioplasty in the majority of patients encountered. The durability of this method of therapy is unknown, and our length of follow-up is not sufficient to answer this question. However, an attempt at angioplasty appears justified before primary amputation and before surgical bypass in those patients at high risk for intervention.

Objective: This study was undertaken to examine recent trends in the outcomes of patients with end-stage renal disease (ESRD) undergoing infrainguinal bypass grafting (IBG) with autogenous vein., Methods: A retrospective analysis of all IBGs performed on patients with ESRD at a single tertiary care institution during the interval 1993 to 1999 was undertaken. The comparison groups consisted of concurrent series of patients with elevated creatinine (creatinine level > 1.2 mg/dL) and patients with normal renal function undergoing IBG. Procedural variables, angiographic runoff scores, and extent of tissue necrosis at presentation were correlated with outcome. Categoric parameters were compared with chi(2) analysis; rates were computed with life-table analysis., Results: Of an overall cohort of 622 IBGs performed during this interval, 78 IBGs (12.5%) were performed on 60 patients with ESRD, with a perioperative mortality rate of 1.3% that was comparable to controls. All reconstructions in the ESRD cohort were for limb salvage indications. Four-year survival, primary, assisted primary, and secondary patency rates for the ESRD group were 51% +/- 9%, 60% +/- 11%, 86% +/- 5%, and 86% +/- 5%, respectively; these were not statistically different from the control groups. Limb salvage in the ESRD group was 77% +/- 6% at 4 years and was significantly less then either the elevated creatinine (92% +/- 4%; P <.02) or the normal renal function group (90% +/- 2%: P <.02). Of 16 amputations in the ESRD group, nine were performed in limbs with patent grafts. The only absolute predictor of limb loss despite a patent graft was the presence of a heel ulcer more than 4 cm in diameter. Age, runoff score of the International Society for Cardiovascular Surgery/Society for Vascular Surgery, isolated tibial bypass graft, and location of distal anastomosis were not predictive of hemodynamic failure., Conclusions: Patients with ESRD constitute an increasing proportion of patients undergoing IBG in a tertiary care setting. Four-year survival, perioperative mortality, and graft patency rates are similar to patients with normal renal function and support an aggressive approach to this population. Major limb amputation despite a patent graft remains a problem of unique frequency in patients with ESRD. Adequate predictors of hemodynamic failure of IBG in this group do not exist, although a heel ulcer more than 4 cm may indicate an unsalvageable foot.

The use of prosthetic material in severe cases of congenital diaphragmatic hernia is complicated by infection, bowel adhesion, and patch dehiscence. We hypothesized that a bioprosthetic collagen patch would reduce these complications and be remodeled into autogenous tissue over a short period of time. Thirty-two New Zealand White rabbits had two 2 x 2-cm left diaphragmatic defects created. One of these defects was repaired with a collagen bioprosthetic patch (n = 20) and the other with a polytetrafluoroethylene (PTFE) patch (n = 20). Members of a control group (n = 12) had their defects closed primarily. The animals were then placed in either a 6- or 12-week survival cohort. At necrosectomy the repairs were assessed histologically, graded for adhesion formation, and tensiometrically tested. The PTFE patch was noted to have a significantly higher average adhesion grade than the collagen patch. The tensile strength of the two repair methods was statistically equivalent at both time intervals. On histologic examination the collagen patches were surrounded by an increased number of macrophages and fibroblasts. The PTFE patch exhibited no neovascularization or fibroblast deposition at the periphery, but had a much greater surrounding inflammatory response. Thus, there was evidence of early remodeling of the collagen with no increase in the amount of adhesions or loss of strength when compared to the PTFE, while the PTFE patches exhibited a more severe grade of adhesions.

Background: Stereoscopic (3-D) monitors and head-mounted displays have promised to facilitate laparoscopic surgery by increasing positional accuracy and decreasing operative time. To test this hypothesis, we evaluated the performance of subjects using these displays to perform standardized laparoscopic dexterity drills., Methods: Fifty laparoscopic novices worked within an abdominal cavity simulator using four videoscopic display configurations: (1) standard (2-D) monitor; (2) 3-D monitor; (3) 2-D head-mounted display; and (4) 3-D head-mounted display. Subjects repeated 3 standardized training exercises 2 times. We measured time to complete each drill and number of errors committed., Results: Mean total times to complete all 3 drills were 455, 459, 485, and 449 sec for configurations 1-4, respectively. Mean total errors committed numbered 11.3, 10.4, 12.3, and 10.8, respectively. Neither comparison reached statistical significance (p < 0.05). When 3-D configurations were compared to 2-D configurations overall, a small but statistically significant reduction in errors was noted for 1 drill only (4.3 vs 5.0, p = 0.018)., Conclusions: Three-dimensional imaging slightly reduced the number of errors committed by laparoscopic novices during one test drill; this improvement, however, was not clinically significant. Neither the 3-D monitor nor the head-mounted display decreased task performance time. Widespread adoption of this technology awaits future improvement in display resolution and ease of use.

Nerve injury has a reported incidence of 2% during laparoscopic hernia repair. These injuries usually involve the femoral branch of the genitofemoral nerve and the lateral cutaneous nerve of the thigh. Recently, in an effort to decrease the size of the port sites, surgeons have been using 5-mm tacking devices. These devices penetrate tissue more deeply and in so doing may injure nerves not classically at risk, such as the ilioinguinal and the iliohypogastric. We report the first documented injury to the ilioinguinal nerve during laparoscopic hernia repair. In addition, we review the anatomy and technique in an effort to help avoid this complication in the future.

Over the last fifty years, energy has been applied to various human tissues for both the diagnosis and therapy of numerous diseases. However, in general, the medical community remains uninformed about the many potential applications of this energy source. We review the many areas in which microwave energy has shown clinical utility.