Antimicrobial effects of a borate-based bioactive glass wound matrix on wound-relevant pathogens.

OBJECTIVE: The antimicrobial effects of a borate-based bioactive glass matrix (BBBGM) on clinically relevant microorganisms was investigated for up to seven days in vitro. METHOD: A total of 19 wound-relevant pathogens were studied using the in vitro AATCC 100 test method. RESULTS: The reduction of viable Gram-negative and Gram-positive bacteria and yeasts at days 4 and 7 post-culture on the BBBGM was significant (> 4log10) in most cases. Mould counts were reduced (<2log10) during the seven-day assessment, indicating that mould viability and reproduction was inhibited. The cell count of each organism was reduced at seven days indicating that the BBBGM not only reduced the viable cell count, but that the cell count did not recover during the seven-day period, indicating a sustained reduction in pathogenic activity. CONCLUSION: Based on the present results, the use of a BBBGM as a pathogenic barrier should be considered as a tool for combating pathogenic colonisation and infection in acute and hard-to-heal (chronic) wounds.

Surfactants: Role in biofilm management and cellular behaviour.

Appropriate and effective wound cleaning represents an important process that is necessary for preparing the wound for improved wound healing and for helping to dislodge biofilms. Wound cleaning is of paramount importance to wound bed preparation for helping to enhance wound healing. Surfactant applications in wound care may represent an important area in the cleaning continuum. However, understanding of the role and significance of surfactants in wound cleansing, biofilm prevention and control, and enhancing cellular viability and proliferation is currently lacking. Despite this, some recent evidence on poloxamer-based surfactants where the surfactants are present in high concentration have been shown to have an important role to play in biofilm management; matrix metalloproteinase modulation; reducing inflammation; and enhancing cellular proliferation, behaviour, and viability. Consequently, this review aims to discuss the role, mode of action, and clinical significance of the use of medically accepted surfactants, with a focus on concentrated poloxamer-based surfactants, to wound healing but, more specifically, the role they may play in biofilm management and effects on cellular repair.

Cell salvage in acute and chronic wounds: a potential treatment strategy. Experimental data and early clinical results.

On 9 May 2018, the authors took part in a closed panel discussion on the impact of cell salvage in acute and chronic wounds. The goal was to deliberate the possible use of plurogel micelle matrix (PMM) as a new treatment strategy for wound healing and the authors openly shared their experiences, thoughts, experimental data and early clinical results. The outcome of the panel discussion has been abridged in this paper. The cell membrane consists of a lipid bilayer, which provides a diffusion barrier separating the inside of a cell from its environment. Cell membrane injury can result in acute cellular necrosis when defects are too large and cannot be resealed. There is a potential hazard to the body when these dying cells release endogenous alarm signals referred to as 'damage (or danger) associated molecular patterns' (DAMPs), which trigger the innate immune system and modulate inflammation. Cell salvage by membrane resealing is a promising target to ensure the survival of the individual cell and prevention of further tissue degeneration by inflammatory processes. Non-ionic surfactants such as poloxamers, poloxamines and PMM have the potential to resuscitate cells by inserting themselves into damaged membranes and stabilising the unstable portions of the lipid bilayers. The amphiphilic properties of these molecules are amenable to insertion into cell wall defects and so can play a crucial, reparative role. This new approach to cell rescue or salvage has gained increasing interest as several clinical conditions have been linked to cell membrane injury via oxidative stress-mediated lipid peroxidation or thermal disruption. The repair of the cell membrane is an important step in salvaging cells from necrosis to prevent further tissue degeneration by inflammatory processes. This is applicable to acute burns and chronic wounds such as diabetic foot ulcers (DFUs), chronic venous leg ulcers (VLUs), and pressure ulcers (PUs). Experimental data shows that PMM is biocompatible and able to insert itself into damaged membranes, salvaging their barrier function and aiding cell survival. Moreover, the six case studies presented in this paper reveal the potential of this treatment strategy.

Tolerance of Biofilms to Antimicrobials and Significance to Antibiotic Resistance in Wounds.

A biofilm is a community of microorganisms that adhere to each other and to surfaces and secrete extracellular polymeric substances (EPS) encasing themselves in a matrix. Biofilms are a major healthcare concern, as they can form on medical devices leading to infection. Additionally, there is growing evidence to show their ability to form in chronic wounds, which leads to delayed wound healing and inflammation. Due to a number of reasons, such as formation of the EPS resulting in sub-inhibitory concentrations of antimicrobials reaching the bacterial cells, slow growth rate of bacterial cells rendering some antibiotics ineffective, and the presence of persister cells, biofilms show increased tolerance to many antimicrobials and antibiotics. Additionally, studies have started to emerge showing a link between resistance to antimicrobials and antibiotics. Cross-resistance can be attributed to a number of factors, for example, increased expression of multidrug efflux pumps that efflux a wide range of substrates and horizontal gene transfer of genetic material encoding multiple resistance genes between different species within the polymicrobial biofilm. Antimicrobial resistance is an increasing threat caused by multiple factors including cross-resistance, and it is a global health concern. This review focuses on current research on antimicrobial and antibiotic resistance and cross-resistance found between antimicrobials and antibiotics commonly used in woundcare to evaluate the significance of this acquired antibiotic resistance. Furthermore, the review discusses the significance of antimicrobial tolerance and the role biofilms play in enhancing antibiotic resistance.

Evaluation of Biofilms on Explanted Shoulder Prostheses Using Functional Biofilm Assay and Scanning Electron Microscopy.

Successfully treating shoulder arthroplasty infection requires diagnosis and bacterial identification. Higher incidence of infection with low-virulence bacteria makes this challenging. This study evaluates shoulder prostheses for infection using sonication and a functional biofilm assay. Nineteen patients undergoing revision shoulder arthroplasty were followed prospectively. Periprosthetic tissue and prosthetic components were obtained during the revision and evaluated with a functional biofilm assay. Results were compared with conventional cultures and laboratory results. Hardware samples were analyzed with scanning electron microscopy. Six of the 19 cases demonstrated growth on the biofilm assay. Three of these had positive conventional culture results and met Musculoskeletal Infection Society (MSIS) criteria for infection. Two other cases met MSIS criteria but demonstrated negative assay and conventional culture results. Of the six cases with positive assay results, three demonstrated evidence of biofilm on scanning electron microscopy. The biofilm assay identifies infections not recognized by traditional culture or MSIS criteria. (Journal of Surgical Orthopaedic Advances 27(3):171-177, 2018).

Pilot Study to Determine Safety and Efficacy of Paclitaxel Infusion in De Novo Peripheral Lesions Using the Atrium ClearWay Balloon.

OBJECTIVE: To evaluate the safety and efficacy of a one-time infusion of paclitaxel through an Atrium ClearWay balloon in infra inguinal de novo peripheral lesions. METHODS: This is a single-center prospective study looking at treatment of 50 limbs. Treatment includes standard infra inguinal endovascular revascularization followed by a pre-prescribed infusion of paclitaxel. Control is standard reintervention without subsequent paclitaxel infusion. Patients were followed at one, four, and 10 months with ankle-brachial index (ABI)s, arterial duplex of the treated limb, and Rutherford classification stage measured before and after procedures and at each follow-up. Freedom from binary restenosis was tracked with duplex ultrasound, and freedom from target lesion revascularization (TLR) was also tracked in the treatment group. Binary restenosis and TLR data was harvested from the patient record for the control group. RESULTS: Average ABI and Rutherford classification stage improved as expected. The treatment group had a freedom from TLR rate of 86 percent and a freedom from binary restenosis rate of 80 percent at 10 months. Average ABI improved from 0.65 at baseline to 0.94 at 10 months in the treatment group. The control group had a 72 percent freedom from TLR and a 58 percent freedom from binary restenosis at 10 months. Average ABI of the control group improved from 0.67 at baseline to 0.85 at 10 months in the control group. There were no amputations, open bypass revascularizations, or hypersensitivity reactions observed in the treatment group. CONCLUSIONS: Infusion of paclitaxel in de novo lesions appears to be a safe and efficacious treatment in the peripheral vasculature when compared to a historical control group. While it is early, it appears that the patients do receive some benefit from this one time infusion, and this approach should be studied further.

A single stent strategy in patients with lifestyle limiting claudication: 3-year results from the Durability II trial.

OBJECTIVES: To evaluate longer-term safety and efficacy of a single self-expanding stent up to 20 cm in length in patients with atherosclerotic disease of the superficial femoral (SFA) and proximal popliteal arteries. BACKGROUND: Angioplasty and stenting are options for revascularization of symptomatic peripheral artery disease. While angioplasty alone is effective in short lesions, outcomes in longer lesions (i.e., mean 8.7 cm) show suboptimal patency rates of 33% at one year. METHODS: Two hundred eighty-seven patients (mean age 68 years, 66% male) were treated with the EverFlex™ Self-Expanding Peripheral Stent System. Patients were followed through 3 years with yearly core lab adjudicated duplex ultrasonography for patency, radiographic assessment of stent fractures, and resting ankle brachial indices. RESULTS: Overall freedom from loss of primary patency at 3 years was 60.0%. Patency was significantly higher for lesions ≤8 cm compared with lesions >8 cm (71.0 vs. 50.5%, P < 0.0001). There was no significant difference in patency between single-stent and multistent recipients (60.4 vs. 52.4%, P = 0.343). The three-year freedom from clinically driven target lesion revascularization was 70.0%. At 3 years, the overall stent fracture rate was 0.9%. CONCLUSIONS: DURABILITY II is the first investigational device exemption trial to report 3-year duplex Doppler defined stent patency and CD-TLR outcomes in long SFA and proximal popliteal lesions and demonstrated acceptable stent patency and freedom from CD-TLR with a low fracture rate. These data suggest that use of a single long stent provides reasonable long-term outcomes when intervention is required for symptomatic SFA and proximal popliteal arterial disease.

Use of Physician-Modified Endografts to Repair Unilateral or Bilateral Aortoiliac Aneurysms.

BACKGROUND: This article presents an endovascular approach to repair a unilateral or bilateral aortoiliac aneurysm with a bifurcated iliac limb that can maintain perfusion to the internal iliac artery (IIA) bilaterally through a brachial access. METHODS: A standard infrarenal aortic aneurysm repair is performed followed by iliac aneurysm exclusion. To obtain exclusion in the common iliac artery aneurysm, a bifurcated Endurant iliac limb is modified to compartmentalize iliac flow 2-3 cm above the internal iliac ostia. Then, a balloon-expandable covered stent graft is used to achieve sealing in the IIA and external iliac artery (EIA). The IIA is stented from the arm and the EIA is stented from the groin. RESULTS: There was no in-hospital or 30-day mortality. The procedural design was followed in each of the patients who received treatment. Technical success was 100%, short-term clinical success was 92%, and midterm clinical success was 83%. Average dosage of contrast medium was 116 mL (range, 55-193 mL), and average fluoroscopy time was 42.1 min (range, 20.8-91.6 min). Average length of hospital stay was 2.6 days (range, 1-9 days). There was 1 recorded endoleak. No reports of gluteal claudication, sexual dysfunction, or bowel or spinal claudication have been found. CONCLUSIONS: The technique described here does not require an up-and-over approach, allowing simplified bilateral repair. Although this is a promising technique, long-term durability needs to be evaluated in a controlled prospective study.

The United States StuDy for EvalUating EndovasculaR TreAtments of Lesions in the Superficial Femoral Artery and Proximal Popliteal By usIng the Protégé EverfLex NitInol STent SYstem II (DURABILITY II).

OBJECTIVE: Angioplasty and stenting are options for revascularization of symptomatic femoral popliteal disease. Although angioplasty alone is effective in short lesions, longer lesions are often treated with stents. Multiple overlapping stents are expensive and may be associated with stent fracture. This trial evaluated the safety and efficacy of a single self-expanding stent up to 20 cm in length in patients with atherosclerotic disease of the superficial femoral artery (SFA) and proximal popliteal artery. METHODS: Patients with lesions >4 cm and <18 cm were enrolled in this nonrandomized, prospective, multicenter trial that evaluated the Protégé EverFlex Self-Expanding Peripheral Stent System (Covidien, Plymouth, Minn). The study's primary end points were the 30-day major adverse event rate and duplex ultrasound-assessed patency at 1 year. These were compared with published performance goals. A preplanned analysis was conducted for the primary effectiveness end points at 1 year. Follow-up, including history, ankle-brachial index, patient-reported outcomes, duplex ultrasound assessment, and radiographs, is planned through 3 years. There was core laboratory review of angiograms, ultrasound scans, and plain radiographs. A subgroup of patients was studied with graded treadmill testing. RESULTS: The study enrolled 287 patients (66% male; mean age, 68 years) with stenotic, restenotic, or occluded lesions of the SFA at 44 investigational sites in the United States and Europe. Systemic comorbidities included hypertension (88%), hyperlipidemia (86%), diabetes (43%), and prior SFA intervention (41%). The mean lesion length measured by the core laboratory was 89 mm. The mean normal-to-normal lesion length measured by sites was 110 mm. A total of 303 stents were implanted, and 95% of patients received a single stent. No major adverse events occurred at 30 days. At 1 year, primary outcome of duplex ultrasound stent patency was 67.7% in evaluable patients, and among 1-year secondary outcomes, the mean ankle-brachial index increased by 0.25. Walking Improvement Questionnaire scores improved in pain by 33.7, distance by 37.1, speed by 18.6, and stair climbing by 24.7. The Kaplan-Meier estimate of primary patency was 77.2%, primary assisted patency was 86.9%, and secondary patency was 87.3%. Rutherford clinical category improved in 83.5% of patients. Stent fracture rate was 0.4%. Matched absolute claudication distance was 412 feet greater and was not statistically different in this subgroup of 29 individuals. CONCLUSIONS: The results of DURABILITY II (StuDy for EvalUating EndovasculaR TreAtments of Lesions in the Superficial Femoral Artery and Proximal Popliteal By usIng the Protégé EverfLex NitInol Stent SYstem II) suggest that a new single stent strategy is safe and effective for the treatment of long lesions of the SFA and proximal popliteal arteries at 1 year.

Stenting and angioplasty with protection in patients at high-risk for endarterectomy: SAPPHIRE Worldwide Registry first 2,001 patients.

BACKGROUND: Previously, the Stenting and Angioplasty with Protection of Patients with High Risk for Endarterectomy (SAPPHIRE) randomized trial showed that carotid artery stenting (CAS) was not inferior to carotid endarterectomy (CEA) in the treatment of high-surgical risk patients. OBJECTIVE: The primary objective of the SAPPHIRE Worldwide Registry is to evaluate 30-day major adverse events (MAE) after CAS performed by physicians with varied experience and utilizing a formal training program. Data will be analyzed on the overall patient population and by high-risk inclusion criteria. METHODS: SAPPHIRE Worldwide is a multicenter, prospective, postapproval registry to evaluate CAS with distal protection in patients at high-risk for surgery using the Cordis PRECISE Nitinol Stent and ANGIOGUARD XP/RX Emboli Capture Guidewire. Participating physicians are encouraged to treat patients according to their standard of practice and consistent with current Food and Drug Administration-approved labeling. RESULTS: Enrollment began in October 2006. Data are available on the first 2,001 patients enrolled and followed to 30 days. Of these patients, the mean age was 72.2 +/- 9.75 yr; 62% were male; and 27.7% were symptomatic. Entry criteria for surgical high-risk included anatomic (n = 716), physiologic (n = 918), or both risk factors (n = 327). At 30-day follow-up, the MAE was 4.4% (death 1.1%, stroke 3.2%, MI 0.7%) for the overall population. Patients with anatomic risk had a significantly lower 30-day MAE than patients with physiologic risk (2.8% vs. 4.9%, P = 0.0306), respectively. CONCLUSIONS: While the number of physicians performing CAS continues to increase, MAE rates seen in this registry (4.4%) are well within an acceptable range, as was first seen in the SAPPHIRE randomized trial (4.8%). A significant decrease in MAE was seen in patients with anatomic risk compared with physiologic risk factors. The SAPPHIRE Worldwide Registry supports the use of CAS as an alternative to CEA in patients who are at high-risk for surgery due to anatomic risk factors.

Antisense inhibition of connective tissue growth factor (CTGF/CCN2) mRNA limits hypertrophic scarring without affecting wound healing in vivo.

Augmented expression of connective tissue growth factor (CTGF/CCN2) is observed in healing wounds and in a variety of fibrotic disorders. It appears to enhance many of the effects of transforming growth factor-beta and has been shown to have independent fibrogenic functions. Despite these observations, its importance to dermal wound healing and the transition from wound to scar remains poorly defined. In this study, we use established rabbit models to evaluate the roles of CTGF in dermal wound healing and hypertrophic scarring. We show that CTGF mRNA demonstrates persistent up-regulation in hypertrophic scars. Treatment of wounds with antisense oligonucleotides to CTGF has no measurable effect on early wound closure. However, antisense therapy significantly limits subsequent hypertrophic scarring. Inhibition of CTGF is associated with a marked reduction in the number of myofibroblasts in scars and decreased transcription of TIMP-1 and types I and III collagen. These findings confirm CTGF to be a key mediator of hypertrophic scarring in this model. Its effect on myofibroblasts in this setting suggests a mechanism whereby it plays this role. Its limited participation in early healing implies that it may be a useful and specific target for modulating hypertrophic scarring following injury.

Wound Biofilm: Current Perspectives and Strategies on Biofilm Disruption and Treatments

The presence of bio lm remains a challenging factor that contributes to the delayed healing of many chronic wounds. The major threat of chronic wound bio lms is their substantial protection from host immunities and extreme tolerance to antimicrobial agents. To help guide the development of wound treatment strategies, a panel of experts experienced in clinical and laboratory aspects of biofilm convened to discuss what is understood and not yet understood about biofilms and what is needed to better identify and treat chronic wounds in which biofilm is suspected. This article reviews evidence of the problem of biofilms in chronic wounds, summarizes literature-based and experience-based recommendations from the panel meeting, and identities future and emerging technologies needed to address the current gaps in knowledge. While currently there is insufficient evidence to provide an accurate comparison of the effectiveness of current therapies/products in reducing or removing biofilm, research has shown that in addition to debridement, appropriate topical antimicrobial application can suppress biofilm reformation. Because the majority of the resistance of bacteria in a biofilm population is expressed by its own secreted matrix of extracellular polymeric substance (EPS), panel members stressed the need for a paradigm shift toward biofilm treatment strategies that disrupt this shield. High-osmolarity surfactant solution technology is emerging as a potential multimodal treatment that has shown promise in EPS disruption and prevention of biofilm formation when used immediately post debridement. Panel members advocated incorporating an EPS-disrupting technology into an antibiofilm treatment approach for all chronic wounds. The activity of this panel is a step toward identifying technology and research needed to improve biofilm management of chronic wounds.

Effect of Negative Pressure Wound Therapy With Instillation on Bioburden in Chronically Infected Wounds.

INTRODUCTION: Standard negative pressure wound therapy (NPWT) has been shown to help close wounds despite increasing planktonic bioburden. Both planktonic and biofilm critical colonization are associated with delayed wound healing; therefore, reducing microbial colonization is thought to aid wound healing. The use of NPWT with topical antimicrobial irrigation solution has previously shown reduction in quantitative planktonic bioburden when combined with sharp debridement in chronic wounds. OBJECTIVE: The goal of this study was to evaluate the effectiveness of NPWT with instillation (NPWTi) on biofilm of chronic wounds. MATERIALS AND METHODS: A prospective, randomized trial was conducted. Following sharp debridement, 20 patients with chronic wounds were randomized to 1 week of either NPWTi with 0.125% sodium hypochlorite solution (n = 10) or NPWT without instillation (n = 10). Serial wound biopsy was performed predebridement, postdebridement, and after 1 week of study therapy to test for quantitative nonplanktonic or biofilm-protected bacteria. RESULTS: As expected, there was no difference in change in wound size between the 2 groups at 1 week. The NPWTi group had a mean reduction in quantitative biofilm-protected bacteria of 48%, while the NPWT without instillation group had a mean increase of 14% (P < .05). DISCUSSION: Consistent with previous studies, this trial demonstrates that NPWTi with dilute sodium hypochlorite solution is effective at reducing nonplanktonic bioburden of chronically, critically colonized wounds. CONCLUSION: Therefore, based on this and previously published work, this therapy provides both planktonic and nonplanktonic bioburden reduction as well as NPWT benefits and may be a tool for the preparation of infected wound beds prior to definitive closure.

Safety and efficacy of ultrasound-accelerated catheter-directed lytic therapy in acute pulmonary embolism with and without hemodynamic instability.

OBJECTIVE: The objective of this study was to evaluate the safety and effectiveness of ultrasound-accelerated thrombolysis in acute pulmonary embolism. METHODS: A retrospective study of 45 patients was performed to evaluate treatment of acute pulmonary embolism at a single center from January 2011 to December 2013. All patients were diagnosed with computed tomography or ventilation-perfusion scan and had hemodynamic instability (systolic blood pressure <100 mm Hg) or right-sided heart strain evidenced by right ventricular dilation, septal deviation, or hypokinesis by echocardiography or computed tomography. EkoSonic catheters (EKOS Corporation, Bothell, Wash) were placed into the affected pulmonary arteries, and recombinant tissue plasminogen activator was infused through the catheters at 0.5 to 1.0 mg/h per catheter. RESULTS: Hypotension (systolic blood pressure <100 mm Hg) was present in 12 patients, with 100% resolution by treatment completion. Tachycardia (heart rate >100 beats/minute) was present in 26 patients and resolved in 92% by treatment completion; the average heart rate for all patients decreased from 109 to 77 beats/minute during the treatment period. Direct pulmonary artery pressure measurement showed average decrease of 21.5 mm Hg, representing a 40.2% reduction. Postprocedure echocardiography demonstrated complete resolution of cardiac dysfunction in 64%. Patients received a total dose of 30.5 mg (range, 14-66 mg) recombinant tissue plasminogen activator during an infusion time of 14.2 hours (range, 8-21 hours). There were no deaths through 90 days of follow-up and no major periprocedural bleeding events. CONCLUSIONS: This retrospective study demonstrates the safety and efficacy of current ultrasound-accelerated thrombolysis methods to treat acute pulmonary embolism.

An overview of tissue types in pressure ulcers: a consensus panel recommendation.

Pressure ulcer assessment is usually performed at the bedside by a clinician with minimal training in wound assessment. A multidisciplinary panel of United States' wound experts was assembled to provide anatomically accurate and practical terms associated with pressure ulcer assessment, healing, and nonhealing in order to help clinicians identify and describe tissue types and pressure ulcer stages. Specifically, anatomical markers and/or structures within the wound are described to facilitate tissue type identification and pressure ulcer staging. The panel agreed that the provision of a common language facilitates quality care across settings. Although some research has been conducted, additional studies to determine the validity and reliability of wound assessment and healing terms and definitions, as well as pressure ulcer staging systems, are needed.