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.
ABSTRACT
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‐β 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.
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.
Background Nitric oxide (NO) plays critical roles in wound healing, including stimuLating vasodilation, angiogenesis and broad antimicrobial activity.
Aim To measure the effect of an acidified ...nitrite foam (ANF) on biofilms created by six different microbes. Methods A novel method of generating, delivering and topically applying NO gas at the point of care was developed using ANF in a mixed bubble foam and was tested in vitro against six common microbial wound pathogens.
Results A single 5-minute topical exposure of the NO bubble gas formulation generated a 5.8-log 10 reduction of mature biofilm of 'Pseudomonas aeruginosa', a 5.1-log 10 reduction of 'Staphylococcus aureus' biofilm, a 4.0-log 10 reduction of 'Staphylococcus epidermidis' biofilm, a 3.2-log 10 reduction of 'Proteus mirabilis' biofilm, a 2.7-log 10 reduction of 'Acinetobacter baumannii' biofilm, and a 1.5-log10 reduction of 'Candida albicans' biofilm. Conclusion The efficacy of a 5-minute treatment of ANF used on biofilms of 'P. aeruginosa', 'A. baumannii', 'S. aureus', 'C. albicans', 'P. mirabilis' and 'S. epidermidis' was confirmed. The treatment resulted in a significant reduction in colony-forming units per square centimetre (CFU/cm 2) comparable to or surpassing other methods of NO gas application, suggesting NO containing foam's utility as a point of care solution for chronic wounds with elevated bioburden and biofilms where levels of endogenously produced NO May be insufficient for wound healing completion.
BACKGROUND:Drug-coated balloons (DCBs) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Because of the differences in excipients, paclitaxel dose, and ...coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease.
METHODS:In the ILLUMENATE Pivotal Study (Prospective, Randomized, Single-Blind, U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon), 300 symptomatic patients (Rutherford class 2–4) were randomly assigned to DCB (n=200) or standard angioplasty (percutaneous transluminal angioplasty PTA) (n=100). The primary safety end point was freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness end point was primary patency through 12 months. In the ILLUMENATE PK study (Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon), paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times (at 1, 4, 24 hours and at 7 and 14 days postprocedure) until no longer detectable.
RESULTS:In the ILLUMENATE Pivotal Study, baseline characteristics were similar between groups50% had diabetes mellitus, 41% were women, mean lesion length was 8.3 cm, and 44% were severely calcified. The primary safety end point was met (92.1% for DCB versus 83.2% for PTA, P=0.025 for superiority) and the primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P=0.003). Primary patency per Kaplan-Meier estimates at day 365 was 82.3% for DCB versus 70.9% for PTA (P=0.002). The rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P=0.023). Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations. Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour (54.4±116.9 ng/mL to 1.4±1.0 ng/mL).
CONCLUSIONS:The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour.
CLINICAL TRIAL REGISTRATION:URLhttp://clinicaltrials.gov. Unique identifiersNCT01858428 and NCT01912937.
The antimicrobial effects of a borate-based bioactive glass matrix (BBBGM) on clinically relevant microorganisms was investigated for up to seven days in vitro.
A total of 19 wound-relevant pathogens ...were studied using the in vitro AATCC 100 test method.
The reduction of viable Gram-negative and Gram-positive bacteria and yeasts at days 4 and 7 post-culture on the BBBGM was significant (> 4log
) in most cases. Mould counts were reduced (<2log
) 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.
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.
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.
PDF
