Low-frequency Ultrasound for Patients With Lower Leg Ulcers Due to Chronic Venous Insufficiency: A Report of Two Cases

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Ostomy Wound Manage. 2014;60(2):52–61.
Sara F. Maher, DScPT; Jessica Halverson, DPT; Rob Misiewicz, DPT; Trisha Reckling, DPT; Ojas Smart, DPT; Carol Benton, BSN, RN, CWCN; and Dawn Schoenherr, RN, MSN, CS, CCRN

Abstract

  Low-frequency ultrasound may facilitate debridement and healing of chronic wounds, including lower leg wounds in patients with chronic venous insufficiency (CVI). To evaluate the use of a low-frequency ultrasound (LFU) device with a curette, two patients with CVI and chronic wounds were treated for a period of 2 to 3 weeks. A 63-year-old woman with rheumatoid arthritis and two wounds, one on the right lower leg (250 cm3) and one wound on the left medial leg (0.80 cm3), present for 12 months; and a 77-year-old man with cardiopulmonary issues with seven wounds, three on the left medial calf (1.2 cm3, 11.40 cm3, and 0.72 cm3), one on the left anterior calf (0.30 cm3), two on the right posterior calf (0.90 cm3, 0.30 cm3), and one on the right anterior calf (0.14 cm3), present for 3 months consented to participate in the study. Both patients received low-intensity (50–70 m), low-frequency (35 kHz) ultrasound at an intensity of 50% through a saline mist in addition to antimicrobial dressing with silver, a multilayer compression bandage system applied at every visit, and pain medication as needed. Both patients received treatments every 1 to 3 weeks that were not timed. Treatment continued until no additional slough or other necrotic tissue could be removed from the wound bed; the female patient received two treatment sessions and the male received three. Average wound volume did not change significantly from the first to last treatment session (t(8) – 1.2, P = 0.26). Five wounds (56%) with initial measurements of 0.8 cm3, 0.72 cm3, 0.3 cm3, 0.3 cm3, and 0.14 cm3 reduced in volume by 100%. Mean wound characteristic scores changed significantly (P <0.05) for amount of fibrin, periwound skin, drainage amount, and color. In addition, the number of wounds filled with slough decreased from 89% at the first session to 22% at the final treatment session. The results of this study suggest LFU may have been beneficial for these patients with CVI. Additional studies using larger sample sizes are needed to evaluate the effect of this treatment on a variety of chronic wounds and to compare its effectiveness to other debridement methods. {C}

 Potential Conflicts of Interest: Arobella Medical, LLC (Minnetonka, MN) provided a grant for the low-frequency ultrasound device used during the study.

Introduction

  Chronic venous insufficiency (CVI), defined as impaired venous return to the heart, is a factor in 60% to 90% of all lower extremity ulcers according to studies from 1997 to 2012.1-7 Approximately 9.4% of individuals in the US are diagnosed with CVI.1 According to a review,8 patients with CVI can exhibit a variety of leg symptoms, including achiness, heaviness, sensations of swelling, and skin irritation. Expeditious wound closure in patients with CVI is important to avoid infections, medical complications, and costly hospital admissions.9 In the US alone, care for ulcers due to CVI resulted in annual treatment costs between $3 million and $750 million in 2006,1,6 or 2% to 3% of the US healthcare budget.10 Many treatment options are available for CVI and include surgery, medications, ultrasound, compression stockings, electrical stimulation, and wound debridement.5

  When granulation and wound bed epithelialization are inhibited due to the presence of necrotic tissue, debridement of nonviable tissue is a common practice, regardless of the wound etiology.11 Sharp debridement is among the quickest ways to remove nonviable tissue3 and is widely accepted as the gold standard for optimal healing in diabetic foot ulcers,12 an accepted practice in “good wound care,”13,14 and “may help expedite healing in chronic venous ulcers.”15 In addition, sharp debridement utilizes few tools and is inexpensive, making it a commonly used treatment option.1,3,5,13,14 In a concurrently controlled, prospective study3 conducted over 12 months with two patient cohorts, sharp debridement (with calcium alginate dressings to control blood loss) in combination with general ulcer management (compression dressings and pain relief as needed) was found to completely heal four chronic venous ulcers (16%) in 8 to 20 weeks, compared to one healed ulcer (4.3%) in the control group that received only general ulcer management. However, the reduction in surface area between the groups over the entire study period did not achieve statistical significance.3 Although it may expedite the healing process for patients with CVI, sharp debridement is not considered the mainstay of venous ulcer management,15 and its effectiveness has not been fully evaluated on patients with CVI.3 Sharp debridement requires a competent practitioner with specialized training,11,16 may be risky in wounds located in the gaiter region of the leg due to post-debridement hemorrhage,7,11 and may require the use of mild analgesics if the patient experiences pain.11 Newly developed technologies are beginning to challenge more traditional methods of wound debridement (eg, sharp debridement), but further evidence is needed to make these techniques more widely accepted.16

  Ultrasound for wound care. Ultrasound has been used in medicine as a diagnostic tool (eg, Doppler blood flow studies) for approximately 50 years; more recently, it has served as a therapeutic device (eg, wound care).17 The two main types of therapeutic ultrasound are high-frequency ultrasound, which oscillates between 1 and 3 MHz (one to three million times per second) and is absorbed into tissue creating heat18; and low-frequency ultrasound (LFU), which oscillates between 30 and 40 kHz (30,000 to 40,000 times per second) and is commonly used to stimulate the tissue beds of chronic wounds.17 The authors of several literature reviews reported that both forms of ultrasound (high- and low-frequency) produce mechanical effects, including cavitation and acoustic streaming (thought to alter cell membrane activity), improve diffusion rates, enhance membrane permeability, fragment necrotic tissue, loosen slough, and destroy bacteria and biofilms on the wound surface.19,20 However, LFU may be reflected at the skin or wound surface, leaving little of the energy from the machine to reach deeper tissue layers.17

  A number of studies utilizing LFU have been published; the results are mixed. A 2003 literature review18 examined 15 studies (meta-analyses, quasi-randomized, or randomized control trials) that utilized LFU on patients with chronic venous leg ulcers, trophic ulcerations, infected wounds, infected diabetic foot ulcers, or pressure ulcers. The reviewers concluded the benefit of LFU was not convincing. A 2011 meta-analysis9 involving 444 patients treated with noncontact, low-frequency ultrasound (NLFU) reported on the results of eight studies (one randomized, double-blind sham-controlled trial, five retrospective analyses, and two prospective, nonrandomized studies). The primary indications for treatment were ulcers due to diabetes mellitus, venous insufficiency, arterial insufficiency, and pressure. The authors concluded NLFU was associated with consistent wound size reduction, alleviation of wound pain, and favorable wound healing results. Over the course of treatment, approximately 85% reduction in wound area was noted over 7 weeks, 80% reduction in wound volume over 12 weeks, and 79% reduction in wound pain (no timeline given). A Cochrane review10 that specifically examined therapeutic ultrasound on patients with venous leg ulcers and utilized the results of eight randomized, controlled trials found no strong evidence for the benefit of LFU on venous ulcer healing. However, because the quality of the evidence was low, a beneficial effect of ultrasound could not be ruled out.

  Based on the results of controlled clinical trials only, the application of NLFU has been shown to be effective in decreasing the size of chronic ulcers and, in some cases, shortening healing times. In one study,4 participants randomly assigned to conventional wound therapy and NLFU delivered by a foot bath (n = 19) were found to have a significant reduction in chronic venous ulcer size when compared to participants randomly assigned to conventional therapy alone (n = 18) (P <0.05). Over a period of 8 weeks, the NLFU-treated participants experienced a 41% reduction in ulcer size compared to an 11% reduction in the conventional treatment group. In another study,21 participants were randomly assigned to receive standard wound care (n = 35) or standard wound care plus ultrasound delivered by a NLFU system (MIST Therapy System, Celleration, Inc, Eden Prairie, MN) (n = 35) that utilized a 40-kHz transducer. The participants had a variety of wound etiologies including diabetes, chronic renal failure, prior vascular reconstructive surgery, and osteomyelitis. At 12 weeks, a significant number of wounds were more than 50% healed in the study group (63% of wounds) compared to the control group (29% of wounds) (P <0.001). A randomized, double-blind, sham-controlled study22 reported similar findings among participants with diabetic foot ulcers. Twenty-seven (27) participants received NLFU, while 28 received treatment with a sham device. A significant difference was seen in the 12-week healing rates of the two groups; 41% of wounds treated with ultrasound healed completely versus 14.3% of wounds in the control group (P = 0.0366, Fisher’s exact test). Mean healing time also significantly differed between the two groups (9.12 weeks for the ultrasound group compared to 11.74 for the sham treatment group; log rank P <0.0144). A prospective, single-arm study23 using historical controls examined healing in wounds of a variety of etiologies (diabetic, venous, ischemic, pressure, postoperative, and inflammation); although the overall percentage of wounds healed during the 8-month study was comparable between participants (69% NLFU participants versus 72% historical controls), the healing times were different. Participants treated with NLFU were healed in a median time of 7 weeks compared to 10 weeks in historical controls. Furthermore, NLFU-treated wounds that healed completely began to respond to the treatment within 4 weeks of treatment initiation, a timeframe that may serve as an indicator for responders to the treatment.

  The Sonica 185 (Soring Gmbh, Soring, Inc, Germany) LFU device operates at a fixed frequency of 25 kHz. Treatment can be provided with either direct contact to the wound bed through a probe or by holding the transducer above the wound bed (noncontact).24 A prospective, pilot study25 in 2005 examined the effects of this device on 17 patients with a variety of wound etiologies, including venous ulcers, foot wounds in persons with diabetes mellitus, pressure, arterial insufficiency, and other nonhealing/surgical wounds. Over a period of 3 to 8 months, 53% of the wounds healed primarily or with the aid of a skin graft, while 35% of the remaining wounds healed at least 50%. A prospective, pilot study by Tan et al5 examined the effect of this same device on 18 patients with ulcers (average initial size 4.72 cm2) due to venous insufficiency (n = 13), rheumatoid (n = 3), or sickle cell (n = 2). After 12 weeks, 38.9% of the ulcers were completely healed. The average number of treatments was 5.7. In a randomized clinical trial26 published in 2013, 40 patients were randomly assigned to either a standard wound care group (n = 20) or standard wound care plus LFU delivered by this device (n = 20). After 2 months, a significant difference was seen in the percent of wound size reduction between the two groups (63.6% ultrasound, 39.3% control, P = 0.01). The significance continued at 3 months (78% ultrasound, 55.7% control, P = 0.02). However, at 6 months no significant differences in wound size reduction were seen between the two groups (87.9% ultrasound, 82.4% control).

  The Qoustic Wound Therapy System (Arobella Medical, LLC, Minnetonka, MN) LFU device received US Food and Drug Administration (FDA) clearance for marketing in 2006. This device combines an ultrasound transducer set at 35 kHz with a special curette designed to scrape away devitalized tissue the ultrasound waves are thought to fragment and soften.27 Karau et al28 reported the system was able to effectively kill planktonic bacteria and decrease biofilm in vitro. In vitro, bacterial counts decreased by a mean of 5.10 (Pseudomonas aeruginosa), 4.99 (Staphylococcus epidermidis), and 5.22 (S. aureus) log 10 colony-forming units/mL. Mean decreases in biofilm were 1.34 (P. aeruginosa), 1.46 (S. epidermidis), and 1.02 (S. aureus) log 10 colony forming units/mL. Conner-Kerr et al29 found the system reduced colony forming units of bacteria, punctured and fractured bacterial cell walls, and altered colonial characteristics of methicillin-resistant S. aureus (MRSA) in vitro.

  Although other LFU devices (MIST therapy, Sonica 185) have been researched with patient populations, the literature review did not find any studies that utilized the Qoustic Wound Therapy system on patients with any wound etiology.

  The purpose of this case study was to evaluate the use of the Qoustic Wound Therapy System in patients with wounds due to CVI.

Methods

  Participants. Approval for this pilot study was obtained through the Institutional Review Board for the Protection of Human Subjects (IRB) at the primary author’s university and through the Human Investigation Committee (HIC) at the facility where the patients were treated. Patients at a metropolitan wound care center were invited to participate if they were 18 years or older, able to provide informed consent, had a confirmed diagnosis of CVI, and at least one chronic wound on a lower extremity. Wounds were defined as chronic if they were present for 3 months or more.4 Patients were excluded if they had previously received LFU treatment.

  Protocol. Before the start of treatment, participants read and signed an informed consent. After each treatment session, participants completed a questionnaire that contained 1) a 10-option Visual Analogue Scale (VAS) to measure pain and 2) five Likert-scale questions designed to assess patient perception of treatment, mobility, self-care, usual activities (work, study, housework), and anxiety/depression. Scores on the Likert scale ranged from 1 to 5, with a higher number indicating a higher rating of the treatment or function (see Table 1). The VAS to measure pain has been found to have good reliability,30–37 validity,30–33,35,38 sensitivity,31,33–35 and responsiveness.38,39 The patient perception and functioning questionnaire was developed for this evaluation and had not been tested for validity or reliability.

  Treatment was provided by an IRB/HIC-approved physician or nurse practitioner familiar with debridement and trained to use the system. Before each ultrasound treatment, patients were pre-medicated with 4% lidocaine liquid on the wound site. Participants received LFU application to every wound at every treatment session. The ultrasound treatment was provided using the wound therapy system that delivers low-intensity (50–70 m), low-frequency (35 kHz) ultrasound through a saline mist (see Figure 1). Necrotic tissue was gently scraped away with the edge of a curette (see Figure 2). This treatment was not timed; each wound was treated at 50% power until no additional slough or other necrotic tissue could be removed from the wound bed. This power intensity was selected based on the recommendation of the manufacturer and because no studies had been published on patient populations, the researchers chose to follow the manufacturer recommendations. Using a foot controller, the flow of saline was stopped when the treating clinician wanted to move the transducer to the next wound. After 10 minutes, the system automatically shut itself off; it can be re-started to continue wound treatment. After each use, the curette was autoclaved. Following the ultrasound, patients were treated with standard wound protocol for CVI ulcers, which included Silvercel (Johnson and Johnson Healthcare, New Brunswick, NJ) antimicrobial dressing, multilayer compression wraps (Profore, Smith & Nephew, London, UK), and pain medication if needed. Patients completed the questionnaire described previously following each treatment session.

  Wound characteristics were documented during each visit and included wound location, wound length/width/depth, amount of fibrin tissue, granular tissue color, presence of slough, periwound appearance, and drainage amount/color. Wound volume was calculated by multiplying wound length, width, and depth. For this study, wound bed characteristics were visually assessed by one of the researchers in the study, a nurse who worked full-time in the wound care center for more than 21 years. Fibrin was identified as a sticky substance present in layers in the wound bed with a clear, milky, or yellow color. Slough was noted to be yellow tissue that consisted of fibrin, pus, and protein material. A wound bed that contained slough always contained fibrin, but not vice versa. Wound bed characteristics were graded using Likert scales (see Table 2). Slough was always documented as present (1) or not present (0)

.   Data analysis. SPSS version 19.0 (IBM Corp, Chicago, IL) was used for data entry and analysis; significance was set at 0.05. Wound volume comparisons have been utilized as an outcome measure in a number of previous studies4,5,9,14,40 using LFU and therefore were compared between the first and last treatment session (eg, second visit for patient 1, third visit for patient 2) using t-tests in this study. Means for amount of wound fibrin, granulation tissue color, presence of slough, periwound appearance, amount of drainage, and drainage color were analyzed using Wilcoxon signed-ranks tests between the first and last treatment sessions. The sample size was too small to analyze pain and patient perception/function scores.

Results

  Two patients met the inclusion criteria and participated in the study. Ms. O was a 63-year-old woman with two wounds: one on her right lower leg and one on her left medial lower leg (see Table 3). Both wounds had been present for 12 months and had been previously treated with wet-to-dry dressings, compression wraps, debridement, and split-thickness skin grafts. She had rheumatoid arthritis at the time of the study. Mr. P was a 77-year-old man with seven wounds, four on the left lower leg and three on the right lower leg (see Table 3). These wounds had been present for 3 months and although the patient had been recommended to utilize compression by his family physician, he reported not using the compression bandages. No other interventions had been provided for Mr. P’s wounds before the start of the study. This patient suffered from heart and lung failure. Ms. O participated in two treatment sessions spread 3 weeks apart. Mr. P participated in three sessions, each occurring 1 week apart. The study participants did not attend additional sessions due to comorbidities that affected their ability to participate in treatment (eg, Mr. P was hospitalized for heart issues before his fourth scheduled visit).

  From the first to the last treatment session, wound characteristics changed significantly (P = 0.01 to P = 0.04); average mean fibrin scores changed from mostly moderate (3.33) to mild (1.67), periwound borders changed from mostly necrotic (3.89) to intact (1.22), drainage decreased from mostly moderate (2.89) to minimal (1.89), and drainage color changed from mostly serosanguinous — tinged with blood (3.22) to serous —pale yellow or transparent (0.89) (see Tables 4 and 5). In addition, eight wounds (89%) were filled with slough at the start of treatments compared to two wounds (22%) at the final session. Changes in granulation color were not statistically significant. Wound volume did not change significantly from the first visit to the last visit (t(8) = 1.2, P = 0.26). However, five wounds (56%) reduced in size by 100% during the study, and the remaining four wounds decreased in size between the first and last treatment (see Table 4). Figure 3 shows Ms. O’s right lower leg wound. Changes can be observed in the wound bed and include a change in color (red to pink) and a change in periwound appearance (macerated, erythema to intact). Overall wound volume decreased from 250.8 cm3 to 184.5 cm3. Other wound characteristics (fibrin, slough, drainage amount, and drainage color) were unchanged from the first to last treatment.

  Figure 4 shows three wounds on Mr. P’s left medial calf. The distal wound reduced in volume by 100%, while the two other wounds decreased in volume by 0.55 cm3 (proximal) and 9.4 cm3 (middle). The characteristics of the proximal wound remained unchanged with the exception of periwound, which became intact by the last treatment. Characteristics of the middle wound changed: fibrin from marked to none, slough from present to none, and drainage from yellow and serous to only serous. Characteristics of the bottom wound changed as well: fibrin from marked to none, slough from present to none, periwound from macerated, erythema to intact, and drainage color from serous, yellow to no drainage.

  Changes in pain were not statistically analyzed. Ms. O reported a pain level on the VAS scale of 8.5 out of 10 before the first treatment. At the second treatment session, she reported taking new medications of methadone and dilaudid and did not report any pain before or during treatment. Mr. P rated his pain levels before treatment as follows: visit 1 = 2 out of 10, visit 2 = 3 out of 10, visit 3 = 3 out of 10. Neither patient reported any changes in pain levels during or at the conclusion of the LFU treatment at any treatment session. Ms. O was not able to complete the questionnaire about perceptions of treatment and functional assessment (see Table 1) at the second visit secondary to being heavily medicated at this visit. Therefore, changes in these measures cannot be reported for Ms. O. Mr. P reported improvements in his perception of treatment that he scored as a 3 (somewhat helpful) on visits 1 and 2 and a 5 (extremely helpful) on visit 3. His functional assessments remained unchanged throughout his treatment; mobility = 5 (no problems walking about), self-care = 5 (no problems), usual activities = 3 (some problems), and anxiety = 3 (moderately anxious or depressed). In addition, neither patient reported any adverse events throughout the duration of the study.

Discussion

  The purpose of this study was to evaluate the use of LFU in patients with chronic wounds due to CVI. All wounds reduced in size (not statistically significant), and statistically significant differences in five of six wound characteristics were observed. No changes in wound pain were reported. Mr. P reported pain levels of 2 to 3 out of 10, and Mrs. O reported pain levels of 8.5 out of 10 before and during their respective LFU treatments.

  Current results are similar to a single-arm retrospective chart review by Bell and Cavorsi41 involving 76 participants with a wide etiology of wounds where the proportion of participants with >75% granulation tissue increased from 32% to 46% following a mean of 2.3 NLFU sessions occurring over a mean of 4.3 weeks. According to these authors, participants had to have >75% healthy granulation tissue in the wound bed to be calculated in these percentages. In addition, the proportion of periwound skin rated as normal increased from 20% at the beginning of the study to >75% by the end of the study. The proportion of participants with no slough in the wound bed increased from 27% at the study’s beginning to 55% by the study’s end. Finally, the amount of exudate was reduced significantly (P = 0.0002), and the amount of drainage decreased from moderate or scant to scant or no drainage.

  The results of this case study were encouraging for these two patients with CVI. Uhlemann et al18 reported previous studies using LFU had primarily involved individuals with foot wounds and diabetes mellitus and recommended testing the LFU on patients with additional diagnoses and comorbidities. The patients in the current study had a number of comorbidities such as rheumatoid arthritis, heart failure, and lung failure; however, all wounds demonstrated a reduction in wound volume following two or three treatment sessions.

  Tan et al5 used ultrasound delivered by a probe held in contact with the wound bed in 19 patients for a total of 5.7 treatments delivered over 2 to 3 weeks; whereas, the two participants in this study received either two or three treatments delivered over the same time period. Although Bell and Cavorsi41 reported the population of participations with >75% granulation tissue increased from 32% before to 46% after treatment, the median duration of treatment was 4.3 weeks. Other authors examined NLFU as a treatment and reported healing times between 5.5 and 12 weeks, and 51 patients with wounds of varying etiologies had a 94.9% reduction in wound volume over a period of 5.5 weeks.22 Twenty-nine (29) wounds of varying etiologies had a 62% reduction in wound volume over the course of 8.71 weeks.23 Foot ulcers in persons with diabetes mellitus were treated for 9.12 weeks, with 41% of the wounds achieving a 100% reduction in wound volume.22 Finally, among 35 patients with limb ischemia, 60% had at least a 50% reduction in wound size over the course of 12 weeks of LFU treatments.41

  Although Tan et al5 reported overall treatment time of 2 to 3 weeks, only 39% of the wounds achieved a 100% reduction in wound volume, compared to 56% of wounds in the present study. Other authors have reported between 5% and 51% of wounds achieving a 100% reduction in wound volume.4,21–23,40

  Additional studies to evaluate the effect of this treatment on lower leg ulcers in patients with CVI are needed. In addition, the use of LFU coupled with a curette should be compared to several control treatments, including other LFU techniques and other debridement methods (ie, surgical, autolytic, or enzymatic).

Limitations

  The limitations to this study include a small sample size with limited power. However, a moderate effect size42 (-0.53 to -0.61) was observed for all five significantly improved wound characteristics from the first to last treatment session (see Table 5). Study enrollment during the first 6 months of the study was not allowed due to contract negotiations between the ultrasound vendor and the facility where the study was conducted. Once the agreement was signed, two patients were recruited during the remaining 6 months of allocated equipment use by the vendor. In addition, the practitioners who provided the treatment felt more comfortable using their standard method of debridement (sharp debridement) and reported a subjective perception that the set-up procedure for the LFU was more time-consuming than the set up time for traditional sharp debridement. A time comparison between the two treatment modalities was not conducted. The LFU requires heating an IV bag, connecting the tip to the curette, and autoclaving the curette at the facility. Although the treating clinicians had been trained in its use, the LFU was a newer motor skill for them. Another limitation includes inability to continue patient follow-up to monitor wound progress or recurrence. Finally, Mr. P had not been compliant with his compression dressings on his own. These small wounds may have healed with the regular use of compression dressings without the addition of ultrasound treatment.

  A larger sample size would allow for correlations between patient, wound variables, and outcomes including pain.

Conclusion

  LFU was shown to be an effective wound care treatment for two patients with nine chronic wounds related to CVI. Wound characteristics — including the presence and amount of fibrin, periwound appearance, drainage amount and color, and percentage of wounds with slough present — improved significantly, and the volume of 56% (n = 5) of the wounds decreased 100%. These changes occurred over a period of 3 weeks and involved either two or three treatment sessions. Additional clinical studies to evaluate the safety and effectiveness of this treatment modality are needed.

Acknowledgment

  The authors of this study acknowledge the Oakland University-William Beaumont Hospital Multidisciplinary Research Grant for supporting the research, the William Beaumont Hospital Wound Care Center for providing the setting for research, and Arobella Medical, LLC for providing a grant for the LFU device used during the study.

 Dr. Maher is an Associate Professor, Physical Therapy Department; and Drs. Halverson, Misiewicz, Reckling, and Smart are physical therapy graduates, Oakland University, Rochester, MI. Mrs. Benton is a nurse manager; and Mrs. Schoenherr is a nurse practitioner, Beaumont Hospital Wound Care Center, Berkley, MI. Please address correspondence to: Sara F. Maher, DScPT, 3174 Human Health Building, Oakland University, Rochester, MI 48309; email: sfmaher@oakland.edu.

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