Poster session 9: Wound healing
P9.01
An assessment of intralesional epidermal growth factor for treating diabetic foot
wounds: the first experiences in Turkey
Bulent Ertugrul, University of Adnan Menderes School of Medicine, Aydın, Turkey
Benjamin A. Lipsky, University of Oxford & University of Geneva, Oxford, United Kingdom
Turkish Study Group of Intralesional Epidermal Growth Factor, University of Adnan
Menderes School of Medicine, Aydın, Turkey
Intralesional EGF was newly registered as a medication in Turkey in 2012. We present the
results of our experience using intralesional EGF in Turkey for patients with a diabetic foot
wound.
Between January 2012 and December 2013 we found a total of 174 patients from 25 Turkish
medical centres who were evaluable for this retrospective study. We recorded the data on
enrolled subjects in custom-designed patient follow-up forms. The application site for EGF
was first cleansed, then debrided of any necrotic or infected soft-tissues and any infected
bone. Then, patients received intralesional injections of 75 µg EGF three times per week on
alternate days. Patients were monitored daily for any adverse reactions to their treatment.
The patients were followed-up for varying periods after termination of their EGF treatments.
Most patients were late middle-aged men who had their foot ulcer for about 3 months.
Median treatment duration was 4 weeks and median frequency of EGF administration was
12 doses. Complete response (granulation tissue >75% or wound closure) was observed in
116 (66.7%) patients (Table 1)., The number of the patients whose wounds closed with only
EGF administration was 81 (46.6%) while the number of patients whose wound closure
occurred in conjunction with various surgical interventions, following EGF administration was
65 (37.3%). Overall, a total of 146 (83.9%) of the evaluable patients’ wounds were closed at
the end of therapy (Table 1). At the end of treatment, 5 patients (2 9%), required major
amputation. A total of 148 patients were followed up during the study period., Recurrence of
the ulcer on treatment site was observed in 12 patients (8 1%) during follow-up. Adverse
effects following EGF applications were reported in 97 patients (55.7%).
This trial suggests that in patients with diabetic foot ulcer who received standard care,
additional intralesional EGF application following infection control provides high healing rates
with low amputation rates. Meanwhile, in patients with adequate granulation tissue on the
ulcer site, performing surgical wound closure procedures may be a rational approach instead
of waiting for the response to EGF alone.
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P9.02
The effect and potential mechanism of VEGF on skeletal muscle fibers and diabetic
foot ulcer
Lijing Jia, Institute of Basic Medicine Science, Chinese PLA General Hospital, Beijing, China
Treatment of diabetic foot is a world-wide medical problem. Angiogenesis is the most key
and main problem which should be solved in the process of diabetic foot therapy. Current
treatments mostly concentrate on improving local micro-circulation and blood supply and
functions of vascular endothelial cell. However, the study of the mechanism in the effects of
musculofibers on wound healing remians elusive. As we know, there are mainly two
phenotypes of striated skeletal muscle fibers: glycolytic and oxidative fiber, the latter owns
higher oxidative mechanism and oxygen delivery capacity.Our hypothesis is increased
oxidative musculofiber provides faster tissue healing. The aim of this study is to observe the
effect and the mechanism of vascular endothelial growth factor(VEGF) on skeletal muscle
fiber transformation and angiogenesis. Thus, we indentify that increased oxidative
musculofiber provides faster tissue healing. In this study, we observe the fiber type
composition and capillary density in both exercise and non-exercise mouse model by
immunofluorescence with an antibody against the endothelial cell marker CD31, MHC I
antibody and MHC IIa antibody.Meanwhile, the concentration of VEGF in muscle is detected
by ELISA.Then we determine that whether VEGF can drive fiber type switching and induce
angiogenesis following VEGF delivery in vitro and vivo and investigate the mitochondrial
number and the level of glucose uptake. Moreover, using animal models, we identify that if
the increase of oxidative musculofibers have positive effect on wound healing.We find that
endurance exercise resulted in a significant increase in capillary density and glycolytic to
oxidative muscle fiber switching. Similary, VEGF can also induce these changs and during
this process the mitochondrial number and the level of glucose uptake increases.These
findings suggest that the VEGF can induce muscle fiber transformation and angiogenesis,
and this was likely mediated by mitochondrial biogenesis and improved glycometabolism
which play a key role in microenvironmet for angiogenesis.We believe this study will provide
further treatment choices to diabetic foot ulcer in clinical work.
This study was supported by the National Natural Science Foundation of China(81100591).
www.diabeticfoot.nl
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P9.03
Split-thickness skin grafting compared to epidermal harvesting in the treatment of
diabetic foot wounds: A literature review
Margot Waldman, Mercy St Vincent Hospital, Perrysburg, OHIO, United States
Aim: In recent decades, there has been an increase in the need for wound care, especially
in diabetic patients. Using autografts instead of conservative wound dressings has proven to
be very reliable and can produce astonishing results. This is a literature review that
compares the traditional method of a split-thickness skin grafting with a new device that uses
epidermal suction blisters to treat non-healing diabetic wounds.
Methods: There is an extensive collection of research on the use of split thickness skin
grafts on a variety of wounds. In examining multiple research studies, it shows that split
thickness skin grafts can lead to a healed wound in a compliant patient. A new device
[Cellutome™] produces epidermal suction blisters and can aid in diabetic foot wounds. Due
to the extreme novelty of this product, there is limited research currently available on this
specific device. However, multiple studies are being conducted at this time in the United
States to explore this product.
Results: Split thickness skin grafts have multiple guidelines that a patient has to achieve
before they will be considered for a graft placement. The graft must be done in a sterile
operative room setting and, after application, has a risk of complications that can include
hematomas, need for re-grafting, and pigmentation changes at the donor sites. Research
has shown that, with patient compliance, chances of the graft taking to the wound and
healing can be good. The new device also has specific guidelines that must be met before
application, but its aim is to treat wounds in a shorter amount of time, without the use of
anesthesia, and claims to have lower complication risks than the traditional approach. The
current studies of the novel device appear to be impressive, with excellent results for both
the patient and physician.
Conclusions: Split thickness skin grafts have had favorable outcomes in the reliable patient;
however, it is possible that a “new kid in town” can outshine traditional grafting with new
technology. Epidermal harvesting appears to be favorable in reduction of possible postoperative complications, decrease in healing time, and ease of application.
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Page 4 of 11
P9.04
An investigation of the effectiveness of a dressing of sodium carboxymethylcellulose
with regenerated cellulose on diabetic foot ulcers
Pauline Wilson, St James' Hospital, Dublin, Ireland
Mark Dooley, St. James' Hospital, Dublin, Ireland
Meave Corcoran, St. James' Hospital, Dublin, Ireland
Aims: The Aim of this case series was to evaluate the use of a new formulation of a
dressing of Sodium Carboxymethyl Cellulose with Regenerated Cellulose fibres, (SCMCRCF) as a treatment modality in the management of diabetic foot ulceration in a Podiatry led
Diabetic Foot Clinic. This case series considers the ability of SCMC-RCF to decrease wound
size, to decrease slough, to increase granulation and to manage exudate.
Methods: 10 Patients were recruited from the Diabetic Foot Clinic with a wound that
clinicians perceived would benefit from the properties of the SCMC-RCF dressing. At each
treatment episode, the wound was inspected, cleaned and sharp debrided as per standard
practice. SCMC-RCF was then applied to the area. This was covered with a secondary
dressing and secured with tape.
Results: The aims of the SCMC-RCF dressing as described were achieved in each of the
10 cases.
Conclusion: This case series suggests that the SCMC-RDF dressing, in conjunction with
standard care can increase healing rates and reduce healing time. The authors believe that
in the moderate to heavily exuding wound the use of SCMC-RCF dressings enabled them to
reduce the number of dressing changes required by individual patients thus reducing Health
Care worker time and associated costs. We also feel that the use of this product may have a
positive impact on the quality of life for patients. We feel that consideration should be paid to
Quality adjusted life years (QALY) as well as Healthcare worker time warrants further
investigation.
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P9.05
Skin grafts and tissue replacements in the treatment of diabetic foot ulcers: the
ultimate cover?
Katrien Santema, AMC, Amsterdam, Netherlands
Paul Poyck, AMC, Amsterdam, Netherlands
Dirk Ubbink, AMC, Amsterdam, Netherlands
Aim: Despite the many strategies available to treat diabetic foot ulcers, not all ulcers achieve
complete healing. Additional treatments with skin grafts and tissue replacement products
have been developed to promote complete wound closure by covering the skin defect. We
systematically reviewed the effectiveness of skin grafts and tissue replacement products in
addition to standard care for diabetic foot ulcers.
Methods: In our Cochrane review we included all available evidence from randomised
clinical trials performed worldwide. Study selection, data extraction and quality assessment
were carried out independently by two review authors.
Results: Fifteen of the 265 identified publications were eligible, and included 1488
randomised participants. Twelve trials compared a skin graft or tissue replacement with
standard care. The remaining three trials compared two types of tissue replacement
products. Most trials assessed the effectiveness of a cultured human dermal replacement
consisting of dermal matrix proteins and fibroblasts.
Pooled results showed that tissue replacements increased ulcer healing rate compared to
standard care (RR 1.50, 95% CI 1.30 to 1.73; RD 0.23, 95% CI 0.14 to 0.32; NNT 6, 95% CI
5 to 9). No significant difference in healing rate was shown by one of the three studies that
compared two types of tissue replacement products. Furthermore, no statistical differences
were found for time to complete ulcer healing and recurrence.
Conclusions: Current best available evidence shows that skin grafts and tissue
replacements can increase the healing rate of diabetic foot ulcers when used in conjunction
with standard care. However, long term results are not yet available and cost-effectiveness
is uncertain.
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P9.06
Chronic non-healing wound closures and amputation prevention: A comprehensive
prospective case report and scrutiny of a novel allograft
Tammer Elmarsafi, Medstar Washington Hospital Center, Washington, DC, United States
John S. Steinberg, MedStar Washington Hospital Center, Washington, DC, United States
Aims:
1: Demonstrate the importance of a multimodal approach to maximize favorable Limb
Salvage outcomes in complex wounds.
2: Examine the efficacy and ease of use of a novel bioengineered alternative tissue allograft
in two year chronic foot ulcer.
Methodology: This is an institutional compliant, single-center, prospective case report with
incorporated retrospective chart analysis. The duration of the prospective analysis is 37
weeks. A comprehensive retrospective chart review begins at the patient’s sentinel podiatric
crisis. Definitive multimodal interventions are examined Prospectively; 92 weeks of review.
This case report covers a total of 129 weeks.
Procedures: Multi-staged operative management included surgical debridement, osseous
resection for ulcer eradication, Peroneus brevis transfer and biotenodesis, and Achilles
tendon and Tibialis anterior tendon lengthenings, with outpatient wound management
utilizing a novel bioengineered alternative tissue allograft.
Results: Surgical and postoperative wound management therapies yielded complete
resolution of, a lateral ulceration [time to closure= 15 days], and 99% closure of the dorsal
wound in 22 weeks; from 5.6cm x 2.3cm x 0.2cm to 0.5cm x 0.1cm x 0.1cm. Results of
previous failed interventions are discussed., The use of the placental membrane matrix was
well suited for this patient, easy to use, and offered optimal results in the first applications.
This was however followed by plateau of wound closure velocity. It did yield the highest
success than with 3 other previously used products in treating a 2 year intractable ulcer.
Conclusions: Use of definitive comprehensive multi-staged surgical correction resulted in
eradication of lateral ulcer etiology and a plantigrade foot., Surgical correction was crucial in
the closure of these wounds. The addition of advanced wound management plan resulted in
100% sustained closure of a lateral wound and 99% reduction of a 2 year old non-healing
dorsal wound. Results required 14 applications of a novel bioengineered allograft consisting
of a cryopreserved placental membrane matrix when all other means failed.
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P9.07
Use of a new gel-like dermal matrix for the treatment of diabetic foot ulcers: efficacy
study on complicated lower limb lesions
Luca Dalla Paola, Maria Cecilia Hospital, Cotignola, Italy
Anna Carone, Maria Cecilia Hospital, Cotignola, Italy
Maria Catena Principato, Maria Cecilia Hospital, Cotignola, Italy
Marco Pattavina, Maria Cecilia Hospital, Cotignola, Italy
Aim: Limb salvage may be a challenging problem in diabetic population affected by foot
ulcers. In presence of infection progression surgical procedures becomes an essential
treatment to save limbs. Cellular or acellular dermal substitutes are used both for covering
lesions after, surgical debridement without primary intention closure, or in the case of
dehiscence of the surgical site. Gel-like dermal matrix* is a dermal substitute developed for
use when the geometry and localization of a lesion and/or the exposure of deep tissue does
not allow the use of dermal substitute sheet.
Method: From June 2013 to October 2014, 71 consecutive diabetic patients with foot
ulcerations were enrolled. 25 patients had lesions resulting from an open minor amputation,
21 patients had open ostectomy with residual exposure of cancellous bone, 10 patients had
dehiscence of the surgical site and 15 patients had deep wounds. All the lesions listed were
staged as grade III B-D according to the classification of the University of Texas.
Results / Discussion: The average follow up was 184 08±130 09 days. 44 (61 97%)
patients healed with complete re-epithelialization of the lesion. Of these, 25 patients received
simultaneous treatment with application of gel-like dermal matrix* and skin grafting, 4
patients were treated with delayed skin grafting after application of the dermal substitute. 16
(22 54%) patients showed an improvement of local conditions through cover of the exposed
bone. 11 (15 49%) patients showed no improvement in relation to recurrence of infection
and/or critical ischemia.
Conclusion: The use of this gel-like dermal matrix* can be considered an affective
treatment for diabetic foot wounds added to a program of multidisciplinary therapy.
Integra®flowable wound matrix
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P9.08
The effects of Hyperbaric Oxygen Therapy (HBOT) as adjunctive treatment for diabetic
foot ulcers
Luinio Tongson, Dr. James G. Dy Wound Healing and Diabetic Foot Center, Manila,
Philippines
Diabetic foot is associated with lower limb amputation and poor quality of life. The use of
Hyperbaric Oxygen Therapy (HBOT) increases the success rate of healing diabetic foot
wounds and decreases the incidence of lower extremity amputation.
Objective: This study aims to evaluate the effects of HBOT on the healing of diabetic foot
wounds, and determine the major amputation rate of diabetic foot patients treated with
HBOT.
Methodology: This prospective cross-sectional study was conducted at a Wound Healing
and Diabetic Foot Center. Ninety-nine patients with diabetic foot Wagner 3 and Wagner 4
ulcers were given HBOT at 2.5 ATA (atmospheric pressure), 90 minutes a day, 5 days a
week, as adjunctive therapy. At the end of the treatment, the ulcers were evaluated.
Results: Twenty-five patients who received less than six sessions of HBOT were excluded
in the study. There were 44 males and 30 females, aged 39 to 97, with a mean age of 63.
They received between 6 and 30 HBOT sessions, with an average of 14. Sixty-seven
patients (91%) who underwent HBOT had the wound improved while seven patients (9%)
underwent major amputation. Among the 67 patients who improved on HBOT, 59 (88%) had
complete healing of the diabetic wound. The other 8 patients (12%) had incomplete healing
but with improvement. There were 7 patients who underwent major amputation, 2 with
Wagner 3 lesions and 5 with Wagner 4 lesions.
Conclusion:Treatment of diabetic foot wounds with an aggressive, multidisciplinary
therapeutic protocol in conjunction with hyperbaric oxygen treatment is effective in
decreasing major amputations. The preliminary result of the study is promising, but large
randomized controlled trials are necessary in order to establish the efficacy of HBOT in the
treatment of diabetic foot.
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P9.09
Hyperbaric oxygen therapy seems to preserve renal function in patients with diabetes
and hard-to-heal foot ulcers
Katarina Fagher, Skåne University Hospital, Lund, Sweden
Per Katzman, Skåne University Hospital, Lund, Sweden
Magnus Londahl, Skane University Hospital, Lund, Sweden
Aim: Systemic hyperbaric oxygen therapy (HBO), a medical treatment for hard-to-heal
diabetic foot ulcers, has been demonstrated to increase oxygenation in hypoxic tissue and
might enhance microvascular function. Whether HBO has any effects on renal function has
to our knowledge previously not been evaluated in humans. The aim of this study was to
evaluate the effect of HBO on estimated glomerular filtration rate (eGFR) and urine
albumin/creatinine ratio (UACR) in patients with diabetes and hard-to-heal foot ulcers.
Methods: In a prospective randomised double-blinded placebo-controlled study effects of
HBO was evaluated. Patients were randomised to 40 treatment sessions with either oxygen
or air, at 2.5 ATA. Patients fulfilling (per-protocol requirement) at least 36 completed
treatment sessions were included. UACR and eGFR based on serum creatinine were
evaluated before and at the one-year follow-up. Patients with end stage renal disease,
defined as eGFR <15 ml min-1 1.73 m-2 or on-going dialysis at baseline were excluded from
analysis. Further, UACR values analysed during acute urinary tract infections or use of
urinary catheter, were excluded. Non-parametric statistics were used and a two-sided
p<0.05 was considered as statistical significant. Data are given as median (interquartile
range).
Results: 75 patients (38 HBO / 37 placebo) completed at least 36 treatment sessions. Of
these, 3 were on dialysis and 4 died before follow-up. Accordingly, 68 patients (35 HBO / 33
placebo) could be evaluated. UACR at baseline and 1 year follow-up was only available in
39 (19 vs. 20) patients.
Baseline characteristics as well as treatment with renin-angiotensin system inhibitors were
similar. Among HBO treated patient at 1-year follow-up there was a statistical significant
increase in eGFR (67.0 (43.3-92.9) vs 68.1 (39.8-91.6), p=0.04) and a decrease in UACR
(75 (12-165) vs 21 (5-63) g/mol, p=0.005), while eGFR (58.9 (39.6-82.7) vs. 57.3 (35.871.7), p=0.09) as well as UACR (30 (5-59) vs 30 (3-124) g/mol, n.s) were similar among
placebo treated patients.
Conclusions: HBO treatment might have beneficial effects on renal function in patients with
diabetes and hard-to-heal foot ulcers.
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P9.10
NO-air-plasma currents and ozone therapy in treatment of patients with diabetic foot
syndrome
Vladimir Obolenskiy, City Hospital #13, RNRMU, Moscow, Russia
Alexander Molotschnikov, City Hospital #13, Moscow, Russia
Aim: to determine the effect of joint use of NO-air-plasma currents (APC) and ozone therapy
(OT) on cellular elements and the level of bacteriological contamination of wounds occurring
as a result of diabetic foot syndrome (DFS).
Methods: A total of 160 patients suffering from purulo-necrotic feet wounds arising from
DFS. Patients’ average age was 63 9+9 7 years, with men slightly outnumbering women, 57
1 vs. 42 9%, respectively. Predominant conditions neuro-ischemic form of DFS (>87%).
The main group consisted of 57 (35 6%) patients that underwent corrective surgery on major
vessels of lower limbs and treated daily with APC and OT. The wound then was dressed
with water-soluble ointment.
The first control group consisted of 75 (46 9%) patients that did not undergo corrective
surgery on major vessels of lower limbs, the second group consisted of 28 (17 5%) patients
with corrective vascular measures. Treatment in these groups involved daily changes of
wound dressings and application of water-soluble ointment.
Results: Proliferation activity of fibroblastic cells, collagenogenesis and mitotic activity of
epithelial cells in the main group exceeded the same indexes in the first control group more
than two times and more than 1 5 times in the second control group. Microbiological
contamination of wound in the main group on the 4-5 day declined down to 103-105
CFM/cm2, however in both control groups this score remained >105 for up to 12 days.
Conclusion: Sequenced application of APC and OT in treatment of patients with DFS is
characterized with pronounced bactericidal effect and boosts epithelialization process,
making it two times faster.
*) «Plazon» & UOTA 60-01 «Medozon»; made in Russia.
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