practice
Use of cryopreserved umbilical cord with negative pressure wound therapy for complex diabetic ulcers with osteomyelitis Objective: The objective of this study was to evaluate the combined use of cryopreserved human umbilical cord (cUC) allograft and negative pressure wound therapy (NPWT) in treating complex diabetic foot ulcers (DFUs) with bone exposure and osteomyelitis. These types of wound are known to carry a high morbidity and mortality. Methods: A single-center, retrospective chart review was performed to assess the efficacy of the combined use of cUC with NPWT, by the same surgeon, to help promote the closure of complex DFUs presenting with biopsy-proven osteomyelitis. Change in wound size and volume, time to wound closure, and number of cUC applications were assessed. Results: We identified of 14 wounds in 13 patients, with an average initial wound area of (mean±standard devaition) 33.2±21.7cm2 and
wound volume of 52±26.2cm3. All achieved complete re-epithelialisation with an average time to closure of 24.0±10.9 weeks, using between 2–5 cUC applications. No adverse events were noted and none of the wounds required limb amputation during the a follow-up of 24 months for each patient. Conclusion: The results suggest that combined use of cUC and NPWT may be effective in improving the healing of complex DFUs that present with osteomyelitis. Prospective, randomised controlled trials are warranted to confirm this efficacy as well as its potential applications in other chronic wounds. Declaration of interest: Dr Raphael is a paid consultant for Amniox Medical and Acelity.
C
omplex ulcers are difficult to heal due to their exposed bone, tendon, muscle, and/ or joint capsule. These ulcers are compromised for a prolonged period of time and are associated with significant morbidity, including limb amputation and high mortality.1 Chronic foot ulceration is the most common, single precursor of lower extremity amputations among people with diabetes, it is a precursor to approximately 85% of the lower extremity amputations within this population.1 After one major lower extremity amputation, the 5-year survival rate is estimated to be 50% and the risk of amputation dramatically increases when the foot ulcer is complicated by osteomyelitis.2 To address the physiological deficiencies underlying chronic wounds, various tissue engineering technologies have been introduced, including cellular, as well as acellular, skin replacement products and extracellular matrix (ECM) replacement therapies. It is a common trend in the diabetic foot care to use advanced moist wound therapy, bioengineered tissue or skin substitute, and negative pressure wound therapy (NPWT).3 While proposed benefits of NPWT comprise
*A. Raphael,1 DPM, FACFAS, Partner Podiatrist ; J. Gonzales,2 Podiatry Resident, PGY-3 *Corresponding authors email: [email protected] 1 Village Podiatry Centers, Smyrna, GA, US. 2 Dekalb Medical Podiatric Residency, Decatur, GA, US.
S38
of improved perfusion and increased granulation tissue, published NPWT clinical trials show only significant reduction in wound size when compared with standard dressings and that the majority of wounds requiring secondary intervention to reach full closure.4 Newer treatment technologies have been introduced that have been shown to increase the probability of complete wound closure in hard-to-heal foot ulcerations. These new treatments include recombinant growth factors, living human skin equivalents, sound-wave technology and dermal substitutes. While advanced tissue therapies are often used to expedite wound healing, they create a physical barrier over the wound, prohibiting their use with NPWT. The first reported clinical application of amniotic membrane (AM) was for skin transplantation.5 However, in the late 20th century the clinical use of AM gained popularity in open wounds,6 skin burns,7 and leg ulcers.8 Surgeons are increasingly turning to AM and umbilical cord (UC) products to promote healing of chronic, complex wounds.9 A recent study showed that cryopreserved umbilical cord (cUC) allograft is effective in promoting wound healing in complex diabetic foot ulcers (DFUs) with exposure of bone, tendon, muscle and joint capsule that also presents with biopsy-proven osteomyelitis.10 The results were encouraging and demonstrated that application of cUC with an average of 1.24 applications
© 2017 MA Healthcare ltd
complex wounds ● diabetic foot ulcer ● NPWT ● osteomyelitis ● cryopreserved umbilical cord
J O U R N A L O F W O U N D C A R E N O R T H A M E R I C A N S U P P L E M E N T, V O L 2 6 , N O 1 0 , O C T O B E R 2 0 1 7
© MA Healthcare Ltd. Downloaded from magonlinelibrary.com by 203.002.032.208 on October 5, 2017. Use for licensed purposes only. No other uses without permission. All rights reserved.
practice
a
b
c
d
e
f
together with surgical sharp debridement, resection of infected bone, and systemic antibiotics can achieve 78.7% wound closure. Here, we retrospectively review the clinical outcome of combined use of cUC and NPWT performed by the same physician at a single center in patients with complex DFUs presenting with biopsy-proven osteomyelitis.
Materials and methods Clinical data retrieval Following the approval by the Western Institutional Review Board (Protocol # 20170571), a retrospective chart review was performed on patients presenting with complex DFUs and treated at Village Podiatry Centers (Smyrna, GA, US) with the combinatorial application of cUC (NEOX CORD 1K, Amniox Medical Inc., Atlanta, GA, US) and NPWT between May 2015 and June 2017. The exclusion criteria were subjects that did not have postoperative outcome measurements and those who were lost to follow-up before complete wound closure. To determine the safety and effectiveness of combined use of cUC and NPWT, we also retrieved clinical data regarding overall wound measurements to document wound healing changes over time as well as demographic information and significant medical history including comorbidities, prior treatments, and amputations. S40
Treatment procedures All study patients underwent the same procedure performed by the same clinician (AR). In brief, they were brought to the surgery suite where the index wound was cleaned and debrided excisionally with sharp instruments (for example with scalpel, curette, and rongeur) to achieve a healthy, bleeding base (Fig 1a). All patients had osteomyelitis confirmed by exposed bone and positive probe to bone and by submitting resected non-viable bone to microbiology. After debridement, the cUC was cut into long strips (Fig 1b and 1c) and woven over the V.A.C. GranuFoam sponge (V.A.C. Therapy, KCI US) (Fig 1d), which was placed directly over the wound bed to cover the entire wound (Fig 1e). The pressure was set to –125mmHg on continuous therapy for constant suction (Fig 1f). The foam was changed four days later and then twice a week until the wound was flush to the surface. After this NPWT was discontinued and a regular absorbent dressing (a non-occlusive wound contact layer such as Cutimed Sorbact WCL, BSN Medical or Conformant wound veil, Smith & Nephew), then a compressive dressing, ABD pad and ACE wrap, was used until the wound healed. Dressing changes were performed according to amount of exudate, typically 2–3 times per week. For the entire follow-up period, wounds were cleansed and wound dressings were re-applied as needed at weekly follow-up visits. In addition, patients were given standard concomitant therapies, such as debridement, as well as offloading and hyperbaric therapy (HBOT) in some cases. Because of residual acute osteomyelitis, confirmed by inter-operative biopsies and cultures, all patients were also treated with appropriate antibiotic therapy with the assistance of an infectious disease specialist when needed. For wounds requiring additional applications of cUC, patients underwent sharp debridement and application of cUC, with or without NPWT, as determined by the surgeon, in the operating room. Outcome measures A baseline wound area was obtained post-debridement using a ruler to determine length and width of the wound before cUC application. Wound measurements were obtained in the same manner at follow-up visits throughout the entire postoperative period. Complete wound healing was defined as 100% re-epithelialisation as determined by the investigator. For those wounds achieving complete healing, the total time needed to achieve initial wound closure was assessed and plotted using Microsoft Excel 2011 (Redmond, WA, US). In addition to wound closure, the relationship between the initial wound area and the time needed to achieve closure was assessed by using a paired two sample for means t-test (Microsoft Excel). The mean wound area was also compared with the average number of applications of cUC using a paired two sample for means t-test (Microsoft Excel). p-values ≤0.05 between groups were considered statistically significant.
© 2017 MA Healthcare ltd
Fig 1. Operation procedure. All study patients underwent the same methods performed by the same clinician. The index wound was cleaned and debrided excisionally with sharp instrumentation to achieve a healthy, bleeding base (a). After debridement, the cryopreserved umbilical cord (cUC) was cut into long strips (b and c) and woven over the V.A.C. GranuFoam sponge (d), which is placed directly over the wound bed to cover the entire wound (e). The pressure was set to –125mmHg on continuous therapy to achieve constant suction (f)
J O U R N A L O F W O U N D C A R E N O R T H A M E R I C A N S U P P L E M E N T, V O L 2 6 , N O 1 0 , O C T O B E R 2 0 1 7
© MA Healthcare Ltd. Downloaded from magonlinelibrary.com by 203.002.032.208 on October 5, 2017. Use for licensed purposes only. No other uses without permission. All rights reserved.
practice Results
© 2017 MA Healthcare ltd
Clinical features After review, a total of 14 wounds in 13 patients met the inclusion criteria. There were 12 males and one female with mean (±standard deviation (SD)) age of 60 ± 16.3 years (Table 1). All DFUs were categorised as ‘complex’ because the wound had bone exposure and positive probe-to-bone. In addition, all these DFU presented with osteomyelitis, confirmed by bone biopsy and microbiology. There were 11 wounds present for 6.0 ± 4.5 weeks before cUC application, while the other three wounds were acutely induced by gangrene. The most significant prior treatments included debridement (14/14), offloading (14/14), NPWT (6/14), and HBOT (2/14). Among the most significant comorbidities were neuropathy (6/14), diabetes (13/14), peripheral vascular disease (PVD) (8/14), thyroid issues (8/14), hypertensive heart disease (12/14), joint contracture (3/14), ischaemia (5/14) and anaemia (3/14). At initial presentation, six wounds were at a transmetatarsal amputation (TMA) site, three were in the midfoot, foue were in the forefoot and one was on the heel. Wound healing following cUC application and NPWT All wounds received cUC application and NPWT as well as standard concomitant therapies such as debridement (14/14), HBOT (3/14), and offloading (12/14). The average initial wound area and volume was 33.2 ± 21.7cm2 and 52 ± 26.2cm3 respectively (Table 1). All wounds achieved complete wound closure defined by complete re-epithelialisation in 24.0 ±v10.9 weeks (range: 10–52 weeks). There were two wounds that healed by 12 weeks, five wounds healed by 16 weeks, and the remaining seven wounds reached complete healing within 30 weeks. Overall, the number of cUC applications ranged between 2–5, with one wound reaching 100% re-epithelisation after two cUC applications, six after three applications, five after four applications and one after five applications. To determine if the initial wound size correlated with either the time to healing or number of cUC applications, two separate paired t-tests were conducted. The result showed that there was an insignificant correlation between the mean wound area and weeks to closure (p=0.13). However, the correlation between mean wound area and the number of cUC applications was statistically significant (p≤0.001). That was reflected by the finding that the two smallest wounds (
Use of cryopreserved umbilical cord with negative pressure wound therapy for complex diabetic ulcers with osteomyelitis Objective: The objective of this study was to evaluate the combined use of cryopreserved human umbilical cord (cUC) allograft and negative pressure wound therapy (NPWT) in treating complex diabetic foot ulcers (DFUs) with bone exposure and osteomyelitis. These types of wound are known to carry a high morbidity and mortality. Methods: A single-center, retrospective chart review was performed to assess the efficacy of the combined use of cUC with NPWT, by the same surgeon, to help promote the closure of complex DFUs presenting with biopsy-proven osteomyelitis. Change in wound size and volume, time to wound closure, and number of cUC applications were assessed. Results: We identified of 14 wounds in 13 patients, with an average initial wound area of (mean±standard devaition) 33.2±21.7cm2 and
wound volume of 52±26.2cm3. All achieved complete re-epithelialisation with an average time to closure of 24.0±10.9 weeks, using between 2–5 cUC applications. No adverse events were noted and none of the wounds required limb amputation during the a follow-up of 24 months for each patient. Conclusion: The results suggest that combined use of cUC and NPWT may be effective in improving the healing of complex DFUs that present with osteomyelitis. Prospective, randomised controlled trials are warranted to confirm this efficacy as well as its potential applications in other chronic wounds. Declaration of interest: Dr Raphael is a paid consultant for Amniox Medical and Acelity.
C
omplex ulcers are difficult to heal due to their exposed bone, tendon, muscle, and/ or joint capsule. These ulcers are compromised for a prolonged period of time and are associated with significant morbidity, including limb amputation and high mortality.1 Chronic foot ulceration is the most common, single precursor of lower extremity amputations among people with diabetes, it is a precursor to approximately 85% of the lower extremity amputations within this population.1 After one major lower extremity amputation, the 5-year survival rate is estimated to be 50% and the risk of amputation dramatically increases when the foot ulcer is complicated by osteomyelitis.2 To address the physiological deficiencies underlying chronic wounds, various tissue engineering technologies have been introduced, including cellular, as well as acellular, skin replacement products and extracellular matrix (ECM) replacement therapies. It is a common trend in the diabetic foot care to use advanced moist wound therapy, bioengineered tissue or skin substitute, and negative pressure wound therapy (NPWT).3 While proposed benefits of NPWT comprise
*A. Raphael,1 DPM, FACFAS, Partner Podiatrist ; J. Gonzales,2 Podiatry Resident, PGY-3 *Corresponding authors email: [email protected] 1 Village Podiatry Centers, Smyrna, GA, US. 2 Dekalb Medical Podiatric Residency, Decatur, GA, US.
S38
of improved perfusion and increased granulation tissue, published NPWT clinical trials show only significant reduction in wound size when compared with standard dressings and that the majority of wounds requiring secondary intervention to reach full closure.4 Newer treatment technologies have been introduced that have been shown to increase the probability of complete wound closure in hard-to-heal foot ulcerations. These new treatments include recombinant growth factors, living human skin equivalents, sound-wave technology and dermal substitutes. While advanced tissue therapies are often used to expedite wound healing, they create a physical barrier over the wound, prohibiting their use with NPWT. The first reported clinical application of amniotic membrane (AM) was for skin transplantation.5 However, in the late 20th century the clinical use of AM gained popularity in open wounds,6 skin burns,7 and leg ulcers.8 Surgeons are increasingly turning to AM and umbilical cord (UC) products to promote healing of chronic, complex wounds.9 A recent study showed that cryopreserved umbilical cord (cUC) allograft is effective in promoting wound healing in complex diabetic foot ulcers (DFUs) with exposure of bone, tendon, muscle and joint capsule that also presents with biopsy-proven osteomyelitis.10 The results were encouraging and demonstrated that application of cUC with an average of 1.24 applications
© 2017 MA Healthcare ltd
complex wounds ● diabetic foot ulcer ● NPWT ● osteomyelitis ● cryopreserved umbilical cord
J O U R N A L O F W O U N D C A R E N O R T H A M E R I C A N S U P P L E M E N T, V O L 2 6 , N O 1 0 , O C T O B E R 2 0 1 7
© MA Healthcare Ltd. Downloaded from magonlinelibrary.com by 203.002.032.208 on October 5, 2017. Use for licensed purposes only. No other uses without permission. All rights reserved.
practice
a
b
c
d
e
f
together with surgical sharp debridement, resection of infected bone, and systemic antibiotics can achieve 78.7% wound closure. Here, we retrospectively review the clinical outcome of combined use of cUC and NPWT performed by the same physician at a single center in patients with complex DFUs presenting with biopsy-proven osteomyelitis.
Materials and methods Clinical data retrieval Following the approval by the Western Institutional Review Board (Protocol # 20170571), a retrospective chart review was performed on patients presenting with complex DFUs and treated at Village Podiatry Centers (Smyrna, GA, US) with the combinatorial application of cUC (NEOX CORD 1K, Amniox Medical Inc., Atlanta, GA, US) and NPWT between May 2015 and June 2017. The exclusion criteria were subjects that did not have postoperative outcome measurements and those who were lost to follow-up before complete wound closure. To determine the safety and effectiveness of combined use of cUC and NPWT, we also retrieved clinical data regarding overall wound measurements to document wound healing changes over time as well as demographic information and significant medical history including comorbidities, prior treatments, and amputations. S40
Treatment procedures All study patients underwent the same procedure performed by the same clinician (AR). In brief, they were brought to the surgery suite where the index wound was cleaned and debrided excisionally with sharp instruments (for example with scalpel, curette, and rongeur) to achieve a healthy, bleeding base (Fig 1a). All patients had osteomyelitis confirmed by exposed bone and positive probe to bone and by submitting resected non-viable bone to microbiology. After debridement, the cUC was cut into long strips (Fig 1b and 1c) and woven over the V.A.C. GranuFoam sponge (V.A.C. Therapy, KCI US) (Fig 1d), which was placed directly over the wound bed to cover the entire wound (Fig 1e). The pressure was set to –125mmHg on continuous therapy for constant suction (Fig 1f). The foam was changed four days later and then twice a week until the wound was flush to the surface. After this NPWT was discontinued and a regular absorbent dressing (a non-occlusive wound contact layer such as Cutimed Sorbact WCL, BSN Medical or Conformant wound veil, Smith & Nephew), then a compressive dressing, ABD pad and ACE wrap, was used until the wound healed. Dressing changes were performed according to amount of exudate, typically 2–3 times per week. For the entire follow-up period, wounds were cleansed and wound dressings were re-applied as needed at weekly follow-up visits. In addition, patients were given standard concomitant therapies, such as debridement, as well as offloading and hyperbaric therapy (HBOT) in some cases. Because of residual acute osteomyelitis, confirmed by inter-operative biopsies and cultures, all patients were also treated with appropriate antibiotic therapy with the assistance of an infectious disease specialist when needed. For wounds requiring additional applications of cUC, patients underwent sharp debridement and application of cUC, with or without NPWT, as determined by the surgeon, in the operating room. Outcome measures A baseline wound area was obtained post-debridement using a ruler to determine length and width of the wound before cUC application. Wound measurements were obtained in the same manner at follow-up visits throughout the entire postoperative period. Complete wound healing was defined as 100% re-epithelialisation as determined by the investigator. For those wounds achieving complete healing, the total time needed to achieve initial wound closure was assessed and plotted using Microsoft Excel 2011 (Redmond, WA, US). In addition to wound closure, the relationship between the initial wound area and the time needed to achieve closure was assessed by using a paired two sample for means t-test (Microsoft Excel). The mean wound area was also compared with the average number of applications of cUC using a paired two sample for means t-test (Microsoft Excel). p-values ≤0.05 between groups were considered statistically significant.
© 2017 MA Healthcare ltd
Fig 1. Operation procedure. All study patients underwent the same methods performed by the same clinician. The index wound was cleaned and debrided excisionally with sharp instrumentation to achieve a healthy, bleeding base (a). After debridement, the cryopreserved umbilical cord (cUC) was cut into long strips (b and c) and woven over the V.A.C. GranuFoam sponge (d), which is placed directly over the wound bed to cover the entire wound (e). The pressure was set to –125mmHg on continuous therapy to achieve constant suction (f)
J O U R N A L O F W O U N D C A R E N O R T H A M E R I C A N S U P P L E M E N T, V O L 2 6 , N O 1 0 , O C T O B E R 2 0 1 7
© MA Healthcare Ltd. Downloaded from magonlinelibrary.com by 203.002.032.208 on October 5, 2017. Use for licensed purposes only. No other uses without permission. All rights reserved.
practice Results
© 2017 MA Healthcare ltd
Clinical features After review, a total of 14 wounds in 13 patients met the inclusion criteria. There were 12 males and one female with mean (±standard deviation (SD)) age of 60 ± 16.3 years (Table 1). All DFUs were categorised as ‘complex’ because the wound had bone exposure and positive probe-to-bone. In addition, all these DFU presented with osteomyelitis, confirmed by bone biopsy and microbiology. There were 11 wounds present for 6.0 ± 4.5 weeks before cUC application, while the other three wounds were acutely induced by gangrene. The most significant prior treatments included debridement (14/14), offloading (14/14), NPWT (6/14), and HBOT (2/14). Among the most significant comorbidities were neuropathy (6/14), diabetes (13/14), peripheral vascular disease (PVD) (8/14), thyroid issues (8/14), hypertensive heart disease (12/14), joint contracture (3/14), ischaemia (5/14) and anaemia (3/14). At initial presentation, six wounds were at a transmetatarsal amputation (TMA) site, three were in the midfoot, foue were in the forefoot and one was on the heel. Wound healing following cUC application and NPWT All wounds received cUC application and NPWT as well as standard concomitant therapies such as debridement (14/14), HBOT (3/14), and offloading (12/14). The average initial wound area and volume was 33.2 ± 21.7cm2 and 52 ± 26.2cm3 respectively (Table 1). All wounds achieved complete wound closure defined by complete re-epithelialisation in 24.0 ±v10.9 weeks (range: 10–52 weeks). There were two wounds that healed by 12 weeks, five wounds healed by 16 weeks, and the remaining seven wounds reached complete healing within 30 weeks. Overall, the number of cUC applications ranged between 2–5, with one wound reaching 100% re-epithelisation after two cUC applications, six after three applications, five after four applications and one after five applications. To determine if the initial wound size correlated with either the time to healing or number of cUC applications, two separate paired t-tests were conducted. The result showed that there was an insignificant correlation between the mean wound area and weeks to closure (p=0.13). However, the correlation between mean wound area and the number of cUC applications was statistically significant (p≤0.001). That was reflected by the finding that the two smallest wounds (
