Effectiveness of Therapeutic Non-operative Management of Wound

Healing in Diabetic Foot Ulcer: A Systematic Review

Titis Eka Apriliyanti, I Komang Leo Triandana Arizona, Fatimah Zahra and Ferry Efendi
Faculty of Nursing, Univesitas Airlangga
titis.eka.apriliyanti-2017@fkp.unair.ac.id, i.komang.leo.triandana-2017@fkp.unair.ac.id,
fatimah.zahra-2017@fkp.unair.ac.id, ferry-e@fkp.unair.ac.id

Keywords: Non-operative management, wound healing, diabetic foot ulcer.

Abstract: Background: Therapeutic non-operative management is an important part in healing the wounds of diabetic
foot ulcer but the most effective methode among this remain questionable. This study aims to identify
effective intervention to treat diabetic foot ulcer with therapeutic non-operative management by systematic
review and followed the PRISMA statetment guidelines. Methods: Scopus, PubMed, and Science Direct
database from 2012 – 2018 were search for the relevant keyword. All included studies were access base on
(1) random controled trial, (2) case-control studies and (3) cohort studies. Results: 19 out of 1651 papers were
including. Two articles suggest that advanced biologic therapy, the bioengineered living cellular construct
(BLCC) of human fibroblast-derived dermal subtitution (HFDS) and advanced skin substitution using grafix
have a significant. Five articles reported electrophysical therapy has significant. Two articles reported
hyperbaric oxygen therapy (HBOT) had a significant and one article reported no effect. Five articles state that
the NPWT has a significant influence on wound healing. Three studies reported that TCC resulted in a
statistically significant to be an effective treatment of diabetic foot ulcers. Conclusions: NPWT should as
promising therapeutic non-operative management in treating diabetic foot ulcer. Additional further
randomized control trial design study needed to strengthen the finding.

1 BACKGROUND the world and in the year 2035 that number an

Diabetes mellitus is not infectious disease issues
figure high incidence of its victims and diabetes
mellitus treatment if not done properly will cause
complications of diabetes mellitus consisting of
acute complications include Diabetic Ketoacidosis,
hyperosmolar non ketotik, and hypoglycemia
(Perkeni, 2011). Neuropathy is one of the
complications that occur in the nervous system
disorders of the foot and alirah peripheral blood
which is early onset of diabetic foot ulcer (Waspadji,
2006). Patients with diabetes mellitus will evolve
into a dibetic foot ulcer (DFU) is estimated to be 15-
25% associated with venous insufficiency,
neuropathy and peripheral artery damage and only
about 24% of the wounds healed after 12 weeks of
therapy, this causes ALOS lengthwise in the
hospital, the costs incurred by the patient as well as
the increased burden of the Government against
health coverage also increases (Lavery, 2014). The
treatment process for the DFU into a challenge for
effective health workforce craft made proper wound
care management to shorten the healing time and
prevent further complications since DFU (Frykberg
et al., 2017).
Prevelention of diabetes mellitus there are an
estimated 382 million people living with diabetes in
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estimated 592 million people stepped on the rise
(International Diabetes Federation, 2014). Sufferers
of diabetes mellitus a number of 382 million people,
175 million of them have not been terdiagnois, so
that threatened developing progressively and
unidentified become unwitting and complications
and without any prevention of sufferers (Kemenkes
RI , 2014). The prevalence in Indonesia there are
around 7% of total population total population
number of 258 million people have diabetes mellitus
(World Health Organization, 2016).
The impact of diabetic foot ulcer treatments that
are not exactly very influential towards the quality
of life, productivity, employment, depression due to
the amputation to death. Risk factors as causes of
DFU one is lack of management to prevention
therapies that have not been appropriately and has
not been used. DFU therapy can be done with the
operative management and non-operative
management (Cychosz, 2016).
Over recent decades, the significance of related
research the healing of wounds in diabetics with
non-operative management of theraputic many do,
some non-operative management strategies include
such Advanced Biologics Therapy, Hyperbaric
Oxygen Therapy, Electrophysical Therapy (HBOT),
Negative Pressure Wound Therapy (NPWT), and the
Total Contact Casting (TCC), the therapy is found in
305
all the review literary review Cychosz (2016) related
preventive and therapeutic strategies for diabetic
foot ulcer, but there has been no sistematic review
that discusses the effectiveness and excellence in the
use of the therapy as a whole on the healing process
of wounds so medical personnel can compare
pengguaan therapy to each other so that right for
granted. The purpose of this review is the sistematic
to know the effectiveness of non-operative
management therapy therapeutic against healing in
diabetic foot ulcer (DFU).
2 METHODS
This systematic review followed the Preferred
Reporting Item for Systematic Reviews and Meta-
Analyses (PRISMA) guidelines (Liberati et al.,
2009).
Search strategy
Scopus, PubMed and Science Direct databases
were searched for articles published from 2012 –
2018. The strategy had eight components which
were combined: (1) non-operative management OR
(2) negative pressure wound therapy OR (3)
hyperbaric oxygen therapy OR (4) total contact
casting OR (5) advanced biology therapy OR (6)
electrophysical therapy AND (7) wound healing
AND (8) diabetic foot ulcer.
Eligibility Criteria
Types of studies
(1) random controlled trial, (2) case-control
studies and (3) cohort studies design were included.
Types of participants
The main inclusion criteria entailed adult (18
years or older), with a type I or type II diabetes.
Type of interventions
Any non-operative management for the treatment
of diabetic foot ulcer was eligible. No studies were
excluded on the basis of the comparator/ control
group used.
Type of outcomes measures
Primary outcomes of interest were any measure
of wound healing. The timing of outcome measures
was variable.
Study selection
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The protocol standard for selecting research
studies is suggested in the PRISMA method for
systematic review followed by screening by
removing duplicates, then three reviewers selecting
titles, abstracts, and keywords, then deleting
irrelevant quotes according to the selection criteria.
Reviewers noted the reasons for choosing such
research studies including selection of inclusion
inclusion data. Selection of research studies that
have been recorded by three reviewers and then
compared to one another to be adjusted feasibility
with the criteria set. Secondly, to minimize the risk
of incorrect study entry in selection there are several
research studies that have been applicable or can be
applied in a review by one or two reviewers to be
included in the next review stage. Full text of the
articles is obtained if the title and abstract meet the
inclusion criteria or if the feasibility study is clearly
resolved by a joint discussion between the
reviewers.
3 RESULTS
Literature search and study selection
A total of 19 studies were identified for inclusion
in the review. The search of Scopus, PubMed and
Science Direct databases provided a total of 1651
citations. After adjusting for duplicates 863
remained. Of these, 595 studies were discarded
because after reviewing the abstract it appeared that
these papers clearly did not meet the criteria. The
full text of the remaining 268 citations was
examined in more detail. It appeared that 250 studies
did not meet the inclusion criteria as described. See
flow diagram Figure 1.
Study Characteristic
Methods
19 studies finally selected for review were eight
randomized controlled trial, eight cohort studies, and
three case-control studies design.
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 al., 2014; Omar et al., 2014; Asadi et al., 2015;
Wirsing et al., 2015).
Records identified through database
searching
(n = 1,651) Outcomes
Identification

In all studies the primary outcome assessed was

Scopus : n = 256, PubMed: n = 473, wound healing. The timing of outcome measures
Science Direct: n = 922
was variable and could include monthly
investigations, evaluations every three months or a
single final evaluation.
Records
excluded based
Records screened after on title and Results of individual studies
Screening

removing duplicates abstract

Advanced Biologic Therapy
(n = 863) (n = 595)
Two articles suggest that advanced biologic
therapy, the Bioengineered living cellular construct
(BLCC) of Human Fibroblast-derived dermal
Full-text articles
excluded, with
substitution (HFDS) and advanced skin substitution
Full-text articles assessed using Grafix have a significant effect on wound
for eligibility reasons
(n = 268 ) (n = 250) healing.
Eligibility

Lavery et al., (2014) reported that grafix can

1. Not human
model improve wound healing, shorten healing time and
2. Not English reduce complications. (Rice et al., 2015) reported
language that BLCC and HFDS can accelerate wound healing
Studies included in 3. No relevant and lead to reduced maintenance costs.
qualitative synthesis study design
(n = 19 ) 4. No relevant
outcome Electrophysical Therapy
Five articles reported Electrophysical Therapy
Included

has significant effect on wound healing.

19 studies included in
systematic review
Figure 1: Flow Diagram
Population
The included studies involved 2.304 participant.
The main inclusion criteria entailed adult (18 years
or older), with a type I or type II diabetes.
Intervention
Table 1 represents the characteristics and content
of the interventions of the 19 studies.
Three studies evaluated Hyperbaric Oxygen
Therapy/HBO (Fedorko et al., 2016; Chen et al.,
2017; Hayes et al., 2017). Five studies evaluated
Negative-Pressure Wound Therapy/
NPWT(Matsuzaki and Kishi, 2016; Kaushik et al.,
2017; Mendame Ehya et al., 2017; Wang et al.,
2017; Yang et al., 2017). Three studies evaluated
Total Contact Casting/ TCC (Kashefsky and
Marston, 2012; Arnold and Marmolejo, 2017;
Merheb et al., 2017). Two studies evaluated
Advanced Behaviour Therapy/ ABT (Lavery et al.,
2014; Rice et al., 2015). Five studies evaluated
Electrophysical Therapy (Keyl et al., 2013; Liani et
Asadi et al., (2015) reported that a cathode-direct
current can increase skin temperature and accelerate
wound closure or reduce injury to DFU ischemia by
comparison of study groups showing significance at
higher skin-temperature changes than in placebo
groups in three sessions and and reduction of injured
areas (52.68%) compared to the placebo group
(38.39%). Keyl et al., (2013) suggest that electrical
stimulation for sciatic nerve motor responses is
increased in patients with DFU gangrene. Liani et
al., (2014) reported that the Pulsating Electrostatic
Field technique has influenced metabolic processes
and accelerated wound healing in foot ulcers with
type 2 diabetes. Wirsing et al., (2015) reported that
Wireless Micro Current Stimulation (WMCS)
technology significantly accelerated progress on
wound healing and reduce the occurrence of
expansion on the surface of the wound with wound
healing achieved for 3 months in aetiologically
difficult to recover patients. WMCS offers
advantages over electrical stimulation because it is
contactless, pain free from being easy to use
Hyperbaric Oxygen Therapy (HBOT)
Two articles reported Hyperbaric Oxygen
Therapy (HBOT) had a significant effect on wound
healing, and one article reported no effect.

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 Chen et al. (2017) reported that hyperbaric
oxygen therapy can significantly improve the
inflammatory index, blood flow and quality of life.
Hayes et al. (2017) suggest hyperbaric therapy may
reduce ulcers by 51% and pain reduction. Fedorko et
al. (2016) reported that there is no significant
influence on decreasing the risk of amputation and
wound healing.
Negative Pressure Wound Therapy (NPWT)
Five articles state that the NPWT has a
significant influence on wound healing.
Matsuzaki and Kishi (2016) reported that NPWT
can accelerate wound healing time after debridement
with an average of 31.3 days. Yang et al. (2017)
reported that NPWT can increase protein and cFN
and TGF-β1 levels compared with Advanced Moist
Wound Therapy consisting of hydrogels, alginates,
and dressings. Wang et al. (2017) reported that
NPWT may decrease TNF-α, IL-6, iNOS, IkB-α and
NF-B P65 expression, increase ATF-3 levels, and
provide anti-inflammatory effects by suppressing
pro-inflammatory enzymes and cytokines as a result
inhibition of Ikb-α and the activation of ATF-3,
which can prevent the activation of the NF-B
pathway in diabetic foot wounds and cause rapid
injury to improve over treatment with debridement.
Mendame Ehya et al. (2017) reported NPWT
reduces expenditures accumulated flap, reduces pain
shorten wound healing time with good aesthetics,
good mobility and satisfactory therapeutic results.
Kaushik et al. (2017) reported that NPWT
accelerates the wound healing period compared with
gauze dressing.
Total Contact Casting (TCC)
Three studies reported that TCC resulted in a
statistically significant to be an effective treatment
of diabetic foot ulcers.
Arnold and Marmolejo (2017) reported there are
similar healing rates and reduced rates of iatrogenic
ulceration, amputation, recurrent ulceration were
attained and an 85.6% healing rate was achieved
with use of a prefabricated roll-on TCC. Kashefsky
and Marston (2012) reported the percentage of
wound healing using TCC at 75% complete and
non-recurrent ulcer coverage during one year of
follow-up and no surgery. Merheb et al. (2017)
reported the average time of wound healing with
TCC is 23.7 ± 16.3 days.
4 DISCUSSION
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A systematic review is to find out about the
effectiveness of the therapeutic management of non-
operative against the wound healing in diabetic foot
ulcer. The articles used to use heterogeneous
research design. There are several related findings of
various interventions concerning the advantage or
disadvantage of some kind of intervention against
the process of wound healing that is composed of
several phases, and in this case the intervention of
NPWT potentially as a treatment effective for
wound healing in diabetic foot ulcer which will be
discussed in detail as follows.
Diabetic foot ulcer treatment outcomes remains a
challenge related effectiveness of treatment.
Intervention or treatment should be assessed or
reviewed, so that less proof of effectiveness of
interventions should be avoided. Review update
results Cychosz (2016), a literary review that
discusses about strategies of preventive and
therapeutic for diabetic foot ulcer management with
operative or non-operative. The review contained an
assessment of interventions that have advantages or
effective in the process of wound healing at every
phase. Wound healing there are three important
phases include inflammatory phase, proliferasi, and
remodelling. Inflammatory phase of wound healing
is a process until the fifth day, acute inflammation
occurs in 24-48 the first hour after injury. The
process of epitalisation were formed then undergo
constricting and reaction accompanied by the release
and activate hemostase cytokines which act for the
occurrence of cemoktasis retrofil, macrophages,
mast cells, endothelial cells and fibrolas which are
then This inflammatory reaction produces
exsudation fluid (Ekaputra, 2013). In the
inflammatory phase in NPWT have advantages and
effective because of the application of the negative
pressure can stimulate the activity of the cells in the
wound, the migration of cells, eliminate excess fluid
cuts, and decrease edema (Borgquist, 2011). In
accordance with the results of the review of research
studies conducted by Wang (2017) explained that
NPWT enhances wound healing of diabetes due to
inflammation of the soft and dense matrix cells are
deposited. NPWT significantly lowered expression
of TNF-α, IL-6 and iNOS (all P < 0.05). The results
of PCR blotting and real-time PCR showed that
NPWT decreases the level of IkB-α and NF-B P65
and raise the level of ATF-3 (all P < 0.05) and can
also provide anti-inflammatory effect with emphasis
pro-inflammatory enzymes and cytokines due to
inhibition of IkB-α and activation of ATF-3, which
can prevent the activation of NF-B pathways on
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diabetic foot wounds and cause wounds quickly
improved (Wang, 2017).
Compared to the four other interventions, such as
advanced Biologics intervention therapy that has a
weakness in the inflammation phase as it cannot
reduce the exudate on the wound. Advanced
Biologics therapy is a therapy of skin grafting on the
wound the granting of appropriate research studies
by Lavery (2014) that describes the advanced skin
grafix substitution on diabetic foot. There are also
similar things in therapy ESWT (extracorporeal
shock wave therapy) is to respond to electrical
stimulation of nerves, therapeutic research study
conducted by Omar (2014) explained that ESWT
therapy can improve perfusion and not on
inflammatory processes. The next therapy HBOT
only gives oxygen on peripheral, in accordance with
the research study conducted by Fedorko (2016) that
the results of the review describes the granting of
hyperbaric oxygen therapy did not significantly
effect against a decreased risk of amputation on the
client with a diabetic foot ulcer (p = 0.846). Total
contact casting is also a therapy that is designed to
protect the ulcer by reducing pressure on the
wounds, according to the research study by Arnold
(2017) the results of the rate of healing using the
TCC roll-on prefabricated reach 85%.
The second phase, i.e. poliferasi, this phase
began on granulation, contraction of wounds and
epitelisasi (Ekaputra, 2013). NPWT in it also have
an important role in which excellence in improving
growth of granulation. Yang (2017) that compares
with NPWT AMWT therapy/advance moist wound
therapy with hydrogel and alginates drassing as the
control group, the results raise the levels of protein
and NPWT cFN and TGF-β1 as compared to the
control group (P. 01 < both), cFN and TGF-β1
granulation tissue through which so speed healing of
wounds of diabetic foot.
Phases of remodeling is the last and longest
phase in the process of wound healing. The dynamic
processes occurring in the form of remodeling of
collagen, scar maturation and wound contraction.
This phase lasts from 3 weeks to 2 years. End of this
healing grated ripe wounds obtained which has 80%
of the strength of the normal skin (Ekaputra,2013).
Advantages of the intervention research studies
described in NPWT Mendame (2017) that there is a
statistically significant difference in clinical
endpoints in two groups (p < 0.001; p < 0.05). VAC
combining perforating applications flap, flap
accumulation reduce spending, reduce pain shorten
the time healing wounds with the aesthetics of good,
good mobility and therapeutic results are
satisfactory.
Limitations
There are some potential limitations related to
this systematic review. (1) Heterogeneity of study
design. (2) What we considered as primary
outcomes (wound healing) was not always the same
as in the original study.
5 CONCLUSIONS
This review explains that systematic intervention
NPWT potentially as effective therapy for DFU
compared four other interventions such as advanced
Biologics electrophysical therapy, therapy, HBOT,
and total contact casting.
Wound infections generally produce higher
levels of exudate causes damage and localized
edema. NPWT can reduce the bacterial load bed
sores (Moues, 2004), besides NPWT also able to
take excess fluid cuts and not only reduce the edema
but also improve local blood flow and nutrients on
the wound. The flow of new blood is able to reduce
the formation of anti-inflammatory mediators such
as metalloproteinase, which lose adhesion proteins
needed to repair wounds. Clinical trial on diabetic
foot wounds showed excellence in producing NPWT
granulation with than conventional dressings.
NPWT also induces angiogenesis and vascular
proliferation, further systemic endothelial cells
mobilize NPWT progenitor (EPCs) which is a
marker of the healing and repair. Design studies
with randomized controlled trial is needed to
strengthen the results of systematic.
REFERENCES
Arnold, J. F. and Marmolejo, V. (2017) ‘Outcomes
Achieved With Use of a Prefabricated Roll-On
Total Contact Cast’, Foot and Ankle International,
38(10), pp. 1126–1131. doi:
10.1177/1071100717716486.
Asadi, M. R. et al. (2015) ‘Effects of electrical stimulation
on the management of ischemic diabetic foot
ulcers’, Journal of Babol University of Medical
Sciences, 17(7), pp. 7–14.
Borgquist, O. et al. (2011). Measurements of wound edge
microvascular blood flow during negative pressure
wound therapy using thermodiffusion and
transcutaneous and invasive laser Doppler
velocimetry. Wound Repair Regen:19:727-33.
Chen, C.-Y. et al. (2017) ‘Adjunctive Hyperbaric Oxygen

The 9th International Nursing Conference 2018

“Nurses at The Forefront in Transforming Care, Science, and research” 309
 Therapy for Healing of Chronic Diabetic Foot
Ulcers’, Journal of Wound, Ostomy and
Continence Nursing, 0(0), p. 1. doi:
10.1097/WON.0000000000000374.
Cychosz, C. C. et al. (2016) ‘Preventive and Therapeutic
Strategies for Diabetic Foot Ulcers’, Foot & Ankle
International, 37(3), pp. 334–343. doi:
10.1177/1071100715611951.
Ekaputera, E. (2013). Evolusi Manajemen Luka Menguak
5 Keajaiban Moist Dressing. Jakarta : TIM
Fedorko, L. et al. (2016) ‘Hyperbaric oxygen therapy does
not reduce indications for amputation in patients
with diabetes with nonhealing ulcers of the lower
limb: A prospective, double-blind, randomized
controlled clinical trial’, Diabetes Care, 39(3), pp.
392–399. doi: 10.2337/dc15-2001.
Frykberg, R. G. et al. (2017) ‘Feasibility and efficacy of a
smart mat technology to predict development of
diabetic plantar ulcers’, Diabetes Care, 40(7), pp.
973–980. doi: 10.2337/dc16-2294.
Hayes, P. D. et al. (2017) ‘Topical oxygen therapy
promotes the healing of chronic diabetic foot
ulcers: a pilot study’, Journal of Wound Care,
26(11), pp. 652–660. doi:
10.12968/jowc.2017.26.11.652.
Kashefsky, H. and Marston, W. (2012) ‘Total contact
casting combined with human fibroblast-derived
dermal tissue in 15 DFU patients.’, Journal of
wound care, 21(5), p. 236,238,240,242-243. doi:
10.12968/jowc.2012.21.5.236.
Kaushik, D. et al. (2017) ‘Negative pressure wound
therapy versus gauze dressings for the treatment of
contaminated traumatic wounds’, Journal of
Wound Care, 26(10), pp. 600–606. doi:
10.12968/jowc.2017.26.10.600.
Kemenkes RI (2014) ‘Situasi dan Analisis Diabetes’,
Pusat Data dan Informasi Kementerian Kesehatan
RI, p. 2. doi: 24427659.
Keyl, C. et al. (2013) ‘Increased electrical nerve
stimulation threshold of the sciatic nerve in
patients with diabetic foot gangrene: A prospective
parallel cohort study’, European Journal of
Anaesthesiology, 30(7), pp. 435–440. doi:
10.1097/EJA.0b013e328360bd85.
Lavery, L. A. et al. (2014) ‘The efficacy and safety of
Grafix ® for the treatment of chronic diabetic foot
ulcers: results of a multi-centre, controlled,
randomised, blinded, clinical trial’, International
Wound Journal, 11(5), pp. 554–560. doi:
10.1111/iwj.12329.
Liani, M. et al. (2014) ‘Effects of a pulsatile electrostatic
field on ischemic injury to the diabetic foot:
Evaluation of refractory ulcers’, Primary Care
Diabetes. Primary Care Diabetes Europe, 8(3), pp.
244–249. doi: 10.1016/j.pcd.2013.11.009.
Liberati, A. et al. (2009) ‘The PRISMA Statement for
Reporting Systematic Reviews and Meta-Analyses
of Studies That Evaluate Health Care
Interventions : Explanation and Elaboration’, 6(7).
doi: 10.1371/journal.pmed.1000100.
310
“Nurses at The Forefront in Transforming Care, Science, and research”
Matsuzaki, K. and Kishi, K. (2016) ‘Negative-pressure
wound therapy for diabetic ischemic foot wounds
in hemodialysis patients’, European Journal of
Plastic Surgery, 39(5), pp. 353–358. doi:
10.1007/s00238-016-1182-x.
Mendame Ehya, R. E. et al. (2017) ‘Comparative
effectiveness study between negative pressure
wound therapy and conventional wound dressing
on perforator flap at the Chinese tertiary referral
teaching hospital’, Journal of Tissue Viability.
Tissue Viability Society, 26(4), pp. 282–288. doi:
10.1016/j.jtv.2017.07.002.
Merheb, M. et al. (2017) ‘Effect of total contact cast in
non-healing diabetic foot ulcers in Lebanese
patients’, International Wound Journal, 14(5), pp.
751–753. doi: 10.1111/iwj.12660.
Moues, CM. et al. (2004). Bacterial load in relation to
vacuum-assisted closure wound therapy: a
prospective randomized trial. Wound Repair
Regen:12(1):11-17.
Omar, M. T. A. et al. (2014) ‘Efficacy of shock wave
therapy on chronic diabetic foot ulcer: A single-
blinded randomized controlled clinical trial’,
Diabetes Research and Clinical Practice. Elsevier
Ireland Ltd, 106(3), pp. 548–554. doi:
10.1016/j.diabres.2014.09.024.
Perkeni. (2011). Konsensus pengelolaan dan pencegahan
diabetes melitus tipe 2 di Indonesia 2011. PB.
Jakarta: Perkeni.
Rice, J. B. et al. (2015) ‘Economic outcomes among
Medicare patients receiving bioengineered cellular
technologies for treatment of diabetic foot ulcers’,
Journal of Medical Economics, 18(8), pp. 586–
595. doi: 10.3111/13696998.2015.1031793.
Wang, T. et al. (2017) ‘Negative pressure wound therapy
inhibits inflammation and upregulates activating
transcription factor-3 and downregulates nuclear
factor-κB in diabetic patients with foot
ulcerations’, Diabetes/Metabolism Research and
Reviews, 33(4). doi: 10.1002/dmrr.2871.
Waspadji, S. (2006). Kaki diabetes. In A. W. Sudoyo, B.
Setiyohadi, I. Alwi, M. S. K & S. Setiati (Eds.),
Buku ajar ilmu penyakit dalam. Jakarta: Penerbit
FK UI
Wirsing, P. G. et al. (2015) ‘Wireless micro current
stimulation - an innovative electrical stimulation
method for the treatment of patients with leg and
diabetic foot ulcers’, International Wound Journal,
12(6), pp. 693–698. doi: 10.1111/iwj.12204.
World Health Organization (2016) ‘Diabetes Country
Profile’, diabetes country profile Indonesia, 48(6),
p. 18882A–18882B. doi: 10.1111/j.1467-
825X.2011.03931.x.
Yang, S. L. et al. (2017) ‘Effect of Negative Pressure
Wound Therapy Cellular Fibronectin and
Transforming Growth Factor- β 1 Expression in
Diabetic Foot Wounds’. doi:
10.1177/1071100717704940.
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