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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_612_Библиотеки_им_академика_М_И_Перельмана
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contamination by aerosolization, and has lower efficacy in venous
and diabetic CW.
Enzymatic debridement adopts chemicals or enzymes (eg,
bromelain and collagenase) to degrade necrotic tissue. This
debridement is pain-free and safe, and often reserved for outpatient
care. It is effective although high-level evidence in its support is
lacking; the strongest evidence supports the role of collagenase in
stimulating fibroblasts’ and keratinocytes’ migration and proliferation.
Biologic debridement leverages of the natural properties of
maggots (larvae of the Australian sheep blow fly or the green bottle
fly) therapeutically. Larvae secrete proteolytic enzymes that degrade
necrotic tissue, and then specifically ingest it while sparing healthy
tissue. Larval debridement (freely applied or in bio-bags) is reserved
to patients who cannot tolerate surgical debridement (or when it is
not available), or in between sessions of surgical debridement.
Larval debridement stimulates healing and reduces the duration of
antibiotic therapy required for infected wounds. Yet, its superiority to
standard dressings is not confirmed, and—despite being safe—
patients’ attitude toward this therapy limits its use.
Wound irrigation is an integral part of debridement and has an
adjuvant role in cleansing, decreasing bacterial load, and removing
loose slough and necrotic tissue. It is performed with low pressure
(eg, syringe, bulb, cysto tubing) or high pressure (eg, pulsed lavage);
the latter usually occurs in the operating room. Some evidence
suggests higher efficacy for high-pressure irrigation, although this
technique is assumed to cause minor tissue damage; despite such
risks, high-pressure irrigation is favored for highly infected wounds.
No evidence recommends specific solutions, as the beneficial effects
of irrigation seem to be mostly bound to its mechanical effect; warm
isotonic saline is most commonly used, and antiseptic substances
(eg, iodine, chlorhexidine, hydrogen peroxide, sodium hypochlorite)
are not necessary and could even be cytotoxic.
Surgical Repair and Wound Coverage
Once a patient with a CW is optimized, risk factors and comorbidities
have been removed or mitigated, underlying etiologies have been
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addressed to the extent possible, proper debridement has been
performed, and infections have been treated, a CW is ready to heal.
Healing can be achieved by secondary (dressing changes) or
primary (surgical repair/coverage) intention.
15,23
A decisional algorithm indicating which strategy is better suited for
each specific case will follow the same indications and guidelines
adopted for acute wounds (eg, traumatic wounds). Similarly, within
CW candidate to surgical repair/coverage, choice of the most
appropriate technique (eg, direct closure, graft, scaffold, local flap,
free flap) will be mostly guided by standard reconstructive principles.
These techniques, indications, guidelines, and principles are
described more in detail in other chapters (Concepts of Skin Grafts
and Skin Substitutes in Chapter 6; Principles of Flap Reconstruction:
Muscle Flaps, Myocutaneous Flaps, and Fasciocutaneous Flaps in
Chapter 7; Lower Extremity, Foot, and Ankle Reconstruction in
Chapter 110, etc.). Some recommendations specific to CW are
provided below.
When primary closure is possible, attention should be focused on
preserving the limited perfusion of wound edges using tension-free
or tension-releasing techniques, obliterating all cavities and dead
space, and gently managing fragile tissue.
For skin grafts, survival might be affected by the lower tissue
perfusion in patients with PAD; this consideration must guide choice
of graft thickness. Biofilm can affect graft take. Skin grafts are often
effective in the repair of venous CW, which are often large but
superficial with no exposure of delicate structures (eg, bone, tendon,
vessels, or nerves).
Tissue-engineered cell cultured constructs (eg, Apligraf,
Dermagraft, and Epicel) are advanced grafts that can be used for
CW. Apligraf and Dermagraft are composed of a scaffold
(respectively, of bovine collagen and of polyglactin) seeded with
allogenic human neonatal fibroblasts and/or neonatal keratinocytes;
instead, Epicel uses autologous cultured epithelial grafts. These
products have shown some efficacy in the treatment of CW,
especially as a second-line approach when traditional dressings or
grafts fail. Genetically modified cultured keratinocytes have also
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been used to cure patients with genetic disorders of the skin, such
as junctional epidermolysis bullosa.
Grafting of scaffolds of human (cadaveric) and nonhuman origin
(eg, porcine or synthesized) can facilitate healing of CW. Several
commercial products are available (eg, Integra, AlloPatch, or Grafix).
Absence of infection is important, because pathogens more easily
grow on acellular matrices. In addition, similar precautions should be
applied as for skin grafts in patients with PAD.
Large and complex CW with exposure of delicate structures (eg,
bone, tendon, vessels, or nerves) always require coverage by a
vascularized flap. Common local tissue flaps include V-to-Y flaps,
rotation flaps, transposition flaps, and other advancement flaps.
When vascularized fascia or muscle is needed (eg, exposed tendon
or bone), pedicled flaps are used. Common options include the
abductor hallucis muscle flap (for medial foot or ankle), the
hemigastrocnemius muscle flap (for the knee), the soleus flap (for
midtibia), the posterior tibial artery perforator flap (for the foot,
calcaneal tendon, medial malleolus, and distal tibia), the medial
plantar artery perforator “instep” flap (for plantar heel), and propeller
flaps or cross-leg flaps (various areas of the lower extremity).
When local/pedicled flaps are not available or sufficient, free tissue
transfer is required. Historically, microsurgical free tissue transfer in
patients with CW was avoided because of concerns that underlying
macrovascular and microvascular disease would lead to flap failure,
as well as because of the assumption that an LEA would be a less
traumatic and equally effective treatment. Recent evidence suggests
those concerns and assumptions are inaccurate, and novel
recommendations for microsurgical limb salvage have been
developed.
KNOWLEDGE GAPS, RESEARCH, AND
INNOVATION IN WOUND HEALING AND WOUND
CARE
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The field of wound healing and CW is extremely broad, and
continuously evolving and innovating. Its significance and relevance
for patient care, already substantial, is growing as incidence and
prevalence of disease and associated comorbid factors rise across
geographical regions, ethnicities, ages, and genetic sexes.
Numerous knowledge gaps exist: from understanding the
molecular and cellular mechanisms guiding normal and abnormal
healing to the assessment of the effectiveness of treatments, for
most of which higher level of supporting evidence is lacking. Overall,
better designed and robust clinical trials are needed, possibly
supported by shared registries. Additional work will also better define
patients’ perspectives and reported outcomes, access to care and
equity of care, and optimization of medical resources.
Advances in biology, therapeutics, tissue engineering, technology,
and surgery offer continuous opportunities for the advancement of
the field and improved care across the spectrum of needs and
challenges. The evolving regulatory landscape and economic
interests by industry will be pivotal in determining the rate at which
innovation will reach patient care.
Among some of the most promising areas of innovation in the field
(some of which have already been mentioned through this chapter)
we cite patient education, primary prevention, prehabilitation,
PROMs, impact of SDOHs, telemedicine, AI/ML and big data,
scarless healing, targeted biologic therapies (GFs, cytokines, stem
cells, exosomes, siRNA, and mRNA), gene therapy, tissue
engineered constructs, role of microbiome and probiotics, role of
lymphatics, role of dermal adipocytes, smart dressings with
monitoring abilities, topical antibiotic therapy, microsurgical limb
salvage and ancillary techniques (targeted muscle reinnervation,
regenerative peripheral nerve interface, neurolysis, lymphatic
supermicrosurgery, osteointegrated prosthetic implants, etc.), and
others.
QUESTIONS
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1. Which of the following patients is at higher risk for developing
a chronic wound that could lead to a lower extremity
amputation (LEA)?
a. A 64-year-old self-employed Caucasian man with known
diabetes, single and living in a rural area
b. An 80-year-old retired Asian woman with lower extremity
venous insufficiency, widow and living in an urban area
c. A 56-year-old unemployed African American man with
obesity, single and living in a semirural area
d. A 62-year-old employed Hispanic woman with known
peripheral artery disease, married with children and living
in rural area
e. A 73-year-old retired African American man with
unknown diabetes, married and in an urban area
2. Which phase and biological process of wound healing is more
often dysregulated in chronic wound healing?
a. The proliferative phase, as defective or senescent
fibroblasts show a lower proliferation rate and a
decreased ability to secreted extracellular matrix content
b. The inflammation phase, as dysregulated
monocytes/macrophages and neutrophils prolong the
secretion of proinflammatory cytokines and prevent the
recruitment of fibroblast
c. The remodeling phase, as excessive and protracted
proliferation of fibroblast, myofibroblasts, and endothelial
vessels prevents reorganization of the extracellular matrix
and reepithelialization
d. The proliferative phase, as unbalanced cytokines cause
fibroblasts and endothelial cells to undergo apoptosis
e. The hemostasis phase, as defective platelets delay
formation of a fibrin scaffold for migration of inflammatory
cells
3. What would be the best initial treatment for a 3 × 3 cm
ischemic arterial wound above the right lateral malleolus
covered by an eschar and with no signs of infection, in a frail
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75-year-old male patient with WIfI stage 2, GLASS score 2,
ASA score 3, mFI-5 of 3, and class 3 obesity? The patient is
married, insured, has access to specialized home wound
care, and lives in an urban area in proximity of a tertiary
wound center.
a. Patient optimization by angiographic study and lower
extremity revascularization with a vascular bypass,
before any local management of the wound
b. Nonsurgical outpatient wound management by
hyperbaric oxygen therapy (HBOT) to improve tissue
perfusion
c. Single-stage inpatient wound management by surgical
debridement and wound coverage by either a splitthickness skin graft (if there is no tendon and/or bone
exposure) or a local flap (if there is tendon and/or bone
exposure)
d. Outpatient wound management by nonsurgical
debridement and healing by second intention using
dressing changes
e. Elective below-knee amputation
4. A 62-year-old female patient is evaluated for a 5 × 5 cm
wound near her left medial malleolus, treated with standard
dressings for the last 4 months. The wound is superficial, with
a yellow/pale red and periwound fibrosis/hyperpigmentation.
The left lower extremity is moderately edematous and
varicose veins are visible; no signs of infection are noted and
there is no malodor. The patient reports some pain and a
major discomfort caused by frequent dressing changes
needed to manage wound exudates, which is also affecting
her work and social life. What would be your first
recommendation for this patient?
a. To introduce compression therapy in association with
manual lymphatic drainage to decrease edema and
exudate, and to facilitate healing
b. To begin adjuvant systemic venotonic/venoactive therapy,
such as with pentoxifylline
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c. To change wound care routine to advanced dressings,
possibly a hydroactive foam
d. To attempt a trial of topical recombinant hPDGF
(becaplermin gel)
e. To complete a thorough vascular evaluation for venous
insufficiency (duplex ultrasonography) and a vascular
surgery evaluation for treatment (sclerotherapy, selective
ligation, or stripping)
5. Your patient is a self-employed 60-year-old man with a
8 × 10 cm diabetic chronic wound on the lateral aspect of his
foot; there is exposure of the distal third of the fifth metatarsal
and the overlying extensors. His comorbidities include longstanding type 2 diabetes, class 3 obesity, and peripheral
artery diseases with claudication. The patient is otherwise
compliant and motivated, and with no disabilities.
Angiography show a single vessel runoff through the posterior
tibial artery (GLASS score 2); MRI confirms presence of
osteomyelitis. What would be the ideal management of this
patient?
a. Transmetatarsal amputation (TMA) and coverage with
plantar flap
b. Extensive surgical debridement of soft tissues and bone,
prolonged negative pressure wound therapy (NPWT),
and second-stage coverage with a split-thickness skin
graft
c. Revascularization, extensive surgical debridement of soft
tissues and bone, and staged coverage with an ipsilateral
superficial circumflex iliac artery perforator (SCIP) flap
(anastomosis end-to-end to the lateral plantar artery)
d. Extensive surgical debridement of soft tissues and bone,
and immediate coverage with a contralateral anterolateral
thigh (ALT) flap (anastomosis end-to-side to posterior
tibial artery)
e. Revascularization, extensive surgical debridement of soft
tissues and bone, staged coverage with an ipsilateral
latissimus dorsi (LD) flap (anastomosis end-to-side to
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posterior tibial artery), and concomitant calcaneal tendon
lengthening
ANSWERS AND EXPLANATIONS
1. Answer: c. Incidence of chronic wounds, access to care,
type of care received, and severity/progression of disease are
significantly impacted by social determinants of health (SDOHs),
socioeconomic factors, and geographical setting. Higher
incidence/prevalence of diseases and higher rates of severe
disease/complications (including lower extremity amputations,
LEA) are observed in patients belonging to minorities, having
unemployment status and food insecurity, less comprehensive
(or no) insurance, lower education levels, lower social or family
support (including being single or divorced), as well as living in
socioeconomically deprived neighborhoods and/or in rural
areas. The patient described in (c) belongs to a minority, is
single, is unemployed (and possibly uninsured), and lives in a
semirural area. In addition, obesity is often caused by
malnutrition, and it is often associated with undiagnosed
diabetes. Chronic wounds caused by diabetes or peripheral
artery disease have a higher association with lower extremity
amputations (LEA), compared to those of venous origin.
2. Answer: b. Although chronic wound healing can be caused
by the dysregulation of multiple biological processes and
differences are observed across wounds of different etiology, a
chronic/excessive inflammatory response is most commonly
recognized as their main and most consistent culprit. Poor
tissue perfusion (which can also cause oxidative stress),
infection or bacterial colonization, deficient immunity (caused by
the underlying disease), and other factors affect migration of
inflammatory cells (neutrophils, monocytes/macrophages,
lymphocytes, eosinophils, etc.), their phenotype, and their
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activity. Inflammation is exuberant but inefficient. Wounds are
locked in an inflammatory status and do not progress to the
proliferative phase.
3. Answer: d. Although surgical debridement and wound
coverage represent the best management for ischemic arterial
wounds, this frail patient has multiple severe comorbidities that
make him a poor surgical candidate. In addition, the poor distal
perfusion might increase the failure rate of a split-thickness skin
graft. Consistently, the patient might not be able to tolerate a
vascular bypass surgery (also, an endovascular approach would
be better suited for this case) or a below-knee amputation. An
amputation is also an excessive option for this wound that is not
showing signs of complications, and it might unnecessarily
increase the patient’s mortality. Hyperbaric oxygen therapy is
recommended as a second-line treatment for recalcitrant
wounds not responding to initial care; in addition, it would not
remove the eschar. Outpatient wound management is the safest
first-line strategy for this patient. Nonsurgical debridement can
be delivered using wet-to-dry, enzymatic, or biological methods.
Dressings (eg, hydrogels or hydrocolloids) can further facilitate
autolytic debridement and provide optimal wound moisture.
Efficient and effective home care should be possible given the
patient’s social support (marital status), insurance status, and
access to specialized home wound care.
4. Answer: c. This patient suffers from a chronic wound of
venous origin, caused by a likely lower extremity venous
insufficiency. She will certainly benefit from proper and
comprehensive vascular evaluation, as well as a possible
referral to a vascular surgeon for assessment and management
of the underlying disease. She will also need to introduce
compression therapy, which has shown to improve wound
healing rates, decrease recurrence, help control symptoms, and
mitigate edema. Adjunct venotonic/venoactive therapy with
pentoxifylline can also contribute to better outcomes. Yet, in
effective wound care, it is critical to listen to and understand the
patients’ needs. In this case, the patient’s work and social life
are being impacted by the need for frequent dressing changes
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caused by her high-exuding wound, which is not properly
managed. Because she has been using standard dressings so
far, more advanced solutions should be recommended to her.
Specifically, hydroactive foam dressings are highly absorbent
products that mitigate wound moisture and reduce risk of
maceration to improve healing; these dressings are also
nonadherent and elastic, which is ideal for wounds near mobile
joint areas such as this one. Recombinant hPDGF is currently
approved for use in chronic wounds of diabetic origin.
5. Answer: e. Despite the severe peripheral vascular disease
and multiple comorbidities, this patient is a potential candidate
for limb salvage, which should be offered to him. A TMA is
unnecessary and will significantly increase the burden of the
disease (including the impact on independent living and the
ability to work), morbidity, and mortality. Prolonged NPWT
followed by a split-thickness skin graft is not indicated in the
management of exposed tendons and bone, and it will not
provide sufficient padding to ensure ambulation and decrease
the risk of recurrence. This patient would benefit from
revascularization, extensive debridement, and flap coverage;
yet, a SCIP flap would not provide sufficient padding—especially
in the plantar region—and would not provide bulk to fill the
cavity created by the debridement of the metatarsal bone (the
wound is also close to the maximum size of a standard SCIP
flap). An ALT would also be less preferable because evidence
has shown that fasciocutaneous flaps carry a higher rate of
complications in limb salvage; in addition, flaps are commonly
harvested from the ipsilateral limb to avoid compromising the
noninjured limb, and evidence seems to suggest that flaps
harvested from the lower extremity have a higher degree of
pedicle calcification. Instead, an LD flap will provide sufficient
padding of the plantar area, bulk to fill the defect created by the
debridement, a lower rate of complications, and potentially a
less calcified pedicle. Calcaneal tendon lengthening will further
help decrease focal plantar pressure, which will lower the rate of
recurrence.
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