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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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risk, wound healing metrics, and expected benefit from
revascularization.
Other historically commonly used classification systems include
the Fontaine and Rutherford classifications, the Wagner-Meggitt
classification (mostly based on ABI values), and the University of
Texas Health Science Center San Antonio diabetic wound
classification (mostly based on absence/presence of infection and/or
ischemia, but not their severity). Other proposed classifications,
especially for diabetic CW, are the S(AD) SAD (size [area and
depth]; sepsis, arteriopathy, and denervation), the PEDIS (perfusion,
extent/size, depth/tissue loss, infection, and sensation; proposed by
the International Working Group on the Diabetic Foot), the SINBAD
(site, ischemia, bacterial infection, area, and depth) system, the
Foster and Edmonds, the DEPA (depth, extent of bacterial
colonization, phase of healing, and associated etiology) system, Van
Acker/Peter classification, and others. Yet, no high-level studies have
validated the reliability of these tools.
Additional classification is used for the severity of underlying
etiologies, which correlates with healing outcomes. Chronic venous
disease is staged with the CEAP (clinical, etiological, anatomical,
and pathological) classification (the Venous Clinical Severity Score
further complements it). PAD is staged using the SVS Lower
Extremity Threatened Limb Classification System, the Global Limb
Anatomic Staging System (GLASS), and the Medial Arterial
Calcification (MAC). Recent work suggests that pedal GLASS and
MAC scores correlate with the risk of LEA in patients with PAD.
Wound infection can be classified using the NERDS (nonhealing,
exudative, red and bleeds easily, debris, and smell) and STONEES
(size increasing, temperature increased, probes to or exposed bone,
new areas of breakdown, exudative, erythema/edema, and smell)
checklists with high sensitivity and specificity (73% and 80% for
NERDS; 90% and 69% for STONEES), the Infectious Disease
Society of America Clinical Classification of a Diabetic Foot Infection,
or the Lipsky classification.
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Several patient-reported outcome measures (PROMs) also exist
for CW (WOUND-Q, SCI-QOL) and scars (SCAR-Q). The
Career/Sexual Well-Being Scale can facilitate the holistic evaluation
of patients presenting with CW.
13
Innovation in diagnosis: Advancement in machine learning (ML)
and artificial intelligence (AI) provides possible disrupting innovation
in the diagnosis and monitoring of CW (automated detection of
infection, triage of CW based on potential severity, or prediction of
response to treatment) especially in low-resource setting or during
home care.
14
Strict glycemic control (diet and/or pharmacologic therapy) is
required in diabetic CW. Pressure modulation (“offloading”) prevents
exacerbation of CW and their recurrence; offloading can be achieved
through a broad range of solutions (eg, wheel chair, crutch-assisted
gait, total contact casts (TCCs), felted foam, half shoes, therapeutic
shoes, removable cast walkers). TCC is the standard for plantar CW
and best allows physical therapy and physical activity.
For infected wounds, systemic antibiotic therapy (parenteral or
oral, 10-day course) is required, following adequate debridement of
necrotic and infected tissue. Local antibiotics are generally less
effective and should not be continued for more than 10 days.
Attention to antibiotic misuse and the development of antibiotic
resistance is a primary concern in wound care. Use of high
concentrations of topical antibiotics and limited systemic toxicity is a
current area of innovation (minocycline and gentamycin are currently
authorized for this purpose). Clinical efficacy of silver-based
dressings is not always validated, and they might have cytotoxicity
on healing tissues. Topical hypochlorous acid is effective and with
low cytotoxicity. Other substances adopted in the management of
infected CW include iodine, dialkylcarbamoyl chloride, cadexomer
iodine, Ag+, and others. Osteomyelitis must be treated for 6 weeks or
more. Furthermore, the therapeutic use of probiotics in CW might
rebalance dysregulated cutaneous microbiomes.
15
Pain management is a determinant of patient adherence to
treatment and healing. New/increasing pain might be a sign of a
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worsening wound and/or of infection. Pain is quantified using
validates scales (eg, visual analog scale) and assessing its impact
on activities of daily living and quality of life (eg, sleep, appetite,
mobility, social life, work). For complex and persistent pain, a
specialist and pain management services are advised. Procedural
pain is prevented or limited using topical anesthetics, systemic
analgesics, and relaxation techniques. Pain management should
follow an incremental approach: nonopioid analgesics such as
NSAIDs (with/without adjuvants such as tricyclic antidepressants,
anticonvulsants, antihistamines, benzodiazepines, steroids, and
phenothiazines) are first-line, addition of an opioid (eg, codeine or
tramadol) is second-line, and eventually oral narcotics are last-line in
patients experiencing most severe and persistent pain.
Nonsurgical Care of CW
Dressings: A plethora of dressings and products are currently
available and continuously evolving. In general, there is a lack of
definitive evidence in support of the use of specific dressings for
particular CW. Surgeons should identify the best dressing on a caseby-case basis, based on their different characteristics and functions.
Multilayer dressings provide mechanical protection, padding, and
protection from shear stress and pressure; occlusive dressings
protect from bacterial contamination; and absorbent dressings
control ideal moisture in exuding CW. Moisture modulation impacts
cell proliferation, migration, and matrix deposition during healing and
scarring; in addition, it exposes wounds to exudate fluid rich in
PDGF, b-FGF, and MMPs. In addition, exudate control affects pain
and facilitates wound management by caregivers and patients.
Because exudate can vary over time (eg, higher after debridement)
and based on type of CW, dressings with different absorbent
capacity exist. Standard dressings include open dressings (eg,
gauze) and semiopen dressings (meshed gauze impregnated with
petroleum, paraffin wax, or other ointment, such as Xeroform,
Adaptic, Jelonet, and Sofra Tulle). For CW, open dressings have
limited application although they can be used in a wet-to-moist or
wet-to-dry fashion for mechanical debridement. Semiopen dressings
are easy to apply (but bulky because of the need for a secondary
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dressing) and inexpensive but provide poor control of wound
moisture and cause wound desiccation. Topical medical-grade honey
(paste, gel, or dressings) has been used in wound healing for
millennia: it can facilitate healing and it can help contrast infection.
Advanced dressings are described below.15-
17
Semipermeable films: Made of thin elastic polyurethane films (eg,
Biofilm, Bioclusive, Hydrofilm, Mepilex Film, OpSite, OpSite Flexifix
Gentle, and Tegaderm) and are permeable to gas but not to bacteria
and liquids. They control some moisture evaporation, provide a
biological barrier to contamination, and allow direct visual inspection.
They are rarely of use in CW, unless used to waterproof another
primary dressing. They should be avoided in highly exuding wounds
(fluid will pool and cause maceration), delayed healing, and infection;
in addition, they can be painful/traumatic to remove.
Polyurethane foams: Are hydrophobic or hydrophilic highly
absorbent and insulating dressings (eg, Allevyn, PermaFoam,
Lyofoam Max, Mepilex, Suprasorb, Spyrosorb). They facilitate
moisture and protect from mechanical stress; a soft silicone coating
allows nontraumatic removal and containment of exudates. Given
their high absorptivity, dressing changes can be less frequent. Main
indications include mildly to moderately exuding CW and burns.
Contraindications include dry/nonexuding wounds or CW requiring
frequent care.
Hydroactive (foamlike) multilayered polymers: Are highly
absorbent dressings (eg, Biatain surface, Cutinova Hydro surface,
PolyMem surface and cavity dressing, and Tielle surface) that trap—
but do not remove, differently from foam dressings—exudate to
maintain moisture. Optimal control of moisture, reduced risk of
maceration, nonadherence to the wound bed, and elasticity make
these dressings ideal for highly exuding superficial wounds (eg,
venous CW, and minor burns), cavity CW, or CW over joints.
Alginates: Are calcium or calcium sodium salts of alginic acid.
When applied to a wound, they form sodium alginate, a hydrophilic
gel, with high absorption of exudates up to 20 times their weight.
Their main advantage are the high absorption capacity (maintain
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wound moisture, avoid maceration), the nonadherence for easy
removal, a hemostatic effect (calcium ions aid clotting), and their
adaptability to different wound shapes. Alginates require a
secondary dressing (eg, hydrocolloids or foams) to avoid drying and
secure adherence. Allergic, inflammatory, or anaphylactic reactions
are described. Main indications are highly exuding wounds,
especially when combined to bleeding. Contraindications are dry
wounds. They can be applied to infected wounds (not recommended
with anaerobic pathogens) with a secondary nonocclusive dressing.
Hydrofibers: Are nonwoven sodium carboxymethyl cellulose spun
into fibers (eg, AQUACEL, AQUACEL Foam, and AQUACEL Extra).
They have similar properties to those of alginates but with higher
absorbing capacity. Other fiber dressings with different composition
but similar properties exist (eg, Exufiber, Durafibee, Carboflex). They
have similar advantages/disadvantages and
indications/contraindications of alginates. In addition, they promote
autolytic debridement.
Hydrocolloids: Contain agents (eg, gelatin, sodium
carboxymethylcellulose, and pectin) that absorb exudate to form a
gel. Their outer layer can be occlusive or semiocclusive; dressings
are also available in powder or paste form. Hydrocolloids promote
moisture and support autolytic debridement when necrotic tissue is
present. They have similar advantages/disadvantages and
indications/contraindications to fiber dressings; in addition, they
create an acidic environment that inhibits potential bacterial growth.
Their use is not recommended in infected wounds, given the
semiocclusive environment, although colonizing bacteria and debris
are trapped and mechanically removed during dressing changes.
Additional risks and limitations associated with prolonged use of
hydrocolloids are wound hypergranulation, allergic contact
dermatitis, malodor, and the need for frequent dressing changes.
Hydrogels: Are semiocclusive dressings of water-insoluble
hydrophilic polymers available as amorphous gel, sheet, or hydrogelimpregnated sheet (eg, Purilon, IntraSite, Solosite, Solugel,
Hydrosorb, HydroTac, HydroTac Comfort, IntraSite Conformable, and
Suprasorb G Sheet). These polymers expand in water to
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hydrate/rehydrate wounds/eschars and to promote autolytic
debridement. Some hydrogels contain antimicrobial agents or
antibiotics (eg, Flaminal Hydro and Forte, Oxyzyme, and Iodozyme).
Hydrogels provide a moist environment but are not an effective
barrier. Main indication is CW with minimal to moderate exudate,
those with granulation tissue, or those under epithelialization. Some
hydrogel may cause allergic reactions.
In summary:
moisture-facilitating dressings should be used in dry
CW/eschars, whereas moisture-mitigating dressing should be
preferred in exuding wounds;
dressings promoting autolytic debridement are helpful in CW
with fibrinoid tissue/slough;
occlusive dressings should be avoided in infected/potentially
infected CW, whereas a barrier to contamination should be
provided in noninfected CW;
dressing with cytotoxic components should be avoided in lack
of a confirmed infection;
elastic/moldable dressings are helpful in joint areas or areas
of high mobility, whereas padded/multilayered dressings are
required in CW at risk for mechanical stress;
low-adherent dressings are preferred in fragile skin or during
the epithelialization stage, and in patients reporting pain;
some dressings have an additional hemostatic effect;
potential for allergic reaction should be taken into
consideration;
patients’ compliance, availability of medical resources, and
scheduled frequency of dressing changes can guide the
choice of the ideal dressing to be used.
Adjunct therapies: Several adjunct therapies can help promote
healing of CW. These can be categorized as biophysical therapies
(eg, NPWT, shock waves) or biological products (eg, HBOT, GFs,
stem cells).
18,19
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NPWT: NPWT is recommended for the temporary management of
large and full-thickness CW, especially when highly exuding. It is
contraindicated or should be used with caution in the presence of
necrotic tissue or slough, exposed structures (eg, blood vessels,
organs, tendons, or nerves), malignancy, fistulas, osteomyelitis, and
active bleeding. NPWT improves wound cleansing and removal of
toxic factors, granulation tissue formation, perfusion/angiogenesis,
wound contraction, and possibly lymphatic drainage. Dressings are
changed every 3 to 4 days with devices available for inpatient and
outpatient/home care. NPWT systems with instillation allow for
combined suction-based therapy and irrigation. Foreign body
retention of pieces of the polyurethane foam interface and/or
ingrowth of granulation tissue within the foam causing mechanical
trauma can occur during dressing changes.
HBOT: HBOT adopts enriched oxygen in a pressurized
environment to facilitate healing. Supersaturation of oxygenated
blood, local vasodilation, increased neutrophil bactericidal activity
through altered redox state, modulation of inflammatory cytokines,
and reduction of edema are supposed to contribute to healing.
Despite widespread use, high-level evidence supporting its efficacy
is lacking. HBOT is recommended for most severe and recalcitrant
CW with limited therapeutic alternatives. Topical oxygen therapy also
increases oxygen concentration within CW, yet more research is
needed to validate its efficacy and to identify optimal indications.
Transcutaneous electrical nerve stimulation (TENS): TENS adopts
noninvasive electrical stimulation to promote healing (eg,
epithelialization, contraction, proliferation and migration of
fibroblasts, and angiogenesis). In vitro, it has shown to decrease
pathogens (eg, S. aureus, P. aeruginosa, and Escherichia coli). This
is a low-cost and painless therapy with potential but higher-level
evidence in support is lacking. Treatments might last hours, and
devices for home treatment are not always available. In addition,
there is extremely broad heterogeneity in protocols of treatment (eg,
direct current, alternating current, and pulsed current on mono or
bipolar devices) with no formal comparison among these.
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ESWT: ESWT can help healing of CW by using high-energy
acoustic pulses to stimulate cell proliferation, angiogenesis, and
cavitation of necrotic tissue (combination of thermal and nonthermal
actions). ESWT is used externally, for 5 to 10 minutes. Most studies
have used in diabetic CW; it is not recommended in the presence of
metal prosthesis, neuropathy, infection, or thrombophlebitis. Adverse
events are common and include bruising, pain, numbness,
headaches, cellulitis, and wound infection.
PBM: PBM uses the biological effects of light on tissue to guide
healing. In research settings, PBM has shown to stimulate
angiogenesis, synthesis and deposition of ECM, mitigation of
inflammation, and cell proliferation or migration. PBM uses lightemitting diodes with varying wavelengths: red light has a deeper
penetration depth than blue, green, violet, and yellow light, whereas
infrared and near-infrared lights penetrate even deeper. Optimization
of dosage and wavelengths to maximize outcomes are lacking.
Small clinical trials have shown improved healing of CW after PBM,
but stronger evidence is needed. Laser therapy is another lightbased therapy, commonly adopted in the treatment and prevention of
scars.
Photodynamic therapy (PDT): PDT combines a photosensitizer in
the wound and an external light to activate it. It seems to have an
antibacterial activity, especially on biofilm.
Electromagnetic fields: Low-frequency pulsed electromagnetic
fields seem to support connective tissue and collagen deposition,
angiogenesis, and release of nitric oxide. Small devices for home
care are available. Some studies have shown promise, but some
mixed validity.
Biological adjunct therapies include topical application of GFs,
PRP, stem cells, and cells exosomes.
20,21
GFs: The use of externally delivered GFs to facilitate healing is
extensively studied. Supplementation of specific molecular/cellular
pathways (eg, angiogenesis, inflammation, cell migration, fibroblast
proliferation, ECM deposition) promotes healing. Several GFs have
pleiotropic effects in wound healing (eg, HGF, TGF-beta, IGF,
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VEGF). Despite substantial research, only limited products are
commercially available, likely because of the regulatory,
manufacturing, and financial challenges faced by biologic therapies.
GFs used in clinical care include recombinant human FGF (hFGF),
recombinant human PDGF (hPDGF), and recombinant human EGF
(hEGF). Recombinant hEGF has been tested (topically or via topical
injection) in small clinical trials, showing positive outcomes. Similar
results have been reported for hFGF (especially as recombinant
hKGF-2) applied as a spray. Recombinant hPDGF is the only GF
currently approved by the Food and Drug Administration (FDA) and
the European Medicines Evaluation Agency for clinical application:
Becaplermin gel (Regranex), the first commercially available PDGF
for diabetic CW, contains an FDA black box warning for increased
mortality risk secondary to malignancy with prolonged use.
PRP: PRP is plasma with high concentrations of platelets, GFs,
and cytokines. These factors are associated with higher proliferation
and migration of epithelial cells, angiogenesis, collagen deposition,
and wound closure. PRP is obtained from blood using a simple
centrifuge, in a process that is fast and relatively inexpensive.
Centrifugation parameters and activation protocols affect the
composition of PRP, but no unique protocol is currently available,
contributing to the heterogeneity of outcomes reported. Clinical trials
have reported positive outcomes (eg, increased rate of wound
closure and time to heal, decreases pain), but evidence supporting
the use of PRP in the management of CW is limited and conflicting.
Stem cells: The use of stem cells of different origins (embryonic,
mesenchymal, bone marrow–derived, and adipose-derived) to
support healing in CW has generated high expectations. Despite
substantial research, translation to humans has been limited to some
experimental trials. Beyond the same limitations of other biologic
products, safety (eg, risk of malignancy) and ethical concerns exist.
Stem cells can be administered topically or systemically (thanks to
their homing to areas of tissue injury) and release GFs and factors
that promote healing. Clinical trials have reported positive outcomes,
yet most studies have included few patients and inadequate controls.
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Exosomes: Exosomes are extracellular vesicles secreted by
various cell populations for endocrine and paracrine regulation of the
surrounding environment and represent one of the latest areas of
innovation in the field of wound healing. Exosome-based therapies
aim to provide a complex mixture of GFs, cytokines, and enzymes
that replicate the paracrine effects of (stem) cells, while avoiding the
challenges associated with cell therapies. Exosomes have long-term
stability at room temperature, can be lyophilized, are immuneprivileged, and can be manufactured relatively homogenously for
composition. Preclinical studies have confirmed the therapeutic
potential of exosomes derived from stem cells in wound healing; yet,
to date clinical literature is lacking.
Wound Bed Preparation and Debridement
Wound bed preparation and debridement (the removal of
nonviable/necrotic tissue and slough/debris from soft tissues,
tendons, and bones) are essential procedures for wound healing,
and the most effective method to remove biofilm and foreign bodies.
It can occur by surgical, mechanical, enzymatic, biologic, or autolytic
methods, based on patient factors, wound characteristics, available
resources, and costs. Commonly, several sessions of debridement
are required before a wound bed is ready for repair; in between
sessions, partial recolonization is possible. Early timing is a critical
factor affecting the efficacy of debridement.
15,17,22
Surgical debridement is the standard; it adopts blades and
curettes, under anesthesia, and often with patient hospitalization.
Debridement must preserve tissue vascularity, especially in ischemic
CW, with bleeding controlled by selective cautery. For necrotic bone
or osteomyelitis, only surgical debridement is effective and it requires
dedicated tools (eg, sagittal saw).
Mechanical debridement includes tangential hydrosurgery,
ultrasound, pulsatile lavage, gauze abrasion, or wet-to-dry dressings.
Hydrosurgery (eg, Versajet) is effective but less precise than surgical
debridement in selectively removing nonviable tissue, can damage
healthy tissue, and is expensive. Low-frequency US allows painless
bedside debridement; yet, it is expensive, may facilitate
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