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DR. TARIK TTORKI
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Diabe
etic U
Ulcerss
In
ntrod
duction
Bac
ckground
Diab betic foot ulc
cers occur ass a result of various facttors. Such faactors includ
de mechanical
chan nges in confformation of the bony arc chitecture off the foot, pe
eripheral neuuropathy, an
nd
athe erosclerotic peripheral arterial diseasse, all of which occur with higher freequency and d
intensity in the diabetic
d poppulation. Non n-enzymatic glycosylatio on predisposses ligamentss to
stifffness. Neuroopathy cause es loss of prootective senssation and lo oss of coord
dination of
mus scle groups ini the foot annd leg, both of which inc crease mech hanical stress
ses during
amb bulation.
Patthophysio
ology
Diabbetic persons, like peoplle who are no ot diabetic, may
m develop p atherosclerrotic disease e of
large-sized and medium-size ed arteries, such
s as aorttoiliac and fe
emoropoplite eal
atheerosclerosis.. However, significant
s attherosclerotiic disease off the infrapop pliteal segments
is paarticularly co
ommon in th he diabetic population. Underlying
U diigital artery d
disease, whe en
commpounded by y an infectedd ulcer in close proximity y, may resultt in complete e loss of digital
collaaterals and precipitate
p g
gangrene. Thhe reason forr the prevalence of this fform of arterial
diseease in diabe etic persons is thought to result from m a number of o metabolic c abnormalities,
incluuding high loow-density lipoprotein (L LDL) and verry-low-densiity lipoprotein (VLDL) lev vels,
elev
vated plasma a von Willebrrand factor, inhibition off prostacyclin n synthesis, elevated
plassma fibrinoge en levels, an
nd increased d platelet adh hesiveness.
Ove
erall, people with
w diabete
es have a hig
gher incidenc
ce of atheros
sclerosis, thickening of
capiillary basement membranes, arteriolar hyalinosis
s, and endotthelial prolife
eration.
II
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Calcification and thickening of the arterial media (Mönckeberg sclerosis) are also noted
with higher frequency in the diabetic population, although whether these factors have any
impact on the circulatory status is unclear.
The result of loss of sensation in the foot is repetitive stress; unnoticed injuries and
fractures; structural foot deformity, such as hammertoes, bunions, metatarsal deformities,
or Charcot foot (see Image 3); further stress; and eventual tissue breakdown. Unnoticed
excessive heat or cold, pressure from a poorly fitting shoe, or damage from a blunt or
sharp object inadvertently left in the shoe may cause blistering and ulceration. These
factors, combined with poor arterial inflow, confer a high risk of limb loss on the patient
with diabetes.
Frequency
United States
According to The National Institute of Diabetes and Digestive and Kidney Diseases, "an
estimated 16 million Americans are known to have diabetes, and millions more are
considered to be at risk for developing the disease." Diabetic foot lesions are responsible
for more hospitalizations than any other complication of diabetes. Among patients with
diabetes, 15% develop a foot ulcer, and 12-24% of individuals with a foot ulcer require
amputation. Indeed, diabetes is the leading cause of nontraumatic lower extremity
amputations in the United States. "In fact, every year approximately 5% of diabetics develop
foot ulcers and 1% require amputation." Diabetic peripheral neuropathy, present in 60% of
diabetic persons and 80% of diabetic persons with foot ulcers, confers the greatest risk of
foot ulceration; microvascular disease and suboptimal glycemic control contribute.
Even after successful management resulting in ulcer healing, the recurrence rate in that
patient population is 66% and the amputation rate rises to 12%. Half of all nontraumatic
amputations are a result of diabetic foot complications, and the 5-year risk of needing a
contralateral amputation is 50%.2
Mortality/Morbidity
• Limb loss: Unfortunately, limb loss is a significant risk in patients with diabetic foot
ulcers, particularly if treatment has been delayed.3
• Charcot foot: Sensory neuropathy involving the feet may lead to unrecognized
episodes of trauma due to ill-fitting shoes. Motor neuropathy, causing intrinsic
muscle weakness and splaying of the foot on weight bearing, compounds this
trauma. The result is a convex foot with a rocker-bottom appearance. Multiple
fractures are unnoticed until bone and joint deformities become marked. This is
termed a Charcot foot (neuropathic osteoarthropathy) and most commonly is
III
DR. TARIK TORKI
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Race
The issue of diabetic foot disease is of particular concern in the Latino communities of the
Eastern United States, African Americans4 , and in Native Americans, who tend to have the
highest prevalence of diabetes in the world.
Age
Diabetes occurs in 3-6% of Americans. Of these, 10% have type 1 diabetes and are usually
diagnosed when they are younger than 40 years. Among Medicare-aged adults, the
prevalence of diabetes is about 10% (of these, 90% have type 2 diabetes). Diabetic
neuropathy tends to occur about 10 years after the onset of diabetes, and, therefore,
diabetic foot deformity and ulceration occur sometime thereafter.
Clinical
History
claudication may occur sooner with more rapid walking or walking uphill or up
stairs. The claudication of infrainguinal occlusive disease typically involves the
calf muscles, while symptoms that occur in the buttocks or thighs suggest
aortoiliac occlusive disease.
o Discomfort, cramping, or weakness in the calves or feet is particularly common
in the diabetic population because they tend to have tibioperoneal
atherosclerotic occlusions. Calf muscle atrophy may also occur. Rest pain is
less common in the diabetic population. In some cases, a fissure, ulcer, or
other break in the integrity of the skin envelope is the first sign that loss of
perfusion has occurred. When a diabetic patient presents with gangrene it is
often the result of infection.
Physical
Physical examination of the extremity having a diabetic ulcer can be divided into 3 broad
categories: (1) examination of the ulcer and general condition of the extremity, (2)
assessment of the possibility of vascular insufficiency5 and (3) assessment for the
possibility of peripheral neuropathy. Remember that diabetes is a systemic disease. Hence,
a comprehensive physical examination of the entire patient is also vital.
Extremity examination
posterior tibial pulse is present in 99.8% of persons aged 0-19 years. Hence, absence of
both pedal pulses is a more specific indicator of peripheral arterial disease.
• Other findings suggestive of atherosclerotic disease include a bruit heard overlying the
iliac or femoral arteries, skin atrophy, loss of pedal hair growth, cyanosis of the toes,
ulceration or ischemic necrosis, and pallor of the involved foot followed by dependent
rubor after 1-2 minutes of elevation above heart level.
• For further details, see Infrainguinal Arterial Occlusive Disease.
Peripheral neuropathy
• Signs of peripheral neuropathy include loss of vibratory and position sense, loss of
deep tendon reflexes (especially loss of the ankle jerk), trophic ulceration, foot
drop, muscle atrophy, and excessive callous formation, especially overlying
pressure points such as the heel.
• The nylon monofilament test helps diagnose the presence of sensory neuropathy6
A 10-gauge monofilament nylon is pressed against each specific site of the foot
just enough to bend the wire. If the patient does not feel the wire at 4 or more of
these 10 sites, the test is positive for neuropathy.
Causes
The etiologies of diabetic ulceration include neuropathy,7 arterial disease,8 pressure,9 and
foot deformity.10
Differential Diagnoses
Atherosclerosis
Chronic Venous Insufficiency
Diabetic Foot Infections
The leg pain of peripheral arterial disease must be distinguished from other causes of leg
pain, such as arthritis, muscle pain, radicular pain, spinal cord compression,
thrombophlebitis, anemia, and myxedema.
Workup
Laboratory Studies
VI
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• CBC count: Leukocytosis may signal plantar abscess or other associated infection.
Wound healing is impaired by anemia. In the face of underlying arterial
insufficiency, anemia may precipitate rest pain.11
• Metabolic profile and glycohemoglobin: Assessment of serum glucose,
glycohemoglobin, and creatinine levels helps to determine the adequacy of acute
and chronic glycemic control and the status of renal function.
• Noninvasive vascular laboratory study: Pulse-volume recording (PVR), or
plethysmography, uses pneumatic cuffs encircling the thighs, calves, ankles, feet,
and, occasionally, toes to sense segmental volume changes with each pulse beat.
The resulting tracings provide useful information about the hemodynamic effects of
the arterial disease at each level. In severe disease, tracings at the transmetatarsal
level may become nearly flat. In mild disease, particularly involving the aortoiliac
segment, PVR tracings may appear normal at rest and become abnormal only after
the patient walks until symptoms occur. PVR is noninvasive and rapid and,
therefore, may be repeated frequently to help assess the overall hemodynamic
response to medical or surgical treatment. Ordinarily, if pedal pulses are
satisfactory, arterial evaluation PVR provides no useful information.
• The ankle-brachial blood pressure index is potentially unreliable because of arterial
calcification.
Imaging Studies
• Duplex scanning can provide images of arterial segments that help localize the
extent of disease, and simultaneous Doppler measurement of flow velocity can help
estimate the degree of stenosis. Duplex scanning is quite useful in visualizing
aneurysms, particularly of the aorta or popliteal segments. Use of this technique
probably is best left to the discretion of the vascular specialist.
• Plain radiograph studies of the diabetic foot may demonstrate demineralization and
Charcot joint and occasionally may suggest the presence of osteomyelitis. Note
that plain radiograph studies have no role in the evaluation of arterial disease. This
is because arterial calcification observed on plain radiographs is not a specific
indicator of severe atherosclerotic disease. Calcification of the arterial media is not
diagnostic of atherosclerosis, and even calcification of the arterial intima, which is
diagnostic of atherosclerotic disease, does not necessarily imply hemodynamically
significant stenosis.
• CT scan and MRI: Although an experienced clinician usually can diagnose a plantar
abscess by physical examination alone, CT scan or MRI is indicated if a plantar
abscess is suspected but not clear on physical examination.
• Bone scans are of questionable use because of a sizable percentage of false-
positive and false-negative results. A recent study suggests 99mTc-labeled
ciprofloxacin is a somewhat useful marker for osteomyelitis12
• Conventional Angiography: If vascular or endovascular surgical treatment is
contemplated, angiography is needed to delineate the extent and significance of
atherosclerotic disease. Major risks associated with conventional contrast-injection
angiography are related to the puncture and to the use of contrast agents.
• Technique: Typically, a catheter is inserted retrograde via a femoral
puncture, and contrast is power-injected into the infrarenal aorta. Films are
VII
DR. TARIK TORKI
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taken as the contrast is followed down to both feet. In certain cases, as with
aortic occlusion, a femoral approach to the aorta may not be possible. In
this case, the radiologist may use an alternate entry such as via an axillary
artery or even directly into the infrarenal aorta via a translumbar approach.
• Puncture-related complications: The arterial catheter is usually passed
through a 5F sheath that is 1.6 mm in diameter. This is a sizable hole in the
femoral artery, which may be only 6-10 mm in diameter. After the catheter is
removed, gentle pressure must be applied to the puncture site for
approximately 30 minutes, and the radiologist must balance the need for
hemostasis against the possibility of arterial occlusion. Risks include
hemorrhage, pseudoaneurysm formation, and clotting or dislodgement of
an intimal flap, which may acutely occlude the artery at or near the entry
site. Currently, newer methods of percutaneous closure of the puncture
sites have significantly reduced the site complication rates.
• Contrast-related risks: Angiographic contrast material is nephrotoxic. The
risk of precipitating acute renal failure is highest in patients with underlying
renal insufficiency and those with diabetes. Patients with both of these risk
factors have a 30% rate of acute renal failure following contrast
angiography. Hence, an acceptable serum creatinine level must be
confirmed prior to elective angiography. Avoid contrast angiography (if
possible) for patients with any significant degree of renal impairment. If
contrast angiography is absolutely required despite renal impairment, use a
minimal volume of contrast material. In addition, providing adequate
hydration prior to, during, and after the procedure is essential. Oral
administration of the antioxidant acetylcysteine (Mucomyst) the night prior
to and then just before angiography may be protective of renal function for
patients at risk of contrast-induced nephropathy.13
• Metformin warning: To prevent the possibility of fatal lactic acidosis,
patients with diabetes who are taking metformin (Glucophage) must not
take this medication immediately following contrast angiography. Patients
may resume taking the medication when normal renal function is confirmed
1-2 days after contrast exposure.
• Alternatives to conventional angiography
• Magnetic resonance angiography: Magnetic resonance angiography (MRA)
is an alternative both for patients for patients who are allergic to iodinated
contrast material. MRA is not innocuous. Gadolinium chelates, the
contrast agents used in MRA, have been linked recently to 3 potentially
serious side effects in patients with renal insufficiency: acute renal injury,
pseudohypocalcemia, and nephrogenic systemic fibrosis (see this article
on Medscape). MRA is contraindicated in patients with implanted hardware
such as a hip prostheses or pacemakers. The resolution may be inadequate
for the vascular surgeon in planning reconstructive procedures, particularly
in the smaller infrapopliteal arteries, although MRA technology and contrast
agents continue to improve.14
• Multidetector computed tomographic angiography (MDCT): MDCT avoids
arterial puncture. By using precisely timed intravenous contrast injection,
multidetector (16 or 64 channel) CT scanners can generate angiographic
VIII
DR. TARIK TORKI
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Other Tests
Staging
Stage diabetic foot wounds based on the depth of soft tissue and osseous
involvement.16,17,18 Any ulcer that seems to track into or is deep to the subcutaneous tissues
should be probed gently, and, if bone is encountered, osteomyelitis is likely.
Treatment
Medical Care
Debriding Hypergel Various products provide some degree of These are useful for necrotic
agents (hypertonic chemical or enzymatic debridement. wounds as an adjunct to surgical
saline gel) debridement.
Santyl
(collagenase)
Accuzyme
(papain
urea)
Foam LYOfoam Polyurethane foam has some absorptive These are useful for cleaning
Spyrosorb capacity. granulating wounds having minimal
Allevyn exudate.
Hydrocolloid Aquacel These are made of microgranular suspension of They are useful for dry necrotic
CombiDERM natural or synthetic polymers, such as gelatin or wounds, wounds having minimal
Comfeel pectin, in an adhesive matrix. The granules exudate, and clean granulating
Duoderm change from a semihydrated state to a gel as the wounds.
CGF Extra wound exudate is absorbed.
Thin
Granuflex
Tegasorb
Hydrogel Aquasorb These are water-based or glycerin-based These are useful for dry, sloughy,
Duoderm semipermeable hydrophilic polymers; cooling necrotic wounds (eschar).
IntraSite Gel properties may decrease wound pain. These gels
Granugel can lose or absorb water depending upon the
Normlgel state of hydration of the wound. They are
Nu-Gel secured with secondary covering.
Purilon Gel
(KY jelly)
Low- Mepore These are various materials designed to remove These are useful for acute minor
adherence Skintact easily without damaging underlying skin. wounds, such as skin tears, or as a
Release final dressing for chronic wounds
dressing
that have nearly healed.
Transparent OpSite These are highly conformable acrylic adhesive These are useful for clean dry
film Skintact film having no absorptive capacity and little wounds having minimal exudate, and
Release hydrating ability, and they may be vapor they also are used to secure an
Tegaderm permeable or perforated. underlying absorptive material.
Bioclusive They are used for protection of
high-friction areas and areas that
are difficult to bandage such as
heels (also used to secure IV
catheters).
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DR. TARIK TORKI
DR.TTORKI@YAHOO.COM
YOUR WAY FOR HEALTHY LIFE
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Surgical Care
All patients harboring diabetic foot ulcers should be evaluated by a qualified vascular
surgeon and/or podiatric surgeon who will consider debridement, revisional surgery on
bony architecture, vascular reconstruction, and options for soft tissue coverage.
The autologous skin graft is the criterion standard for viable coverage of the partial
thickness wound. The graft can be harvested under local anesthesia as an
outpatient procedure. Meshing the graft allows wider coverage and promotes
drainage of serum and blood.
A cadaveric skin allograft is a useful covering for relatively deep wounds following
surgical excision when the wound bed does not appear appropriate for application
of an autologous skin graft. The allograft is, of course, only a temporary solution.
Tissue-cultured skin substitutes
Consultations
Any of the following evaluations may prove productive:
• Endocrinologist
• Cardiologist
• Nephrologist
• Infectious diseases specialist
• Vascular surgeon
• Podiatrist
• Orthopedic specialist
• Plastic surgeon
• Wound care specialist
• Nutritionist
Diet
The recommended diet is diabetic and low in saturated fat.
Activity
Offloading of the ulcerated area is imperative. This may require bed rest acutely. Custom
footwear or custom clamshell orthosis (for severe deformities) or total contact casting (a
fiberglass shell with a walking bar on the bottom) are required for patients who are
ambulatory.
Medication
The basic principle of topical wound management is to provide a moist, but not wet, wound
bed.26,41 After debridement, apply a moist sodium chloride dressing or isotonic sodium
chloride gel (eg, Normlgel, IntraSite gel) or a hydroactive paste (eg, Duoderm). Optimal
wound coverage requires wet-to-damp dressings, which support autolytic debridement,
XIII
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absorb exudate, and protect surrounding healthy skin. A polyvinyl film dressing (eg,
OpSite, Tegaderm) that is semipermeable to oxygen and moisture and impermeable to
bacteria is a good choice for wounds that are neither very dry nor highly exudative. Wound
coverage recommendations for some other wound conditions are as follows (see Table):
Other topical preparations that occasionally may be useful in the management of diabetic
foot ulcers are as follows:
Topical agents to avoid: Avoid cytotoxic agents, such as hydrogen peroxide, povidone
iodine, acetic acid, and Dakin solution (sodium hypochlorite), except as noted above under
infected wounds.
Hemorrheologic Agents
Many medications may have a role in the treatment of diabetes, the complications of
diabetes, and the etiologies of diabetic ulcer. For example, hemorheologic agents and
antiplatelet agents are sometimes used in the management of underlying atherosclerotic
disease.
Cilostazol (Pletal) is an alternative hemorheologic agent for patients who cannot tolerate
pentoxifylline42 . Cilostazol is contraindicated in patients with congestive heart failure. The
product's black box warning reads as follows:
Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several
drugs with this pharmacologic effect have caused decreased survival compared to placebo
in patients with class III-IV congestive heart failure. Pletal is contraindicated in patients with
congestive heart failure of any severity.
Pentoxifylline (Trental)
Indicated to treat intermittent claudication. May alter rheology of red blood cells, which in
turn reduces blood viscosity.
From 2-8 wk of therapy may be required before symptomatic improvement occurs, and only
about 60% of patients respond to this drug.
• Dosing
• Interactions
• Contraindications
• Precautions
Adult
400 mg PO tid with meals; if digestive or CNS adverse effects develop, decrease dose to
400 mg PO bid or discontinue
XV
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Pediatric
Not established
• DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosingInteraction
sContraindicationsPrecautions
Cilostazol (Pletal)
• Dosing
• Interactions
• Contraindications
• Precautions
Adult
100 mg PO bid taken at least 0.5 h before or 2 h after breakfast and dinner; consider 50 mg
bid if coadministering with inhibitors of CYP3A4, such as ketoconazole, itraconazole,
erythromycin, and diltiazem, or with inhibitors of CYP2C19 such as omeprazole
Pediatric
Not established
• DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosingInteraction
sContraindicationsPrecautions
Antiplatelet agents
Antiplatelet therapy with aspirin or clopidogrel (Plavix) may be warranted in some cases for
the prevention of the complications of atherosclerosis, although neither has a direct benefit
in healing diabetic foot ulcers. Antiplatelet agents inhibit platelet function by blocking
cyclooxygenase and subsequent platelet aggregation.
Clopidogrel (Plavix)
• Dosing
• Interactions
• Contraindications
• Precautions
XVI
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Adult
75 mg PO qd
Pediatric
Not established
• DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosingInteraction
sContraindicationsPrecautions
• Dosing
• Interactions
• Contraindications
• Precautions
Adult
75-325 mg PO qd
Pediatric
Not established
Follow-up
• For the most part, diabetic ulcers are managed in the outpatient setting, with brief
hospital stays often occurring for initial evaluation and debridement, subsequent
vascular procedures, and, possibly, flap or skin graft wound management.
• Hyperbaric oxygen therapy may be beneficial in certain cases of intractable foot
ulcers accompanied by uncorrectable arterial insufficiency.43
• Antibiotics
• Hemorheologic agents
• Antiplatelet agents
• Hypoglycemic medications
XVII
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• ACE inhibitors
Deterrence/Prevention
• The risk of ulceration and limb amputation in people with diabetes can be improved
by routine preventive podiatric care, appropriate shoes, and patient education.44
Diabetic clinics should screen all patients for altered sensation and peripheral
vascular disease.31 Of diabetic foot ulcers, 85% are estimated to be preventable with
appropriate preventive medicine.
o Daily foot inspection
o Gentle soap and water cleansing
o Application of skin moisturizer
o Inspection of the shoes to ensure good support and fit: Medicare covers
custom shoes with appropriate physician documentation confirming that
the patient is at risk for ulceration.
o Minor wounds require prompt medical evaluation and treatment.
o Prophylactic podiatric surgery to correct high-risk foot deformities may be
indicated.
o Avoid hot soaks, heating pads, and irritating topical agents.
• Glycemic control
o The Diabetes Control and Complications Trial performed by The Diabetes
Control and Complications Trial Research Group studied the effect of
intensive treatment of diabetes on the development and progression of
long-term complications in insulin-dependent diabetes mellitus (1993).45
This trial found that uncontrolled hyperglycemia correlates with the onset
of diabetic microvascular complications and that good glycemic control
can reduce or even prevent the complications of diabetes, including
nephropathy, neuropathy, and retinopathy.
o Cigarette smoking should be stopped, and hypertension and
hyperlipidemia should be controlled.
Prognosis
• Among people with diabetes, 1 in 20 will develop a foot ulcer and 1 in 100 will
require amputation annually. Hence, diabetes is the predominant etiology for
nontraumatic lower extremity amputations in the United States, accounting for half
of all nontraumatic leg amputations. Contralateral amputation will be required in
50% of these patients during the subsequent 5-year interval.
• Peripheral neuropathy—which occurs in 60% of people with diabetes—confers the
greatest risk of foot ulceration; microvascular arterial disease and suboptimal
glycemic control also contribute. In diabetic people with neuropathy,46 even if
successful management results in healing of the foot ulcer, the recurrence rate is
66% and the amputation rate rises to 12%.
Patient Education
XVIII
DR. TARIK TTORKI
DR.TTORKI@ @YAHOO.C COM
YOUR WAY Y FOR HEA ALTHY LIFFE
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• The risk
k of foot ulce
eration and liimb amputattion in peoplle with diabe
etes is lessen
ned
by patie
ent education n stressing the
t importan nce of routine
e preventive
e podiatric ca
are,
approprriate shoes, avoidance
a off cigarette sm
moking, conntrol of hyperlipidemia, and
a
adequatte glycemic control.
c
• For exceellent patient education resources, visit
v eMedicine's Diabetees Center. Also,
see eMeedicine's patient educatio on article Dia
abetic Foot Care.
C
Mis
scellaneo
ous
Med
dicolegal Pitfalls
Physicians of diiabetic patients with ulceers must dec cide between n the sometimes conflictting
options of (1) pe
erforming invvasive proce edures (eg, angiography
a y, bypass surrgery) for limmb
salv
vage and (2) avoiding thee risks of unn necessarily aggressive managemen
m t in these
patie
ents, who may have sign nificant card
diac risk. In general,
g the greatest
g lega
al risks are
assoociated with delay in diagnosis of isc chemia asso ociated with diabetic ulce eration, failu
ure
to ag
ggressively débride and d treat infectiion, and failu
ure to treat th
he wound ca arefully. If a
patie
ent presentss with a new diabetic fooot ulcer, he or
o she should d receive carre from
physsicians, surg
geons, podia atrists, and pedorthotists
p s who have an a active interest in this
commplex problemm.
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ultimedia
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