Nutritional Management in Adults with Wound Healing Needs ...

Nutritional Management in Adults
with Wound Healing Needs
Product Monograph
Therapeutic NutritionTM Drink Mix
A Medical Food That Supports Wound Healing and Helps Build Lean Body Mass
Use under medical supervision
Slows Protein Breakdown Enhances Tissue Growth

Table of contents
Executive summary ......................................................................................................................5
Introduction to Abound ® and wound care .................................................................................6
Hard-to-heal wounds ..................................................................................................................7
The link between nutrition and wounds ......................................................................................8
Prevalence and impact of wounds by type .............................................................................11
Pressure ulcers ..........................................................................................................................12
Diabetic foot ulcers ...................................................................................................................13
Venous leg ulcers ......................................................................................................................14
Burns .........................................................................................................................................15
Surgical incisions ......................................................................................................................16
Wounds and healing ...................................................................................................................17
Normal wound healing ..............................................................................................................17
Conditions that impair wound healing ......................................................................................19
Care of hard-to-heal wounds ....................................................................................................21
The wound care team ................................................................................................................21
Cleaning and dressing a wound ................................................................................................22
Nutritional care: rationale to implementation ............................................................................23
Overall nutrition for wound healing ........................................................................................24
Specific nutritional guidelines by wound type ......................................................................24
Macronutrient recommendations ..........................................................................................26
Roles of specific nutrients .....................................................................................................27
Use of Abound ® as part of optimal wound care .....................................................................28
Abound ® and its ingredients .....................................................................................................28
Clinical trial results ....................................................................................................................32
Abound ® and wound healing .................................................................................................32
Abound ® in clinical practice ......................................................................................................34
People who can benefit from Abound ® .....................................................................................34
How to incorporate Abound ® into the therapeutic regimen .....................................................34
Forms and Flavors .....................................................................................................................36
Directions for use ......................................................................................................................36
Conclusions .................................................................................................................................37
References ................................................................................................................................. 38

Executive summary
Wound healing depends on a combination of good nutrition and hygienic wound care. But
sometimes good nutrition—based on a diet of varied foods and/or on a complete and balanced
nutritional supplement—is not enough. Despite these usual strategies, some wounds persist.
Abound ® is a therapeutic nutrition product that can benefit people with hard-to-heal wounds.
Abound ® is formulated to meet specific nutritional stresses of healing wounds such as pressure
ulcers, diabetic foot ulcers, venous leg ulcers, surgical incisions with complications, and burns.
Abound works because it is a unique blend of ingredients that support wound healing above
and beyond the limits of basic nutrition; it contains amino acids arginine and glutamine, and
beta-hydroxy-beta-methylbutyrate (HMB; a metabolite of the amino acid leucine). Because
these ingredients are vital for the anabolic processes of wound healing, short supplies can
limit healing.
Combined, the 3 key components of Abound ® help support specific anabolic processes and
immune functions that are vital to healing wounds. HMB has been shown to inhibit muscle
proteolysis and modulate protein turnover, functions important to overcoming the metabolic
toll of hard-to-heal wounds. Glutamine and arginine support synthesis of collagen, a protein
essential to skin integrity and elasticity. Glutamine and arginine also serve as metabolic fuels
for immune cells, thereby enhancing immune function to prevent or fight infections that can
complicate wound healing. In addition, arginine is also recognized to play a key role in producing
mediators that stimulate activity of immune cells and enhance formation of new blood vessels.
Proper wound care also requires a diet planned for wound healing. Appropriate nutrition for
healing of acute or chronic wounds includes increased caloric energy, adequate protein, ample
fluid supplies, and increased doses of certain vitamins and minerals (zinc, and vitamins A, C,
and E).
Abound therapeutic nutrition, along with a diet planned for wound healing, must also be
accompanied by all-around good care for wounds and total health. Wound healing requires
a multi-disciplinary team of health care professionals who take care of nutrition, surgical
procedures, wound hygiene, wound dressings, and the general health status of the patient.
5

6
Introduction to Abound ®
wound care
and
When the latest principles of wound management are paired with the newest nutritional science,
it is possible to design medical nutrition therapy that targets the needs of patients with
hard-to-heal wounds. For such individuals, healing can be enhanced by ensuring an adequate
supply of nutrients recognized to support tissue growth and repair, sustain immune responses,
and compensate other special metabolic needs. Abound ® is a therapeutic nutrition product
intended to benefit people who need treatment for hard-to-heal wounds.
This monograph reviews the personal and economic impact of hard-to-heal wounds; discusses
the pathology of hard-to-heal wounds; describes the role of nutrition in wound healing; explains
how, when, and why to use Abound ® to support healing; and summarizes the clinical evidence
underlying the benefits delivered by Abound.
Abound ® is a therapeutic
nutrition product intended
to benefit people who need
treatment for hard-to - heal
wounds.

Hard-to-heal wounds
• Wounds may be acute or chronic. Surgical incisions, burns, and traumatic injuries are
examples of acute injuries. If acute injuries are extensive or complicated by infection, they
may become hard-to-heal. Other hard-to-heal wounds—venous leg ulcers, diabetic foot
ulcers, and pressure ulcers—develop in people with chronic health conditions. 1 Hard-toheal
wounds fail to progress through an orderly sequence of repair in a timely fashion. 2 A
wound is usually considered chronic if it takes more than 30 days to heal.
Figure 1. Hard-to-heal wounds fail to progress through an orderly sequence of repair in a timely fashion.
• Hard-to-heal wounds occur in the general population, but older individuals who are
hospitalized or reside in long-term care facilities are at particular risk. Up to 3% of
individuals over 60 years in the UK are reported to suffer from hard-to-heal skin wounds
such as leg and pressure ulcers. 3 Approximately 3.5% of the US population older than 65
years have venous leg ulcers. 4 Of the 150 million people in the world with diabetes, at least
15% are expected to develop one or more foot ulcers in their lifetime, especially in older
years. 1 The prevalence of pressure ulcers among elderly people living in long-term care
5, 6
facilities exceeds 20% in the US and Canada.
• The prevalence of hard-to-heal wounds and the costs of management have continued
to rise over time, despite increasing availability of advanced wound-care specialists and
wound-healing centers.
The prevalence of
hard-to-heal wounds and
the costs of management
have continued to rise over
time, despite increasing
availability of advanced
wound-care specialists
and wound-healing
centers.
7

8
The link between nutrition and wounds
• A key factor for wound healing is the patient’s nutritional status. Hard-to-heal wounds will
heal faster and with fewer complications when the patient is well nourished. But in many
cases, even a diet planned for healing wounds is not enough.
• If adequate protein—including dietary supplies of essential and conditionally-essential
amino acids—is not consumed in the diet, impaired wound healing will result from limits on
protein synthesis. A conditionally-essential amino acid is one that is normally synthesized
by the body, but an additional dietary supply is needed during times of rapid growth, as in
infancy or wound healing.
• Conditionally-essential amino acids arginine and glutamine play multiple roles in wound
healing. Glutamine 7-10 and arginine 11, 12 support synthesis of collagen, a protein that
determines skin integrity and elasticity. Glutamine 13 and arginine 14 also serve as metabolic
fuels for immune cells, thereby enhancing immune function to prevent or fight infections
that can complicate wound healing. In addition, arginine is recognized to play a key role in
production of mediators that stimulate activity of immune cells and enhance formation of
new blood vessels.
• Beta-hydroxy-beta-methylbutyrate (HMB; a metabolite of the amino acid leucine) increases
collagen deposition, an action important to wound closure and healing. 7 HMB has been
shown to inhibit muscle proteolysis, 15-17 a function important to overcoming the metabolic
toll of hard-to-heal wounds. HMB also increases nitrogen retention, a general indicator of
lowered protein catabolism, 18 and it has anti-inflammatory properties as well. 19
• Abound ® is a therapeutic nutrition product that can help wound healing. Abound ® has
a unique blend of key ingredients—amino acids arginine and glutamine, and HMB.
Combined, the 3 key components of Abound ® help support specific anabolic processes
and immune functions that are vital to healing wounds.
• In addition to rate-limiting nutrients, wound healing requires a diet planned for wound
healing. Appropriate nutrition for treating hard-to-heal wounds includes increased caloric
energy, adequate protein, ample fluid supplies, and increased doses of certain vitamins and
minerals (zinc, and vitamins A, C, and E).
A key factor for wound
healing is the patient’s
nutritional status. But in
many cases, even a diet
planned for healing
wounds is not enough.
ORANGE
NATURAL FLAVOR WITH
OTHER NATURAL FLAVORS
POWDER • ADD WATER
30 PACKETS • each packet 0.85 oz (24 g) • NET WT 0.74 lb (720 g)
* See back panel
Abound supports wound
healing with 3 key
ingredients—glutamine,
arginine, and HMB.
Slows Protein Breakdown Enhances Tissue Growth

Abound ® ingredients support processes involved in wound healing
ARgInInE glUtAmInE HmB (lEUCInE mEtABolItE)
12, 20-22
• Enhances wound healing
• Stimulates synthesis and deposition
11, 12
of collagen
• Supports protein synthesis 23
• Supports immune function 14
• Enhances wound healing, especially
by stimulating collagen synthesis 7-10
10, 13
• Supports protein synthesis
• Supports gut integrity and immune
function 13
• Decreases breakdown of
muscle proteins 15-17
• Increases nitrogen retention,
a measure of protein anabolism 18
• Anti-inflammatory effects 19
9

10
A Case Study From the US–a man with a diabetic foot ulcer
Mr. S is a 62-year-old man with a 20-year history of diabetes mellitus. During the cold winter season, he noticed that
the skin on the sole of his foot was cracking, a condition he attributed to extremely dry indoor air. Over several weeks,
he developed a severely inflamed and necrotic plantar sore on his right foot. His general physician referred him to a
wound care center, where the lesion was debrided, and Mr. S. was given instruction to care for his wound.
Unfortunately, the ulcer worsened and was complicated by osteomylelitis, which required repeated antibiotic
treatments. After 7 months, the wound care team recommended Mr. S for another surgical debridement, which
resulted in a wound 6 cm long, 5 cm wide, and 2.5 cm deep. Mr. S was directed to clean the wound and change
the dressings daily, take an oral antibiotic (levofloxacin), and follow his usual diabetic diet. Despite careful attention
to wound care and nutrition, Mr. S could not control his blood glucose levels, the foot ulcer failed to heal, and
osteomyelitis persisted.
On return to the clinic, the wound care team recommended that Mr. S have hyperbaric oxygen therapy, a consulting
surgeon recommended a below-the-knee amputation, and a wound care nutritionist recommended a trial with
Abound medical nutrition therapy. Mr. S opted to try Abound first. For the next 2 months, he added 2 packets of
Abound to his daily diet. Typically he mixed one pack of Abound powder with 8 to 10 fl oz of cold water. He had
one serving of Abound at 7:30 AM and another at 6:30 PM. Each Abound serving was counted as ½ starch or
carbohydrate exchange.
On a follow-up visit to the wound care center, Mr. S reported that he felt stronger and more energetic. He noted that
his foot ulcer appeared to be healing. On examination, the wound had closed, and the ulcer surface had diminished
to 3.8 cm long and 1.2 cm wide. Because of this satisfactory ulcer healing, the wound care team decided that neither
surgery nor hyperbaric therapy was needed.

Prevalence and impact of wounds
by type
Wounds and wound care take high personal and financial tolls. The most common types of
hard-to-heal chronic wounds are pressure ulcers, diabetic foot ulcers, and venous leg ulcers;
hard-to-heal acute wounds are complicated incisions and serious burns. For people with
wounds, non-healing decreases quality of life by causing social isolation, impaired physical
mobility, pain, emotional stress, loss of self image, and depression. 1 In the UK, the annual cost
of caring for hard-to-heal wounds was reported as 3% of the total health care budget, i.e. £3.1
billion out of £89.4 billion GBP per year. 24 On a global scale, costs for hard-to-heal wounds
could exceed $100 billion USD each year (when estimated at 3% of total costs for worldwide
health care expenditures of $4.1 trillion USD). 25 Indirect costs, such as days absent from work,
loss of employment, or forced retirement, considerably increase the overall burden.
The most common types
of hard-to-heal wounds
are pressure ulcers,
diabetic foot ulcers, and
venous leg ulcers; most
common, hard-to-heal
acute wounds are
complicated surgical
incisions and serious burns.
11

12
Pressure ulcers
Pressure ulcers are a common problem in all health care settings and can result in severe
patient discomfort and treatment cost. Current standards of care in the US recognize that
most pressure ulcers are preventable. 26
• Pressure ulcer prevalence varies greatly by health care setting and provider.
– In the US, prevalence ranges from 0 to 38% in hospitalized patients; 2 to 24% of
those in long-term care, and 0 to 17% in home care. 27
– A recent study covering five European countries found a prevalence of 18% for all
pressure ulcers. The study found that only 9.7% of patients in need of care received
adequate treatment. 28
– In Canada, pressure ulcers were found in 25% of patients in acute care facilities and
30% of patients in non-acute care facilities. 6
• Costs of pressure ulcer treatment are considerable and are likely to increase as the
population ages. 29
– Pressure ulcer treatment costs are 4% of total health care expenditures in the UK (NHS) 30
and 1% of the total Dutch health care budget. 31
– Most of the cost is absorbed by nurses’ time, and the severity of the sore increases the
cost dramatically: a stage IV ulcer is over 10 times more costly to treat than a
stage I ulcer. 30
– In the US, it is estimated that treatment cost per patient ranges from $500
to $40,000. 27
• Pressure ulcers are painful, slow to heal, and susceptible to infections that further
impair healing. 32

Diabetic foot ulcers
Diabetic foot ulcers are relatively common among persons with diabetes mellitus. Such ulcers
often become painfully infected, reducing quality of life and resulting in considerable treatment
expense. The most costly and feared consequence of these ulcers is limb amputation.
• 171 million people around the world were estimated to have diabetes in the year 2000. 33
– Diabetes prevalence is predicted to double to 366 million by 2030.
– The number of people over the age of 65 with diabetes will increase two and a half times
in the same period.
• Among people with diabetes, estimates of lifetime risk for diabetic foot ulcers range from
15% to a high of 25%, 34 35, 36
and prevalence from 3% to 13%
– In a US study, prevalence was reported as 13%. 36
– In a German study, prevalence was approximately 3%. 35
• Diabetic foot ulcers seriously impact quality of life and long-term health; diabetic foot ulcers
result in significant medical treatment expense.
– Foot ulcers can result in loss of mobility that affects everyday tasks and leisure activities. 37
– One third of diabetic individuals with their first foot ulcer suffered from clinical depression,
which was in turn associated with increased mortality. 38
– A European study found 23% of diabetic patients with foot ulcers had not healed after a
year; 39 the rate of recurrence was high, up to 50% after 3 years, 40 further impacting quality
of life, costs, and amputation risks.
• Foot ulcers continue to be the most common underlying factor leading to
lower-extremity amputation. 41
– Limb amputation occurs 10 to 30 times more often in diabetic persons than in the
general population. 34
– A UK study found that 19% of diabetic patients newly reporting a foot ulcer had a lower
extremity amputation within 5 years, and 44% died within that same period. 42
The most costly and
feared consequence of
diabetic foot ulcers is
limb amputation.
13

14
• A Swedish study estimated the direct costs of treatment for a diabetic foot ulcer were
$17,500 (1998 US$); costs rose to $33,500 when amputation was required. 43 Cost
estimates in a 2003 US study were $9,000 to $45,000 USD for annual treatment of a
diabetic foot ulcer (depending on severity) and about $50,000 for leg amputation. 44
• Diabetic foot ulcers have a large negative impact on patients, both psychologically and
socially. These ulcers are associated with a reduction in social activities, increased family
tensions, limited employment and financial distress. 45
Venous leg ulcers
Venous leg ulcers are wounds that result from underlying chronic venous insufficiency. 46 These
leg ulcers are common in adults, and are costly to treat due to prolonged healing time.
• Venous ulcers are common. Estimates of prevalence of venous leg ulcers vary considerably
due to differing sampling methods, ulcer definition, and population ages. A rough estimate
places prevalence at 0.3%, or about 1 in 350 adults. 46
– Studies found a history of either unhealed or healed ulcers occurs in about 1 to 2% of the
adult population. 47, 48 Studies in Sweden and Australia found prevalence rates of 0.16%
and 0.06%, respectively. 49
– Prevalence of venous leg ulcers increases with age, 47, 48 with no difference between men
and women at any age. 49
• The significant cost associated with treatment of venous leg ulcers is attributed to
prolonged healing time.
– A US study found the average duration of follow-up care for venous ulcer patients was
119 days with an average of seven clinic visits. 50
– At home treatment accounted for nearly half of medical costs incurred in the US study;
the 18% of patients requiring hospitalization consumed 25% of all medical costs. 50
– In France and Belgium, the cost of venous ulcer treatments was about 2.5% of the
countries’ total health budgets in 1995. 46
• Patients report leg ulcers affect nearly every aspect of their daily lives, commonly
experiencing pain, interrupted sleep and reduced mobility. 51 Furthermore, patients’ social
activities are often restricted due to fear of injury and negative body image. 52

Burns
Burns are a devastating trauma requiring immediate, specialized care. Burn survival rates have
dramatically increased in the developed world. In the US, the burn-related death rate declined
by more than half in the last 40 years. 53 This improvement is a result of advances in the care
of severely burned patients, such as fluid resuscitation, nutritional support, wound care and
infection control. 54
• 500,000 people with burn injuries seek medical care annually in the US, and
40,000 require hospitalization. 55
– The proportion of hospital admissions for burn injury per 1000 people in the general
population varies greatly around the world: Finland = .042/1000; 56 Singapore = 0.07/
1000; 57 United States = 0.14/1000 (40,000 admissions for burn injuries annually); 55
India = 0.75/1000 (with 700,000 to 800,000 hospital admissions for burn
injuries annually). 58
– Men around the world are at risk for burn injuries in the workplace. Most burn injuries,
particularly among women and children, occur at home. 59 Scald burns account
for most burn injuries in children around the world, and for 33% of all burns in
57, 60, 61
the US.
• Expenses associated with hospitalized burn injuries in developed countries are enormous,
with per patient expenses for the initial, specialized care of a person with a major burn injury
estimated to be $200,000 in the US. 54
– In Israel, mean length of hospitalization was nearly 14 days; 15% of burn patients were in
an intensive care unit for a mean duration of 12.1 days. 61 In the US, length of hospital stay
averaged just over 8 days in 2005, down from 13 days in 1995. 62
• Severe burns inflict devastating physical and psychological injuries to victims; pain and
suffering continue long after the initial trauma. 63
15

16
Surgical incisions
WHO estimates that 230 million major operations are performed around the world each year,
one for every 25 people, or nearly twice as many surgeries as childbirths. 64 Current guidelines
emphasize patient nutrition before and after surgery as a means of promoting recovery and
helping prevent infections. 65
• Surgical site infections (SSIs) are a major source of illness in post-operative patients and a
significant source of increased costs. Though rates vary from procedure-to-procedure and
from physician-to-physician, on average these infections make up about one quarter of all
hospital-acquired infections in the US. 66
– In the US (1994), about 1.8% of surgeries resulted in a severe (non-superficial) SSI. 66 More
recently, a study conducted in the southeastern US (1994) found site infections occurred
in 1.4% of surgical procedures. 67
– In the UK, one study found 4.2% of surgical procedures resulted in a surgical site
infection, though about half of these were superficial incisional infections, which other
measures noted here exclude. 68
– A Canadian study identified 2.5 site infections per 100 surgical procedures; similar
measures in Thailand 69 and Indonesia 70 found 1.4 SSIs and 1.7 SSIs per 100 surgical
procedures, respectively.
• Surgical site infections have serious health consequences for patients and are very costly
to manage.
– In a US study of 255 matched patients, patients with SSIs were twice as likely to die, 60%
more likely to spend time in intensive care, and five times more likely to be readmitted to
the hospital. On average, patients with an infection stayed 6.5 days longer in the hospital
than patients without a surgical site infection. 71
– A study in the UK found a wide range of increased length of stay, depending on the type
of surgery. The extra post-operative days attributable to the infection ranged from 3 days
to 21 days depending on the type of surgery. 68
– Worldwide, at least 7 million disabling complications and 1 million deaths result from
surgical procedures; at least half of these could be avoided, both in the developed and
developing worlds, if certain basic standards of care are followed. 64

Wounds and healing
Normal wound healing
Wound healing is a complex interaction between epidermal and dermal cells, the extracellular
matrix, and plasma-derived proteins; all of these activities are coordinated by an array of
signaling molecules, including cytokines and growth factors. 72 The dynamic process of healing
normal wounds is characterized by three overlapping phases—inflammation, proliferation, and
remodeling. 72 Understanding the healing process is critical to successful management of
wound patients. 8
Inflammation. Wound healing begins with clotting, also called hemostasis. Platelets, endothelial
cells, and coagulation factors interact to stop bleeding and form a clot. Cells trapped within the
fibrin clot, mainly platelets, release vasodilators and chemoattractants, including tissue growth
factor-beta (TGF-β) and platelet-derived growth factor (PDGF). These signaling molecules trigger
an inflammatory response. 72
Neotrophil
Epidermis
Dermis
Fat
Fibroblast
Fibrin Clot
Platelet Plug
Macrophage
The inflammatory phase of wound healing. Figure with permission from the New England
Journal of Medicine. 73 As discussed in this monograph, successful wound healing requires
adequate supplies of energy, protein (including essential and conditionally-essential amino
acids), vitamins A, C, and E, and the mineral zinc.
Wound healing occurs
normally as predictable
and overlapping phases:
• Inflammation
• Proliferation
• Remodeling
17

18
In the early inflammatory phase, neutrophils are the most prominent cell type in the wound.
Neutrophils release enzymes and perform phagocytosis, thus beginning processes for
breakdown and removal of bacteria and debris. Circulating monocytes are attracted
to the wound site, ultimately maturing into macrophages responsible for finishing the
cleanup process.
Macrophages secrete proteases and clear dead cells, bacteria, and expended neutrophils
by phagocytosis. Macrophages also secrete substances that trigger production of cells that
are important in the subsequent proliferative phase. As the wound site is cleared of damaged
tissues and bacteria, the numbers of neutrophils and macrophages decline, thus ending the
inflammatory phase and beginning the proliferative phase.
Proliferation. The proliferation phase is characterized by buildup of connective tissue, starting
with granulation tissue. Granulation tissue is made up of macrophages, fibroblasts, immature
collagen, blood vessels, and ground substance. 4
Fibroblasts enter and proliferate in the wound site. Fibroblasts secrete collagen molecules,
which are assembled into fibers and cross-linked into bundles, thus affording tensile strength
and structure. This newly-formed matrix is host to angiogenesis, so that new vascular structures
can deliver nutrients as well as plasminogen activator and collagenase to the fibroblasts. Some
fibroblasts differentiate into myofibroblasts, which bind to and draw the wound edges closer
together, thereby reducing the size of the wound. 4 While new matrix is built, existing matrix
around the wound margins is degraded by enzymes, i.e. metalloproteinases and plasminogen
activators. 72 Activity of these enzymes is regulated, so excessive matrix degradation will
not occur. In the final step of the proliferation phase, some keratinocytes migrate from the
wound margins and divide until they form a contiguous epidermis, or surface layer of the
skin. Other keratinocytes phagocytose debris. Keratinocyte-mediated changes, coupled with
wound contraction, result in re-epithelialization and wound closure. 4, 72 A scar forms when
epithelialization is complete. Fibroblasts produce collagen molecules, which are assembled
into fibers that rebuild the matrix of tissue so that blood vessels can be restored (angiogenesis).
Keratinocytes help close the wound and remove dead cells and other debris.

Epidermis
Dermis
Fat
Granulation Tissue
Collagen
Fibrin Clot
Blood Vessel
Keratinocytes
The proliferative phase of wound healing. Figure with permission from the New England
Journal of Medicine. 73 Anabolic processes of the proliferative phase involve structural proteins
(mainly collagen) as well as functional proteins (regulatory enzymes). Protein synthesis,
supported by ample supplies of constituent amino acids, is therefore critical to supporting this
phase of wound healing.
19

20
Remodeling. Once the wound has closed, remodeling of the wound commences, a phase
that can continue for months or years. 72 Early, randomly-placed collagen is remodeled into a
better-organized structure, providing greater tensile strength. Over time, cell content and
blood flow in the scar tissue decreases.
Conditions that impair wound healing
Hard-to-heal wounds lack anatomic and functional integrity, so they heal slowly or do not heal
at all. These wounds remain in the inflammatory or proliferative phase, allowing the excessive
accumulation of extracellular matrix components, which in turn may lead to the premature
degradation of collagen and growth factors. 74 Various factors, both local and systemic, are
known to impede wound healing; wound infection and nutritional deficiencies are common
contributors (Table 1). 1, 2 Less common factors include local or distant cancers, use of certain
anti-cancer drugs, and genetic healing abnormalities. 1
1, 2
Table 1. Factors commonly involved in hard-to-heal wounds.
loCAl FACtoRS SYStEmIC FACtoRS
• Wound Infection
• Ischemia
• Venous insufficiency
• Mechanical trauma
(i.e., pressure sores)
• Tissue maceration
• Presence of a foreign body
• Nutritional deficiencies (i.e., deficiencies of proteins,
vitamins, minerals)
• Chronic diseases (i.e., diabetes mellitus, renal disease)
• Advanced age and general immobility
• Smoking

Care of hard-to-heal wounds
The wound care team
Taking a team approach is essential to treating hard-to-heal wounds—with effective interactions
between the patient, his or her family members, and the health caregivers. 75 Successful wound
management particularly requires communication among members of the wound care team,
including nurses, physicians, and other health professionals in:
• Specialty areas
– Wound care specialists
– Dermatology
– Surgery
• Nutrition
– Dietitians
– Medical nutrition specialists, including Certified Diabetes Educators
• Primary care
– Geriatrics
– Family medicine
– Social worker
The patient and his or her personal/professional support team members will be involved in
cleaning and dressing the wound as it heals, as well as in maintaining a nutritional status that
can facilitate wound healing.
21

22
Cleaning and dressing a wound
Normal wound healing requires proper vascular circulation, infection prevention, and
avoidance of negative mechanical forces; these principles are the basis for cleaning and
dressing a wound. 75
Debridement. Debridement is the process of removing dead, damaged, or infected tissues
to improve the potential for healing the remaining healthy tissue in a wound site. A variety of
techniques accomplish debridement—sharps (scalpel, forceps, scissors), enzymes (collagenase
or papain-containing ointments), or autolysis (self-digestion in the context of a wound dressing
that afford moisture at the wound site). 75
Moisture control. Moisture is essential for proper healing. Acute wounds with occlusive
or semi-occlusive dressings that retain moisture have been shown to heal twice as fast as
wounds exposed to air. Since highly exudative wounds may cause excessive wetness and
tissue maceration, the ideal dressing is one that absorbs exudates without excessive drying. 75
Wound dressings. Many wound dressings are available around the world, so it is challenging to
select the dressing best suited for each wound. The ideal dressing is one that removes excess
exudates, maintains a moist healing environment, protects against contamination, is easily
removable when appropriate, leaves no debris in the wound, provides thermal insulation, and
does not induce allergic reactions. 75 Wound dressings include barrier creams to protect skin
around the wound, semi-occlusive films, hydrogels to moisturize the wound site, hydrocolloids
or alginates to absorb excessive exudates fluids, and collagen-containing products to provide a
matrix for deposition of new tissue. 75
Prevention and treatment of infections. Topical antimicrobial agents help prevent excessive
colonization of the wound site by bacteria, while systemic antibiotics are usually reserved for
clinically infected wound sites. 75

Nutritional care: rationale to implementation
• Rationale. Nutrition is a key component of the health care team’s approach to wound
treatment. 22, 76 Hard-to-heal wounds will heal faster and with fewer complications when
the host is well nourished.
• Action plan. Nutrition-based prevention and treatment of wounds uses a multi-step
strategy: 1) assess nutritional status, 2) estimate nutritional needs, and 3) implement
appropriate and comprehensive nutritional interventions. 77-79
• Basic nutrition. Adequate basic nutrition for healing wounds includes caloric energy,
protein, fluid supplies, and certain vitamins and minerals. 8, 22, 76, 80 Caloric energy from
carbohydrates and fats is essential needed to meet basic energy needs, thus sparing
breakdown of proteins for energy. Dietary protein supplies, including essential
and conditionally-amino acids, are needed for synthesis of proteins that are involved in
wound healing and immune function. Fluid intake is critical to compensate for loss from
wound injury and wound exudates. Despite efforts to maintain normal nutritional status
through basic nutrition strategies, wound healing may be suboptimal because of specific
nutritional deficiencies.
• Targeted nutrition. For wound healing, “targeted nutrition” products may be necessary to
meet conditionally-essential needs. Under normal conditions, such nutrients are derived
from regular foods or oral nutrition supplements. However, to meet the high demands of
wound healing, additional sources are often needed. If these special needs are unmet,
wounds will fail to heal.
– There is evidence for the use of Abound ® (HMB + arginine + glutamine) to support wound
healing, increase protein synthesis and lessen protein breakdown, and immune function
[see section below on Abound ® Clinical Trial Results].
Nutrition is a key
component of the health
care team’s approach to
wound treatment.
Nutrition for healing of
wounds includes:
• Caloric energy
• Protein (including
ample supplies of
conditionally-essential
amino acids such as
arginine and glutamine)
• Fluid supplies
• Certain vitamins and
minerals, such as
vitamins A, C, and E,
and zinc
Abound ® is a “targeted
nutrition” product
formulated to meet
condition-essential needs
that are associated with
wound healing.
23

24
Overall nutrition for wound healing
If adequate dietary nutrition is not consumed, malnutrition can lead to impaired wound healing
and immune function. 22, 76 Immune compromise correlates clinically with increased wound
complication and infection rates.
Malnutrition may pre-date wounding or may be secondary to the catabolism resulting from
the wound itself. Wounding increases metabolic rates, catecholamine levels, loss of total body
22, 76
water, and turnover of protein in cells, thus resulting in an overall catabolic state.
Specific nutritional guidelines by wound type
Pressure ulcers. The US Agency for Healthcare Research and Quality provides specific
nutritional guidelines for a person who has a pressure ulcer and is malnourished: 29
• 30 to 35 cal/kg body weight per day
• 1.25 g – 1.5g of protein/kg of body weight per day
• Water intake from beverages + foods = 2.7 L/day (adult female)
and 3.7 L/day (adult male)
The European Pressure Ulcer Advisory Panel provides similar, specific nutritional guidelines. 79
Guidelines begin by recommending that patients at risk should be screened and assessed for
possible malnutrition, and offered nutritional support, as needed. The presence of established
pressure ulcers may demand greater supplementation (normal feeding, then oral supplements
and finally tube-feeding). The amount of supplementation required by each individual varies, but
guidelines suggest:
• a minimum of 30–35 kcal per kg body weight per day
• 1.25 to 1.5 g/kg/day protein, and
• 1ml of fluid intake per kcal per day.

Adequate nutrition and fluid intake have long been recognized as important to maintaining
tissue integrity and promoting healing of pressure ulcers, while weight loss, low weight status,
low albumin levels, and low body mass index are associated with pressure ulcer development
and poor healing. 81-84 Results of a meta analysis of outcomes for elderly hospitalized patients
showed that enteral nutritional support, particularly high-protein oral nutrition supplement, can
significantly reduce the risk of developing pressure ulcers by 25%; there was a trend toward
improved healing of pre-existing pressure ulcers. 85
Diabetic foot ulcers. There is considerable evidence to support the practice of maintaining
glycemic status as close to normal as possible in order to prevent and delay complications
of diabetes. 86 Optimal glycemic control is thus recognized as a key strategy for preventing
development of diabetic foot ulcers. 34 The American Diabetes Association recommends: 87
• monitoring nutritional status indicators (e.g. change in body weight) and
glycemia to ensure that needs are met and hyperglycemia is prevented
• protein needs of 1.25-1.5 g/kg body weight, with the higher end for more
stressed patients; protein intake will not decrease catabolism, but it will
enhance protein synthesis
Nutritional recommendations for people with diabetes are targeted to prevention of microvascular
and neuropathic complications by maintaining blood glucose as close to normal as possible
with a goal of maintaining hemoglobin A1c below 7%. 86 Singh and colleagues summarized
compelling evidence to support the importance of glycemic control as a means of preventing
development of foot ulcers. 34
25

26
Burns. Patients with burns have the highest metabolic rate of all critically ill or injured patients,
and survival among these patients has been shown to be inversely correlated with loss of lean
mass. 88 A guideline for burned patients aged 16-60 yrs is 25kcal/kg/day plus an additional
40kcal/%burn/day. 88
Burn injuries can lead to extensive nitrogen loss, increased metabolic rates, malnutrition, and
immunologic deficiencies. These changes predispose burn patients to frequent infections,
poor wound healing, increased length of hospitalization, and increased mortality. 89 Early and
adequate nutritional support is vital to restoring protein synthesis and normal immune function. 54
A number of studies have shown beneficial effects of increased dietary components such as
glutamine, arginine, and (n-3) fatty acids and related compounds in burn victims. 89 Providing
adequate nutrition to burn patients promotes wound healing while reducing the loss of lean
body mass. 88
Macronutrient recommendations
Calories. Although caloric needs vary for each person based on activity level and health
conditions, guidelines consistently recommend intake of 30-35 cal/kg body weight per day. 26,79
Lower intake may be appropriate for certain people with diabetes in order to maintain glycemia
within the normal range. 87 Higher intake may be needed for people with severe wounds,
e.g. burns can increase energy requirements as much as 100%. 90
Protein. Although normal adults need just 0.8 g protein/kg body weight, people with wounds,
e.g. pressure ulcers, need more protein to support healing—in the range of 1.25 to 1.5 g
protein/kg of body weight. 80
Fluid. Fluid is essential to normal functioning of cells. Wound drainage can be a major source
of fluid loss and can lead to dehydration and electrolyte imbalance. Dehydration is a risk factor
for pressure ulcer development because it can reduce blood volume, thereby interfering with
peripheral circulation and decreasing nutrient and oxygen supply to tissues. 91, 92 The average
adult needs between 2000 to 3000 mL of fluid per day to replace losses from urine, stool,
exhalation, and the skin. 80

Roles of specific nutrients
Vitamins and minerals. Vitamins A, C, and E, and the mineral zinc have recognized roles in
healing wounds. 22, 76, 80 Nutritional deficiencies allow development of pressure ulcers and impair
healing of wounds. Vitamin A seems to enhance the inflammatory response and contribute to
wound healing by increasing monocyte influx and macrophage activation and by stimulating the
synthesis of collagen and wound closure. 76, 80 Vitamin C facilitates wound healing by enhancing
collagen synthesis and increasing angiogenesis; vitamin C also supports immune function to
help prevent infection and promote recovery. 76 Vitamin E is thought to maintain and stabilize
cellular membrane integrity by its anti-oxidant capacity. 22
Zinc is a cofactor for both DNA and RNA polymerases and is therefore a key micronutrient to
support DNA synthesis, protein synthesis, and cellular proliferation. 76
nUtRIEnt PRoVIDES SUPPoRt FoR
Energy Increased requirements due to inflammation and
metabolic stress
Protein Collagen synthesis, wound contraction, scar formation,
immune response
Zinc Protein synthesis, cellular growth
Note: deficiency impairs healing
Vitamin A Collagen synthesis, immune response, wound closure
Vitamin C Collagen synthesis, immune response, wound strength,
angiogenesis
Vitamin E Wound strength, antioxidant
Vitamins A, C, and E,
and the mineral zinc
have recognized roles in
healing wounds.
27

28
Use of Abound ®
wound care
as part of optimal
Abound ® is a therapeutic nutrition product intended for people who have non-healing wounds.
Abound ® is intended for use in concert with a complete and balanced diet (oral food intake,
oral nutrition supplements, enteral tube feedings, or some combination) along with optimal
management of the wound (debridement, moisture control, wound dressings, and
infection control).
Abound ® and its ingredients
Abound ® is a therapeutic nutrition product that combines 3 key active ingredients—arginine,
glutamine, and HMB—with other ingredients affording flavor and stability of the blend.
• Abound ® supports wound healing. 22
• Abound ® supports immune function to help prevent or recover from
complicating infections. 93
• The ingredients of Abound—arginine, glutamine, and HMB—play multiple roles:
1) slow protein breakdown, 2) facilitate synthesis of collagen and other proteins
involved in wound healing, and 3) promote function of numerous cells involved
in immune responses.
Arginine. Arginine is a conditionally-essential amino acid; it is made by the body in sufficient
quantities under usual conditions, but a dietary source becomes necessary during periods
of healing. 94 Recognized to play a wide range of roles in wound-healing processes, arginine:
(1) induces secretion of the anabolic hormones insulin and growth hormone, (2) stimulates
T-lymphocyte responses for wound healing (3) serves as a metabolic precursor for nitric oxide,
which in turn mediates bacterial killing by macrophages, and (4) is catabolized to ornithine and
22, 23, 76
converted to proline, which is used for collagen synthesis.
Optimal wound
management
• Abound ® therapeutic
nutrition
• Diet designed for wound
healing: food or oral
nutrition supplement
or tube-fed meal
replacement
• Wound dressing
and care
Arginine is a conditionallyessential
amino acid; it
is made by the body in
sufficient quantities under
usual conditions, but a
dietary source becomes
necessary during periods
of healing.

The metabolism of arginine is central to processes involved in wound healing. 23
Growth factors
Stimulates release of insulin
and other growth factors
Arginine
from dietary sources
and synthesized in
kidneys from citrulline
NO
Arginine is converted
to nitric oxide, which in
turn mediates bacterial
killing by macrophages
Ornithine
Precursor to polyamines and other
wound-healing molecules; also
converted to amino acids glutamines
and proline for collagen synthesis
Citrulline
synthesized in intestines
from dietry glutamine,
glutamate, and proline
Glutamine. Glutamine is the most abundant amino acid in the body, and it has numerous
metabolic roles. Glutamine is conditionally-essential during times rapid tissue growth, especially
during wound healing. 22, 76, 80 Glutamine is a nitrogen donor for synthesis of amino acids and
amino sugars, and it is a precursor for synthesis of nucleotides in cells such as fibroblasts and
macrophages, thereby supporting cell proliferation and function. Glutamine serves as a source
of metabolic energy for lymphocytes and macrophages (immune cells), and it is also converted
in the liver to glucose, which ultimately serves as an energy source for wound healing in the
periphery. 22 In addition, glutamine is a metabolic fuel for cells of the intestinal mucosa, thereby
13, 95
playing an important role to maintain gut integrity and function, including gut immune function.
Glutamine is a
conditionally-essential
amino acid during times
rapid tissue growth,
especially during
wound healing.
29

30
In conditions such as trauma, infection, wound healing, and burns, the inflammatory processes
involved in recovery increase needs for energy and for specific nutrients, particularly the
conditionally-essential amino acid glutamine. If adequate glutamine is not available, muscle
proteins will be broken down to meet the body’s energy needs. Supplemental glutamine has
been shown to:
• Help maintain muscle protein during stress
• Support and regulate synthesis of proteins, including collagen,
as needed for wound healing
• Helps maintain function of gut cells, including gut-associated
lymphoid tissues (immune cells)
HMB, a leucine metabolite. Leucine is a member of the branched-chain amino acid family,
along with valine and isoleucine. The branched-chain amino acids play a role in maintaining
nitrogen balance in adults, especially in conditions such as sepsis, trauma, and burns; they
support protein synthesis after injury and decrease muscle proteolysis. 22 Beta-hydroxy-betamethylbutyrate
(HMB) occurs naturally in the body as a leucine metabolite; HMB has been
15-17, 96, 97
shown to inhibit muscle proteolysis and modulate protein turnover.
Muscle converts approximately 5% of available leucine to HMB. 16 A 70 kg person would thus
produce 0.2 to 0.4 g of HMB each day, a quantity that is insufficient to support metabolic needs
during times of rapid growth and healing. 16
A 70 kg person produces
0.2 to 0.4 g of HMB each
day, a quantity that is
insufficient to support
metabolic needs during
times of rapid growth
and healing

Abound ® Label Information
SERVIng SIZE 1 PACkEt oRAngE FlAVoR (24 g)
SERVIngS PER ContAInER 1
Energy
79.0kcal = carbohydrates 23kcal, amino acids 56kcal
• HMB 1.2g, provided as 1.5g of calcium HMB
• Amino acids
- L-arginine 7 g
- L-glutamine 7 g
• Carbohydrate
- Sugars 2 g
• Minerals per serving
- Calcium 200 mg
Ingredients of Abound ®
ACtIVE IngREDIEntS otHER IngREDIEntS
• L-arginine
• L-glutamine
• Calcium beta-hydroxy-beta-methylbutyrate
(HMB)
• Citric acid
• Orange juice powder
• Sugar (sucrose)
• Natural flavors
• Aspartame
• Medium-chain triglycerides (MCT oil)
• Acesulfame potassium
• FD&C Yellow #6
31

32
A Case Study From the US–an elderly woman with pressure ulcers
Mrs. B is an 84 year-old woman with diabetes and Alzheimer’s disease; she resided in a facility for skilled nursing
care. During the summer, she developed multiple pressure ulcers, including a severe Stage IV wound, on her right
gluteal fold.
Due to the severity of her condition, Mrs. B was limited to bed, and a Foley catheter was placed. Mrs. B’s initial
treatment course involved routine wound care, a specialty mattress, protein powder supplement, and vitamin C, zinc,
and multi-vitamins. She received oral food but only finished 50 to 75% of the meals, so she was also given
high-calorie liquid medical nutrition supplements.
Mrs. B’s routine was maintained for 6 months. During that time, she made several trips to a wound care center
for debridement and medication adjustments. Despite these efforts, the Stage IV wound did not heal, and Mrs. B
experienced an overall decline in her health status.
In January, Mrs. B was transferred to hospice care with comfort measures only. After another 7 months, her health
status was sufficiently stable for her return to the skilled nursing care facility. In October, 14 months after her pressure
ulcer was first documented, twice-daily treatments with Abound ® medical nutrition was initiated. She was continued
on the specialty mattress, protein powder supplement, and vitamin C, zinc, and multi-vitamins. Her Foley catheter
remained in place.
Just 10 weeks after Abound ® was added to Mrs. B’s treatment regimen, her Stage IV wound was completely closed.
The catheter was removed, and the specialty mattress was no longer needed. Mrs. B was able to get out of bed
and walk.
Clinical trial results
The safety and efficacy of Abound ® , a proprietary blend of HMB, arginine, and glutamine, have
been tested in seven clinical trials, including tests in healthy adult volunteers, 7 critically injured
trauma patients, 18 men in resistance-training, 98 cancer patients, 99-101 and people with HIV/AIDS. 93
These studies provided evidence for safety of Abound ® , 100 as well as support for efficacy in
93, 99-101
attenuating loss of lean tissue and increasing body mass.
Abound ® and wound healing
The principal evidence for enhancement of processes involved in wound healing comes
from studies by Williams and colleagues. 7 In addition, a study by Clark et al. provides
evidence that Abound ® helps enhance immune function, 93 an important way to lower risk
for wound complications.

Abound ® testing in healthy elderly volunteers. Collagen deposition, a means of enhancing
wound strength and integrity, was tested in a study of 35 healthy volunteers aged 70 years
or older; subjects were randomized to receive twice-daily treatment with the HMB/glutamine/
arginine mixture (Abound ® ) or an isonitrogenous, isocaloric supplement of nonessential amino
acids. 7 Prior to amino acid treatment, sterile catheter tubes were implanted into deltoid muscles
of subjects to evaluate ingrowth of fibroblasts and deposition of collagen matrix (measured as
hydroxyproline content). Results showed a significant 67% increase in hydroxyproline content
after 14 days of treatment with Abound ® compared to control. The authors concluded that oral
administration of Abound ® mixture significantly enhanced collagen synthesis in healthy elderly
adults, thus providing a safe nutritional means for supporting wound repair in patients. 7
Williams et al. study of Abound ® and collagen synthesis 7
Hydroxy-Proline (nmol/cm)
80
60
40
20
0
Hydroxy-proline content 14 days
after catheter insertion
43.2
Placebo
72.2
Abound
67%
Increase
p

34
Abound ®
in clinical practice
Abound ® is a brand-new approach for patients with hard-to-heal wounds. Abound ® fills
an important gap in wound care practice.
People who can benefit from Abound ®
Individuals who may benefit from Abound ® include those with hard-to-heal wounds:
• Pressure ulcers
• Venous leg ulcers
• Diabetic foot ulcers
• Burn injury
• Complicated surgical incisions
How to incorporate Abound ® into the
therapeutic regimen
Patients with hard-to-heal wounds can benefit from Abound ® in combination with an overall
nutrition plan that be combined effectively with regular food or with other Abbott nutritional
products to meet nutritional guidelines for wound healing. 26, 79, 80 For individuals who can
consume oral foods, Abound ® can be given in combination with regular food or with regular
food as well as a medical nutrition supplement such as Ensure (for malnourished individuals) or
Glucerna ® (for malnourished people with diabetes). For those who cannot consume oral food,
Abound ® can be combined with a complete and balanced tube-fed nutritional supplement such
as a product in the Jevity ® family.
ORANGE
NATURAL FLAVOR WITH
OTHER NATURAL FLAVORS
POWDER • ADD WATER
30 PACKETS • each packet 0.85 oz (24 g) • NET WT 0.74 lb (720 g)
* See back panel
Slows Protein Breakdown Enhances Tissue Growth

Able to consume oral foods?
Regular food
+
Abound
Normal nutrition status
BMI 18-21
No weight loss
Yes No
Patients with hard-to-heal wounds
Jevity to meet
kcal and
protein needs
+
Abound
Guidelines: 30-40 kcal/kg; 1.25-1.5 g protein/kg
Malnourished nutrition status
BMI < 18
Weight loss > 5% over 2 months
Able to consume oral foods?
Yes No
Combination
feeding
Regular food
+
Ensure or Glucerna
+
Abound
Jevity to meet
kcal and
protein needs
+
Abound
35

36
Forms and Flavors
Because free glutamine has limited stability in liquid, Abound ® is a powder that must be mixed
with liquid. It is available in convenient single-serving packets of orange-flavored and neutral
powders. Abound ® neutral is for patients who prefer to mix it with their choice of juice, smoothie,
or food.
Directions for use
Each packet of Abound ® is dissolved with liquid to make one serving; the recommended dose
is 2 servings (packets) a day. The 2 daily servings of product are best consumed with a morning
meal and an evening meal. Each serving of Abound ® provides 7 g of arginine, 7 g of glutamine,
and 1.2 g of HMB (from 1.5 g CaHMB).
Preparation for oral consumption
1. Mix one packet of Abound ® with 237 mL to 296 mL of cold water (use juice/other
liquid for neutral product), and stir with a spoon until all powder is dissolved.
2. Note: Do not mix Abound ® with hot or boiling water/juice.
3. Only use Abound ® under medical supervision.
Administering as Tube Feeding
1. Abound ® should not be mixed with formula in a tube-feeding bag.
2. For mixing, place one packet of Abound ® in a small, clean container
(about 177 mL to 237 mL volume).
3. Add 120 mL of water at room temperature.
4. Mix well with a spoon until all particles are dissolved.
5. Verify correct tube placement.
6. Flush feeding tube with 30 mL of water.
7. Administer Abound ® through feeding tube using a 60 cc or larger syringe.
8. Flush with an additional 30 mL of water. A smaller amount of water can
be used to flush the tube if the patient is on fluid-restriction.
9. Only use Abound ® under medical supervision.

Conclusions
1
2
3
Abound ® is a therapeutic nutrition product with a unique blend of key
ingredients—amino acids arginine and glutamine, and beta-hydroxy-betamethylbutyrate
(HMB; a metabolite of the amino acid leucine). Combined, these
Abound ® components help maintain body proteins, which are vital for resolving
hard-to-heal wounds. Glutamine and arginine also serve as metabolic fuels for
immune cells, thereby enhancing immune function to prevent or fight infections
that may otherwise complicate wound healing.
Individuals who may benefit from Abound ® include those with:
• Pressure ulcers
• Venous leg ulcers
• Diabetic foot ulcers
• Burn injury
• Non-healing surgical incisions
Abound ® is part of total care for wound healing. Abound is used along with a diet
designed for wound healing and appropriate wound care. Overall nutrition can be
provided as a food diet, food in combination with an oral nutritional supplement,
or complete and balanced tube-fed nutrition. Proper wound care includes wound
debridement, moisture maintenance by appropriate dressings, and prevention and
treatment of infection.
37

38
References
1. Medina A, Scott PG, Ghahary A, Tredget EE. Pathophysiology of chronic nonhealing
wounds. J Burn Care Rehabil. 2005;26:306-319.
2. Grey J, Enoch S, Harding K. Wound assessment. BMJ. 2006;332:285-288.
3. Action.org.uk. From chronic wounds to tooth loss - when skin cells behave badly. http://
www.action.org.uk/research_projects/grant/273/. Accessed May 5, 2008.
4. Hess K, Kirsner R. Orchestrating wound healing: assessing and preparing the wound
bed. Adv Skin Wound Care. 2003;16:246-259.
5. Horn SD, Bender SA, Ferguson ML, et al. The National Pressure Ulcer Long-Term Care
Study: pressure ulcer development in long-term care residents. J Am Geriatr Soc.
2004;52:359-367.
6. Woodbury MG, Houghton PE. Prevalence of pressure ulcers in Canadian healthcare
settings. Ostomy Wound Manage. 2004;50:22-24, 26, 28, 30, 32, 34, 36-28.
7. Williams JZ, Abumrad N, Barbul A. Effect of a specialized amino acid mixture on human
collagen deposition. Ann Surg. 2002;236:369-374; discussion 374-365.
8. Campos A, Groth A, Branco A. Assessment and nutritional aspects of wound healing.
Curr Opin Clin Nutr Medab Care. 2008;11:281-288.
9. Karna E, Miltyk W, Wolcynski S, Patka J. The potential mechanism of glutamine-induced
collagen biosynthesis in cultured human fibroblasts. Cmmp Biochem Physiol B Biochem
Mol Biol. 2001;130:23-32.
10. Peng X, Yan H, You Z, Wang P, Wang S. Clinical and protein metabolic efficacy of
glutamine granules-supplemented enteral nutrition in severely burned patients. Burns.
2005;31:342-346.
11. Barbul A, Lazarou SA, Efron DT, Wasserkrug HL, Efron G. Arginine enhances wound
healing and lymphocyte immune responses in humans. Surgery. 1990;108:331-336;
discussion 336-337.
12. Curran JN, Winter DC, Bouchier-Hayes D. Biological fate and clinical implications of
arginine metabolism in tissue healing. Wound Repair Regen. 2006;14:376-386.
13. Wilmore DW. The effect of glutamine supplementation in patients following elective
surgery and accidental injury. J Nutr. 2001;131:2543S-2549S; discussion 2550S-2541S.
14. Kirk SJ, Hurson M, Regan MC, Holt DR, Wasserkrug HL, Barbul A. Arginine stimulates
wound healing and immune function in elderly human beings. Surgery. 1993;114:155-159;
discussion 160.

15. Alon T, Bagchi D, Preuss HG. Supplementing with beta-hydroxy-beta-methylbutyrate
(HMB) to build and maintain muscle mass: a review. Res Commun Mol Pathol Pharmacol.
2002;111:139-151.
16. Nissen S, Sharp R, Ray M, et al. Effect of leucine metabolite beta-hydroxy-betamethylbutyrate
on muscle metabolism during resistance-exercise training. J Appl Physiol.
1996;81:2095-2104.
17. Gallagher P, Carrithers J, Godard M, Schulze K, Trappe S. β−hydroxy−β−methylbutyrate
ingestion, Part I: effects on strength and fat free mass. Med Sci Sport Exerc.
2000;32:2109-2115.
18. Kuhls DA, Rathmacher JA, Musngi MD, et al. Beta-hydroxy-beta-methylbutyrate
supplementation in critically ill trauma patients. J Trauma. 2007;62:125-131; discussion
131-122.
19. Hsieh L, Chien S, Huang M, RTseng H, CHang C. Anti-inflammatory and anticatabolic
effects of shot-term beta-hydroxy-beta-methylbutyrate supplementation on chronic
obstructive pumlonary disease patients in intensive care unit. Asia Pac J Clin Nurs.
2006;15:544-550.
20. Shi HP, Wang SM, Zhang GX, Zhang YJ, Barbul A. Supplemental L-arginine enhances
wound healing following trauma/hemorrhagic shock. Wound Repair Regen. 2007;15:
66-70.
21. Wilmore D. Enteral and parenteral arginine supplementation to improve medical outcomes
in hospitalized patients. J Nutr. 2004;134:263S-2867S.
22. Williams JZ, Barbul A. Nutrition and wound healing. Surg Clin North Am. 2003;83:
571-596.
23. Stechmiller J, Childress B, Cowan L. Arginine supplementation and wound healing.
Nutr Clin Pract. 2005;20:52-61.
24. Posnett J, Franks PJ. The burden of chronic wounds in the UK. Nurs Times. 2008;
104:44-45.
25. WHO. National health accounts. http://www.who.int/nha/en/. Accessed May 5, 2008.
39

40
26. Bergstrom N, Allman R, Carlson C, Eaglestein W. Clinical practice guideline No. 3:
pressure ulcers in adults, prediction and prevention: Public Health Service US
DHHS; 1992.
27. Lyder CH. Pressure ulcer prevention and management. J Amer Med Assoc.
2003;289:223-226.
28. Vanderwee K, Clark M, Dealey C, Gunningberg L, Defloor T. Pressure ulcer prevalence in
Europe: a pilot study. J Eval Clin Pract. 2007;13:227-235.
29. Bergstrom N, Allman R, Alvarez O, et al. Clinical guideline No. 15: treatment of pressure
ulcers US Department of Health and Human Services. Public Health Service, Agency for
Health Care Policy and Research 1994.
30. Bennett G, Dealey C, Posnett J. The cost of pressure ulcers in the UK. Age Ageing.
2004;33:230-235.
31. Severens JL, Habraken JM, Duivenvoorden S, Frederiks CM. The cost of illness of
pressure ulcers in The Netherlands. Adv Skin Wound Care. 2002;15:72-77.
32. Duncan K. Preventing pressure ulcers: the goal is zero. Joint Commission J Qual Pat
Safety. 2007;33.
33. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for
the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047-1053.
34. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes.
J Amer Med Assoc. 2005;293:217-228.
35. Samann A, Tajiyeva O, Muller N, et al. Prevalence of the diabetic foot syndrome at the
primary care level in Germany: a cross-sectional study. Diabet Med. 2008.
36. CDC. History of Foot Ulcer Among Persons with Diabetes --- United States, 2000--2002.
MMWR. 2003;52:1098-1102. http://www.cdc.gov/MMWR/preview/mmwrhtml/mm5245a3.
htm#tab1. Accessed April 18, 2008.
37. Vileikyte L. Diabetic foot ulcers: a quality of life issue. Diabetes Metab Res Rev.
2001;17:246-249.
38. Ismail K, Winkley K, Stahl D, Chalder T, Edmonds M. A cohort study of people with
diabetes and their first foot ulcer: the role of depression on mortality. Diabetes Care.
2007;30:1473-1479.
39. Prompers L, Schaper N, Apelqvist J, et al. Prediction of outcome in individuals with
diabetic foot ulcers: focus on the differences between individuals with and without
peripheral arterial disease. The EURODIALE Study. Diabetologia. 2008;51:747-755.

40. Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic
foot disease. Lancet. 2005;366:1719-1724.
41. Lavery LA, Armstrong DG, Wunderlich RP, Tredwell J, Boulton AJ. Diabetic foot
syndrome: evaluating the prevalence and incidence of foot pathology in Mexican
Americans and non-Hispanic whites from a diabetes disease management cohort.
Diabetes Care. 2003;26:1435-1438.
42. Moulik PK, Mtonga R, Gill GV. Amputation and mortality in new-onset diabetic foot ulcers
stratified by etiology. Diabetes Care. 2003;26:491-494.
43. Ragnarson Tennvall G, Apelqvist J. Health-economic consequences of diabetic foot
lesions. Clin Infect Dis. 2004;39 Suppl 2:S132-139.
44. Gordois A, Scuffham P, Shearer A, Oglesby A, Tobian JA. The health care costs of
diabetic peripheral neuropathy in the US. Diabetes Care. 2003;26:1790-1795.
45. Goodridge D, Trepman E, Embil JM. Health-related quality of life in diabetic patients with
foot ulcers: literature review. J Wound Ostomy Continence Nurs. 2005;32:368-377.
46. Abbade LP, Lastoria S. Venous ulcer: epidemiology, physiopathology, diagnosis
and treatment. Int J Dermatol. 2005;44:449-456.
47. Fowkes FG, Evans CJ, Lee AJ. Prevalence and risk factors of chronic venous
insufficiency. Angiology. 2001;52 Suppl 1:S5-15.
48. Graham ID, Harrison MB, Nelson EA, Lorimer K, Fisher A. Prevalence of
lower-limb ulceration: a systematic review of prevalence studies. Adv Skin Wound Care.
2003;16:305-316.
49. Bello YM, Phillips TJ. Management of venous ulcers. J Cutan Med Surg. 1998;3 Suppl
1:S1-6-12.
50. Olin JW, Beusterien KM, Childs MB, Seavey C, McHugh L, Griffiths RI. Medical costs
of treating venous stasis ulcers: evidence from a retrospective cohort study. Vasc Med.
1999;4:1-7.
41

42
51. Phillips T, Stanton B, Provan A, Lew R. A study of the impact of leg ulcers on quality of
life: financial, social, and psychologic implications. J Am Acad Dermatol. 1994;31:49-53.
52. Jull A, Walker N, Hackett M, et al. Leg ulceration and perceived health: a population
based case-control study. Age Ageing. 2004;33:236-241.
53. ABA, American Burn Association. Burn incidence and treatment in the US: 2000
fact sheet. 2000.
54. Church D, Elsayed S, Reid O, Winston B, Lindsay R. Burn wound infections.
Clin Microbiol Rev. 2006;19:403-434.
55. ABA, American Burn Association. Burn incidence and treatment in the US: 2007 fact
sheet. http://www.ameriburn.org/resources_factsheet.php?PHPSESSID=a116a8aa0e9d7
e5f747608cb8f2e1b5a.
56. Papp A, Rytkonen T, Koljonen V, Vuola J. Paediatric ICU burns in Finland
1994-2004. Burns. 2008;34:339-344.
57. Song C, Chua A. Epidemiology of burn injuries in Singapore from 1997 to 2003. Burns.
2005;31 Suppl 1:S18-26.
58. Ahuja RB, Bhattacharya S. ABC of burns. Burns in the developing world and burn
disasters. Bmj. 2004;329:447-449.
59. WHO. Facts about injuries: Burns 2007.
60. Tung KY, Chen ML, Wang HJ, et al. A seven-year epidemiology study of 12,381 admitted
burn patients in Taiwan—using the Internet registration system of the Childhood Burn
Foundation. Burns. 2005;31 Suppl 1:S12-17.
61. Haik J, Liran A, Tessone A, Givon A, Orenstein A, Peleg K. Burns in Israel: demographic,
etiologic and clinical trends, 1997-2003. Isr Med Assoc J. 2007;9:659-662.
62. Miller SF, Bessey PQ, Schurr MJ, et al. National Burn Repository 2005: a ten-year review.
J Burn Care Res. 2006;27:411-436.
63. Hettiaratchy S, Dziewulski P. ABC of burns. Introduction. Brit J Med. 2004;328:1366-
1368.
64. WHO. Safe Surgery Saves Lives 2007.
65. Weimann A, Braga M, Harsanyi L, et al. ESPEN Guidelines on Enteral Nutrition: surgery
including organ transplantation. Clin Nutr. 2006;25:224-244.
66. Nichols RL. Preventing surgical site infections. Clin Med Res. 2004;2:115-118.

67. Anderson DJ, Sexton DJ, Kanafani ZA, Auten G, Kaye KS. Severe surgical site infection
in community hospitals: epidemiology, key procedures, and the changing prevalence of
methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol. 2007;28:
1047-1053.prevalence of methicillin-resistant Staphylococcus aureus. Infect Control
Hosp Epidemiol. 2007;28:1047-1053.
68. Coello R, Charlett A, Wilson J, Ward V, Pearson A, Borriello P. Adverse impact of surgical
site infections in English hospitals. J Hosp Infect. 2005;60:93-103.
69. Kasatpibal N, Jamulitrat S, Chongsuvivatwong V. Standardized incidence rates of surgical
site infection: a multicenter study in Thailand. Am J Infect Control. 2005;33:587-594.
70. Duerink DO, Roeshadi D, Wahjono H, et al. Surveillance of healthcare-associated
infections in Indonesian hospitals. J Hosp Infect. 2006;62:219-229.
71. Kirkland KB, Briggs JP, Trivette SL, Wilkinson WE, Sexton DJ. The impact of surgical-site
infections in the 1990s: attributable mortality, excess length of hospitalization, and extra
costs. Infect Control Hosp Epidemiol. 1999;20:725-730.
72. Harding K, Morris H, Patel G. Healing chronic wounds. Brit Med J. 2002;324:160-163.
73. Singer A, Clark R. Cutaneous wound healing. New Eng J Med. 1999;341:738-746.
74. Bello YM, Phillips TJ. Recent advances in wound healing. J Amer Med Assoc.
2000;283:716-718.
75. Fonder MA, Lazarus GS, Cowan DA, Aronson-Cook B, Kohli AR, Mamelak AJ. Treating
the chronic wound: A practical approach to the care of nonhealing wounds and wound
care dressings. J Am Acad Dermatol. 2008;58:185-206.
76. Arnold M, Barbul A. Nutrition and wound healing. Plast Reconst Surg. 2006;117:42S-58S.
77. Kondrup J, Allison S, Elia M, Ma EL, Vellas B, Plauth M. ESPEN Guidelines for nutrition
screening 2002. Clin Nutr. 2003;22:415-421.
78. ASPEN. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric
patients. J Parenter Enteral Nutr. 2002;26:1SA-138SA.
43

44
79. European Pressure Ulcer Advisory Panel. Nutritional guidelines for pressure ulcer
prevention and treatment. http://www.epuap.org/guidelines/english1.html.
Accessed May 2, 2008.
80. Scholl D, Langkamp-Henken B. Nutrient recommendations for wound healing.
J Intraven Nurs. 2001;24:124-132.
81. Breslow RA, Bergstrom N. Nutritional prediction of pressure ulcers. J Am Diet Assoc.
1994;94:1301-1304; quiz 1305-1306.
82. Allman RM, Goode PS, Patrick MM, Burst N, Bartolucci AA. Pressure ulcer risk factors
among hospitalized patients with activity limitation. Jama. 1995;273:865-870.
83. Gilmore SA, Robinson G, Posthauer ME, Raymond J. Clinical indicators associated with
unintentional weight loss and pressure ulcers in elderly residents of nursing facilities.
J Am Diet Assoc. 1995;95:984-992.
84. Strauss EA, Margolis DJ. Malnutrition in patients with pressure ulcers: morbidity,
mortality, and clinically practical assessments. Adv Wound Care. 1996;9:37-40.
85. Stratton RJ, Ek AC, Engfer M, et al. Enteral nutritional support in prevention and treatment
of pressure ulcers: a systematic review and meta-analysis. Ageing Res Rev. 2005;4:
422-450.
86. ADA. Standards of medical care in diabetes--2008. Diabetes Care. 2008;31 Suppl 1:
S12-54.
87. Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition principles and
recommendations for the treatment and prevention of diabetes and related complications.
Diabetes Care. 2002;25:148-198.
88. Lee JO, Benjamin D, Herndon DN. Nutrition support strategies for severely burned
patients. Nutr Clin Pract. 2005;20:325-330.
89. De-Souza DA, Greene LJ. Pharmacological nutrition after burn injury. J Nutr.
1998;128:797-803.
90. Gudaviciene D, Rimdeika R, Adamonis K. Nutrition of burned patients. Medicina (Kaunas).
2004;40:1-8.
91. Casimiro C, Garcia-de-Lorenzo A, Usan L. Prevalence of decubitus ulcer and associated
risk factors in an institutionalized Spanish elderly population. Nutrition. 2002;18:408-414.
92. Stotts NA, Hopf HW. The link between tissue oxygen and hydration in nursing home
residents with pressure ulcers: preliminary data. J Wound Ostomy Continence Nurs.
2003;30:184-190.

93. Clark RH, Feleke G, Din M, et al. Nutritional treatment for acquired immunodeficiency
virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and
arginine: a randomized, double-blind, placebo-controlled study. J Parenter Enteral Nutr.
2000;24:133-139.
94. Matarese LE. Enteral feeding solutions. Gastrointest Endosc Clin N Am. 1998;8:593-609.
95. Holecek M. Relation between glutamine, branched-chain amino acids, and protein
metabolism. Nutrition. 2002;18:130-133.
96. Smith HJ, Mukerji P, Tisdale MJ. Attenuation of proteasome-induced proteolysis in
skeletal muscle by {beta}-hydroxy-{beta}-methylbutyrate in cancer-induced muscle loss.
Cancer Res. 2005;65:277-283.
97. Smith HJ, Wyke SM, Tisdale MJ. Mechanism of the attenuation of proteolysis-inducing
factor stimulated protein degradation in muscle by beta-hydroxy-beta-methylbutyrate.
Cancer Res. 2004;64:8731-8735.
98. Panton L, Rathmacher J, Baier S, Nissen S. Nutritional supplementation of the leucine
metabolite beta-hydroxy-beta-methylbutyrate (HMB) during resistance training. Nutrition.
2000;16:734-739.
99. May PE, Barber A, D’Olimpio JT, Hourihane A, Abumrad NN. Reversal of cancer-related
wasting using oral supplementation with a combination of beta-hydroxy-
beta-methylbutyrate, arginine, and glutamine. Am J Surg. 2002;183:471-479.
100. Rathmacher JA, Nissen S, Panton L, et al. Supplementation with a combination of betahydroxy-beta-methylbutyrate
(HMB), arginine, and glutamine is safe and could improve
hematological parameters. J Parenter Enteral Nutr. 2004;28:65-75.
101. Berk L, James J, Schwartz A, et al. A randomized, double-blind, placebo-controlled trial
of a beta-hydroxyl beta-methyl butyrate, glutamine, and arginine mixture for the treatment
of cancer cachexia (RTOG 0122). Support Care Cancer. 2008.
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Notes:

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