1. Nutritional Assessment.

Kesari A(1), Noel JY(2).

In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024

Jan–.
2023 Apr 10.

Author information:
(1)UTHSC
(2)Le Bonheur Children's Hospital

Food and nutrition are basic indispensable needs of humans. Nutrition plays a
critical role in maintaining the health and well-being of individuals and is
also an essential component of the healthcare delivery system. The nutritional
status of individuals affects the clinical outcomes. Essential nutrients are
classified into six groups, namely carbohydrates, proteins, lipids, minerals,
vitamins, and water. Nutritional requirements of healthy individuals depend on
various factors, such as age, sex, and activity. Hence, recommended values of
dietary intakes vary for each group of individuals. In the United States, the
Food and Nutrition Board of the Institutes of Medicine (IOM) under the National
Academy of Sciences issues nutrition recommendations for populations throughout
the life span called Dietary Reference Intakes (DRIs). An imbalance in
nutritional intake leads to malnutrition. The word ‘malnutrition’ is defined in
multiple ways, and there is still no consensus. Traditionally, the term
malnutrition has been used in the context of lack of energy intake or
deficiencies of nutrients, under which two main conditions, namely marasmus, and
kwashiorkor, are discussed. Marasmus primarily refers to energy or calorie
deficiency, whereas kwashiorkor refers to protein deficiency characterized by
peripheral edema. However, the term malnutrition now includes conditions
caused by both insufficient as well as excess intake of macronutrients and
micronutrients. As per WHO guidelines, malnutrition encompasses three
categories, namely, Undernutrition (low weight-for-height, low height-for-age,
and low weight-for-age), Micronutrient (vitamins and minerals) deficiency or
excess, and Overnutrition (overweight, obesity, and other diet-related health
conditions such as type 2 diabetes mellitus, cardiovascular disorders, etc.).
The presentation of malnutrition can be acute, sub-acute, or chronic and may or
may not be associated with underlying inflammation. Furthermore, the double
burden of malnutrition has also been emphasized in various studies. This
involves the dual manifestation of overnutrition and undernutrition, which makes
the diagnosis of malnutrition a challenge. Hence, a comprehensive,
multi-faceted evaluation of a patient's nutritional status is warranted. A
comprehensive nutritional assessment, however, should be differentiated from
nutritional screening. Nutritional screening is done to quickly identify
individuals at risk of developing malnutrition. For example, the mini
nutritional assessment (MNA) is used in the geriatric patient population to
screen for individuals at risk of malnutrition. This screening tool consists of
a questionnaire and has a scoring system that helps identify at-risk
individuals. On the other hand, a comprehensive nutritional assessment is
performed to evaluate the nutritional status of patients already identified at
nutritional risk. Nutritional assessment allows healthcare providers to
systematically assess the overall nutritional status of patients, diagnose
malnutrition, identify underlying pathologies that lead to malnutrition, and
plan necessary interventions.

Copyright © 2024, StatPearls Publishing LLC.

PMID: 35593821
Conflict of interest statement: Disclosure: Aditi Kesari declares no relevant
financial relationships with ineligible companies. Disclosure: Julia Noel
declares no relevant financial relationships with ineligible companies.

2. Dyslipidemia.

Pappan N(1), Awosika AO(2), Rehman A(3).

In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024

Jan–.
2024 Mar 4.

Author information:
(1)St. George’s University (SGU) School of Medicine
(2)University of Illinois College of Medicine
(3)District Endocrine/Sentara Northern Virginia Medical Center

Lipids, such as cholesterol or triglycerides, are absorbed from the intestines

and carried throughout the body via lipoproteins for energy, steroid production,
or bile acid formation. Major contributors to these pathways are cholesterol,
low-density lipoprotein (LDL) cholesterol, triglycerides, and high-density
lipoprotein (HDL). An imbalance of any of these factors, either from organic or
nonorganic causes, can lead to dyslipidemia. Dyslipidemia results in abnormal
levels of lipids (fats) in the blood that can increase the risk of
cardiovascular diseases. Lipids include LDL cholesterol, high-density
lipoprotein (HDL) cholesterol, and triglycerides. Dyslipidemia is classified
into 2 types: primary and secondary. Primary dyslipidemia is inherited and
caused by genetic mutations that affect lipid metabolism. Secondary dyslipidemia
is acquired and caused by lifestyle factors or other medical conditions that
alter lipid levels. The most common forms of dyslipidemia are: High LDL
cholesterol is considered “bad” cholesterol because it can form plaques in the
arteries and reduce blood flow. Low HDL cholesterol is considered “good”
cholesterol because it can help remove LDL from the blood and protect against
atherosclerosis. High triglycerides are stored in fat cells and released as
energy when needed. High triglycerides can also contribute to plaque formation
and inflammation in the arteries. High total cholesterol is the sum of LDL, HDL,
and half of the triglyceride level. High total cholesterol can indicate an
increased risk of heart disease and stroke. Dyslipidemia usually does not cause
any symptoms, but it can be detected by a blood test measuring different lipids
levels. The optimal lipid level varies depending on the individual’s age, sex,
and other risk factors, but generally, the following ranges are recommended: LDL
cholesterol: less than 100 mg/dL. HDL cholesterol: more than 40 mg/dL for men
and more than 50 mg/dL for women. Triglycerides: less than 150 mg/dL. Total
cholesterol: less than 200 mg/dL. Treating dyslipidemia depends on the type and
severity of the condition and the presence of other risk factors such as
diabetes, hypertension, obesity, or smoking. The main goals of treatment are to
lower LDL cholesterol, raise HDL cholesterol, and reduce triglycerides.
Preventing dyslipidemia is essential to reduce the risk of cardiovascular
complications and improve the quality of life. The prevention strategies
include: Screening for dyslipidemia regularly, especially for people with a
family history or other risk factors. The frequency and type of screening depend
on the individual’s age, sex, and health status, but generally, a lipid profile
test is recommended every 4 to 6 years for adults and every 2 years for children
and adolescents. Adopting a healthy lifestyle by eating a balanced diet with
plenty of fruits, vegetables, whole grains, lean proteins, and healthy fats,
such as omega-3 fatty acids from fish, nuts, and seeds. Avoid foods high in
cholesterol, saturated fats, trans fats, added sugars, and salt. If possible,
engage in physical activity for at least 150 minutes weekly. Maintaining a
healthy weight and body mass index, quitting smoking, and limiting alcohol
intake are all recommended. Comorbidities such as diabetes, hypertension,
hypothyroidism, chronic kidney disease, or liver disease can affect lipid levels
or increase the risk of cardiovascular disease; therefore, it is important to
remain compliant with any medications.

Copyright © 2024, StatPearls Publishing LLC.

PMID: 32809726

Conflict of interest statement: Disclosure: Nikos Pappan declares no relevant

financial relationships with ineligible companies. Disclosure: Ayoola Awosika
declares no relevant financial relationships with ineligible companies.
Disclosure: Anis Rehman declares no relevant financial relationships with
ineligible companies.

3. Anti-Inflammatory Diets.

Scheiber A(1), Mank V(1).

In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024

Jan–.
2023 Oct 28.

Author information:
(1)Tripler Army Medical Center

The average human life expectancy has more than doubled in the last 150 years
worldwide; much of this increase is attributed to the rapidly advancing practice
of medicine. As general medical knowledge and treatments expand and improve,
many once lethal diseases are now treatable or have been eradicated, and disease
prevalence has shifted away from acute, communicable processes. The chronic
inflammatory state significantly contributes to the development and progression
of many noncommunicable disease processes, including cancer, cardiovascular
disease, and neurocognitive decline. The inflammatory response is crucial to
human survival. Inflammation is a normal and vital responsive process to
internal injury and many external assaults, including foreign substances or
trauma. When regulated appropriately, the inflammatory response facilitates the
eradication of the invader, tissue repair, and a return to homeostasis.
Inflammation may be acute or chronic. The acute inflammatory response begins
within minutes to hours, lasts for hours to days, and is typically initiated by
tissue-resident macrophages and dendritic cells. In response to a stimulus
perceived as harmful, these cells release a cascade of proinflammatory
cytokines, chemokines, and prostaglandin E2 (PGE2). The acute inflammatory
process is characterized by three main phases: enhanced blood flow to the target
area via dilation of small vessels, increased vascular permeability, and
phagocytic leukocyte migration into the affected tissue. An effective acute
inflammatory response eradicates foreign pathogens or necrotic cells, followed
by the repair of the host tissue. However, leukocytes are important causes of
injury to normal cells and tissues during a normal inflammatory response. If the
acute inflammatory response cannot resolve normally because of persistent tissue
injury or dysregulation of normal processes, chronic inflammation will ensue.
Chronic inflammation may occur in a tissue when an inflammatory process is
activated by an overabundance of triggering factors, such as free radicals,
oxidative stress, or foreign pathogens. With repeated stimulus from the
triggering factor, an unregulated inflammatory response can be initiated,
causing chronic local or systemic organ damage. Chronic inflammation is
characterized by continued proinflammatory processes being unchecked by
anti-inflammatory processes. The presentation of chronic inflammation will vary
with the affected tissue and the injurious agent. Atherosclerosis is a form of
chronic inflammation within the arterial vasculature that underlies the
pathogenesis of peripheral, cerebral, and coronary vascular disease,
predisposing to limb ischemia, stroke, and myocardial infarction. Cardiovascular
disease is the most common underlying cause of death in the United States.
Atherosclerosis is considered to be a chronic inflammatory response within the
arterial wall to ongoing endothelial injury. As part of a complex response to
injury, macrophages accumulate within the vessel wall, are chronically activated
to release proinflammatory cytokines, recruit other inflammatory cells to the
area, exert a catabolic effect on fibrous atheromatous plaques, and increase the
overall risk of plaque rupture and thrombosis. Cancer is another complex disease
state characterized by a chronic inflammatory response. Cancer cells express
antigens that may be recognized by the human immune system, thereby upregulating
proinflammatory cytokines and mediators and the ongoing activation of immune
cells. Cancer cells also frequently undergo necrosis, which promotes a
continuous influx of leukocytes to the tumor. However, cancer cells also possess
the ability to evade the normal immune system while promoting immune responses
that support tumor growth. This dysregulated and dysfunctional chronic
inflammatory promotes the progression of the malignancy. An unregulated
inflammatory response also significantly negatively affects neurocognitive
function. The blood-brain barrier is a bidirectional communication system
between the innate immune system of the brain and the peripheral immune system
and was initially thought to be an insulator against peripheral
inflammation. However, increased peripheral immune system activity chronically
activates the specialized macrophages of the brain parenchyma known as
microglia, promoting a blood-brain barrier breakdown. This breakdown may allow
peripheral inflammatory mediators to enter the central nervous system,
increasing neuroinflammation and the risk of neurocognitive diseases. Chronic
inflammation contributes to the risk of disease development and progression to
some degree. While not completely understood, this process has encouraged
healthcare practitioners to include the reduction of inflammation in
preventative and treatment planning. Clinicians, particularly primary care
practitioners, are uniquely poised to offer various modalities of inflammatory
reduction, including adherence to an anti-inflammatory diet.

Copyright © 2024, StatPearls Publishing LLC.

PMID: 37983365

Conflict of interest statement: Disclosure: Alexander Scheiber declares no

relevant financial relationships with ineligible companies. Disclosure: Victoria
Mank declares no relevant financial relationships with ineligible companies.

4. The Role of Milk Nutrition and Ketogenic Diet in Epileptic Disorders.

Ciliberti MG(1), Santillo A(1), Polito R(2), Messina G(2), Albenzio M(1).

In: Czuczwar SJ(3), editor. Epilepsy [Internet]. Brisbane (AU): Exon

Publications; 2022 Apr 2. Chapter 8.

Author information:
(1)Department of Agriculture, Food, Natural Resources, and Engineering (DAFNE),
University of Foggia, Foggia, Italy
(2)Department of Clinical and Experimental Medicine, University of Foggia,
Foggia, Italy
(3)Department of Pathophysiology, Medical University of Lublin, Lublin, Poland
This chapter explores the role of the gut-brain axis, ketogenic diet, and cow’s
milk allergy on epileptic seizures, with a special focus on childhood. Milk
nutrition is particularly relevant for normal growth and health in childhood;
however, some studies report an association between cow’s milk allergy and
epileptic events. It is necessary to clarify the role of protein polymorphisms
in these events and the influence of milk protein fractions on gut microbiota in
the pathophysiology of epilepsy. The rationale for the discussion assumes that
appropriate nutrition in infants offers the possibility of minimizing
diet-induced proinflammatory mediators in the brain, and at the peripheral
level. The putative role of diet on inflammation and intestinal microbiome in
infants with generalized epilepsy are presented. Furthermore, the potential
benefits of ketogenic diet along with non-bovine milk alternatives to manage
epilepsy in children are discussed.

Copyright: The Authors.; The authors confirm that the materials included in this
chapter do not violate copyright laws. Where relevant, appropriate permissions
have been obtained from the original copyright holder(s), and all original
sources have been appropriately acknowledged or referenced.

DOI: 10.36255/exon-publications-epilepsy-ketogenic-diet
PMID: 35605080

Conflict of interest statement: Conflict of Interest: The authors declare no

potential conflict of interest with respect to research, authorship and/or
publication of this chapter.

5. NTP Developmental and Reproductive Toxicity Technical Report on the Modified

One-Generation Study of 2-Hydroxy-4-methoxybenzophenone (CASRN 131-57-7)
Administered in Feed to Sprague Dawley (Hsd:Sprague Dawley(®) SD(®)) Rats with
Prenatal and Reproductive Performance Assessments in F(1) Offspring: DART Report
05 [Internet].

National Toxicology Program(1).

Research Triangle Park (NC): National Toxicology Program; 2022 Jun.

NTP Developmental and Reproductive Toxicity Reports.

Collaborators: McIntyre BS, Brix AE, Betz LJ, Blystone CR, Brown P, Cesta MF,
Cristy TA, Cunny HC, Fostel JM, Foster PM, Graves SW, Haney RE, Hooth MJ,
Johnson CL, King-Herbert AP, Kissling GE, Malarkey DE, McBride S, Myers C, Price
CJ, Raghuraman A, Richey JS, Roberts GK, Robinson VG, Sayers N, Seely JC,
Shackelford CC, Shipkowski KA, Shockley KR, Snow SJ, Stout MD, Sutherland VL,
Turner KJ, Tyl RW, Vallant MK, Waidyanatha S, Walker NJ, Youn V.

Author information:
(1)Division of the National Toxicology Program, National Institute of
Environmental Health Sciences, Research Triangle Park, North Carolina, USA

2-Hydroxy-4-methoxybenzophenone (2H4MBP), also known as oxybenzone and

benzophenone-3, is approved by the U.S. Food and Drug Administration for use in
sunscreens and other personal care products in concentrations of <6%, either
alone or in combination formulations, and as an indirect food additive in
acrylic and modified acrylic plastics that come into contact with food.
Mechanistic screening studies have shown that 2H4MBP and its metabolites are
capable of activating the estrogen receptor and antagonizing the androgen
receptor to varying degrees. The objective of the present study was to
characterize the potential for 2H4MBP to adversely affect any phase of
development, maturation, and ability to reproduce in Sprague Dawley (Hsd:Sprague
Dawley® SD®) rats administered 2H4MBP in 5K96 feed, a diet low in
phytoestrogens, using the National Toxicology Program (NTP) modified
one-generation (MOG) study design. 2H4MBP exposure via diet, rather than topical
application, was selected for this study to sustain internal exposure; if
applied topically, the internal dose would have been influenced by intra- and
interanimal grooming behavior. Exposure concentrations were based on a dose
range-finding study that demonstrated 25,000 ppm 2H4MBP did not induce excessive
maternal toxicity or affect parturition, litter size, or pup viability. 2H4MBP
intake by F0 females in the 3,000, 10,000, 25,000, and 50,000 ppm 2H4MBP groups,
based on feed consumption and dietary concentrations from gestation day (GD) 6
through GD 21, was approximately 215, 695, 2,086, and 6,426 mg 2H4MBP/kg body
weight/day (mg/kg/day), respectively; from lactation day (LD) 1 through LD 14,
2H4MBP intake was approximately 577, 1,858, 4,460, and 12,029 mg/kg/day,
respectively. Exposure concentrations of 3,000, 10,000, and 30,000 ppm were
selected for the subsequent MOG study; ethinyl estradiol (EE), a synthetic form
of estrogen, was included at 0.05 ppm as a positive reference control.
MODIFIED ONE-GENERATION STUDY: F0 exposure began on GD 6 and was continual. At
weaning on postnatal day (PND) 28, F1 offspring were assigned to either
reproductive performance (2/sex/litter), prenatal (1/sex/litter), or biological
sampling (1/sex/litter) cohorts. Upon sexual maturity, F1 mating and pregnancy
indices were evaluated. In the prenatal cohort, F2 prenatal development (litter
size, fetal weight, and morphology) was assessed on GD 21. In the reproductive
performance cohort, littering indices, F2 viability, and growth were assessed
until PND 28. The likelihood of identifying potential 2H4MBP-induced adverse
effects (similarity and magnitude thereof) at any phase of growth or development
was increased by examining related endpoints in multiple pups within a litter
throughout life, across cohorts, and across generations. 2H4MBP exposure at the
tested concentrations did not induce any effects on mating or pregnancy indices.
In the prenatal cohort, exposure to 30,000 ppm was associated with a slight but
significant decrease in the mean numbers of corpora lutea and F2 implants and a
slightly lower number of live fetuses on GD 21 than in the control group. In the
reproductive performance cohort, total F2 mean litter size on PND 0 was also
significantly decreased compared to the control group. 2H4MBP exposure might
have affected litter size, although the effect was small in magnitude.
Collectively, given the minimal apparent response that may or may not be a
direct effect of 2H4MBP, this was considered equivocal evidence of an adverse
effect on reproductive performance. EE exposure did not affect F1 live litter
size on PND 0, but significantly decreased mean number of corpora lutea and
total F2 implants were observed. 2H4MBP was associated with lower F1 and
F2 preweaning and F1 postweaning mean body weights. At 30,000 ppm 2H4MBP,
preweaning F1 mean body weights of both males and females were progressively
lower over time, relative to their respective control groups. The response was
lessened in F2 males and even more so in F2 females. The significantly decreased
F1 postweaning mean body weights were not associated with concurrent lower feed
consumption. The effects on body weights associated with exposure to 2H4MBP were
considered some evidence of developmental toxicity. 2H4MBP intake by F0 females
in the 3,000, 10,000, and 30,000 ppm 2H4MBP groups, based on feed consumption
and dietary concentrations from GD 6 through GD 21 was approximately 205, 697,
and 2,644 mg/kg/day, respectively; from LD 1 through LD 13, 2H4MBP intake was
approximately 484, 1,591, and 5,120 mg/kg/day, respectively. 2H4MBP intake by
the F1 generation postweaning (PND 28 through PND 91) in the 3,000, 10,000, and
30,000 ppm groups was approximately 267, 948, and 3,003 mg/kg/day (males) and
287, 983, and 3,493 mg/kg/day (females), respectively. 2H4MBP intake by the
adult F1 females in the 3,000, 10,000, and 30,000 ppm groups was approximately
240, 825, and 2,760 mg/kg/day (GD 0 through GD 21) and 426, 1,621, and
5,944 mg/kg/day (LD 1 through LD 13), respectively. Diaphragmatic hernias were
observed at a low incidence in 2H4MBP-exposed animals in both the F1 and
F2 generations but were not observed in any control animals. Most of the
diaphragmatic hernias were associated histologically with hepatodiaphragmatic
hernias. Low incidences of diaphragmatic and hepatodiaphragmatic hernias have
been reported in control groups in other NTP MOG studies. Therefore, it is
unclear whether the occurrences of diaphragmatic and hepatodiaphragmatic hernias
in both the F1 and F2 generations were related to 2H4MBP exposure. 2H4MBP did
not alter estrogen or androgen-mediated developmental markers, and no gross
lesions were observed at adult necropsy consistent with perturbation of normal
estrogen receptor- or androgen-receptor-mediated development. Expected
estrogenic responses were observed in the EE group. In the 30,000 ppm group,
adult weights of male androgen-dependent reproductive tissues were slightly
lower than those of the control males, likely secondary to the apparent growth
retardation, and occurred in the absence of histopathological findings. Sperm
and spermatid counts were not affected by 2H4MBP exposure. The ability of
F1 males in either cohort to successfully mate, resulting in pregnancy, also was
not affected. Unlike findings reported for in vitro cell models, 2H4MBP had no
apparent effect on estrogen receptor- or androgen-receptor-dependent processes,
nor did it affect mating or pregnancy indices. 2H4MBP exposure in F1 rats was
associated with significantly increased kidney weights, renal tubule epithelial
regeneration, interstitial chronic active inflammation, renal tubule and pelvic
concretions, renal tubule dilation, papillary necrosis, urothelial hyperplasia,
and urothelial ulcers. F1 females also displayed renal tubule epithelial
degeneration, pelvic dilation, chronic progressive nephropathy, and
mineralization. 2H4MBP-exposed F1 males and females displayed significantly
increased liver weights relative to their respective control groups. The
absolute weight of the adrenal glands was significantly decreased in the
30,000 ppm female group relative to the control group in the reproductive
performance cohort. Several other decreases in organ weights were not associated
with histological correlates and were considered related to changes in body
weights. F2 fetal findings of hydronephrosis of the kidney and enlarged liver
were observed in the 30,000 ppm group. F2 offspring in the 30,000 ppm group
exhibited dilation of the renal pelvis. The observed fetal, PND 28, and adult
necropsy findings were consistent with previously reported studies that
identified the kidney and liver as target tissues of 2H4MBP-mediated toxicity.
CONCLUSIONS: Under the conditions of this modified one-generation (MOG) study,
there was equivocal evidence of reproductive toxicity of
2-hydroxy-4-methoxybenzophenone (2H4MBP) in Hsd:Sprague Dawley® SD® rats based
on a decrease in F2 litter size in both the prenatal and reproductive
performance cohorts. Under the conditions of this MOG study, there was some
evidence of developmental toxicity of 2H4MBP in Hsd:Sprague Dawley® SD® rats
based on the observed postnatal growth retardation. The relationship of the
increased occurrence of diaphragmatic and hepatodiaphragmatic hernias in
F1 adults and F2 pups to 2H4MBP exposure is unclear. Exposure to 2H4MBP was not
associated with signals consistent with alterations in estrogenic, androgenic,
or antiandrogenic action. Exposure to 2H4MBP was associated with lower F1 and
F2 mean body weights; this effect on body weight contributed to the apparent
2H4MBP-related decreases in male reproductive organ weights. Mating and
littering were not significantly affected by 2H4MBP exposure. Exposure to 2H4MBP
was associated with nonneoplastic kidney lesions in the F0, F1, and
F2 generations. Expected estrogenic responses were observed in the EE group.
SYNONYMS: benzophenone-3; (2-hydroxy-4-methoxyphenyl)-phenylmethanoneoxybenzone;
oxybenzone [Table: see text]

DOI: 10.22427/NTP-DART-05
PMID: 35877944

6. Lipid Formulations for Patients Requiring Parenteral Nutrition: A Review of

Clinical Effectiveness, Cost-Effectiveness, and Guidelines – An Update
[Internet].
Tran K, Butcher R.

Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Aug 2.
CADTH Rapid Response Reports.

Parenteral nutrition (PN) is provided through intravenous administration to

patients who are unable to meet their nutritional needs either through oral
intake or enteral nutrition (EN) due to pathological or surgical conditions.–
Decades of research have resulted in the development of relatively safe PN
formulations containing amino acids, glucose, lipids (as emulsions),
electrolytes, vitamins and trace elements. PN may be used for short or long
periods of time depending on the morbidity and its severity. However, prolonged
use of PN may be associated with increased risk of long-term adverse events
including hypertriglyceridemia, infections, metabolic bone disease, and
PN-associated liver disease (PNALD)., The source of oil present in lipid
emulsions is believed to play an important role in the development of long-term
complications. Soybean oil (SO) is not only an excellent source of non-protein
energy, but also rich in essential fatty acids such as linoleic acid (18:2 n-6)
and alpha-linolenic acid (18:3 n-3) and non-essential oleic acid (18:1 n-9). The
letters “n” and “ω” for omega are used interchangeably. These fatty acids are
precursors of longer chain fatty acids, arachidonic acid (AA; 20:4 n-6),
eicosapentaenoic acid (EPA; 20:5 n-3), and eicosatrienoic acid (Mead acid, 20:3
n-9), respectively. AA and Mead acid have more proinflammatory properties than
EPA. Prolonged use of SO emulsions in PN has been associated with
hypertriglyceridemia, proinflammatory profile, and PNALD., As a result,
different lipid formulations have been developed. For instance, olive oil (OO)
has been added to reduce the amount of SO in lipid emulsions for PN. OO is the
main source of lipid in the Mediterranean diet, consisting of monounsaturated
fatty acids such as oleic acid (18:1 n-9), phenolic compounds, and squalene.
Diets enriched with OO have been linked to health benefits such as prevention of
cancer, heart disease, and aging through its antioxidant properties. Compared
with pure SO emulsion in PN, a mixture of 80% OO/20% SO has been shown to have
some clinical benefits, despite the concern about the increase in Mead acid
levels in OO enriched lipid emulsions. Another lipid has been used to reduce the
level SO component in lipid emulsions for PN was medium chain triglycerides
(MCT), containing fatty acids of 6 to 12 carbon atoms. Unlike long chain
triglycerides (LCT) with fatty acid chains ranging from 14 to 21 carbon atoms,
MCT are more water soluble and readily oxidized in the mitochondria for the
production of energy. A mixture of 50% MCT/50% LCT has been developed and
considered to be safe and tolerable in patients requiring PN. However, the
beneficial effects of MCT/LCT compared with other lipid emulsions for PN remains
unclear. Fish oil (FO) has lately been considered as an ideal choice of lipid to
partially or completely replace SO. FO has a high content of n-3 polyunsaturated
fatty acids (20% to 40%), particularly EPA and docosahexaenoic acid (DHA; 22:6
n-3), which have been shown to reduce inflammation by competing with AA for
eicosanoid synthesis, producing the 3-series of prostaglandins and thromboxanes
and the 5-series of leukotrienes. Mixed-oil containing FO for use in PN such as
SO/MCT/OO/FO (30%/30%/25%/15%) or MCT/SO/FO (50%/40%/10%) has been recently
developed and is available for PN use. From small-scale clinical trials, fish
oil enriched PN appears to have some clinical benefits compared with non-fish
oil enriched PN., In a recent CADTH report, published in 2017, entitled “Lipid
Formulations for Patients Requiring Parenteral Nutrition: A Review of Clinical
and Cost-Effectiveness and Guidelines”, low quality evidence found no difference
in comparative clinical effectiveness among lipid emulsions examined in preterm
infants. There was some evidence that fish oil enriched PN had some clinical
benefits in non-surgical and surgical adult patients in intensive care unit
(ICU). Economic evaluations from low-quality studies showed that FO emulsion was
more cost-effective than SO-based emulsions. None of the identified guidelines
could make strong recommendations regarding the type of lipid emulsions for PN
due to insufficient evidence. The aim of this report is to update the clinical
effectiveness, cost-effectiveness, and evidence-based guidelines on the use of
lipid formulations for patients requiring PN.

Copyright © 2019 Canadian Agency for Drugs and Technologies in Health.

PMID: 33939350

7. Health Technol Assess. 2022 Dec;26(46):1-172. doi: 10.3310/UWNB3375.

Photobiomodulation in the management of oral mucositis for adult head and neck
cancer patients receiving irradiation: the LiTEFORM RCT.

Nugent M(1), Bryant V(2), Butcher C(3), Fisher H(4), Gill S(3), Goranova R(5),
Hiu S(4), Lindley L(6), O'Hara J(7), Oluboyede Y(4), Patterson J(8), Rapley
T(9), Robinson T(4), Rousseau N(4)(10), Ryan V(4), Shanmugasundaram R(11), Sharp
L(4), Smith Whelan R(3), Stocken DD(10), Ternent L(4), Wilson J(4), Walker J(3).

Author information:
(1)Department of Oral and Maxillofacial Surgery, City Hospitals Sunderland NHS
Foundation Trust, Sunderland, UK.
(2)Change Head and Neck Cancer Research Patient Involvement Group, Sunderland,
UK.
(3)Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne,
UK.
(4)Population Health Sciences Institute, Newcastle University, Newcastle upon
Tyne, UK.
(5)Plymouth Oncology Centre, University Hospitals Plymouth NHS Trust, Plymouth,
UK.
(6)Social Policy Research Unit, University of York, York, UK.
(7)Ear, Nose and Throat Department, Newcastle upon Tyne Hospitals NHS Foundation
Trust, Newcastle upon Tyne, UK.
(8)School of Health Sciences, University of Liverpool, Liverpool, UK.
(9)Department of Social Work, Education and Community Wellbeing, Northumbria
University, Newcastle upon Tyne, UK.
(10)Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
(11)Clinical Oncology, University Hospital Southampton NHS Foundation Trust,
Southampton, UK.

BACKGROUND: Oral mucositis is a debilitating and painful complication of head

and neck cancer irradiation that is characterised by inflammation of the mucous
membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck
cancer patients per year in England and Wales. Current treatments have not
proven to be effective. International studies suggest that low-level laser
therapy may be an effective treatment.
OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of
low-level laser therapy in the management of oral mucositis in head and neck
cancer irradiation. To identify barriers to and facilitators of implementing
low-level laser therapy in routine care.
DESIGN: Placebo-controlled, individually randomised, multicentre Phase III
superiority trial, with an internal pilot and health economic and qualitative
process evaluations. The participants, outcome assessors and therapists were
blinded.
SETTING: Nine NHS head and neck cancer sites in England and Wales.
PARTICIPANTS: A total of 87 out of 380 participants were recruited who were aged
≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy.
INTERVENTION: Random allocation (1 : 1 ratio) to either low-level laser therapy
or sham low-level laser therapy three times per week for the duration of
irradiation. The diode laser had the following specifications: wavelength
660 nm, power output 75 mW, beam area 1.5 cm2, irradiance 50 mW/cm2, exposure
time 60 seconds and fluence 3 J/cm2. There were 20-30 spots per session. Sham
low-level laser therapy was delivered in an identical manner.
MAIN OUTCOME MEASURE: The mean Oral Mucositis Weekly Questionnaire-Head and Neck
Cancer score at 6 weeks following the start of irradiation. Higher scores
indicate a worse outcome.
RESULTS: A total of 231 patients were screened and, of these, 87 were randomised
(low-level laser therapy arm, n = 44; sham arm, n = 43). The mean age was 59.4
years (standard deviation 8.8 years) and 69 participants (79%) were male. The
mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks
was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4
(standard deviation 13.8) in the sham arm.
LIMITATIONS: The trial lacked statistical power because it did not meet the
recruitment target. Staff and patients willingly participated in the trial and
worked hard to make the LiTEFORM trial succeed. However, the task of
introducing, embedding and sustaining new low-level laser therapy services into
a complex care pathway proved challenging. Sites could deliver low-level laser
therapy to only a small number of patients at a time. The administration of
low-level laser therapy was viewed as straightforward, but also time-consuming
and sometimes uncomfortable for both patients and staff, particularly those
staff who were not used to working in a patient's mouth.
CONCLUSIONS: This trial had a robust design but lacked power to be definitive.
Low-level laser therapy is relatively inexpensive. In contrast with previous
trials, some patients found low-level laser therapy sessions to be difficult.
The duration of low-level laser therapy sessions is, therefore, an important
consideration. Clinicians experienced in oral cavity work most readily adapt to
delivering low-level laser therapy, although other allied health professionals
can be trained. Blinding the clinicians delivering low-level laser therapy is
feasible. There are important human resource, real estate and logistical
considerations for those setting up low-level laser therapy services.
FUTURE WORK: Further well-designed randomised controlled trials investigating
low-level laser therapy in head and neck cancer irradiation are needed, with
similar powered recruitment targets but addressing the recruitment challenges
and logistical findings from this research.
TRIAL REGISTRATION: This trial is registered as ISRCTN14224600.
FUNDING: This project was funded by the National Institute for Health and Care
Research ( NIHR ) Health Technology Assessment programme and will be published
in full in Health Technology Assessment; Vol. 26, No. 46. See the NIHR Journals
Library website for further project information.

Plain Language Summary: Around 9 out of 10 head and neck cancer patients
undergoing treatment experience pain, swelling and sores in their mouth (oral
mucositis). This can lead to weight loss, painful ulcers, difficulty talking,
eating and drinking, and even hospitalisation. Current care includes helping
patients to keep their mouth and teeth clean, encouraging them to have a healthy
diet and prescribing mouthwashes, painkillers and mouth-coating gels. However,
these treatments give limited help in preventing or treating this condition. The
LiTEFORM trial looked at whether or not low-level laser therapy could be used to
prevent and treat oral mucositis. Patients were allocated to one of two arms at
random: active laser or fake (sham) laser. Neither the patients nor the hospital
staff knew which laser was being used. Eighty-seven people joined the study
during the time allowed (44 received low-level laser therapy and 43 received
sham treatment); however, this was a smaller number than the planned target of
380 people. As a result, no meaningful conclusion can be drawn from the results
about whether the therapy is beneficial or cost-effective. People receiving the
low-level laser therapy reported slightly more soreness in their mouth than
those receiving the sham laser, but this could be down to chance. The number of
participants is too small to draw conclusions about whether or not the low-level
laser is helpful. Some patients found the laser treatment sessions to be
difficult. Setting up a new service delivering laser therapy at the same time as
cancer treatments was more complicated than originally anticipated. Problems
included the scheduling of appointments, finding suitable rooms and having
enough trained staff with time to deliver laser therapy. However, this study has
provided us with knowledge on how best to set up a laser therapy service in the
NHS as part of the cancer treatment pathway and the costs involved. These
findings could help future studies looking into low-level laser therapy for
those with head and neck cancer.

DOI: 10.3310/UWNB3375
PMCID: PMC9761526
PMID: 36484364 [Indexed for MEDLINE]