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Professor Pennington was an advocate for quality in all aspects of nutrition support and its delivery, ensuring that the patient remained at the centre of all decisions, and that specialist artificial nutrition support was best managed by the multidisciplinary nutrition team and the education of the wider healthcare community. Within the conference theme of ‘Quality’, this commentary aims to outline drivers for and risks to aspects of quality in parenteral nutrition (PN) services. Quality is defined as a particular property or attribute associated with excellence; in the context of the provision of PN this can be translated to quality processes and standards in the assessment, prescription, preparation, administration and monitoring of PN. Quality products and services are delivered through the timely application of knowledge, competence, procedures and standards. Quality can be so easily compromised; inattention, ignorance and arrogance all play their part. PN is a high-risk therapy; the quality of its delivery should not be entirely dependent on the skills, knowledge and competence of those delivering this care but on accepted standards, procedures, communication, resource and infrastructure. Identification of key steps in the provision of PN and a review of the relevant patient safety data reveal points where safeguards can be put in place to ensure quality is not compromised. Full evaluation of standardisation, computerisation and competency-based training as risk-reduction strategies is required.
Symposium 1: Options in enteral feeding: to perform percutaneous endoscopic gastrostomy or not to perform percutaneous endoscopic gastrostomy: that is the question
Enteral feeding (or ‘tube feeding’) is a very common inpatient intervention to maintain nutritional status where the oral route is inadequate, unsafe or inaccessible. A proportion of patients will need to continue tube feeding in the community after their admission and will require a gastrostomy tube. Although gastrostomy insertion is relatively straightforward, it is not without complications in an often frail and vulnerable group of patients and a multidisciplinary approach is necessary to ensure that the procedure is appropriate. Some patients are better managed with careful assisted hand feeding or nasogastric tubes. Particular care needs to be taken in deciding whether patients with dementia should have a gastrostomy in view of data suggesting that this group of patients have a particularly poor prognosis after the procedure. Decisions regarding the provision of enteral nutrition at the end of life or where patients are not competent to make an informed judgement are particularly challenging and need to be made on a case-by-case basis.
Aluminium is the most common metallic element, but has no known biological role. It accumulates in the body when protective gastrointestinal mechanisms are bypassed, renal function is impaired, or exposure is high – all of which apply frequently to preterm infants. Recognised clinical manifestations of aluminium toxicity include dementia, anaemia and bone disease. Parenteral nutrition (PN) solutions are liable to contamination with aluminium, particularly from acidic solutions in glass vials, notably calcium gluconate. When fed parenterally, infants retain >75% of the aluminium, with high serum, urine and tissue levels. Later health effects of neonatal intravenous aluminium exposure were investigated in a randomised trial comparing standard PN solutions with solutions specially sourced for low aluminium content. Preterm infants exposed for >10 d to standard solutions had impaired neurologic development at 18 months. At 13–15 years, subjects randomised to standard PN had lower lumbar spine bone mass; and, in non-randomised analyses, those with neonatal aluminium intake above the median had lower hip bone mass. Given the sizeable number of infants undergoing intensive care and still exposed to aluminium via PN, these findings have contemporary relevance. Until recently, little progress had been made on reducing aluminium exposure, and meeting Food and Drug Administration recommendations (<5 μg/kg per d) has been impossible in patients <50 kg using available products. Recent advice from the UK Medicines and Healthcare regulatory Authority that calcium gluconate in small volume glass containers should not be used for repeated treatment in children <18 years, including preparation of PN, is an important step towards addressing this problem.
Symposium 3: Nutrition is the cutting edge in surgery: peri-operative feeding
The metabolic response to surgical trauma is mainly characterised by an increase in BMR, a negative N balance, increased gluconeogenesis and increased synthesis of acute-phase proteins. These reactions aim at ensuring the availability of endogenous substrates for healing wounds while the synthesis of acute-phase proteins enhances the scavenging process and helps repair. However, if this process is excessive or continues for too long, it leads to a progressive depletion of body compartment with a consequent adverse outcome. Obviously, the severity of such depletion is magnified if the patient is starving or is already malnourished and the consumption of lean body mass is not compensated by an exogenous supply of nutrients. The nutritional control of this metabolic reaction represents the traditional rationale for nutritional support of surgical patients. Subsequent data have shown that the negative effects of starvation are not simply due to the starvation per se but due to the starving gut, and peri-operative enteral nutrition has proven successful in blunting the metabolic response after injury and improving protein kinetics, net balance and amino acid flux across peripheral tissue and consequently in decreasing the complications. Finally, further clinical research has shown that many post-operative infections may result from immune suppression and that such state might be reversed to some degree by modulation of the immune response through specialised nutritional support in surgical patients, regardless of their nutritional status. This paper will focus on the updated evidence-based research on peri-operative nutrition (parenteral, enteral and immune-enhancing) in patients undergoing major surgery.
An optimal nutritional state is an important consideration in providing successful operative outcomes. Unfortunately, many aspects of surgery are not constructive to providing this. In addition, the metabolic and immune response to injury induces a catabolic state and insulin resistance, a known risk factor of post-operative complications. Aggressive insulin therapy post-operatively has been shown to reduce morbidity and mortality but similar results can be achieved when insulin resistance is lessened by the use of pre-operative carbohydrate loading. Consuming carbohydrate-containing drinks up to 2 h before surgery has been found to be an effective way to attenuate insulin resistance, minimise protein losses, reduce hospital stays and improve patient comfort without adversely affecting gastric emptying. Enhanced recovery programmes have employed carbohydrate loading as one of several strategies aimed at reducing post-operative stress and improving the recovery process. Studies examining the benefits of these programmes have demonstrated significantly shorter post-operative hospital stays, faster return to normal functions and lower occurrences of surgical complications. As a consequence of the favourable evidence they are now being implemented in many surgical units. Further benefit to post-operative recovery may be found with the use of immune-enhancing diets, i.e. supplementation with n-3 fatty acids, arginine, glutamine and/or nucleotides. These have the potential to boost the immune system, improve wound healing and reduce inflammatory markers. Research exploring the benefits of immunonutrition and solidifying the use of carbohydrate loading is ongoing; however, there is strong evidence to link good pre-operative nutrition and improved surgical outcomes.
Patients undergoing oesophagectomy often have nutritional needs at the time of diagnosis and in the post-operative period. The aim of this article is to review the current literature and report on the author's experience of routine feeding jejunostomy insertion following oesophagectomy. The records of forty-eight consecutive patients undergoing oesphagectomy under the author's care were reviewed. Although the evidence of benefit of peri-operative feeding in patients undergoing oesophagectomy is limited, there is a clear need to establish a feeding route at the time of surgery. Oesophagectomy is associated with a mortality rate of 5–10% and a morbidity rate of 30–40% even in high-volume specialist centres. Over 50% of patients developing complications will require an alternative to oral feeding beyond 30 d. The enteral route is preferred in terms of safety and cost. A surgical feeding jejunostomy is associated with a low complication rate and a mortality rate of less than 1%. In forty-eight patients undergoing oesophagectomy the average weight loss at 6 months was 8·4 kg with only 8% regaining their pre-operative weight. Large reductions in weight at 6 months post-operatively were recorded irrespective of the development of post-operative complications or early recurrent disease. Routine jejunostomy insertion is recommended to ensure adequate nutrition in patients who develop post-operative complications and for those patients with long-term reduced appetite and poor oral intake.
Symposium 4: Home parenteral nutrition and intestinal failure clinical network (HIFNET) and parenteral nutrition
Intestinal failure (IF) occurs when intestinal absorptive function is inadequate to maintain hydration and nutrition without enteral or parenteral supplements. It has been classified into three types depending on duration of nutrition support and reversibility. Type 1 IF is commonly seen in the peri-operative period as ileus and usually spontaneously resolves within 14 d. Type 2 IF is uncommon and is often associated with an intra-abdominal catastrophe, intestinal resection, sepsis, metabolic disturbances and undernutrition. Type 3 IF is a chronic condition in a metabolically stable patient, which usually requires long-term parenteral nutrition. This paper focuses on Types 1 and 2 IF (or acute IF) that are usually found in surgical wards. The objectives of this paper are to review the incidence, aetiology, prevention, management principles and outcome of acute IF. The paper discusses the resources necessary to manage acute IF, the indications for inter-hospital transfer and the practicalities of how to transfer and receive a patient with acute IF.
Symposium 7: Nutrition in inflammatory bowel disease
Nutritional assessment and dietary advice are fundamental to inflammatory bowel disease (IBD) patient management and all patients should have access to a dietitian. Newly diagnosed patients often think that their pre-illness diet has contributed to the development of their IBD. However, epidemiological evidence to support diet as a risk factor is lacking. How the diet contributes to the gastrointestinal microbiota is interesting, although the role is not yet clearly defined. Nutritional problems in IBD are common. Malnutrition occurs in up to 85% of patients and weight loss affects up to 80% of patients with Crohn's disease and 18–62% of patients with ulcerative colitis. Nutritional deficiencies are prevalent, particularly in relation to anaemia and osteoporosis. Intestinal strictures can be problematic in Crohn's disease and limiting fibrous foods that may cause a mechanical obstruction in the gastrointestinal tract is helpful. Patients often explore dietary exclusion to alleviate symptoms but such changes may be self-directed or inappropriately advised and can lead to further nutritional deficiencies. Some patients experience concurrent functional symptoms (e.g. abdominal bloating, abdominal pain, flatulence and diarrhoea) that can significantly affect quality of life. Recently, a group of poorly absorbed carbohydrates that occur naturally in the diet called fermentable oligo-, di-, mono-saccharides and polyols have been associated with functional symptoms by intestinal bacterial fermentation leading to rapid gas production, and an osmotic effect increasing fluid delivery to the colon. Emerging evidence indicates that a diet low in fermentable oligo-, di-, mono-saccharides and polyols can alleviate functional symptoms in IBD.
Crohn's disease is one of the leading causes of intestinal failure. The term ‘type 2’ intestinal failure is used to describe the relatively rare type of intestinal failure that occurs in association with septic, metabolic and complex nutritional complications, typically following surgical resection and/or laparostomy for intra-abdominal sepsis. A multidisciplinary approach to the management of patients with type 2 intestinal failure is crucial, and it is helpful to approach patient care in a structured manner using the ‘sepsis-nutrition-anatomy-plan’ algorithm: resolution of sepsis is required before adequate nutritional repletion can be achieved, and it is crucial to optimise nutritional status, and define intestinal anatomy before delineating a definitive medical or surgical plan. A structured approach to the management of patients with inflammatory bowel disease, who have developed type 2 intestinal failure, should reduce the likelihood of these patients developing ‘type 3’ intestinal failure, which is characterised by the need for long-term parenteral nutrition. However, Crohn's disease is still the commonest indication for home parenteral nutrition in the UK.
Most postprandial studies have investigated the response of a single meal, yet the ingestion of sequential meals is more typical in a Western society. The aim of this review is to explain how natural and stable isotope tracers of fatty acids have been used to investigate the metabolism of dietary fat after single and multiple meals, with a focus on in vivo measurements of adipose tissue metabolism. When stable isotope tracers are combined with arteriovenous difference measurements, very specific measurements of metabolic flux across tissues can be made. We have found that adipose tissue is a net importer of dietary fat for 5 h following a single test meal and for most of the day during a typical three-meal eating pattern. When dietary fat is cleared from plasma, some fatty acids ‘spillover’ into the plasma and contribute up to 50% of postprandial plasma NEFA concentrations. Therefore, plasma NEFA concentrations after a meal reflect the balance between intracellular and extracellular lipolysis in adipose tissue. This balance is altered after the acute ingestion of fructose. The enzyme lipoprotein lipase is a key modulator of fatty acid flux in adipose tissue and its rate of action is severely diminished in obese men. In conclusion, in vivo studies of human metabolism can quantify the way that adipose tissue fatty acid trafficking modulates plasma lipid concentrations. This has implications for the flux of fatty acids to tissues that are susceptible to ectopic fat deposition such as the liver and muscle.
Conference on ‘Functional genomic biomarkers, nutrition and disease susceptibility’
Nutrition refers to the process by which a living organism ingests and digests food and uses the nutrients therein for growth, tissue maintenance and all other functions essential to life. Food components interact with our body at molecular, cellular, organ and system level. Nutrients come in complex mixtures, in which the presence and concentration of single compounds as well as their interactions with other compounds and the food matrix influence their bioavailability and bioefficacy. Traditionally, nutrition research mainly concentrated on supplying nutrients of quality to nourish populations and on preventing specific nutrient deficiencies. More recently, it investigates health-related aspects of individual ingredients or of complete diets, in view of health promotion, performance optimisation, disease prevention and risk assessment. This review focuses on proteins and peptides, their role as nutrients and biomarkers and on the technologies developed for their analysis. In the first part of this review, we provide insights into the way proteins are currently characterised and analysed using classical and emerging proteomic approaches. The scope of the second part is to review major applications of proteomics to nutrition, from characterisation of food proteins and peptides, via investigation of health-related food benefits to understanding disease-related mechanisms.
Micronutrients are essential for optimal human health. However, in some cases,
raising intake by supplementation has not proven to be beneficial and there is
even some evidence that supplementation may increase disease risk, highlighting
the importance of assessing the functional status of micronutrients. Techniques
such as gene microarrays and single-nucleotide polymorphism analysis have the
potential to examine effects of micronutrient intake on patterns of gene
expression and inter-individual variation in micronutrient metabolism. Recent
genomic research related to selenium (Se) provides examples illustrating how
studies of functional single-nucleotide polymorphism and gene expression
patterns can reveal novel biomarkers of micronutrient function. Both in
vitro and in vivo experiments show that there are
functionally relevant polymorphisms in genes encoding glutathione peroxidases 1,
3 and 4, selenoprotein P, selenoprotein S and the 15 kDa selenoprotein. Disease
association studies investigating these gene variants have so far been
relatively small but an association of a polymorphism in the selenoprotein S
gene with colorectal cancer risk has been replicated in two distinct
populations. Future disease association studies should examine effects of
multiple variants in combination with nutritional status. Gene microarray
studies indicate that changes in Se intake alter expression of components of
inflammatory, stress response and translation pathways. Our hypothesis is that
Se intake and genetic factors have linked effects on stress response,
inflammation and apoptotic pathways. Combining such data in a systems biology
approach has the potential to identify both biomarkers of micronutrients status
and sub-group populations at particular risk.
Epigenetic changes may be causal in the ageing process and may be influenced by diet, providing opportunities to improve health in later life. The aim of this review is to provide an overview of several areas of research relevant to this topic and to explore a hypothesis relating to a possible role of epigenetic effects, mediated by sirtuin 1, in the beneficial effects of dietary restriction, including increased lifespan. Epigenetic features of ageing include changes in DNA methylation, both globally and at specific loci, which differ between individuals. A major focus of research on dietary influences on epigenetic status has been on nutrition in utero, because the epigenome is probably particularly malleable during this life-course window and because epigenetic marking by early exposures is a compelling mechanism underlying effects on lifelong health. We explore the potential of diet during adulthood, including the practice of dietary restriction, to affect the epigenetic architecture. We report progress with respect to deriving data to support our hypothesis that sirtuin 1 may mediate some of the effects of dietary restriction through effects on DNA methylation and note observations that resveratrol affects DNA methylation and other epigenetic features. Disentangling cause and effect in the context of epigenetic change and ageing is a challenge and requires better understanding of the underlying mechanisms and also the development of more refined experimental tools to manipulate the epigenetic architecture, to facilitate hypothesis-driven research to elucidate these links and thus to exploit them to improve health across the full life-course through dietary measures.
The Sheila Bingham Memorial Lecture
Conference on ‘Functional genomic biomarkers, nutrition and disease susceptibility’
Despite extensive research it has proved difficult to establish the role of diet
in the aetiology of common types of cancer. Obesity and alcohol definitely
increase the risk for several types of cancer, but the importance of particular
foods and nutrients is not clear. Part of the difficulty is our poor
understanding of the physiological changes that might mediate the effect of diet
on cancer risk. Recent research in prospective studies with biobanks of stored
blood samples has shown that the serum concentration of insulin-like growth
factor-1 (IGF-1) is positively associated with the risk for both breast cancer
in women and prostate cancer in men. It is also known that circulating IGF-1
concentrations can change in response to nutritional changes including energy
and protein restriction, and some studies suggest that, even within
well-nourished western populations, men and women with relatively high intakes
of protein from dairy products have higher blood levels of IGF-1. These
observations have led to the hypothesis that high intakes of protein from dairy
products might increase the risk for some cancers by increasing the endogenous
production of IGF-1. Further evaluation of this hypothesis requires clinical
nutritional studies of the effects of diet on IGF-1 metabolism, and large
epidemiological studies of cancer risk incorporating reliable measures of diet
and serum IGF-1 concentrations.
Session 3: Influences of food constituents on gut health
Symposium on ‘Nutrition: getting the balance right in 2010’
Plant-based diets contain a plethora of secondary metabolites that may impact on health and disease prevention. Much attention has been focused on the potential bioactivity and nutritional relevance of several classes of phytochemicals such as flavonoids, carotenoids, phyto-oestrogens and glucosinolates. Less attention has been paid to simple phenolic acids that are widely found in fruit, vegetables, herbs, spices and beverages. Daily intakes may exceed 100 mg. In addition, bacteria in the gut can perform reactions that transform more complex plant phenolics such as anthocyanins, procyanidins, flavanones, flavonols, tannins and isoflavones into simple phenolic metabolites. The colon is thus a rich source of potentially active phenolic acids that may impact both locally and systemically on gut health. Both the small and large intestine (colon) contain absorption sites for phenolic acids but low post-prandial concentrations in plasma indicate minimal absorption early in the gastrointestinal tract and/or rapid hepatic metabolism and excretion. Therefore, any bioactivity that contributes to gut health may predominantly occur in the colon. Several phenolic acids affect the expression and activity of enzymes involved in the production of inflammatory mediators of pathways thought to be important in the development of gut disorders including colon cancer. However, at present, we remain largely ignorant as to which of these compounds are beneficial to gut health. Until we can elucidate which pro-inflammatory and potentially carcinogenetic changes in gene expression can be moderated by simple phenolic acids, it is not possible to recommend specific plant-based foods rich in particular phenolics to optimise gut health.