The political debate in Britain over the withdrawal of universal winter fuel payments to pensioners reminded us of research conducted in the 1980s on thermoregulation, the factors which affect it, and the consequences of any impairments in the mechanisms involved. Admission rates of older adult patients with fractured femur rose as ambient temperature fell, with that of severely malnourished patients rising by 300 % and of normally nourished ones by only 30 %. The severely malnourished had a reduction in core temperature of ≥1 °C, whereas the well-nourished maintained normothermia. The studies also suggested that there was a causal link between undernutrition, mild hypothermia and accidents which might be due to more than just a lack of insulating fat. Whereas the well-nourished had a normal response to a cooling stimulus, i.e. a 10 % increase in metabolic rate, sufficient to maintain core temperature, this response was lost in the malnourished group. Annually, there are about 9 cold deaths for every 1 heat death. Similar thermoregulatory problems have faced polar explorers as they suffer hypothermia and physical incapacity due to malnutrition consequent on high energy expenditure and negative energy balance. The physiology of thermoregulation, its relationship to nutritional state and the consequences of any impairment in function are the same in older adults and fit polar explorers. Hence, there are sound medical as well as humanitarian reasons for ensuring that older adults are kept warm and well fed in winter.

Albumin is a relatively small molecule with a radius of 7.5 nm and a molecular weight of 65 kDa. It is the most abundant protein in plasma, accounting for 60-75% of its oncotic pressure. Its concentration in plasma is merely one static measurement reflecting a dynamic and complex system of albumin physiology, and is the net result of several different processes, one or more of which may become deranged by disease or its treatment. It is also unsurprising that hypoalbuminaemia has proved to be an indicator of morbidity and mortality risk since the underlying conditions which cause it, including protein energy malnutrition, crystalloid overload, inflammation, and liver dysfunction are themselves risk factors. In some cases, its underlying cause may require treatment but mostly it is just a parameter to be monitored and used as one measure of clinical progress or deterioration. While malnutrition, associated with a low protein intake, may be a contributory cause of hypoalbuminaemia, in the absence of inflammation and/or dilution with crystalloid its development in response to malnutrition alone is slow compared with the rapid change caused by inflammatory redistribution or dilution with crystalloids. Other significant causes include liver dysfunction and serous losses. These causal factors may occur singly or in combination in any particular case. Treatment is that of the underlying causes and associated conditions such as a low plasma volume, not of hypoalbuminaemia per se. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

“The absence of evidence is not evidence of absence”, is an aphorism attributed to Carl Sagan [[1]Sagan C. The demon-haunted world: science as a candle in the dark. Ballantine, New York1997Google Scholar], which is invoked when claims of the existence of God are encountered. Nonetheless, it is a succinct and elegant statement, which in this instance is simultaneously beautiful and wrong. At first glance, the lack of evidence is not evidence of absence, would suggest that for every treatment: medical, nutritional, or alternative therapy unless science has exhausted every mechanistic process available we cannot state it does not work even after randomised, double-blind studies, or as is the case here, multiple systematic reviews, none of which have found survival benefit. However, our recent study [[2]Adiamah A. Rollins K.E. Kapeleris A. Welch N.T. Iftikhar S.Y. Allison S.P. et al.Postoperative arginine-enriched immune modulating nutrition: long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.Clin Nutr. 2021; 40: 5482-5485Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar], that Dr. Eckert has shown interest in and has commented on, does not fit into this logical argument. Immune modulating nutrition has been studied for over 30 years now, in medicine, surgery and in critical care. We have over the years gained better understanding of how it works, and perhaps when best to administer it. Over the years, several studies have been performed on immune modulating nutrition and several meta-analyses have been generated from these. The utility of the latter is in allowing us to pool data from several studies to answer questions when perhaps individual studies might not have had power to do so. Our own recent meta-analysis on 1387 patients [[3]Adiamah A. Skorepa P. Weimann A. Lobo D.N. The impact of preoperative immune modulating nutrition on outcomes in patients undergoing surgery for gastrointestinal cancer: a systematic review and meta-analysis.Ann Surg. 2019; 270: 247-256Crossref PubMed Scopus (132) Google Scholar] showed that immune modulating nutrition given at least 5-days, but preferably 7-days, prior to surgery for gastrointestinal cancer was beneficial in reducing infective complications but not mortality. Similarly, Probst et al. [[4]Probst P. Ohmann S. Klaiber U. Huttner F.J. Billeter A.T. Ulrich A. et al.Meta-analysis of immunonutrition in major abdominal surgery.Br J Surg. 2017; 104: 1594-1608Crossref PubMed Scopus (76) Google Scholar] studied the use of immune modulating nutrition in 83 randomised controlled trials that included 7116 participants and found no survival benefit. All of these studies, however, were reporting short-term mortality. As detailed in our paper [[2]Adiamah A. Rollins K.E. Kapeleris A. Welch N.T. Iftikhar S.Y. Allison S.P. et al.Postoperative arginine-enriched immune modulating nutrition: long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.Clin Nutr. 2021; 40: 5482-5485Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar], there are now studies which suggest potential long-term survival benefit, which prompted the assessment of long-term survival in our cohort, showing no benefit. We agree that the confidence intervals are wide, but as described by Sackett et al. [[5]Sackett D.L. Why randomized controlled trials fail but needn't: 2. Failure to employ physiological statistics, or the only formula a clinician-trialist is ever likely to need (or understand!).CMAJ (Can Med Assoc J). 2001; 165: 1226-1237PubMed Google Scholar], to improve the precision around this estimate, would require a quadrupling of the study participants.Confidence=SignalNoise×Samplesize The noise (or uncertainty) in a randomised controlled trial is the sum of all the factors (“sources of variation”) that can affect the absolute risk reduction or absolute difference. In this case, compliance with the intervention, the exact tumour type, additional therapies that patients might have had such as neoadjuvant and adjuvant therapy might have all influenced the noise. As our study [[2]Adiamah A. Rollins K.E. Kapeleris A. Welch N.T. Iftikhar S.Y. Allison S.P. et al.Postoperative arginine-enriched immune modulating nutrition: long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.Clin Nutr. 2021; 40: 5482-5485Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar] was a follow-up of a previous study [[6]Lobo D.N. Williams R.N. Welch N.T. Aloysius M.M. Nunes Q.M. Padmanabhan J. et al.Early postoperative jejunostomy feeding with an immune modulating diet in patients undergoing resectional surgery for upper gastrointestinal cancer: a prospective, randomized, controlled, double-blind study.Clin Nutr. 2006; 25: 716-726Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar], it was both impossible and impractical to quadruple the sample size at this stage, to improve the precision of the estimate. Therefore, if we cannot employ an increase in the sample size to reduce the signal-to-noise ratio, we have to rely on biological plausibility. Immune modulating nutrition, given for 10–15 days postoperatively is always going to be hard to justify as a mechanism of improving long-term survival in patients with gastrointestinal cancer, and we would suggest that this should not be the intention of using immune modulating nutrition. That is not to say, we do not think it could improve survival. Infectious complications after gastrointestinal cancer surgery can cause delays to chemotherapy, radiotherapy and other adjuvant treatments which might have improved overall survival. In critical care, Bear et al. [[7]Bear D.E. Puthucheary Z.A. Designing nutrition-based interventional trials for the future: addressing the known knowns.Crit Care. 2019; 23: 53Crossref PubMed Scopus (9) Google Scholar] suggest that mortality should not be used as the primary indicator in nutrition trials. They state: “the biological plausibility that small alterations in protein/energy delivery or changes in the timing or mode of nutrition delivery will result in detectable changes in mortality is low.” They continue, “Our patients are subjected to many other potential threats to mortality, independent of nutrition. For this reason, discussions around more appropriate outcomes to measure..” need to be had. Finally, Dr. Eckert also incorrectly interpreted our conclusions. They read as follows [[2]Adiamah A. Rollins K.E. Kapeleris A. Welch N.T. Iftikhar S.Y. Allison S.P. et al.Postoperative arginine-enriched immune modulating nutrition: long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.Clin Nutr. 2021; 40: 5482-5485Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar]:“Despite, and perhaps because of all these possible shortcomings of our study and those of others, there is currently very little evidence upon which to base a recommendation that, in patients undergoing major surgery for cancer, feeds containing extra immune modulating nutrients have any benefit in terms of mortality, either in the short-term or long-term, over standard feeds aimed at treating or preventing malnutrition and its consequences.” In this conclusion, we do not argue against immune modulating nutrition in the perioperative setting. However, based on biological plausibility, evidence from meta-analyses, and our findings of no mortality difference (with complete follow-up), we feel that we do not have any evidence at this point to justify the use of immune modulating nutrition solely for long-term survival benefit. Indeed, if any benefit existed (which could not be demonstrated in studies that have pooled data from over 7000 patients), then it would be so negligible as to not be clinically relevant. No external funding.

BACKGROUND & AIMS:Immune modulating nutrition (IMN) has been shown to reduce postoperative infectious complications and length of stay in patients with gastrointestinal cancer. Two studies of IMN in patients undergoing surgery for head and neck cancer also suggested that this treatment might improve long-term survival and progression-free survival. In the present study, we analysed follow-up data from our previous randomised controlled trial of IMN, in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer, in order to evaluate the long-term impact on survival of postoperative IMN versus an isocaloric, isonitrogenous control feed. METHODS:This study included patients undergoing surgery for cancers of the pancreas, oesophagus and stomach, who had been randomised in a double-blind manner to receive postoperative jejunostomy feeding with IMN (Stresson, Nutricia Ltd.) or an isonitrogenous, isocaloric feed (Nutrison High Protein, Nutricia) for 10-15 days. The primary outcome was long-term overall survival. RESULTS:There was complete follow-up for all 108 patients, with 54 patients randomised to each group. There were no statistically significant differences between groups by demographics [(age, p = 0.63), sex (p = 0.49) or site of cancer (p = 0.25)]. 30-day mortality was 11.1% in both groups. Mortality in the intervention group was 13%, 31.5%, 70.4%, 85.2%, 88.9%, and 96.3% at 90 days, and 1, 5, 10, 15 and 20 years respectively. Corresponding mortality in the control group was 14.8%, 35.2%, 68.6%, 79.6%, 85.2% and 98.1% (p > 0.05 for all comparisons). CONCLUSION:Early postoperative feeding with arginine-enriched IMN had no impact on long-term survival in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer.

Many theories have been advanced concerning the cause of Charlotte Brontë's death, none of which fully explain all the symptoms she experienced in the course of her final illness. Her death certificate records the cause of death as phthisis (tuberculosis), but there is no evidence, other than circumstantial, to support this diagnosis. A diagnosis of Addison's disease, caused by tuberculosis of the adrenals, has been proposed, but this is unlikely, since it does not fit well with two and a half months of severe anorexia, nausea and vomiting, followed by remission of these symptoms and eventual death. We agree, as suggested by some authors, that the most likely diagnosis was hyperemesis gravidarum, but suggest that this was complicated by the refeeding syndrome consequent on recovery of her appetite after resolution of hyperemesis gravidarum and that this was the cause of her death. These two diagnoses are compatible with the remission in her symptoms of anorexia, nausea and vomiting in the third week of March 1855, followed by further decline and death.

Surgery involves a deliberate injury to the body inflicted for the overall benefit of the patient. The surgical insult results in several responses that cause a change in metabolism towards catabolism. Recovery from surgery requires a reversal of the trauma-induced catabolism towards anabolism. There are many ways by which the catabolic responses can be minimized and anabolism supported. Nutrition, the supply of energy and protein, represents an essential part of the perioperative treatment. It is important to understand that for the majority of patients undergoing surgery, the nutritional treatment stimulates faster recovery. Most of these patients can eat and should be given oral food. The target of nutritional treatment should be to optimise fluid intake and ensure sufficient energy and protein intake orally. A much smaller group of surgical patients are malnourished. These patients have a higher risk of mortality, complications, pro- longed hospital stay and delayed rehabilitation and convalescence. Although some early studies of perioperative nutritional support were conflicting, over the last twenty years a succession of studies have begun to define those groups of patients who benefit, particularly those with prior malnutrition. Because of the risks associated with malnutrition and surgery, all patients about to undergo surgery should be screened and assessed for nutritional status. Those with malnutrition should be considered for perioperative nutritional support. It is useful to consider the problem in three phases pre-, per- and postoperative.

Objective: To study the changes in blood volume and hormones controlling sodium and water homeostasis after infusions of 0.9% saline, Gelofusine (4% succinylated gelatin in 0.7% saline, weight-average molecular weight 30 kD), and Voluven (6% hydroxyethyl starch in 0.9% saline, weight-average molecular weight 130 kD) in healthy volunteers. Design: Randomized, three-way crossover study. Setting: University teaching hospital. Subjects: Ten healthy adult male volunteers. Interventions: Volunteers received 1-L infusions of 0.9% saline, Gelofusine, and Voluven over 1 hr on three occasions. Body weight, hematocrit, serum biochemistry, and plasma concentrations of vasopressin, aldosterone, brain natriuretic peptide, and total renin were measured before infusion and hourly thereafter for 6 hrs. Changes in body water, blood volume, and extravascular fluid volume were calculated. Measurements and Main Results: Although changes in body weight (total body water) after the infusions were similar, blood volume expansion by the two colloids was significantly greater than that produced by 0.9% saline (p < .01). At the end of infusions, 68%, 21%, and 16% of the infused volumes of 0.9% saline, Gelofusine, and Voluven, respectively, had escaped from the intravascular space to the extravascular space. Over the 6 hrs, the magnitude and duration of blood volume expansion by the two colloids were similar (p = .70). There were no significant differences in urinary volume, osmolality, and sodium content after the three infusions. Hormonal changes were similar after the three infusions, with the increase in natriuretic peptide being transient. The reduction in aldosterone and total renin concentrations was more sustained. Conclusions: The effects of Gelofusine and Voluven were similar despite the 100 kD difference in weight-average molecular weight. Excretion of an acute fluid load containing sodium and chloride may be dependent on a sustained suppression of the renin-angiotensin-aldosterone system rather than on natriuretic peptides.

Starting in October 2006 the Association of Surgeons of Great Britain and Ireland, the Society of Academic and Research Surgery, BAPEN Medical, the Intensive Care Society, the Association for Clinical Biochemistry and the Renal Association, nominated core members of a steering committee who came together to establish consensus for good peri-operative fluid prescribing. Concern arose regarding a high incidence of postoperative sodium and water overload, and evidence to suggest that preventing or treating this, by more accurate fluid therapy, would improve outcome. The following recommendations (28 in total) are extracted from the complete document which can be found on the ICS website ( http://www.ics.ac.uk/downloads/2008112340_GIFTASUP%20FINAL_31-10-08.pdf ). Members of the steering committee used the definitions of the Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001) accessed from http://www.cebm.net/index.aspx?o=1025 to assign levels of evidence, each of which, after debate, was accepted unanimously. However, debate is on-going and you are encouraged to have your say. Please communicate your thoughts on this published summary to the editor of JICS who will seek response from the authors.

You need to develop a system, which suits your needs and circumstances, and to train your team so that monitoring is undertaken and recorded on a regular and systematic basis, so that each member of the team understands the purpose of this process and is able to participate in the interpretation of the recorded data. Use serial data forms, either paper or electronic, and place these on the patient’s door or at the bottom of the bed, so that any member of the team can see not only the current data, but the previous data in a serial manner, so that any change can be perceived immediately and appropriate action taken. This saves an enormous amount of time sorting through notes or a disorganised collection of data arranged in no proper order. The team soon get used to such a system and learn to respond quickly when adverse trends are observed, e.g. rapid fall in Kþ and PO 4 in refeeding syndrome. Such a system coordinates clinical, nutritional and laboratory measurements, allowing observation of changing patterns, thereby assisting interpretation.

Water and electrolytes are essential components of the ‘‘milieu interieur’’ of the body, creating an environment which surrounds nearly all cells and through which the metabolites and gases pass to and fro. They are also major intracellular components, being 75% of muscle cells but less than 5% of fat cells. The electrolyte gradient across cell membranes is a prerequisite for cell excitability, signal conduction, transport processes and cell movement.

Background & aims: We aimed to trace the historical origins of 0.9% saline, how it came to be used so commonly today, and to consider whether its continued use can be justified.Methods: We searched the Medline, Science Citation Index, ScienceDirect and Google (TM) databases using the key words saline, physiological, salt solution, sodium chloride, 0.9%, intravenous, injection, fluid, cholera, resuscitation, parenteral, history, historical and origins.Results: The use of 0.9% saline is believed to have originated during the cholera pandemic that swept across Europe in 1831. However, an examination of the composition of the fluids used by the pioneering physicians of that era reveals solutions that bear no resemblance to 0.9% or so-called 'normal' saline which appears to have very little scientific or historical basis for its routine use, except for Hamburger's in vitro studies of red cell lysis.Conclusions: The currently used 0.9% saline solution is without convincing historical basis. Given that the composition of 0.9% sodium chloride is dissimilar to most solutions used in the past, and is in no way 'normal' or 'physiological', our current practice may be based on historical fallacy and misconception. (c) 2008 Elsevier Ltd and European Society for Clinical, Nutrition and Metabolism. All. rights reserved.

European Society for Clinical Nutr glycogen stores and re-esterification of triglycerides see Figs. 1 and 2). Reaction to fasting is dependent on energy reserves, duration of starvation and any additional stressful influences. Long-term partial or total cessation of energy intake leads to marasmic wasting. Although very obese individuals have been described as surviving fasting for periods of up to a year, those of normal initial body composition rarely survive more than three months’ starvation, 40% body weight loss or a BMI less than 10 in women or 11 in man.

BACKGROUND & AIMS:We aimed to determine if a structured workshop on fluid and electrolyte balance for junior surgical trainees led to an improvement in knowledge on the subject and to evaluate the perceived helpfulness of such a workshop.METHODS:Surgical trainees attended an interactive lecture-based workshop on fluid and electrolyte balance. Participants had online access to the presentation prior to the training event. They completed a multiple choice question (MCQ) test, derived from topics covered in the presentation, prior to the lecture. The MCQ test was repeated after the lecture to assess retention and application of knowledge. Participants were unaware that they would be tested and provided written feedback on their perceptions of the session.RESULTS:Thirty-seven trainees from speciality training years 1 and 2 participated in the workshop. There was a significant improvement in mean test scores after the lecture when compared with pre-lecture scores (24.6/30 vs. 19.7/30, p<0.001). Trainees felt the topic and event were relevant to everyday practice (mean score 4.9/5) and that it would improve their clinical skills (4.5/5).CONCLUSIONS:The provision of a dedicated fluid and electrolyte physiology interactive workshop to postgraduate trainees is a successful way of tackling current inadequacies in training.

To know water and electrolyte requirements in patients receiving artificial nutrition.-To know electrolyte content in commercial enteral diets.-To be aware of the changes in water and electrolyte requirements during nutritional support.

Background Et Aims: Starvation and weight toss are common accompaniments of severe illness. The functional consequences of such malnutrition include not only physical changes but also psychological changes such as depression, anxiety, irritability, apathy, poor steep pattern and loss of concentration. We carried out a pilot observational. study in 22 undernourished patients at the time of referral to the nutritional team and after 8 days of nutritional support, using the Profile of Mood States Score (POMS) questionnaire to determine whether measurable and clinically significant changes in mood occurred with treatment.Methods: Twenty-two undernourished patients with gastrointestinal disease were studied during the first week of treatment by the nutrition team. Psychological assessment was performed using a structured and standardised questionnaire assessing mood states (tension, depression, anger, vigour, fatigue, confusion). The questionnaire was administered to the patients by the same interviewer on days 1 (start of treatment by the nutrition team) and 8.Results: Median (IQR) scores for tension, depression, anger, vigour, fatigue and confusion were 21.5 (11.5), 29.0 (15.8), 15.0 (11.8), 6.0 (7.5), 20.0 (8.5) and 12.0 (7.0) respectively on day 1. Corresponding scores on day 8 were 4.0 (8.8), 3.5 (6.0), 1.0 (1.8), 20.0 (7.5), 10.0 (8.8) and 2.5 (6.8). The improvement in scores seen on day 8 was statistically significant (P<0.01).Conclusion: Nutritional status and treatment have important effects on the psychology of patients and formal measurements of psychological function will form an important part of nutritional assessment and monitoring in the future. (c) 2007 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Fasting, anaesthesia and surgery affect the body's physiological capacity not only to control its external fluid and electrolyte balance but also the internal balance between the various body fluid compartments. Conversely, abnormalities of fluid and electrolyte balance may adversely affect organ function and surgical outcome. Perioperative fluid therapy has a direct bearing on outcome, and prescriptions should be tailored to the needs of the patient. The goal of fluid therapy in the elective setting is to maintain the effective circulatory volume while avoiding interstitial fluid overload whenever possible. Weight gain in elective surgical patients should be minimized in an attempt to achieve a ‘zero fluid balance status’. On the other hand, these patients should arrive in the anaesthetic room in a state of normal fluid and electrolyte balance so as to avoid the need to resuscitate fluid-depleted patients in the anaesthetic room or after the induction of anaesthesia. Optimal fluid delivery should be part of an overall care package that involves minimization of the period of preoperative fasting, preoperative carbohydrate loading, thoracic epidural analgesia, avoidance of nasogastric tubes, early mobilization, and early return to oral feeding, as exemplified by the enhanced recovery after surgery programme.

Objective. Activated neutrophils have been implicated as effectors of tissue injury and end-organ damage in adult respiratory distress syndrome and multi-organ dysfunction syndrome. Recent research has shown that hypertonic saline may abrogate neutrophil activation and in turn attenuate end-organ damage, while lactated Ringer's solution causes neutrophil activation. There has been little research investigating the effects of iso-osmolar solutions such as 0.9% saline on neutrophil activation. The aim of this study was to determine the effect of an infusion of 0.9% saline on the activation of human neutrophils in healthy volunteers. Material and methods. A 2-l bolus infusion of 0.9% saline was administered to eight healthy volunteers over a 1-h period after an overnight fast. Venous blood samples were taken on three occasions: pre-infusion (time 0), on completion of the infusion (time 1) and 1 h later (time 2). Neutrophil activation was quantified by flow cytometric analysis of CD11b expression. Submaximal and maximal stimulation of neutrophils were achieved using different concentrations of N-formyl-methionyl-leucyl-phenylalanine. Results. Median (interquartile range) baseline neutrophil activation (median fluorescence intensity of CD11b expression) at times 0, 1 and 2 was 178 (162–237), 180 (152–350) and 175 (129–212), respectively. Corresponding values for submaximal stimulation were 620 (412–921), 711 (342–972) and 586 (364–924), and those for maximal stimulation were 2410 (1913–2846), 2410 (1968–2945) and 2455 (1823–2645). The differences at each time point were not significant for any of the parameters. Conclusion. Infusion of 0.9% saline does not confer the potentially beneficial effects of the inhibition of neutrophil activation witnessed with hypertonic saline in other studies.