Exaggerated postprandial GLP-1 secretion following esophagectomy is not associated with gastric emptying and intestinal transit.

Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1 year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT). Serial plasma samples were collected before, and for 300 minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1 year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.

Temporal changes in bile acid levels and 12α-hydroxylation after Roux-en-Y gastric bypass surgery in type 2 diabetes.

Since the publication of the above article it has been noted that the author S O'Brien should have been listed as CS O'Brien. The authors should therefore appear as follows: R Dutia, M Embrey, CS O'Brien, RA Haeusler, KK Agénor, P Homel, J McGinty, RP Vincent, J Alaghband-Zadeh, B Staels, CW le Roux, J Yu and B Laferrère The corrected article html and online pdf versions have been amended. The authors wish to apologise for any inconvenience caused.

Analysis of cerebrospinal fluid for xanthochromia versus modern computed tomography scanners in the diagnosis of subarachnoid haemorrhage: experience at a tertiary trauma referral centre.

BACKGROUND: Diagnosis of subarachnoid haemorrhage, a neurosurgical emergency in patients with headache remains a logistical challenge. The rationale of the traditional pathway of cerebrospinal fluid xanthochromia analysis following negative computed tomography head scans to exclude subarachnoid haemorrhage has been challenged by the increasing accuracy of modern computed tomography scanners. AIM: We set out to establish whether our xanthochromia service was adding value to the diagnostic pathway for subarachnoid haemorrhage or whether it was acting merely as a supportive test. METHOD: A retrospective audit of all cerebrospinal fluid requests received since the inception of Xanthochromia service at a tertiary trauma centre. Cases interpreted as being consistent with subarachnoid haemorrhage based on cerebrospinal fluid xanthochromia analysis were selected for in-depth review from the total number of cases. RESULTS: In total 660 requests were received for cerebrospinal fluid xanthochromia between August 2009 and July 2012. A total 28 of these were interpreted as being consistent with subarachnoid haemorrhage. Only 18 (64.3%) of requests were deemed appropriate as the clinical presentation in the remaining 10 (35.7%) was strongly suggestive of other causes of headache. A final clinical diagnosis of subarachnoid haemorrhage was made in 11 of the 18 patients who had cerebrospinal fluid xanthochromia requested appropriately. From these 11, five (45%) were deemed initially computed tomography negative and cerebrospinal fluid analysis led to final correct diagnosis of subarachnoid haemorrhage and appropriate surgical management. CONCLUSION: Despite improved computed tomography scanning technology, cerebrospinal fluid xanthochromia interpretation aids in the definitive diagnosis of subarachnoid haemorrhage. When requested appropriately cerebrospinal fluid xanthochromia analysis remains a vital service as results impact on clinical decision making, especially when computed tomography scan results are equivocal and is also important in later presenting patients when computed tomography accuracy decreases.

Systematic review: bile acids and intestinal inflammation-luminal aggressors or regulators of mucosal defence?

BACKGROUND: Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis (UC), are chronic conditions attributed to an aberrant immune response to luminal triggers. Recently, published work suggests a pathogenic role for bile acids in this context. AIM: To perform a systematic review of studies investigating the role of bile acids in intestinal inflammation and present potentially relevant clinical implications. METHODS: Pubmed search for English language articles published up to May 2015. Terms used were: 'bile', 'bile acid', 'barrier', 'small bowel injury', 'Crohn's' and 'colitis'. RESULTS: Experimental studies support a variable role for bile acids in intestinal barrier homoeostasis. This may be attributed to different physicochemical properties, variable effects on epithelia and immune cells via bile acids-specific receptors, or through a cross-talk with the gut microbiome. A reduction in the bile acids pool, with lower concentrations of secondary forms, has been recognised for some time in Crohn's disease and associated to ileal dysfunction and bile acids malabsorption. Recent work suggests that these changes, including an increase in sulphated forms, are related to inflammatory activity in both Crohn's disease and UC. The detrimental effects of 'western diet' elements such as emulsifiers and fat, which have been implicated in the development of the current IBD and obesity epidemics, may also be bile acid-mediated. CONCLUSIONS: Although there are only a few observational clinical studies to support an interaction, in vivo human and animal studies support an association between bile acids metabolism, the gut microbiome and intestinal inflammation. This may well prove to have significant diagnostic and therapeutic implications.

Temporal changes in bile acid levels and 12α-hydroxylation after Roux-en-Y gastric bypass surgery in type 2 diabetes.

INTRODUCTION: Gastric bypass surgery (GBP) leads to sustained weight loss and significant improvement in type 2 diabetes (T2DM). Bile acids (BAs), signaling molecules which influence glucose metabolism, are a potential mediator for the improvement in T2DM after GBP. This study sought to investigate the effect of GBP on BA levels and composition in individuals with T2DM. METHODS: Plasma BA levels and composition and fibroblast growth factor (FGF)-19 levels were measured during fasting and in response to an oral glucose load before and at 1 month and 2 years post GBP in 13 severely obese women with T2DM. RESULTS: A striking temporal change in BA levels and composition was observed after GBP. During the fasted state, BA concentrations were generally reduced at 1 month, but increased 2 years post GBP. Postprandial BA levels were unchanged 1 month post GBP, but an exaggerated postprandial peak was observed 2 years after the surgery. A significant increase in the 12α-hydroxylated/non12α-hydroxylated BA ratio during fasting and postprandially at 2 years, but not 1 month, post GBP was observed. Significant correlations between BAs vs FGF-19, body weight, the incretin effect and peptide YY (PYY) were also found. CONCLUSIONS: This study provides evidence that GBP temporally modifies the concentration and composition of circulating BAs in individuals with T2DM, and suggests that BAs may be linked to the improvement in T2DM after GBP.

Bone mineral density and expression of vitamin D receptor-dependent calcium uptake mechanisms in the proximal small intestine after bariatric surgery.

BACKGROUND: Roux-en-Y gastric bypass may lead to impaired calcium uptake. Therefore, operation-specific effects of gastric bypass and vertical banded gastroplasty on bone mineral density (BMD) were examined in a randomized clinical trial. Bone resorption markers and mechanisms of decreased calcium uptake after gastric bypass were investigated using blood and endoscopic samples from two additional patient cohorts. METHODS: Total BMD and non-weight-bearing skull BMD were measured by dual-energy X-ray absorptiometry at baseline, and 1 and 6 years after gastric bypass or vertical banded gastroplasty in patients who were not receiving calcium supplements. Bone resorption markers in serum and calcium uptake mechanisms in jejunal mucosa biopsies were analysed after gastric bypass by proteomics including radioimmunoassay, gel electrophoresis and mass spectrometry. RESULTS: One year after surgery, weight loss was similar after gastric bypass and vertical banded gastroplasty. There was a moderate decrease in skull BMD after gastric bypass, but not after vertical banded gastroplasty (P < 0·001). Between 1 and 6 years after gastric bypass, skull BMD and total BMD continued to decrease (P = 0·001). C-terminal telopeptide levels in serum had increased twofold by 18 months after gastric bypass. Proteomic analysis of the jejunal mucosa revealed decreased levels of heat-shock protein 90ß, a co-activator of the vitamin D receptor, after gastric bypass. Despite increased vitamin D receptor levels, expression of the vitamin D receptor-regulated calcium transporter protein TRPV6 decreased. CONCLUSION: BMD decreases independently of weight after gastric bypass. Bone loss might be attributed to impaired calcium absorption caused by decreased activation of vitamin D-dependent calcium absorption mechanisms mediated by heat-shock protein 90ß and TRPV6.

An association between post-meal bile acid response and bone resorption in normal subjects.

BACKGROUND: The mechanism surrounding bone suppression after a meal may involve several mediators, but is yet to be clarified. Bile acids (BA) function as signalling molecules in response to feeding, and may be directly involved in bone suppression acutely after a meal. The aim of this study was to test the hypothesis that BA are involved in the acute bone suppression observed after a meal. METHODS: A prospective study in which samples collected from volunteers fed a 400 Kcal test meal after an overnight fast were analysed for parathyroid hormone (PTH), BA, and carboxyterminal of type 1 collagen telopeptide (CTX). The study was carried out in 10 healthy male volunteers. Ethical approval was obtained from the Local Research and Ethics Committee at King's College Hospital. RESULTS: Total BA, glycine conjugated bile acids (GCBA), PTH and CTX showed a response to meal ingestion. There was a negative correlation between percentage change in PTH and CTX (R (2 )= -0.82, P = 0.004), and between PTH and GCBA (R (2 )= -0.39, P = 0.005). CONCLUSION: This study demonstrated an association between GCBA and PTH suppression after a meal. The drop in PTH concentration after a meal may be responsible for the suppression of bone resorption as observed by the decrease in CTX concentration.

Improved blood pressure, nitric oxide and asymmetric dimethylarginine are independent after bariatric surgery.

BACKGROUND: Obesity is associated with hypertension, but the exact mechanism is not fully understood. Bariatric surgery significantly decreases weight and blood pressure (BP). Low plasma nitric oxide (NO) and raised asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO, concentrations are associated with both obesity and hypertension. Correlations between the changes in these parameters were studied after bariatric surgery. METHODS: Weight, BP, plasma ADMA and NO were measured in 29 obese patients (24 female, 5 male) before and six weeks after bariatric surgery. RESULTS: Patients were 39.2 ± 1.2 (mean ± SEM) years old and weighed 126 ± 3 kg. Six weeks after the surgery, patients had lost 10 ± 0.7 kg (P < 0.0001) and mean arterial pressure (MAP) decreased by 11 ± 1.0 mmHg (P < 0.0001). The plasma ADMA concentration decreased by 24 ± 2% from 5 ± 0.4 to 4.0 ± 0.3 µmol/L (P < 0.0001). The plasma total nitrite concentration increased by 15 ± 1% from 51.4 ± 2.6 to 60 ± 3 µmol/L (P < 0.0001). The correlation between the decrease of ADMA and increase of NO subsequent to weight loss was significant (P < 0.0001). However, MAP was not correlated to the changes in ADMA or NO. CONCLUSIONS: After bariatric surgery, beneficial changes in BP, NO and ADMA occur, but our findings suggest that these BP changes are independent of changes in the NO-ADMA axis. Other causes for the changes in BP should therefore be considered.

Influence of adherence to the national guidance on nutrition screening and dietitian referral on clinical outcomes of those requiring parenteral nutrition.

BACKGROUND: National guidance in the UK on nutrition support suggests that all patients should be screened on initial admission to hospital and, where appropriate, be referred to a healthcare professional. The present study aimed to investigate whether initial nutrition screening influenced the outcome of patients who received parenteral nutrition (PN). METHODS: Data were prospectively evaluated on 100 consecutive patients referred to the multidisciplinary PN team in a teaching hospital. Information was obtained from medical notes, electronic patient records, completed PN prescription charts, dietetic record cards and nursing care plans. Patients who were treatable by nutritional supplements or enteral nutrition were not included. Patients were divided into two groups: guidance compliant and guidance noncompliant, in order to compare outcome measures such as the duration of PN treatment, total number of PN bags used per patient and length of hospital stay. Comparison of data between the two groups was carried out using either the independent samples t-test or the Mann-Whitney U-test. RESULTS: There was no difference in outcome measures between the guidance compliant and noncompliant groups. Patients in the guidance noncompliant group were more likely to be in general (77%) than critical wards (23%). Patients who were in the guidance compliant group received nutrition support earlier. CONCLUSIONS: Compliance with the national guidance in the UK on screening did not improve outcomes in patients requiring parenteral nutrition in this cohort. Initial nutrition screening prior to PN administration warrants further investigation to ensure value is added to patient care.

The satiety hormone peptide YY as a regulator of appetite.

Obesity is a major cause of premature death in the UK, and may contribute to as many as 30 000 deaths a year in the UK. Although effective treatment for obesity is still awaited, many developments have occurred to improve our understanding of neuroendocrine regulation of food intake and weight gain, especially regarding the role of gut hormones. One such gut hormone is peptide tyrosine-tyrosine also known as PYY where Y depicts the abbreviation for tyrosine. PYY is a 36 amino acid hormone, first isolated from porcine intestine. PYY, along with few other gut hormones, has been suggested as a potential therapeutic agent for obesity. This review examines the relationship of PYY to appetite regulation, energy homeostasis and the relevant neuroendocrine feedback mechanism.

Changes in gut hormones after bariatric surgery.

Bariatric surgery is one of the most effective treatments for achieving long-term weight loss in morbidly obese patients. Bariatric surgery causes weight loss through substantial decline of hunger and increased satiety. Recently our understanding of neuroendocrine regulation of food intake and weight gain, especially regarding the role of gut hormones, has significantly increased. The changes in these hormones following bariatric surgery can partly explain the mechanism behind weight loss achieved through these procedures. In this paper, we review the effect bariatric procedures have on different gut hormone levels and how they in turn can alter the complex neuroendocrine regulation of energy homeostasis.

New agents in development for the management of obesity.

Obesity is fast becoming the major cause of premature death in the developed world. The rising prevalence of obesity and obesity-related comorbidities also elevates healthcare costs, and reduced quality of life. The National Institute of Clinical Excellence in the UK recommends pharmacotherapy, in conjunction with lifestyle modification, for obese individuals [i.e. body mass index (BMI) of 30 kg/m(2)] and for overweight persons with a BMI greater than 27 kg/m(2), accompanied by at least one comorbidity. However, the current pharmaceutical treatment available to combat this epidemic remains limited. We review the efficacy and pharmacology of the anti-obesity agents currently used in clinical practice as well as some of the potential agents in phase II and III trials.

Attenuated peptide YY release in obese subjects is associated with reduced satiety.

The responses of the gut hormone peptide YY (PYY) to food were investigated in 20 normal-weight and 20 obese humans in response to six test meals of varying calorie content. Human volunteers had a graded rise in plasma PYY (R2 = 0.96; P < 0.001) during increasing calorific meals, but the obese subjects had a lower endogenous PYY response at each meal size (P < 0.05 at all levels). The ratio of plasma PYY(1-36) to PYY(3-36) was similar in normal-weight and obese subjects. The effect on food intake and satiety of graded doses of exogenous PYY(3-36) was also evaluated in 12 human volunteers. Stepwise increasing doses of exogenous PYY(3-36) in humans caused a graded reduction in food intake (R2 = 0.38; P < 0.001). In high-fat-fed (HF) mice that became obese and low-fat-fed mice that remained normal weight, we measured plasma PYY, tissue PYY, and PYY mRNA levels and assessed the effect of exogenous administered PYY(3-36) on food intake in HF mice. HF mice remained sensitive to the anorectic effects of exogenous ip PYY(3-36). Compared with low-fat-fed fed mice, the HF mice had lower endogenous plasma PYY and higher tissue PYY but similar PYY mRNA levels, suggesting a possible reduction of PYY release. Thus, fasting and postprandial endogenous plasma PYY levels were attenuated in obese humans and rodents. The PYY(3-36) infusion study showed that the degree of plasma PYY reduction in obese subjects were likely associated with decreased satiety and relatively increased food intake. We conclude that obese subjects have a PYY deficiency that would reduce satiety and could thus reinforce their obesity.

Postprandial plasma ghrelin is suppressed proportional to meal calorie content in normal-weight but not obese subjects.

Circulating levels of the gastric hormone ghrelin rise before and decrease after a meal. In normal-weight subjects, postprandial suppression of ghrelin is proportional to calories consumed. Obese individuals have lower fasting ghrelin levels; however, it is unclear whether the obese show normal postprandial suppression. This study aimed to compare postprandial ghrelin responses in normal-weight and obese subjects, using mixed macronutrient meals with varied fat and calorie content. Postprandial ghrelin response was measured in normal-weight insulin-sensitive subjects and obese insulin-resistant subjects, after six test meals with different fat and calorie content (250-3000 kcal). Increasing the calorie content of meals in normal-weight subjects progressively lowered nadir levels of ghrelin. The obese had lower fasting ghrelin levels, and the reduction after the consumption of all test meals was less than the normal-weight subjects. The lowest postprandial levels in the obese were no different to the nadir in normal-weight volunteers after 1000-, 2000-, and 3000-kcal meals. Thus, circulating ghrelin levels decreased in normal-weight subjects after mixed meals. Obese subjects demonstrated a much reduced ghrelin postprandial suppression. This reduced suppression may influence satiety, thus reinforcing obesity.