- Consultant Chemical Pathologist & Clinical Lead for Biochemistry (King's College Hospital NHS Foundation Trust)
Honorary Senior Lecturer (King's College London)edit
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Accurate diagnosis, classification and risk stratification for chronic kidney disease (CKD) allow for early recognition and delivering optimal care. Creatinine-based glomerular filtration rate (GFR), urinary albumin: creatinine ratio... more
Accurate diagnosis, classification and risk stratification for chronic kidney disease (CKD) allow for early recognition and delivering optimal care. Creatinine-based glomerular filtration rate (GFR), urinary albumin: creatinine ratio (UACR) and the kidney failure risk equation (KFRE) are important tools to achieve this, but understanding their limitations is important for optimal implementation.When accurate GFR is required (eg, chemotherapy dosing), GFR is measured using an exogenous filtration marker. In routine clinical practice, in contrast, estimated GFR (eGFR) from serum creatinine (SCr), calculated using the enzymatic method±UACR, is recommended. Limitations of SCr include non-GFR determinants such as muscle mass, diet and tubular handling. An alternative or additional endogenous filtration marker is cystatin C, which can be used alongside SCr for confirmatory testing of CKD. However, its role in the UK is more limited due to concerns regarding false positive results.The recommended creatinine-based eGFR equation in the UK is the CKD Epidemiology Collaboration 2009 equation. This was recently updated to a race-neutral 2021 version and demonstrated reduced bias in people of Black ethnicity, but has not been validated in the UK. Limitations are extremes of age, inaccuracy at greater GFRs and reduced generalisability to under-represented ethnicity groups.The KFRE (based on age, sex, SCr and UACR) has recently been developed to help determine 2-year and 5-year risk of progression to end-stage kidney disease. It has been validated in over 30 countries and provides meaningful quantitative information to patients. However, supporting evidence for their performance in ethnic minority groups and kidney diseases such as glomerulonephritis remains modest.In conclusion, early identification, risk stratification of kidney disease and timely intervention are important to impact kidney disease progression. However, clinician awareness of the limitations and variability of creatinine, cystatin C and the eGFR equations, is key to appropriate interpretation of results.
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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... more
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 ( R2 = −0.82, P = 0.004), and betw...
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Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex... more
Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and...
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Bariatric surgical procedures are classified by their presumed mechanisms of action: restrictive, malabsorptive or a combination of both. However, this dogma is questionable and remains unproven. We investigated post-operative changes in... more
Bariatric surgical procedures are classified by their presumed mechanisms of action: restrictive, malabsorptive or a combination of both. However, this dogma is questionable and remains unproven. We investigated post-operative changes in nutrient absorption and transit time following bariatric surgery. Participants were recruited into four groups: obese controls (body mass index (BMI) >30 kg/m2, n = 7), adjustable gastric banding (n = 6), Roux-en-Y gastric bypass (RYGB, n = 7) and biliopancreatic diversion with duodenal switch (DS, n = 5). Participants underwent sulphasalazine/sulphapyridine tests (oro-caecal transit time); fasting plasma citrulline (functional enterocyte mass); 3 days faecal collection for faecal elastase 1 (FE-1); calprotectin (FCp); faecal fatty acids (pancreatic exocrine function, gut inflammation and fat excretion, respectively); and 5 h D-xylose, L-rhamnose and lactulose test (intestinal absorption and permeability). Age and gender were not different but BMI differed between groups (p = 0.001). No difference in oro-caecal transit time (p = 0.935) or functional enterocyte mass (p = 0.819) was detected. FCp was elevated post-RYGB vs. obese (p = 0.016) and FE-1 was reduced post-RYGB vs. obese (p = 0.002). Faecal fat concentrations were increased post-DS vs. obese (p = 0.038) and RYGB (p = 0.024) and were also higher post-RYGB vs. obese (p = 0.033). Urinary excretion of D-xylose and L-rhamnose was not different between the groups; however, lactulose/rhamnose ratio was elevated post-DS vs. other groups (all p < 0.02), suggesting increased intestinal permeability. Following RYGB, there are surprisingly few abnormalities or indications of severe malabsorption of fats or sugars. Small bowel adaptation after bariatric surgery may be key to understanding the mechanisms responsible for the beneficial metabolic effects of these operations.
Research Interests: Bariatric Surgery, Treatment Outcome, England, Humans, Intestinal Mucosa, and 15 moreFemale, Male, Body Mass Index, Obesity Surgery, Clinical Sciences, Intestinal absorption, Middle Aged, Adult, Public health systems and services research, Gastrointestinal Tract, Xylose, Gastric Bypass, Cross Sectional Studies, Gastrointestinal Transit Time, and Rhamnose
Research Interests: Bariatric Surgery, Obesity, Treatment Outcome, Adolescent, Endoscopy, and 23 moreHumans, Blood Glucose, Insulin, Glucagon, Fasting, Weight Loss, Female, Male, Netherlands, Jejunum, Body Mass Index, Obesity Surgery, Eating, Clinical Sciences, Aged, Middle Aged, Adult, Public health systems and services research, Time Factors, Type 2 Diabetes Mellitus, Pilot Projects, Area Under Curve, and Duodenum
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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... more
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). 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. 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. 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.
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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... more
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.
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The rate at which people eat has been suggested to be positively associated with obesity, although appetite and related gut hormones have not been measured. The objective of the study was to determine whether eating the same meal at... more
The rate at which people eat has been suggested to be positively associated with obesity, although appetite and related gut hormones have not been measured. The objective of the study was to determine whether eating the same meal at varying speeds elicits different postprandial gut peptide responses. This was a crossover study at a clinical research facility. Seventeen healthy adult male volunteers participated in the study. A test meal consisting of 300 ml ice cream (675 kcal) was consumed in random order on two different sessions by each subject: meal duration took either 5 or 30 min. The postprandial response of the orexigenic hormone ghrelin and the anorexigenic peptides peptide YY and glucagon-like peptide-1 over 210 min was assessed. Visual analog scales for the subjective feelings of hunger and fullness were completed throughout each session. Peptide YY area under the curve (AUC) was higher after the 30-min meal than after the 5-min meal (mean +/- sem AUC 5 min meal: 4133 +/- 324, AUC 30 min meal: 5250 +/- 330 pmol/liter . min, P = 0.004), as was glucagon-like peptide-1 AUC (mean +/- sem AUC 5 min meal: 6219 +/- 256, AUC 30 min meal: 8794 +/- 656 pmol/liter . min, P = 0.001). There was a trend for higher visual analog scale fullness ratings immediately after the end of the 30-min meal compared with immediately after the 5-min meal. There were no differences in ghrelin response. Eating at a physiologically moderate pace leads to a more pronounced anorexigenic gut peptide response than eating very fast.
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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... more
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.
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To investigate the rate of type 2 diabetes remission after gastric bypass and banding and establish the mechanism leading to remission of type 2 diabetes after bariatric surgery. Glycemic control in type 2 diabetic patients is improved... more
To investigate the rate of type 2 diabetes remission after gastric bypass and banding and establish the mechanism leading to remission of type 2 diabetes after bariatric surgery. Glycemic control in type 2 diabetic patients is improved after bariatric surgery. In study 1, 34 obese type 2 diabetic patients undergoing either gastric bypass or gastric banding were followed up for 36 months. Remission of diabetes was defined as patients not requiring hypoglycemic medication, fasting glucose below 7 mmol/L, 2 hour glucose after oral glucose tolerance test below 11.1 mmol/L, and glycated haemoglobin (HbA1c) <6%. In study 2, 41 obese type 2 diabetic patients undergoing either bypass, banding, or very low calorie diet were followed up for 42 days. Insulin resistance (HOMA-IR), insulin production, and glucagon-like peptide 1 (GLP-1) responses after a standard meal were measured. In study 1, HbA1c as a marker of glycemic control improved by 2.9% after gastric bypass and 1.9% after gastric banding at latest follow-up (P < 0.001 for both groups). Despite similar weight loss, 72% (16/22) of bypass and 17% (2/12) of banding patients (P = 0.001) fulfilled the definition of remission at latest follow-up. In study 2, within days, only bypass patients had improved insulin resistance, insulin production, and GLP-1 responses (all P < 0.05). With gastric bypass, type 2 diabetes can be improved and even rapidly put into a state of remission irrespective of weight loss. Improved insulin resistance within the first week after surgery remains unexplained, but increased insulin production in the first week after surgery may be explained by the enhanced postprandial GLP-1 responses.
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Parenteral nutrition (PN) is widely used when enteral feeding is contraindicated or not possible in patients who are malnourished or at risk of malnutrition, but it is not without complications. We describe the rare complication of... more
Parenteral nutrition (PN) is widely used when enteral feeding is contraindicated or not possible in patients who are malnourished or at risk of malnutrition, but it is not without complications. We describe the rare complication of PN-related chylothorax that can lead to extensive investigations if not picked up early with clinical suspicion and simple biochemical tests.
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The short synacthen test (SST) is used to investigate patients with suspected hypothalamus-pituitary-adrenal (HPA) axis pathology. A rise of serum total cortisol (total cortisol) above 550 nmol/L is accepted as sufficient adrenal reserve.... more
The short synacthen test (SST) is used to investigate patients with suspected hypothalamus-pituitary-adrenal (HPA) axis pathology. A rise of serum total cortisol (total cortisol) above 550 nmol/L is accepted as sufficient adrenal reserve. In total, 80% of cortisol is bound to cortisol-binding globulin (CBG) and 10% to albumin. In the acute phase responses CBG concentrations decrease and can influence the interpretation of SST. The free cortisol index (FCI) is a surrogate marker for free cortisol and is defined as total cortisol (nmol/L)/CBG (mg/L) with an FCI > 12 representing sufficient adrenal reserve. The aim of this study was to compare total cortisol and FCI in the interpretation of SST in patients with liver impairment. SST was done on 26 patients with liver impairment. Total cortisol was measured on Advia Centaur; serum CBG by radioimmunoassay and FCI calculated. Eleven (42%) patients had a total cortisol >550 nmol/L (range 555-2070) and FCI > 12 (12.0-68.9) suggesting sufficient cortisol reserve. Three patients (13%) had total cortisol <550 nmol/L (268-413) and FCI < 12 (3.5-11.6) consistent with cortisol deficiency. Twelve patients (46%) had a total cortisol <550 nmol/L (144-529), but an FCI > 12 (12.0-52.9). None of the patients had a total cortisol >550 nmol/L and FCI < 12. When total cortisol alone is used to interpret SST in patients with liver impairment, 46% may have been classified as having adrenal insufficiency because of low CBG. FCI may be better for the evaluation of HPA axis insufficiency in patients with liver impairment.
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Research Interests: Engineering, Algorithms, Diet, Anorexia Nervosa, Humans, and 6 moreFemale, Androgens, Young Adult, American, Body Mass Index, and Adult
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Objectives Procalcitonin (PCT) is an acute-phase reactant with concentrations ≥0.5 μg/L indicative of possible bacterial infection in patients with SARS-CoV-2 infection (COVID-19). Some with severe COVID-19 develop cytokine storm... more
Objectives Procalcitonin (PCT) is an acute-phase reactant with concentrations ≥0.5 μg/L indicative of possible bacterial infection in patients with SARS-CoV-2 infection (COVID-19). Some with severe COVID-19 develop cytokine storm secondary to virally driven hyper-inflammation. However, increased pro-inflammatory cytokines are also seen in bacterial sepsis. This study aimed to assess the clinical utility of a cytokine panel in the assessment of COVID-19 with bacterial superinfections along with PCT and C-reactive protein (CRP). Methods The retrospective analysis included serum cytokines (interleukins; IL-1β, IL-6, IL-8 and tumour necrosis factor (TNFα)) measured using Ella™ (Bio-Techne, Oxford, UK) and PCT measured by Roche Cobas (Burgess Hill, UK) in patients admitted with COVID-19 between March 2020 and January 2021. Patients enrolled into COVID-19 clinical trials, treated with Remdesivir/IL-6 inhibitors were excluded. The cytokine data was compared between intensive care unit (ICU...
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Background: To our knowledge, changes in steroid metabolism in subjects with anorexia nervosa (AN) after weight gain have not been elucidated. Objective: We characterized urinary steroid excretion and metabolism in AN patients and... more
Background: To our knowledge, changes in steroid metabolism in subjects with anorexia nervosa (AN) after weight gain have not been elucidated. Objective: We characterized urinary steroid excretion and metabolism in AN patients and investigated the effects of refeeding. Design: In an intervention study, we recruited 7 women with lifethreatening weight loss upon admission and after a median [interquartile range (IQR)] of 95 d (88–125 d) of intensive refeeding; 15 age-matched women were recruited as control subjects. The major urinary metabolites were quantified in 24-h collections by capillary gas chromatography. A single examiner measured weights, heights, and skinfold thicknesses. Results: The median (IQR) age of patients was 24 y (21–26 y), and the duration of AN was 4.0 y (3.3–8.0 y). Body mass index (BMI; in kg/m 2 ) increased from 12.8 (12.7–13.1) to 18.6 (18.0–19.6) after refeeding (P , 0.0001). Steroid values [median pre-, post-refeeding (P value)] were as follows: androgen me...
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Research Interests: Bariatric Surgery, Obesity, Endocrinology & Metabolism, Medicine, Urinary incontinence, and 11 moreWeight Loss, Psychological Intervention, Behaviour Modification, Body Mass Index, Meta Analysis, Systematic review, Clinical Sciences, Randomized Controlled Trial, Science Technology, Clinical Obesity, and Life Sciences & Biomedicine
Aims: To investigate the mechanism of hyperglycaemia in women with Polycystic Ovary Syndrome (PCOS) by modelling physiological insulin secretion. Methods: 45 non-diabetic women with PCOS (defined by Rotterdam criteria) and 47 controls... more
Aims: To investigate the mechanism of hyperglycaemia in women with Polycystic Ovary Syndrome (PCOS) by modelling physiological insulin secretion. Methods: 45 non-diabetic women with PCOS (defined by Rotterdam criteria) and 47 controls were studied. Insulin secretion was modelled from glucose and C-peptide concentrations during a 6-point oral glucose tolerance test (OGTT) and insulin resistance (IR) was determined by the Matsuda Insulin Sensitivity Index (ISI). Results: (1). b-Cell Glucose Sensitivity (bCGS) is not intrinsically impaired in PCOS, but IR is increased. (2) However, women with PCOS and 2-hour hyperglycaemia (glucose >7.5 mmol/l]) were characterized by worse bCGS compared with women with 2-hour glucose <7.5 mmol/l (mean [SD]) 43.5 [23.6] versus 109.0 [68.5] pmol/min/ml/mmol; p 1⁄4 0.04), and had higher waist circumference (116.8 [15.8] vs 93.5 [15.9] cm; p < 0.01) and 120 minute insulin concentrations (964.0 [579.2e1214.7] vs 328.2 [242.2e475.7] pmol/l; p 1⁄4 0....
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