The association of depressive symptoms and diabetes distress with glycaemic control and diabetes complications over 2 years in newly diagnosed type 2 diabetes: a prospective cohort study.

AIMS/HYPOTHESIS: We examined the associations between depressive symptoms and diabetes distress with glycaemic control and diabetes complications over 2 years, after diagnosis of type 2 diabetes. METHODS: In a multi-ethnic, primary care cohort (n = 1735) of adults, all with recent (<6 months) diagnosis of type 2 diabetes, we measured the associations between depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score ≥10) and diabetes distress (Problem Areas in Diabetes [PAID] score ≥40), with change in 2 year HbA1c as the primary outcome and with incident rates of diabetes complications as secondary outcomes. Multivariate models were used to account for potential confounders. RESULTS: Of the 1651 participants (95.2%) of the total primary care cohort with available baseline PHQ-9 and PAID scores, mean ± SD age was 56.2 ± 11.1 years, 55.1% were men and 49.1% were of non-white ethnicity; 232 (14.1%) and 111 (6.7%) had depressive symptoms and diabetes distress, respectively. After adjustment for confounders, depressive symptoms were not associated with worsening HbA1c. After adjustment for age, sex, ethnicity, vascular risk factors and diabetes treatments, depressive symptoms were associated with increased risk of incident macrovascular complications (OR 2.78 [95% CI 1.19, 6.49], p = 0.018) but not microvascular complications. This was attenuated (p = 0.09) after adjustment for IL-1 receptor antagonist concentration. Diabetes distress was not associated with worsening HbA1c or incident complications. CONCLUSIONS/INTERPRETATION: In the first 2 years of type 2 diabetes, the effect of depressive symptoms and diabetes distress on glycaemic control is minimal. There was, however, an association between depressive symptoms and incidence of macrovascular complications. Elevated innate inflammation may be common to both depression and macrovascular diabetes complications, but these findings require replication.

A randomized double-blind placebo-controlled trial of a multi-strain probiotic in treatment of symptomatic uncomplicated diverticular disease.

BACKGROUND: Diverticular disease is a significant burden on healthcare systems that is managed, surgically or medically, mainly as an emergency or acute condition. There are no standardized treatment recommendations for symptomatic uncomplicated disease. We hypothesized that a probiotic would reduce abdominal pain in such patients. METHODS: We conducted a single-center, double-blind, placebo-controlled trial of probiotic treatment (Symprove) in adult patients with moderate-to-severe chronic, non-acute symptomatic diverticular disease. 143 patients were randomized to receive 1 mL/kg/day of probiotic liquid (N = 72) or placebo (N = 71) daily for 3 months. The primary endpoint was abdominal pain severity. Secondary endpoints consisted of the change in the frequency of eight abdominal symptoms and the level of intestinal inflammation (fecal calprotectin). RESULTS: 120 patients completed the trial. Abdominal pain score, the primary end point, decreased in both groups, but no significant difference between the groups was found (P = 0.11). In relation to placebo, the probiotic significantly decreased the frequency of four of the eight secondary endpoints: constipation, diarrhea, mucorrhea, and back pain (P < 0.04). No significant differences were found in frequency of abdominal pain, PR bleeding, dysuria, and bloating. CONCLUSIONS: Multi-strain liquid probiotic did not improve abdominal pain scores significantly, but significantly improved the frequency of four other symptoms associated with chronic, non-acute symptomatic diverticular disease.

Composite biomarker panel for prediction of severity and diagnosis of acute GVHD with T-cell-depleted allogeneic stem cell transplants-single centre pilot study.

AIMS: Acute graft-versus-host disease (aGVHD) is a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical utility of a composite biomarker panel to help identify individuals at risk of developing aGVHD, and to help predict and differentiate between severity of aGVHD following T-cell-depleted allogeneic HSCT. METHODS: We retrospectively analysed our cohort of biopsy confirmed patients with aGVHD, who underwent T-cell-depleted HSCT and matched them with negative controls without any evidence of aGVHD. Post-transplant serum samples on days 0 and 7 and at onset of aGVHD were analysed for elafin, regenerating islet-derived 3-α, soluble tumour necrosis factor receptor-1, soluble interleukin-2 receptor-α and hepatocyte growth factor. Biomarker data were combined as composite panels A-F (table 2) using logistic regression analysis. Receiver operating characteristic analysis was performed to study sensitivity and specificity of the composite panels. RESULTS: Our composite biomarker panels significantly differentiated between aGVHD and no GVHD patients at time of onset (panel E) and reliably predicted severity of GVHD grades at days 0 and 7 post-transplant (panels B and D). The area under the curve for the composite panel at time of onset was 0.65 with specificity, sensitivity, positive and negative predictive values of 100%, 55.6%, 100% and 78.9%, respectively (p=0.03). CONCLUSIONS: This pilot data support the usefulness of these composite biomarker panels in the prediction of severity and diagnosis of aGVHD in patients undergoing T-cell-depleted reduced intensity allogeneic HSCT.

Elevated fasting and postprandial C-terminal telopeptide after Roux-en-Y gastric bypass.

Background Roux-en-Y gastric bypass increases circulating bile acid concentrations, known mediators of postprandial suppression of markers of bone resorption. Long-term data, however, indicate that Roux-en-Y gastric bypass confers an increased risk of bone loss on recipients. Methods Thirty-six obese individuals, median age 44 (26-64) with median body mass index at baseline of 42.5 (40.4-46) were studied before and 15 months after Roux-en-Y gastric bypass. After an overnight fast, patients received a 400 kcal mixed meal. Blood samples were collected premeal then at 30-min periods for 120 min. Pre and postmeal samples were analysed for total bile acids, parathyroid hormone and C-terminal telopeptide. Results Body weight loss post Roux-en-Y gastric bypass was associated with a median 4.9-fold increase in peak postprandial total bile acid concentration, and a median 2.4-fold increase in cumulative food evoked bile acid response. Median fasting parathyroid hormone, postprandial reduction in parathyroid hormone and total parathyroid hormone release over 120 min remained unchanged after surgery. After surgery, median fasting C-terminal telopeptide increased 2.3-fold, peak postprandial concentrations increased 3.8-fold and total release was increased 1.9-fold. Conclusions Fasting and postprandial total bile acids and C-terminal telopeptide are increased above reference range after Roux-en-Y gastric bypass. These changes occur in spite of improved vitamin D status with supplementation. These results suggest that post-Roux-en-Y gastric bypass increases in total bile acids do not effectively oppose an ongoing resorptive signal operative along the gut-bone axis. Serial measurement of C-terminal telopeptide may be of value as a risk marker for long-term skeletal pathology in patients post Roux-en-Y gastric bypass.

Clinical relevance of trace element measurement in patients on initiation of parenteral nutrition.

Background and Aims Serum zinc, copper and selenium are measured in patients prior to commencing on parenteral nutrition; however, their interpretation can be difficult due to acute phase reactions. We assessed (i) the relationship of raised C-reactive protein with trace elements and albumin (ii) benefits of measuring trace elements when C-reactive protein is raised in patients requiring short-term parenteral nutrition. Methods Samples were collected for zinc, copper, selenium and albumin at baseline and then every two weeks and correlated with C-reactive protein results in patients on parenteral nutrition. Results were categorized into four groups based on the C-reactive protein concentrations: (i) <20 mg/L, (ii) 20-39 mg/L, (iii) 40-79 mg/L and (iv) ≥80 mg/L. Results In 166 patients, zinc, selenium and albumin correlated (Spearman's) negatively with C-reactive protein; r = -0.26, P < 0.001 (95% CI -0.40 to -0.11), r = -0.44, P < 0.001 (-0.56 to -0.29) and r = -0.22 P = 0.005 (-0.36 to -0.07), respectively. Copper did not correlate with C-reactive protein (r = 0.09, P = 0.25 [-0.07 to 0.25]). Comparison of trace elements between the four groups showed no difference in zinc and copper (both P > 0.05), whereas selenium and albumin were lower in the group with C-reactive protein > 40 mg/L ( P < 0.05). Conclusion In patients on short-term parenteral nutrition, measurement of C-reactive protein is essential when interpreting zinc and selenium but not copper results. Routine measurement of trace elements prior to commencing parenteral nutrition has to be considered on an individual basis in patients with inflammation.

Fecal calprotectin in inflammatory bowel disease.

Inflammatory bowel disease (IBD) and irritable bowel syndrome share many symptoms. While irritable bowel syndrome is a functional bowel disorder for which no specific treatment is available, the range of effective therapies for IBD is evolving rapidly. Accurate diagnosis of IBD is therefore essential. Clinical assessment, together with various imaging modalities and endoscopy, has been the mainstay of diagnosis for many years. Fecal biomarkers of gastrointestinal inflammation have appeared in the past decade, of which calprotectin, a neutrophil cytosolic protein, has been studied the most. Crohn's disease and ulcerative colitis are chronic remitting and relapsing diseases, and objective assessment of disease activity and response to treatment are important. This review focuses on the use of fecal calprotectin measurements in the diagnosis and monitoring of patients with IBD.

Changes in biomarkers of bone turnover in an aripiprazole add-on or switching study.

BACKGROUND: The association between mental illness and osteoporosis and fractures is particularly pronounced in psychotic disorders. Antipsychotic use has previously been described to affect bone density. METHOD: A 52-week follow-up of patients switched to aripiprazole or with aripiprazole added on, conducting a specific analysis of markers of bone turnover: urinary NTX (a biomarker of bone resorption) and serum BSAP (a biomarker of bone formation). Baseline and serial measurements of bone markers NTX, BSAP and of hormones prolactin, oestrogen and testosterone were done at weeks 0 and 1, 2, 6, 12, 26 and 52, respectively. RESULTS: NTX concentration reduced over time but this did not reach significance in the whole group (log-NTX: ß=-0.0012, p=0.142). For BSAP the addition of or replacement with aripiprazole produced a significant reduction (log-BSAP: ß=-0.00039, p=0.002). Analysis with prolactin similarly showed a significant reduction (log-prolactin: ß=-0.0024, p<0.001); other hormones did not change significantly. Sensitivity analysis to compare the switchers to aripiprazole versus the "add-on" showed that the former group had a significant reduction in NTX. CONCLUSIONS: We found that switching to aripiprazole was associated with changes in molecular biomarkers of bone resorption, indicating a more favourable profile for bone health.

Serial soluble ST2 for the monitoring of pharmacologically optimised chronic stable heart failure.

BACKGROUND: Soluble ST2 (sST2) is an emerging biomarker of cardiac remodelling and fibrosis. Studies indicate that it is predictive of mortality in acutely decompensated heart failure. The role of sST2 in chronic heart failure (CHF) is less well defined. No studies have examined serial measurements in optimised patients as a potential monitoring tool. This study aimed to prospectively determine the prognostic utility of serial sST2 in patients with pharmacologically optimised stable CHF. METHODS: 41 patients with pharmacologically optimised CHF and left ventricular ejection fraction ≤40% were recruited. Clinical review and blood sampling took place at baseline, and one, three and six months. N-terminal pro-brain natriuretic peptide (NTproBNP), sST2 and renal profile were measured on all samples. 12 lead electrocardiogram (ECG) was performed at baseline. Decompensation was defined as a composite endpoint of cardiovascular admission or worsening renal function (≥25% increase in serum creatinine from baseline). RESULTS: Receiver operator curve analysis of percentage change in sST2 from baseline to six months was strongly reflective of decompensation with area under the curve (AUC) of 0.778. This was significantly better than NTproBNP (AUC 0.425; p=0.013). Correlation of baseline concentrations to surface ECG showed that both sST2 and NTproBNP were positively correlated with duration of the QRS wave, with higher level of significance demonstrated by sST2 (0.415 (p=0.007) and 0.362 (p=0.020) respectively). CONCLUSIONS: Percentage changes in sST2 are better able to predict cardiovascular admission or worsening renal function in patients with pharmacologically optimised CHF than NTproBNP. Compared with NTproBNP, sST2 appears to be a promising candidate for monitoring these patients.

Predicting refeeding hypophosphataemia: insulin growth factor 1 (IGF-1) as a diagnostic biochemical marker for clinical practice.

BACKGROUND: Refeeding syndrome (RS) is a potentially fatal condition that can occur following the re-introduction of nutrition after a period of starvation. Hypophosphataemia following the reintroduction of nutrition is often the only reliable biochemical marker of RS. Refeeding index (RI) generated from baseline insulin-like growth factor-1 (IGF-1) and leptin has been proposed as a useful biochemical marker for the identification of patients at risk of developing refeeding hypophosphataemia (RH). METHODS: A prospective study included 52 patients referred for parenteral nutrition (PN). The sensitivity and specificity of IGF-1 measured using a sensitive assay was compared to the RI in predicting the development of RH (a ≥ 30% drop in PO4 during the first 36-h of PN administration). Leptin and IGF-1 were analysed on baseline samples using a quantitative enzyme-linked immunoassay. Daily blood samples were collected from all patients for routine biochemistry for the full duration of PN administration. RESULTS: High sensitivity IGF-1 measurement alone was comparable with the RI, using receiver-operating characteristic (ROC) curve analysis, with areas under the curve being 0.79 and 0.80, respectively, and superior to leptin alone (0.72) for predicting ≥ 30% drop in PO4. The cut-off value for IGF-1 that gave best sensitivity (91% [95% CI 75-98%]) and specificity (65% [95% CI 41-85%]) was 63.7 µg/L, with a likelihood ratio of 2.59. CONCLUSION: Baseline IGF-1 is an objective, sensitive and specific biochemical marker in identifying patients who are at high risk of developing RH prior to PN administration and therefore may have a role in clinical practice.

The association between depressive symptoms and systemic inflammation in people with type 2 diabetes: findings from the South London Diabetes Study.

OBJECTIVE: The prevalence of depression and depressive symptoms is increased twofold in people with type 2 diabetes compared with the general population and is associated with worse biomedical outcomes and increased mortality. Type 2 diabetes, cardiovascular disease, and depression in nondiabetes subjects are independently associated with raised concentrations of circulating inflammatory markers, but it is not known if a similar association is observed in type 2 diabetes. We tested the hypothesis that higher depressive symptom scores in newly diagnosed type 2 diabetes patients were associated with higher concentrations of inflammatory markers. RESEARCH DESIGN AND METHODS: Depressive symptoms in adults with newly diagnosed type 2 diabetes recruited from primary care were assessed using the Patient Health Questionnaire-9. Twelve markers of inflammation (C-reactive protein [hs-CRP], interleukin-4 [IL-4], IL-6, IL-10, vascular endothelial growth factor [VEGF], tumor necrosis factor-α [TNF-α], IL-1ß, IL-1 receptor antagonist [IL-1RA], monocyte chemotactic protein-1 [MCP-1], white blood cell count [WBC], adiponectin, and triglyceride [TG]) were measured. Covariates included sociodemographic factors, adiposity, macrovascular disease, HbA1c, and prescribed medication. The association between each inflammatory marker and depressive symptom score was estimated by multiple linear regression. RESULTS: The baseline cohort consisted of 1,790 participants. After adjusting for covariates, CRP (B = 0.13, P < 0.001), IL-1ß (B = 0.06, P = 0.047), IL-1RA (B = 0.13, P < 0.001), MCP-1 (B = 0.11, P = 0.001), WBC (B = 0.13, P < 0.001), and TG (B = 0.10, P < 0.001) were associated with depressive symptoms. CONCLUSIONS: Increased inflammation may be involved in the pathogenesis of depressive symptoms in type 2 diabetes and contribute to the increased risk of complications and mortality in this group.

Ethyl glucuronide and ethyl sulfate.

Alcohol misuse is associated with significant morbidity and mortality. Although clinical history, examination, and the use of self-report questionnaires may identify subjects with harmful patterns of alcohol use, denial or under-reporting of alcohol intake is common. Existing biomarkers for detecting alcohol misuse include measurement of blood or urine ethanol for acute alcohol consumption, and carbohydrate-deficient transferrin and gamma-glutamyl transferase for chronic alcohol misuse. There is a need for a biomarker that can detect excessive alcohol consumption in the timeframe between 1 day and several weeks. Ethyl glucuronide (EtG) is a direct metabolite of ethanol detectable in urine for up to 90 h and longer in hair. Because EtG has high specificity for excess alcohol intake, it has great potential for use in detecting "binge" drinking. Using urine or hair, this noninvasive marker has a role in a variety of clinical and forensic settings.

The effect of bariatric surgery on intestinal absorption and transit time.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Higher circulating bile acid concentrations in obese patients with type 2 diabetes.

BACKGROUND: Bile acids (BAs) play an important role in releasing incretin hormones via the enteroendocrine L-cell surface TGR5 receptors. The aim of this study was to investigate the difference in BA concentration at baseline and in response to a meal stimulus between type 2 diabetes mellitus (T2DM) and a matched normoglycaemic group. MATERIALS AND METHODS: A cross-sectional study of 12 patients with known T2DM and 12 matched normoglycaemic controls compared BA fractions after an overnight fast and following a standard meal. RESULTS: The T2DM group had higher baseline glucose (P < 0.001), but baseline total BA, total glycine conjugated BAs (GCBA) and total taurine conjugated BA (TCBA) were similar between both groups. The T2DM group compared to the normoglycaemic group had a higher post-prandial peak change in total BAs 4.28 (3.51-5.38) µmol/L vs. 0.88 (0.60-1.57) µmol/L (P < 0.001) and peak total GCBA 2.77 (1.07-4.19) µmol/L vs. 0.94 (0.34-1.15) µmol/L (P < 0.0001), but similar peak total TCBA 0.36 (0.02-0.76) µmol/L vs. 0.08 (0.04-0.22) µmol/L (P=0.91). CONCLUSION: The post-prandial bile acid response is elevated in obese patients with T2DM compared to matched normoglycaemic individuals.

Total protein, albumin and low-molecular-weight protein excretion in HIV-positive patients.

BACKGROUND: Chronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART). Tenofovir (TFV) in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP) have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP) such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients. METHODS: In a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR). Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI) or TFV and a protease-inhibitor (TFV/PI). RESULTS: Proteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 µg/mmol (343 µg/g) (p = 0.003). In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77) and eGFR <75 mL/min/1.73 m2 (OR 3.54, 95 % CI 1.61, 7.80) were independently associated with upper quartile (UQ) RBPCR. RBPCR correlated well to CCR (r2 = 0.71), but not to NGALCR, PCR or ACR. CONCLUSIONS: In HIV positive patients, proteinuria was predominantly of tubular origin and microalbuminuria was common. RBPCR in patients without overt renal tubular disease was generally within the reference range, including those receiving TFV. RBP therefore appears a promising biomarker for monitoring renal tubular function in patients receiving TFV and for distinguishing patients with normal tubular function or mild tubular dysfunction from those with severe renal tubular disease or Fanconi syndrome.

Faecal markers of gastrointestinal inflammation.

Gastrointestinal (GI) symptoms including abdominal pain, bloating and diarrhoea are a relatively common reason for consulting a physician. They may be due to inflammatory bowel disease (inflammatory bowel disease; Crohn's disease, ulcerative colitis and indeterminate colitis), malignancy (colorectal cancer), infectious colitis or irritable bowel syndrome (IBS). Differentiation between these involves the use of clinical, radiological, endoscopic and serological techniques, which are invasive or involve exposure to radiation. Serological markers include C-reactive protein, erythrocyte sedimentation rate and antibodies (perinuclear antineutrophil cytoplasm antibody and anti-Saccharomyces cerevisiae antibody). Faecal markers that can aid in distinguishing inflammatory disorders from non-inflammatory conditions are non-invasive and generally acceptable to the patient. As IBS accounts for up to 50% of cases presenting to the GI clinic and is a diagnosis of exclusion (Rome III criteria), any test that can reliably distinguish IBS from organic disease could speed diagnosis and reduce endoscopy waiting times. Faecal calprotectin, lactoferrin, M2-PK and S100A12 will be reviewed.

Ethyl glucuronide.

Alcohol is associated with significant morbidity and mortality. Subjects abusing alcohol can be identified through clinical history, examination or self-report questionnaires. A range of biomarkers is available for detecting alcohol misuse, but there is still a need for a marker that can detect alcohol consumption in the time window between one day (ethanol) and one week (gamma-glutamyl transpeptidase and carbohydrate-deficient transferrin). Ethyl glucuronide is a direct metabolite that can be detected in urine for up to 90 h and has the potential to become a useful marker of 'binge' drinking. As a non-invasive marker, it could have a role in a variety of clinical and forensic settings.

Substance use by liver transplant candidates: an anonymous urinalysis study.

Toxicological urinalysis is a highly sensitive and specific test that detects recent substance use. It has been established for substance misuse treatment but has not been routinely used at liver transplantation (LT) centers. Patients with a history of substance misuse are required to be abstinent from alcohol and illicit drugs before they are listed for LT. In this cross-sectional study, we sought to determine the prevalence of recent substance use in LT candidates via toxicological urinalysis. One hundred nine adults who were admitted for an LT assessment provided data, and they were categorized by the etiology of their liver disease [alcohol-related liver disease (ALD), hepatitis C virus (HCV), or other liver diseases]. Urine was toxicologically screened for drugs and their metabolites as well as the urinary alcohol metabolites ethyl glucuronide and ethyl sulfate. The prevalence of alcohol metabolites in patients with ALD was 20%. Licit and illicit substances together provided a positive toxicological result in 30% of the patients. Positive results were more common among patients with HCV (40%) and ALD (38%) versus patients with other liver diseases (18%). During the clinical assessment, 4% of the patients with ALD or HCV self-reported current alcohol or illicit drug use. These results correspond to the findings of other studies and emphasize the uncertainty of self-reported substance use data for LT candidates.

Faecal M2-pyruvate kinase: a novel, noninvasive marker of ileal pouch inflammation.

BACKGROUND: Dimeric M2-pyruvate kinase (dM2-PK) is overexpressed in tumour cells with rapid cell turnover. Its concentrations correlate well with the staging and metastatic capability of the tumour cells. We investigated the use of faecal dM2-PK as a noninvasive marker of pouch inflammation (pouchitis) in patients having undergone restorative proctocolectomy. METHODS: Stool samples were obtained from 46 patients with ulcerative colitis (UC) and eight with familial adenomatous polyposis. Pouchitis was defined using the objective pouchitis score (OPS) and the pouch disease activity index. Faecal dM2-PK was measured using a quantitative sandwich-type enzyme immunoassay (ScheBo Biotech UK) and the results compared with reciprocal faecal calprotectin concentrations. RESULTS: Using the OPS, 6 of the 46 patients with UC had pouchitis and prepouch ileitis, 13 had UC pouchitis alone, and 27 had a non-inflamed UC pouch. One patient with familial adenomatous polyposis had pouchitis and prepouch ileitis and 7 had an non inflamed pouch. Respective median dM2-PK values (U/ml) for these five groups were 49.5 (4.5-110), 12 (1-192.3), 2.2 (0.1-95.2), 19.5 and 1 (0.1-3). Statistically significant differences were noted between inflamed and non inflamed pouches (P<0.0001). dM2-PK correlated significantly with the OPS, pouch disease activity index, endoscopic appearances, acute histological and neutrophil scores (<0.0001). The receiver operating characteristic analysis demonstrated a sensitivity and specificity of 80 and 70.6%, respectively. dM2-PK and faecal calprotectin concentrations correlated closely (r=0.87, P<0.0001). CONCLUSION: This study demonstrates that faecal dM2-PK is a sensitive marker of pouch inflammation and that its concentration directly correlates with the objective markers of pouchitis severity.

Faecal calprotectin: a noninvasive diagnostic tool and marker of severity in pouchitis.

INTRODUCTION: In pouchitis, the mucosa is infiltrated by activated polymorphonuclear neutrophils capable of producing calprotectin, a stable antimicrobial myelomonocytic protein. AIM: The aim is to assess the ability of faecal calprotectin to differentiate between inflamed and noninflamed ileal pouches, and to correlate this with inflammation severity using the newly developed Objective Pouchitis Score. METHOD: Fifty-four stool samples were collected from patients who had undergone restorative proctocolectomy; 46 from patients with ulcerative colitis and eight from those with familial adenomatous polyposis coli. Faecal calprotectin concentrations were determined by quantitative enzyme-linked immunosorbant assay. RESULTS: Of the ulcerative colitis patients, six were diagnosed with pouchitis and pre-pouch ileitis (median faecal calprotectin: 865 microg/g, with a range of 95-2350 microg/g); 13 had pouchitis alone (145, 33-3350 microg/g) and 27 were uninflamed (56, 4-705 microg/g). Of the familial adenomatous polyposis patients, one had pouchitis and pre-pouch ileitis (305 microg/g), and seven had noninflamed pouches (9, 6-26 microg/g). Stool samples obtained from pouchitis patients had significantly higher calprotectin concentrations compared with those obtained from uninflamed pouches (Mann-Whitney: P<0.0001). Faecal calprotectin concentrations correlated closely with the Objective Pouchitis Score, the Pouch Disease Activity Index and endoscopic and histological inflammatory scores (Spearman rank test: P values <0.0001). Using a faecal calprotectin threshold of >or=92.5 microg/g to define a positive result, Receiver Operating Characteristic analysis demonstrated a sensitivity of 90% and a specificity of 76.5%. CONCLUSION: Faecal calprotectin measurement is a useful noninvasive tool in the diagnosis of acutely inflamed ileal pouches and correlates well with the severity of pouchitis.