A single faecal bile acid stool test demonstrates potential efficacy in replacing SeHCAT testing for bile acid diarrhoea in selected patients.

This study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the 75selenium-homotaurocholic acid (SeHCAT) scan. A prospective observational study was undertaken. Patients with chronic diarrhoea (> 6 weeks) being investigated for potential BAD with SeHCAT scan provided stool samples for measurement of FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group, post-cholecystectomy, idiopathic BAD and post-operative terminal ileal resected Crohn's disease. Stool samples were collected at baseline and 8-weeks post treatment to determine whether FBA measurement could be used to monitor therapeutic response. 113 patients had a stool sample to directly compare with their SeHCAT result. FBA concentrations (µmol/g) and interquartile ranges in patients in the control group (2.8; 1.6-4.2), BAD (3.6; 1.9-7.2) and post-cholecystectomy cohort 3.8 (2.3-6.8) were similar, but all were significantly lower (p < 0.001) compared to the Crohn's disease cohort (11.8; 10.1-16.2). FBA concentrations in patients with SeHCAT retention of < 15% (4.95; 2.6-10.5) and < 5% (9.9; 4.8-15.4) were significantly higher than those with a SeHCAT retention > 15% (2.6; 1.6-4.2); (p < 0.001 and p < 0.0001, respectively). The sensitivity and specificity using FBA cut-off of 1.6 µmol/g (using ≤ 15% SeHCAT retention as diagnostic of BAD) were 90% and 25% respectively. A single random stool sample may have potential use in diagnosing severe BAD or BAD in Crohn's patients. Larger studies are now needed to confirm the potential efficacy of this test to accurately diagnose BAD in the absence of SeHCAT testing.

Utility of plasma NGAL for the diagnosis of AKI following cardiac surgery requiring cardiopulmonary bypass: a systematic review and meta-analysis.

The objective of this study was to assess the diagnostic value of plasma neutrophil gelatinase-associated lipocalin (pNGAL) for the early diagnosis of acute kidney injury (AKI) in adult patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Electronic databases and other resources were systematically searched for relevant studies. Risk of bias was assessed using the Quality Assessment for Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Studies were assigned to a sub-group based on the timing of the pNGAL sample in relation to the cessation of CPB. These were < 4 h, 4-8 h, 12 h or 24 h post-cessation of CPB. Summary values for sensitivity and specificity were estimated using the hierarchical summary receiver operator characteristic (ROC) curve model. A random-effects meta-analysis of each pair of sensitivity and specificity estimates from each included study was performed. In total, 3131 patients from 16 studies were included. When taken at 4-8 h following CPB, pNGAL had superior performance for the diagnosis of AKI in the defined population when compared to earlier and later time points. Prediction regions and confidence intervals, however, demonstrated significant variability in pooled estimates of sensitivity and specificity. This is likely due to population and study design heterogeneity, lack of standardisation of assays and thresholds, and inability to distinguish the different molecular forms of NGAL. In conclusion, the diagnostic utility of pNGAL in this clinical setting is inconclusive and large individual studies of representative populations of cardiac surgery patients using assays that specifically detect NGAL in its monomeric form are required.

Comparative Evaluation of Two NGAL Automated Immunoassays in Urine and Plasma.

BACKGROUND: Acute kidney injury (AKI), a frequent and serious complication of hospitalized patients, is associated with increased mortality and morbidity. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for the early identification of AKI. We report a comparative laboratory verification of the Abbott Diagnostics (ARCHITECT® urine NGAL) and BioPorto Diagnostics (NGAL TestTM) assays including an assessment of the Abbott assay's performance in EDTA plasma. METHODS: Intra-/interbatch imprecision, linearity, recovery, and limit of quantitation (LoQ) were assessed and an interassay comparison performed (n = 51). Between-laboratory agreement was assessed against other laboratories using the Abbott (n = 48) and BioPorto (n = 94) assays. Plasma NGAL (pNGAL) levels were measured in non-AKI patients with a range of estimated glomerular filtration rates (n = 80). RESULTS: Coefficients of variation (CVs) for intra- and interbatch imprecision were 0.7%-12.4% and 1.9%-27.5% for the BioPorto assay, respectively, and 1.4%-6.3%/3.4%-6.8%, respectively, for the Abbott assay. The BioPorto assay exhibited a higher LoQ (27.5 ng/mL vs 1.2 ng/mL). Both assays were linear over the range 5-6000 ng/mL. Recovery of recombinant NGAL was 113.1 ± 7.1% and 96.5 ± 7.8% for the Abbott and BioPorto assays, respectively. On average, the Abbott assay gave results 9.2% lower than the BioPorto assay. Mean differences of 0.2% (Abbott) and 20.2% (BioPorto) were observed in the between-laboratory comparison. In patients without AKI, pNGAL levels were inversely proportional to eGFR. CONCLUSIONS: Performance of the Abbott and BioPorto assays was similar although the latter performed less well at lower NGAL concentrations. The Abbott assay tended to yield lower results, exhibited a lower LoQ and over-recovered NGAL. Although only Conformité Européenne-marked and marketed for use in urine, the Abbott assay demonstrated equivalent performance to the BioPorto assay with EDTA plasma.

Acid freezes uricolysis in addition to glycolysis: Utility of fluoride-EDTA-citrate tube in the measurement of uric acid for patients administered rasburicase.

BACKGROUND: In samples from patients administered rasburicase, ex vivo uricolysis leads to spuriously low uric acid results. The manufacturer's recommendation of storing the sample in ice-water until analysis, however, does not fully arrest uricolysis. Since uricase activity is affected by pH and metal chelators, we assessed uricolysis inhibition in sodium fluoride-ethylenediaminetetraacetic acid (EDTA)-citrate sample tube (FC Mix tube, Greiner) used primarily for plasma glucose. METHOD: A serum pool was spiked with rasburicase and uric acid measured at 15, 45, 90, 150, 240 and 1080 min in a lithium heparin tube in ice-water, plain tube at room temperature (RT), EDTA tube at RT, FC Mix tube in ice-water, FC Mix tube at RT and FC Mix tube at RT prepared by dissolving FC Mix in serum. RESULTS: The rate of urate decay was lowest in the FC Mix tube independent of temperature, then lithium heparin tube in ice-water, then EDTA tube at RT and highest in the plain tube at RT. Uric acid concentrations in the prepared FC Mix tube at RT and heparin tube in ice-water were, respectively, 98.2% and 93.8% of control values at 90 min, 97.1% and 89.3% of control values at 4 h, and remained higher in the prepared FC Mix tube at all time points. CONCLUSION: NaF-EDTA-citrate mixture largely arrested rasburicase mediated ex vivo uricolysis without the need for sample cooling. We propose that sample tubes containing NaF-EDTA-citrate be used for the measurement of uric acid in patients administered rasburicase.

A service evaluation: impact of nurse-led regional familial hypercholesterolaemia service on a hospital adult lipid clinic.

The authors evaluated the impact of genetic screening for familial hypercholesterolaemia (FH) in a lipid clinic cohort of patients with definite and possible FH as defined by the Simon Broome Register (SBR) criteria. METHODS: Patients with a lipid clinic diagnosis of definite and possible FH based on the SBR criteria were referred to a nurse-led regional service for FH genetic testing. FINDINGS: 140 patients were referred for genetic testing. Six had SBR-definite FH due to the presence of tendon xanthomata and 134 had SBR-possible FH. A monogenic FH mutation was detected in all six patients (100%) with SBR-definite FH and in 34 (25%) of patients with possible FH. CONCLUSION: The appropriate use of molecular genetics in a lipid clinic will greatly facilitate the management of hyperlipidaemia and cardiovascular risk since the management of FH patients (National Institute for Health and Care Excellence (NICE) Clinical Guideline 71) is different from non-FH patients (NICE Clinical Guideline 181).

Do reflex comments on laboratory reports alter patient management?

INTRODUCTION: Laboratory comments appended on clinical biochemistry reports are common in the UK. Although popular with clinicians and the public, there is little evidence that these comments influence the clinical management of patients. METHODS: We provided reflex automated laboratory comments on all primary care lipid results including, if appropriate, recommendation of direct referral to the West Midlands Familial Hypercholesterolaemia service (WMFHS). Over a two-year period, the number GP referrals from the Wolverhampton City Clinical Commissioning Group (CCG) to the WMFHS were compared with four comparator CCGs of similar population size, who were not provided with reflex laboratory comments. RESULTS: Over the study period, the WMFHS received more referrals from Wolverhampton GPs (241) than any other comparator CCG (range 8-65) and greater than the combined referrals (172) from all four comparator CCGs. CONCLUSION: Targeted reflex laboratory comments may influence the clinical management of patients and may have a role in the identification of individuals with familial hypercholesterolaemia.

Effect of faecal calprotectin assay variability on the management of inflammatory bowel disease and potential role of faecal S100A12.

AIMS: To prospectively evaluate whether between-assay variability of different faecal calprotectin (f-Cp) assays influences diagnostic accuracy for inflammatory bowel disease (IBD) in a cohort of patients with confirmed IBD and irritable bowel syndrome (IBS). To also evaluate the diagnostic accuracy of faecal S100A12 (f-S100A12) against f-Cp in the same patient cohort and assess whether f-S100A12 offers additional diagnostic value. METHODS: F-Cp using four commercially available f-Cp assays, f-S100A12 and blood biomarkers were measured in patients, recruited from the local IBD clinic, who had established IBS or active ulcerative colitis (UC) and Crohn's disease (CD). Diagnostic sensitivities and specificities for each assay and biomarker were calculated and compared. RESULTS: Median f-Cp levels in all assays were significantly higher in UC (347-884 µg/g; n=28) and CD (377-838 µg/g; n=15) compared with IBS (6-27 µg/g; n=17). Sensitivities and specificities at 50 µg/g were 94%-100% and 82%-100%, respectively. Median f-S100A12 levels were significantly higher in UC (81.0 µg/g; IQR 38.3-159.8) and CD (47.2 µg/g; IQR 5.3-108.9) compared with IBS (0.7 µg/g; IQR 0.5-0.8). At 2.8 µg/g, f-S100A12 had a sensitivity of 97% and specificity of 94%. The blood biomarkers demonstrated sensitivities and specificities of 44%-63% and 80%-92%, respectively. CONCLUSIONS: The diagnostic sensitivity of the calprotectin assays was similar despite inter-kit variability in absolute values. There is a need for f-Cp assay standardisation, but in its absence assay-specific cut-off values may optimise their diagnostic performance. F-S100A12 demonstrated comparable sensitivity and specificity to f-Cp and although a research tool at present, may have a future role to play in the diagnosis and management of these patients.

Postmenopausal hyperandrogenism: the under-recognized value of inhibins.

We report a 70-year-old female presenting with increased libido and mild but rapid onset virilism. Investigations showed markedly elevated androstenedione and 17 hydroxyprogesterone misdirecting to possible late-onset congenital adrenal hyperplasia. High serum testosterone and oestrogens with suppressed gonadotrophins, however, indicated an androgen-secreting tumour. A normal dehydroepiandrosterone sulphate and elevated inhibins A and B indicated the tumour was ovarian in origin, which was confirmed on pelvic examination and imaging. At laparotomy, a right ovarian sertoliform endometrioid carcinoma was removed, following which the patient developed menopausal vasomotor symptoms and improvement of her virilism. Serum testosterone, oestradiol, inhibins A and B became undetectable, gonadotrophins appropriately increased and 17 hydroxyprogesterone and androstenedione normalized. We propose that inhibins may be of diagnostic value and should be included in investigative algorithms of females with virilization and hyperandrogenaemia, especially if postmenopausal. Androgen-secreting tumours must be excluded before raised 17 hydroxyprogesterone concentrations are used to diagnose late-onset congenital adrenal hyperplasia in females with new-onset virilization.

Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c. Methods HbA1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

Post-thyroidectomy hypocalcemia: Impact on length of stay.

Hypocalcemia is a recognized complication following thyroid surgery. Variability in the definition of hypocalcemia and different opinions on its management can lead to unnecessary patient morbidity and longer hospital stays as a result of inappropriate or untimely treatment. Therefore, we developed a management guideline for the recognition and treatment of post-thyroidectomy hypocalcemia, and we conducted a retrospective study to assess its impact on length of stay (LOS). Between April 1, 2007, and March 31, 2009, 29 adults had undergone a total or completion thyroidectomy at our large district general hospital. Of this group, postoperative hypocalcemia (defined as a serum calcium level of <2.00 mmol/L) developed in 13 patients (44.8%) during the first 3 postoperative days. Our guideline went into effect on July 1, 2009, and from that date through June 30, 2010, 18 more adults had undergone a total or completion thyroidectomy. Of that group, hypocalcemia developed in 7 patients (38.9%); the guideline was actually followed in 5 of these 7 cases (71.4%). In the preguideline group, the development of hypocalcemia increased the mean LOS from 2.0 days to 7.0 days (p < 0.001). The management of postoperative hypocalcemia in these cases was highly variable and was dictated by variations in practice rather than patient needs. In the postguideline group, postoperative hypocalcemia increased the mean LOS from 2.7 days to only 3.7 days (p = 0.07). While the difference between LOS in the two hypocalcemic groups did not reach statistical significance, we believe it merely reflects the relatively small number of patients rather than any lack of guideline efficacy. The implementation of a simple flowchart guideline for the management of postoperative hypocalcemia in our hospital has resulted in more uniform management and a reduced LOS.

Vitamin D: a negative acute phase reactant.

OBJECTIVE: We evaluated the effect of the systemic inflammatory response (SIR), as provoked by elective orthopaedic surgery, on serum vitamin D [25-(OH)D]. METHODS: Serum 25-(OH)D, serum vitamin D binding protein (VDBP) and urinary VDBP were measured in 30 patients before and 48-hours after knee or hip arthroplasty. C-reactive protein (CRP) was measured to assess the SIR. RESULTS: The mean (SD) CRP increased following surgery [5.0 (5.5) vs 116.0 (81.2) mg/L; P<0.0001] as did urine VDBP/Creatinine ratio [8 (9) vs 20 (25) pg/mmol; p=0.0004]. Serum 25-(OH)D [56.2 (30.3) vs 46.0 (27.6) nmol/L; p = 0.0006] and serum VDBP [334 (43) vs 298 (37) mg/L]; P<0.0001] decreased. CONCLUSIONS: Serum 25-(OH)D is a negative acute phase reactant, which has implications for acute and chronic inflammatory diseases. Serum 25-(OH)D is an unreliable biomarker of vitamin D status after acute inflammatory insult. Hypovitaminosis D may be the consequence rather than cause of chronic inflammatory diseases.

The effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on serum uric acid in patients without gout: a prospective study.

OBJECTIVE: Acute gout is associated with a decrease in serum uric acid (SUA) that is considered to be in response to acute inflammation but it may be a feature of gout itself. We, therefore, aimed to investigate the effect of the acute systemic inflammatory response (SIR) on SUA concentrations in subjects without gout. METHODS: SUA and urinary excretion of uric acid (UA) (expressed as fractional excretion of UA; FEua%) were measured in 30 patients before and 48 h after elective knee or hip surgery. The SIR was assessed by measuring serum CRP and urine microalbumin excretion [expressed as the albumin-creatinine ratio (ACR)] before and after surgery in the same patients. RESULTS: The mean (s.d.) serum CRP increased following surgery [5.0 (5.5) vs 116.0 (81.2) mg/l; P < 0.0001) as did urine ACR [0.85 (1.03) vs 2.10 (2.60) mg/mmol; P = 0.004]. SUA decreased following surgery [312 (64) vs 282 (82) µmol/l; P = 0.0033] but FEua% was unchanged [6.4 (2.3) vs 7.3 (3.3)%; P = 0.1726]. CONCLUSION: The SIR is associated with a decrease in SUA concentrations in normouricaemic patients without gout. The decrease in SUA concentrations is not due to increased urinary excretion of UA. This study supports the notion that the decrease in SUA during acute gout is due to the associated SIR rather than gout per se.

'Sweet Dreams', 'Happy Days' and elevated 24-h urine 5-hydroxyindoleacetic acid excretion.

We report two patients with markedly elevated 24-h urine 5-hydroxyindoleacetic acid (5-HIAA) excretion due to over-the-counter (OTC) self-medication with 5-hydroxytryptophan (5-HTP). It is important to recognize that OTC medication may cause increased 'false-positive' 5-HIAA excretion to prevent undue patient anxiety and unnecessary further investigation for carcinoid disease. Discordance between chromogranin A and 24-h urine 5-HIAA results should alert to the possibility of false-positive or -negative laboratory results.

Hypergonadotrophic hypogonadism due to testicular adrenal rest tumours presenting with hypogonadotrophic hypergonadism.

Primary testicular failure is characterized by low serum testosterone with appropriately high serum gonadotrophins, that is hypergonadotrophic hypogonadism. We report on a 27-year-old man with congenital adrenal hyperplasia (CAH) and infertility due to testicular adrenal rest rumours (TART) resulting in primary testicular failure but presenting with azoospermia, elevated serum testosterone and very low serum gonadotrophins. Hypergonadotrophic hypogonadism was unmasked by increasing glucocorticoid dosage. It is important to recognise the limitations of follicle-stimulating hormone, luteinising hormone and testosterone in assessing testicular function in men with CAH. Abnormal semen analysis may be the best indicator of testicular dysfunction in men with CAH.

Shortness of breath: flushing out the diagnosis.

We report a 63-year-old man who presented with breathlessness and weight loss and was diagnosed on echocardiography to have carcinoid heart disease. It was later transpired that he underwent surgical removal of an ileal carcinoid tumour 19 years previously.