Diabetes is a driver of non-alcoholic fatty liver disease (NAFLD) and fibrosis. We determine current practices in examining liver fibrosis in people with diabetes and record prevalence levels in primary and secondary care. We extracted HbA1c results ≥48 mmol/mol to identify people with diabetes, then examined the proportion who had AST, ALT, and platelets results, facilitating calculation of non-invasive fibrosis tests (NIT), or an enhanced liver fibrosis score. Fibrosis markers were requested in only 1.49% (390/26,090), of which 29.7% (n = 106) had evidence of significant fibrosis via NIT. All patients at risk of fibrosis had undergone transient elastography (TE), biopsy or imaging. TE and biopsy data showed that 80.6% of people with raised fibrosis markers had confirmed significant fibrosis. We also show that fibrosis levels as detected by NIT are marginally lower in patients treated with newer glucose lowering agents (sodium-glucose transporter protein 2 inhibitors, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists). In conclusion by utilising a large consecutively recruited dataset we demonstrate that liver fibrosis is infrequently screened for in patients with diabetes despite high prevalence rates of advanced fibrosis. This highlights the need for cost-effectiveness analyses to support the incorporation of widespread screening into national guidelines and the requirement for healthcare practitioners to incorporate NAFLD screening into routine diabetes care.
Background Azole-based antifungals are the first-line therapy for some of the most common mycoses and are now also being used prophylactically to protect immunocompromised patients. However, due to variability in both their metabolism and bioavailability, therapeutic drug monitoring is essential to avoid toxicity but still gain maximum efficacy. Methods Following protein precipitation of serum with acetonitrile, 20 µL of extract was injected onto a 2.1 × 50 mm Waters Atlantis dC18 3 µm column. Detection was via a Waters Quattro Premier XE tandem mass spectrometer operating in ESI-positive mode. Multiple reaction monitoring (MRM) detected two product ions for each compound and one for each isotopically labelled internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of measuring interval and detection were all assessed. Results Optimal chromatographic separation was achieved using gradient elution over 8 minutes. Voriconazole, posaconazole and itraconazole eluted at 1.71, 2.73 and 3.41 min, respectively. The lower limits of measuring interval for all three compounds was 0.1 mg/L. The assay was linear to 10 mg/L for voriconazole (R= 0.995) and 5 mg/L for posaconazole (R= 0.990) and itraconazole (R= 0.991). The assay was both highly accurate and precise with % bias of voriconazole, posaconazole and itraconazole, respectively, when compared with previous NEQAS samples. The intra-assay precision (CV%) was 1.6%, 2.5% and 1.9% for voriconazole, posaconazole and itraconazole, respectively, across the linear range. Conclusion A simple and robust method has been validated for azole antifungal therapeutic drug monitoring. This new assay will result in a greatly improved sample turnaround time and will therefore vastly increase the clinical utility of azole antifungal drug monitoring.
INTRODUCTION Since the beginning of the SARS-CoV-2 pandemic in December 2019 multiple metabolomics studies have proposed predictive biomarkers of infection severity and outcome. Whilst some trends have emerged, the findings remain intangible and uninformative when it comes to new patients. OBJECTIVES In this study, we accurately quantitate a subset of compounds in patient serum that were found predictive of severity and outcome. METHODS A targeted LC-MS method was used in 46 control and 95 acute COVID-19 patient samples to quantitate the selected metabolites. These compounds included tryptophan and its degradation products kynurenine and kynurenic acid (reflective of immune response), butyrylcarnitine and its isomer (reflective of energy metabolism) and finally 3’,4’-didehydro-3’-deoxycytidine, a deoxycytidine analogue, (reflective of host viral defence response). We subsequently examine changes in those markers by disease severity and outcome relative to those of control patients’ levels. RESULTS & CONCLUSION Finally, we demonstrate the added value of the kynurenic acid / tryptophan ratio for severity and outcome prediction and highlight the viral detection potential of ddhC.
With the increasing volume of diagnostic imaging undertaken in an ageing population, adrenal incidentalomas (AIs) are increasingly commonly seen. These masses are most likely to be benign, but a small proportion may be malignant. Similarly, they are usually non-functional, but ∼14% are functional, ie hormone-secreting tumours. Clinical, biochemical and radiological assessment is mandated to stratify patients into those requiring radiological surveillance, medical management or surgical intervention or who can be discharged. Mass characteristics on cross-sectional (CT/ MRI) imaging influence the need for radiological surveillance. Functional tumours where excess cortisol, aldosterone or catecholamine are secreted should be excluded, with mild autonomous cortisol secretion (MACS) and primary aldosteronism (PA) as the two most common functional states. MACS and PA are associated with an increased risk of cardiometabolic disease (eg hypertension, type 2 diabetes) and cardiovascular morbidity/mortality (eg coronary heart disease). Multidisciplinary management is critical for selected cases; the majority of adrenal incidentalomas only require a single assessment.
POINTS TO CONSIDER• PCC should always be considered in the differential diagnosis of hypertension during pregnancy, especially when presentation is before 20 weeks and when patients are resistant to pharmacological treatment.• Biochemical evaluation of PCC during pregnancy is essential as the use of diagnostic radiology if often limited. It is therefore vital that patients have their diet and or medications optimised prior to testing.• Genetic testing of a pregnant patient is highly important in evaluating the familial basis of PCC and the future risk of malignancy.• A multidisciplinary approach involving biochemistry, radiology, obstetrics, anaesthetics, and surgery colleagues is important in cases of PCC in pregnancy due to the unique difficulties in diagnosis and management of both mother and baby. Case DescriptionA pregnant (13/40) 23-year-old female with severe resistant hypertension was referred to our specialist unit. BP on arrival was 240/140 mmHg after one month of Labetalol (200mg tds). Clinical symptoms included headaches, migraines and flushing for several years, especially after eating, and worse during pregnancy. She had pre-eclampsia in her first pregnancy, diagnosed at 20 weeks, with hypertension and proteinuria. She was untreated and no repeat BP was recorded between her first child's birth and this pregnancy.Urine metadrenalines showed a high urine NMN (Table 1) Medical managementLabetalol was stopped and phenoxybenzamine (10mg tds) prescribed. Propranolol (10mg) was also administered as required, when heart rate exceeded 100 bpm lying down. Plasma metadrenalines prior (off medications) revealed elevated NMN and 3-MT concentrations ( Table 1). Other than mildly raised white cells (15.6 x 10 9 /L, RR 3.5-11.0), all other investigations (including parathyroid hormone, calcitonin, chromogranin A and gastrin) were unremarkable. An ultrasound of the neck showed no abnormalities suggestive of a paraganglioma. SurgeryPrior to surgery phenoxybenzamine was increased gradually from 10mg tds to 40mg qds; propranolol was also increased to 30mg qds. After adequate α-and β-blockade, a left laparoscopic adrenalectomy was performed (at 15/40). The patient's BP stabilised to 118/65 mmHg and she was discharged four days later. At discharge plasma metadrenaline concentrations had normalised ( Table 1) Follow upPlanned annual plasma metadrenaline concentrations with imaging if appropriate. Genetic evaluation of RET, VHL, SDHB and SDHD genes; mutations which are linked to hereditary conditions such as multiple endocrine neoplasia type-2, Von Hippel-Lindau disease and familial paraganglioma and PCC, respectively. Family history revealed an older sister had a PCC removed 14 years previously aged 12, suggesting family members should also be offered testing for familial PCC. Genetic testing was not considered at that time as it was not widely available. DiscussionDiagnosis: Endocrine Society Clinical Practice Guideline for PPGL 1 recommends:• Biochemical testing for PCC should include measurement of plasma free or ur...
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