A novel blood based triage test for colorectal cancer in primary care: a pilot study.

BACKGROUND: The majority of colorectal cancers (CRCs) are detected after symptomatic presentation to primary care. Given the shared symptoms of CRC and benign disorders, it is challenging to manage the risk of missed diagnosis. Colonoscopy resources cannot keep pace with increasing demand. There is a pressing need for access to simple triage tools in primary care to help prioritise patients for referral. AIM: To evaluate the performance of a novel spectroscopy-based CRC blood test in primary care. DESIGN & SETTING: Mixed-methods pilot study of test performance and GP focus group discussions in South Wales. METHOD: Patients on the urgent suspected cancer (USC) pathway were recruited for the Raman spectroscopy (RS) test coupled to machine learning classification ('Raman-CRC') to identify CRC within the referred population. Qualitative focus group work evaluated the acceptability of the test in primary care by thematic analysis of focus group theorising. RESULTS: A total of 532 patients aged ≥50 years referred on the USC pathway were recruited from 27 GP practices. Twenty-nine patients (5.0%) were diagnosed with CRC. Raman-CRC identified CRC with sensitivity 95.7%, specificity 69.3% with area under curve (AUC) of 0.80 compared with colonoscopy as the reference test (248 patients). Stage I and II cancers were detected with 78.6% sensitivity. Focus group themes underlined the convenience of a blood test for the patient and the test's value as a risk assessment tool in primary care. CONCLUSION: The findings support this novel, non-invasive, blood-based method to prioritise those patients most likely to have CRC. Raman-CRC may accelerate access to diagnosis with potential to improve cancer outcomes.

The influence of time on the sensitivity of SARS-CoV-2 serological testing.

Sensitive serological testing is essential to estimate the proportion of the population exposed or infected with SARS-CoV-2, to guide booster vaccination and to select patients for treatment with anti-SARS-CoV-2 antibodies. The performance of serological tests is usually evaluated at 14-21 days post infection. This approach fails to take account of the important effect of time on test performance after infection or exposure has occurred. We performed parallel serological testing using 4 widely used assays (a multiplexed SARS-CoV-2 Nucleoprotein (N), Spike (S) and Receptor Binding Domain assay from Meso Scale Discovery (MSD), the Roche Elecsys-Nucleoprotein (Roche-N) and Spike (Roche-S) assays and the Abbott Nucleoprotein assay (Abbott-N) on serial positive monthly samples collected as part of the Co-STARs study ( www.clinicaltrials.gov , NCT04380896) up to 200 days following infection. Our findings demonstrate the considerable effect of time since symptom onset on the diagnostic sensitivity of different assays. Using a time-to-event analysis, we demonstrated that 50% of the Abbott nucleoprotein assays will give a negative result after 175 days (median survival time 95% CI 168-185 days), compared to the better performance over time of the Roche Elecsys nucleoprotein assay (93% survival probability at 200 days, 95% CI 88-97%). Assays targeting the spike protein showed a lower decline over the follow-up period, both for the MSD spike assay (97% survival probability at 200 days, 95% CI 95-99%) and the Roche Elecsys spike assay (95% survival probability at 200 days, 95% CI 93-97%). The best performing quantitative Roche Elecsys Spike assay showed no evidence of waning Spike antibody titers over the 200-day time course of the study. We have shown that compared to other assays evaluated, the Abbott-N assay fails to detect SARS-CoV-2 antibodies as time passes since infection. In contrast the Roche Elecsys Spike Assay and the MSD assay maintained a high sensitivity for the 200-day duration of the study. These limitations of the Abbott assay should be considered when quantifying the immune correlates of protection or the need for SARS-CoV-2 antibody therapy. The high levels of maintained detectable neutralizing spike antibody titers identified by the quantitative Roche Elecsys assay is encouraging and provides further evidence in support of long-lasting SARS-CoV-2 protection following natural infection.

The Influence of Time on the Sensitivity of SARS-CoV-2 Serological Testing.

Background: Serological testing is used to quantify SARS-CoV-2 seroprevalence, guide booster vaccination and select patients for anti-SARS-CoV-2 antibodies therapy. However, our understanding of how serological tests perform as time passes after infection is limited. Methods: Four assays were compared in parallel: 1) the multiplexed spike, nucleoprotein and receptor binding domain Meso Scale Discovery (MSD) assay 2) the Roche Elecsys-Nucleoprotein assay (Roche-N) 3) the Roche Spike assay (Roche-S) and 4) the Abbott Nucleoprotein assay (Abbott-N) on serial positive monthly samples from hospital staff up to 200 days following infection as part of the Co-Stars study. Results: We demonstrate that 50% of the Abbott-N assays give a negative result after 175 days (median survival time 95% CI 168-185 days) while the Roche-N assay (93% survival probability at 200 days, 95% CI 88-97%) maintained seropositivity. The MSD spike (97% survival probability at 200 days, 95% CI 95-99%) and the Roche-S assay (95% survival probability at 200 days, 95% CI 93-97%) also remained seropositive. The best performing quantitative Roche-S assay showed no evidence of waning Spike antibody titres over 200-days. Conclusions: The Abbott-N assay fails to detect SARS-CoV-2 antibodies as time passes since infection. In contrast the Roche and the MSD assays maintained high sensitivity. The limitations of the Abbott assay must be considered in clinical decision making. The long duration of detectable neutralizing spike antibody titres by the quantitative Roche-S assay provides further evidence in support of long-lasting SARS-CoV-2 protection to pre-existing strains of SARS-CoV-2 following natural infection. Trial registration : Co-STARs study was registered with ClinicalTrials.gov on May 8th, 2020, with trial number NCT04380896 (www.clinicaltrials.gov, NCT04380896).

External quality assessment: best practice.

There is a requirement for accredited laboratories to participate in external quality assessment (EQA) schemes, but there is wide variation in understanding as to what is required by the laboratories and scheme providers in fulfilling this. This is not helped by a diversity of language used in connection with EQA; Proficiency testing (PT), EQA schemes, and EQA programmes, each of which have different meanings and offerings in the context of improving laboratory quality. We examine these differences, and identify what factors are important in supporting quality within a clinical laboratory and what should influence the choice of EQA programme. Equally as important is how EQA samples are handled within the laboratory, and how the information provided by the EQA programme is used. EQA programmes are a key element of a laboratory's quality assurance framework, but laboratories should have an understanding of what their EQA programmes are capable of demonstrating, how they should be used within the laboratory, and how they support quality. EQA providers should be clear as to what type of programme they provide - PT, EQA Scheme or EQA Programme.

Isomaltulose Improves Postexercise Glycemia by Reducing CHO Oxidation in T1DM.

PURPOSE: individuals with type 1 diabetes mellitus (T1DM) are encouraged to consume CHO to prevent hypoglycemia during or after exercise. However, the research comparing specific types of CHO is limited. This study compared the alterations in metabolism and fuel oxidation in response to running after preexercise ingestion of isomaltulose or dextrose in T1DM. METHODS: after preliminary testing, on two occasions, eight T1DM individuals consumed 75 g of either dextrose (DEX; GI = 96) or isomaltulose (ISO; GI = 32), 2 h before performing 45 min of treadmill running at 80% ± 1% VO(2peak). Blood glucose (BG) was measured for 2 h before and 3 h after exercise. Cardiorespiratory parameters were collected at rest and during exercise. Data (mean ± SEM) were analyzed using repeated-measures ANOVA. RESULTS: there was a smaller increase in BG in the preexercise period under ISO with peak BG occurring at 120 min after ingestion compared with 90 min under DEX (Δ+4.5 ± 0.4 vs Δ+9.1 ± 0.6 mmol·L, P < 0.01). During the final 10 min of exercise, there were lower CHO (ISO 2.85 ± 0.07 vs DEX 3.18 ± 0.08 g·min, P < 0.05) and greater lipid oxidation rates (ISO 0.33 ± 0.03 vs DEX 0.20 ± 0.03 g·min, P < 0.05) under ISO. After exercise, ISO BG was lower than DEX for the entire 180-min period, with BG area under the curve and mean BG concentrations being 21% ± 3% and 3.0 ± 0.4 mmol·L lower, respectively (P < 0.05). CONCLUSIONS: consumption of ISO improves BG responses during and after exercise through reduced CHO and improved lipid oxidation during the later stages of exercise.

A combined insulin reduction and carbohydrate feeding strategy 30 min before running best preserves blood glucose concentration after exercise through improved fuel oxidation in type 1 diabetes mellitus.

In this study, we examined the glycaemic and fuel oxidation responses to alterations in the timing of a low glycaemic index carbohydrate and 75% reduced insulin dose, prior to running, in type 1 diabetes individuals. After carbohydrate (75 g isomaltulose) and insulin administration, the seven participants rested for 30 min, 60 min, 90 min or 120 min (conditions 30MIN, 60MIN, 90MIN, and 120MIN, respectively) before completing 45 min of running at 70% peak oxygen uptake. Carbohydrate and lipid oxidation rates were monitored during exercise and blood glucose and insulin were measured before and for 3 h after exercise. Data were analysed using repeated-measures analysis of variance. Pre-exercise blood glucose concentrations were lower for 30MIN compared with 120MIN (P < 0.05), but insulin concentrations were similar. Exercising carbohydrate and lipid oxidation rates were lower and greater, respectively, for 30MIN compared with 120MIN (P < 0.05). The drop in blood glucose during exercise was less for 30MIN (3.7 mmol · l(-1), s(x) = 0.4) compared with 120MIN (6.4 mmol · l(-1), s(x) = 0.3) (P = 0.02). For 60 min post-exercise, blood glucose concentrations were higher for 30MIN compared with 120MIN (P < 0.05). There were no cases of hypoglycaemia in the 30MIN condition, one case in the 60MIN condition, two in the 90MIN condition, and five in the 120MIN condition. In conclusion, a low glycaemic index carbohydrate and reduced insulin dose administered 30 min before running improves pre- and post-exercise blood glucose responses in type 1 diabetes.

A rare cause of Cushing's syndrome demonstrates analytical discrepancies between the Roche E170 and Bayer Centaur testosterone assays.

The initial biochemical investigations of a female patient with suspected Cushing's syndrome revealed abnormal endocrine results, including a marked elevation of serum testosterone. Overnight and low-dose dexamethasone suppression tests confirmed the diagnosis of Cushing's syndrome. Imaging investigations revealed an appearance compatible with adrenocortical carcinoma with metastases in the lungs and liver. This tumour is a rare cause of Cushing's syndrome. Two different automated testosterone immunoassays were used during the investigation of this patient, and analytical discrepancies in the patient's testosterone results were found. The two assays used, as well as potential causes of the difference in results will be discussed.