Annals of Clinical Biochemistry: International Journal of Laboratory Medicine

To provide theoretical support for clinical diagnosis of lung cancer through an overview of systematic reviews (SRs) of the diagnostic value of miRNA.

We searched PubMed, Embase, and the Cochrane Library to collect SRs of the diagnostic value of microRNA for lung cancer until April 2021. A comprehensive database search was carried out, screened, and extracted information independently by two researchers, to compare and analyze the sensitivity and specificity of relevant literatures. The ROBIS tool was applied to assess the risk of bias of included SRs and meta-analysis.

A total of 10 SRs were included the results of risk of bias assessment by ROBIS tool showed: 10 SRs completely matched the four questions of phase one. In phase two, nine SRs were low risk of bias in the including criteria field; one study was uncertain; nine SRs were low risk of bias, one study was uncertain in the literature search and screening field; nine SRs were low risk of bias in the data abstraction and quality assessment field, one SR was high; and 10 SRs were low risk of bias in the data synthesis field. In the phase three of comprehensive risk of bias results, 8 studies were low risk, one was high risk, and one study was uncertain. MiRNA had a pooled sensitivity of 0.77 (95% CI: 0.73–0.81) and specificity of 0.81 (95% CI: 0.79–0.84). The summarized area under the SROC curve was 0.86 (95% CI: 0.83–0.89), and combined diagnostic odds ratio was 14.68 (10.87–19.81). The sensitivity and specificity of multiple MicroRNA was 0.80 (0.73–0.85) and 0.80 (0.76–0.83); the sensitivity and specificity of single MicroRNA was 0.74 (0.69–0.79) and 0.83 (0.80–0.88).

MiRNA is a promising biomarker for the diagnosis of lung cancer in Chinese population, with advanced sensitivity and specificity. It provides a faster and less invasive assessment of lung cancer than other markers that require histopathological analysis. We should improve the reliability of the conclusion. The construction of diagnosis for lung cancer provides reliable evidence support.

Faecal Immunochemical tests (FITs) in the assessment of patients presenting with symptoms have generally used a single sample. Little evidence pertains to the use of replicate, where a number of tests are done prior to decision-making or repeat FIT, where additional FIT are performed following clinical decision-making. Overwhelmingly, research has focussed on FIT to help identify colorectal cancer (CRC). The aim of this review is to assess the available literature concerning replicate and repeat FIT in symptomatic patients to help generate consensus and guide future research.

The terms ‘faecal immunochemical test’ or ‘FIT’ were combined with ‘multiple’ or ‘repeat’. EMBASE, Medline and PubMed database and other searches were conducted. All papers published in English were included with no exclusion date limits until November 2021.

Of the 161 initial papers screened, seven were included for review. Qualitative and quantitative FIT outcomes were assessed in the studies. The primary aims of most related to whether replicate FIT increased diagnostic yield of CRC, with colonoscopy used as the reference standard. One publication assessed the impact of a new COVID-adapted pathway on CRC detection. No consensus on replicate FIT was apparent. Some concluded that FITs may help minimise missed CRC diagnoses: others showed no increase in diagnostic yield of CRC.

Current evidence on replicate and repeat FIT is both minimal and conflicting. FIT is a superb clinical tool, but significant gaps surrounding application remain. Further studies relating to replicate and repeat FIT are required.

Laboratories are recommended to use patient data to derive their local adjusted calcium (adjCa) equation, using numerous criteria to exclude patients with potential calcium metabolism abnormalities. It is not known which, if any, of the exclusions influence the final equation formula, or to what extent. This study investigated the effect using fewer exclusions has on adjCa equations and on patient results when compared to a reference equation.

A reference ACB adjCa equation was derived from the total calcium and albumin pairs of 1305 individuals who, from an initial 22,906 adults, met recommended criteria (excluding abnormalities in either calcium, albumin, creatinine, magnesium, ALP or ALT, and specific clinical areas). This reference equation was compared to seven alternatives derived using fewer criteria, including one with no exclusions. All equations were applied to a validation cohort (n=19,640) to determine their effect on adjCa results and on categorizing patients into hypo-, normo- or hypercalcaemia.

Most alternative adjCa equations, including the one without any exclusions, showed no statistical (p < 0.05) difference in their slope or intercept compared to the ACB reference. Nor did any of the validation cohort have a clinically significantly different adjCa result (>5% and >0.1 mmol/L different) when applying an alternative rather than the reference equation. Additionally, no alternative equation changed the kappa categorization of the validation population’s calcium status.

When deriving adjCa equations, most exclusion criteria have little influence on the equation or patient results, including using none at all. This knowledge could simplify deployment of local equations.

Ethylenediaminetetraacetic acid (EDTA) contamination of serum samples is common but under-recognized unless EDTA is measured. Incorrect order of draw with closed phlebotomy (vacutainer) does not cause EDTA contamination. EDTA contamination occurs largely or solely during open phlebotomy due to syringe tip or needle-tip contamination when delivering blood into EDTA sample tubes before other sample tubes or direct transfer of blood from EDTA containing tubes to other tubes. Therefore, preference for closed phlebotomy or following the order of tube fill when open phlebotomy is used may reduce EDTA contamination.

The laboratory’s comments for EDTA-contaminated serum samples were amended to encourage closed phlebotomy and with open phlebotomy filling of serum tubes before EDTA and fluoride-EDTA tubes. The weekly frequency of EDTA sample contamination, normalized for weekly urea and electrolyte (U&E) requests, was studied 52 weeks before and 43 weeks after amending the comments.

Median (IQR) frequency of EDTA-contaminated samples per week per 10,000 U&Es decreased by 58% [5.6 (3.1–9.2) versus 2.3 (1.1–4.4); P < 0.001] after the introduction of the new comment.

Explicit automated laboratory feedback comments promoting closed phlebotomy and order of tube fill with open phlebotomy were associated with a 58% reduction in EDTA-contaminated samples and thus may play a role in improving phlebotomy practise.

Pancreatic elastase-1 (PE1) can be measured to assess exocrine activity of the pancreas. A semi-automated particle-enhanced, open-channel turbidimetric immunoassay has been introduced by Bühlmann (fPELA turbo, Bühlmann Laboratories AG, Schoenenbuch, Switzerland). Published evaluation data is lacking. We therefore verified performance of the assay on the Binding Site Optilite benchtop analyser and undertook a sample comparison with the DiaSorin PE1 assay on the Liaison.

Accuracy, imprecision, lower limit of quantitation (LLoQ) and linearity of the Bühlmann fPELA turbo assay on the Binding Site Optilite analyser was ascertained. Comparison with the DiaSorin Liaison PE1 assay was also undertaken. Difference between assays was evaluated using the Wilcoxon signed-rank test and method comparison was undertaken using Spearman’s rank correlation (rs), Bland–Altman and Passing–Bablok regression analyses.

The fPELA turbo assay was linear between 5 and 2500 μg/g. The LLoQ was 5 µg/g. Intra- and inter-assay imprecision was <6%. There was a good agreement (rs = 0.92) and no significant bias (5.8 µg/g, P = 0.29) present between the Bühlmann fPELA turbo and DiaSorin PE1 assays.

The Bühlmann fPELA turbo assay performs well on the Binding Site Optilite analyser. Faecal elastase results are commutable between with Bühlmann fPELA turbo and DiaSorin Liaison PE1 assays.

Low faecal elastase-1 (FE-1) results are suggestive of pancreatic insufficiency, but watery diarrhoea may lead to falsely low results.

FE-1 results reported on watery samples over a three-year period were reviewed. Results in watery samples were compared to those from a formed sample. The follow-up of patients in whom an FE-1 result ≤199 ug/g stool (Schebo ELISA) was reported on a watery sample was also reviewed.

In total, 288 watery samples were identified. All results (19/19) ≥200 ug/g in watery samples were also ≥200 ug/g when measured in a formed sample from the same patient. There were 41 results ≤199 ug/g in watery samples, of which 29 (71%) were ≥200 ug/g when measured in a formed sample. Thirty-seven patients with a single FE-1 value ≤199 ug/g from a watery sample were followed up. Pancreatic Enzyme Replacement Therapy (PERT) was commenced in 15 patients. This was inappropriate in at least one patient. Reporting practice was subsequently changed to not report FE-1 values ≤199 ug/g in watery samples. This change was assessed after 12 months. Repeat samples were received from 15/56 (27%) of patients. Overall, 10/15 (67%) of samples were ≥200 ug/g on repeat. PERT was not commenced inappropriately in any of these patients.

There is value in measuring FE-1 in watery samples, as 144/288 (50%) of watery samples analysed were ≥200 ug/g, enabling a diagnosis of exocrine pancreatic insufficiency to be excluded. Not reporting FE-1 values ≤199 ug/g in a first-time watery stool samples appears clinically safe and has potentially reduced inappropriate diagnoses and prescribing.