Faecal immunochemical test for patients with ‘high-risk’ bowel symptoms: a large prospective cohort study and updated literature review

Background We evaluated whether faecal immunochemical testing (FIT) can rule out colorectal cancer (CRC) among patients presenting with ‘high-risk’ symptoms requiring definitive investigation. Methods Three thousand five hundred and ninety-six symptomatic patients referred to the standard urgent CRC pathway were recruited in a multi-centre observational study. They completed FIT in addition to standard investigations. CRC miss rate (percentage of CRC cases with low quantitative faecal haemoglobin [f-Hb] measurement) and specificity (percentage of patients without cancer with low f-Hb) were calculated. We also provided an updated literature review. Results Ninety patients had CRC. At f-Hb < 10 µg/g, the miss rate was 16.7% (specificity 80.1%). At f-Hb < 4 µg/g, the miss rate was 12.2% (specificity 73%), which became 3.3% if low FIT plus the absence of anaemia and abdominal pain were considered (specificity 51%). Within meta-analyses of 9 UK studies, the pooled miss rate was 7.2% (specificity 74%) for f-Hb < 4 µg/g. Discussion FIT alone as a triage tool would miss an estimated 1 in 8 cases in our study (1 in 14 from meta-analysis), while many people without CRC could avoid investigations. FIT can focus secondary care diagnostic capacity on patients most at risk of CRC, but more work on safety netting is required before incorporating FIT triage into the urgent diagnostic pathway.

Saliva is superior over nasopharyngeal swab for detecting SARS-CoV2 in COVID-19 patients

Scaling up of diagnostic capacity is needed to mitigate the global pandemic of SARS-CoV2. However, there are challenges including shortage of sample collection swabs and transport medium. Saliva has been recommended as a simple, low-cost, non-invasive option. However, data from different populations and settings are limited. Here, we showed that saliva could be a good alternative sample to diagnose COVID-19 patients. Pair of NPS-saliva samples was collected from 152 symptomatic; confirmed COVID-19 patients, and compared their positivity rate, viral load, and duration of viral shedding. From 152 patients, 80 (52.63%) tested positive and 72 (47.37%) were negative for SARSA-CoV2 in NPS sample. In saliva, 129 (92.14%) were tested positive and 11 (7.86%) were negative on the day of admission to hospital. The overall percent agreement of RT-PCR result of Saliva to NPS was 70% (196/280). A comparison of viral load from 72 NPS-saliva pair samples on day of admission shows saliva contains significantly higher viral load (P < 0.001). In conclusion, saliva has higher yield in detecting SARS-CoV2, and COVID-19 patients show higher viral load and prolonged period of viral shedding in saliva. Therefore, we recommend saliva as a better alternative sample to NPS to diagnose COVID-19 patients.

Prediction of P-tau/Aβ42 in the cerebrospinal fluid with blood microRNAs in Alzheimer’s disease

Background The most common biomarkers of Alzheimer’s disease (AD) are amyloid β (Aβ) and tau, detected in cerebrospinal fluid (CSF) or with positron emission tomography imaging. However, these procedures are invasive and expensive, which hamper their availability to the general population. Here, we report a panel of microRNAs (miRNAs) in serum that can predict P-tau/Aβ42 in CSF and readily differentiate AD from other dementias, including vascular dementia (VaD), Parkinson disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). Methods RNA samples were extracted from the participant’s blood. P-tau/Aβ42 of CSF was examined for diagnostic purposes. A pilot study (controls, 21; AD, 23), followed by second (controls, 216; AD, 190) and third groups (controls, 153; AD, 151), is used to establish and verify a predictive model of P-tau/Aβ42 in CSF. The test is then applied to a fourth group of patients with different dementias (controls, 139; AD,155; amnestic mild cognitive impairment [aMCI], 55; VaD, 51; PDD, 53; bvFTD, 53; DLB, 52) to assess its diagnostic capacity. Results In the pilot study, 29 upregulated and 31 downregulated miRNAs in the AD group were found. In Dataset 2, these miRNAs were then included as independent variables in the linear regression model. A seven-microRNA panel (miR-139-3p, miR-143-3p, miR-146a-5p, miR-485-5p, miR-10a-5P, miR-26b-5p, and miR-451a-5p) accurately predicted values of P-tau/Aβ42 of CSF. In Datasets 3 and 4, by applying the predicted P-tau/Aβ42, the predictive model successfully differentiates AD from controls and VaD, PDD, bvFTD, and DLB. Conclusions This study suggests that the panel of microRNAs is a promising substitute for traditional measurement of P-tau/Aβ42 in CSF as an effective biomarker of AD.

Serum Long Non-Coding RNA SCARNA10 Serves As A Potential Diagnostic Biomarker For Hepatocellular Carcinoma

Background: Circulating long non-coding RNAs (lncRNAs) have been demonstrated to serve as diagnostic or prognosis biomarkers for various disease. We aimed to elucidate the diagnostic efficacy of serum lncRNA SCARNA10 for the hepatocellular carcinoma (HCC).Methods: In this study, a total of 127 patients with HCC, 55 patients with benign liver disease (BLD), and 99 healthy controls (HC) were enrolled in this study. According to different classifications, the levels of serum SCARNA10 were assessed by quantitative real-time polymerase chain reaction (qPCR). The correlations between serum SCARNA10 and clinicopathological charcaterisstics were further analyzed. The receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to estimate the diagnostic capacity of serum SCARNA10 and its combination with AFP for HCC. Results: The results demonstrated that the levels of serum SCARNA10 were significantly higher in HCC patients than in patients with BLD and healthy controls, and significantly increased in HCC patients with hepatitis B or C infection, or with liver cirrhosis. Furthermore, positive correlations were noted between serum SCARNA10 level and some clinicopathological characteristics, including tumor size, differentiation degrees, tumor stage, vascular invasion, tumor metastasis and complications. ROC analysis revealed that SCARNA10 had a significantly predictive value for HCC, the combination of SCARNA10 and AFP gained the higher accuracy. SCARNA10 retained significant diagnosis capabilities for AFP-negative HCC patients. Conclusions: In summary, lncRNA SCARNA10 may serve as a novel and non-invasive biomarker with relatively high sensitivity and specificity for HCC diagnosis.

The usefulness of antigen testing in predicting contagiousness in COVID-19

Increasing the diagnostic capacity of COVID-19 (SARS-CoV-2 infection) is required to improve case detection, reduce COVID-19 expansion, and boost the world economy. Rapid antigen detection tests are cheaper and easier to implement, but their diagnostic performance has been questioned compared to RT-PCR. Here, we evaluate the performance of the Standard Q COVID-19 antigen test for diagnosing SARS-CoV-2 infection and predicting contagiousness compared to RT-PCR and viral culture, respectively. The antigen test was 100.0% specific but only 40.9% sensitive for diagnosing infection compared to RT-PCR. Interestingly, SARS-CoV-2 contagiousness is highly unlikely with a negative antigen test since it exhibited a negative predictive value of 99.9% than viral culture. Furthermore, a cycle threshold (Ct) value of 18.1 in RT-PCR was shown to be the one that best predicts contagiousness (AUC 97.6%). Thus, screening people with antigen testing is a good approach to prevent SARS-CoV-2 contagion and allow returning to daily activities.

Disentangling the Progression of Non-alcoholic Fatty Liver Disease in the Human Gut Microbiota

Gut microbiome dysbiosis has been known to be associated with all stages of non-alcoholic fatty liver disease (NAFLD), but questions remain about microbial profiles in progression and homogeneity across NAFLD stages. We performed a meta-analysis of three publicly shotgun datasets and built predictive models to determine diagnostic capacity. Here, we found consistently microbiome shifts across NAFLD stages, of which co-occurrence patterns and core sets of new biomarkers significantly correlated with NAFLD progression were identified. Machine learning models that are able to distinguish patients with any NAFLD stage from healthy controls remained predictive when applied to patients with other NAFLD stages, suggesting the homogeneity across stages once again. Focusing on species and metabolic pathways specifically associated with progressive stages, we found that increased toxic metabolites and decreased protection of butyrate and choline contributed to advanced NAFLD. We further built models discriminating one stage from the others with an average of 0.86 of area under the curve. In conclusion, this meta-analysis firmly establishes generalizable microbiome dysbiosis and predictive taxonomic and functional signatures as a basis for future diagnostics across NAFLD stages.

Accuracy of cone-beam CT in detecting vertical root fractures in teeth with post-endodontic restorations: an in vitro study

The aim of this study was to evaluate the accuracy of cone-beam CT (CBCT) for the detection of artificially created vertical root fractures (VRF) in extracted teeth restored with metallic (MP) and fiberglass (FGP) posts. After root canal obturation, 60 extracted human premolars were scanned by using the highest-resolution settings of a CBCT unit. The prepared roots were randomly divided into three groups: group C (control group): non-restored and non- endodontically treated teeth (n = 20); group MP (n = 20); group FGP (n = 20). In all groups, 10 teeth were artificially fractured. Two external and independent observers blindly recorded the presence or absence of VRF. Sensitivity, specificity, accuracy, intra- and interobserver agreement were calculated. Kappa value for inter- and intraobserver agreement was 0.82 and 0.84 respectively, demonstrating good agreement. The highest values for sensitivity (0.80 - 0.90), specificity (1.00) and accuracy (0.90 - 0.95) were found in the control group. The teeth with FGP restoration presented the lowest sensitivity (0.30 - 0.50) and accuracy (0.60 - 0.65) values. Both examiners had a good performance in the diagnosis of fractures in teeth with MP, with accuracy ranging between 0.85 - 0.90. The presence of MP did not influence accuracy; however, the presence of FGP reduced the diagnostic capacity of CBCT.