Meta-analysis of variable-temperature PCR technique performance for diagnosising Schistosoma japonicum infections in humans in endemic areas

Background As China is moving onto schistosomiasis elimination/eradication, diagnostic methods with both high sensitivity and specificity for Schistosoma japonicum infections in humans are urgently needed. Microscopic identification of eggs in stool is proven to have poor sensitivity in low endemic regions, and antibody tests are unable to distinguish between current and previous infections. Polymerase chain reaction (PCR) technologies for the detection of parasite DNA have been theoretically assumed to show high diagnostic sensitivity and specificity. However, the reported performance of PCR for detecting S. japonicum infection varied greatly among studies. Therefore, we performed a meta-analysis to evaluate the overall diagnostic performance of variable-temperature PCR technologies, based on stool or blood, for detecting S. japonicum infections in humans from endemic areas. Methods We searched literatures in eight electronic databases, published up to 20 January 2021. The heterogeneity and publication bias of included studies were assessed statistically. The risk of bias and applicability of each eligible study were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2). The bivariate mixed-effects model was applied to obtain the summary estimates of diagnostic performance. The hierarchical summary receiver operating characteristic (HSROC) curve was applied to visually display the results. Subgroup analyses and multivariate regression were performed to explore the source of heterogeneity. This research was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered prospectively in PROSPERO (CRD42021233165). Results A total of 2791 papers were retrieved. After assessing for duplications and eligilibity a total of thirteen publications were retained for inclusion. These included eligible data from 4268 participants across sixteen studies. High heterogeneity existed among studies, but no publication bias was found. The pooled analyses of PCR data from all included studies resulted in a sensitivity of 0.91 (95% CI: 0.83 to 0.96), specificity of 0.85 (95% CI: 0.65 to 0.94), positive likelihood ratio of 5.90 (95% CI: 2.40 to 14.60), negative likelihood ratio of 0.10 (95% CI: 0.05 to 0.20) and a diagnostics odds ratio of 58 (95% CI: 19 to 179). Case-control studies showed significantly better performances for PCR diagnostics than cross-sectional studies. This was further evidenced by multivariate analyses. The four types of PCR approaches identified (convention PCR, qPCR, Digital droplet PCR and nested PCR) differed significantly, with nested PCRs showing the best performance. Conclusions Variable-temperature PCR has a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas. More high quality studies on S. japonicum diagnostic techniques, especially in low endemic areas and for the detection of dual-sex and single-sex infections are required. These will likely need to optimise a nested PCR alongside a highly sensitive gene target. They will contribute to successfully monitoring endemic areas as they move towards the WHO 2030 targets, as well as ultimately helping areas to achieve these goals.

Pretherapeutic Assessment of Pancreatic Cancer: Comparison of FDG PET/CT Plus Delayed PET/MR and Contrast-Enhanced CT/MR

PurposeThis study aims to determine the diagnostic performance of whole-body FDG PET/CT plus delayed abdomen PET/MR imaging in the pretherapeutic assessment of pancreatic cancer in comparison with that of contrast-enhanced (CE)-CT/MR imaging.Materials and MethodsForty patients with pancreatic cancer underwent nonenhanced whole-body FDG PET/CT, delayed abdomen PET/MR imaging, and CE-CT/MR imaging. Two nuclear medicine physicians independently reviewed these images and discussed to reach a consensus, determining tumor resectability according to a 5-point scale, N stage (N0 or N positive), and M stage (M0 or M1). With use of clinical-surgical-pathologic findings as the reference standard, diagnostic performances of the two imaging sets were compared by using the McNemar test.ResultsThe diagnostic performance of FDG PET/CT plus delayed PET/MR imaging was not significantly different from that of CE-CT/MR imaging in the assessment of tumor resectability [area under the receiver operating characteristic curve: 0.927 vs. 0.925 (p = 0.975)], N stage (accuracy: 80% (16 of 20 patients) vs. 55% (11 of 20 patients), p = 0.125), and M stage (accuracy: 100% (40 of 40 patients) vs. 93% (37 of 40 patients), p = 0.250). Moreover, 14 of 40 patients had liver metastases. The number of liver metastases detected by CE-CT/MR imaging, PET/CT, and PET/MR imaging were 33, 18, and 61, respectively. Compared with CE-CT/MR imaging, PET/MR imaging resulted in additional findings of more liver metastases in 9/14 patients, of which 3 patients were upstaged. Compared with PET/CT, PET/MR imaging resulted in additional findings of more liver metastases in 12/14 patients, of which 6 patients were upstaged.ConclusionsAlthough FDG PET/CT plus delayed PET/MR imaging showed a diagnostic performance similar to that of CE-CT/MR imaging in the pretherapeutic assessment of the resectability and staging of pancreatic tumors, it still has potential as the more efficient and reasonable work-up approach for the additional value of metastatic information provided by delayed PET/MR imaging.

Deep Learning in Prostate Cancer Diagnosis Using Multiparametric Magnetic Resonance Imaging With Whole-Mount Histopathology Referenced Delineations

Background: Multiparametric magnetic resonance imaging (mpMRI) plays an important role in the diagnosis of prostate cancer (PCa) in the current clinical setting. However, the performance of mpMRI usually varies based on the experience of the radiologists at different levels; thus, the demand for MRI interpretation warrants further analysis. In this study, we developed a deep learning (DL) model to improve PCa diagnostic ability using mpMRI and whole-mount histopathology data.Methods: A total of 739 patients, including 466 with PCa and 273 without PCa, were enrolled from January 2017 to December 2019. The mpMRI (T2 weighted imaging, diffusion weighted imaging, and apparent diffusion coefficient sequences) data were randomly divided into training (n = 659) and validation datasets (n = 80). According to the whole-mount histopathology, a DL model, including independent segmentation and classification networks, was developed to extract the gland and PCa area for PCa diagnosis. The area under the curve (AUC) were used to evaluate the performance of the prostate classification networks. The proposed DL model was subsequently used in clinical practice (independent test dataset; n = 200), and the PCa detective/diagnostic performance between the DL model and different level radiologists was evaluated based on the sensitivity, specificity, precision, and accuracy.Results: The AUC of the prostate classification network was 0.871 in the validation dataset, and it reached 0.797 using the DL model in the test dataset. Furthermore, the sensitivity, specificity, precision, and accuracy of the DL model for diagnosing PCa in the test dataset were 0.710, 0.690, 0.696, and 0.700, respectively. For the junior radiologist without and with DL model assistance, these values were 0.590, 0.700, 0.663, and 0.645 versus 0.790, 0.720, 0.738, and 0.755, respectively. For the senior radiologist, the values were 0.690, 0.770, 0.750, and 0.730 vs. 0.810, 0.840, 0.835, and 0.825, respectively. The diagnosis made with DL model assistance for radiologists were significantly higher than those without assistance (P < 0.05).Conclusion: The diagnostic performance of DL model is higher than that of junior radiologists and can improve PCa diagnostic accuracy in both junior and senior radiologists.

Change in Computed Tomography-Derived Fractional Flow Reserve Across the Lesion Improve the Diagnostic Performance of Functional Coronary Stenosis

Aims: This study sought to evaluate the diagnostic performance of change in computed tomography-derived fractional flow reserve (CT-FFR) across the lesion (ΔCT-FFR) for identifying ischemia lesions with FFR as the reference standard.Methods: Patients who underwent coronary CT angiography (CCTA) and FFR measurement within 1 week from December 2018 to December 2019 were retrospectively enrolled. CT-FFR within 2 cm distal to the lesion, ΔCT-FFR and plaque characteristics were analyzed. The diagnostic accuracy of CCTA (coronary stenosis ≥ 50%), CT-FFR ≤ 0.80, and ΔCT-FFR ≥ 0.15 (based on the largest Youden index) were assessed with FFR as the reference standard. The relationship between plaque characteristics and ΔCT-FFR was analyzed.Results: The specificity of ΔCT-FFR and CT-FFR were 70.8 and 67.4%, respectively, which were both higher than CCTA (39.3%) (both P < 0.001), while there were no statistical significance in sensitivity among the three (84.5, 77.4, 88.1%, respectively; P = 0.08). The area under the curves (AUCs) of ΔCT-FFR and CT-FFR were 0.803 and 0.743, respectively, which were both higher than that of CCTA (0.637) (both P < 0.05), and the AUC of ΔCT-FFR was higher than that of CT-FFR (P < 0.001). Multivariable analysis showed that low-attenuation plaque (LAP) volume (odds ratio [OR], 1.006) and plaque length (OR, 1.021) were independently correlated with ΔCT-FFR (both P < 0.05).Conclusions: CT-FFR and ΔCT-FFR and here especially the ΔCT-FFR could improve the diagnostic performance of ischemia compared with CCTA alone. LAP volume and plaque length were the independent risk factors of ΔCT-FFR.

Diagnostic performance of oral swabs for non-sputum based TB diagnosis in a TB/HIV endemic setting

Objective We evaluated diagnostic performance of oral swab analysis (OSA) for tuberculosis (TB) in a high HIV/TB burden setting in Kenya. Methods In this cross-sectional study, buccal swabs and sputum were collected from 100 participants with suspected TB in outpatient clinics in Kenya at enrollment and subsequent morning visits. Buccal swabs underwent IS6110-targeted qPCR analysis. Sputum was evaluated by Xpert MTB/RIF (Xpert) and culture. Diagnostic performance of OSA for TB diagnosis was evaluated relative to a combined reference of sputum Xpert and culture. Results Among 100 participants, 54% were living with HIV (PLHIV). Twenty percent (20/100) of participants had confirmed TB (19/20 [95%] culture-positive, 17/20 [85%] Xpert-positive). Overall buccal swab sensitivity was 65.0% (95% CI 40.8–84.6%) vs. sputum Xpert/culture and 76.5% (95% CI 50.1–93.2%) vs. sputum Xpert alone. Specificity was 81.3% (95% CI 71.0–89.1%) and 81.9% (95% CI 72.0–89.5%) compared to sputum Xpert/culture and Xpert alone, respectively. Sensitivity among PLHIV (n = 54) with suspected TB was 83.3% (95% CI 35.9–99.6%) vs. sputum Xpert/culture and 100% (95% CI 47.8–100.0%) vs. sputum Xpert alone. Among participants with TB, mean OSA threshold quantitation cycle (Cq) value was lower (stronger signal) at subsequent morning compared to enrolment visit (33.4 SD ± 3.7 vs. 35.2 SD ± 2.9, p = 0.009). Conclusions In this pilot study, results confirm M. tuberculosis DNA is detectable in oral swabs including among PLHIV with fair diagnostic performance. Further work is needed to optimize OSA and evaluate its utility in diverse settings.