Percentage Of False Positive Results Research Articles

Role of exosomes in false-positive COVID-19 PCR tests: Non-specificity of SARS-CoV-2-RNA in vivo detection explains artificial post-pandemic peaks

Background: The COVID-19 pandemic priorities have focused on prevention by detection and response. National governments’ prevention response decisions are based upon detection statistics from PCR (polymerase chain reaction) tests that are used to define numbers of (i) COVID-19 infected persons, (ii) COVID-19 hospitalisations, and (iii) COVID-19 deaths. These statistics assume a priori that PCR tests are nigh 100% true detectors of COVID-19 infections. Here we will provide an alternative interpretation, along with the compelling evidence, that false positives have distorted to some degree the statistics of the primary outbreaks, and account for almost the whole of the 2nd and subsequent apparent COVID-19 outbreak peaks in various countries. Methods: We extract from the published literature on PCR-test outcomes graphical data that reveals the evidence for a very large percentage of false positive results. We review the role of exosomes in the immune response to all respiratory viral infections and its effect on PCR tests. We hypothesise that exosomes, triggered by all viral respiratory infections, are largely responsible for positive outcomes from PCR tests for COVID-19. We test our alternative interpretation for consistency with the empirical epidemiological trends as published by the World Health Organization (WHO). The Scientific Method is used to direct our research efforts. Findings: We find that PCR testing data for the second and following waves of the COVID-19 pandemic indicate that these waves are mainly artefacts of false-positive results. We find that this interpretation provides a more consistent explanation of the known epidemiology of COVID-19 than the hitherto consensus notion of extremely contagious and rapidly mutating viruses. Interpretation: The RNA (ribonucleic acid) code detected in PCR tests, previously attributed to SARS-CoV-2, belongs instead to a respiratory-virus-induced immune system response by human cells that liberate exosomes, and that vitiate PCR test results. PCR tests have zero specificity in vivo due to the exosome RNA. PCR tests exhibit excellent specificity in vitro on pure samples of other respiratory viruses. The low success rate of vaccines in preventing COVID-19 is explained by the inexact identification of the SARS-CoV-2 RNA.

Vulvoscopy: anachronism or a time-tested method?

Objective. Due to the growing number of patients with various diseases of the vulva, there is a need to evaluate the available diagnostic tools. Vulvoscopy is one of the widely used methods, the diagnostic sensitivity and specificity of which varies significantly.Purpose of the work. Based on the analysis of publications to determine the diagnostic significance of vulvoscopy.Material and methods. The data of modern research and publications were used in the preparation of the work.Results. The authors of a number of publications warn against considering vulvoscopy as a variant of colposcopy. A high percentage of false positive results when performing tests with acetic acid may be due to a variety of reasons and is not highly specific for papillomavirus infection. The use of the test with toluidine blue is not recommended due to low sensitivity.Conclusions. A positive aspect of vulvoscopy is the ability to examine the vulva area with optical magnification, in a position convenient for examining the patient, which makes it possible to identify areas to be biopsied. The use of additional tests with acetic acid should be limited, and tests with toluidine blue and Lugol solution are not recommended due to low sensitivity.

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The use of handheld ultrasound device in cardiac examination of patients with history of COVID-19

Abstract Background Clinical usefulness of Handheld Ultrasound Device [HUD] was previously confirmed in numerous clinical scenarios. During the previous two years Covid-19 patients become a focal point of healthcare worldwide. The assessment of long term consequences of this infection is bound to overload already burdened healthcare system. Purpose To assess clinical usefulness of HUD as an adjunct to physical cardiac examination of patients with history of COVID-19. Methods Study population consisted of randomly selected patients with no symptoms of cardiovascular pathology, who had been hospitalized due to COVID-19 one year prior to examination. Physical examination and clinical assessment was augmented with short examination with the use of HUD, which included: visual evaluation of the global and regional LV function, measurement of RV size, screening for the significant valve defects and the presence of pericardial effusion. Subsequently full echocardiographic examination with the use of high-end workstation was performed, which results were treated as reference. Results 54 patients (35 men, mean age 63±13 years) were enrolled into the study. In clinical examination no significant cardiovascular abnormalities were discovered. In 30 [56%] of patients cardiac abnormalities in HUD examination were detected. In 18 patients [33%] LV function assessment was not performed, due to insufficient quality of registered view. In the remaining group significant impairment of LV ejection fraction (<50%) was detected in HUD examination in 3 [6%] patients (2 confirmed in full examination, positive predictive value [PPV] 57%, negative predictive value [NPV] 97%, AUC 0,82±0,17, P 0,057). WMA were diagnosed in 6 [11%] patients (4 confirmed in full examination, PPV 84% NPV 78%, AUC 0,69±0,17, P 0,02). RV enlargement was identified in 21 [39%] patients (PPV 57%, NPV 97%, AUC 0,85±0,05, P<0,0001), mild pericardial effusion in 3 [6%] patient (1 confirmed in full echocardiographic examination; 2 false positive, no false negative), at least moderate mitral/tricuspid/aortic valve insufficiency in 7 [13%] patients (3 confirmed, 4 false positive cases, no false negative). A total mean time of the heart and lungs HUD examination was 2,1±0,6 minute. Conclusion Cardiac abnormalities exposed in brief assessment with the use HUD are a relatively common finding in asymptomatic patients previously hospitalized due to COVID infection in a 1-year follow-up, despite normal physical examination. Normal HUD examination excludes the presence of significant cardiac abnormalities with high probability. However one should keep in mind a relatively high percentage of false positive results, which may lead to an exceeding number of patients referred for a full echocardiographic examination. Funding Acknowledgement Type of funding sources: None.

The use of handheld ultrasound device in cardiac examination of patients with history of COVID-19

Abstract Background Clinical usefulness of Handheld Ultrasound Device [HUD] was previously confirmed in numerous clinical scenarios. During the previous two years Covid-19 patients become a focal point of healthcare worldwide. The assessment of long term consequences of this infection is bound to overload already burdened healthcare system. Purpose To assess clinical usefulness of HUD as an adjunct to physical cardiac examination of patients with history of COVID-19. Methods Study population consisted of randomly selected patients with no symptoms of cardiovascular pathology, who had been hospitalized due to COVID-19 one year prior to examination. Physical examination and clinical assessment was augmented with short examination with the use of HUD, which included: visual evaluation of the global and regional LV function, measurement of RV size, screening for the significant valve defects and the presence of pericardial effusion. Subsequently full echocardiographic examination with the use of high-end workstation was performed, which results were treated as reference. Results 54 patients (35 men, mean age 63±13 years) were enrolled into the study. In clinical examination no significant cardiovascular abnormalities were discovered. In 30 [56%] of patients cardiac abnormalities in HUD examination were detected. In 18 patients [33%] LV function assessment was not performed, due to insufficient quality of registered view. In the remaining group significant impairment of LV ejection fraction (<50%) was detected in HUD examination in 3 [6%] patients (2 confirmed in full examination, positive predictive value [PPV] 57%, negative predictive value [NPV] 97%, AUC 0,82±0,17, P 0,057). WMA were diagnosed in 6 [11%] patients (4 confirmed in full examination, PPV 84% NPV 78%, AUC 0,69±0,17, P 0,02). RV enlargement was identified in 21 [39%] patients (PPV 57%, NPV 97%, AUC 0,85±0,05, P<0,0001), mild pericardial effusion in 3 [6%] patient (1 confirmed in full echocardiographic examination; 2 false positive, no false negative), at least moderate mitral/tricuspid/aortic valve insufficiency in 7 [13%] patients (3 confirmed, 4 false positive cases, no false negative). A total mean time of the heart and lungs HUD examination was 2,1±0,6 minute. Conclusion Cardiac abnormalities exposed in brief assessment with the use HUD are a relatively common finding in asymptomatic patients previously hospitalized due to COVID infection in a 1-year follow-up, despite normal physical examination. Normal HUD examination excludes the presence of significant cardiac abnormalities with high probability. However one should keep in mind a relatively high percentage of false positive results, which may lead to an exceeding number of patients referred for a full echocardiographic examination. Funding Acknowledgement Type of funding sources: None.

The use of artificial intelligence in MRI diagnostics of rectal cancer

AIM: development of medical decision support systems for MRI diagnostics of rectal cancer: localization and segmentation of the primary tumor. PATIENTS AND METHODS: the research included 450 MRI studies of patients with rectal cancer and 450 MRI studies of patients without a tumor lesion of the rectum. All patients with tumors of rectum had histological verification of the malignant process. Data were collected in T2Wcoronal and axial projections (MRI Philips Achieva 1.5 T). Object marking was carried out only for T2W projections, where the area of interest was segmented - rectum, sigmoid colon and tumor. The ITK-Snap program was used to label MRI images. The validated studies and labeling were used to create a machine learning model that demonstrates the capability of the dataset to build medical decision support systems. SegResNet, TransUnet, 3D Unet neural networks were used to create a basic artificial intelligence model. The data set of patients and the direct marking of MRI studies were carried out by doctors of Ryzhikh National Medical Research Center of Coloproctology. The development of the artificial intelligence model, markup validation was carried out by employees of JSC "National Center of Service Integration" and LLC "Medical Screening Systems". RESULTS: dice similarity coefficient (DSC) of various neural networks were: TransUnet - 0.33, SegResNet - 0.50, 3D Unet - 0.42. The diagnostic efficiency of the SegResNet neural network in detecting rectal tumors with the addition of negative examples and post-processing was: accuracy 77.0%; sensitivity 98.1%; specificity 45.1%; positive predictive value 72.9%; negative predictive value of 94.1%. At this stage, AI has a fairly high sensitivity and accuracy, which indicates a high diagnostic efficiency in terms of visualizing the primary tumor and determining localization in the rectum. However, the specificity of the method is still at an unsatisfactory level (45.1%), which indicates a high percentage of false positive results in healthy patients and does not allow the model to be used as a screening method at this stage of development. CONCLUSION: the collected dataset of MRI studies and their markup made it possible to obtain an AI model that allows solving the problem of segmenting a rectal tumor and determining its localization. The next stage in the development of AI is to improve its specificity, expand the analyzed parameters, such as the depth of tumor invasion, visualization of metastatic lymph nodes and the status of the resection margin. To further develop the model metric and improve its diagnostic capabilities, we should experiment with training parameters and increase the dataset.

The use of artificial intelligence in MRI diagnostics of rectal cancer

AIM: development of medical decision support systems for MRI diagnostics of rectal cancer: localization and segmentation of the primary tumor. PATIENTS AND METHODS: the research included 450 MRI studies of patients with rectal cancer and 450 MRI studies of patients without a tumor lesion of the rectum. All patients with tumors of rectum had histological verification of the malignant process. Data were collected in T2Wcoronal and axial projections (MRI Philips Achieva 1.5 T). Object marking was carried out only for T2W projections, where the area of interest was segmented - rectum, sigmoid colon and tumor. The ITK-Snap program was used to label MRI images. The validated studies and labeling were used to create a machine learning model that demonstrates the capability of the dataset to build medical decision support systems. SegResNet, TransUnet, 3D Unet neural networks were used to create a basic artificial intelligence model. The data set of patients and the direct marking of MRI studies were carried out by doctors of Ryzhikh National Medical Research Center of Coloproctology. The development of the artificial intelligence model, markup validation was carried out by employees of JSC "National Center of Service Integration" and LLC "Medical Screening Systems". RESULTS: dice similarity coefficient (DSC) of various neural networks were: TransUnet - 0.33, SegResNet - 0.50, 3D Unet - 0.42. The diagnostic efficiency of the SegResNet neural network in detecting rectal tumors with the addition of negative examples and post-processing was: accuracy 77.0%; sensitivity 98.1%; specificity 45.1%; positive predictive value 72.9%; negative predictive value of 94.1%. At this stage, AI has a fairly high sensitivity and accuracy, which indicates a high diagnostic efficiency in terms of visualizing the primary tumor and determining localization in the rectum. However, the specificity of the method is still at an unsatisfactory level (45.1%), which indicates a high percentage of false positive results in healthy patients and does not allow the model to be used as a screening method at this stage of development. CONCLUSION: the collected dataset of MRI studies and their markup made it possible to obtain an AI model that allows solving the problem of segmenting a rectal tumor and determining its localization. The next stage in the development of AI is to improve its specificity, expand the analyzed parameters, such as the depth of tumor invasion, visualization of metastatic lymph nodes and the status of the resection margin. To further develop the model metric and improve its diagnostic capabilities, we should experiment with training parameters and increase the dataset.

Bioinformatic analysis of genomes of commercial breeds of domestic pigs for identification of breed-specific SNPs

Determining the purebredity of farm animals in a breeding system is of key importance for the entire livestock industry. Purebred breeding of plant breeds is designed to ensure the production of high-value improving breeding material for commercial livestock breeding. Determination of purebredity of pigs can be carried out using single nucleotide polymorphisms (SNP). The multiplexing technology today has reached a level that makes it possible to characterize tens and hundreds of thousands of polymorphic variants simultaneously for hundreds of animals in one run of the device. For the first time, using bioinformatics methods, an analysis of genome-wide projects was carried out for 264 individuals of the species Sus scrofa located in the Sequence Read Archive (NCBI-SRA). The in silico genotype was determined for 692 SNPs, of which 59 SNPs showed a significant potential for differentiation of four commercial breeds: large white (the most significant SNPs are Chr. 6: g.85845403T> G and Chr.16: g.74053569T> C), duroc (Chr. 4: g.55661608A> G, Chr. 14: g.107689091T> C and Chr. 14: g.107939105T> C), landrace (Chr. 5: g.99925204A> G, Chr. 18: g .40100481A> G and Chr. 18: g.7664624A> G) and pietrain (Chr. 13: g.136017764T> C and Chr.17: g.47595840A> G). For breeds of duroc and pietrain pigs, the accuracy of differentiation was at least 99%, for breeds of large white and landrace pigs - over 80%, however, the sensitivity indicator characterizing the percentage of false positive results of classification was slightly over 65%. Creation of models for molecularand-genetic studies of these breeds will allow for a genetic examination of their purebredity, which will contribute to an increase in their breeding value and preservation of the national gene pool.

In chemico sequential testing strategy for assessing the photoallegic potential

Several non-animal testing methods to assess photoallergic potential have been developed so far, while none of them have yet to be validated and regulatory accepted. Currently, some photoreactivity assays such as UV-VIS spectral analysis and ROS assay are generally used for initial photosafety assessments because of their high sensitivity. However, they have a low specificity, generating a high percentage of false positive results, and the development of a follow-up assessment method is desired. Therefore, this study aimed to develop an in chemico photoallergy testing method, photo-direct peptide reactivity assay (photo-DPRA). Based on photosafety information, 34 photoallergens and 16 non-photoallergens were selected and subjected to UV-VIS spectral analysis, ROS/micellar ROS assays, photo-DPRA, sequential testing strategy (STS) consisting of all three methods, and 3T3 neutral red uptake phototoxicity testing (3T3 NRU PT). Combination of the methods addressing the key events of photoallergy exhibited high prediction performance. Our results showed the proposed strategy would be useful to predict the photoallergic potential of chemicals as the follow-up assessment for false positive chemicals by UV/VIS spectral analysis and ROS assay.

Selection of nutritive compounds to improve growth and indicative properties of the DTM-Expert medium for dermatophytic fungi

The study describes optimization stages of Russian medium “DTM-Expert” for express detection of dermatophytic fungi. In order to improve the growth promotion and indicative properties of the medium, several variations of nutritive compounds were studied. The medium containing mannitol and glucose as carbon sources showed the best indicative and growth promotion properties. The pH optimum for dermatophytes growth on the DTM-Expert was in the range 4.7-5.5. The indicative properties of the medium were optimal at an initial pH value of 4.8. No significant differences were found when using bromothymol blue as an indicator compared to phenol red. The diagnostic efficiency of the optimized version of the DTM-Expert was 100% while the percentage of false positive results was 5.6%. The efficiency of the control medium was 87% accompanied by 9.2% of false positive reactions. The average reddening time was 10 days on the DTM-Expert and 11 days on the control medium.

Abstract P377: Real-Word Performance of Two Automated Software Platforms for Large-Vessel Occlusion Identification in Acute Ischemic Stroke Patients: A Single Center Experience

Background and purpose: Modern stroke treatment has been revolutionized by image-guided selection of patients for endovascular thrombectomy. Current automated platforms allow for real-time identification of large vessel occlusion and salvageable brain tissue. We had previously demonstrated that a “CTA for all” policy for stroke patients immediately upon arrival assists in the earlier identification of treatment candidates. We now sought to evaluate the performance of these platforms under this policy. Methods: All patients that presented to Henry Ford Health System hospitals over a period of 6 weeks received CTA of the head and neck upon initial presentation. The images were processed with two automated software platforms. We prospectively collected processing times, large-vessel-occlusion alerts, performance warnings, and LVO density ratios. We compared these with the interpretations of board-certified radiologists, and analyzed the performance of each platform. Results: 276 patients presented with stroke symptoms and received CT angiography upon presentation. Both platforms were able to image all stroke patients within their FDA-approved indications. Both platforms were noted to have comparable sensitivity, specificity, PPV and NPV, and excellent accuracy. The overall prevalence of LVO was extremely low (8/276). As a result, for both, NPV was much better than PPV because of the percentage of false positive results. Further ROC analysis, demonstrated an area under the ROC curve of 0.982, and overall model quality of 0.97. Optimal LVO density cutoff was <0.093 in order to maximize overall accuracy, or < 0.271, in order to maintain a sensitivity of 100% as an absolute priority (both significantly lower than the current threshold of <0.45). Conclusions: Automated software platforms are an invaluable aid in the selection of patients for endovascular thrombectomy. Different LVO detection algorithmic thresholds may be necessary (and should be part of individual stroke center validation pathways) to avoid fatigue alert, and optimize test accuracy, when LVO prevalence is low. Stroke teams should be aware of the limitations of automated analysis and need for expert review.

Correlation of Electrodiagnostic Findings in C8 Radiculopathies With Radiographic Data: A Retrospective Chart Review.

Signs and symptoms of a C8 radiculopathy could mimic common comorbidities such as entrapment and peripheral neuropathies. These conditions and a C8 radiculopathy both can result in abnormal findings on needle examination of intrinsic hand muscles. It was hypothesized that needle examination of C8-innervated muscles in the forearm might improve concordance with magnetic resonance imaging (MRI) in the presence of underlying comorbidities. A retrospective analysis of electromyogram and C-spine MRI data in 80 patients with negative MRI of C-spine for C8-T1 neuroforaminal stenosis was performed. The percentage of false-positive results in the MRI-negative group undergoing electromyogram testing for hand and forearm muscles (MRI-NH + F) was 3% compared with 18% (P = 0.06) in the group with electromyogram of the hand intrinsic muscles only (MRI-NH). The false-positive result tends to be lower in the MRI-NH + F group in comparison with the MRI-NH group especially in the presence of underlying peripheral and entrapment neuropathies.

Retrospective assessment of Lung-RADS® performance in the Silesian Lung Cancer Screening Pilot Study

Background. A high percentage of false positive results, observed in lung cancer screening studies with low-dose computed tomography (LDCT), caused the modification of radiological assessment methods. According to the International Early Lung Cancer Action Program (IELCAP) all non-calcified nodules with a dimension ≥ 4 mm were considered as positive. Implementation of classification the Lung CT screening Reporting and Data System (Lung-RADS®) recommends additional testing only for nodules ≥ 6 mm, which reduced of false positive results. Methods. We provided a retrospective analysis of 601 LDCT scans, in asymptomatic volunteers of Pilot Silesian Study of Early Lung Cancer Detection, with at least 20 pack-years of cigarette smoking. The analysis of non- and invasive interventions was done. Assessment of nodules according to the Lung-RADS® system was done. Then the percentage of interventions that could be avoided using the Lung-RADS® criteria was estimated. Results. In total, 1016 nodules were identified in 265 participants. The positive result of screening was defined as a presence of solid or part-solid nodule ≥ 5 mm and ≥ 8 mm in the case of a nonsolid nodule in line with the IELCAP protocol. Screening based on the IELCAP protocol resulted in 200 positive results and based on Lung-RADS® in the 116 positives. The frequency of lung cancers among participants with a positive result was 7 of 200 (4.0%) (95% CI: 1.0%, 6.0%) for IELCAP and 7 of 116 (6.0%) (95% CI: 2.7%, 9.3%) for Lung-RADS®. The Lung-RADS® criteria reduced number of non- and invasive procedures by 48.8% and 24.1%, compared to IELCAP protocol. Conclusions. Adopting the Lung-RADS® classification system may reduce harms and improve the efficiency of lung cancer screening programs.

Validation of Diaporthe toxica resistance markers in European Lupinus angustifolius germplasm and identification of novel resistance donors for marker-assisted selection

The fungus, Diaporthe toxica, anamorph Phomopsis sp., previously classified as P. leptostromiformis, is a plant endophyte and occasional pathogen, causing Phomopsis stem blight. This disease is damaging not only to lupins but also to the animals grazing on infected plants, due to the toxic secondary metabolites called phomopsins. The aim of this work was to validate markers for resistance to Phomopsis stem blight in narrow-leafed lupins and identify novel germplasm with increased levels of resistance to the disease. Plant inoculations were performed using ten isolates of D. toxica, originating from Australia and Poland. The European core collection of L. angustifolius was evaluated both in a controlled environment and with field experiments to classify the accessions based on their resistance to the disease. Simultaneously, the accessions were assayed with disease resistance markers to identify donors of hypothetical resistance alleles. We have found that the European lupin germplasm collection preserves wild and domesticated donors of at least two resistance genes to Phomopsis stem blight, including Phr1 and PhtjR. Molecular markers PhtjM7, InDel2, and InDel10, tagging PhtjR gene, were applicable for marker-assisted selection targeting the European gene pool with an expected accuracy of 95%. None of diagnostic markers for the Phr1 locus was found useful for European breeding programs; two existing markers Ph258M1 and Ph258M2 were unreliable, due to a high percentage of false-positive results (up to 58%) and a high recombination rate between markers (~ 30%).

P5621Diagnostic accuracy of resting full-cycle ratio in the non-culprit artery of acute patients

Abstract Introduction Resting full-cycle ratio (RFR) is a novel non-hyperemic index of coronary stenosis severity, independent of the timing within the cardiac cycle. Recent data has demonstrated good correlation between RFR and Fractional Flow Reserve (FFR) in stable coronary disease (SCD). However, there are no data regarding the reliability of RFR in non-culprit arteries of patients presenting with acute myocardial infarction (AMI). Purpose To study the diagnostic accuracy of RFR versus FFR in the non-culprit artery in AMI compared to stable lesions. Methods RFR, FFR, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistance Reserve Ratio (RRR) were calculated in 67 patients with AMI and an intermediate lesion in a non-culprit artery (median time from primary PCI to study: 48 hours). Data were compared with those of a retrospective group of 66 patients with SCD. Results There was a higher proportion of males among patients of the AMI group (85% vs 62%, p=0.0026). Mean age was 64.5±11 years, being AMI cohort younger at presentation [62±11 vs 67±12 years in SCD cohort (p=0.04)]. Patients with AMI had a significantly lower prevalence of hypertension (52% vs 75%, p=0.006), diabetes (10% vs 32%), p=0.002) and hyperlipemia (37% vs 79%, p=0.002). Coronary physiology parameters showed a non-normal distribution, and are expressed as median [IQR] (Table 1). In patients with AMI, FFR was lower than in patients with SCD. In contrast, RFR showed no significant difference. Both CFR and RRR were higher in the AMI group. No significant differences in IMR were found between cohorts. Importantly, in the AMI group the correlation between RFR and FFR was 0.84 and the overall agreement 82%, with rates of false positive and negative of 15% and 3%, respectively. In SCD the correlation was 0.81 with a lower overall agreement of 69%, due mostly to a higher rate of false positive RFR (28%) (Figure 1). Table 1. Microcirculatory parameters in non-culprit artery (AMI) and stable coronary disease (SCD) AMI (N=66) Stable (N=67) p value FFR 0.84 [0.76–0.9] 0.84 [0.76–0.9] 0.006 RFR 0.89 [0.82–0.94] 0,9 [0.84–0.94] 0.24 CFR 2.2 [1.7–3.1] 1.8 [1.1–2.6] 0.011 IMR 17 [14–27] 25 [14–38] 0.051 RRR 2.7 [2.17 - 3.9] 2.1 [1.4–3.1] 0.005 Median [IQR]. Figure 1. Correlation between RFR and FFR valueS Conclusions RFR shows a good correlation with FFR in AMI. Surprisingly, overall agreement is higher in the non-culprit artery in an acute setting, with a lower percentage of false positive results. Acknowledgement/Funding None

Correction to: Community Low-Dose CT Lung Cancer Screening: A Prospective Cohort Study.

The original version of this article contained an error in the usage of the term "false positive rate". The intention of the authors in those instances was simply to compare the absolute percentage of false positive results in the study vs the NLST, not to make any observations about false positive rate in the strict statistical sense (i.e. Type I error probability).

Abstract PL04-01: Screening for nasopharyngeal carcinoma using plasma Epstein-Barr virus DNA: Technological and clinical insights

Abstract Epstein-Barr virus (EBV) DNA is released by a number of EBV-associated malignancies into the plasma. Examples of such malignancies include nasopharyngeal carcinoma (NPC), certain lymphomas and EBV-associated gastric carcinoma. Plasma EBV DNA in such malignancies exhibits a strong correlation with tumor stage, clinical progress and prognosis; and is thus an archetypal circulating tumor DNA species. Our group is interested in exploring the use of plasma EBV DNA to screen for NPC. We have recently completed a prospective population screening project involving over 20,000 middle aged men in Hong Kong. Using plasma EBV DNA as a screening tool, NPC could be found at a much earlier stage than was normally possible. Furthermore, the prognosis of the NPC patients identified through such screening was much more favorable than those diagnosed without such screening. The positive predictive value of this approach was 11%. False-positive results were observed a proportion of subjects without NPC. Factors that contributed to increased false-positive results included advancing age and surprisingly, the ambient temperature of the day when samples were collected. Hence, a higher percentage of false-positive results were observed when samples were collected in colder weather. We hypothesized that such results might be related to the fluctuations in the effectiveness of the immune system in certain individuals due to ambient temperature. Since the reporting of the above-mentioned results, we have been exploring approaches for further enhancing the positive predictive value. Through the use of targeted massively parallel paired-end sequencing, we found that the size profiles of plasma EBV DNA in subjects with NPC and those without were different. Indeed, by combining such size profile and the concentration of plasma EBV DNA as measured by sequencing, the positive predictive value could be further enhanced. Very recently, we investigated the epigenetic profile of plasma EBV DNA in subjects with NPC and those without cancer, in an attempt to further enhance the positive predictive value of the approach. We believe that the development of a robust approach for NPC screening using circulating EBV DNA would have major public health impact, allowing the earlier detection and treatment of NPC in high prevalence areas. We also believe that such developments would also guide the development of other circulating tumor DNA markers for early cancer detection. Citation Format: Yuk Ming Dennis Lo. Screening for nasopharyngeal carcinoma using plasma Epstein-Barr virus DNA: Technological and clinical insights [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr PL04-01.

Evaluation of diagnostic methods for the detection of intestinal schistosomiasis in endemic areas with low parasite loads: Saline gradient, Helmintex, Kato-Katz and rapid urine test.

BackgroundIn some tropical countries, such as Brazil, schistosomiasis control programs have led to a significant reduction in the prevalence and parasite burden of endemic populations. In this setting, the Kato-Katz technique, as the standard diagnostic method for the diagnosis of Schistosoma mansoni infections, which involves the analysis of two slides from one fecal sample, loses its sensitivity. As a result, a significant number of infected individuals are not detected. The objective of this study was to perform extensive parasitological testing of up to three fecal samples and include a rapid urine test (POC-CCA) in a moderate prevalence area in Northern Minas Gerais, Brazil, and evaluate the performance of each test separately and in combination.Methods and findingsA total of 254 individuals were examined with variants of the standard Kato-Katz technique (up to18 Kato-Katz slides prepared from three fecal samples), a modified Helmintex (30 g of feces), the saline gradient (500 mg of feces), and the POC-CCA methods. We established a reference standard taking into consideration all the positive results in any of the parasitological exams. Evaluation of the parasite burden by two Kato-Katz slides confirmed that most of the individuals harbored a light infection. When additional slides and different parasitological methods were included, the estimated prevalence rose 2.3 times, from 20.4% to 45.9%. The best sensitivity was obtained with the Helmintex method (84%). All parasitological methods readily detected a high or moderate intensity of infection; however, all lost their high sensitivity in the case of low or very low intensity infections. The overall sensitivity of POC-CCA (64.9%) was similar to the six Kato-Katz slides from three fecal samples. However, POC-CCA showed low concordance (κ = 0.34) when compared with the reference standard.ConclusionsThe recommended Kato-Katz method largely underestimated the prevalence of S. mansoni infection. Because the best performance was achieved with a modified Helmintex method, this technique might serve as a more precise reference standard. An extended number of Kato-Katz slides in combination with other parasitological methods or with POC-CCA was able to detect more than 80% of egg-positive individuals; however, the rapid urine test (POC-CCA) produced a considerable percentage of false positive results.

Screening for antibodies against Treponema pallidum with chemiluminescent microparticle immunoassay: analysis of discordant serology results and clinical characterization.

Traditionally, testing for syphilis has consisted of initial screening with a non-treponemal test, then retesting reactive specimens with a treponemal test. Recent availability of a chemiluminescent microparticle immunoassay for detecting antibodies against Treponema pallidum has led several laboratories in China to adopt chemiluminescent microparticle immunoassay for screening of syphilis, with subsequent testing of reactive serum samples with non-treponemal tests. We evaluated the utility of chemiluminescent microparticle immunoassay for routine screening of syphilis. Antibodies against Treponema pallidum were screened in 20,550 serum samples using chemiluminescent microparticle immunoassay. Chemiluminescent microparticle immunoassay-positive samples were reflexively tested with rapid plasma reagin tests and Treponema pallidum particle agglutination assays. Dot-immunoblot assays were used to confirm results of chemiluminescent microparticle immunoassay-positive and Treponema pallidum particle agglutination-negative serum samples. Overall, 267 samples (1.3%) were chemiluminescent microparticle immunoassay-positive, and 185 (69.3%) of those chemiluminescent microparticle immunoassay-positive serum samples were also Treponema pallidum particle agglutination-positive. Samples' signal to cut-off ratio for chemiluminescent microparticle immunoassay correlated with diagnostic reliability, as greater samples' signal to cut-off ratio corresponded with greater concordance between chemiluminescent microparticle immunoassay and Treponema pallidum particle agglutination results. Dot-immunoblot testing of 82 chemiluminescent microparticle immunoassay-positive and Treponema pallidum particle agglutination-negative serum samples showed that 16 samples (19.5%) were Dot-immunoblot-positive, 28 (34.2%) were indeterminate and 38 (46.3%) were negative. Because there is a certain percentage of false-positive results using chemiluminescent microparticle immunoassay for routine screening of syphilis, further analysis by Treponema pallidum particle agglutination is recommended to confirm diagnostic results. While in screening populations discrepancies between chemiluminescent microparticle immunoassay and Treponema pallidum particle agglutination results are quite prevalent, confirmation by immunoblot assay may be useful.

Detection of Squamous Cell Carcinoma Antigen with Two Systems in the follow-up of Patients with Cervical Cancer

Since squamous cell carcinoma antigen (SCC-Ag) testing became commercially available on the Architect platform, the previously established method on the Abbott IMx platform has been progressively replaced. Aim of this work was to compare SCC-Ag values obtained with the 2 methods. Clinical and laboratory data of 188 patients for whom SCC-Ag determination was requested, were reviewed. IMx was used to determine the levels of SCC-Ag from June 2007 to May 2009, while the Architect system was used from June 2009 to April 2011. Only patients consistently diagnosed with no evidence of disease, for whom at least 2 determinations with each analyzer were available were used. Comparison of the results obtained with the 2 systems was then performed. Mean values for SCC-Ag were 0.56 ng/mL (Standard Error (SE): 0.08) with the IMx method, and 1.08 ng/mL (SE 0.10) with Architect (p<0.0001). False positive results were found in 4.8% of patients with the IMx method and in 9.5% of patients with Architect (p=0.049). The values of SCC-Ag determined on the Architect platform are higher than those obtained on the IMx, with a higher percentage of false positive results.