False-positive Results Research Articles

A step‐by‐step progressive strategy exploring whole metabolic profiles in vivo for Polygalae Radix with/without licorice

AbstractIntroductionPolygalae Radix (PR) is known to relieve toxicity and increase efficiency in various diseases after processing. However, there were few studies for aromatic carboxylic acids (ACAs) due to the limited detection, especially for the metabolites within m/z 100–2000.ObjectivesThis study aims to elucidate the whole metabolism of PR with/without licorice (LP), focusing on metabolites within m/z 100–2000 and pharmacodynamics in vivo.Material and methodsThis study was established by the combination of multidimensional ultra‐high performance liquid chromatography coupled with a mass spectrometer (UPLC–MS) technology with protein sedimentation method to analyze metabolites in plasma, brain, colon, and stomach contents. Quantitative monitoring ACAs was enhanced with our novel stable isotope derivatization (SILD) technique. And then the pharmacokinetics (PK) study of relatively large metabolites was carried out. A targeted network pharmacology approach was established to avoid false positive results, mapping interactions relevant to Alzheimer's disease (AD), and other conditions.ResultsThe 85 polygala metabolites were qualitatively analyzed in plasma, brain, colon, and stomach contents. The 11 types of relatively large metabolites and 8 types of ACAs were quantitatively monitored. Among them, nine types of relatively large metabolites were assessed through PK studies. In targeted network pharmacology, it highlighted the significance of small molecular metabolites, including ACAs et al, which were frequently overlooked. LP may play a more key role mainly through neural active ligand‐receptor interaction, AD, and pertussis pathways. These findings have outlined a step‐by‐step strategy for in‐depth research in vivo, laying a foundation for further verification of biological function.

Immunity to Non-Dengue Flaviviruses Impacts Dengue Virus Immunoglobulin G Enzyme-Linked Immunosorbent Assay Specificity in Cambodia.

Seroprevalence studies are the standard for disease surveillance, and serology determined eligibility for the first dengue vaccine. Expanding flavivirus co-circulation and vaccination complicate testing. We evaluate the accuracy of a common dengue virus serological assay, examine immunity to non-dengue flaviviruses as a contributor to decreased performance, and assess whether alternative cut points may improve assay performance. Children (n = 770) aged 2-9 years in Kampong Speu, Cambodia were enrolled in a prospective longitudinal study, and PanBio indirect dengue virus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) was performed. Plaque reduction neutralization tests (PRNTs) using dengue viruses were performed on a subset to assess the accuracy of the IgG ELISA, and PRNTs with Zika, Japanese encephalitis, and West Nile viruses evaluated immunity to non-dengue flaviviruses. Receiver operating curve analysis identified an alternative cut point to improve IgG ELISA accuracy. The dengue IgG ELISA had a lower specificity than previously reported (58% vs 93%-100%). Of those with false-positive IgG results, 46% had detectable neutralizing antibodies against other flaviviruses including 14% against West Nile virus. A higher IgG cut point improved the test accuracy in this population. Physicians and public health authorities should be alert for West Nile in Cambodia. Immunity to non-dengue flaviviruses can impact dengue surveillance. NCT03534245.

Benefits and Harms of Hepatocellular Carcinoma Screening Outreach in Patients with Cirrhosis: A Multi-Center Randomized Clinical Trial.

The value of hepatocellular carcinoma (HCC) screening is defined by the balance of benefits from early tumor detection vs harms due to false positive results. We evaluated the value of a mailed outreach strategy for HCC screening in patients with cirrhosis. We conducted a multi-center pragmatic randomized clinical trial comparing mailed outreach for HCC screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at three health systems from March 2018 to September 2021. Outcomes of interest were early-stage HCC detection (ie, screening benefit) and diagnostic evaluation for false positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses. Of 125 patients diagnosed with HCC (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan Criteria. Early tumor detection did not significantly differ between the outreach and usual care arms (64.2% vs 79.3%, p = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%, p = .95) with 5.9% in both arms having mild harms, 4.0% and 3.8% respectively with moderate harms, and 0.9% and 1.0% respectively with severe harms. Most patients enrolled in HCC screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not significantly increase early HCC detection or physical harms compared to usual care. NCT02582918 and NCT03756051.

MIDF-DMAP: Multimodal information dynamic fusion for drug molecule activity prediction

BackgroundComputer-aided drug development can alleviate limitations in drug research and development processes, such as long cycles, high costs, and limited targeting. Deep learning models can be used to predict the activity of drug compound molecules. However, existing models still need to adequately address semantic redundancy, conflicts, and noise between different data modalities. It results in low accuracy in predicting molecular activity and many false positive results that need further resolution. ObjectiveThis study aims to design a parallel deep learning model for processing multimodal molecular information fusion, dynamically adjusting the weights of different modal features during the fusion process. This approach ensures that high-quality modal information is more significant in molecular activity prediction, improving the model’s predictive accuracy. MethodsFirst, three modal features of drug molecules are extracted: one-dimensional fingerprints, two-dimensional topological structures, and three-dimensional geometric structures. Then, a dynamic weighting mechanism is proposed to fuse these three modal features organically. Finally, the fused features are input into the model classifier to obtain molecular activity prediction results. ResultsExperimental results show that the proposed model improved the Receiver Operating Characteristic-Area Under the Curve (ROC-AUC) value by 29.96% compared to the Weave model and 26.38% compared to the GC model on the BBBP dataset. Compared to the GraphMVP model and the multi-channel substructure graph model MSGG, the ROC-AUC value increased by 20.44% and 15.80%, respectively. This method also achieved good results on imbalanced samples and small molecule datasets. ConclusionThis study provides an effective multimodal dynamic fusion method for virtual drug screening, enriching computer-aided drug development theory and improving drug research and development efficiency.

Development and validation of highly sensitive multiplex real-time RT-PCR assay for detection of classical swine fever virus genome

Classical swine fever (CSF) remains a challenge for pig farming industrial lover the world despite the measures taken. The last CS case in the Russian Federation was reported in 2020, however, the threat of the disease emerging still persists. A set of anti-epidemic measures including mainly preventive vaccination and annual diagnostic monitoring using molecular-genetic and serological methods is required for CSF virus introduction prevention and rapid eradication of potential disease out breaks. Therefore, areal-time reverse transcription-polymerase chain reaction using an internal control sample has been developed. Therefore, areal time reverse transcription-polymerase chain reaction using an internal control sample has been developed. Modified primers (locked nucleic acids containing conformationally blocked nucleosides) providing a higher affinity to the DNA matrix and physico-chemical stability and a FAM-labeled TaqMan probe were selected for 5’-untranslatedregion of the genome. The following validation parameters were defined: accuracy, repeatability, reproducibility, specificity and sensitivity. For comparative analysis of the developed as say sensitivity, swabs, samples of organs and tissues collected from pigs experimentally infected with an epizootic strain of the classical swine fever virus (spleen, kidney, liver, blood, lymph nodes, rectal and oral smears), animal-contaminated feed and virus-containing material with known virus titres were also tested in parallel with coded test systems No. x1 andx2. The developed assay was shown to have 100% diagnostic sensitivity and detection limit of 0,23 lgCCID50/cm3. Therewith, there sults of analysis of test systems No. x1, x2 based on above parameters were lower that could give rise to false positive real-time RT-PCR results and incorrect diagnosis. Thus, described assay can be used for extensive monitoring of classical swine fever in the Russian Federation

False-Positive Human Immunodeficiency Virus-1 Test Results With Rapid Seroreversion After Third-Trimester Tdap Booster Vaccination.

False-positive and false-negative results in human immunodeficiency virus (HIV) testing are expected at some frequency. False-positive results have been reported in association with various conditions, including pregnancy, autoimmune disease, and infection. We present an atypical case of a pregnant patient receiving false-positive HIV results for both screening and antibody confirmatory tests after a recent routine vaccination. A 34-year-old woman, G4P1021, with a negative first-trimester HIV test result received a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) booster at 35 2/7 weeks of gestation. Test results at 36 2/7 weeks of gestation were positive in both HIV-1/2 antigen-antibody screening and a confirmatory HIV-1 antibody differentiation immunoassay, but follow-up test results at 36 5/7 weeks and later were negative. Repeat testing and erythrocyte typing confirmed that this was not a result of laboratory error or specimen mishandling. HIV antiretroviral therapy was started and was later discontinued. A scheduled primary cesarean delivery performed at 39 1/7 weeks of gestation due to breech presentation was uncomplicated. False-positive results in HIV screen and confirmation testing were associated with receipt of a Tdap vaccine booster 7 days prior. This test result pattern is similar to that seen very rarely in previous cases, and the rapid seroreversion to negative suggests an acute immunologic trigger leading to a falsely reactive antibody. Clinicians should be aware of the potential for false-positive HIV test results in patients who recently received vaccination or with other immune triggers and retest at a short interval if suspected.

Thymoglobulin therapy leads to false positive antibody and crossmatch results

Thymoglobulin therapy leads to false positive antibody and crossmatch results

Performance and value of 18F‑FDG PET/CT in patients with fever of unknown origin.

Fever of unknown origin (FUO) is a common clinical and diagnostic challenge. The main aim of the present study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT in patients who present with FUO. Overall, 105 consecutive patients (61 men and 44 women) with a mean age of 51±35 years with FUO underwent 18FDG PET/CT scans. The performance of 18FDG PET/CT in determining the etiology of FUO was assessed. According to the PET/CT results, patients were classified into four groups: Group 1, patients with true-positive results (n=51; 49%), in whom abnormal 18FDG uptake identified the final diagnosis; group 2, patients with false-positive results (n=24; 23%), in whom 18FDG uptake was not consistent with the final diagnosis; group 3, patients with true-negative results (n=10; 9.5%), in whom the 18FDG uptake was normal and no final disease was established; and group 4, patients with false-negative results (n=20; 19%), in whom 18FDG uptake was normal and disease was finally established. Of the 51 patients with true-positive PET/CT results, 51% had infections, 35% had malignancies and 14% had inflammatory processes. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 72, 29, 68, 33 and 58%, respectively. In conclusion, the present results demonstrated that 18FDG PET/CT established the final diagnosis of FUO in the majority of patients (72%). These results support the use of 18FDG PET/CT in the initial evaluation and management of patients with FUO.

Quantitative Compliance Based Classification of Submental Sign or Javid Sign

Prediction of difficult intubation is still a dilemma. Despite various predictors of difficult airway reported and discussed in the literature, no definite test exists to prevent mortality and morbidity related to difficult airway. Using a combination of different predictors of difficult intubation is logical to help minimizing this difficulty and establishing a safe anesthesia. Detection and presentation of any novel predictor can be helpful in achieving this goal. “Submental Sign” or “Javid Sign” a new predictor of difficult intubation, was reported by MJ Javid in 2011, but qualitative characteristic of this predictor was the most considerable drawback for using Submental Sign as an accurate predictor. The goal of this study is quantitative classification of Submental Sign or Javid classification to overcome false positive and false negative results of Submental Sign. In this article a novel scale is introduced for evaluating submental compressibility quantitatively.

Tips for Addressing Screening Concerns: "Harms of Screening".

Early detection decreases deaths from breast cancer. Yet, there are conflicting recommendations about screening mammography by major professional medical organizations, including the age and frequency with which women should be screened. The controversy over breast cancer screening is centered on 3 main points: the impact on mortality, overdiagnosis, and false positive results. Some studies claim that adverse psychological effects such as anxiety or distress are caused by screening mammography. The purpose of this article is to address negative breast cancer screening concerns including overdiagnosis and overtreatment, effect on mortality, false positive results, mammography-related anxiety, and fear of radiation.

Calculating the similarity between prescriptions to find their new indications based on graph neural network

BackgroundDrug repositioning has the potential to reduce costs and accelerate the rate of drug development, with highly promising applications. Currently, the development of artificial intelligence has provided the field with fast and efficient computing power. Nevertheless, the repositioning of traditional Chinese medicine (TCM) is still in its infancy, and the establishment of a reasonable and effective research method is a pressing issue that requires urgent attention. The use of graph neural network (GNN) to compute the similarity between TCM prescriptions to develop a method for finding their new indications is an innovative attempt.MethodsThis paper focused on traditional Chinese medicine prescriptions containing ephedra, with 20 prescriptions for treating external cough and asthma taken as target prescriptions. The remaining 67 prescriptions containing ephedra were taken as to-be-matched prescriptions. Furthermore, a multitude of data pertaining to the prescriptions, including diseases, disease targets, symptoms, and various types of information on herbs, was gathered from a diverse array of literature sources, such as Chinese medicine databases. Then, cosine similarity and Jaccard coefficient were calculated to characterize the similarity between prescriptions using graph convolutional network (GCN) with a self-supervised learning method, such as deep graph infomax (DGI).ResultsA total of 1340 values were obtained for each of the two calculation indicators. A total of 68 prescription pairs were identified after screening with 0.77 as the threshold for cosine similarity. Following the removal of false positive results, 12 prescription pairs were deemed to have further research value. A total of 5 prescription pairs were screened using a threshold of 0.50 for the Jaccard coefficient. However, the specific results did not exhibit significant value for further use, which may be attributed to the excessive variety of information in the dataset.ConclusionsThe proposed method can provide reference for finding new indications of target prescriptions by quantifying the similarity between prescriptions. It is expected to offer new insights for developing a scientific and systematic research methodology for traditional Chinese medicine repositioning.

Diagnostic accuracy of Truenat MTB Plus, Truenat MTB Ultima and Xpert MTB/RIF Ultra for the diagnosis of pulmonary TB in an HIV-endemic setting.

Truenat MTB Plus (MTB Plus) and MTB Ultima (Ultima) are World Health Organization-endorsed low-complexity tuberculosis (TB) tests, however, performance data are scarce. Adults (≥18 years; n=498) self-presenting with symptoms to primary care clinics in Cape Town, South Africa (19/02/2016-22/02/2023) provided sputa. We evaluated the accuracy of MTB Plus and Ultima, with Xpert MTB/RIF Ultra (Ultra) as a comparator, vs. a single culture (TB reference standard) or MTBDRplus on an isolate (rifampicin susceptibility reference standard). The proportion of MTB Plus and Ultima unsuccessful results was 20% (95% confidence interval 17, 23) and 14 (11, 16), respectively, with ≥half resolving upon retesting the same eluate. In a three-way analysis, MTB Plus, Ultima and Ultra had sensitivities of 84% (78, 88), 90% (85, 93), and 92% (87, 95), and specificities of 95% (92, 97), 85% (80, 88) and 95% (92, 97) for TB. The proportion of unsuccessful results for MTB-RIF Dx done the same day as DNA extraction was 9% (3, 16; MTB Plus-positives) and 18% (10, 26; Ultima-positives) [if after day-of-extraction, these were 27% (18, 35) and 44% (35, 51)]. Same-day rifampicin susceptibility testing was often unsuccessful in samples with "very low" load [73% (58, 89) MTB Plus, 75% (65, 86) Ultima] but had 100% (40, 100) sensitivity and 99% (96, 100) specificity (for both MTB Plus- or Ultima-positive DNA). Lot variation in unsuccessful and false-positive results was observed. Ultima showed comparable sensitivity to Ultra but specificity, lot variation, and, like MTB-RIF Dx, unsuccessful result rates were suboptimal. European & Developing Countries Clinical Trials Partnership, and South African Medical Research Council.

ThP8.6 - A real-world diagnostic algorithm for identifying carotid artery stenosis

Abstract Aim Eighty-five percent of ischaemic strokes are caused by extracranial atheromatous lesions involving a narrowing of the Internal Carotid Artery so accurate and timely diagnosis is vital for management. The aim of this study was to correlate CT angiogram (CTA) and ultrasound doppler (US) derived measurements of carotid artery stenosis (CAS), with a view to identify those cases where second modality is required to reduce potential errors. Methods All consecutive carotid US and CTA examinations performed in 2021 and 2022 were included for comparison in this retrospective cohort study. Collected data was then reviewed and evaluated by a multidisciplinary team. North American Symptomatic Carotid Endarterectomy Trial (NASCET) and St Mary’s criteria were used to narrow down the percentage stenosis. Result There were fifty-one patients (102 carotid arteries) over this period who had both studies performed. Twenty-nine males and twenty-three females with a median age of seventy-three. Initial data analysis showed no discrepancy in ninety-one (90%) carotid arteries between both modalities. After MDT review, there were eight (7.1%) false positive results and three (2.9%) true positive (2 symptomatic & 1 asymptomatic). In three (2.9%) cases quantification was significantly inaccurate in the initial imaging modality because of heavily calcified vessels. Conclusion This study supports the use of US or CTA as a single modality in grading CAS. Heavily calcified vessels on the first test should be a ‘red flag’ for triggering further alternative imaging to reduce the risk of error. Persistent discrepancies even after the second modality will require a further modality e.g. enhanced magnetic resonance angiography.

Enhancing UAV-Based Precision Agriculture: A Deep Learning Approach to Targeted Maize Disease Management

Corn/maize is the third most globally produced crop, and there are over eighty diseases impacting it, creating significant concerns in the agricultural sector. As a result, Unmanned Aerial Vehicles (UAVs) and their ability to spray specifically diseased crops have become increasingly popular. When using UAVs, Normalized Difference Vegetation Index (NDVI) calculations are frequently used to determine whether a crop should be sprayed with pesticides. However, NDVI alone is not a sufficient metric. NDVI indicates plant stress in general, which could be drought or poor soil quality, and this will not be addressed by pesticides. The solution is then to create a custom deep learning model that uses a sufficiently low NDVI value as a starting point. Once a low NDVI value is detected, the same near infrared imagery used to retrieve the NDVI calculations will be used in the model where object detection will be used to determine whether there are diseased lesions on the maize. Near infrared imagery has been proven to increase the detection of maize diseases, achieving a higher accuracy than RGB imagery. The model will mimic aspects of YOLOv10 to facilitate rapid detection times, providing the opportunity for real-time spraying. While scholars have modified YOLOv5 to achieve detection times as low as 0.064 s/sheet, a custom deep learning model used only on the contingency of low NDVI values is less computationally intensive and should then take less time overall. Finally, Keyhole Markup Language (KML) and Geographic Information Systems (GIS) will be used to create an output map indicating where pesticides were sprayed. The research will reduce the number of false positive results, which will limit the quantity of pesticides used, consequently reducing financial costs and negative environmental impacts.

Discovery and validation of colorectal cancer tissue-specific methylation markers: a dual-center retrospective cohort study

Background and purposeEarly detection, diagnosis, and treatment of colorectal cancer and its precancerous lesions can significantly improve patients’ survival rates. The purpose of this research is to identify methylation markers specific to colorectal cancer tissues and validate their diagnostic capability in colorectal cancer and precancerous changes by measuring the level of DNA methylation in stool samples.MethodWe analyzed samples from six cancer tissues and adjacent normal tissues and fecal samples from 758 participants, including 62 patients with interfering diseases. Bioinformatics databases were used to screen for candidate biomarkers for CRC, and quantitative methylation-specific PCR methods were applied for identification. The methylation levels of the candidate biomarkers in fecal and tissue samples were measured. Logistic regression and random forest models were built and validated using fecal sample data from one of the centers, and the independent or combined diagnostic value of the candidate biomarkers in fecal samples for CRC and precancerous lesions was analyzed. Finally, the diagnostic capability and stability of the model were validated at another medical center.ResultsThis study identified two colorectal cancer CpG sites with tissue specificity. These two biomarkers have certain diagnostic power when used individually, but their diagnostic value for colorectal cancer and colorectal adenoma is more significant when they are used in combination.ConclusionThe results indicate that a DNA methylation biomarker combined diagnostic model based on two CpG sites, cg13096260 and cg12587766, has the potential for screening and diagnosing precancerous lesions and colorectal cancer. Additionally, compared to traditional diagnostic models, machine learning algorithms perform better but may yield more false-positive results, necessitating further investigation.

Association Between False-Positive Results and Return to Screening Mammography in the Breast Cancer Surveillance Consortium Cohort.

False-positive results on screening mammography may affect women's willingness to return for future screening. To evaluate the association between screening mammography results and the probability of subsequent screening. Cohort study. 177 facilities participating in the Breast Cancer Surveillance Consortium (BCSC). 3 529 825 screening mammograms (3 184 482 true negatives and 345 343 false positives) performed from 2005 to 2017 among 1 053 672 women aged 40 to 73 years without a breast cancer diagnosis. Mammography results (true-negative result or false-positive recall with a recommendation for immediate additional imaging only, short-interval follow-up, or biopsy) from 1 or 2 screening mammograms. Absolute differences in the probability of returning for screening within 9 to 30 months of false-positive versus true-negative screening results were estimated, adjusting for race, ethnicity, age, time since last mammogram, BCSC registry, and clustering within women and facilities. Women were more likely to return after a true-negative result (76.9% [95% CI, 75.1% to 78.6%]) than after a false-positive recall for additional imaging only (adjusted absolute difference, -1.9 percentage points [CI, -3.1 to -0.7 percentage points]), short-interval follow-up (-15.9 percentage points [CI, -19.7 to -12.0 percentage points]), or biopsy (-10.0 percentage points [CI, -14.2 to -5.9 percentage points]). Asian and Hispanic/Latinx women had the largest decreases in the probability of returning after a false positive with a recommendation for short-interval follow-up (-20 to -25 percentage points) or biopsy (-13 to -14 percentage points) versus a true negative. Among women with 2 screening mammograms within 5 years, a false-positive result on the second was associated with a decreased probability of returning for a third regardless of the first screening result. Women could receive care at non-BCSC facilities. Women were less likely to return to screening after false-positive mammography results, especially with recommendations for short-interval follow-up or biopsy, raising concerns about continued participation in routine screening among these women at increased breast cancer risk. National Cancer Institute.

Myositis -specific and -associated antibodies in neurological disorders - A retrospective study of 727 patients

ObjectiveMyositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are assessed in clinical neurology, serving as a non-invasive tool for the differential diagnosis of autoimmune myopathies. However, the presence of MSAs and MAAs in neurological disorders remains uncertain. MethodsRetrospective analysis was conducted on 878 serum samples from the neurological laboratory of the University Hospital Tübingen, Germany. The EUROLINE Myositis Profil 3 (IgG) Line Blot was used for antibody evaluation (anti-Mi2, -Ku, -PM-Scl100, -PM-Scl75, -Jo1, -SRP, -PL7, -PL12, -EJ, -OJ, and -Ro52). Samples were categorized into 19 disease groups, with consideration for myositis-linked and non-myositis-linked diseases. Then, the distribution of positive findings and the concurrent presence of more than one MAA/MSA were analyzed. ResultsAmong 727 included line blots, 84 could be assigned to myositis-linked diseases (thereof 44 positive for MAA/MSA). MAA and MSA taken together were more frequently positive for the main group of myositis-linked disease (52.4 %) compared to the non-myositis-linked group (14.6 %, overall specificity 85.4 %). However, individual antibodies were specific, ranging above 97.5 %. False positive antibody results can also occur in neurological differential diagnoses such as muscle dystrophy or cramp fasciculation syndrome. Furthermore, the concurrent presence of more than one MAA/MSA does not show a significant association with the presence of a myositis-linked disease for antibody-positive samples (p = 0.136). DiscussionTesting MSA and MAA simultaneously may not be suitable as a primary screening method for myositis-linked diseases in clinical neurological groups. However, MSAs and MAAs may offer valuable diagnostic support, particularly in cases where myositis is strongly considered.

Evaluating CA-125 and PET/CT for cancer detection in idiopathic inflammatory myopathies.

This study aims to evaluate the diagnostic accuracy of CA-125 and PET/CT in detecting cancer among adult patients with idiopathic inflammatory myopathy (IIM). We conducted a retrospective study of a single-centre cohort of adult IIM patients enrolled from 2003 to 2020. Data on CA-125 and PET/CT tests conducted within five years of IIM symptom onset were extracted from electronic medical records. The outcomes assessed included true positive, false-positive, true negative, and false-negative results. Among 1432 patients with IIM, 250 CA-125 tests were conducted on 205 patients within the first five years of symptom onset, yielding a false-positive rate of 3.1% and a false-negative rate of 14.3%. Most false positives were associated with endometriosis or uterine fibroids, but additional medical procedures were often carried out to investigate the false-positive results. For PET/CT, 149 tests were performed on 139 patients, resulting in a false-positive rate of 5.5% and a false-negative rate of 28.6%. Lymphadenopathy and lung nodules were the predominant causes of false positives, while melanoma, low-stage breast cancer, and prostate cancer were the most frequent cancers missed (false negatives). False positive and false-negative results are prevalent in CA-125 and PET/CT testing for adult patients with newly diagnosed idiopathic inflammatory myopathy. Understanding the causes of these inaccuracies can aid clinicians in making informed decisions during patient care.

Primary HPV screening compared with other cervical cancer screening strategies in women with HIV: a cost-effectiveness study.

To compare the model-predicted benefits, harms, and cost-effectiveness of cytology, cotesting, and primary HPV screening in U.S. women living with HIV (WLWH). We adapted a previously published Markov decision model to simulate a cohort of U.S. WLWH. United States. A hypothetical inception cohort of WLWH. We simulated five screening strategies all assumed the same strategy of cytology with HPV triage for ASCUS for women aged 21 to 29 years. The different strategies noted are for women aged 30 and older as the following: continue cytology with HPV triage, cotesting with repeat cotesting triage, cotesting with HPV16/18 genotyping triage, primary hrHPV testing with cytology triage, and primary hrHPV testing with HPV16/18 genotyping triage. The outcomes include colposcopies, false-positive results, treatments, cancers, cancer deaths, life-years and costs, and lifetime quality-adjusted life-years. Compared with no screening, screening was cost-saving, and > 96% of cervical cancers and deaths could be prevented. Cytology with HPV triage dominated primary HPV screening and cotesting. At willingness-to-pay thresholds under $250,000, probabilistic sensitivity analyses indicated that primary HPV testing was more cost-effective than cotesting in over 98% of the iterations. Our study suggests the current cytology-based screening recommendation is cost-effective, but that primary HPV screening could be a cost-effective alternative to cotesting. To improve the cost-effectiveness of HPV-based screening, increased acceptance of the HPV test among targeted women is needed, as are alternative follow-up recommendations to limit the harms of high false-positive testing.

Cut-offs for relapse detection in men with stage I testicular germ cell tumors during active surveillance within a prospective multicentre cohort study using either raw or housekeeper normalized miR-371a-3p serum levels

PurposeMiR-371a-3p represents a novel liquid biomarker that detects all histologies of germ-cell tumors (GCT) except teratoma. However, it is currently unclear whether miR-371a-3p results obtained directly from RT-PCR (raw Cq) or normalized for housekeeper genes and transformed into the relative quantity (RQ) value should be used and at what cut-off level. The purpose of this research was to evaluate, which values should be used, and a potential cut-off level for relapse-detection to inform subsequent studies. Materials and MethodsWe applied a CE-certified qRT-PCR test to measure miR-371a-3p at each follow-up visit during active surveillance in 34 men with stage I testicular GCT. MiR-371a-3p levels were calculated by the ΔΔ method. ResultsAbout 18 Patients had pure seminoma and 16 had mixed or nonseminomatous testicular GCT. Recurrences were detected in 10 patients and were correctly identified by both raw and housekeeper-normalized miR-371a-3p serum levels. The raw Cq, with a cut-off value of <28, resulted in only 1 false positive (3%), whereas RQ, with a cut-off value of >15, produced 6 false positive results (17%). Most of these false positive results normalized in subsequent measurements. The RQ approach detected recurrence in 1 patient 6 months earlier than the raw Cq approach. ConclusionOur preliminary data suggest that this CE-certified assay, using previously suggested cut-off values, is a promising method for detecting disease recurrence, provided a confirmatory second test is conducted to identify false positive results. To avoid unnecessary scans or overtreatment, we are currently validating this assay and cut-offs in a prospective cohort study.