[Retroperitoneal schwannoma mimicking colorectal cancer metastases: a false positive result report.] / Schwannoma retroperitoneal simulando metástasis de cáncer colorrectal: reporte de un resultado falso positivo.

Introduction: schwannomas are benign and common soft tissue tumors. They are usually asymptomatic and are discovered for other reasons. Materials: we present the case of an 82-year-old male patient with a recent diagnosis of moderately differentiated adenocarcinoma of the colon and a hypermetabolic periaortic nodule as an incidental finding. Results: percutaneous biopsy of the periaortic nodule confirmed the diagnosis of schwannoma. At one year of follow-up, growth of the schwannoma has been demonstrated. There are no signs of progression of his oncological disease. Conclusions: schwannomas are benign tumors, rarely found in the retroperitoneum and can be sources of false-positive positron emission tomography results.

Introducción: los schwannomas son tumores benignos y frecuentes de las partes blandas. Habitualmente son asintomáticos y son descubiertos por otros motivos. Materiales y métodos: presentamos el caso de un paciente masculino de 82 años con diagnóstico reciente de adenocarcinoma de colon moderadamente diferenciado y con un nódulo periaórtico hipermetabólico como hallazgo incidental. Resultados: la biopsia percutánea del nódulo periaórtico confirmó el diagnóstico de schwannoma. Al año de seguimiento, se ha demostrado crecimiento del schwannoma. No hay signos de progresión de su enfermedad oncológica. Conclusión: los schwannomas son tumores benignos, infrecuentes en el retroperitoneo y pueden ser fuentes de resultados falsos positivos en tomografía por emisión de positrones.

Benign Prostatic Hyperplasia-Related False-Positive of Prostate-Specific Membrane Antigen-Positron Emission Tomography in the Diagnosis of Prostate Cancer: The Achilles' Heel of Biopsy-Free Radical Prostatectomy?

PURPOSE: Radical prostatectomy is one of the primary treatments for localized clinically significant prostate cancer. Generally, its application is based on prior biopsy. PSMA (prostate-specific membrane antigen)-PET (positron emission tomography) is considered promising in biopsy-free radical prostatectomy. The expression of PSMA in benign prostatic hyperplasia tissue and corresponding positive reaction are crucial concerns for a no-biopsy strategy. Currently, no study has explored the benign prostatic hyperplasia-related false-positive of PSMA-PET in the detection of prostate cancer. Furthermore, the influence of maximum standardized uptake value and Prostate Imaging Reporting & Data System on biopsy-free radical prostatectomy is also poorly characterized. MATERIALS AND METHODS: A retrospective study was conducted on patients who received PSMA-PET because of clinical suspicion of prostate cancer and were confirmed to have benign prostatic hyperplasia or prostate cancer. The receiver operating characteristic curve was generated for maximum standardized uptake value. Results of interest were the false-positive rate of PSMA-PET and the efficacy of maximum standardized uptake value or multiparametric MRI in excluding false-positives. RESULTS: The benign prostatic hyperplasia-related false-positive rate of PSMA-PET in detecting prostate cancer was 30%. Maximum standardized uptake value could effectively exclude benign prostatic hyperplasia and Grade Group 1 patients with an area under the curve of 0.86; the optimal maximum standardized uptake value cutoff value with 100% specificity was 15, with a sensitivity of 41%. Notably, the sensitivity and specificity of stringent PET score and Prostate Imaging Reporting & Data System criteria (both ≥4) in diagnosing clinically significant prostate cancer were 49% and 100%, respectively. CONCLUSIONS: Our findings revealed benign prostatic hyperplasia-related false-positive rate of PSMA-PET and provided a preliminary reference in biopsy-free radical prostatectomy.

A high Z-score might increase the positive predictive value of cell-free noninvasive prenatal testing for singleton-pregnant women.

OBJECTIVE: To explore the positive predictive value (PPV) in noninvasive prenatal testing (NIPT)-positive cases and analyze the effect of the Z-score intervals on PPV performance. METHODS: In this retrospective study, 26,667 pregnant women underwent NIPT from November 2014 to August 2022, of which 169 were NIPT-positive cases. NIPT-positive cases were divided into three groups according to the Z-score: 3 ≤ Z < 6, 6 ≤ Z < 10, and Z ≥ 10. RESULTS: The PPVs of NIPT were 91.26% (94/103) for trisomy (T) 21, 80.65% (25/31) for T18, and 36.84% (7/19) for T13. The PPVs for the 3 ≤ Z < 6, 6 ≤ Z < 10, and Z ≥ 10 groups were 50%, 84.62%, and 87.95%, respectively. A higher PPV was found in the NIPT results when the Z-score was larger, with significant differences. The PPVs for T21/T18/T13 were 71.43%/42.86%/25% for 3 ≤ Z < 6, 90.32%/85.71%/57.14% for 6 ≤ Z < 10, and 93.85%/100%/25% for Z ≥ 10. For T21, T18, and T13, the correlations between the Z-score and fetal fraction concentration in true positives were r = 0.85, r = 0.59, and r = 0.71 (all p < .001), respectively. CONCLUSION: Z-score is associated with the PPV performance of NIPT in fetal T13, T18, and T21. The possibility of false positives caused by placental chimerism should be considered when determining whether high Z-values lead to high PPVs.

Multivariable stratification of PI-RADS version 2.1 categories for the risk of false-positive target biopsy: Impact on prostate biopsy decisions.

PURPOSE: To identify clinical and multiparametric magnetic resonance imaging (mpMRI) factors predicting false positive target biopsy (FP-TB) of prostate imaging reporting and data system version 2.1 (PI-RADSv2.1) ≥ 3 findings. METHOD: We retrospectively included 221 men with and without previous negative prostate biopsy who underwent 3.0 T/1.5 T mpMRI for suspicious clinically significant prostate cancer (csPCa) between April 2019-July 2021. A study coordinator revised mpMRI reports provided by one of two radiologists (experience of > 1500/>500 mpMRI examinations, respectively) and matched them with the results of transperineal systematic biopsy plus fusion target biopsy (TB) of PI-RADSv2.1 ≥ 3 lesions or PI-RADSv2.1 ≤ 2 men with higher clinical risk. A multivariable model was built to identify features predicting FP-TB of index lesions, defined as the absence of csPCa (International Society of Urogenital Pathology [ISUP] ≥ 2). The model was internally validated with the bootstrap technique, receiving operating characteristics (ROC) analysis, and decision analysis. RESULTS: Features significantly associated with FP-TB were age < 65 years (odds ratio [OR] 2.77), prostate-specific antigen density (PSAD) < 0.15 ng/mL/mL (OR 2.45), PI-RADS 4/5 category vs. category 3 (OR 0.15/0.07), and multifocality (OR 0.46), with a 0.815 area under the curve (AUC) in assessing FP-TB. When adjusting PI-RADSv2.1 categorization for the model, mpMRI showed 87.5% sensitivity and 79.9% specificity for csPCa, with a greater net benefit in triggering biopsy compared to unadjusted categorization or adjustment for PSAD only at decision analysis, from threshold probability ≥ 15%. CONCLUSION: Adjusting PI-RADSv2.1 categories for a multivariable risk of FP-TB is potentially more effective in triggering TB of index lesions than unadjusted PI-RADS categorization or adjustment for PSAD alone.

Renal impairment and abnormal liver function tests in pre-therapeutic phenotype-based DPD deficiency screening using uracilemia: a comprehensive population-based study in 1138 patients.

Background: Dihydropyrimidine dehydrogenase (DPD) deficiency screening is a pre-therapeutic standard to prevent severe fluoropyrimidine-related toxicity. Although several screening methods exist, the accuracy of their results remains debatable. In France, the uracilemia measurement is considered the standard in DPD deficiency screening. The objective of this study was to describe the hyperuracilemia (⩾16 ng/mL) rate and investigate the influence of hepatic and renal impairment in uracilemia measurements since the guidelines were implemented. Patients and methods: Using a cohort of 1138 patients screened between 18 October 2018 and 18 October 2021, basic demographic characteristics, date of blood sampling, and potential biological confounders including liver function tests [aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and bilirubin] and estimated glomerular filtration rate (eGFR) were collected. The second same-patient uracilemia analysis was also performed. Temporal change was graphically represented while potential confounders were stratified to show linearity when suspected. Results: Hyperuracilemia was diagnosed in 12.7% (n = 150) samples with 6.7%, 5.4%, 0.5%, and 0.08% between 16 and 20 ng/mL, 20 and 50 ng/mL, 50 and 150 ng/mL, and >150 ng/mL, respectively. The median uracilemia concentration was 9.4 ng/mL (range: 1.2 and 172.3 ng/mL) and the monthly hyperuracilemia rate decreased steadily from >30% to around 9%. Older age, normalized AST, γGT, ALP results, bilirubin levels, and decreased eGFR were linearly associated with higher plasma uracil concentrations (all p < 0.001). In the adjusted multivariate linear model, AST, eGFR, and ALP remained associated with uracilemia (p < 0.05). When measured twice in 39 patients, the median uracilemia rate of change was -2.5%, which subsequently changed the diagnosis in nine patients (23.1%). Conclusions: Better respect of pre-analytical conditions may explain the steady decrease in monthly hyperuracilemia rates over the 3 years. Elevated AST, ALP levels, and reduced eGFR could induce a false increase in uracilemia and second uracilemia measurements modified the first DPD deficiency diagnosis in almost 25% of the patients.

Risco de resultado falso positivo no rastreamento mamográfico do Brasil / Risk of false-positive result in mammography screening in Brazil / Riesgo de resultados falsos positivos en el cribado mamográfico en Brasil

Resultados falsos positivos na mamografia de rastreamento são comuns a essa intervenção e trazem ônus para as mulheres e o sistema de saúde. O objetivo deste estudo foi estimar o risco de resultado falso positivo no rastreamento mamográfico brasileiro com base em dados de sistemas de informação do Sistema Único de Saúde (SUS). Foi realizado estudo de coorte histórica de mulheres de 40-69 anos, que realizaram mamografia de rastreamento e exame histopatológico de mama no SUS, nos anos de 2017 a 2019. A taxa de resultados falsos positivos foi estimada a partir da prevalência de resultados BI-RADS alterados na mamografia de rastreamento e da proporção de resultados benignos no exame histopatológico de mama. Das 10.671 mulheres com exame histopatológico no SUS, 46,2% apresentaram resultado benigno, sendo essa proporção significativamente maior em mulheres de 40-49 anos comparada à de mulheres de 50-69 anos. A estimativa de resultados falsos positivos foi de 8,18 casos por 100 mulheres na faixa etária de 40-49 anos, e de 6,06 por 100 mulheres na faixa de 50-69 anos. Essas informações são úteis aos gestores na avaliação de programas de rastreamento do câncer de mama, assim como aos profissionais de saúde, para que orientem a mulher sobre as implicações do rastreamento mamográfico.

False-positive results on mammography screening are common, putting a burden on both women and the health care system. This study aimed to estimate the risk of false-positive results in Brazilian mammography screening based on data from the Brazilian Unified National Health System (SUS) information systems. A retrospective cohort study was conducted with women aged 40-69 years, who underwent mammography screening and breast histopathological examination at SUS from 2017 to 2019. The rate of false-positive results was estimated based on the prevalence of altered BI-RADS results on mammography screening and the proportion of benign results on breast histopathological examination. Of the 10,671 women with histopathological examination at SUS, 46.2% had a benign result, and this proportion was significantly higher in women aged 40-49 years compared to women aged 50-69 years. The estimate of false-positive results was 8.18 cases per 100 women aged 40-49 years and 6.06 per 100 women aged 50-69 years. This information is useful for public managers in evaluating mammography screening programs, as well as for health care providers to guide women on the implications of mammography screening.

Los resultados falsos positivos en la mamografía de cribado son comunes en esta intervención y suponen prejuicios para las mujeres y el sistema de salud. El objetivo de este estudio fue estimar el riesgo de resultados falsos positivos en el cribado mamográfico brasileño a partir de los datos del sistema de información del Sistema Único de Salud (SUS). Se realizó un estudio de cohorte histórica de mujeres de 40-69 años, que se sometieron a mamografía de cribado y examen histopatológico de mama en el SUS, de 2017 a 2019. La tasa de resultados falsos positivos se estimó a partir de la prevalencia de resultados de BI-RADS alterados en la mamografía de cribado y la proporción de resultados benignos en el examen histopatológico de mama. De las 10.671 mujeres que se sometieron a examen histopatológico en el SUS, el 46,2% tuvo un resultado benigno, siendo esta proporción significativamente mayor en mujeres de 40-49 años en comparación con las mujeres de 50-69 años. La estimación de resultados falsos positivos fue de 8,18 casos por 100 mujeres en el grupo de edad de 40-49 años y 6,06 por 100 mujeres en el grupo de 50-69 años. Esta información es útil para los gestores en la evaluación de los programas de cribado de cáncer de mama, así como para los profesionales sanitarios en orientar a las mujeres sobre las implicaciones del cribado mamográfico.

Application value of modified magnetic bead screening for enrichment of cell-free fetal DNA from maternal peripheral blood in non-invasive prenatal testing / 中华围产医学杂志

Objective:To evaluate the value of modified magnetic bead screening for enrichment of cell-free fetal DNA (cffDNA) in non-invasive prenatal testing (NIPT).Methods:This study retrospectively recruited 31 cases with low concentration of cffDNA (<6.00%), Z value in the gray zone (3.00-4.00) at the first detection, or false-positive (confirmed by invasive prenatal diagnosis) or false-negative (confirmed by postnatal chromosome test) results among 11 000 pregnant women who underwent routine NIPT in Beijing Haidian District Maternal and Child Health Care Hospital from October 2017 to December 2019. Plasma samples collected for the first-time routine NIPT were used to enrich cffDNA using modified magnetic beads for NIPT (modified NIPT). Wilcoxon rank sum test was used to compare the modified NIPT with the routine NIPT in detecting the cffDNA concentrations of male fetuses.Results:Among the 31 pregnant women, there were 13 cases with low cffDNA concentration in routine NIPT, 11 having false-positive results in the routine NIPT (three for trisomy 13, four for trisomy 18 and four for trisomy 21, all were confirmed by invasive prenatal diagnosis), six with gray-zone Z values in the first-time NIPT (retesting indicating low risk) and one having false negative result for trisomy 21 (confirmed by postnatal chromosome test). Cell-free DNA (cfDNA) fragments less than 150 bp were effectively enriched using the modified magnetic bead screening and the concentration of cffDNA was increased from 4.43% (2.45%-17.61%) in routine NIPT to 13.46% (7.75%-36.64%) in the modified NIPT ( Z=-14.22, P<0.01). Results of the modified NIPT indicated that 13 cases with low cffDNA concentration of routine NIPT were successfully detected as low risk, as well as the risks in the six cases with gray-zone Z value and six of the 11 false-positive cases in the routine NIPT were low, which were consistent with the retest results of the routine NIPT, while high risk was found in one false-negative case. Conclusions:The modified NIPT could reduce the false positive rate by lowering the failure rate caused by low concentration of cffDNA and is able to identify false-negative cases. Compared with the routine NIPT, it shows a higher success rate and a lower false positive rate.

Positive drug provocation with beta-lactam antibiotics in children: A single test may not be enough.

BACKGROUND: Drug provocation tests (DPTs) are considered the gold standard for diagnosing beta-lactam allergy. However, positive results tend to be mild and difficult to interpret. This study aimed to describe pediatric patients with a presumedly positive or inconclusive DPT, assess the decision to repeat the DPT, and describe its outcome. METHODS: Retrospective review of all presumedly positive or inconclusive DPTs performed in six pediatric allergy clinics from 2017 to 2019. We describe the interpretation of results, focusing on the decision to repeat the DPT and its outcome. RESULTS: Of 439 children challenged with a beta-lactam, 26 (5.9%) with a presumedly positive or inconclusive result were included in this study. Most were girls (n = 16, 61.5%), and the median age was 5 years (range 1-13). The initial DPT used amoxicillin (n = 13, 50.0%), amoxicillin-clavulanic acid (n = 12, 46.2%), or cefadroxil (n = 1, 3.8%). Reactions were early (n = 11, 42.3 %), delayed (n = 14, 53.8 %), or not registered (n = 1, 3.8 %), but mild in all cases. A second confirmatory DPT was proposed in 19 patients (73.1%) and performed in 17 patients (65.4%). Nine DPTs were performed from 1 day to 4 months after the first DPT, and the remaining eight took place 6 months to 2 years later. Fifteen children tolerated the drug in the second DPT: 88.2% of those reevaluated and 57.5% of the whole study group. CONCLUSION: The positive predictive value of DPT may be lower than expected. Given the mildness of observed reactions, a second confirmatory DPT is warranted within a few weeks or months.

Positive drug provocation with beta-lactam antibiotics in children: A single test may not be enough

Background: Drug provocation tests (DPTs) are considered the gold standard for diagnosing beta-lactam allergy. However, positive results tend to be mild and difficult to interpret. This study aimed to describe pediatric patients with a presumedly positive or inconclusive DPT, assess the decision to repeat the DPT, and describe its outcome.Methods: Retrospective review of all presumedly positive or inconclusive DPTs performed in six pediatric allergy clinics from 2017 to 2019. We describe the interpretation of results, focusing on the decision to repeat the DPT and its outcome.Results: Of 439 children challenged with a beta-lactam, 26 (5.9%) with a presumedly positive or inconclusive result were included in this study. Most were girls (n = 16, 61.5%), and the median age was 5 years (range 1–13). The initial DPT used amoxicillin (n = 13, 50.0%), amoxicillin-clavulanic acid (n = 12, 46.2%), or cefadroxil (n = 1, 3.8%). Reactions were early (n = 11, 42.3 %), delayed (n = 14, 53.8 %), or not registered (n = 1, 3.8 %), but mild in all cases. A second confirmatory DPT was proposed in 19 patients (73.1%) and performed in 17 patients (65.4%). Nine DPTs were performed from 1 day to 4 months after the first DPT, and the remaining eight took place 6 months to 2 years later. Fifteen children tolerated the drug in the second DPT: 88.2% of those reevaluated and 57.5% of the whole study group.Conclusion: The positive predictive value of DPT may be lower than expected. Given the mildness of observed reactions, a second confirmatory DPT is warranted within a few weeks or months (AU)

False-positive Xpert® Xpress SARS-CoV-2 assay in an emergency room and trauma center: A retrospective chart review study.

OBJECTIVES: To review reports false-positive Xpert results in an emergency room and trauma center. METHODS: Patients' data with false-positive Xpert results from November 2020 to February 2022 at Pusan National University Hospital, Busan, Republic of Korea, were extracted from the electronic medical records. RESULTS: The positive predictive value of Xpert was 40%. Of the 12 patients with false-positive results, 5 (41.7%) were re-positives (such as, patients recovered from coronavirus disease-19 [COVID-19]), and 4 (33.3%) had head or facial trauma. Two out of 4 head or facial trauma cases had documented sample contamination with blood. CONCLUSION: We found a high incidence of false-positive Xpert results among patients who recovered from COVID-19 and those with head or facial injury. Careful history taking for COVID-19 and physical examination of the sample collection site is essential before Xpert analysis.

Three cases of clinically significant inaccurate carboxyhemoglobin measurement.

Background: Clinicians often rely on measurement of carboxyhemoglobin (COHb) to confirm or rule out a diagnosis of carbon monoxide (CO) poisoning. Methods: We report two cases of false negative COHb in patients with CO poisoning and one case of false positive COHb in a patient without CO poisoning. Results: In the first case, a 20-year-old male developed headache, confusion, and near-syncope while operating a gasoline-powered pressure washer in an enclosed space. In the emergency department (ED), his COHb was 1.8%, but this level was disregarded, and he was referred for hyperbaric oxygen. His COHb just before hyperbaric oxygen was 4.1%, and later analysis of his blood collected at ED arrival revealed a COHb of 20.1%. The referral ED blood gas machine calibration and controls were within specification. In the second case, a 45-year-old male presented with several others to the ED with symptoms of CO poisoning after exposure at a conference. All others had elevated COHb levels, but his COHb was 2%. He was discharged but returned shortly with continued symptoms and requested his COHb be repeated. The repeat COHb was 17% (84 minutes after the first). After three hours of oxygen, his COHb was 7%. In the final case, an 83-year-old non-smoking male presented to an ED with breathlessness and tachypnea and was diagnosed with COVID-19 pneumonia. His COHb was 7.1%, but he reported living in an all-electric home. Another adult who lived with him and rode with him to the ED was asymptomatic and had a COHb of 3%. Later, COHb of 1.9% was measured from blood collected at ED arrival, and gas chromatography/mass spectrometry confirmed this result (2%). Conclusions: COHb levels are not always accurate. Clinicians should use clinical judgment to manage their patients, including rejecting laboratory values that do not fit the clinical situation.

Cumulative risk of a false-positive screening result: A retrospective cohort study using empirical data from 10 biennial screening rounds in BreastScreen Norway.

BACKGROUND: False-positive screening results are an inevitable and commonly recognized disadvantage of mammographic screening. This study estimated the cumulative probability of experiencing a first false-positive screening result in women attending 10 biennial screening rounds in BreastScreen Norway, which targets women aged 50 to 69 years. METHODS: This retrospective cohort study analyzed screening outcomes from 421,545 women who underwent 1,894,523 screening examinations during 1995-2019. Empirical data were used to calculate the cumulative risk of experiencing a first false-positive screening result and a first false-positive screening result that involved an invasive procedure over 10 screening rounds. Logistic regression was used to evaluate the effect of adjusting for irregular attendance, age at screening, and number of screens attended. RESULTS: The cumulative risk of experiencing a first false-positive screening result was 18.04% (95% confidence interval [CI], 18.00%-18.07%). It was 5.01% (95% CI, 5.01%-5.02%) for experiencing a false-positive screening result that involved an invasive procedure. Adjusting for irregular attendance or age at screening did not appreciably affect these estimates. After adjustments for the number of screens attended, the cumulative risk of a first false-positive screening result was 18.28% (95% CI, 18.24%-18.32%), and the risk of a false-positive screening result including an invasive procedure was 5.11% (95% CI, 5.11%-5.22%). This suggested that there was minimal bias from dependent censoring. CONCLUSIONS: Nearly 1 in 5 women will experience a false-positive screening result if they attend 10 biennial screening rounds in BreastScreen Norway. One in 20 will experience a false-positive screening result with an invasive procedure. LAY SUMMARY: A false-positive screening result occurs when a woman attending mammographic screening is called back for further assessment because of suspicious findings, but the assessment does not detect breast cancer. Further assessment includes additional imaging. Usually, it involves ultrasound, and sometimes, it involves a biopsy. This study has evaluated the chance of experiencing a false-positive screening result among women attending 10 screening examinations over 20 years in BreastScreen Norway. Nearly 1 in 5 women will experience a false-positive screening result over 10 screening rounds. One in 20 women will experience a false-positive screening result involving a biopsy.

Improved radiation expression profiling in blood by sequential application of sensitive and specific gene signatures.

PURPOSE: Combinations of expressed genes can discriminate radiation-exposed from normal control blood samples by machine learning (ML) based signatures (with 8-20% misclassification rates). These signatures can quantify therapeutically relevant as well as accidental radiation exposures. The prodromal symptoms of acute radiation syndrome (ARS) overlap those present in influenza and dengue fever infections. Surprisingly, these human radiation signatures misclassified gene expression profiles of virally infected samples as false positive exposures. The present study investigates these and other confounders, and then mitigates their impact on signature accuracy. METHODS: This study investigated recall by previous and novel radiation signatures independently derived from multiple Gene Expression Omnibus datasets on common and rare non-neoplastic blood disorders and blood-borne infections (thromboembolism, S. aureus bacteremia, malaria, sickle cell disease, polycythemia vera, and aplastic anemia). Normalized expression levels of signature genes are used as input to ML-based classifiers to predict radiation exposure in other hematological conditions. RESULTS: Except for aplastic anemia, these blood-borne disorders modify the normal baseline expression values of genes present in radiation signatures, leading to false-positive misclassification of radiation exposures in 8-54% of individuals. Shared changes, predominantly in DNA damage response and apoptosis-related gene transcripts in radiation and confounding hematological conditions, compromise the utility of these signatures for radiation assessment. These confounding conditions (sickle cell disease, thrombosis, S. aureus bacteremia, malaria) induce neutrophil extracellular traps, initiated by chromatin decondensation, DNA damage response and fragmentation followed by programmed cell death or extrusion of DNA fragments. Riboviral infections (e.g. influenza or dengue fever) have been proposed to bind and deplete host RNA binding proteins, inducing R-loops in chromatin. R-loops that collide with incoming replication forks can result in incompletely repaired DNA damage, inducing apoptosis and releasing mature virus. To mitigate the effects of confounders, we evaluated predicted radiation-positive samples with novel gene expression signatures derived from radiation-responsive transcripts encoding secreted blood plasma proteins whose expression levels are unperturbed by these conditions. CONCLUSIONS: This approach identifies and eliminates misclassified samples with underlying hematological or infectious conditions, leaving only samples with true radiation exposures. Diagnostic accuracy is significantly improved by selecting genes that maximize both sensitivity and specificity in the appropriate tissue using combinations of the best signatures for each of these classes of signatures.

Clinical value of noninvasive prenatal testing in vanishing twin pregnancies / 中华围产医学杂志

Objective:To analyze the clinical value of noninvasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies.Methods:A total of 164 VT pregnancies that underwent NIPT in Peking University Third Hospital from January 2017 to December 2020 were enrolled. Gestational age at onset of vanishing, results of NIPT and invasive prenatal diagnosis, blood sampling time points, and pregnancy outcomes were retrospectively analyzed using two independent samples t test and Chi-square test. Results:(1) Of the 164 cases, six had positive results for NIPT, but negative results for karyotype analysis or single nucleotide polymorphism genotyping, with a false positive rate of 3.7% (6/164) for NIPT and all of them were delivered at term. Four pregnancies terminated in the second trimester, including two fetal malformation cases and one unexplained intrauterine death whose single nucleotide polymorphisms results are all normal and one inevitable abortion case due to premature rupture of membrane who refused amniocentesis. The other 154 women all gave birth to normal phenotype babies including 12 preterm ones. (2) The false-positive rate of NIPT was lower in VT pregnancies diagnosed at less than eight gestational weeks than those diagnosed after [1.5% (2/134) vs 13.3% (4/30), χ2=6.68, P=0.010]. The false-positive rate was 6.9% (4/58) in women diagnosed at or below eight weeks between the occurrence of VT and blood sampling and was 1.9% (2/106) in those with interval more than eight weeks, but without significant difference ( χ2=1.44, P=0.231). Conclusions:Although VT pregnancies exist false-positive results in NIPT, screening is still recommended based on fully informed consent to reduce unnecessary invasive prenatal diagnosis. The earlier the onset of VT, the lower the NIPT false positive rate, but whether extending the sampling interval would reduce the risk of false-positive needs further study.

False-positive drug test results in patients taking psychotropic drugs. A literature review. / Falszywie dodatnie wyniki testów narkotykowych u pacjentów przyjmujacych leki psychotropowe ­ przeglad literatury.

INTRODUCTION: The study reviews the literature on false-positive drug test results in patients taking psychotropic medications. METHOD: A narrative review of available literature in English and Polish was conducted by searching MEDLINE/PubMed and Google Scholar databases using the search phrase ?falsepositive drug test' and names of selected registered antidepressant, antipsychotic and mood stabilizing medications as well as pharmaceuticals used in the treatment of ADHD. Review articles, case reports and original papers from years 1990-2019 were analyzed. RESULTS: False-positive drug test results have been reported for many psychiatric drugs: clomipramine, amitriptyline, bupropion, trazodone, sertraline, venlafaxine, hydroxyzine, haloperidol, sulpiride, perazine, levomepromazine, aripiprazole, risperidone, amisulpride, quetiapine, lamotrigine, carbamazepine, methylphenidate, and atomoxetine. No such reports have been found for other drugs considered in this study. CONCLUSIONS: When interpreting urine drug tests, caution should be exercised, especially when the tested person categorically denies the use of psychoactive substances. In such situations, the patient's medication list should be analyzed to ascertain that the obtained result is not false-positive. When test results are unclear, the presence of drugs in the urine can be effectively confirmed or excluded using gas chromatography. Unfortunately, most of the data available in the literature are case reports, which means they require further support from studies of large cohorts of patients taking psychotropic medications.

A systematic review of the outcomes of false-positive results on newborn screening for congenital hypothyroidism.

OBJECTIVES: The potential of harm to infants or their parents from a false positive (FP) newborn screening (NBS) result for congenital hypothyroidism (CH) is often cited as an argument against lowering of screening thresholds for CH. This systematic review (SR) examines the evidence of harm and factors that possibly contribute. STUDY DESIGN: PRISMA guidelines were followed and the protocol was registered online (Prospero, ID CRD42019123950, 20 August 2019) before the search was conducted. Multiple electronic databases and grey literature were searched. Articles were included/excluded based on predetermined eligibility criteria. Included articles were appraised for quality, using the relevant Critical Appraisal Skills Program (CASP) tool. Data were extracted and results were tabulated and summarised as part of a narrative synthesis. RESULTS: A total of six studies met the inclusion criteria. All were qualitative and three were based on the same cohort. Studies were published between 1983 and 1996. CASP appraisals scored 2/6 studies as moderate quality and 4/6 as low quality. Studies reported that FP results on CH screening may cause initial stress for parents and poorly defined behavioural disturbance in a small number of children, though these effects were generally not long-lasting. Poor screening processes and inadequate communication with parents, increased the risk of harm to parents and children, from FP results. CONCLUSION: This SR found a small number of dated, qualitative studies of low to moderate quality, conducted soon after the initiation of NBS for CH. Conclusive evidence of the risks of harm from FP results and ways to mitigate harm, awaits further, well-designed studies.

Neuromonitoring in Cervical Spine Surgery: When Is a Signal Drop Clinically Significant?

STUDY DESIGN: Retrospective cohort study. PURPOSE: To identify the clinical significance of different patterns of intraoperative neuromonitoring (IONM) signal alerts. OVERVIEW OF LITERATURE: IONM is a long-established valuable adjunct to complex spine surgeries. IONM for cervical spine surgery is in the form of somatosensory evoked potential (SSEP) and motor evoked potential (MEP). The efficacy of both modalities (individually or in combination) to detect clinically significant neurological compromise is constantly being debated and requires conclusive suggestions. METHODS: Clinical and neuromonitoring data of 207 consecutive adult patients who underwent cervical spine surgeries at multiple surgical centers using bimodal IONM were analyzed. Signal changes were divided into three groups. Group 0 had transient signal changes in either MEPs or SSEPs, group 1 had sustained unimodal changes, and group 2 had sustained changes in both MEPs and SSEPs. The incidences of true neurological deficits in each group were recorded. RESULTS: A total of 25% (52/207) had IONM signal alerts. Out of these signal drops, 96% (50/52) were considered to be false positives. Groups 0 and 1 had no incidence of neurological deficits, while group 2 had a 29% (2/7) rate of true neurological deficits. The sensitivities of both MEP and SSEP were 100%. SSEP had a specificity of 96.6%, while MEP had a lower specificity at 76.6%. C5 palsy rate was 6%, and there was no correlation with IONM signal alerts (p=0.73). CONCLUSIONS: This study shows that we can better predict its clinical significance by dividing IONM signal drops into three groups. A sustained, bimodal (MEP and SSEP) signal drop had the highest risk of true neurological deficits and warrants a high level of caution. There were no clear risk factors for false-positive alerts but there was a trend toward patients with cervical myelopathy.

The utility of second single antigen bead assay: Clearing the water or stirring up mud?

Though solid-phase single antigen bead (SAB) testing has provided major advances to the HLA community and organ allocation, it has not been without limitations. In particular, false-positive reactions lead to interpretative challenges and the potential to preclude a transplant if the corresponding antigens are deemed unacceptable. Two different vendor platforms are commercially available for SAB testing, one more recent than the other. The aim herein was to assess the benefit of using the newer SAB platform in situations where the primary platform yielded suspicious (specifically, false positive) reactions. Therefore, 42 serum samples with commonly encountered false-positive patterns observed in our laboratory were tested with the newer platform. Cases were classified as resolved, equivalent, or divergent based on whether the second platform produced no reactivity, the same pattern, or a distinctly different pattern compared to the primary platform, respectively. Approximately 33% of cases were resolved, 46% were equivalent, and 21% were divergent. The project revealed advantages of adding a second SAB platform to the laboratory's test menu including resolving challenging samples and including broader coverage of different alleles and unique class II alpha/beta subunit combinations. However, the challenges of validating, maintaining, and billing for another test method in the laboratory may be barriers to routine use.