Hidden blind spot and pseudofixation loss

Background: Correct mapping of the blind spot is important, as it serves as an estimate of fixation reliability. When the blind spot is not seen in the expected location in Humphrey visual field (HVF) printout, the clinician should give a thought to why this might be the case. Purpose: This video describes a series of cases, in which due to different reasons the blind spot could not be seen in the presumed expected location in the grayscale and numeric data of the HVF printout and the possible explanation behind this. Synopsis: When interpreting perimetry results, it is important to know whether the field test is reliable or not. A stimulus presented at the location of physiologic blind spot should not be seen by a patient with a steady fixation in Heijl– Krakau method. Responses will also occur, however, if the patient has a tendency for false?positive responses, or when the blind spot of the properly fixing eye is not in the location where the test stimulus is presented, because of anatomic variation, or if the patient's head is tilted while performing the test. Highlights: Perimetrist should recognize these potential artifact, during the test and relocate the blind spot. In case, such results are seen after finishing the test, it is recommended for the clinician to repeat the test

Causes of False-Positive Results in 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT Imaging / 中国医学科学院学报

Objective To investigate the causes of false-positive results in the 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) PET/CT imaging. Methods The imaging data of 547 patients undergoing 68Ga-FAPI-04 PET/CT examination in the Department of Nuclear Medicine of the Affiliated Hospital of Southwest Medical University from September 2020 to May 2021 were retrospectively collected.Two experienced nuclear medicine diagnostic physicians analyzed the clinical data,relevant imaging examinations,laboratory examinations,pathological results and follow-up results of the patients with false-positive results. Results The 68Ga-FAPI-04 PET/CT imaging of 547 patients showed false-positive results in 99 (18.1%) patients,including 56 males and 43 females.The postoperative pathological examination confirmed false-positive results in 13 patients,including 1 patient of thyroiditis,2 patients of pulmonary tuberculosis,1 patient of bone tuberculosis,2 patients of pulmonary inflammatory pseudotumor,1 patient of pulmonary sarcoidosis,1 patient of pulmonary benign fibroma,1 patient of organic pneumonia,2 patients of renal angiomyolipoma,1 patient of mass pancreatitis,and 1 patient of pancreatic mucinous cystadenoma.The medical history,relevant imaging examination,and long-term follow-up confirmed false-positive results in 86 patients.Specifically,the false-positive uptake in the neck,chest,abdomen,bone joint,and skin occurred in 8 (9.3%),13 (15.1%),5 (5.8%),57 (66.3%),and 3 (3.5%) patients,respectively.Inflammation-related uptake appeared in 83 (83.8%) patients with false-positive imaging results,of which arthritis (23 patients) and osteophyte (29 patients) were the most common.Sixteen (16.2%) patients showed the false-positive uptake related to fibroblasts. Conclusion 68Ga-FAPI-04 PET/CT imaging will show non-malignant tumor false-positive results,which are mainly associated with inflammation and fibroblasts.

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.

“Trigger happy” visual field: Ten pointers

Background: While performing the visual field test, some patients press the response button, at random and not in response to seeing a stimulus, resulting in a classical trigger happy visual field. Purpose: This can be identified by 10 pointers as shown in this single field analysis printout of Humphrey visual field (HVF), 24?2, Swedish interactive threshold algorithm (SITA) standard test of the right eye. These points are useful teaching points for the students to recognize. Synopsis: The video describes classical 10 points, which can be identified in an HVF 24?2 printout in a patient with high false?positive (FP) error. Highlights: The FP index is the most useful of the reliability indices. In SITA strategy, the FP rate is based upon the assessment of patient’s reaction time over the entire course of the test, and hence is not calculated until the test is completed. Therefore, it is important for the perimetrist to be alert to recognize the signs early during the test, such as high fixation los s (despite good fixation as seen on screen monitor) and unusually high retinal sensitivity values (up to 50 dB), and reinstruct the patient. If the test is completed, it should be repeated. This is important as the FP rates >15% are associated with compromised test results and are automatically removed from the glaucoma progression analysis.

Placenta Accreta Spectrum Prenatal Diagnosis Performance: Are Ultrasound False-positive Results Acceptable in Limited-resources Settings? / Desempenho do diagnóstico pré-natal do espectro da placenta acreta: Os resultados falso-positivos do ultrassom são aceitáveis em ambientes com recursos limitados?

Abstract Objective The immediate referral of patients with risk factors for placenta accreta spectrum (PAS) to specialized centers is recommended, thus favoring an early diagnosis and an interdisciplinary management. However, diagnostic errors are frequent, even in referral centers (RCs). We sought to evaluate the performance of the prenatal diagnosis for PAS in a Latin American hospital. Methods A retrospective descriptive study including patients referred due to the suspicion of PAS was conducted. Data from the prenatal imaging studies were compared with the final diagnoses (intraoperative and/or histological). Results A total of 162 patients were included in the present study. The median gestational age at the time of the first PAS suspicious ultrasound was 29 weeks, but patients arrived at the PAS RC at 34 weeks. The frequency of false-positive results at referring hospitals was 68.5%. Sixty-nine patients underwent surgery based on the suspicion of PAS at 35 weeks, and there was a 28.9% false-positive rate at the RC. In 93 patients, the diagnosis of PAS was ruled out at the RC, with a 2.1% false-negative frequency. Conclusion The prenatal diagnosis of PAS is better at the RC. However, even in these centers, false-positive results are common; therefore, the intraoperative confirmation of the diagnosis of PAS is essential.

Resumo Objetivo Recomenda-se o encaminhamento imediato de pacientes com fatores de risco para espectro placentário acreta (PAS, na sigla em inglês) para centros especializados, favorecendo assim o diagnóstico precoce e o manejo interdisciplinar. No entanto, erros diagnósticos são frequentes, mesmo em centros de referência (CRs). Buscou-se avaliar o desempenho do diagnóstico pré-natal para PAS em um hospital latino-americano. Métodos Um estudo descritivo retrospectivo incluindo pacientes encaminhados por suspeita de SAP foi realizado. Os dados dos exames de imagem do pré-natal foram comparados com os diagnósticos finais (intraoperatórios e/ou histológicos). Resultados Foram incluídos 162 pacientes no presente estudo. A idade gestacional mediana no momento da primeira ultrassonografia suspeita de PAS foi de 29 semanas, mas as pacientes chegaram ao CR de PAS com 34 semanas. A frequência de resultados falso-positivos nos hospitais de referência foi de 68,5%. Sessenta e nove pacientes foram operadas com base na suspeita de PAS com 35 semanas e houve 28,9% de falso-positivos no CR. Em 93 pacientes, o diagnóstico de PAS foi descartado no CR, com frequência de falso-negativos de 2,1%. Conclusão O diagnóstico pré-natal de PAS é melhor no CR. Entretanto, mesmo nestes centros, resultados falso-positivos são comuns; portanto, a confirmação intraoperatória do diagnóstico de SAP é essencial.

Prevalence of hypertension based on three separate visits among primaryand middle school students in Suzhou City / 预防医学

Objective@#To investigate the prevalence of hypertension among primary and middle school students living in Suzhou City, Jiangsu Province, so as to provide insights into comprehensive hypertension control among children and adolescents.@*Methods@# Primary and middle school students at ages of 7 to 17 years were recruited for a questionnaire survey in Suzhou City using the stratified cluster random sampling method from September to December, 2020, and the height and body weight were measured. Blood pressure was measured at three separate clinic visits according to the national criteria Reference of Screening for Elevated Blood Pressure among Children and Adolescents Aged 7-18 Years ( WS/T 610-2018 ), and the detection of elevated blood pressure was estimated at three separate visits. In addition, factors affecting elevated blood pressure were identified. @*Results@#A total of 3 713 students were enrolled, including 1 924 boys ( 51.82% ) and 1 789 girls ( 48.18% ). The detection of elevated blood pressure was 13.63%, 5.36%, and 3.37% at three separate visits, respectively, and the prevalence of hypertension ( elevated blood pressure at all three visits ) was 3.37%. The detection rates of elevated blood pressure were all higher at three visits ( 16.90%, 8.40%, and 5.26% ) among students at ages of 12 to 17 years than among students at ages of 7 to 11 years ( 9.65%, 1.67%, and 1.07%, P<0.05 ). The detection of elevated blood pressure was significantly higher in boys ( 15.23% ) than in girls (11.91%) at the first visit ( P<0.05 ), while no significant differences were seen at the second or third visit ( P>0.05 ). In addition, higher detection rates of elevated blood pressure were seen in obese ( 27.62%, 11.51%, and 7.06% ) and overweight students ( 17.45%, 6.95%, and 4.85% ) than in students with normal weight ( 9.44%, 3.54%, and 2.15% ) at all three visits, and greater detection rates of elevated blood pressure were found in obese students than in overweight students at the first and second visits ( P<0.017 ).@*Conclusions @#The prevalence of hypertension was 3.37% based on three separate visits among primary and middle school students in Suzhou City. Measurement of blood pressure at three separate visits within different days is effective to reduce the false positive rate of hypertension and decrease misdiagnosis among children and adolescents.

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 positives of screening in large-scale population with low infection rate of an infectious diseasea： a modeling analysis / 上海预防医学

ObjectiveTo explore the positive predictive value （PPV） and false positive （FP） number of screening test in mass testing when the prevalence of infection is low. MethodsAssuming a population of 20 million with the prevalence of disease infection ranging from 0.1% to 5.0%， PPV， true positive （TP） and FP numbers were calculated under different scenarios of combination of sensitivity （99.0%， 99.5%， and 100.0%） with specificity （97.0%， 97.5%， 98.0%， 98.5%， 99.0%， 99.5%， and 99.9%）. ResultsFor low infection prevalence （≤5.0%）， specificity has a greater impact on PPV than sensitivity； with the decrease of infection prevalence， the increase in PPV elevates when the specificity increases. When the infection prevalence is >1.0%， the closer the specificity is to 99.9%， the closer the PPV is to 100.0%. However， when the infection prevalence is <1.0%， the maximum PPV is only about 90.0%. When the infection rate is 0.1%， a screening test with more than 99.0% sensitivity could detect about 20 thousand TP cases in a population of 20 million. Additionally， the FP and PPV are estimated to be 599 thousand and 3.2% if the specificity is 97.0%， and 20 thousand and 50.0% if the specificity is 99.9%. When the infection rate is 1.0%， a screening test with ≥99.0% sensitivity and ≥97.0% specificity could detect about 0.198‒0.200 million TP cases； and the number of FP decreases from 594 thousand to 20 thousand when the specificity increases from 97.0% to 99.9%. When the infection rate is 5.0%， a screening test with ≥99.0% sensitivity and ≥97.0% specificity could detect about 0.99‒1.00 million TP cases； and the number of FP decreases from 570 thousand to 19 thousand when the specificity increases from 97.0% to 99.9%. When the infection prevalence is ≤5.0% in a total population of 20 million， there are about 20，000 FP cases even if the sensitivity and specificity reach the maximum values of 100.0% and 99.9%， respectively. ConclusionWhen the population is large and the infection prevalence is low， in addition to improving the specificity of the screening test in mass testing， the problem of a large number of false positives cannot be ignored.

Falsos positivos del cribado de trisomía 21 y 18 del primer trimestre y complicaciones obstétricas / Adverse outcomes in pregnancies with false positive trisomy 21 and 18 screening results

OBJETIVO: Analizar si los casos positivos de cribado combinado de trisomía 21 (t21) o trisomía 18 (t18) en ausencia de aneuploidía (falsos positivos- FP) se relacionan con complicaciones de la gestación, ajustando por factores demográficos y clínicos de riesgo. MATERIAL Y MÉTODOS: Estudio retrospectivo de casos y controles anidado en una cohorte de pacientes que acudieron para cribado del primer trimestre. Los casos fueron las pacientes con FP de riesgo combinado de t21 superior a 1/270 o riesgo de t18 superior a 1/100. Se consideraron complicaciones de la gestación: óbito fetal, parto prematuro menor de 34 semanas o prematuro menor de 37 semanas, preeclampsia, retrasos de crecimiento, pequeño para la edad gestacional (CIR, PEG) y diabetes gestacional (DG). Se ajustó por obesidad, edad, paridad, tabaquismo, y técnicas de reproducción asistida. RESULTADO: Se obtuvieron 204 casos de FP, 149 FP para trisomía 21, 41 para trisomía 18, y 14 FP para ambos riesgos. Se encontró asociación estadísticamente significativa de FP t21 con óbito fetal (OR=3,5; ic95% 1,4-8,7; p=0,01), parto prematuro menor de 37 semanas (OR=2,2; IC95% 1,4-3,4; p=0,001), preeclampsia (OR =2,6; IC95% 1,17-6,1; p=0,02), PEG (OR =2,2; IC95% 1,2-4,1; p=0,02), CIR (OR=2,8; IC95% 1,6-5,1; p=0,001), y DG (OR=2,1; IC95% 1,2-3,7; p=0,01). Los FP t18 se asociaron con óbito (OR=8,9; IC95% 2,9-27; p=0,002). CONCLUSIÓN: Los FP del cribado del primer trimestre, para trisomía 21 y trisomía 18, se asocian con resultados obstétricos adversos.

We have studied whether positive cases of combined trisomy 21 (t21) or 18 (t18) screening in the absence of aneuploidy (false positives -FP-) are related to pregnancy complications adjusting for demographic and clinical risk factors. METHODS: Retrospective case-control study nested in a cohort of patients who came for first trimester aneuploidy screening. The cases were patients with FP combined risk of t21 (greater than 1/270) or t18 risk (greater than 1/100). The control group was a sample of patients with low-risk screening. We considered pregnancy complications: stillbirth, premature delivery before 34 and 37 weeks, preeclampsia, growth retardation, small for gestational age (FGR, SGA), and gestational diabetes (GD). Or were adjusted for obesity, age, parity, smoking, and assisted reproduction techniques. RESULTS: 204 cases of FP were obtained, 149 FP for trisomy 21, 41 for trisomy 18, and 14 FP for both risks. A statistically significant association between t21 FP was found with stillbirth (OR = 3.5; 95% CI 1.4-8.7; p = 0.01), preterm delivery less than 37 weeks (OR = 2.2; 95% CI 1.4-3.4; p = 0.001), preeclampsia (OR = 2.6; 95% CI 1.17-6.1; p = 0.02), SGA (OR = 2.2; 95% CI 1, 2-4.1; p = 0.02), FGR (OR = 2.8; 95% CI 1.6-5.1; p = 0.001), and GD (OR = 2.1; 95% CI 1.2 −3.7; p = 0.01). FP t18s were associated with fetal loss (OR= 8.9 (95% CI 2.9-27) p = 0.002. CONCLUSION: FP from first trimester screening for t21 and t18 are associated with adverse obstetric outcomes.

Analysis of cytopathologic and sonographic features for false-positive diagnosis in fine-needle aspiration of thyroid nodules / 中华超声影像学杂志

Objective:To analyze the cytopathologic and sonographic features of false-positive diagnosis in fine-needle aspiration (FNA) of thyroid nodules.Methods:The false-positive diagnosis of thyroid nodules FNA which was confirmed by histopathology in the Affiliated Hospital of Sun Yat-sen University from Jan 2016 to Sep 2020 were collected and analyzed.Results:A total of 2, 626 patients with 2, 971 thyroid nodules were performed ultrasonography (US)-guided FNA, and 1, 061 thyroid nodules (35.7%) were confirmed by histopathology.Among these 1, 061 nodules, 817 (77.0%) were histopathologic malignancy, and 748(70.5%) were cytopathologic malignancy (TBSRTC Ⅴ-Ⅵ). Twenty-one patients with 23 thyroid nodules were false-positive diagnosis, showing TBSRTC Ⅴ, with a false-positive rate of 9.4%. In these false-positive cases, 18 patients showed normal thyroid function and 13 showed negative thyroid antibodies. All the false-positive nodules showed part of cytopathologic features of papillary thyroid carcinoma, but were insufficient to diagnose TBSRTC Ⅵ. In sonographic features, 16 nodules (69.6%) were classified as ACR TI-RADS 2-4, 12 (52.2%) were classified as C-TIRADS 3-4A or sonographic benign, and none of the nodules were found suspicious cervical lymph nodes metastasis.Conclusions:The overlapping of cytopathologic features is the main cause of false-positive diagnosis in thyroid nodules FNA. Sonographic features may play a role in decreasing the false-positive diagnosis.

Impak Densiti Payudara dalam Pengesanan Kanser Payudara The Impact of Breast Density on Breast Cancer Detection / Jurnal Sains Kesihatan Malaysia

@#The purpose of this research was to identify which category of breast density had higher possibility led to missed breast cancer and incorrect diagnosis. Ethics approval was granted by the Instituitional Research Ethics Committee. A total of 495 mammographic cases were chosen from the Radiology Department, University Kebangsaan Malaysia Medical Centre. All the mammographic cases were grouped into four groups which is true negative, true positive, false positive and false negative. Next, the mammograms were classified according to breast density categories (BI-RADS (a, b, c and d). Logistic regression was used to estimate the odds ratios of a false-positive and false-negative mammograms being associated with each category of breast density. Women with breast density BI-RADS d were four times more likely to have a false-positive mammogram than women with breast density BI-RADS a (odd ratio [OR], 4.27; 95% CI,0.88- 20.67). While women with breast density BI-RADS b and BI-RADS c were almost two times more likely (odd ratio [OR], 1.59, 1.32; 95% CI, 0.29-8.77, 0.25-7.01) to have a false-negative mammogram than women with fatty breast tissue (BI-RADS a). Mammographic image with breast density BI-RADS d has higher possibility to be falsely diagnosed, while mammographic image with breast density BI-RADS b and c have high possibility to miss the cancer. Thus, radiologist should be more cautious when interpreting mammograms with breast density BI-RADS b, c and d, so that the number of missed cancer and falsely diagnosis can be reduced at very early stage. Early detection of breast cancer can increase patients’ survival rate.

Dificultades en la detección de genomas del nuevo coronavirus 2 (SARS CoV-2) / Pandemic and social inequiality: the popular neighborhoods of the Buenos Aires suburbs in preventive social isolation

RESUMEN El manejo de las infecciones virales respiratorias, tanto a nivel nacional como a nivel mundial, requiere resultados científicos de calidad. La reacción en cadena de la polimerasa de transcriptasa inversa (rRT-PCR, por su sigla en inglés) es considerada el "patrón de oro" para detectar el genoma del nuevo coronavirus 2 (SARS-CoV-2), agente causal de la enfermedad por el nuevo coronavirus (COVID-19) sobre todo en la fase aguda de la infección. Su uso es controvertido fuera de un contexto de exposición viral. El objetivo del presente trabajo es analizar escollos encontrados durante la detección del genoma del SARS-CoV-2 que pueden producir resultados falsos. Los falsos negativos de rRT-PCR pueden deberse al momento y la eficacia de la toma de la muestra, la congelación, el almacenamiento y la descongelación, y a la inactivación térmica de la virulencia. Además, las señales retardadas de los controles internos invalidan la negatividad. Por otra parte, las muestras con escaso material biológico llevan a conclusiones negativas falsas, por lo que determinar un umbral (número mínimo de células epiteliales) contribuirá a reducirlas. Sin embargo, la mayoría de los kits detectan ADN humano, pero no fueron calibrados para cuantificar carga celular. Los ácidos ribonucleicos nucleares (ARN) virales adheridos a guantes, tubos y gorros, -entre otros elementos-, son fuente de falsos positivos. Las farmacopeas sugieren que la contaminación externa se controle en series de 100 muestras con al menos una representatividad del 10%. Si se extrapola esta aproximación al laboratorio de análisis clínicos, en lugar de uno se deberían procesar al menos 10 controles negativos contiguos a 10 positivos cada 100 pruebas. Mejorar la detección por rRT-PCR implica un aumento de al menos 20% en el costo de los reactivos, por lo que se necesitan recursos adicionales.

ABSTRACT Emerging respiratory viral infections like the severe coronavirus disease (CoVID 19) caused by novel coronavirus 2 (SARS-CoV-2) require quality results for science-based responses. The reverse transcriptase polymerase chain reaction (rRT-PCR) is considered the gold standard for detecting SARS-CoV-2 (particularly in the acute phase of infection). The aim of the present work was to analyze pitfalls during the search of viral genomes. False negative conclusions are result of sampling timing, performances of swabbing, storage, and thawing and heat-infectivity inactivation. Samples with low biologic material also lead to false negatives. Qualitative controls to detect the presence of human DNA are available in several kits but they were not calibrated for quantification of human cell loads. Moreover, negativity cannot be reported for samples with delayed signals for the internal control (due to deficiency in extraction and/or retro transcription and/or or to the presence of rRT-PCR inhibitors). The viral RNA that may have stick on gloves, on tubes, caps, etc. may produce false positives. The International Pharmacopoeias recommend for external contamination to test at least 10% of the samples. Couples of 10 negative contiguous to 10 positive controls randomly distributed should be therefore included in each series of 100 rRT-PCR tests. These improvements increase the cost of each determination (at least by 20% only for the reactants) and require additional resources.

Elevación persistente de troponina I / Persistent elevation of troponin I

Resumen La troponina cardiaca es el marcador bioquímico más sensible y específico de daño/necrosis miocárdica, de ahí que desempeñe un papel crucial en el diagnóstico del síndrome coronario agudo. Sin embargo, en ocasiones, como en el caso clínico que se describirá, la elevación anormal de troponina no siempre obedece a un síndrome coronario agudo trombótico, sino a causa cardiaca sin enfermedad coronaria significativa, causa extracardiaca o alteración analítica (verdaderos falsos positivos). El interés de este caso radica en que siempre debería tenerse en mente la posibilidad de que se produzca un falso positivo de troponina por causa analítica, en especial en situaciones clínicas sin una razón obvia de daño miocárdico y cuando no sea evidente la confirmación de daño miocárdico mediante pruebas complementarias.

Abstract Cardiac troponin is the most sensitive and specific biochemical marker for myocardial damage / necrosis, and thus has a crucial role in the diagnosis of acute coronary syndrome. However, occasionally, as in the clinical case that will be described, the abnormal elevation of troponin does not always obey that of an acute coronary syndrome, but also to a cardiac cause with no significant coronary disease, extra-cardiac cause, or analytical change (true false positives). The interest in this case lies in that it should always be borne in mind that a false positive troponin can be produced due to an analytical cause. This can be the case in clinical situations with no obvious reason for myocardial damage and when the confirmation of myocardial damage may not be evident using complementary tests.

Reasons and solutions for 'false positive results' of 2019 Novel Coronavirus-specific antibodies detection / 中华检验医学杂志

Assays of specific immunoglobulin M (IgM) and immunoglobulin G (IgG) have been supplemented in 'diagnosis and treatment guidelines of Novel Coronavirus pneumonia' (7th edition) issued by National Health Commission of the People’s Republic of China as an auxiliary evidence to diagnose Novel Coronavirus pneumonia. However, the false positive results is a major problem in the application of antibody assays. The factors causing the false positive results were analyzed and the ways were discussed to reduce the false positive results. The false positive results of antibody assays can be reduced, but they cannot be fully resolved. Antibody assays are valuable criteria for the diagnosis of suspected cases with negative nucleic acid results only if at least two dynamic tests are used.

Potential false-positive rate among the 'asymptomatic infected individuals’ in close contacts of COVID-19 patients / 中华流行病学杂志

Objective@#As the prevention and control of COVID-19continues to advance, the active nucleic acid test screening in the close contacts of the patients has been carrying out in many parts of China. However, the false-positive rate of positive results in the screening has not been reported up to now. But to clearify the false-positive rate during screening is important in COVID-19 control and prevention.@*Methods@#Point values and reasonable ranges of the indicators which impact the false-positive rate of positive results were estimated based on the information available to us at present. The false-positive rate of positive results in the active screening was deduced, and univariate and multivariate-probabilistic sensitivity analyses were performed to understand the robustness of the findings.@*Results@#When the infection rate of the close contacts and the sensitivity and specificity of reported results were taken as the point estimates, the positive predictive value of the active screening was only 19.67%, in contrast, the false-positive rate of positive results was 80.33%. The multivariate-probabilistic sensitivity analysis results supported the base-case findings, with a 75% probability for the false-positive rate of positive results over 47%.@*Conclusions@#In the close contacts of COVID-19 patients, nearly half or even more of the 'asymptomatic infected individuals’ reported in the active nucleic acid test screening might be false positives.

Performance of urea-mediated dissociation in reducing false-positive of 2019-nCoV IgM test / 中华检验医学杂志

Objective@#To investigate the interference factors causing false-positive result of novel coronavirus IgM antibody (SARS-CoV-2 IgM) detected by gold immunochromatography assay (GICA) and enzyme-linked immunosorbent assay (ELISA).@*Methods@#A total of 71 serum from different pathogen infections and related chronic diseases patients were collected from the Affiliated Hospital of North Sichuan Medical College from January 25, 2020 to February 15, 2020. GICA and ELISA were used to detect 2019-nCoV IgM in 71 serum, including 5 influenza A virus (Flu A) IgM positive serum, 5 influenza B virus (Flu B) IgM positive serum, 5 Mycoplasma pneumonia (MP) IgM positive serum, 5 Legionella pneumophila (LP) IgM positive serum, 29 rheumatoid factor (RF) IgM positive serum, 5 hypertension patients serum, 5 diabetes mellitus patients serum, 6 human immunodeficiency virus (HIV) infection patients serum and 6 Corona Virus Disease 2019 (COVID-19) patients serum. The interference factors causing false positive results of the two methods were analyzed, and urea dissociation test was employed to dissociate the 2019-nCoV IgM positive serum using the best dissociation concentration. Statistical analyses were performed by SPSS, version 19.0.@*Result@#s 2019-nCoV IgM was positive in 18 cases of middle-high level RF-IgM positive serum and 6 cases of 2019-nCoV-infected serum detected by two methods, and the other 47 serum were negative. When the dissociation concentration of urea was 6 mol/L, 2019-nCoV IgM was negative in 17 cases of middle-high level RF-IgM positive serum and positive in 6 cases of 2019-nCoV-infected serum detected by GICA. When the urea dissociation concentration was 4 mol/L, dissociation time was 10 min and the avidity index<0.46 was set as negative, 2019-nCoV IgM was negative in 15 cases of middle-high level RF-IgM positive serum and positive in 6 cases of 2019-nCoV-infected serum detected by ELISA.@*Conclusion@#The middle-high level of RF-IgM could cause false positive results of SARS-CoV-2 IgM detected by GICA and ELISA, and the urea dissociation test would be helpful for reducing the probability of false-positive results of SARS-CoV-2 IgM test.

Implementation of a Targeted Next-Generation Sequencing Panel for Constitutional Newborn Screening in High-Risk Neonates

PURPOSE: Newborn screening (NBS) programs are important for appropriate management of susceptible neonates to prevent serious clinical problems. Neonates admitted to neonatal intensive care units (NICU) are at a potentially high risk of false-positive results, and repetitive NBS after total parenteral nutrition is completely off results in delayed diagnosis. Here, we present the usefulness of a targeted next-generation sequencing (TNGS) panel to complement NBS for early diagnosis in high-risk neonates. MATERIALS AND METHODS: The TNGS panel covered 198 genes associated with actionable genetic and metabolic diseases that are typically included in NBS programs in Korea using tandem mass spectrometry. The panel was applied to 48 infants admitted to the NICU of Severance Children's Hospital between May 2017 and September 2017. The infants were not selected for suspected metabolic disorders. RESULTS: A total of 13 variants classified as likely pathogenic or pathogenic were detected in 11 (22.9%) neonates, including six genes (DHCR7, PCBD1, GAA, ALDOB, ATP7B, and GBA) associated with metabolic diseases not covered in NBS. One of the 48 infants was diagnosed with an isobutyl-CoA dehydrogenase deficiency, and false positive results of tandem mass screening were confirmed in two infants using the TNGS panel. CONCLUSION: The implementation of TNGS in conjunction with conventional NBS can allow for better management of and earlier diagnosis in susceptible infants, thus preventing the development of critical conditions in these sick infants.

Accuracy of SPECT/CT fusion imaging in differential diagnosis of benign and malignant spinal lesions / 中国基层医药

Objective@#To analyze and discuss the clinical value of single photon emission computed tomography(SPECT)/CT fusion imaging in differentiating benign and malignant spinal lesions.@*Methods@#From January 2017 to January 2018, 70 cases with benign and malignant spinal lesions in Shanxida Hospital were studied.SPECT/CT fusion imaging and SPECT examination were used to compare the diagnosis results between the two groups.@*Results@#After SPECT diagnosis, a total of 98 bone metastatic lesions were detected, including 10 false positive lesions, 60 benign lesions and 28 false negative lesions.After SPECT/CT fusion imaging, there were 100 lesions, including 4 false positive lesions, 59 benign lesions and 37 false negative lesions.In this study, a total of 145 lesions were found in 70 patients with benign and malignant spinal lesions, including 95 benign lesions and 50 malignant lesions.The specificity, sensitivity and accuracy of SPECT/CT fusion imaging [95.79%(91/95), 92.00%(46/50), 93.79%(136/145)] were higher than those of the control group [82.11%(78/95), 64.00%(32/50), and 82.76%(120/145)], the differences were statistically significant(χ2=9.048, 11.422, 9.578, all P<0.05).@*Conclusion@#In the diagnosis of benign and malignant spinal diseases, SPECT/CT fusion imaging can accurately distinguish benign and malignant lesions, and clearly reflect the development of the disease, which lay a solid foundation for good treatment in the future.

Evidence of National Lung Cancer Screening Program in Korea

Lung cancer is a leading cause of cancer death worldwide. The effectiveness of lung cancer targeted high-risk population using low dose chest computed tomography has been reported several randomized controlled trials. Thus, recently, lung cancer screening to high-risk group is recommended internationally. National Cancer Center reported a lung cancer screening guideline by evidence-based methods in 2015. Korean national lung cancer screening program started from 2019 after evaluation of Korean lung cancer screening demonstration project (K-LUCAS) nationwide. K-LUCAS obtained comparable high early lung cancer detection rate, lower false positive rate and lower complication rate compared with clinical trials conducted in other countries. Also psychological anxiety of screening participants had been low, but willingness of smoking cessation had been increased after screening. This paper will review the evidence of lung cancer screening from clinical trials, also, evaluate the benefits and harms of screening based on K-LUCAS.