Cause Of False-positive Results Research Articles

131I Accumulation Due to an Intrauterine Device in a Papillary Thyroid Carcinoma Patient.

A 46-year-old woman underwent 131I radiotherapy following thyroidectomy for papillary thyroid carcinoma. Posttherapeutic 131I scintigraphy was performed 4 days later. Both attenuation-corrected and non-attenuation-corrected 131I tomography images elucidated an intrauterine device with avid 131I uptake in her uterus. This case illustrated that an intrauterine device should be considered as a potential cause of false-positive results in posttherapeutic 131I scintigraphy, highlighting the need for accurate image interpretation to avoid unnecessary treatment.

Inter-Laboratory Comparison of qPCR Assays for Piscirickettsia salmonis in Atlantic Salmon (Salmo salar L.) in 11 Chilean Laboratories.

Real-time PCR (qPCR) testing is an essential component of early detection surveillance systems for Piscirickettsia salmonis infection in Atlantic salmon farms in Chile. Currently, all 11 laboratories in the authorised diagnostic laboratory network use assays based on published protocols. Compared with other P. salmonis qPCR assays, these assays have the advantage of targeting two different genes, that is, the 16S ribosomal gene and the internal transcribed spacer (ITS), potentially allowing for higher diagnostic accuracy. However, variation and lack of harmonisation of qPCR testing systems (e.g., primers/probe, RNA/DNA as target, extraction methods, etc.) may contribute to among-laboratory variation in qPCR results and an increased frequency of false-negative and false-positive results. The purpose of the ring trial reported herein was to compare qPCR results from 11 laboratories in Chile routinely testing Atlantic salmon for P. salmonis as part of a national control program. The panel of 14 samples included duplicates of three concentrations of P. salmonis in a homogenised head kidney, LF89 and EM90 bacteria and two negative controls (blank and a suspension of Flavobacterium psychrophilum). The sample order was randomised across labs, samples were tested blinded and analysed without knowledge of the source lab. Of the laboratories, 8 (72.7%) had at least one incorrect result out of 14 tested samples. Low-concentration samples (Ct of about 30) were more often incorrectly classified by reverse transcription-qPCR (RT-qPCR) (3/6 labs) than by qPCR (0/5). Six (54.5%) labs had at least one false-positive result indicating that cross-contamination was likely during sample processing. Affected laboratories are advised to conduct internal investigations to confirm the causes of false-positive results and recommendations for design and implementation of future ring trials are discussed.

Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs.

Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR). This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate). Receiver operating characteristic curves for steroid-probability scores and the ARR were examined with and without interfering medications. Impacts of individual medications on plasma aldosterone, 18-oxocortisol, 18-hydroxycortisol, steroid-probability scores, renin, and ARRs were examined by multivariable and paired analyses in patients with and without PA. Receiver operating characteristic curves indicated a significant impact of interfering antihypertensive medications on the diagnostic performance of the ARR and minimal impact on steroid-probability scores. Mineralocorticoid receptor antagonists increased plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol in patients without PA and resulted in false-positive test results for steroid-probability scores and false-negative results for the ARR. Diuretics increased aldosterone, 18-oxocortisol, and steroid-probability scores in patients without PA, whereas angiotensin-converting enzyme inhibitors decreased aldosterone, steroid-probability scores, and ARRs. Beta-adrenoceptor blockers, dihydropyridine calcium channel blockers, and angiotensin receptor blockers had negligible impact on mineralocorticoids and steroid-probability scores. Among antihypertensive drugs that impact plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol, mineralocorticoid receptor antagonists stood out as a cause of false-positive results for derived steroid-probability scores. Other antihypertensives have minimal or no impact, an advantage for use of steroid-probability scores over the ARR when those medications cannot be withdrawn. URL: https://drks.de/search/en/trial/DRKS00017084; Unique identifier: DRKS00017084.

Highly Sensitive Interleukin Score for Intra-Ocular Lymphoma Diagnosis: Evidence from Analysis of 5-Year Real-Life of Use

Introduction Primary vitreoretinal lymphoma (PVRL) is a rare and aggressive subset of large B-cell lymphoma of immune-privileged sites. It can occur independently or concomitantly to primary central nervous system lymphoma. Symptoms are not specific and can easily be confused with other uveitis. Diagnosis of intra-ocular lymphoma (IOL), including PVRL and secondary lymphoma localization, is based on malignant lymphoid cells identification in vitrectomy(cytology, flow cytometry, molecular analysis). Nevertheless, the fragility of lymphoma cells and low cellularity of samples make diagnosis difficult with these cellular tools. The quantification of interleukin (IL) in intraocular fluids is a promising soluble alternative approach. Based on IL-10 and IL-6 levels, an Interleukine Score for intra-Ocular Lymphoma Diagnosis (ISOLD) designed for aqueous humor (AH) and vitreous was published to guide the diagnosis of IOL (Costopoulos et al, Ophtalmology, 2016). The aim of this work was to evaluate ISOLD performances in real-life practice after five-year of use in a hospital laboratory. Material and methods IL-10 and IL-6 were measured in intra-ocular sample in a single laboratory using the cytometric bead array® kit (BD Biosciences TM) on a FACS Canto II cytometer, with a limit of quantification of 2.5 pg/ml. ISOLD is calculated at diagnosis in AH (AH-ISOLD) or vitreous (V-ISOLD) samples and is associated with a probability of having a large B-cell IOL. This score classifies patients according to two groups: i) reliable zone: ISOLD < -4.6 (<1% probability to have IOL) and ISOLD > +4.6 (>99% probability to have IOL) ; ii) doubtful zone: ISOLD ranging from -4.6 to +4.6 for which the probability and the clinical context have to be considered. All calculated ISOLD from January 2017 to December 2021 were collected. Centers with more than 30 intraocular samples with a calculated ISOLD were contacted to retrieve patients' definitive diagnosis and potential treatments. Results During these 5 years, IL-10 and IL-6 levels have been quantified for 2796 intraocular samples from 70 centers. ISOLD was calculated at diagnosis for 2013 ocular samples. Clinical data were obtained for 1449 samples (1220 AH and 229 vitreous) corresponding to 1243 patients from 13 out of the 18 centers contacted. 9.7% of patients had an IOL, 82.2% had another diagnosis than IOL and 8.1% of patients had no established diagnosis (Figure 1). Considering the 1341 samples with an established diagnosis, 92.7% were in the reliable zone and 7.3% were in the doubtful zone. For the 1128 AH samples, 1050 AH-ISOLD (93.1%) were in the reliable interpretation zone, with a concordant result for 98.6% of them (n=1035 samples) and a discordant result for 1.4% of them (n=15) (Table 1). The sensitivity and specificity were respectively estimated at 90.6% and 99.3% with a positive predictive value (PPV) of 91.7% and a negative predictive value (NPV) of 99.2%. Seventy-eight AH-ISOLD were in doubtful zone including 23 LIO and 55 others diagnoses than IOL. For the 213 vitreous samples, 193 V-ISOLD (90.6%) were in the reliable interpretation zone, with a concordant result for 98.4% of them (n=190 samples) and a discordant result for 1.6% of them (n=3) (Table 1). The sensitivity and specificity were estimated at 97.6% and 99.1%, respectively with a PPV of 98.8% and a NPV of 98.2%. Twenty V-ISOLD were in doubtful zone including 5 LIO and 15 others diagnoses than IOL. Three patients of the 8 who had a false-negative AH-ISOLD had a positive V-ISOLD. For the 17 AH-ISOLD in the doubtful zone, 4 of them had a V-ISOLD concordant with the diagnosis and 2 had an AH-ISOLD in the other eye concordant with the diagnosis. Independently of the sample type, the main cause of false-negative results was administration of corticosteroids prior to sampling and the main causes of false-positive results were infectious diseases (varicella and herpes virus, toxoplasmosis, syphilis). Conclusion This study confirmed on a 5-year period of real life practice that ISOLD, based on IL-10 and IL-6 levels, is a powerful tool to guide the diagnosis towards IOL. In more than 90% of intra-ocular samples, ISOLD was in reliable interpretation zone with very high sensitivity and specificity levels. In case of positive or doubtful AH-ISOLD, a vitrectomy is needed to make the diagnosis. Easy to use, not expansive, this score appears very useful to optimize the diagnostic approach of this rare and aggressive large B-cell lymphoma.

SAT185 Parathyroid Adenoma Localized By Cytogenetic Testing

Abstract Disclosure: S. Khadija: None. A. Rao: None. Introduction: Primary hyperparathyroidism can be caused by a parathyroid adenoma, hyperplasia or rarely by parathyroid carcinoma. Most patients have few or no symptoms. Diagnosis of primary hyperparathyroidism can be challenging in the setting of secondary/tertiary hyperparathyroidism. Correct diagnosis can be reached by clinical evaluation, biochemical and radiological tests. We describe a case that was diagnosed by cytogenetic testing of the biopsy specimen. Case Report: We report a case of a 64-year-old man. He was referred to the endocrine clinic for an incidental thyroid nodule on CT scan. He had hypothyroidism after I-131 treatment for Graves’ disease 15 years back. He had a long history of hypertension with renal failure. He had a renal transplant in 2017 and had hypercalcemia intermittently with elevated PTH since 2012. Ultrasound of thyroid reported a 1.6 x 1.7 x 2.0 cm nodule in the left thyroid lobe. He denied any compressive symptoms and was euthyroid on levothyroxine. An ultrasound guided FNA of the left thyroid nodule was reported as Bethesda III FLUS and sent to Veracyte for Affirma, which indicated a parathyroid adenoma. A sestamibi scan indicated a left lower parathyroid adenoma. He had surgery and intraoperative parathyroid hormone (PTH) dropped from 122pg/ml to 35.8pg/ml(29.1-79.7 pg/ml). Pathology confirmed parathyroid adenoma 3.8 grams in weight. Postoperatively calcium normalized with drop in PTH to 36.1pg/ml. After 2 weeks his calcium remained normal. Discussion: Parathyroid adenoma is a relatively rare condition and causes a majority of cases of primary hyperparathyroidism. A few cases are due to hyperplasia, more common in secondary hyperparathyroidism due to renal disease. Parathyroid adenoma is difficult to diagnose in patients with underlying hyperplasia due to chronic renal disease. Sonography and 99mTc preoperative sestamibi (MIBI) scan are the primary imaging modalities utilized for the visualization of diseased glands. MIBI scan is approximately 90% sensitive for localizing a parathyroid adenoma. Ultrasonography is the first-line imaging modality and parathyroid adenomas are nearly always homogeneously hypoechoic to the overlying thyroid gland and are commonly detected using gray-scale imaging alone when they are larger than 1 cm in diameter. Nodular goiter or enlarged lymph nodes are causes of false-positive results. Biopsy is very rarely used to diagnose a parathyroid adenoma with cytogenetic testing. Conclusion: Parathyroidectomy is the main stay in management of primary hyperparathyroidism due to parathyroid adenoma. Cervical sonography and sestamibi imaging are used for prediction of adenoma location. Both are limited by increased thyroid volume. Biopsy with cytogenetic testing can help in diagnosis in difficult patients. Presentation: Saturday, June 17, 2023

A-315 Pregnant Women Showed Lower Incidence Rates of False-positive Treponemal Antibody Screening Results When Compared with Nonpregnant Women and Men at an Appalachian Academic Medical Center

Abstract Background Screening for syphilis infection is recommended for all pregnant women and any adult or adolescent with increased risk for infection. Many clinical labs have adopted the reverse syphilis serology testing algorithm, that employs an automated and high-throughput treponemal antibody test as the initial screen followed by a non-treponemal antibody test to confirm all reactive samples. For specimens with discordant results, a second treponemal antibody test is used as the adjudicator. Syphilis serological tests can have false-positive results, causing discordant results between screening test and confirmatory test and complicating result interpretation. It is controversial from the literature whether pregnancy is a cause of false-positive results. This study is to determine the incidence rate of false-positive treponemal screening results among pregnant and nonpregnant patients, and to assess whether false-positivity is associated with pregnancy and age. Methods This is a retrospective study of sequential results from two treponemal antibody screening tests, including BioPlex 2200 Syphilis Total immunoassay between May 2020 and Jan 2022, and Alinity i Syphilis TP assay between Feb 2022 and Nov 2022. For each screening test, the incidence rates of false-positive results were calculated based on the reverse algorithm criteria and compared among pregnant women, nonpregnant women and men. The age differences between patients with false-positive results and patients with nonreactive results were also evaluated. Results Overall, 0.32% of 9 575 samples tested by Alinity assay showed false-positive results not confirmed by RPR or TP-PA. This is significantly lower (P < 0.01) than 0.60% of 14 983 samples observed for BioPlex assay. However, the lower incidence rate of false-positive results for Alinity assay relative to the Bioplex assay is only observed in pregnant women (0.18% vs 0.44%, P < 0.01) and nonpregnant women (0.32% vs 0.71%, P = 0.06), but not in men (0.68% vs 0.63%, P = 0.81). For both assays, male patients with false-positive results had an older median age than those with nonreactive results, and female patients showed the opposite trend, although statistical significance was only observed in nonpregnant women for Bioplex assay (median [IQR], 25 [19–35] vs 30 [22–43], P = 0.047). For both assays, pregnant women had lower incidence rates of false-positive results than nonpregnant women, although the differences did not reach statistical significance without age adjustment (Bioplex assay: 0.44% vs 0.71%, P = 0.07; Alinity assay: 0.18% vs 0.32%, P = 0.26). When age is adjusted, binary logistic regression analysis showed that pregnant women had significantly lower incidence rates of false-positive results relative to nonpregnant women for both assays (BioPlex assay: P = 0.049; Alinity assay: P < 0.01). Conclusion Although the incidence rates of false-positive results in BioPlex and Alinity treponemal antibody screening tests were overall within a low range, a significantly lower rate was observed for Alinity assay in pregnant women but not in men. For both assays, pregnant women showed a significantly lower incidence rate of false-positive results in comparison with nonpregnant women after age adjustment.

Causes of False-Positive Results in 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT Imaging

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.

Evaluation of the NG-Test CARBA 5 Lateral Flow Assay with an IMP-27-Producing Morganella morganii and Other Morganellaceae.

An isolate of Morganella morganii (MMOR1) that tested susceptible to 3rd/4th-generation cephalosporins and intermediate to meropenem was characterized as positive for NDM and IMP carbapenemases by NG-Test CARBA 5. Our objective was to further investigate this result, given the inconsistent susceptibility profile and unusual epidemiological profile for our region. The MMOR1 isolate was retested for antimicrobial susceptibilities and characterized for carbapenemase production. MMOR1 tested susceptible to ceftazidime, ceftriaxone, cefepime, aztreonam, and ertapenem, and intermediate to meropenem and imipenem. The isolate tested positive by carbapenem inactivation method (CIM) and CIM+EDTA (eCIM) testing, indicating metallo-β-lactamase production. The isolate tested negative for all carbapenemase genes on Xpert Carba-R, but positive for IMP on repeat testing of NG-Test CARBA 5. Whole-genome sequencing revealed MMOR1 contained blaIMP-27, but no other carbapenemase genes. Additional testing with NG-Test CARBA 5 revealed a false-positive NDM band when the assay was overloaded with test inoculum. Supplementary isolates were tested with an overloaded inoculum (n = 6 M. morganii; n = 1 P. mirabilis; n = 1 IMP-27-producing P. rettgeri; n = 1 IMP-1-producing E. coli; n = 1 K. pneumoniae), and two non-carbapenemase-producing carbapenem non-susceptible M. morganii also generated a false-positive NDM band; though, this was not universal among this species. A dual IMP+/NDM+ M. morganii is an unusual result that should prompt additional investigation, especially in nonendemic regions and when the susceptibility profile is incompatible. IMP-27 is not detected by Xpert Carba-R but is variably detected by NG-Test CARBA 5. The microorganism inoculum used for NG-Test CARBA 5 must be carefully controlled for accurate results. IMPORTANCE The detection of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) is an important function of the clinical microbiology laboratory, where positive identifications have immediate implications for infection control and surveillance strategies in the inpatient setting and can inform appropriate selection of therapy among the various novel anti-CP-CRE agents. NG-Test CARBA 5 is a relatively new lateral flow assay used for detection of carbapenemases in CP-CRE. Here, we describe the characterization of a Morganella morganii isolate that generated a false-positive NDM carbapenemase detection by this assay, and perform bacterial test inoculum experiments with additional isolates to further investigate a cause of false-positive results using the NG-Test CARBA 5. While a lateral flow assay like the NG-Test CARBA 5 is a very desirable test format for clinical laboratories, there are pitfalls to avoid when performing this test and interpreting results, including recognizing an overloaded test assay, which could lead to false-positive results.

Maternal opioid addiction: A potential cause of elevated 17-OH progesterone in neonatal screening

BackgroundCongenital adrenal hyperplasia (CAH) is a disease that is part of neonatal screening. There are many causes of false-positive results on neonatal screening, and maternal opioid consumption during pregnancy is suspected to increase 17-hydroxyprogesterone (17-OHP) levels at birth. The aim of this study was to determine the effect of maternal drug consumption on 17-OHP values on neonatal screening. Material and methodsWe studied 17-OHP levels of term newborns with reported maternal drug consumption born at the Maternity Hospital of Nancy between 2002 and 2018. These infants were matched with newborns of mothers without drug addiction. The 17-OHP levels, withdrawal syndromes, birth parameters, and maternal characteristics were compared between the two groups. ResultsThe study included 241 patients (121 in the drug-exposed group, 120 in the control group). The mean 17-OHP levels in newborns of mothers with substance addiction were 9.83 nmol/L compared to 4.90 nmol/L (p=0.0001) in the control group. Newborns exposed to drugs were smaller (p=0.0001), lighter (p=0.0001), had smaller head circumference (p=0.0001), and had lower Apgar scores (p=0.004 at 1 min and p=0.0001 at 5 min). The 17-OHP level did not differ in cases of withdrawal syndrome in drug-exposed newborn (p=0.911). ConclusionA significant increase in 17-OHP levels was observed in newborns exposed to drugs, with no influence of withdrawal syndrome on 17-OHP levels. Maternal substance addiction may be associated with moderately increased 17-OHP levels during neonatal screening.

New insights into SARS-CoV-2 Lumipulse G salivary antigen testing: accuracy, safety and short TAT enhance surveillance.

The rapid, accurate and safe detection of SARS-CoV-2 is the key to improving surveillance and infection containment. The aim of the present study was to ascertain whether, after heat/chemical inactivation, SARS-CoV-2N antigen chemiluminescence (CLEIA) assay insaliva remains a valid alternative to molecular testing. In 2022, 139 COVID-19 inpatients and 467 healthcare workers were enrolled. In 606 self-collected saliva samples (Salivette), SARS-CoV-2 was detected by molecular (TaqPath rRT-PCR) and chemiluminescent Ag assays (Lumipulse G). The effect of sample pre-treatment (extraction solution-ES or heating) on antigen recovery was verified. Salivary SARS-CoV-2 antigen assay was highly accurate (AUC=0.959, 95% CI: 0.943-0.974), with 90% sensitivity and 92% specificity. Of the 254 antigen positive samples, 29 were false positives. We demonstrated that heterophilic antibodies could be a cause of false positive results. A significant antigen concentration decrease was observed after ES treatment (p=0.0026), with misclassification of 43 samples. Heat had a minimal impact, after treatment the correct classification of cases was maintained. CLEIA SARS-CoV-2 salivary antigen provides accurate, timely and high-throughput results that remain accurate also after heat inactivation, thus ensuring a safer work environment. This supports the use of salivary antigen detection by CLEIA in surveillance programs.

Clinical Significance of Clonal Hematopoiesis of Indeterminate Potential in Hematology and Cardiovascular Disease.

Liquid profiling uses circulating tumor DNA (ctDNA) for minimal invasive tumor mutational profiling from peripheral blood. The presence of somatic mutations in peripheral blood cells without further evidence of a hematologic neoplasm defines clonal hematopoiesis of indeterminate potential (CHIP). CHIP-mutations can be found in the cell-free DNA (cfDNA) of plasma, are a potential cause of false positive results in liquid profiling, and thus limit its usage in screening settings. Various strategies are in place to mitigate the effect of CHIP on the performance of ctDNA assays, but the detection of CHIP also represents a clinically significant incidental finding. The sequelae of CHIP comprise the risk of progression to a hematologic neoplasm including therapy-related myeloid neoplasms. While the hematological risk increases with the co-occurrence of unexplained blood count abnormalities, a number of non-hematologic diseases have independently been associated with CHIP. In particular, CHIP represents a major risk factor for cardiovascular disease such as atherosclerosis or heart failure. The management of CHIP requires an interdisciplinary setting and represents a new topic in the field of cardio-oncology. In the future, the information on CHIP may be taken into account for personalized therapy of cancer patients.

Republication de : Allergie à l’arachide en Afrique sub-saharienne

Peanut was imported from South America into West Africa first during the XVIth century, but its culture and its use as a source of oil and proteins expanded in Africa only in the mid-XIXth century. In rural areas of sub-Saharan Africa, the extent of peanut sensitisation and clinical allergy is very low compared to populations living in Europe and the U.S.A. This could be due to the protective effect of anti-CCD IgE and IgG, which can cross-react between peanut and parasites’ carbohydrate epitopes. These anti-CCD IgE are cause of false positive results for anti-peanut IgE tests, when whole peanut extracts are used in place of non-glycosylated molecular allergens. Several studies in southern Africa have used oral food challenges and show that the low incidence of peanut allergy is limited to rural areas and do not exist among African urban populations. No influence of ethnicity was found. This suggests that environmental factors related to urban living are crucial for the incidence of peanut allergy and probably also for food allergies in general.

Kedi tırmığı hastalığında F18 FDG PET/BT bulguları: olgu sunumu

Cat-scratch disease is a bacterial infection caused by Bartonella Henselae which affects lymph nodes that drain the sites of inoculation. Axillary, cervical and inguinal lymph nodes are the most common regions being involved. The disease can be considered as an FDG-avid disease, given the granulomatous nature of the infection. We herein report F18 FDG PET/CT findings of a 49-year-old woman, who has abdominal lymphadenopathy revealed on ultrasonography (USG). PET/CT scan demonstrated bilateral axillary and abdominopelvic hypermetabolic enlarged lymph nodes with SUVmax value of 6.2 to 18.5. Moreover, a hypermetabolic hypodense lesion in the spleen with SUVmax value of 11.3 was detected. Excisional biopsy of the axillary lymph node performed. Based on clinical-histopathological findings and the history of being scratched by a cat recently, the patient was diagnosed with cat-scratch disease. In conclusion, cat-scratch disease represents a cause of false-positive results in oncological PET/CT scans. Furthermore, PET/CT may have a role in revealing the applicable biopsy area and showing the additional involvement sites. Keywords: Cat-Scratch Disease, PET-CT, Lymphadenopathy.

SARS-CoV-2 detection by reverse transcriptase polymerase chain reaction testing: Analysis of false positive results and recommendations for quality control measures

Testing for SARS-CoV-2 has become a critical component for the management of the COVID-19 pandemic. Reverse transcriptase polymerase chain reaction (RT-PCR) assays are currently the predominate method for testing. Quality control (QC) measures utilize known positive and known negative controls to ensure the adequacy of extraction and RT-PCR steps but do not evaluate all components of testing. We have conducted a quality assurance review of our RT-PCR testing for COVID-19 to determine the rate of false positive results in asymptomatic patients and causes for these errors. DesignWe have developed a quality control procedure in which all specimens from asymptomatic unexposed persons with SARS-CoV-2 positive tests were retested. When a second test was “non-detected” a third test was performed and a root cause analysis of the erroneous result undertaken. ResultsIn the study period, 24,717 samples were tested and 6251 were from asymptomatic patients. Of the 288 initial positive tests, 20 (6.9%) were negative on retesting. Review of cycle threshold curves, technologists’ records, location of specimen on testing plates and relationships with high viral load specimens was undertaken. Analysis revealed technologists’ errors (misplacement of specimen in testing plate or contamination) and cross contamination from high viral load specimens in adjacent wells of testing plates were common causes for false positive results. DiscussionSARS-CoV-2 RT-PCR testing is associated with a small number of false positive results, most easily recognized in asymptomatic non-exposed patients. Implementation of a limited retesting protocol identifies clinically significant testing errors and allows review and improvement of laboratory procedures.

Effects of 105 traditional Chinese medicines on the detection of β-agonists in medicine extracts and swine urine based on colloidal gold immunochromatographic assay

Colloidal gold immunochromatographic assay (CGIA) is commonly used for the on-site detection of β-agonists that are sometimes used illegally as feed additives in swine diets. However, few studies have evaluated the causes of false-positive results that sometimes occur when applying CGIA in agricultural settings. In this study, we investigated if this false-positive phenomenon is related to the addition of certain traditional Chinese medicines (TCMs) to swine feed. We established and verified an extraction method for TCMs, and then applied CGIA to detect β-agonists in the extracts of 105 TCMs and in the urine of swine dosed with TCMs, respectively. Liquid chromatography-tandem mass spectrometry was used to validate the results of the urine samples tested positive for β-agonists using CGIA. The results were also verified using TCMs and colloidal gold test strips produced by different manufacturers. The extracts of Citri Reticulatae Pericarpium Viride, Citri Reticulatae Pericarpium, Magnoliae Officinalis Cortex, Chaenomelis Fructus, and Rhodiolae Crenulatae Radix Et Rhizoma were tested positive for β-agonists. Meanwhile, the addition of Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium to swine feed resulted in false-positive results for β-agonists in swine urine. The results provide a new way to explain false-positive CGIA results and provide valuable information for livestock feeding programs.

Evaluation of monomeric prolactin level by TRACE method and precipitation with polyethylene glycol

Prolactin exists in various forms including the monomeric biologically active form (23kDa) and a higher molecular weight form, bound most commonly to IgG, known as macroprolactin (>100kDa). Macroprolactin lacks biological activity and is one of the causes of false-positive results. In Russian Federation the most common method for macroprolactin determination is PEG precipitation test. We had conducted a retrospective analysis of 37 samples of patients with hyperprolactinemia (3 of them were males). The mean age was 30 [25;35] years. Prolactin level was measured by the immunoenzyme method with manual PEG precipitation and TRACE. The mean values found by the immunoenzyme method with manual PEG precipitation were 461,6 [375,0;821,2] mU/l, by TRACE - 449,9 [357,2;749,2] mU/l. The number of patients with normal prolactin levels was 30% (11) confirmed by two methods, high prolactin level at 46% (17). The prevalence of clinical symptoms of hyperprolactinemia was not differ depend the groups. The phenomenon of macroprolactinemia was registered in 32% (12) of patients. In 8 persons of this group normal prolactin level was revealed and in 4 patients hyperprolactinemia was found by TRACE. Measurements of prolactin levels by the TRACE method is useful for correct diagnosis in patients with equivocal results received by traditional method with PEG precipitation.

Fully Automatic Coronary Calcium Score Software Empowered by Artificial Intelligence Technology: Validation Study Using Three CT Cohorts.

ObjectiveThis study aimed to validate a deep learning-based fully automatic calcium scoring (coronary artery calcium [CAC]_auto) system using previously published cardiac computed tomography (CT) cohort data with the manually segmented coronary calcium scoring (CAC_hand) system as the reference standard.Materials and MethodsWe developed the CAC_auto system using 100 co-registered, non-enhanced and contrast-enhanced CT scans. For the validation of the CAC_auto system, three previously published CT cohorts (n = 2985) were chosen to represent different clinical scenarios (i.e., 2647 asymptomatic, 220 symptomatic, 118 valve disease) and four CT models. The performance of the CAC_auto system in detecting coronary calcium was determined. The reliability of the system in measuring the Agatston score as compared with CAC_hand was also evaluated per vessel and per patient using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. The agreement between CAC_auto and CAC_hand based on the cardiovascular risk stratification categories (Agatston score: 0, 1–10, 11–100, 101–400, > 400) was evaluated.ResultsIn 2985 patients, 6218 coronary calcium lesions were identified using CAC_hand. The per-lesion sensitivity and false-positive rate of the CAC_auto system in detecting coronary calcium were 93.3% (5800 of 6218) and 0.11 false-positive lesions per patient, respectively. The CAC_auto system, in measuring the Agatston score, yielded ICCs of 0.99 for all the vessels (left main 0.91, left anterior descending 0.99, left circumflex 0.96, right coronary 0.99). The limits of agreement between CAC_auto and CAC_hand were 1.6 ± 52.2. The linearly weighted kappa value for the Agatston score categorization was 0.94. The main causes of false-positive results were image noise (29.1%, 97/333 lesions), aortic wall calcification (25.5%, 85/333 lesions), and pericardial calcification (24.3%, 81/333 lesions).ConclusionThe atlas-based CAC_auto empowered by deep learning provided accurate calcium score measurement as compared with manual method and risk category classification, which could potentially streamline CAC imaging workflows.

Performance of nucleocapsid and spike-based SARS-CoV-2 serologic assays.

There is an urgent need for an accurate antibody test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have developed 3 ELISA methods, trimer spike IgA, trimer spike IgG, and nucleocapsid IgG, for detecting anti-SARS-CoV-2 antibodies. We evaluated their performance along with four commercial ELISAs, EDI™ Novel Coronavirus COVID-19 ELISA IgG and IgM, Euroimmun Anti-SARS-CoV-2 ELISA IgG and IgA, and one lateral flow assay, DPP® COVID-19 IgM/IgG System (Chembio). Both sensitivity and specificity were evaluated and the probable causes of false-positive reactions were determined. The assays were evaluated using 300 pre-epidemic samples and 100 PCR-confirmed COVID-19 samples. The sensitivities and specificities of the assays were as follows: 90%/100% (in-house trimer spike IgA), 90%/99.3% (in-house trimer spike IgG), 89%/98.3% (in-house nucleocapsid IgG), 73.7%/100% (EDI nucleocapsid IgM), 84.5%/95.1% (EDI nucleocapsid IgG), 95%/93.7% (Euroimmun S1 IgA), 82.8%/99.7% (Euroimmun S1 IgG), 82.0%/91.7% (Chembio nucleocapsid IgM), 92%/93.3% (Chembio nucleocapsid IgG). The presumed causes of false positive results from pre-epidemic samples in commercial and in-house assays were mixed. In some cases, assays lacked reproducibility. In other cases, reactivity was abrogated by competitive inhibition (spiking the sample with the same antigen that was used for coating ELISAs prior to performing the assay), suggesting positive reaction could be attributed to the presence of antibodies against these antigens. In other cases, reactivity was consistently detected but not abrogated by the spiking, suggesting positive reaction was not attributed to the presence of antibodies against these antigens. Overall, there was wide variability in assay performance using our samples, with in-house tests exhibiting the highest combined sensitivity and specificity. The causes of “false positivity” in pre-epidemic samples may be due to plasma antibodies apparently reacting with the corresponding antigen, or spurious reactivity may be directed against non-specific components in the assay system. Identification of these targets will be essential to improving assay performance.

Deep learning for automated glaucomatous optic neuropathy detection from ultra-widefield fundus images

Background/AimsTo develop a deep learning system for automated glaucomatous optic neuropathy (GON) detection using ultra-widefield fundus (UWF) images.MethodsWe trained, validated and externally evaluated a deep learning system for GON detection...

Looking for Metastasis in Early Breast Cancer: Does Bone Scan Help? A Retrospective Review

BackgroundRoutine staging investigations are not recommended for early breast cancer (EBC). Staging scans and further confirmatory tests add to the cost of breast cancer treatment. Despite recommendations from international guidelines, whole body bone scan (BS) is commonly used for staging EBC. We examined our experience with BS as a staging investigation when selectively used in EBC. Patients and MethodsAll EBC patients who underwent treatment through the Eastern Health breast unit during a 50-month period from January 2012 were included in this study. All staging BS results were reviewed to evaluate yield and false-positive rate. The causes of false-positive results were analyzed. The role of BS when performed along with computed tomographic scans of chest, abdomen, and pelvis (CTCAP) was evaluated. ResultsEven with the selective use of BS, we could only achieve a yield of 1% (95% confidence interval, −0.6, 2.7) in EBC. When combined with CTCAP, only one additional metastasis was detected in 194 BSs. ConclusionBS plays only a limited role in staging EBC. Patients who have undergone CTCAP will experience minimal benefit by undergoing additional BS.