The Utility and Limitations of Universal Polymerase Chain Reaction Screening for SARS-CoV-2 During Hospital Admission.

OBJECTIVE: Universal polymerase chain reaction (PCR) screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admission is an effective approach to preventing coronavirus disease 2019 (COVID-19) outbreaks in medical facilities. However, false-positive test results due to a recent infection are a concern. We investigated the usefulness and limitations of universal PCR screening for SARS-CoV-2 on hospital admission in a real-world setting. METHODS: We retrospectively analyzed 1320 attempted hospital admissions for 775 patients at the Department of Respiratory Medicine, Kyushu University Hospital, between January 1, 2022, and May 2, 2023. RESULTS: Thirty-nine out of 1201 PCR tests (3.2%) yielded a positive result, with 22 of these results being considered false positives on the basis of a recent infection. We found that 39% of cases showed a positive PCR result between 31 and 60 days after the onset of COVID-19, although the threshold cycle (Ct) for target 1 (ORF1ab gene) of the Cobas SARS-CoV-2 test (Roche Diagnostics, Basel, Switzerland) was >30 in most instances. CONCLUSION: Hospital admission based on the results of PCR screening for SARS-CoV-2 should take into account not only PCR positivity but also the Ct value and recent COVID-19 history.

Characterization of the alcohol biomarker phosphatidylethanol in donor whole blood and apheresis red blood cells: Implications for transfusion recipients.

INTRODUCTION: Phosphatidylethanol (PEth) is a long-term marker of alcohol consumption used frequently in clinical scenarios such as liver transplant evaluation. Recent cases have demonstrated that packed red blood cell (pRBC) transfusion creates the potential for artificial elevation or decrease of observed PEth concentrations in recipients. Very little is known about the prevalence or stability of PEth in pRBCs. METHODS: Apheresis and whole-blood (WB) donations were tested for PEth using liquid chromatography - tandem mass spectrometry with limit of quantitation 10 ng/mL. Units were stored under routine blood bank conditions to evaluate the stability of PEth and the impact of irradiation. RESULTS: Over 40% of apheresis and WB donors had PEth ≥10 ng/mL (maximum observed 587 ng/mL). As WB units were processed into component pRBCs, PEth concentrations increased and were higher than donor WB levels (EDTA sample) prior to collection (maximum observed 711 ng/mL). Storage for up to 5 weeks post donation resulted in mean 17.3% decrease in PEth-positive units; in contrast to a prior report, we observed no PEth formation in units with negative (<10 ng/mL) baseline concentrations. Irradiation of pRBCs did not substantially affect PEth concentrations in either PEth-positive or PEth-negative units. DISCUSSION: PEth concentrations in healthy blood donors may potentially confound alcohol use or abstinence assessment in pRBC recipients. Transfusion medicine services and clinical practices such as transplantation and behavioral medicine should recognize this phenomenon and collaborate on testing protocols to appropriately interpret PEth in pRBC recipients.

False-Positive Iodine-131 Uptake Due to Wasp Sting.

A 38-year-old woman with papillary carcinoma of the thyroid who underwent total thyroidectomy followed by high-dose radioiodine ablation was called for Iodine-131 (I-131) whole-body follow-up scan. Her follow-up scan revealed focal tracer accumulation in the lower aspect of the right posterior neck region. Her stimulated serum thyroglobulin and anti-thyroglobulin antibodies were 0.27 ng/ml and undetectable, respectively. Further clinical examination of the patient revealed a black scab in the same region. The patient revealed a history of wasp bite 2 days before iodine administration.

Kaiser score diagnosis of breast MRI lesions: Factors associated with false-negative and false-positive results.

PURPOSE: We sought factors associated with false-negative and false-positive results in the diagnosis of breast lesions using the Kaiser score (KS) on breast magnetic resonance imaging (MRI). METHODS: We retrospectively analyzed 1058 patients with 1058 breast lesions who underwent preoperative breast MRI with successful histopathologic results. Two radiologists assessed each lesion according to KS criteria, and clinicopathologic features and MRI findings were analyzed. Multivariate regression analysis was conducted to identify factors associated with false-negative and false-positive KS results. RESULTS: Of the 1058 lesions, 859 were malignant and 199 were benign. Particularly high misdiagnosis rates were observed for intraductal papilloma, inflammatory lesion, and mucinous carcinoma. For breast cancer, KS yielded 821 (95.6 %) true-positive and 38 (4.4 %) false-negative results. Multivariate analysis showed that smaller lesion size (≤1 cm) (OR, 3.698; 95 %CI, 1.430-9.567; p = 0.007), absence of ipsilateral breast hypervascularity (OR, 3.029; 95 %CI, 1.370-6.693; p = 0.006), and presence of hyperintensity on T2WI (OR, 2.405; 95 %CI, 1.121-5.162; p = 0.024) were significantly associated with false-negative breast cancer results. For benign lesions, KS yielded 141 (70.9 %) true-negative and 58 (29.1 %) false-positive results. Multivariate regression analysis revealed that non-mass enhancement lesions (OR, 4.660; 95 %CI, 2.018-10.762; p＜0.001), moderate/high background parenchymal enhancement (OR, 2.402; 95 %CI, 1.180-4.892; p = 0.016), and the presence of hyperintensity on T2WI (OR, 2.986; 95 %CI, 1.386-6.433; p = 0.005) were significantly associated with false-positive KS results. CONCLUSION: Several clinicopathologic and MRI features influence the accuracy of KS diagnosis. Understanding these factors may facilitate appropriate use of KS and guide alternative diagnostic approaches, ultimately improving diagnostic accuracy in the evaluation of breast lesions.

[Development of a PCR Method to Detect a Mysid Species Causing False Positives in Tests for Crustacean Allergens].

Mysids are small crustaceans that are closely related to shrimp/prawns and crabs but not subject to food allergen labeling requirements for raw materials. In the past, a processed food that contained Japanese smelt (wakasagi) was suspected of producing a false-positive result in shrimp/prawn and crab allergen test because of the presence of consumed mysids. However, there was no reported methods to confirm mysid presence. Therefore, we developed a PCR method to detect mysids. The developed PCR method had high specificity for a mysid species, with no amplification observed from samples of shrimp, crab, krill, mantis shrimp, or the meat of Japanese smelt. In addition, DNA extracted from the internal organs of Japanese smelt was amplified by this PCR method, and sequencing revealed mysid DNA. This confirmed that mysids remained in the internal organs of Japanese smelt following consumption. This PCR method for mysid detection even amplified Japanese smelt-containing processed food samples that were suspected to have produced a false-positive result in shrimp/prawn and crab ELISA. Thus, this PCR method would enable to detect such false positives are caused by mysid contamination.

Assessing the Correlation between Allostatic Load and False-Positive Image-Guided Breast Biopsies.

Background: Allostatic load (AL) is the accumulation of physiological dysregulation attributed to repeated activation of the stress response over a lifetime. We assessed the utility of AL as a prognostic measure for high-risk benign breast biopsy pathology results. Method: Eligible patients were women 18 years or older, with a false-positive outpatient breast biopsy between January and December 2022 at a tertiary academic health center. AL was calculated using 12 variables representing four physiological systems: cardiovascular (pulse rate, systolic and diastolic blood pressures, total cholesterol, high-density lipoprotein, and low-density lipoprotein); metabolic (body mass index, albumin, and hemoglobin A1C); renal (creatinine and estimated glomerular filtration rate); and immune (white blood cell count). Multivariable logistic regression was used to assess the association between AL before biopsy and breast biopsy outcomes controlling for patients' sociodemographics. Results: In total, 170 women were included (mean age, 54.1 ± 12.9 years): 89.4% had benign and 10.6% had high-risk pathologies (radial scar/complex sclerosing lesion, atypical ductal or lobular hyperplasia, flat epithelial atypia, intraductal papilloma, or lobular carcinoma in-situ). A total of 56.5% were White, 24.7% Asian, and 17.1% other races. A total of 32.5% identified as Hispanic. The mean breast cancer risk score using the Tyrer-Cuzick model was 11.9 ± 7.0. In multivariable analysis, with every one unit increase in AL, the probability of high-risk pathology increased by 37% (odds ratio, 1.37; 95% confidence interval, 1.03, 1.81; p = 0.03). No significant association was seen between high-risk pathology and age, ethnicity, breast cancer risk, or area deprivation index. Conclusion: Our findings support that increased AL, a biological marker of stress, is associated with high-risk pathology among patients with false-positive breast biopsy results.

[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.

Diagnostic Challenge for Positive 1,3-ß-D-Glucan in an Immunocompromised Patient Receiving Intravenous Immunoglobulin Presenting With Respiratory Failure.

Diagnosing Pneumocystis jirovecii pneumonia (PJP) can be complex, particularly in cases of significant respiratory failure. The 1,3-ß-D-glucan (BDG) serum assay has emerged as a promising non-invasive diagnostic tool for detecting fungal infections, including PJP. However, factors that can confound the interpretation of BDG levels by causing elevation in serum levels have been documented. Here, we present the case of 51-year-old woman with underlying autoimmune disorder, hematologic malignancy, and chronic steroid use, who was admitted for acute hypoxemic respiratory failure. Obtaining the BDG assay after the administration of intravenous immunoglobulin (IVIG) posed a diagnostic challenge, as the patient was unable to undergo bronchoscopy. This circumstance led to a debate regarding the possibility of a false-positive BDG due to IVIG use or the presence of PJP. Ultimately, the patient was empirically treated for PJP. This case underscores the importance of comprehending factors that may contaminate BDG results, particularly in immunocompromised individuals.

Machine learning model with output correction: Towards reliable bradycardia detection in neonates.

Bradycardia is a commonly occurring condition in premature infants, often causing serious consequences and cardiovascular complications. Reliable and accurate detection of bradycardia events is pivotal for timely intervention and effective treatment. Excessive false alarms pose a critical problem in bradycardia event detection, eroding trust in machine learning (ML)-based clinical decision support tools designed for such detection. This could result in disregarding the algorithm's accurate recommendations and disrupting workflows, potentially compromising the quality of patient care. This article introduces an ML-based approach incorporating an output correction element, designed to minimise false alarms. The approach has been applied to bradycardia detection in preterm infants. We applied five ML-based autoencoder techniques, using recurrent neural network (RNN), long-short-term memory (LSTM), gated recurrent unit (GRU), 1D convolutional neural network (1D CNN), and a combination of 1D CNN and LSTM. The analysis is performed on ∼440 hours of real-time preterm infant data. The proposed approach achieved 0.978, 0.73, 0.992, 0.671 and 0.007 in AUC-ROC, AUC-PRC, recall, F1 score, and false positive rate (FPR) respectively and a false alarms reduction of 36% when compared with methods without the correction approach. This study underscores the imperative of cultivating solutions that alleviate alarm fatigue and encourage active engagement among healthcare professionals.

Dynamic changes in serum (1-3)-ß-D-glucan caused by intravenous immunoglobulin infusion: A prospective study.

PURPOSE: The purpose of this study was to investigate the dynamic changes in serum (1-3)-ß-D-glucan (BDG) caused by intravenous immunoglobulins (IVIG) infusion in adults. METHODS: This study included patients who received IVIG infusion from October 2021 to October 2022 during hospitalization. We randomly examined two IVIG samples for every patient. Serum samples were collected at nine time points: before (Tpre), immediately (T1-0), 6h (T1-1) and 12h (T1-2) later on the first day; immediately (T2-0) and six hours later (T2-1) on the second day during IVIG infusion, and within three days after IVIG infusion (Ta1, Ta2, and Ta3, respectively). The Friedman test was used for statistical analysis. RESULTS: A total of 159 serum BDG from 19 patients were included in the analysis. The BDG content of IVIG ranged from 249 pg/ml to 4812 pg/ml. Patients had significantly elevated serum BDG on T1-0 (176 (113, 291) pg/ml, p = 0.002) and Ta1 (310 (199, 470) pg/ml, p < 0.001), compared with Tpre (41 (38, 65) pg/ml). The increments of serum BDG (ΔBDG) were associated with BDG concentration of IVIG (Spearman r = 0.59, p = 0.02). Individuals with abnormal renal function indexes showed higher serum ΔBDG values at Ta1 (403 (207, 484) pg/ml) than patients with normal renal function (172 (85, 316) pg/ml, p = 0.036). CONCLUSION: Patients who received IVIG had significantly higher serum BDG values. Elevated BDG levels correlate with BDG content of IVIG and abnormal renal function indexes.

Pitfalls in the Diagnostic Evaluation of Pheochromocytomas.

Pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors arising from chromaffin cells, present a significant diagnostic challenge due to their clinical rarity and polymorphic symptomatology. The clinical cases demonstrate the importance of an integrated approach that combines clinical assessment, biochemical testing, and imaging to distinguish PPGLs from mimicking conditions, such as obstructive sleep apnea and interfering medication effects, which can lead to false-positive biochemical results. Although a rare condition, false-negative metanephrine levels can occur in pheochromocytomas, but imaging findings can give some clues and increase suspicion for a pheochromocytoma diagnosis. This expert endocrine consult underscores the critical role of evaluating preanalytical conditions and pretest probability in the biochemical diagnosis of PPGLs. Moreover, a careful differentiation of PPGLs from similar conditions and careful selection and interpretation of diagnostic tests, with focus on understanding and reducing false positives to enhance diagnostic accuracy and patient outcomes, is crucial.

Pitfalls of Iodine-131 Whole-Body Scan Mimicking Metastases in Differentiated Thyroid Carcinoma: A Case Series.

Thyroid cancer is the most common endocrine malignant tumor and accounts for 1% of all cancers. Management of differentiated thyroid carcinoma is total thyroidectomy, followed by iodine-131 (I-131) radioactive iodine (RAI) therapy for thyroid remnant tissue. I-131 whole-body scan helps in the follow-up evaluation in remnant, residual, and recurrence cases. Principle of uptake of I-131 is through sodium-iodide symporter expression on the cells. Physiological uptake of iodine is usually seen in salivary glands and gastrointestinal tract, and false-positive uptakes are seen in lesions such as mucinous cystadenoma, struma ovarii, hepatic, renal, thymic, and meibomian cysts. Here, we present the review of literature of series of cases observed in our department presenting with false-positive uptake of RAI in vertebral hemangioma, lipoma, sinusitis, teratoma, and uterine leiomyoma.

The Case of the Positive Pregnancy Pretender: A Potential Cause of Erroneous Test Results in Active-Duty Personnel.

The detection of pregnancy is common among those who participate in the care of reproductive-age females. This is especially true in the medical care of active-duty personnel in the armed forces. Considering the impact of a positive urine pregnancy test in this population, it is important to recognize the possibility of false-positive results and their causes. In this case, we explore a false-positive urine pregnancy test due to injectable positive beta-human chorionic gonadotropin (beta-hCG) supplementation used for weight loss. This report concludes that the use of exogenous beta-hCG by physicians and other clinicians should be avoided. Additionally, clinicians should be aware of its use in the community and its possible effect on laboratory testing used to evaluate for pregnancy.

Comparison of diagnostic performance between Oncomine Dx target test and AmoyDx panel for detecting actionable mutations in lung cancer.

Companion diagnostic (CDx) tests play important roles in identifying oncogenic driver genes and tailoring effective molecularly targeted therapies for lung cancer patients. In Japan, the Oncomine Dx target test (ODxTT) and the AmoyDx pan lung cancer PCR panel (AmoyDx) are prominent CDx tests and only one of these tests is covered by the domestic insurance system. However, these CDx tests cover different target regions and apply different technologies (ODxTT is amplicon-based next-generation sequencing and AmoyDx is multiplex PCR-based assay), which may lead to missing of actionable mutations affecting patient prognosis. Here, we performed a direct comparison analysis of 1059 genetic alterations of eight driver genes from 131 samples and evaluated the concordance between two CDx tests for detecting actionable variants and fusions. When excluding the eight uncovered variants (ODxTT: two variants, AmoyDx: six variants), the overall percent agreement was 97.6% (1026/1051) with 89.0% of overall positive percent agreement (89/100) and 98.5% of overall negative percent agreement (937/951). Of the 25 discordant genetic alterations, two were undetected despite being covered in the AmoyDx (one EGFR variant and one ROS1 fusion). Furthermore, there were potential false positives in the ODxTT (nine MET exon 14 skippings) and in the AmoyDx (five variants, six ROS1 and three RET fusions). These potential false positives in the AmoyDx likely due to non-specific amplification, which was validated by the unique molecular barcoding sequencing. The ODxTT missed two uncovered EGFR rare variants, which was visually confirmed in the raw sequencing data. Our study provides insights into real-world performance of CDx tests for lung cancer and ensures reliability to advance precision medicine.

The impact of confined placental mosaicism on prenatal cell-free DNA screening: Insights from a monocentric study of 99 cases.

INTRODUCTION: Confined placental mosaicism (CPM) is thought to be one of the main sources of false-positive prenatal cell-free DNA (cfDNA) screening results, but extensive and systematic studies to prove this statement are limited. We evaluate the contribution of CPM to false-positive prenatal cfDNA screening results in the largest cohort published to date. METHOD: We systematically offered postnatal analysis on placenta and umbilical cord to women who had a negative amniocentesis following a positive prenatal cfDNA screening result. A standardized protocol was used in which (when available) biopsies were taken at five locations in the placenta and umbilical cord. RESULTS: We analyzed a series of 99 placentas. CPM could be confirmed in 32.3 % of cases (32/99). CPM was detected across all subtypes of chromosomal aberrations (common and rare autosomal trisomies, sex chromosome abnormalities, copy number variations and autosomal monosomies). A lower detection rate was present in umbilical cord biopsies in comparison with placental biopsies. When comparing different sections of the placenta, no clear difference could be observed with regard to the probability of CPM being present nor to the grade of mosaicism. DISCUSSION: We confirm an important role for CPM in explaining false-positive prenatal cfDNA screening results. Placental regional differences are common. Given its limited clinical relevance, we do however not advocate placental studies in a diagnostic setting.

Melting curve analysis reveals false-positive norovirus detection in a molecular syndromic panel.

BACKGROUND: Molecular syndromic panels can improve rapidity of results and ease clinical laboratory workflow, although caution has been raised for potential false-positive results. Upon implementation of a new panel for infectious diarrhea (BioFire® FilmArray® Gastrointestinal [GI] Panel, bioMérieux) in our clinical laboratory, a higher than expected number of stool samples with norovirus were detected. OBJECTIVES: The goal of this study was to investigate positive percent agreement and the false-positive rate of norovirus detected by the multiplex BioFire GI panel compared to a singleplex commercial assay. STUDY DESIGN: From October 2023 to January 2024, all prospective stool samples with a positive norovirus result by BioFire had melting curves reviewed manually using the BioFire FilmArray Torch System. Stool samples further underwent testing by a supplementary real-time RT-PCR assay (Xpert® Norovirus, Cepheid) for comparative analysis. RESULTS: Of the 50 stool samples with norovirus detected by BioFire, 18 (36 %) tested negative by Xpert (deemed "false-positives"). Furthermore, melting curve analysis revealed nearly all of these samples had atypical melting curve morphologies for the "Noro-1" target on BioFire (16/18, 89 %), which was statistically significant (Odds Ratio 173.2, 95 % CI [22.2, 5326.9], p < 0.0001). Stool samples with multiple pathogens detected by BioFire including norovirus were not more likely to produce false-positive norovirus results (Odds Ratio 1, 95 % CI [0.3, 3.3], p = 1). CONCLUSIONS: Although not described in the manufacturer's Instructions for Use, we propose routine manual review of melting curves for the BioFire GI panel prior to reporting, to mitigate potential false-positive norovirus results.

Positive Reframing of Psychosis Risk Is Seen as More Beneficial and Less Harmful Than Negative Framing by Clinicians: An Experimental Videotaped Simulated Feedback Study.

BACKGROUND AND HYPOTHESIS: Recent studies show that, despite providing some relief, feedback about being at risk for psychosis often triggers negative emotional reactions. Inspired by Tversky and Kahneman's (1981) work on the framing effect and medical framings that favors positive framing like "life-threatening" over "high-risk for death," this study tested the hypothesis that positive reframing of psychosis risk (PR) could alleviate these concerns. To establish the justifiability and feasibility of testing this hypothesis with patients and their families, the study first sought to test whether mental health professionals (MHPs) view positive framing as superior to present state-of-the-art approaches. STUDY DESIGN: The study used an experimental design utilizing a simulated feedback session, recorded with professional actors, featuring a clinician, an adolescent, and his mother. One hundred forty-eight MHPs were randomly assigned to view either negatively or positively framed feedback and were asked about its induced impact on the adolescent and mother. STUDY RESULTS: The study results supported our main hypothesis, indicating significant benefits of positive framing over negative in areas like empathy, stress reduction, stigma, help-seeking, and hope. Contrary to our second hypothesis, familiarity with PR did not affect these results. CONCLUSIONS: These findings suggest that MHPs view positive reframing of PR as more beneficial and less harmful than present negative framing approaches. This sets the stage for subsequent phases that will assess the perceptions and preferences of individuals at risk and their families. The discussion highlights possible misconceptions of positive framing, such as labeling, positive psychology, and de-medicalization.

Case Report: Visceral Leishmaniasis Falsely Diagnosed as Viral Hepatitis C Without Febrile Symptoms.

Background: Visceral leishmaniasis (VL), also known as kala-azar, is caused by an intracellular parasite transmitted to humans by the bite of a sand fly, and with the source of the infection mainly being dogs. The main features of the disease are irregular fever, weight loss, hepatosplenomegaly and anaemia. Diagnosis relies mainly on bone marrow aspiration tests to find Leishman-Donovan(LD) bodies. And we report the case without febrile symptoms and hepatitis C virus antibody was probably false positive. Case Presentation: The case was a 74-year-old male residing in Yangquan City, Shanxi Province, a VL endemic area. He presented with generalised malaise, hepatosplenomegaly and scarring pigmentation on the skin as a result of scratching. Laboratory tests showed pancytopenia, positive hepatitis C virus antibody (HCV-Ab), positive direct anti-human globulin test (DAT), positive anti-cardiolipin antibody IgG, IgM (+), and increased immunoglobulin IgG. Symptomatic treatments such as hepatoprotection and blood transfusion were given, but the patient's symptoms still persisted and his spleen and liver further enlarged. Further repeat tests were performed and found to be negative for hepatitis C virus antibodies and antigens. The patient was eventually found to be infected with Leishmania protozoa by rk39 rapid diagnostic test and metagenomic next-generation sequencing(mNGS). And the patient quickly relieved after one course of treatment with sodium stibogluconate. Conclusion: Patients with VL may cause abnormalities in the immune system, leading to false positives for various antibodies without clear febrile symptoms, resulting in misdiagnosis or delayed diagnosis. It is important to consider VL in cases where there is a significant hepatosplenomegaly with a relevant epidemiological history. If the diagnosis cannot be confirmed through bone marrow aspiration and the patient is not suitable for splenic aspiration, the rk39 test can be used for initial exclusion and further verified through mNGS.