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.

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.

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.

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.

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.

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.

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.

[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.

Opioid-positive urine drug screen during treatment with oral naltrexone and the clinical implications.

Introduction: Naltrexone is an opioid antagonist that is FDA approved to treat alcohol dependence and opioid dependence. It is available as an oral tablet and an extended-release injectable suspension. Naltrexone is metabolized to the primary metabolite, 6-ß-naltrexol, and to 2 minor metabolites, 2-hydroxy-3-methoxy-6-ß-naltrexol and 2-hydroxy-3-methyl-naltrexone. One of the lesser-known metabolites of naltrexone is noroxymorphone. Methods: A 27-year-old man taking oral naltrexone seen in the outpatient setting for alcohol use disorder and cannabis use disorder was found to have multiple positive urine drug screens (UDSs) for oxycodone. Confirmatory urine drug testing was completed and noroxymorphone was detected. A naloxone challenge test was conducted with negative results and the patient tolerated the transition from oral naltrexone to the extended-release injectable suspension of naltrexone. Results: This case illustrates that it is possible for a patient stabilized on oral naltrexone to have a false-positive oxycodone UDS. Confirmatory urine drug testing was used to substantiate that the metabolite of naltrexone, noroxymorphone, was the cause of the false-positive oxycodone UDS. Conclusions: One of the lesser-known metabolites of naltrexone, noroxymorphone, can cause a positive oxycodone UDS during treatment with oral naltrexone. Confirmatory urine drug testing should be conducted to confirm the presence of noroxymorphone and rule out alternative opioids.

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.

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.

Psychosocial Impact of False-Positive Newborn Screening Results: A Scoping Review.

Psychosocial consequences of false-positive results following newborn bloodspot screening have been identified as a potential risk to this highly successful public health initiative. A scoping review was undertaken in October 2023 underpinned by the Arksey and O'Malley framework. Twenty-four papers were included in the review, many of which focused on cystic fibrosis. The results indicated that impact of false-positive results is variable; some studies suggest false-positive results have the potential to result in negative sequelae including increased stress and changes in parental perceptions of their child, while others suggest these impacts are transient and, in some instances, may even lead to positive outcomes. Further evidence is needed to ensure the representation of other conditions included in newborn bloodspot screening and to support strategies to overcome potential negative sequela.

Patient with suspected co-infection of hemorrhagic fever with renal syndrome and malaria: a case report.

Background: Hemorrhagic fever with renal syndrome (HFRS) is a natural epidemic disease that can be caused by the Hantaan virus (HTNV). Malaria is caused by plasmodium and can be transmitted by a mosquito bite. The similar manifestations shared by these disorders pose a challenge for clinicians in differential diagnosis, in particular, coupled with a false-positive serological test. Case presentation: A 46-year-old man was admitted for fever and chills for over 10 days and was suspected of being co-infected with HFRS and malaria due to a history of travel to malaria-endemic areas and a positive HTNV-immunoglobulin M (IgM) test. Although leukocytosis, thrombocytopenia, renal injury, lymphocytosis, overexpression of interleukin-6, and procalcitonin were observed during the hospitalization, the hypotensive, oliguria, and polyuria phases of the HFRS course were not observed. Instead, typical symptoms of malaria were found, including a progressive decrease in erythrocytes and hemoglobin levels with signs of anemia. Furthermore, because the patient had no history of exposure to HFRS endemic areas, exposure to an HTNV-infected rodent, or a positive HTNV-IgG test, and false serological tests of IgM can be caused by various factors, the HFRS coinfection with malaria was ruled out. Conclusion: Misdiagnosis can be easily induced by a false serological test, in particular the IgM test which can be influenced by various factors. A combination of health history, epidemiology, physical examination, precise application of specific examinations involving tests of conventional laboratory parameters as well as well-accepted methods such as the immunochromatographic (ICG) test, real-time reverse transcription-polymerase chain reaction (PCR), and Western blot (WB), and acquaintance with disorders with similar manifestations will contribute to the precise diagnosis in clinical treatment.

Trust in cervical screening and attributions of blame for interval cancers following a national controversy.

OBJECTIVES: This study investigated levels of trust and attributions of blame in connection with a cervical screening programme following a controversy related to the programme's audit, incorporating an experimental test of the effectiveness of new information materials. DESIGN: We compared responses in Ireland (N = 872) to equivalent responses in Scotland (N = 400). Participants in Ireland were randomly assigned to either a treatment group that received the information materials or a control group that did not. Participants then responded to questions about their trust in cervical screening and to whom they would attribute blame in a range of scenarios describing women diagnosed with cervical cancer between screening rounds. RESULTS: Results showed that the control group in Ireland had lower trust and attributed higher blame towards screening services than participants in Scotland. However, exposure to information materials in the treatment group improved trust and reduced blame. CONCLUSIONS: The findings suggest that public controversies influence perceptions of screening programmes and underscore the importance of transparent, choice-based communication in mitigating these effects. The findings have valuable implications for screening services worldwide as all screening programmes will have associated false negative and false positive results.

John Cunningham Virus and Progressive Multifocal Leukoencephalopathy: A Falsely Played Diagnosis.

Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition. The so-called JCPyV was initially reported in lymphoma and Human Immunodeficiency Virus (HIV) cases, whereas nowadays, its incidence is increasing in Multiple Sclerosis (MS) cases treated with natalizumab (Tysabri). However, there are conflicting literature data on its pathology and diagnosis, whereas some misdiagnosed reports exist, giving rise to further questions towards the topic. In reality, the so-called PML and the supposed JCPyV are not what they seem to be. In addition, novel and more frequent PML-like conditions may be reported, especially after the Coronavirus Disease 2019 (COVID-19) pandemic.

A phantom human chorionic gonadotropin in the case of molar pregnancy.

Accurately interpreting persistent, low human chorionic gonadotropin (hCG) levels is essential for managing gestational trophoblastic disease. Erroneous interpretation can lead to inappropriate interventions, including unnecessary chemotherapy or hysterectomy, or unjustified changes in chemotherapeutic regimens due to misidentification of a false-positive hCG as a true positive. The predominant etiology of phantom hCG is the presence of heterophilic antibodies. Consequently, screening for urine hCG is indispensable for its diagnosis because immunoglobulin is not generally present in urine. Here, we report about phantom hCG after a complete hydatidiform mole. Initial urine hCG evaluations were negative, although the serum hCG levels remained positive, leading to the diagnosis of phantom hCG. After subsequent delivery, urine hCG levels persisted at diminished levels. However, a different assay yielded negative hCG results for both serum and urine samples. The patient subsequently gave birth. The absence of hCG was consistently confirmed over five years.

A Systematic Review and Case Illustrations of Misdiagnosing Intracranial Aneurysms.

Modern neuroimaging methods do not completely rule out false diagnoses of intracranial aneurysms which can lead to an unwarranted operation associated with risks of complications. However, surgical interventions for falsely diagnosed aneurysms are quite rare. The purpose of this study is to demonstrate two clinical cases of false-positive aneurysms and a systematic review of the literature dedicated to the incidence and etiology of false-positive aneurysms, identifying risk factors associated with false-positive aneurysms. A literature search in two databases (PubMed and Web of Science) using keywords "mimicking an intracranial aneurysm", "presenting as an intracranial aneurysm", "false positive intracranial aneurysms", and "neurosurgery" was conducted. A total of 243 papers were found in the initial search in two databases. Sixteen papers (including 20 patients) were included in the final analysis. There were 10 women and 10 men. The most common location of false-positive aneurysms was the bifurcation of the middle cerebral artery (MCA). In the posterior circulation, false-positive aneurysms were identified either on the basilar artery, or at the vertebro-basilar junction. The main causes of false intracranial aneurysm diagnosis included artery occlusion with vascular stump formation, infundibular widening, fenestration, arterial dissection, contrast extravasation, and venous varix. In conclusion, summarizing the results of our analysis, we can say that surgical interventions for false-positive aneurysms are an underestimated problem in vascular neurosurgery. Despite extremely rare published clinical observations, the actual frequency of erroneous surgical interventions for false-positive aneurysms is unknown.

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.