High Incidence Of False Positive Results Research Articles

Preoperative Alkaline Phosphatase-adjusted CA19-9 as a Superior Prognosticator for Extrahepatic Biliary Tract Cancer With Jaundice.

The major limitation of carbohydrate antigen (CA)19-9 as a tumor marker is the high incidence of false-positive results during cholestasis. We evaluated preoperative CA19-9 and its adjusted values [ratios of CA19-9 to total-bilirubin (TB), direct-bilirubin (DB), and alkaline phosphatase (ALP)] to investigate the most suitable prognostic parameter in extrahepatic biliary tract cancer (eBTC) patients with or without jaundice. eBTC patients (n=140) who underwent resection were divided based on the absence (TB <2.0 mg/dl, n=90) or presence (TB ≥2.0 mg/dl, n=50) of preoperative jaundice. Within each group, the associations with overall survival (OS) were assessed for CA19-9, CA19-9/TB, CA19-9/DB and CA19-9/ALP ratios using Cox regression, receiver operating characteristic (ROC) analyses, and area under the curve (AUC) estimates. In univariate analysis in the group without jaundice, both high CA19-9 and high CA19-9/TB ratio were associated with poor OS, whereas other parameters were not. ROC-AUC for OS prediction was greater in CA19-9 than in the CA19-9/TB ratio, and CA19-9 was identified as an independent prognosticator in multivariate analysis. In the group with jaundice, CA19-9 was not significant; however, CA19-9/TB, CA19-9/DB, and CA19-9/ALP ratios were all associated with poor OS. In ROC-AUC analysis, CA19-9/ALP ratio showed the highest predictive value; furthermore, it was an independent prognosticator in multivariate analysis. Adjustment of the CA19-9 value was less useful as a predictor in the absence of jaundice. On the other hand, the CA19-9/ALP ratio showed superior prognostic value in jaundiced patients with eBTC.

Characteristics of False-Positive Alarms in the BacT/Alert 3D System.

ABSTRACTThe BacT/Alert system has been used for detecting the presence of bacteria in various clinical settings as well as in blood services, but it is associated with a relatively high incidence of false-positive results. We analyzed the results of our quality control sterility testing of blood products by BacT/Alert 3D to understand the mechanism of false-positive results. Anaerobic and aerobic bottles were inoculated with 10 mL of samples and cultured in BacT/Alert 3D for 10 days. Positive-reaction cases were classified as true positive if any bacterium was identified or false positive if the identification test had a negative result. The detection algorithm and the bottle graph pattern of the positive reaction cases were investigated. Among the 43,374 samples, 25 true positives (0.06%) and 29 false positives (0.07%) were observed. Although the detection algorithm of all true positives and 25 of 29 false positives was accelerating production of CO2, a steep rise in the bottle graph was observed only in the true positives, and it was not observed in either of the false positives. Four of 29 false positives were dependent on high baseline scatter reflections. Furthermore, evaluating the bottle graph pattern of Streptococcus pneumoniae, a bacterium known to autolyze, we confirmed that no viable bacterium was detected even if a steep rise was observed. In conclusion, the bottle graph pattern of positive reactions allows the differentiation between true positives and false positives. In case of a steep rise without bacterium detection, the bacterium might have autolyzed. Moreover, positive reactions with high baseline scatter reflections, despite immediate loading of bottles after sampling, are potentially false positive.IMPORTANCE In clinical settings, false-positive results are treated as positive until bacterial identification. It may result in the discarding of blood products in blood centers or affect clinical decisions in hospitals or testing facilities. Moreover, the management of these samples is usually time- and labor-consuming. The results of our study may help clinicians and laboratory staff in making a more precise evaluation of positive reactions in BacT/Alert.

Value of diffusion tensor imaging and tractography in unilateral lumbar disc prolapse

BackgroundConventional MR imaging is not enough for evaluation of symptomatic foraminal stenosis, because there is high incidence of false-positive results in asymptomatic elderly patients. Conventional MR cannot quantitatively assess the severity of the nerve lesion. DTI is a non-invasive way to effectively trace the nerve fiber bundle and quantitatively evaluate the nerve injury. DTI with fiber tracking may describe abnormalities beyond the resolution of conventional MR techniques. The aim of this work was to compare between the mean values of diffusion parameters such as fractional anisotropy and apparent diffusion coefficient of the compressed lumbar spinal nerve roots and of the contralateral normal nerve roots. Correlate these parameters with the severity of neurological symptoms. This is a prospective study that was conducted on 50 patients with symptomatic unilateral posterolateral lumbar disc prolapse at a university hospital. They were investigated with diffusion tensor imaging with tractography on a 1.5-T MR. The changes in the mean fractional anisotropy and apparent diffusion coefficient values of the compressed nerves and the relationship between these changes and the severity of the neurological side effects using Japanese Orthopedic Association score and visual analogue scale were investigated.ResultsThe mean fractional anisotropy values were significantly lower (p ≤ 0.001), and mean apparent diffusion coefficient values were significantly higher (p ≤ 0.001) in compressed nerves than in contralateral intact nerves. There were strong correlations between the DTI parameters and the severity of the neurological symptoms as assessed using the Japanese Orthopedic Association score and the visual analogue scale.ConclusionIn patients with lumbar disc prolapse, radicular diffusion parameters are affected in the compressed roots in comparison to the healthy roots and this affection is correlated with the degree of prolapse and with the severity of neurological symptoms. DTI with fiber tracking provide clinically relevant information and describe abnormalities beyond the resolution of conventional MR techniques.

Clinical, Bronchoscopic, and Imaging Findings of e-Cigarette, or Vaping, Product Use–Associated Lung Injury Among Patients Treated at an Academic Medical Center

e-Cigarette, or vaping, product use-associated lung injury (EVALI) has caused more than 2800 illnesses and 68 deaths in the United States. Better characterization of this novel illness is needed to inform diagnosis and management. To describe the clinical features, bronchoscopic findings, imaging patterns, and outcomes of EVALI. This case series of 31 adult patients diagnosed with EVALI between June 24 and December 10, 2019, took place at an academic medical center in Salt Lake City, Utah. e-Cigarette use, also known as vaping. Symptoms, laboratory findings, bronchoscopic results, imaging patterns, and clinical outcomes. Data from 31 patients (median [interquartile range] age, 24 [21-31] years) were included in the study. Patients were primarily men (24 [77%]) and White individuals (27 [87%]) who used e-cigarette products containing tetrahydrocannabinol (THC) (29 [94%]). Patients presented with respiratory (30 [97%]), constitutional (28 [90%]), and gastrointestinal (28 [90%]) symptoms. Serum inflammatory markers were elevated in all patients. Bronchoscopy was performed in 23 of 28 inpatients (82%) and bronchoalveolar lavage (BAL) revealed the presence of lipid-laden macrophages (LLMs) in 22 of 24 cases (91%). BAL samples tested positive for Pneumocystis jirovecii (3 patients [13%]), rhinovirus (2 patients [8%]), human metapneumovirus and Aspergillus (1 patient each [4%]); all except human metapneumovirus were determined to be false-positives or clinically inconsequential. The exclusive or dominant computed tomography (CT) pattern was organizing pneumonia in 23 of 26 cases (89%). Patients received antibiotics (26 [84%]) and corticosteroids (24 [77%]), and all survived; 20 patients (65%) seen in follow-up showed marked improvement, but residual symptoms (13 [65%]), radiographic opacities (8 [40%]), and abnormal pulmonary function tests (8 of 18 [44%]) were common. In this case series, patients with EVALI characteristically presented with a flu-like illness with elevated inflammatory markers, LLMs on BAL samples, and an organizing pneumonia pattern on CT imaging. Bronchoscopic testing for infection had a high incidence of false-positive results. Patients had substantial residual abnormal results at early follow-up. These data suggest a limited role for bronchoscopy in typical presentations of EVALI without risk factors for alternative diagnoses and the need for careful longitudinal follow-up.

Is Surveillance of Uveal Melanoma Just a Screen?

Despite the realization that half of patients with uveal melanomawill ultimatelydevelopmetastaticdisease, questions remain regarding theutility of routine surveillance. In2011, a literature review of 31 articles failed to demonstrate convincing evidence of a survival advantage from routine surveillance.1 However, these studies were conducted in the context of traditional chemotherapy regimens, none of which demonstrated adequate response rates for uvealmelanoma.Aphase 2 trial of selumetinib conductedbetween2010 and 2013 yielded improved response rates and progressionfreesurvival (despiteno improvement inoverall survival) compared with chemotherapy.2 These landmark findings shed somehope on the dismal landscape ofmetastatic uvealmelanoma andhave thus reignited the potential benefit of routine surveillance and early detection of disease. For this reason, establishing the optimal surveillance method for uveal melanoma, should it prove to be meaningful, is an important proposition. Key characteristics of a screening regimen include adequate sensitivity and specificity as well as balancing the toxicity of the screening examination with the financial and emotional costs. Because 90% of metastases are first recognized in the liver, it is logical to focus on tests of the liver. Computed tomography is limited by its emission of radiation (especially if repeated every 6-12 months for many years) and the very high incidence of false-positive results.3 While magnetic resonance imaging (MRI) is perceived as being the most sensitive test, it is expensive and less accessible and also has many false-positive results. As Choudhary et al4 have pointed out in this issue of JAMA Ophthalmology, abdominal ultrasonography is an attractive screening modality. Historically, owing to its operator dependence and limitation by body habitus, abdominal ultrasonography was rarely used as a surveillance tool in the United States and has been more commonly adopted in Europe.5,6 Almost a decade ago, a study from Finland estimated that semiannual ultrasonography in concert with liver function tests could detect metastases in more than 95% of asymptomatic patients.6 At the time, the authors could not justify the expense of such a regimen in the face of poor response from the conventional chemotherapy used at the time.6 However, the promising results of targeted and immunotherapy treatments for metastatic disease2,7 may now justify an exploration of this proposed screening regimen. The work of Choudhary et al4 is most intriguing because it addresses themodel that was raised by the Finnish study a decade ago, in a US population that was historically believed to be less eligible for such a screening approach. The authors Related article page 174 Research Original Investigation Hepatic Ultrasonography for Surveillance in Uveal Melanoma

089 REGIONAL VARIATION IN MYOCARDIAL BLOOD FLOW IN PATIENTS WITH LEFT BUNDLE BRANCH BLOCK: A QUANTITATIVE PERFUSION CMR STUDY

IntroductionLeft bundle branch block is often associated with underlying coronary artery disease (CAD) but its presence can limit the diagnostic accuracy of non-invasive imaging tests. In particular, there is a...

Regional variation in myocardial blood flow in patients with left bundle branch block evaluated with quantitative perfusion CMR

Background This study is the first to use quantitative perfusion CMR to evaluate regional differences in myocardial blood flow (MBF) in patients with left bundle branch block (LBBB). LBBB is often associated with underlying CAD but its presence can limit the diagnostic accuracy of non-invasive imaging tests. In particular, there is a high incidence of false-positive results with exercise SPECT due to apparent septal perfusion defects. The use of vasodilator stress has reduced but not eliminated this problem. Several hypotheses have been postulated to explain the cause of such perfusion defects, and these include early activation of the septum, leading to shortened diastole and reduced blood flow; partial volume effects caused by impaired septal thickening; and increased septal intra-myocardial pressure during diastole, resulting in reduced flow reserve. A number of small studies using PET or early quantitative SPECT techniques have evaluated regional differences in MBF in patients with LBBB, but the results have been conflicting and have shown either no regional differences or a relative but not absolute reduction in septal perfusion. This study re-evaluates the unresolved question of septal perfusion in LBBB using quantitative perfusion CMR.

Hematocrit Influences Immunoassay Performance for the Measurement of Tacrolimus in Whole Blood

The comparison between the MEIA II and the EMIT assays for tacrolimus measurement and the interference by the hematocrit were evaluated in 93 samples from routine therapeutic monitoring at tacrolimus concentrations less than 9 microg/L (group A). Additionally, the incidence of false-positive results were determined in samples (n=46) from patients who were not receiving the drug (group B). In group A, no statistical differences were observed between the mean+/-SD values obtained by MEIA II (5.14+/-2.28 microg/L) and EMIT (4.61+/-1.79 microg/L). The correlation coefficient and the regression equation (95% CI) between both assays, were 0.761 and EMIT=1.088 (0.90, 1.35) MEIA II -0.38 (-1.65, -0.46), respectively. When the samples were stratified according to the hematocrit, the median differences between the methods (MEIA II minus EMIT) were as follows: hematocrit<or=25%, 0.45 microg/L; hematocrit 25%-35%, 0.30 microg/L; and hematocrit>35%, 0.25 microg/L (P=0.02). In group B, false-positive results (above the detection limit) were observed in 63.04% of samples analyzed by MEIA II and in 2.17% of samples analyzed by EMIT. The median differences in apparent tacrolimus results were significantly higher in the samples with the lowest hematocrit: 2.2 microg/L, 1.4 microg/L, and 0.0 microg/L in samples with hematocrit<or=25%, 25%-35%, and >35%, respectively. In conclusion, the differences in the tacrolimus results obtained by MEIA and EMIT assays were higher in samples from patients with hematocrit less than 25%, and the MEIA assay demonstrated a high incidence of false-positive results.

A Primary Care Approach to the Use and Interpretation of Common Rheumatologic Tests

The results of common rheumatologic laboratory tests play an important part in the diagnosis and management of rheumatic diseases. Rheumatologic test results can often be ambiguous and can sometimes be misleading, particularly in primary care settings. Because the diagnosis of most rheumatic conditions depends on information derived from sources other than serum tests, these laboratory values are usually supportive rather than diagnostic [1]. Few serum test results are pathognomonic for a specific rheumatic disease and alone are insufficient to determine a diagnosis [2]. Test results should be interpreted in a clinical context, which includes information derived from the history and physical examination, basic laboratory tests, radiographic and other imaging studies, and synovial fluid analysis. Serum rheumatologic tests are most useful for confirming a clinically suspected diagnosis. Because there is a high incidence of false-positive results in the general population, these tests have little clinical utility when there is a low pretest probability. Furthermore, the predictive value of serum rheumatologic tests is limited when performed in settings in which the prevalence of rheumatic conditions is low. Studies suggest that primary care physicians overuse common rheumatologic tests [3]. The practice of routinely ordering a battery of rheumatologic laboratory tests to ‘‘rule out’’ rheumatologic disease is not uncommon [1]. This approach rarely leads to a definitive diagnosis and

Detection of specific IgE to quinolones

Background In the last years, immediate reactions to quinolone antibiotics have been observed with increasing frequency, mainly urticaria, angioedema, and shock. No test was available because of the high incidence of false-positive results on skin tests. Thus the pathogenesis, value of diagnostic procedures, and cross-reactivity have not been evaluated in a systematic way. Objective We sought to assess whether these reactions are IgE mediated and whether an in vitro test for quinolone-specific IgE is useful in the diagnosis and understanding of cross-reactivity. Methods We assayed specific serum IgE to quinolones using epoxy-activated sepharose 6B as the solid phase in 55 patients with immediate adverse reactions; specificity of IgE binding was demonstrated by inhibition tests. Results The test yielded positive results in 30 (54.5%) patients who were tested 1 to 48 months after the reaction had occurred. The quinolone-specific IgE seems to disappear more slowly in atopic patients. The cross-reactivity between various quinolones allowed us to identify a common structural motif within quinolones that might be responsible for clinical and serologic cross-reactivity. Conclusion A substantial portion of immediate reactions to quinolones appear to be IgE mediated. Cross-reactivity of IgE among different quinolones is frequent and suggests that a common avoidance of quinolones should be attempted in all patients with respective symptoms.

Numerical computation as a tool to aid thermographic interpretation

Thermography is an non-invasive and a painless tool for the detection of breast cancer. However, performing and interpreting thermograms requires meticulous training. It was found that women with an abnormal thermogram are at a higher risk and have a poorer prognosis. One of the main drawbacks of the thermogram is the high incidence of false-positive results. The authors believe that the fault lies in misinterpretation of the thermogram, rather than the thermogram itself. The paper aims to show that computer simulations could be an adjunct tool to help the clinician in the interpretation. This would greatly reduce the false-positive diagnosis.

Use of heparinase I in a patient with protamine allergy undergoing redo myocardial revascularization

TRUE ANAPHYLAXIS to protamine is extremely difficult to document because no clinically useful preoperative test for protamine sensitivity with good predictive value has been developed.1 Although a humorally mediated immune response to protamine has been suggested, Weiss et al2 showed elevated IgE levels only in diabetic patients receiving long-term protamine-insulin preparations; it remains to be determined whether antiprotamine IgG antibodies were related causally to protamine reactions. Skin testing appears to have a limited applicability in the assessment of protamine sensitivity3,4 and with the high incidence of false-positive results found by Horrow et al4 using enzyme-linked immunosorbent assays to detect circulating antibodies to protamine, neither skin testing nor enzyme-linked immunosorbent assays are as yet reliable.

Neither Skin Tests nor Serum Enzyme-Linked Immunosorbent Assay Tests Provide Specificity for Protamine Allergy

Neither Skin Tests nor Serum Enzyme-Linked Immunosorbent Assay Tests Provide Specificity for Protamine Allergy

Optic gliomas in neurofibromatosis type 1: Role of visual evoked potentials

Optic gliomas occur in 15% of patients with neurofibromatosis type 1 (NF 1) and are a significant cause of morbidity. Of these tumors, 20–30% become symptomatic, usually before age 10 years. Previous studies have suggested that visual evoked potentials (VEPs) are a sensitive method for the detection of asymptomatic optic gliomas. Because routine neuroimaging of children with NF 1 is currently not recommended, the role of pattern-shift VEPs (PS VEPs) as a screening test for optic gliomas was evaluated. PS VEPs were performed on 10 children with NF 1 and optic gliomas and 20 children with NF 1 and normal visual pathways (as defined on MRI). PS VEPs had 90% sensitivity for detecting optic gliomas, with an increase in sensitivity to 100% when hemifield stimulation was used. The specificity of the test was 60%. Four of 20 children without optic gliomas had thickened optic nerves on computed tomography which represented dural ectasia with normal visual pathways on MRI; PS VEPs were normal in these patients. The efficacy of PS VEPs as a routine screen for optic gliomas is limited by the age at which children will cooperate with the test procedure and the high incidence of false-positive results; however, VEPs do provide a useful adjunct to routine clinical ophthalmologic assessment in the detection of optic gliomas in children with NF 1. Abnormal test results provide a stronger indication for neuroimaging. The early detection of optic gliomas allows for close monitoring of tumor progression and earlier intervention prior to significant visual loss.

Interference of Digoxin-Like Immunoreactive Substances with TDx Digoxin II Assay in Different Patients

The TDx digoxin II immunoassay was used in controls and in patients not taking digoxin or any other cardiac glycoside. We report the frequency of interference thought to be caused by digoxin-like factors (DLFs). We found a high incidence of false-positive results in 15 patients with severe hepatic disease (60% false-positive results). In newborn infants we found false-positive results both when their blood was drawn from a peripheral vein (89% false-positive results) and, more strikingly (100% false-positive results), when it was obtained from an umbilical cord vein (p less than 0.001). Compared to a control group, no statistically significant false-positive results were found in patients with mild to moderate chronic renal failure (n = 21) or in pregnant women (n = 15). In patients with chronic renal failure undergoing hemodialysis six of 25 had false-positive results. These results suggest that digoxin levels must be interpreted carefully in patients with chronic liver disease and chronic renal failure and in newborns until new methods that eliminate the interference caused by DLFs become readily available.

Maternal Hormone Measurements

<h3>To the Editor.—</h3> In a recent reply in the QUESTIONS AND ANSWERS section ofThe Journal(1982;248:1109) relating to the use of maternal hormone measurements in the management of high-risk pregnancies, Duenhoelter correctly emphasizes the high incidence of false-positive results (ie, low values in the absence of fetal jeopardy) from maternal estriol and human placental lactogen assays. However, I believe that the companion assertion of a high incidence of false-negative estriol results would probably be challenged by most contributors to this area of inquiry. In fact, properly performed (radioimmunoassay) serum or urine estriol assays have low incidences of false-negative results (normal values in the presence of fetal jeopardy), probably lower than any of the other chemical or biophysical measurements. Even so, one cannot predict how long the safety inherent in a normal estriol value will last, in contrast, for instance, to the five- to seven-day assurance offered by a normal

Heparin-Latex Test in Rheumatoid and Non-Rheumatoid Serums.

SummaryThe rather high incidence of false-positive results with serums containing elevated a-globulin levels, limits the practical value of the heparin-latex test for routine testing in rheumatoid arthritis.