Cause Of False-positive Results Research Articles

SAT-192 Eletriptan (RelpaxaTm) Causing False Positive Elevations in Urinary Metanephrine

Background:The diagnosis of pheochromocytoma depends crucially on the demonstration of excessive production of catecholamines. This step, however, is fraught with several difficulties, in particular with false-positive test results. Drugs such as phenoxybenzamine and tricyclic antidepressants are the most frequently associated causes for false-positive results. Other medications are also known to cause a false positive elevation of urinary metanephrines. We are reporting a patient with markedly elevated urine metanephrines associated with the use of Eletriptan hydrobromide (RelpaxaTM), a drug commonly used for treating migraine.Clinical Case:A 29-year-old man with a history of migraine managed on ibuprofen and recently started Eletriptan presented to the emergency room complaining of a 24-hour history of progressively worsening headaches. At the time of initial evaluation his blood pressure was in the 220s/160s with a creatinine of 1.9 mg/dL with unknown baseline. He was managed on an IV nicardipine drip. Due to his young age he underwent an evaluation for secondary causes of his hypertension. Laboratory: normal aldosterone/renin level (ratio was 0.4), normal midnight salivary cortisol and normal thyroid function studies. Urine screening for drug abuse was also negative. A 24-hour urine metanephrine level, while the patient was taking Eletriptan, was markedly elevated (normetanephrine 1341mcg (ref 82–500) and metanephrine level of 2494 mcg (ref 45–290). In contrast, the plasma metanephrines were only mildly elevated (metanephrines level 27 pg/ml (ref 0–62) and normetanephrine level of 255 pg/ml (ref 0–145)). Adrenal CT did not reveal any evidence of adrenal nodules. Additionally a Gallium-68 PET/CT scan did not reveal any evidence of pheochromocytoma or paraganglioma. Eletriptan was discontinued and his blood pressure was controlled on oral medications. Within one week of stopping Eletriptan his urine metanephrines (metanephrine 76 mcg/ 24 hrs, normetanephrine 277 mcg/dL) and plasma metanephrines (metanephrine 39 pg/mL, normetanephrine 148 pg/mL) normalized. Conclusion: The discrepancy between plasma and urine metanephrines in our patient suggests the possibility of a false positive test. Eletriptan, a second generation triptan drug, is a selective 5-hydroxytryptamine 1B/1D receptor agonist and has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. However, Eletriptan has no significant affinity or pharmacological activity at adrenergic α1, α2, or β; dopaminergic D1 or D2; muscarinic; or opioid receptors. It is also interesting to note that Eletriptan use is contraindicated in uncontrolled hypertension. It is possible Eletriptan may affect the assay of urine metanephrines. However, the exact mechanism of Eletriptan causing elevated urine metanephrines in our patient is not clear.

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.

Monoclonal antibody-based capture ELISA in the diagnosis of previous dengue infection

BackgroundDengue is an important mosquito-borne disease. There is currently only one licensed vaccine for dengue prevention. The vaccine provides higher efficacy in pre-vaccination dengue-seropositive persons but a higher risk of subsequent more severe dengue in dengue-seronegative persons. It is recommended that the dengue vaccine may be given in dengue-seropositive individuals or as mass vaccination without individual pre-vaccination screening in areas where the dengue seroprevalence is > 80% in children aged 9 years. We evaluated a dengue specific immunoglobulin G monoclonal antibody-based capture enzyme-linked immunosorbent assay (MAb-ELISA) in the diagnosis of previous dengue infection using serum samples from the cohort study in Ratchaburi Province, Thailand.MethodsThe MAb-ELISA was compared to 70% plaque reduction neutralization test (PRNT70) in 453 serum samples from children aged 3–11 years in Ratchaburi Province, Thailand.ResultsThe sensitivity and specificity of MAb-ELISA at the positive to negative (P/N) ratio cut-off level of > 3 were both 0.91 in the diagnosis of previous dengue infection, compared to PRNT70. The false positivity was mainly in Japanese encephalitis (JE) seropositive subjects.ConclusionsThis research provides evidence that MAb-ELISA is useful for dengue seroprevalence study and dengue pre-vaccination screening. JE seropositivity was the major cause of false positive result in the study population.

SUPER DIMENSION NAVIGATIONAL BRONCHOSCOPE-ASSISTED MINI-BAL ROLE IN CASE OF FUNGAL BALL

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Aspergillus species are ubiquitous and exposure to their spores is frequent. Aspergillosis can be confused with malignancy on imaging and sometimes creates challenge. The sensitivity and specificity of a positive result of BAL fluid are about 50% and 97%, respectively, but this diagnostic yield of BAL in the diagnosis of aspergillosis is not consistent. Eosinophilia is often reported in BAL of aspergillosis but degree of eosinophilia varies and may not be helpful. In this presented case we noted the mini-BAL performed at the site of fungal ball show significant elevation and high percentage of eosinophilia as compared to regular BAL and can be assuring in evaluation of mass for aspergilloma vs malignancy. CASE PRESENTATION: 79-year-old male ex-smoker treated with chemotherapy and radiotherapy for adenocarcinoma of the distal esophagus and had definitive surgery. He had been cancer free for 4yrs. Pt started having nonproductive cough without any fever, chills, rigors, chest pain, weight loss, hemoptysis or night sweats. Chest x-ray revealed 3.1 cm irregular and nodular opacity in right mid lung field and this finding was confirmed with CT scan. There were some infiltrates but no lymphadenopathy. Repeat CT scan showed mass in distal right upper lobe worsening in size. There was concern for endobronchial mass in right upper lobe. He went through Super-Dimension navigational bronchoscopy. Biopsy results confirmed no malignancy but there were gram-positive hyphae suggestive for Aspergillus species. Interestingly mini BAL through the working channel of super-dimension navigation al bronchoscope showed 38% eosinophils at the site of aspergilloma and regular BAL was having 11% eosinophils. He was given voriconazole and repeated CT scan showed significant improvement in Aspergillosis. DISCUSSION: Fungal balls can occasionally put potential diagnostic dilemma especially in a patient who had gone through the surgical and chemotherapeutic treatment of lung malignancy and are immunocompromised. Such patient can have a diagnostic challenge even after bronchoscopic approach if mass vs fungal ball is located in distal bronchi. Comparing the mini-BAL from the working channel of super dimension navigational bronchoscope from the site of the lesion to regular BAL can be reassuring for fungal etiology if there is a higher degree of eosinophilia from the site of lesion and empiric antifungal treatment trial can be considered in appropriately selected patients. CONCLUSIONS: Through the Super Dimension Navigational Bronchoscope working channel mini Bronchoalveolar lavage eosinophilic comparison with regular BAL can increase the sensitivity for the diagnostic yield for mycetoma if there is a higher percentage of eosinophilia is found at the site of lesion and can help to differentiate from other pulmonary eosinophilic conditions like lung malignancy, and other DPLDs. Reference #1: Hage CA, Reynolds JM, Durkin M, Wheat LJ, Knox KS. Plasmalyte as a cause of false-positive results for Aspergillus galactomannan in bronchoalveolar lavage fluid. J Clin Microbiol 2007; 45:676–7. Reference #2: Du Rand IA, Barber PV, Goldring J, et al. British Thoracic Society guideline for advanced diagnostic and therapeutic flexible bronchoscopy in adults. Thorax 2011; 66(suppl 3):1–21. Reference #3: Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60. https://doi.org/10.1093/cid/ciw326. Epub 2016 Jun 29. DISCLOSURES: No relevant relationships by Amnah Andrabi, source=Web Response No relevant relationships by Kashif Aslam, source=Web Response No relevant relationships by Bindu Gandrapu, source=Web Response No relevant relationships by Preeyanka Sundar, source=Web Response

Ischemic Complications After High-Grade Glioma Resection Could Interfere With Residual Tumor Detection With 18F-Fluorocholine PET/CT.

Ischemic complications after resection of high-grade glioma are frequent and may constitute potential cause of false-positive results in postsurgical evaluation using F-fluorocholine PET/CT. On the other hand, hypoxia caused by ischemia promotes invasive glioma growth. We present 3 cases of patients with different grades of ischemic injury after resection of high-grade glioma. The combined interpretation of diffusion-weighted imaging and apparent diffusion coefficient map on MRI, in this clinical setting, is mandatory to avoid PET/CT misinterpretations.

Evaluation of positron emission tomography and contrast-enhanced computed tomography scan in nodal staging of early operable uterine cancers

Introduction:In early operable stages of cervical an endometrial malignancies, surgical staging of lymph nodes is advocated as contrast-enhanced computed tomography (CECT) has limited sensitivity and accuracy. Although fluorine-18 (F-18) fluorodeoxyglucose (FDG)/positron emission tomography (PET)-CT has potential to identify subcentimeter-sized nodal metastases, higher prevalence of pelvic inflammatory disease in developing countries could result in lower accuracy. The present study was undertaken to assess the incremental value of PET scan over CECT for nodal staging before radical surgery.Methods:Forty-four patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IA2–IIb carcinoma cervix and 28 patients of FIGO Stage I–II carcinoma endometrium underwent F-18 FDG-PET-CECT scan. A SUVmax value >2.5 g/ml based on body weight was considered as positive. An enhancing node with >1 cm size in the shortest dimension, with loss of fatty hilum was considered positive on CT images. The histological findings were considered the gold standard against which the two modalities were compared.Results:All 1226 pelvic nodes were dissected, of which 65 were found to be metastatic (i.e., 5.3%). Of the 72 patients, 15 (20.83%) had pelvic nodal metastases. The overall accuracy of PET and CECT for assessment of pelvic nodal metastases was comparable (i.e., 86% vs. 85%).Conclusion:PET and CECT scans have similar accuracy in pelvic nodal staging of operable uterine malignancies. Granulomatous inflammation may not be a major cause of false-positive results. The sensitivity and negative predictive values are not high enough to obviate need of surgical nodal staging.

Chinese Military Evaluation of a Portable Near-Infrared Detector of Traumatic Intracranial Hematomas.

Secondary brain injury is the main cause of mortality from traumatic brain injury (TBI). One hallmark of TBI is intracranial hemorrhage, which occurs in 40-50% of severe TBI cases. Early identification of intracranial hematomas in TBI patients allows early surgical evacuation and can reduce the case fatality rate of TBI. As pre-hospital care is the weakest part of Chinese emergency care, there is an urgent need for a capability to detect brain hematomas early. In China, in addition to preventing injuries and diseases in military staff and in enhancing the military armed forces during war, military medicine participates in actions such as emergency public health crises, natural disasters, emerging conflicts, and anti-terrorist campaigns during peacetime. The purpose of this observational study is to evaluate in the Chinese military general hospital the performance of a near-infrared (NIR)-based portable device, developed for US Military, in the detection of traumatic intracranial hematomas. The endpoint of the study was a description of the test characteristics (sensitivity, specificity, and positive and negative predictive values [NPV]) of the portable NIR-based device in identification of hematomas within its detection limits (volume >3.5 mL and depth <2.5 cm) compared with computed tomography (CT) scans as the gold standard. The Infrascanner Model 2000 NIR device (InfraScan, Inc., Philadelphia, PA, USA) was used for hematoma detection in patients sustaining TBI. Data were collected in the People's Liberation Army General Hospital in Beijing using the NIR device at the time of CT scans, which were performed to evaluate suspected TBI. One hundred and twenty seven patients were screened, and 102 patients were included in the per protocol population. Of the 102 patients, 24 were determined by CT scan to have intracranial hemorrhage. The CT scans were read by an independent neuroradiologist who was blinded to the NIR measurements. The NIR device demonstrated sensitivity of 100% (95% confidence intervals [CI] 82.8-100%) and specificity of 93.6% (95%CI 85-97.6%) in detecting intracranial hematomas larger than 3.5 mL in volume and that were less than 2.5 cm from the surface of the brain. Blood contained within scalp hematomas was found to be a major cause of false-positive results with this technology. The study showed that the Infrascanner is a suitable portable device in Chinese population for detecting preoperative intracranial hematomas in remote locations, emergency rooms, and intensive care units. It could aid military medics, physicians, and hospital staff, permitting better triage decisions, earlier treatment, and reducing secondary brain injury caused by acute and delayed hematomas.

Is MMTV associated with human breast cancer? Maybe, but probably not

BackgroundConflicting results regarding the association of MMTV with human breast cancer have been reported. Published sequence data have indicated unique MMTV strains in some human samples. However, concerns regarding contamination as a cause of false positive results have persisted.MethodsWe performed PCR assays for MMTV on human breast cancer cell lines and fresh frozen and formalin fixed normal and malignant human breast epithelial samples. Assays were also performed on peripheral blood mononuclear cells from volunteer blood donors and subjects at risk for human retroviral infections. In addition, assays were performed on DNA samples from wild and laboratory mice. Sequencing of MMTV positive samples from both humans and mice were performed and phylogenetically compared.ResultsUsing PCR under rigorous conditions to prevent and detect “carryover” contamination, we did detect MMTV DNA in human samples, including breast cancer. However, the results were not consistent and seemed to be an artifact. Further, experiments indicated that the probable source of false positives was murine DNA, containing endogenous MMTV, present in our building. However, comparison of published and, herein, newly described MMTV sequences with published data, indicates that there are some very unique human MMTV sequences in the literature.ConclusionWhile we could not confirm the true presence of MMTV in our human breast cancer subjects, the data indicate that further, perhaps more traditional, retroviral studies are warranted to ascertain whether MMTV might rarely be the cause of human breast cancer.

β-d-Glucan Testing Is Overused in Patients Without Solid Organ/Stem Cell Transplant or Hematologic Malignancies

Background The β-d-glucan (BDG) assay aids in diagnosis of some invasive fungal infections (IFI) in at-risk patients. Due to an increase in the number of BDG tests ordered at Johns Hopkins Hospital in patients not at high risk for IFI, we evaluated the appropriateness of testing and conducted a survey to understand providers’ knowledge about the test.Methods From December 2015 to July 2016, we identified inpatients >17 years with at least one BDG test. We did not evaluate patients with solid organ/stem cell transplant or hematologic malignancies as they generally have indications for BDG testing. Using a standard data collection form, one infectious disease (ID) physician reviewed all test for appropriateness; 20% of cases were reviewed by an additional ID physician. Students, housestaff and allied staff from departments of medicine and surgery were surveyed regarding their knowledge of BDG test characteristics including indications and causes of false-positive results.Results355 patients with at least one BDG were included. 33% (n = 116) had a risk factor for IFI (e.g., AIDS, immunosuppressing medication, malignancy, total parenteral nutrition, and prolonged ICU stay) although only 13% (n = 48) of these had proved or possible IFI. 49% (n = 173) had no indication for testing. Of these, 4% (n = 8) had inappropriate antifungals started based on BDG results. Being at an intensive care unit or having cirrhosis was associated with inappropriate BDG use (P = 0.03). Most of the 47 clinicians surveyed recognized the utility of BDG in the diagnosis of candidiasis (63%) and Aspergillosis (78%) but only 49% recognized its utility in diagnosis of Pneumocystis. Fifty-two percent identified its lack of utility for diagnosis of Cryptococcus infection but only 44% recognized lack of utility for diagnosing Zygomycetes. The majority of those surveyed were unable to identify causes of false-positive results of the assay.Conclusion In patients without solid organ/stem cell transplant or hematologic malignancies, clinicians ordered the BDG assay in the absence of clinical risk or evidence of IFI in almost 50% of patients. Survey results suggest an incomplete understanding of organisms associated with positive BDG tests. Clinicians must be educated about the correct patient population in which a new test should be used.Disclosures All authors: No reported disclosures.

Contamination with HIV antibody may be responsible for false positive results in specimens tested on automated platforms running HIV 4th generation assays in a region of high HIV prevalence.

IntroductionIn South Africa where the prevalence of HIV infection is very high, 4th generation HIV antibody/p24 antigen combo immunoassays are the tests of choice for laboratory based screening. Testing is usually performed in clinical pathology laboratories on automated analysers. To investigate the cause of false positive results on 4th generation HIV testing platforms in public sector laboratories, the performance of two automated platforms was compared in a clinical pathology setting, firstly on routine diagnostic specimens and secondly on known sero-negative samples.MethodsFirstly, 1181 routine diagnostic specimens were sequentially tested on Siemens and Roche automated 4th generation platforms. HIV viral load, western blot and follow up testing were used to determine the true status of inconclusive specimens. Subsequently, known HIV seronegative samples from a single donor were repeatedly tested on both platforms and an analyser was tested for surface contamination with HIV positive serum to identify how suspected specimen contamination could be occurring.ResultsSerial testing of diagnostic specimens yielded 163 weakly positive or discordant results. Only 3 of 163 were conclusively shown to indicate true HIV infection. Specimen contamination with HIV antibody was suspected, based on the following evidence: the proportion of positive specimens increased on repeated passage through the analysers; viral loads were low or undetectable and western blots negative or indeterminate on problem specimens; screen negative, 2nd test positive specimens tested positive when reanalysed on the screening assay; follow up specimens (where available) were negative. Similarly, an increasing number of known negative specimens became (repeatedly) sero-positive on serial passage through one of the analysers. Internal and external analyser surfaces were contaminated with HIV serum, evidence that sample splashes occur during testing.ConclusionsDue to the extreme sensitivity of these assays, contamination with minute amounts of HIV antibody can cause a negative sample to test positive. Better contamination control measures are needed on analysers used in clinical pathology environments, especially in regions where HIV sero-prevalence is high.

Improving the Positive Predictive Value of Non-Invasive Prenatal Screening (NIPS).

We evaluated performance characteristics of a laboratory-developed, non-invasive prenatal screening (NIPS) assay for fetal aneuploidies. This assay employs massively parallel shotgun sequencing with full automation. GC sequencing bias correction and statistical smoothing were performed to enhance discrimination of affected and unaffected pregnancies. Maternal plasma samples from pregnancies with known aneuploidy status were used for assay development, verification, and validation. Assay verification studies using 2,085 known samples (1873 unaffected, 69 trisomy 21, 20 trisomy 18, 17 trisomy 13) demonstrated complete discrimination between autosomal trisomy (Z scores >8) and unaffected (Z scores <4) singleton pregnancies. A validation study using 552 known samples (21 trisomy 21, 10 trisomy 18, 1 trisomy 13) confirmed complete discrimination. Twin pregnancies showed similar results. Follow-up of abnormal results from the first 10,000 clinical samples demonstrated PPVs of 98% (41/42) for trisomy 21, 92% (23/25) for trisomy 18, and 69% (9/13) for trisomy 13. Adjustment for causes of false-positive results identified during clinical testing (eg, maternal duplications) improved PPVs to 100% for trisomy 21 and 96% for trisomy 18. This NIPS test demonstrates excellent discrimination between trisomic and unaffected pregnancies. The PPVs obtained in initial clinical testing are substantially higher than previously reported NIPS methods.

Interferences on microbial inhibitor tests related to ivermectin treatment in lactating dairy goats.

This Research Communication reports interferences related to the administration of ivermectin in lactating dairy goats on the response of microbial tests for screening antibiotics in milk. Twenty-eight Murciano-Granadina goats, naturally infested with Sarcoptes scabiei var. caprae, were treated with a subcutaneous injection of ivermectin (200 µg/kg b.w.). To prevent re-infestation, a second dose was applied 7 d later. Individual milk samples were collected, daily, up to 15 d post-treatment. Milk samples were analysed by microbial inhibitor tests (BRT MRL, Delvotest SP-NT MCS and Eclipse 100) and ivermectin residues were quantified by HPLC. A large number of positive results were obtained for all microbial tests, especially on the first day after treatment (BRT MRL = 46·4%; Delvotest SP-NT MCS = 14·3%; and Eclipse 100 = 17·8%). However, the highest concentration of drug residues in milk (24·3 ng/ml) was detected on the tenth day after treatment, when positive outcomes were relatively lower (BRT MRL = 17·8%; Delvotest SP-NT MCS = 10·7%; and Eclipse 100 = 7·4%). Results herein suggest that factors related to the ivermectin treatment other than drug residues in milk, or alterations produced by the parasitic disease itself affecting the immune response of animals, could be the cause of false-positive results in microbial tests. It can be concluded that the application of ivermectin in dairy goats infested with sarcoptes mange during lactation produces persistent drug residues in milk, and could also cause false-positive results in microbial inhibitor tests for screening antibiotics.

Toll like receptor mediated immune stimulation can be visualized in vivo by [18F]FDG-PET

IntroductionHigh uptake of [18F]-2-fluorodeoxyglucose ([18F]FDG) by inflammatory cells is a frequent cause of false positive results in [18F]FDG-positron-emission tomography (PET) for cancer diagnostics. Similar to cancer cells, immune cells undergo significant increases in glucose utilization following activation, e.g., in infectious diseases or after vaccination during cancer therapy. The aim of this study was to quantify certain immune effects in vitro and in vivo by [18F]FDG-PET after stimulation with TLR ligands and specific antibodies. MethodsIn vivo [18F]FDG-PET/magnetic resonance imaging (MRI) and biodistribution was performed with C57BL/6 mice immunized with CpG or LPS. Cellular [18F]FDG-uptake assays were performed with B cells and T cells or with whole spleen cells after stimulation with CpG, LPS and anti-CD3/CD28. In vitro and in vivo activation of B and T cells was examined by concomitant FACS analysis to correlate immune cell activation with the strength of [18F]FDG accumulation. ResultsWe could show that TLR mediated activation of B cells increases [18F]FDG uptake, and that B cells show faster kinetics and greater effect than T cells stimulated by the CD3/CD28 pathway. In the whole spleen cell population the [18F]FDG signal was triggered mainly by the activation of B cells, corresponding closely to expression of typical stimulation markers. This finding could also been seen in vivo in [18F]FDG-PET/MRI, where the spleen was clearly visible after TLR stimulation and B cells showed upregulation of CD80 and CD86. ConclusionIn vivo TLR stimulation can be visualized by increased [18F]FDG uptake in lymphoid organs. The signal generated in the spleen after immunization might be mainly attributed to the activation of B cells within. Advances in Knowledge and Implications for Patient CareKnowledge of the composition of cells that take up [18F]FDG during vaccination or in response to therapy may improve successful treatment of cancer patients in the future.

Confined placental mosaicism and its impact on confirmation of NIPT results.

Non-invasive prenatal testing (NIPT) has been widely used to screen for common aneuploidies since 2011. While NIPT is highly sensitive and specific, false positive results can occur. One important cause of false positive results is confined placental mosaicism (CPM). This can occur through a mitotic nondisjunction event or through aneuploidy rescue. CPM is usually associated with normal fetal outcomes, but has been associated with intrauterine growth restriction, pregnancy loss, or perinatal death in some cases. CPM may also be a marker for uniparental disomy. Given that NIPT can result in false positives, positive results should be confirmed with invasive testing before any irreversible procedure is performed. Whether to perform CVS or amniocentesis to confirm a positive NIPT result is controversial. While CVS can be performed earlier than amniocentesis, CPM can also cause false positive results. Our practice is to proceed with CVS, and to examine all cell lines using both an uncultured sample using fluorescence in situ hybridization (FISH) or short-term culture, as well as long-term culture of the sample. If the results all show aneuploidy, the results are reported to the patient. Otherwise, if the results are also mosaic, amniocentesis is recommended and analyzed by both FISH and karyotype. © 2016 Wiley Periodicals, Inc.

Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis.

BackgroundStudying the uptake of 2-deoxy glucose (2-DG) analogs such as 2-Deoxy-2-[18F] fluoroglucose (FDG) is a common approach to identify and monitor malignancies and more recently chronic inflammation. While pancreatitis is a common cause for false positive results in human studies on pancreatic cancer using FDG, the relevance of these findings to acute pancreatitis (AP) is unknown. FDG has a short half-life. Thus, with an aim to accurately characterize the metabolic demand of the pancreas during AP in real-time, we studied the uptake of the non-radioactive, near infrared fluorescence labelled 2-deoxyglucose analog, IRDye® 800CW 2-DG probe (NIR 2-DG; Li-Cor) during mild and severe biliary AP.MethodsWistar rats (300 g; 8–12/group) were administered NIR 2-DG (10 nM; I.V.). Mild and severe biliary AP were respectively induced by biliopancreatic duct ligation (DL) alone or along with infusing glyceryl trilinoleate (GTL; 50 μL/100 g) within 10 minutes of giving NIR 2-DG. Controls (CON) only received NIR 2-DG. Imaging was done every 5–10 minutes over 3 hrs. Average Radiant Efficiency [p/s/cm²/sr]/[μW/cm²] was measured over the pancreas using the IVIS 200 in-vivo imaging system (PerkinElmer) using the Living Image® software and verified in ex vivo pancreata. Blood amylase, lipase and pancreatic edema, necrosis were measured over the course of AP.ResultsNIR 2-DG uptake over the first hour was not influenced by AP induction. However, while the signal declined in controls and rats with mild AP, there was significantly higher retention of NIR 2-DG in the pancreas after 1 hour in those with GTL pancreatitis. The increase was > 3 fold over controls in the GTL group and was verified to be in the pancreas ex vivo. In vitro, pancreatic acini exposed to GTL had a similar increase in NIR 2-DG uptake which was followed by progressively worse acinar necrosis. Greater retention of NIR 2-DG in vivo was associated with worse pancreatic necrosis, reduced ATP concentrations and mortality, which were not predicted by the blood parameters.ConclusionIn-vivo fluorescent imaging of a non-radioactive near infrared 2-DG optical probe can predict the AP severity early during the disease.

Prospective neonatal screening for severe T- and B-lymphocyte deficiencies in Seville.

Early diagnosis of primary immunodeficiency such as severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) improves outcome of affected children. T-cell-receptor-excision circles (TRECs) and kappa-deleting-recombination-excision circles (KRECs) determination from dried blood spots (DBS) identify neonates with severe T- and/or B-lymphopenia. No prospective data exist of the impact of gestational age (GA) and birth weight (BW) on TRECs and KRECs values. TRECs and KRECs determination using triplex RT-PCR (TRECS-KRECS-β-actin-Assay) from prospectively collected DBS between 02/2014 and 02/2015 in three hospitals in Seville, Spain. Cut-off levels were TRECs < 6/punch, KRECs < 4/punch and -β-actin>700/punch. Internal (SCID, XLA, ataxia telangiectasia) and external controls (NBS quality assurance program, CDC) were included. A total of 5160 DBS were tested. Re-punch was needed in 77 samples (1.5%) due to insufficient β-actin (<700 copies/punch). Pre-term neonates (GA<37 weeks) and neonates with a BW<2500 g showed significantly lower TRECs and KRECs levels (p < 0.001). Due to repeat positive results five neonates were re-called (<0.1%): Fatal chromosomopathy (n = 1; TRECs 1/KRECs 4); extreme pre-maturity (n = 2; TRECs 0/KRECs 0 and TRECs 1/KRECs 20 copies/punch); neonates born to mothers receiving azathioprine during pregnancy (n = 2; TRECs 92/KRECs 1 and TRECs 154/KRECs 3 copies/punch). All internal and external controls were correctly identified. TRECS-KRECS-β-actin-Assay correctly identifies T- and B-cell lymphopenias. Pre-maturity and low BW is associated with lower TREC and KREC levels. Extreme pre-maturity and maternal immune suppressive therapy may be a cause for false positive results of TRECs and KRECs values, respectively. To reduce the rate of insufficient samples, DBS extraction and storage need to be improved.

Copy-Number Variation and False Positive Prenatal Aneuploidy Screening Results

Investigations of noninvasive prenatal screening for aneuploidy by analysis of circulating cell-free DNA (cfDNA) have shown high sensitivity and specificity in both high-risk and low-risk cohorts. However, the overall low incidence of aneuploidy limits the positive predictive value of these tests. Currently, the causes of false positive results are poorly understood. We investigated four pregnancies with discordant prenatal test results and found in two cases that maternal duplications on chromosome 18 were the likely cause of the discordant results. Modeling based on population-level copy-number variation supports the possibility that some false positive results of noninvasive prenatal screening may be attributable to large maternal copy-number variants. (Funded by the National Institutes of Health and others.)

The customer is always right, even when you are justifiably wrong.

Customer surveys are useful tools for understanding and improving a business. If performed well and interpreted in the appropriate context, they are also useful vehicles for the education of staff members and for the stimulation of positive corporate change. Whether we choose to acknowledge it or not, imaging is a service industry that provides a product. That product is our opinion and advice in the form of a written report. Although our training and the traditions of western medicine may lead us to believe otherwise, in imaging the client is generally the patient’s doctor rather than the patient. Through the process of referral, we are at least one step away from direct involvement in patient care, even though the information that we provide may be absolutely crucial to treatment choices and patient outcomes. Accordingly, a survey of the opinions of referring clinicians regarding imaging reports is, in essence, an assessment of customer satisfaction. The article by Karantanis et al. in the current issue of The Journal of Nuclear Medicine (1 )p rovides some interesting insights with respect to oncologic 18 FFDG PET/CT reporting. The authors surveyed 662 clinicians from See page 1925 a range of pertinent specialties, with the major groups being oncologists (36.1%) and surgeons (33.8%). There was representation from several continents, but most respondents were from Europe (47.3%) or North America (35.0%), and the vast majority (85.8%) of respondents were practicing in an academic environment. Because PET/CT systems have been widely available in academic centers in both of these regions for more than a decade, one can assume a reasonably high level of experience in both the users and the providers of PET/CT services. The specified aim of the survey was to understand the frequency and nature of errors in reporting, as perceived by the end user of the information provided. Overall, 59.3% of respondents estimated that rates of misinterpretation ranged from 5% to 20%. Although this range reflects the typical accuracy reported in individual series and meta-analyses of PET/CT across various malignancies, the upper end of this range may be higher than we, as providers, would like to imagine is the proportion of cases in which we are incorrect. Perhaps the most instructive finding of the survey was that a significantly greater proportion of respondents believed that the major source of errors in reporting of PET/CT studies related to overinterpretation (68.9%) rather than underinterpretation (8.7%). This finding may come as a surprise to many expert PET/CT interpreters, who may have expected the opposite. Since the days of stand-alone 18 F-FDG PET, multiple causes of falsepositive results have been recognized (2). The availability of the additional information provided by the CT component should fur

False-positive interferences of common urine drug screen immunoassays: a review.

Urine drug screen (UDS) immunoassays are a quick and inexpensive method for determining the presence of drugs of abuse. Many cross-reactivities exist with other analytes, potentially causing a false-positive result in an initial drug screen. Knowledge of these potential interferents is important in determining a course of action for patient care. We present an inclusive review of analytes causing false-positive interferences with drugs-of-abuse UDS immunoassays, which covers the literature from the year 2000 to present. English language articles were searched via the SciFinder platform with the strings 'false positive [drug] urine' yielding 173 articles. These articles were then carefully analyzed and condensed to 62 that included data on causes of false-positive results. The discussion is separated into six sections by drug class with a corresponding table of cross-reacting compounds for quick reference. False-positive results were described for amphetamines, opiates, benzodiazepines, cannabinoids, tricyclic antidepressants, phencyclidine, lysergic acid diethylamide and barbiturates. These false-positive results support the generally accepted practice that immunoassay positive results are considered presumptive until confirmed by a second independent chemical technique.

Pulmonary sequestration: a 131I whole body scintigraphy false-positive result

A 35-year-old woman affected by a well-differentiated papillary thyroid carcinoma was referred to our hospital to perform a (131)Iodine ((131)I) whole body scintigraphy for restaging purpose. The patient had been previously treated with total thyroidectomy and three subsequent doses of (131)I for the ablation of a remnant jugular tissue and a suspected metastatic focus at the superior left hemi-thorax. In spite of the previous treatments with (131)I, planar and tomographic images showed the persistence of an area of increased uptake at the superior left hemi-thorax. This finding prompted the surgical resection of the lesion. Histological examination of the surgical specimen showed the presence of a pulmonary tissue consistent with pulmonary sequestration. Even though rare, pulmonary sequestration should be included in the potential causes of false-positive results of radioiodine scans.