Eric S. Bensadoun

Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay

ABSTRACT The second-generation MVista Blastomyces antigen enzyme immunoassay was not quantitative; therefore, specimens obtained previously were tested in the same assay as new specimens to assess the change in antigen levels. Furthermore, the sensitivity in serum had not been fully evaluated. The purpose of this study was to evaluate a quantitative Blastomyces antigen assay and detection of antigen in serum. Calibrators containing known concentrations of Blastomyces galactomannan were used to quantify antigen in urine and serum from patients with proven blastomycosis and from controls. Paired current and previously obtained urine specimens were tested to determine if quantification eliminated the need for concurrent testing to assess change in antigen. Pretreatment of serum with EDTA at 104°C was evaluated to determine if dissociation of immune complexes improved detection of antigenemia. Antigenuria was detected in 89.9% of patients with culture- or histopathology-proven blastomycosis. Specificity was 99.0% in patients with nonfungal infections and healthy subjects, but cross-reactions occurred in 95.6% of patients with histoplasmosis. Change in antigen level categorized as increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in ng/ml determined from different assays. Pretreatment increased the sensitivity of detection of antigenemia from 35.7% to 57.1%. Quantification eliminated the need for concurrent testing of current and previously obtained specimens for assessment of changes in antigen concentration. Pretreatment increased the sensitivity for detection of antigenemia. Differentiation of histoplasmosis and blastomycosis is not possible by antigen detection.

Detection of Blastomyces dermatitidis antigen in patients with newly diagnosed blastomycosis.

Blastomycosis is a serious and potentially fatal infection, and diagnosis can be difficult at times. We evaluated the diagnostic utility of a commercially available assay for detection of Blastomyces dermatitidis antigen, recently modified to permit quantitation, in subjects with newly diagnosed blastomycosis. Twenty-three of 27 (85.1%) subjects had detectable B. dermatitidis antigenuria. In 2 of these 23, positive results were obtained after concentration of the urine specimen. Nine of 11 (81.8%) subjects had detectable B. dermatitidis antigen in serum, including 3 subjects with negative results before treatment of serum with ethylenediaminetetraacetic acid (EDTA) and positive results after EDTA treatment. B. dermatitidis antigen was not detected in specimens from 50 control subjects but was detected in 15 patients with histoplasmosis. B. dermatitidis antigen was detected in most of the patients with blastomycosis and can be a useful tool for timely diagnosis.

PET imaging in patients with coal workers pneumoconiosis and suspected malignancy

Positron Emission Tomography (PET) with F-18-fluorodeoxyglucose is commonly used in the evaluation of lung nodules; however, there is limited data on the PET appearance of coal worker’s pneumoconiosis (CWP) and its utility for diagnosing lung malignancy in this setting. Six cases of CWP and suspected malignancy are reported. Each patient had at least one nodule >1 cm in diameter for a total of 19 nodules >1 cm. On PET imaging 18 of the 19 nodules were hypermetabolic and five of the six patients had at least one nodule that was PET positive. Based on pathologic data and clinical follow-up, none of the six patients had any evidence of malignancy. In this series, PET imaging was often positive in patents with CWP; however, all were false positives with standardized uptake value measurements in the range that are typically seen with malignant nodules. Due to its high rate of false positives, PET imaging seems to be of limited utility in diagnosing malignancy in patients with underlying coal worker’s pneumoconiosis.

A clinical-laboratory algorithm incorporating optical density value to predict heparin-induced thrombocytopenia

The diagnosis of heparin-induced thrombocytopenia (HIT) is complex and involves integrating both clinical and laboratory findings. Readily available diagnostic tests such as the heparin-dependant antibody assay (HDAA) lack desired specificity when utilised alone. A diagnostic algorithm incorporating the 4T pretest probability score, HDAA, and optical density (OD) value was implemented as a tool to assist in the diagnosis of HIT and with the decision to treat patients. Patients with a 4T score >3 and/or positive HDAA result with an OD ≥1 were considered positive. Utilisation of this algorithm was hypothesised to improve the identification of patients without SRA confirmed HIT and improve overall specificity compared to other diagnostic strategies. Retrospective chart review was conducted and included patients with a positive or equivocal HDAA result and a serotonin release assay result during a two-year period. Each patient was evaluated for the diagnosis of HIT using the algorithm. The specificity and sensitivity of the diagnostic algorithm to identify subjects with SRA confirmed HIT was evaluated. A total of 83 patients were identified for inclusion in the study. The diagnostic algorithm identified 22 patients for direct thrombin inhibitor (DTI) therapy. Nine of these patients were SRA positive. The sensitivity of the algorithm was 0.9 with a specificity of 0.822. The diagnostic algorithm was found to be both more specific and sensitive than other diagnostic strategies including the 4T score alone, HDAA alone, and the combination of the 4T score and HDAA results. This preliminary data suggest a diagnostic algorithm combining 4T score, HDAA, and OD value may be a tool to aid in the identification SRA positive patients for DTI therapy.

Increased disease activity in a patient with sarcoidosis after high dose interleukin 2 treatment for metastatic renal cancer

Sarcoidosis is a disease of unknown aetiology in which cytokines such as interleukin 2 (IL-2) are thought to play an important role. We present the case history of a 48 year old man with sarcoidosis who received treatment with high dose IL-2 for metastatic renal cell cancer, following which he developed hypercalcaemia characterised by a raised level of 1,25-dihydroxyvitamin D (1,25-(OH)2-D3), a finding consistent with sarcoidosis associated hypercalcaemia. The increased activity in his sarcoidosis following IL-2 treatment provides direct supportive evidence for the role of IL-2 in the pathogenesis of sarcoidosis.

Autoantibody Profiling for Lung Cancer Screening Longitudinal Retrospective Analysis of CT Screening Cohorts

Recommendations for lung cancer screening present a tangible opportunity to integrate predictive blood-based assays with radiographic imaging. This study compares performance of autoantibody markers from prior discovery in sample cohorts from two CT screening trials. One-hundred eighty non-cancer and 6 prevalence and 44 incidence cancer cases detected in the Mayo Lung Screening Trial were tested using a panel of six autoantibody markers to define a normal range and assign cutoff values for class prediction. A cutoff for minimal specificity and best achievable sensitivity were applied to 256 samples drawn annually for three years from 95 participants in the Kentucky Lung Screening Trial. Data revealed a discrepancy in quantile distribution between the two apparently comparable sample sets, which skewed the assay’s dynamic range towards specificity. This cutoff offered 43% specificity (102/237) in the control group and accurately classified 11/19 lung cancer samples (58%), which included 4/5 cancers at time of radiographic detection (80%), and 50% of occult cancers up to five years prior to diagnosis. An apparent ceiling in assay sensitivity is likely to limit the utility of this assay in a conventional screening paradigm. Pre-analytical bias introduced by sample age, handling or storage remains a practical concern during development, validation and implementation of autoantibody assays. This report does not draw conclusions about other logical applications for autoantibody profiling in lung cancer diagnosis and management, nor its potential when combined with other biomarkers that might improve overall predictive accuracy.

A mass in the right cardiophrenic angle.

Accessible online at: www.karger.com/res A 38-year-old male was seen in consultation for an abnormal chest radiograph. His only complaint had been tingling in his hands and some vague right-sided lower chest discomfort. He denied cough, shortness of breath, hemoptysis, weight loss or history of trauma. He was physically active and had no other medical problems. He had recently quit smoking, but had smoked 11⁄2 pack per day for 10 years. As part of his evaluation he had a chest x-ray, which was abnormal and prompted the consultation. On examination his vital signs were normal and the remainder of the physical exam was unremarkable. Laboratory tests including a CBC and chemistry panel were normal. His chest x-ray (fig. 1) showed a large mass in the area of the right cardiophrenic angle. A CT scan of the chest was performed (fig. 2). What is your diagnosis?

Vitamin C in Sepsis: When It Seems Too Sweet, It Might (Literally) Be

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Eosinophilia and Fever with Levetiracetam: A Case Report

Levetiracetam is considered by many clinicians to be one of the most benign antiepileptic medications available. We report the case of a 24‐year‐old man presenting with seizures for which he was started on levetiracetam. Despite an extensive work‐up and treatment of possible infectious and noninfectious issues, the patient remained intermittently febrile. When a marked peripheral eosinophilia was noted, the patients levetiracetam was discontinued and phenytoin prescribed. The fever resolved within 24 hours, and the patients eosinophilia count returned to normal limits following discharge back to his long‐term care facility. We estimate the probability of this reaction related to levetiracetam as probable based on a score of 7 on the Naranjo scale. Clinicians should be aware of the possibility that levetiracetam may be an offending agent in a patient with unexplained fever and eosinophilia. These may be early signs of the progression to a more serious drug hypersensitivity reaction, such as drug rash, eosinophilia, and systemic symptoms (DRESS) syndrome.

New-onset dyspnea and right heart failure.

tient’s hypoxemia worsened and he was transferred to the intensive care unit. A pulmonary artery catheter was inserted which revealed a pulmonary artery pressure of 64/24 mm Hg, a pulmonary capillary wedge pressure of 8 mm Hg, and a cardiac index of 3.7 l/min/m 2 . What is your diagnosis? A 65-year-old male was admitted to hospital with nausea, vomiting and dehydration. He had been diagnosed 6 months earlier with adenocarcinoma of the prostate (Gleason grade 3 + 4) and had completed a course of pelvic radiation 6 weeks prior to admission. He also had a history of rheumatoid arthritis treated with methotrexate, which had been stopped 2 weeks prior to admission due to pancytopenia and elevated liver enzymes. Upon examination, his vital signs were normal and his physical exam was unremarkable. His laboratory data on admission revealed a hemoglobin of 11.2 g/dl and a platelet count of 90,000. Serum electrolyes, glucose, blood urea nitrogen and creatinine were normal. The electrocardiogram was normal and a chest X-ray was unremarkable. During his admission, his hematocrit and platelet continued to drop and he was noted to have evidence of hemolysis on his peripheral blood smear with an elevated serum LDH of 12,000 U/l. A presumptive diagnosis of thrombotic thrombocytopenic purpura was made and plasmapheresis was started. After 2 days of plasmapheresis, the platelet count had stabilized; however, the patient began to complain of dyspnea and his oxygen saturation was noted to be 85% on room air. A CT angiogram of the chest (see fig. 1 ) was performed and was negative for pulmonary embolism. An echocardiogram revealed right ventricular enlargement with decreased right ventricular systolic function with an estimated right ventricular systolic pressure of 74 mm Hg. Two months earlier, the patient had an echocardiogram that was normal. The paReceived: August 3, 2013 Accepted after revision: August 23, 2013 Published online: December 11, 2013