scholarly journals Cart before the horse: use of Aspergillus PCR to increase the diagnostic yield from BAL in hematological patients at risk of invasive aspergillosis

2017 ◽  
Vol 58 (12) ◽  
pp. 2773-2776 ◽  
Author(s):  
Olivia Catherine Smibert ◽  
Monica A. Slavin
Keyword(s):  
At Risk ◽  
Invasive Aspergillosis ◽  
Diagnostic Yield ◽  
Hematological Patients ◽  
Patients At Risk

scholarly journals Autopsy-Controlled Prospective Evaluation of Serial Screening for Circulating Galactomannan by a Sandwich Enzyme-Linked Immunosorbent Assay for Hematological Patients at Risk for Invasive Aspergillosis

1999 ◽  
Vol 37 (10) ◽  
pp. 3223-3228 ◽  
Author(s):  
Johan Maertens ◽  
Jan Verhaegen ◽  
Hilde Demuynck ◽  
Penelope Brock ◽  
Gregor Verhoef ◽  
...  
Keyword(s):  
At Risk ◽  
Invasive Aspergillosis ◽  
Immunosorbent Assay ◽  
Predictive Value ◽  
Sandwich Elisa ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Hematological Patients ◽  
Increased Risk ◽  
Patients At Risk

Efforts to improve the diagnosis of invasive aspergillosis (IA) have been directed towards the detection of fungal antigens, including galactomannan (GM). However, previous evaluations of GM detection have been hampered by a lack of proven cases of IA and by a nonserial study design. This prospective study assessed the diagnostic value of serial screening for circulating GM by using a recently developed sandwich enzyme-linked immunosorbent assay (ELISA) for prolonged-neutropenic and/or steroid-treated patients with hematological disorders. Serum GM levels were monitored twice weekly for 186 consecutive patients at increased risk for IA. The patients were stratified according to the likelihood of IA (proven, probable, possible, and no evidence of IA) by using stringent criteria. Proven IA was defined by characteristic histopathological findings together with a positive culture forAspergillus species. Autopsy and culture from autopsy specimens was used to verify both positive and negative test results. A total of 2,172 serum samples were tested from 243 episodes (mean, 9 samples/episode). Based on the analysis of 71 patients with confirmed disease status (culture and histology), the sensitivity and specificity of serial GM monitoring were 92.6 and 95.4%, respectively. The positive predictive value was almost 93%, the negative predictive value was 95%, and the efficacy was 94%. False-positive reactions occurred at a rate of nearly 8%, although this figure might have been overestimated. Less than 1% of all tested sera were considered inconclusive. In more than half of the cases, antigenemia was detected before clinical suspicion of IA (median, 6 days before). Serial determination of serum GM by the sandwich ELISA technique is a sensitive tool for the diagnosis of IA in hematological patients at risk. This approach may substantially influence clinical management with regard to preemptive and empirical antifungal therapy.

Benefits and safety of multigene panel testing in patients at risk for hereditary breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 16-16
Author(s):  
Nimmi S. Kapoor ◽  
Lisa D. Curcio ◽  
Carlee A. Blakemore ◽  
Amy K. Bremner ◽  
Rachel E. McFarland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Genetic Testing ◽  
Hereditary Breast Cancer ◽  
Diagnostic Yield ◽  
Gene Panel ◽  
Panel Testing ◽  
Gene Testing ◽  
Gene Panel Testing ◽  
Patients At Risk

16 Background: Recently introduced multi-gene panel testing including BRCA1 and BRCA2 genes (BRCA1/2) for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study is to evaluate rates of pathogenic BRCA1/2mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multi-gene testing. Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2testing only (limited group, n = 629) to those who underwent multi-gene testing with 5-43 cancer-related genes (panel group, n = 337). Results: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0% vs 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5% vs 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9% (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified. Conclusions: Multi-gene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly due to non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from upfront, more efficient, multi-gene panel testing.

scholarly journals Aspergillus fumigatus Antigen Detection in Sera from Patients at Risk for Invasive Aspergillosis

2000 ◽  
Vol 38 (1) ◽  
pp. 438-443
Author(s):  
Bernabé F. F. Chumpitazi ◽  
Claudine Pinel ◽  
Bernadette Lebeau ◽  
Pierre Ambroise-Thomas ◽  
Renee Grillot
Keyword(s):  
At Risk ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Polyclonal Antibodies ◽  
Latex Agglutination ◽  
Control Group ◽  
Molecular Weights ◽  
Circulating Antigens ◽  
Patients At Risk ◽  
Sensitivity Specificity

ABSTRACT We have developed an inhibition enzyme immunoassay (inhibition-EIA) to monitor for the occurrence of invasive aspergillosis (IA) in sera from 45 immunocompromised (IC) patients. The test uses rabbit polyclonal antibodies and a mixture of components from Aspergillus fumigatus , containing three predominant antigens with molecular weights of 18,000, 33,000, and 56,000. Circulating antigens were found in five of seven proven cases of IA due to A. fumigatus . In two of the five positive cases, antigenemia was detected with inhibition-EIA earlier than with X ray or other biological methods. No antigens were detected in the sera from two patients with proven IA due to Aspergillus flavus and Aspergillus terreus nor in the sera from four patients with probable IA. Circulating antigens were not detected in the control group, composed of 30 healthy adult blood donors. Four of the 32 at-risk patients examined, though they displayed no definite evidence of IA, gave a positive result in this test. The sensitivity, specificity, and positive predictive value of inhibition-EIA were 71.4, 94.4, and 71.2%, respectively. The data were compared with those obtained by a latex agglutination assay of galactomannan (GM) that was positive in only one patient with probable IA. The higher sensitivity obtained by inhibition-EIA may well be due to its ability to detect circulating antigens other than GM in the sera of IC patients with IA. Detecting these antigens may improve the diagnosis of IA, as they may serve as markers of this infection.

Validation of Serum Aspergillus Galactomannan Index as a Surrogate Endpoint for Outcome of Invasive Aspergillosis: Clinical and Research Implications.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2861-2861 ◽  
Author(s):  
Gail Woods ◽  
Marisa Miceli ◽  
Monica Grazziutti ◽  
Somashekar Krishna ◽  
Nayyar Syed ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Outcome ◽  
Invasive Aspergillosis ◽  
Composite Endpoint ◽  
Surrogate Endpoint ◽  
Laboratory Findings ◽  
Hematological Cancer ◽  
Non Invasive ◽  
Patients At Risk ◽  
Neutropenic Patients

Abstract Background: Assessing clinical outcome of aspergillosis with conventional clinical and laboratory criteria is difficult. A composite “global outcome response” (clinical, radiologic, pathologic and microbiologic criteria) is frequently used but suffers from poor sensitivity and specificity, and has not been standardized or validated. A reliable, quantitative, non-invasive, and easy to measure laboratory test than can substitute for this composite endpoint, i.e. serve as a surrogate endpoint for aspergillosis outcome is highly desirable. Galactomannan (GM) is an Aspergillus-specific polysaccharide released during aspergillosis and detected by the serum GM test. The test which is reported as an index of optical density (OD) is an accepted diagnostic marker for aspergillosis and preliminary data suggest a correlation between GM index (GMI) and outcome. Purpose: To evaluate serum GMI as a surrogate endpoint for outcome of invasive aspergillosis in patients with hematological cancer. Patients and Methods: patients at risk for aspergillosis (11/03-2/06) underwent GMI screening during periods at risk. The clinical and laboratory findings of patients with ≥ 2 (+) GMI (OD ≥ 0.5) were reviewed. To validate GMI as a surrogate endpoint for aspergillosis, a k correlation concordance coefficient test between GMI and an objective clinical outcome of aspergillosis (death) was applied. The correlation is considered perfect when k is 1.0; excellent when ≥ 0.75. Results: 30 patients had GMI (+) aspergillosis of the respiratory tract [myeloma 92%; median age: 59 years (27–75); 15 males]. Aspergillosis developed following stem cell transplantation [autologous (11), allogeneic (1)], or after conventional chemotherapy (18). Among 25 neutropenic patients (<1000/ml), persistent GMI elevation was associated with death (5/5 patients) while return to negative values predicted survival (20/20 patients). Among 5 non-neutropenic patients, 1 with persistently elevated GMI died compared to no death among the remaining 4 whose GMI became negative. Overall, the GMI correlated with clinical outcome in all 30 patients with a perfect 1.0 k correlation concordance coefficient. Conclusion: we have validated GMI as an excellent surrogate endpoint for the outcome of invasive aspergillosis among patients with hematological cancer. This FDA-approved test is reproducible, quantitative, non-invasive, easy to measure and widely available. These findings have important implications for patient care and for the design of clinical trials of mould-active antifungal agents.

scholarly journals Invasive Aspergillosis as an Under-recognized Superinfection in COVID-19

2020 ◽  
Vol 7 (7) ◽  
Author(s):  
George R Thompson III ◽  
Oliver A Cornely ◽  
Peter G Pappas ◽  
Thomas F Patterson ◽  
Martin Hoenigl ◽  
...  
Keyword(s):  
At Risk ◽  
Invasive Aspergillosis ◽  
Viral Infections ◽  
Pulmonary Aspergillosis ◽  
Large Numbers ◽  
Patients At Risk ◽  
Respiratory Viral Infections

Pulmonary aspergillosis has been increasingly reported following severe respiratory viral infections. Millions have been infected by SARS-CoV-2, placing large numbers of patients at-risk for COVID-19 associated pulmonary aspergillosis (CAPA). Prompt recognition of this syndrome and is paramount to improve outcomes.

70 Early diagnostic yield of mycobacterial testing in patients at risk of lung cancer

Lung Cancer ◽  
2014 ◽  
Vol 83 ◽  
pp. S26
Author(s):  
C. O'Connell ◽  
A. Parnell ◽  
M. Hannan ◽  
B. Keogh ◽  
D.S. O'Callaghan
Keyword(s):  
Lung Cancer ◽  
At Risk ◽  
Diagnostic Yield ◽  
Patients At Risk ◽  
Early Diagnostic
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