scholarly journals Performance of the sōna Aspergillus Galactomannan Lateral Flow Assay in a Cancer Patient Population

2021 ◽  
Author(s):  
Krupa Jani ◽  
Tracy McMillen ◽  
Sejal Morjaria ◽  
N. Esther Babady
Keyword(s):  
Cancer Patient ◽  
Bronchoalveolar Lavage ◽  
Cancer Patients ◽  
Medical Records ◽  
Patient Population ◽  
Clinical Performance ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Wide Range ◽  
Galactomannan Antigen

Background: The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sōna Aspergillus Galactomannan Lateral Flow Assay (GM LFA) was evaluated and its performance compared to that of the Bio-Rad Galactomannan EIA (GM EIA). Materials/methods: Serum and Bronchoalveolar lavage (BAL) fluids received for GM EIA testing between March-August 2019 were included. Positive and negative percent agreement (PPA and NPA) were calculated for the GM LFA compared to the GM EIA. Discrepant analysis was performed by review of the patient‘s medical records assessing for any evidence of a fungal infection. Results: 533 samples (85 BALs and 448 serums) from 379 patients were included in the study. The overall PPA and NPA were 100% (95% CI: 72.2-100%) and 97.5% (95% CI: 95.5-98.4%) respectively. 14/24 samples were positive by LFA only. The sensitivity of the GM LFA for proven and probable IA was 100% (95% CI: 51.0-100%) and 87.5% (95% CI: 55.9-99.4%) with a specificity of 95.5% (95% CI: 92.3-97.2%) and 96.2% (95% CI: 93.4-97.7%) respectively. The sensitivity of the GM EIA for proven and probable IA was 25% (95% CI: 1.28-69.9%) and 62.5% (95% CI: 30.6-86.3%) with a specificity of 98.2% (95% CI: 96.2-99.1%) and 99.2% (95% CI: 97.7-99.8%) respectively. Conclusions: The Aspergillus GM LFA outperformed the Aspergillus GM EIA for the detection of the galactomannan antigen in our patient population. The simplicity and rapid time to results makes the Aspergillus GM LFA easy to implement in a wide range of laboratory settings.

Diagnostic accuracy of theAspergillus-specific bronchoalveolar lavage lateral-flow assay in haematological malignancy patients

Mycoses ◽  
2015 ◽  
Vol 58 (8) ◽  
pp. 461-469 ◽  
Author(s):  
Juergen Prattes ◽  
Michaela Lackner ◽  
Susanne Eigl ◽  
Frederike Reischies ◽  
Reinhard B. Raggam ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Bronchoalveolar Lavage ◽  
Haematological Malignancy ◽  
Lateral Flow ◽  
Lateral Flow Assay

scholarly journals Identification of Prion Disease-Related Somatic Mutations in the Prion Protein Gene (PRNP) in Cancer Patients

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1480 ◽  
Author(s):  
Yong-Chan Kim ◽  
Sae-Young Won ◽  
Byung-Hoon Jeong
Keyword(s):  
Cancer Patient ◽  
Cancer Patients ◽  
Prion Protein ◽  
Patient Population ◽  
Somatic Mutations ◽  
Protein Gene ◽  
Prion Diseases ◽  
Prnp Gene ◽  
Prion Protein Gene ◽  
Total Cancer

Prion diseases are caused by misfolded prion protein (PrPSc) and are accompanied by spongiform vacuolation of brain lesions. Approximately three centuries have passed since prion diseases were first discovered around the world; however, the exact role of certain factors affecting the causative agent of prion diseases is still debatable. In recent studies, somatic mutations were assumed to be cause of several diseases. Thus, we postulated that genetically unstable cancer tissue may cause somatic mutations in the prion protein gene (PRNP), which could trigger the onset of prion diseases. To identify somatic mutations in the PRNP gene in cancer tissues, we analyzed somatic mutations in the PRNP gene in cancer patients using the Cancer Genome Atlas (TCGA) database. In addition, to evaluate whether the somatic mutations in the PRNP gene in cancer patients had a damaging effect, we performed in silico analysis using PolyPhen-2, PANTHER, PROVEAN, and AMYCO. We identified a total of 48 somatic mutations in the PRNP gene, including 8 somatic mutations that are known pathogenic mutations of prion diseases. We identified significantly different distributions among the types of cancer, the mutation counts, and the ages of diagnosis between the total cancer patient population and cancer patients carrying somatic mutations in the PRNP gene. Strikingly, although invasive breast carcinoma and glioblastoma accounted for a high percentage of the total cancer patient population (9.9% and 5.4%, respectively), somatic mutations in the PRNP gene have not been identified in these two cancer types. We suggested the possibility that somatic mutations of the PRNP gene in glioblastoma can be masked by a diagnosis of prion disease. In addition, we found four aggregation-prone somatic mutations, these being L125F, E146Q, R151C, and K204N. To the best of our knowledge, this is the first specific analysis of the somatic mutations in the PRNP gene in cancer patients.

scholarly journals Cancer Patient Perspectives on Sharing of Medical Records and Mobile Device Data for Research Purposes

2020 ◽  
Vol 7 (6) ◽  
pp. 1115-1121
Author(s):  
Elizabeth F Franklin ◽  
Helen M Nichols ◽  
Linda House ◽  
Joanne Buzaglo ◽  
Kim Thiboldeaux
Keyword(s):  
Cancer Patient ◽  
Cancer Patients ◽  
Medical Records ◽  
Health Care Services ◽  
Survey Methodology ◽  
Cross Sectional Study ◽  
Patient Perspectives ◽  
Cross Sectional ◽  
Care Services ◽  
Application Data

Sharing data is critical to advancing science, improving health, and creating advances in the delivery of health care services. The value of sharing data for cancer research purposes is well established, and there are multiple initiatives under way that address this need. However, there has been less focus on cancer patient perspectives regarding the sharing of their health information for research purposes. This study examined cancer patient perspectives on the sharing of de-identified health data for research purposes including both data from medical records and mobile applications. This cross-sectional study used survey methodology to collect data from cancer patients/survivors (N = 677). Overall, we found that participants were largely willing (71%) to share de-identified medical data and were most motivated (88%) by a desire to help other cancer patients. Patients were less likely to be comfortable sharing mobile application data (34%). It is vital that we understand patient perspectives on data sharing and work with them as partners, valuing their unique contributions, and attending to their preferences.

scholarly journals Engineered CRISPR/Cas12a Enables Rapid SARS-CoV-2 Detection

2020 ◽  
Author(s):  
Long T. Nguyen ◽  
Santosh R. Rananaware ◽  
Brianna L.M. Pizzano ◽  
Brandon T. Stone ◽  
Piyush K. Jain
Keyword(s):  
High Sensitivity ◽  
High Specificity ◽  
Single Copy ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Magnesium Concentration ◽  
Clinical Validation ◽  
Respiratory Pathogens ◽  
Reporter Assay ◽  
Wide Range

ABSTRACTThe coronavirus disease (COVID-19) caused by SARS-CoV-2 has swept through the globe at an unprecedented rate. CRISPR-based detection technologies such as DETECTR, SHERLOCK, and STOPCovid have emerged as a rapid and affordable platform that can shape the future of diagnostics. Recently, we reported engineered crRNAs for Cas12a, called ENHANCE, that enables enhanced detection of nucleic acids. Here we report development, clinical validation, and advancement of ENHANCE platform for detecting SARS-CoV-2. With an RT-LAMP pre-amplification step, ENHANCE detects samples down to a single copy with 95% accuracy and shows high specificity towards various isolates of SARS-CoV-2 against 31 highly similar and common respiratory pathogens. Utilizing LbCas12a-mediated trans-cleavage activity, ENHANCE works robustly in a wide range of magnesium concentration (3 mM-13 mM), allowing for further assay optimization. Additionally, ENHANCEv2 is developed to further improve the previously reported ENHANCE. ENHANCEv2 employs mutated LbCas12aD156R, engineered chimeric DNA-extended crRNA, and a dual reporter for both fluorescence-based reporter assay and lateral flow assay. Both ENHANCE and ENHANCEv2 are validated in 62 clinical nasopharyngeal swabs, showing 60/62 (96.7%) agreement with RT-qPCR results, and using only 5 μL of sample and 20 minutes of CRISPR reaction. Lateral flow assay on paper strips displays 100% agreement with fluorescence-based reporter assay in the clinical validation. Following a 30-minute pre-amplification RT-LAMP step, the lyophilized ENHANCEv2 is shown to achieve high sensitivity and specificity while reducing CRISPR reaction time to as low as 3 minutes and maintaining its detection capability upon storage at room temperature for several weeks.

Longitudinal investigation of Distress Thermometer scores in patients with cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24200-e24200
Author(s):  
Fauzia Ullah ◽  
Emily Brugioni ◽  
Matthew M Gannon ◽  
Hayden L Smith ◽  
Joshua Cole Lukenbill
Keyword(s):  
Cancer Patient ◽  
Cancer Patients ◽  
Patient Population ◽  
Large Scale ◽  
Well Being ◽  
Distress Thermometer ◽  
Average Score ◽  
Cancer Type ◽  
Initial Screening ◽  
Study Results

e24200 Background: The Distress Thermometer (DT) is a tool used to evaluate distress among cancer patients. The DT can provide information for intervention recommendations such as social work, psychological, and other ancillary services. The National Comprehensive Cancer Network (NCCN) recommends recurrent use of the tool. The DT is widely used as a standard of care for an initial screening of cancer patients, but data on subsequent use is lacking. The aim of this research was to evaluate repeat DT scores in a heterogeneous cancer patient population. Methods: Clinical investigators conducted a longitudinal study of DT ratings for cancer patients receiving outpatient care at a community-based oncology subspecialty practice in a mid-sized city from 2018 to 2019. Study objectives included reviewing referrals and evaluating the relationship between the initial screening and the screening at the 6-month checkup. The Distress Thermometer was used (i.e., 0-10; zero is “no distress” and ten “extreme distress”) with scores of four or greater regarded as a signal of greater risk for patient distress. Results: The study sample included 79 patients with an average score of 4.3 and 4.0 at baseline and the 6-month screening, respectively. Patient referrals included physical and emotional therapy (n=1) or social/psychosocial worker assessment (n=26). Patients with a documented referral had a crude 1.7 (95% CI: 0.6, 3.3) greater point decrease in scores compared to patients not offered a service referral. When adjusting for baseline scores and the time between scores, referral accounted for 1% (95% CI: 0%, 14%) of variability in score changes, while baseline scores accounted for 40% (95% CI: 22%, 52%) and time accounted for 3% (95% CI: 0%, 14%). Conclusions: Study results reveal a possible decrease in higher scores from the initial screening to the 6-month check-up. Patients with a referral did not have their service utilization confirmed and this study failed to show an additional decrease in scores based on referrals when controlling for baseline score and time. Most previous research has focused on one specific cancer type. This study revealed the possible importance in understanding DT scores in a heterogenous cancer patient population. Furthermore, large scale research is needed to confirm preliminary data and further expound on distress at initial and subsequent screenings after interventions. A better understanding of this content area may function to improve future care and patient well-being.

scholarly journals The Role of Direct Oral Anticoagulants in Treatment of Cancer-Associated Thrombosis

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 271 ◽  
Author(s):  
Hanny Al-Samkari ◽  
Jean Connors
Keyword(s):  
Cancer Patient ◽  
Cancer Patients ◽  
Patient Population ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Population Data ◽  
Standard Of Care ◽  
Published Data ◽  
Onset Of Action ◽  
Recurrent Vte

Venous thromboembolism (VTE) complicates the clinical course of approximately 5–10% of all cancer patients. Anticoagulation of the cancer patient often presents unique challenges as these patients have both a higher risk of recurrent VTE and a higher risk of bleeding than patients without cancer. Although low molecular weight heparins (LMWH) are the standard of care for the management of cancer-associated VTE, their use requires once or twice daily subcutaneous injections, which can be a significant burden for many cancer patients who often require a long duration of anticoagulation. The direct oral anticoagulants (DOACs) are attractive options for patients with malignancy. DOACs offer immediate onset of action and short half-lives, properties similar to LMWH, but the oral route of administration is a significant advantage. Given the higher risks of recurrent VTE and bleeding, there has been concern about the efficacy and safety of DOACs in this patient population. Data are now emerging for the use of DOACs in the cancer patient population from dedicated clinical trials. While recently published data suggest that DOACs hold promise for the treatment of cancer associated VTE, additional studies are needed to establish DOACs as the standard-of-care treatment. Many such studies are currently underway. The available data for the use of DOACs in the treatment of cancer-associated VTE will be reviewed, focusing on efficacy, safety, and other considerations relevant to the cancer patient.

scholarly journals 257. Aspergillus Galactomannan Lateral Flow Assay for Rapid Diagnosis of Invasive Aspergillosis in Bronchoalveolar Lavage

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S143-S143
Author(s):  
Martin Hoenigl ◽  
Sharon L Reed ◽  
Sanjay R Mehta ◽  
Nancy Law ◽  
Saima Aslam ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Hematological Malignancies ◽  
Invasive Pulmonary Aspergillosis ◽  
Rapid Test ◽  
Lavage Fluid ◽  
Rapid Diagnosis ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Lower Specificity ◽  
Neutropenic Patients

Abstract Background Early diagnosis and treatment of invasive pulmonary aspergillosis (IPA) remain the most important factor to reduce mortality. Diagnosis remains a challenge, however, due to unspecific clinical presentation and radiological findings. Only very recently rapid tests for IPA have been developed. The objective of this study was to evaluate the performance of the new CE-marked Aspergillus Galactomannan Lateral Flow Assay (LFA; IMMY, Oklahoma, USA; figure) for IPA in patients with and without hematological malignancies. Methods The Aspergillus Galactomannan LFA was retrospectively performed according to the manufacturer’s instructions in 106 previously frozen bronchoalveolar lavage fluid (BAL) samples from 106 patients at risk for IPA (23% with underlying hematological malignancies). Samples were collected between September 2016 and September 2018 at the University of California, San Diego. Performance of the LFA was compared with Galactomannan, BAL culture and the Aspergillus-specific LFD (another rapid test for IPA). IPA was classified according to revised EORTC/MSG criteria. Results Overall, 22 patients met criteria of probable or proven IPA, 9 possible IPA, while 75 patients did not fulfill criteria of IPA. Sensitivity of the Apergilllus Galactomanann LFA for probable/proven IPA was 77% (17/22). Sensitivity was similar to BAL GM (77% with a cutoff of 1.0 ODI), but higher compared with the Aspergillus-specific LFD (59%), and BAL culture (23%). The LFA resulted negative in 7/9 cases with possible IPA and 47/73 cases without IPA (overall specificity 66%, 54/82). The less than perfect specificity was driven particularly by non-neutropenic patients (specificity 62%, 43/69), while specificity was 85% among patients with underlying hematological malignancies. Lower specificity among non-neutropenic patients was also observed for the BAL GM (overall 77%, non-neutropenic patients 72%), the Aspergillus-specific LFD (overall 70%, non-neutropenic patients 67%) and BAL culture (overall 90%, non-neutropenic 88%). Conclusion Our study indicates that the LFA may be useful for rapid diagnosis of IPA in BALF when IPA is clinically suspected. The lower specificity in non-neutropenic patients may be explained by limited applicability of the EORTC/MSG criteria in those patients. Disclosures All authors: No reported disclosures.

scholarly journals Engineered CRISPR/Cas12a Enables Rapid SARS-CoV-2 Detection

2021 ◽  
Author(s):  
Long Nguyen ◽  
Santosh Rananaware ◽  
Brianna Pizzano ◽  
Brandon Stone ◽  
Piyush Jain
Keyword(s):  
High Sensitivity ◽  
High Specificity ◽  
Single Copy ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Magnesium Concentration ◽  
Clinical Validation ◽  
Respiratory Pathogens ◽  
Reporter Assay ◽  
Wide Range

Abstract The coronavirus disease (COVID-19) caused by SARS-CoV-2 has swept through the globe at an unprecedented rate. CRISPR-based detection technologies such as DETECTR, SHERLOCK, and others have emerged as a rapid and affordable platform that can shape the future of diagnostics. Recently, we reported engineered crRNAs for Cas12a, called ENHANCE, that enables enhanced detection of nucleic acids. Here we report development, clinical validation, and advancement of ENHANCE platform for detecting SARS-CoV-2. With an RT-LAMP pre-amplification step, ENHANCE detects samples down to a single copy with 95% accuracy and shows high specificity towards various isolates of SARS-CoV-2 against 31 highly similar and common respiratory pathogens. Utilizing LbCas12a-mediated trans-cleavage activity, ENHANCE works robustly in a wide range of magnesium concentration (3 mM-13 mM), allowing for further assay optimization. Additionally, ENHANCEv2 is developed to further improve the previously reported ENHANCE. ENHANCEv2 employs mutated LbCas12aD156R, engineered chimeric DNA-extended crRNA, and a dual reporter for both fluorescence-based reporter assay and lateral flow assay. Both ENHANCE and ENHANCEv2 are validated in 62 clinical nasopharyngeal swabs, showing 60/62 (96.7%) agreement with RT-qPCR results, and using only 5 µL of sample and 20 minutes of CRISPR reaction. Lateral flow assay on paper strips displays 100% agreement with fluorescence-based reporter assay in the clinical validation. Following a 30-minute pre-amplification RT-LAMP step, the lyophilized ENHANCEv2 is shown to achieve high sensitivity and specificity while reducing CRISPR reaction time to as low as 3 minutes and maintaining its detection capability upon storage at room temperature for several weeks.

scholarly journals Performance of the Bronchoalveolar Lavage Fluid Aspergillus Galactomannan Lateral Flow Assay With Cube Reader for Diagnosis of Invasive Pulmonary Aspergillosis: A Multicenter Cohort Study

2020 ◽  
Author(s):  
Jeffrey D Jenks ◽  
Juergen Prattes ◽  
Johanna Frank ◽  
Birgit Spiess ◽  
Sanjay R Mehta ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Multicenter Study ◽  
Diagnostic Performance ◽  
Bronchoalveolar Lavage Fluid ◽  
Invasive Pulmonary Aspergillosis ◽  
Rapid Test ◽  
Lavage Fluid ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
University Hospital

Abstract Background The Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with hematologic malignancies. An automated digital cube reader that allows for quantification of results has recently been added to the test kits. Methods We performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California, San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany. Results Cases were classified as proven (n = 2), probable (n = 56), putative (n = 30), possible (n = 45), and no IA (n = 162). The LFA showed an area under the curve (AUC) of 0.865 (95% confidence interval [CI] .815–.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cutoff of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 vs 0.893, respectively). LFA performance was consistent across different patient cohorts and centers. Conclusions In this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available.

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