bluuebunny/crossref_metadata_2025 huggingface dataset:
Attention-based generative adversarial networks improve prognostic outcome prediction of cancer from multimodal data
Authors: Shi Mingguang , Li Xuefeng , Li Mingna , Si Yichong
Published: September 2023

The prediction of prognostic outcome is critical for the development of efficient cancer therapeutics and potential personalized medicine. However, due to the heterogeneity and diversity of multimodal data of cancer, data integration and feature selection remain a challenge for prognostic outcome prediction. We proposed a deep learning method with generative adversarial network based on sequential channel-spatial attention modules (CSAM-GAN), a multimodal data integration and feature selection approach, for accomplishing prognostic stratification tasks in cancer. Sequential channel-spatial attention modules equipped with an encoder–decoder are applied for the input features of multimodal data to accurately refine selected features. A discriminator network was proposed to make the generator and discriminator learning in an adversarial way to accurately describe the complex heterogeneous information of multiple modal data. We conducted extensive experiments with various feature selection and classification methods and confirmed that the CSAM-GAN via the multilayer deep neural network (DNN) classifier outperformed these baseline methods on two different multimodal data sets with miRNA expression, mRNA expression and histopathological image data: lower-grade glioma and kidney renal clear cell carcinoma. The CSAM-GAN via the multilayer DNN classifier bridges the gap between heterogenous multimodal data and prognostic outcome prediction.
Bridging the gaps: management of lichen planus subtypes in a joint dermatology–oral surgery clinic
Authors: Pawlowski Johannes , Beczinski Janina , Stege Henner , Mann Caroline , Butsch Florian , Al-Nawas Bilal , Kaya Sebahat , Wittmann Miriam
Published: September 2023

Lichen planus (LP) presents with a range of clinical subtypes. It can affect the outer skin, involve the nails and present with alopecia and mucosal symptoms to varying degrees. LP of the outer skin mostly shows a self-limiting course; however, this is not the case for lichen planopilaris and the mucosa-affecting subtypes. The pathogenesis of LP is still incompletely understood. As a result, an effective, targeted therapy is currently lacking and different immunomodulatory approaches are being used in clinical practice. The management of patients with severe oral LP mucosae can be particularly challenging. Although the true risk remains controversial, oral LP is considered a risk factor for the development of squamous cell carcinoma and there is a need for regular screening. The quality of life in patients with LP is significantly impaired because of frequent clinical visits, pain, soreness, inability to eat certain foods, side effects to medication, frustrating therapy attempts and worry regarding cancer risk. We highlight here the advantages of an interdisciplinary dermatology and oral surgery clinic, which can address the domains of tooth status, nutrition, pain and malignant transformation and optimized patient management.
A-016 Clinical Performance Comparison Between the Vitros Immunodiagnostic Products NT-proBNP II and Roche Elecsys proBNP II Assays to Aid in the Diagnosis of Heart Failure
Authors: Ott-Vasconi A , Ajongwen P , Alvey S , Herman J
Published: September 2023

Background

The International Collaborative of NT-proBNP (ICON) study established NT-proBNP levels for the diagnosis and exclusion of acute heart failure for patients presenting to the emergency department (ED). Following the development of the Vitros Immunodiagnostic Products NT-proBNP II assay, a multi-center prospective study was conducted at 20 EDs across the United States. The study enrolled subjects presenting with dyspnea and clinical suspicion of heart failure (HF). Clinical performance of the Vitros Immunodiagnostic Products NT-proBNP II assay using the cutoffs established in the ICON study was compared to that of the Roche Elecsys proBNP II assay using samples from the multi-center study.

Methods

Clinical sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were determined by comparing the assay result interpretation using the corresponding cutoffs against the adjudicated diagnosis of HF/non-HF. Clinical performances were then compared between the VITROS NT-proBNP II and the Roche Elecsys proBNP II assays. Analyses were performed using both the age-independent and age-dependent cutoffs within and across age groups.

Results

After applying the rule-in cutoffs from the ICON study to the Vitros NTproBNP II and the Roche Elecsys proBNP II assay results, the clinical performance of the Vitros NT-proBNP II assay was comparable to that of the Roche Elecsys proBNP II assay (see Table 1).

Conclusion

The use of the ICON cutoffs resulted in high assay specificity to rulein HF and excellent sensitivity to ruleout HF. The Vitros NT-proBNP II assay demonstrated comparable clinical performance to the Roche Elecsys proBNP II assay.
A-018 Biological Variation Estimates for N-terminal pro-B-type Natriuretic Peptide from Eight Healthy Turkish Women
Authors: Coşkun A , Abou-Diwan C , Rhea-McManus J , Serteser M , Unsal I , Locatelli M , Carobene A
Published: September 2023

Background

B-type natriuretic peptide (BNP) and its precursor N-terminal pro-B-type natriuretic peptide (NT-proBNP) are released primarily by the ventricles in the heart in response to volume or pressure overload. Measurements of NT-proBNP are used as an aid in the diagnosis and assessment of severity of congestive heart failure (CHF). Within- (CVI) and between-subject (CVG) biological variation (BV) estimates for NT-proBNP are limited. Here biological variability (BV) estimates from eight apparently healthy Turkish women for NT-proBNP are provided.

Methods

Serum samples were collected weekly from 24 healthy subjects (12 male, 12 female) for 10 consecutive weeks and stored at −80 °C prior to analysis. Study participant samples were analyzed in duplicate within a single run using the Atellica® IM NT-proBNP (PBNP) assay* on the Atellica IM Analyzer. Outlier detection, variance homogeneity analyses, and trend analysis were performed followed by CV-ANOVA to determine BV and analytical variation (CVA) estimates with 95% CI. The asymmetrical reference change values (RCV) using the lognormal approach, index of individuality (II), and analytical performance specification (APS), based on the CVA estimate derived in our study, were also calculated.

Results

PBNP results from 11 males and 3 females were lower than the limit of quantitation (LoQ) of the assay (<35 pg/mL). The remaining male sample was not included in the analysis. One female sample was identified as an outlier between individuals and was excluded from the analysis. To fulfil criteria for variance homogeneity of the data from eight women, 7% of results were excluded. In total, 104 analytical results were included in the analysis. PBNP data for the female group was normally distributed, and no trends were identified by regression analysis. The BV estimates derived from females were CVI: 23.7%, (95% CI 19.0–30.4) and CVG: 8.22%, (95% CI 0.0–24.7). The CVA obtained from replicate test results was 11.2% (95% CI 9.4–13.9), which was lower than the desirable APS for imprecision. The II, calculated as the ratio of CVI/CVG, indicated a low individuality of PBNP (defined as II > 1.6). Thus, use of a population-based reference interval for interpreting serial PBNP measurements is more appropriate than use of the RCV.

Conclusions

This study provides updated BV estimates for NT-proBNP derived from a protocol consistent with European Federation of Clinical Chemistry and Laboratory Medicine recommendations. The availability of BV estimates allows for refined APS and associated II and RCV, which are applicable when using PBNP as an aid in the diagnosis and assessment of severity of congestive heart failure.

*The products/features mentioned here are not commercially available in all countries. Their future availability cannot be guaranteed.
A-069 Atellica® Ci 1900 Sample Carryover Performance Evaluation
Authors: Pham T , Kolewe K , Ho M , Lewisch S , Snyder J
Published: September 2023

Background

The Atellica® CI 1900 Analyzer uses independent integration and random-access sampling to process chemistry (CH) and immunoassay (IM) tests. A single-use, disposable sample tip is used for IM assays, whereas a reusable dilution probe is used for CH assays. When a sample tube is first accessed by the CH dilution probe to process CH assays, then accessed by the IM disposable tip to process IM assays, there is the potential for sample carryover that could affect IM assay results. The purpose of this investigation was to evaluate sample-to-sample carryover performance on the Atellica® CI 1900 Analyzer.

Methods

Hepatitis B surface antigen (HBsAg) was selected as the test analyte, given the extreme HBsAg concentrations that can exist in clinical samples. High HBsAg pools ranging from 25 to 55 million Index values were prepared by spiking purified HBsAg into serum. Eleven low (L) samples containing 600 µL of HBsAg-negative control QC and 10 high (H) samples containing 300 µL of the high HBsAg serum pool were created. The samples were first processed with one replicate per sample with the Atellica® CH ALT assay on the Atellica® CI 1900 Analyzer so that the CH dilution probe would aspirate 50 µL of sample. Sample-to-sample carryover testing was performed in a defined high (H)- and low (L)-sample consecutive sequence: L1, L2, L3, H1, H2, L4, H3, H4, L5, L6, L7, L8, H5, H6, L9, H7, H8, L10, H9, H10, L11. All low (L) samples were next assayed for HBsAg using the Atellica® CI 1900 Analyzer. The sample carryover study was conducted on three Atellica® CI 1900 Analyzers. Carryover in parts per million (ppm) was determined by multiplying the difference of the “high-low” mean (L4, L5, L9, L10, L11) and “low-low” mean (L2, L3, L6, L7, L8) by 1 000 000 and dividing by the high HBsAg sample concentration.

Results

The measured sample carryover results were 0.00, 0.00, and 0.00 ppm. All three Atellica® CI 1900 Analyzers produced sample-to-sample carryover of <0.1 ppm using HBsAg as the analyte.

Conclusions

The Atellica® CI 1900 Analyzer* demonstrated the capability to ensure sample-to-sample carryover of <0.1 ppm into primary sample containers with a minimum of 600 µL sample volume.

*Not available for sale in the US. Product availability varies by country.
A-078 Accuracy Based Sigma Metrics of Alinity c System as Benchmarked against Roche c701
Authors: Cheng L , Guan Q , Li H , Miao J , Sun P , Chen C
Published: September 2023

Background

Assay performance is dependent on the accuracy and precision of a given method. Sigma metric is a well-established tool for objectively assessing such performances. The objective of the study is to evaluate the Alinity c system using a representative set of clinical chemistry assays in an independent central laboratory setting. The analytical performance of the Alinity c assays was compared with the Roche c701 assays using accuracy-based Sigma metrics.

Methods

Analytical performance of 7 clinical chemistry assays, including sodium, potassium, chloride (Integrated Chip Technology or ICT), Glucose, ALT, AST and creatine kinase (CK), was assessed on the Alinity c System as benchmarked against the Roche c701. The accuracy of the assays was evaluated by testing reference standard materials sourced from Reference Material Institute for Clinical Chemistry Standards (ReCCS)) in Japan or National Institute of Standards and Technology (NIST) in America. The 5-day precision evaluation per CLSI EP15-A3 was performed using the Bio-Rad Lyphochek® Assayed Chemistry Control and two patient sample pools. Linearity was assessed using 9 levels of patient sample pools covering the measuring interval of each assay. Method comparison with Roche c701 assays was performed per CLSI EP9-A3 using 60 patient samples spanning the measurement range. Sigma metrics for each assay were determined relative to the total allowable errors according to the Clinical Laboratory Improvement Amendments (CLIA) specifications.

Results

Within-lab (total) imprecision for the 7 assays on Alinity c and Roche were all <3.5% CV for both the Bio-Rad Control and patient pools. Alinity c assays showed a better precision performance in all of assays tested. Bias of the 7 assays in reference to the assigned values was all below 7.5% for both platforms. Alinity c exhibited a good correlation with Roche c701 on all 7 assays in the method comparison evaluation. Linearity of the Alinity c assays was validated for the measuring intervals as claimed by the manufacturer. Majority of the assays on both analzyers demonstrated at least 6 sigma performance with Alinity c showing better sigma scores.

Conclusion

The Alinity c System demonstrated excellent accuracy, precision and linearity in an evaluation of 7 clinical chemistry assays. A majority of the assays demonstrated at least 6 sigma performance, supporting the fitness for clinical use.
A-096 Novel Gastrointestinal Testing: Comparative Performance of the ALPCO Five-Plex Gastrointestinal Marker Assay compared to Conventional ELISA/CLIA testing for Human Stool Samples
Authors: Cacicedo J M , Papkov S , Petzke J , Schmidt W , Vedrani H , Veenstra K , Wisherd C
Published: September 2023

Background

All modern gastrointestinal (GI) testing laboratories face a similar challenge: How to test a panel of analytes from the same stool or plasma/serum sample and deliver clinically accurate results in a timely fashion. GI analytes are tested primarily on ELISAs that while accurate, manual ELISA testing is time-consuming and work intensive. In this study, we utilize the automated ALPCO five-plex assay (AutoPlex™) to measure five key GI biomarkers: Calprotectin (CP), Pancreatic Elastase (PE), Lactoferrin (LF), Eosinophil derived neurotoxin (EDN), and Hemoglobin (Hgb). These biomarkers are widely recognized indicators of gut inflammation and disease, including inflammatory bowel disease, pancreatic insufficiency, and colorectal cancer. The assay employs a simple and efficient sample preparation protocol and utilizes multiplexed bead-based technology to quantify each biomarker at the same dilution and time point in an automated fashion. In this study, we determine how this new assay performs against gold standard ELISA/CLIAs that measure the same analytes.

Methods

Capture and detector antibodies were optimized for each of the analytes to perform on beads, and buffers were optimized to allow for all the analytes to be measured simultaneously. A stool extraction device was utilized to extract 386 human stool samples from both healthy controls and populations with suspected GI impairment. Samples were analyzed using the ALPCO 5-Plex (AutoPlex) assay run on the Multiplier® - a fully-automated chemiluminescence analyzer (DYNEX® Technologies, Chantilly, VA), and conventional Chemiluminescence ELISA/CLIA methods.

Results

Comparative analysis of 386 human stool samples run on both the 5-Plex and ELISAs for each respective analyte, showed strong clinical correlation between the two platforms. With a clinical cut-off of 50 ug/g calprotectin had a 91% clinical correlation between the two platforms. Similarly, with a cut-off of 200 µg/g PE was at 91%, LF with a cut-off of 7.24 µg/g at 83%, EDN with a cut-off of 4.6 was at 97%, and Hgb with a cut-off of 20 µg/g was at 98% clinical correlation between the two platforms.

Conclusions

The results generated by ALPCO five-plex assay demonstrated on average >90% clinical matching for all 5 GI analytes tested when compared to their gold standard ELISA/CLIA counterparts. Since this assay allows for the simultaneous measurement of five common GI analytes that occur from a single stool extract in one concurrent and automated workflow, this saves time as it eliminates the need for multiple ELISA/CLIA tests and reduces processing time for stool samples.
A-097 Stability Study of 21 Common Plasma Biochemistries in Unspun Whole Blood
Authors: Ospina Romero M , Robakowski T , Nelson A , Grant K , Jin Z , Galior K
Published: September 2023

Background

Most blood collection tube manufacturers typically recommend separating serum/plasma from red blood cells within 2 h of collection prior to biochemical analysis to minimize cell contact and thus maintain stability of analytes. This can lead to rejected testing when uncentrifuged samples are transported from ambulatory sites to core laboratories over long distances, leading to delayed patient care and decreased patient satisfaction from having to be redrawn. Few studies are available to make recommendations of specimen acceptance with delayed centrifugation time. Our study aimed to assess whole blood stability of routinely ordered chemistry tests.

Methods

Between November 30–December 1, 2022, venous blood from 20 non-fasting healthy adults(30% male) with ages ranging from 23 to 57 years were collected into 3-mL plastic Becton Dickinson(BD) Vacutainer™plasma separated tubes(PST). For each person, 6 PST were collected. One whole blood sample was centrifuged immediately(T0) at 4000g for 3 min at room temperature(RT) and analyzed. Remaining 5 whole blood samples were stored at either RT or 4 °C and the subsequent centrifugation of the samples occurred at 2, 4, 6, 12 and 24 h after collection. The analytes studied using Abbott Alinity instrumentation were comprehensive metabolic panel(CMP), lipid panel, TSH and FT4. Absolute and percent bias at various time points for each participant were calculated using the reference sample(T0). Observed biases were compared to allowable total error based on desirable biological variation(BV) from European-Federation-of-Laboratory-Medicine(EFLM) database and Clinical-Laboratory-Improvement-Amendments(CLIA) 2024 upcoming limits.

Results

Analytes stable in the whole blood at both RT and 4 °C up to 24 h based on EFLM-BV and CLIA were ALP, ALT, AST, BUN, cholesterol, creatinine, HDL, total bilirubin, triglycerides, and TSH. Analytes with variable stability times are shown in the table below:

Conclusion

This study provides a guideline of acceptable times for whole blood samples sent for routine chemistry tests when centrifugation was not performed within 2 h from collection.
A-128 Analytical Performance Evaluation of Assays Used for Iron Studies on the Atellica® CI 1900 Analyzer
Authors: Freeman J , Kolewe K , Singh S , Valdivia B , Varhue W , Arrode-Bruses G , Rhea-McManus J , Snyder J , Leipold H
Published: September 2023

Background

The Atellica® CI 1900 Analyzer is an automated, mid-throughput, integrated chemistry and immunoassay analyzer employing both Atellica CH and Atellica IM assays. This study was designed to evaluate the analytical performance of the Atellica CH Iron_2 (Iron_2), Total Iron Binding Capacity (TIBC), and Transferrin (Trf) assays* and the Atellica IM Ferritin (Fer) assay on the Atellica CI 1900 Analyzer.

Methods

The Atellica CI 1900 Iron_2, TIBC, and Trf assays use the same reagents and calibrators as the comparable Atellica chemistry assays. The Atellica CI 1900 Fer assay uses the same reagents and calibrators as the Atellica immunoassay. Precision and method comparison (MC) were used as performance indicators for the Atellica CI 1900 Analyzer. Precision studies were performed according to CLSI EP05-A3 using native and contrived human serum samples. MC studies were performed according to CLSI EP09-A3. Native and contrived human samples were analyzed using the Atellica CH Iron_2, TIBC, and Trf assays on both the Atellica® CH 930 and Atellica CI 1900 Analyzers. For Fer, native and contrived human samples were analyzed using the Atellica IM Fer assay on both the Atellica® IM 1600 and Atellica CI 1900 Analyzers.

Results

Representative precision and MC results for each assay are listed in the table. For the four assays tested, repeatability and within-lab %CVs were <3.5% and <4.5%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusion

Evaluation of the Atellica CH Iron_2, TIBC, and Trf and Atellica IM Fer assays using the Atellica CI 1900 Analyzer demonstrated good precision and equivalent performance compared to the same assays on their respective Atellica CH 930 and Atellica IM 1600 Analyzers.

*The products mentioned are not commercially available in all countries. Their future availability cannot be guaranteed.
A-134 Correlation Study of Haematology Analyser Sysmex XS 1000 vs Beckman DXH 520
Authors: Teng J
Published: September 2023

Background

An evaluation was conducted on 2 different haematology analysers to determine its result correlation. Both Sysmex XS1000i and Beckman DXH 520 are 5 part differential count analysers.

Methods

The evaluation was conducted on Sysmex XS 1000 and 2 units of Beckman DXH 520 at NHGD YIS lab in 2020. All instruments underwent precision study, carryover test and linearity to ascertain its performance prior to the concordance study.63 samples were used in the correlation all reportable parameters and WBC differential count and its flagging.

Results

The 2 units of DXH 520 demonstrated acceptable performance in precision, carryover and Linearity. The correlation of the parameters were within RCPA allowable error. However, we noted a low concordance of 39% in the WBC differential count flagging. To validate the flagging, manual differential count was conducted.

Conclusion

During the correlation, Sysmex XS appeared to be more sensitive to Atypical lymphocytes where manual differential count read <5%. This inevitably resulted in more manual slide review. In the 63 samples, 4 cases with high atypical lymphocytes (>5%) seen in manual differential count and they were flagged as lymphocytes in sysmex XS1000i and as monocytes in DxH 520. To counter the potential missed out in the reporting of Atypical lymphocytes in DXH, a lower threshold for monocytes in slide review may be needed.
A-216 Measuring Inflammation and Cardiovascular Markers at Benchtop NMR using Diffusion and Relaxation Edited Experiments
Authors: Wist J , Nitschke P , Masuda R , Lodge S , Schaefer H , Cannet C , Holmes E , Nicholson J K
Published: September 2023

Background

Metabolic phenotyping is an established tool in systems medicine that captures a profile of one’s individual health status and reflects the interaction between genes and external stressors. It uses analytical platforms such as NMR or MS to acquire molecular profiles, and modelling to extract actionable knowledge. Applying these techniques to a cohort of Australians infected by SARS-CoV-2 revealed a strong alteration in regions of 1D NMR spectra associated with lipoproteins and glycoproteins, and referred as Supramolecular Phospholipid Composite SPC (δ = 3.2 ppm) and Glyc (δ = 2.07 ppm). The latter is an established marker of inflammation. These results were later confirmed using larger cohorts from Spain (n = 525) and the UK (n = 1022). The urgent need for very rapid testing, at the early stage of the pandemic, prompted the development of bespoke NMR experiments able to measure this lipoproteins/glycoproteins signature without requiring complex modelling.

Methods

Physico-chemical properties of lipoprotein particles, such as diffusion, transverse and longitudinal relaxation rates, differ from low molecular weight metabolites. Therefore, an edited experiment JEDI (PGPE) was designed that combines diffusion, relaxation and scalar coupling editing blocks to produce a lipoprotein profile devoid of chemical noise (overlapping peaks) and where peaks give quantitative results.

Results

The SPC peak was further broken down into 3 sub-regions that are related to the main subfraction HDL and LDL (choline headgroups of phospholipids). Interestingly the ratio of SPC3/SPC2 highly correlates with the Apo-B100/Apo-A1 ratio, an established cardiovascular risk marker that is increased in patients with COVID19. Longitudinal data suggest this latter remains elevated even 30 days after onset in some patients. Furthermore, the edited experiment performs equally well at low field using a benchtop NMR.

Conclusion

Translation of a spectral signature relevant for monitoring COVID patients from high to low field NMR is possible using sophisticated editing techniques.
A-221 Evaluation of Apolipoprotein B Equivalent Low-density Lipoprotein Cholesterol Measurements
Authors: Hornseth J M , Donato L J , Jaffe A S , Meeusen J W
Published: September 2023

Background

Low-density lipoprotein cholesterol (LDL-C) is the primary biomarker for assessing risk for atherosclerotic cardiovascular disease (ASCVD). However, multiple large studies have demonstrated greater accuracy using Apolipoprotein B (apoB). One obstacle to its widespread use is the lack of guideline endorsed apoB treatment targets. A recently published solution has proposed using population percentiles to calculate LDL-C using apoB values (PMID: 36366949). The LDL-C concentration correlated to an individual’s ApoB percentile may more appropriately reflect ASCVD risk compared to lipid panel LDL-C. Here we evaluated this approach using a cohort where LDL-C was measured with the gold-standard beta-quantification method (LDL-CBQ).

Method

Results from clinically ordered apoB, LDL-CBQ, and lipid panel were included (n = 18 852). Samples with triglycerides >1000 mg/dL or LpX were excluded. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and apoB were measured using Roche Cobas c501 analyzers. LDL-CBQ was performed using Beckman LE-80K ultracentrifuge and dextran sulfate-Mg/Cl precipitation. ApoB equivalent LDL-C (eqLDL-CapoB) was calculated according to linear regression of LDL-C percentiles against apoB percentiles described by the equation eqLDL-CapoB = 1.45(apoB)-25. Concordance was determined based on clinical thresholds for LDL-CBQ and eqLDL-CapoB.

Results

Median (IQR) apoB and LDL-CBQ was 98 (79−119) mg/dL and 120 (94−150) mg/dL, respectively. LDL-CBQ and eqLDL-CapoB were concordant in 60% of samples overall.

Discordance between eqLDL-CapoB and LDL-CBQ shifted from primarily overestimating to underestimating as LDL-CBQ increased. Discordant eqLDL-CapoB was directly associated with TG and inversely associated with HDL-C.

Conclusion

The eqLDL-CapoB calculation is a useful tool to present apoB results in a more familiar context of LDL-C-equivalent units. The concordance findings largely confirm previously published results using eqLDL-CapoB. Furthermore, the pattern of HDL-C and TG suggests that a discordantly elevated eqLDL-CapoB is an indicator of a higher risk lipid profile. More investigation is needed to determine if eqLDL-CapoB is appropriate for widespread adoption.
A-239 Comparison Between Blood Culture and MeMed BV Test Results
Authors: Zuretti A , Christian M , Motov S , Kogan M
Published: September 2023

Background

The rate of cultures ordered for patients in which infection is suspected is approximately 40% on Emergency Department patients at Maimonides Medical Center and represents a significant financial burden for our institution. Most blood cultures in clinical practice do not grow organisms suggesting that suboptimal blood culture collection practices (e.g., suboptimal blood volume) or suboptimal selection of patients to culture (patients with low likelihood of bacteremia may be occurring.

•BV is a new host-protein test based on TRAIL, TNF-related apoptosis inducing ligand protein, IP-10, interferon gamma -induced protein 10 and CRP, C- reactive protein that produces a score between 1–100 indicating the likelihood of a bacterial vs viral infection. It has been validated in multiple studies to have sensitivity and specificity of more than 90%.• In this study we compare blood culture and BV results.

Methods

BV test were taken at ED physician discretion from March 2022 to December 2022

• BV score 0–35 is viral, 35–65 is equivocal and 65–100 is bacterial.

• BV test was measured using MeMed BV (MeMed, Israel) and MeMed Key (MeMed, Israel) from serum samples.

• This sub analysis focuses on patients presenting at the ED for whom blood culture was ordered and there was a record of the result.

Results

• BV test was taken for 545 patients during their ED visit, of these, 389 had blood cultures drawn and results recorded.

• There were 233 cases with BV score bacterial, 42 with BV score equivocal and 114 with BV score viral

• Out of the BV score viral, there were 7 with positive findings, of which 5 were considered contaminants

Conclusion

There is a high agreement between viral BV results and negative cultures. Ongoing collection of this data in real time will help establish this finding further in order to provide guidance for our clinicians to reduce the financial burden of unwarranted cultures as well as the unnecessary administration of antibiotics.
A-302 Agreement Assessment Between Molecular and Rapid Tests in Respiratory Viruses Detection
Authors: Martins L A , Domingues R S , Silva J D , Zauli D A , de Lima A B
Published: September 2023

Background

Diseases caused by respiratory viruses are the most frequent diseases in humans and have a significant impact on morbidity and mortality worldwide. Due to their transmission nature, these viruses are able to widespread dissemination. The pandemic caused by COVID-19 highlights this potential, however, other respiratory viruses also continue to circulate such as Respiratory Syncytial Virus (RSV) and Influenza (FLU). Efficient diagnostic tools are necessary, especially in endemic regions. Although molecular tests are gold standards, rapid tests (RTs) represent a great alternative once they are more accessible, faster, easier to manage, and can be performed at the point of care. Therefore, this work aimed to evaluate the analytical performance of RTs compared to molecular tests in the detection of viral antigens of RSV or FLU in swab samples.

Methods

Swab samples in saline solution (n = 60) were tested by qPCR molecular assay Multiplex Alinity m Resp-4-Plex Assay (Abbott Molecular) and RTs immunofluorescence-based (ECO-F RSV ag and ECO-F Influenza A/B—ECO Diagnostica). For the molecular assay, samples were prepared according to the manufacturer's instructions. For RTs, samples were submitted to the extraction buffer, incubated for 10 or 15 minutes respectively, and analyzed by ECO Reader F200 equipment, according to the manufacturer's instructions. It uses a cut-off value ≥1.00 for positive samples and <1.00 for negative samples.

Results

All negative samples (RSV = 20; FLU = 20) in molecular test were concordant with RTs results. The number of positive samples detected by molecular test was 4 and 16 for FLU and RSV respectively, while RTs detected a lower number of positive samples (FLU = 2; RSV = 10). Both RTs achieved a specificity of 100%; sensibility was 62, 50% for RSV and 50% for FLU. Using Cohen's Kappa index to assess the agreement between the compared tests, it was obtained the expected and observed values of 0.83 and 0.53 for RSV and 0.92 and 0.78 for FLU, which represents an index of 0.649 and 0.625 respectively. These results indicate substantial agreement between the tests, although the sensitivity of the molecular assay was superior.

Conclusion

Molecular tests can be used to confirm the results of RTs, once they are the gold standard for diagnosis. However, they have a high operational cost, which makes RTs a good alternative to help in the screening of these respiratory diseases, especially in resource-limited settings, allowing effective treatment and management for the patient.
A-309 Challeging Diagnostic of Neurosyphilis: Use of CXCL13 Concentration in Cerebrospinal Fluid
Authors: Carvalho R D , Rangel I D , Bacarov N B , Soane M M , Herbst V , Ferry F D
Published: September 2023

Background

Previous retrospective has been demonstrated the concentration of chemokine ligand CXCL13 in cerebrospinal fluid (CSF-CXCL13) is a promising biomarker in the diagnosis of neurosyphilis (NS) and monitoring of therapeutic efficacy. The goal of this study was to measure CXCL13 concentrations in CSF of NS suspected patients and compare with patients with syphilis non-NS and patients with treated syphilis.

Methods

One hundred and eleven NS-suspected participants from Rio de Janeiro (Brazil) were investigated for the detection of IgG antibodies against Treponema pallidum, using ELISA and Indirect Immunofluorescence tests (EUROIMMUN, Lübeck, Germany). CSF-CXCL13 concentration was prospectively performed by ELISA (EUROIMMUN, Lübeck, Germany) assay in all participants at baseline and in participants diagnosed with NS in follow-up visits at 3, 6, and 12 months after therapy.

Results

CSF-CXCL13 concentrations were significantly higher in patients with established NS presenting a median concentration of 207.4 pg/mL (IQR 69.3–1515.5 pg/mL) than in patients with syphilis non-NS with a median of 1.0 pg/mL (IQR 0.1–11.0 pg/mL, P < 0.001) or patients with treated syphilis with a median of 0.1 pg/mL (IQR 0.1–7.1 pg/mL, P < 0.001). The CSF-CXCL13 concentrations decreased after 3, 6 and 12 months of therapy compared to baseline in all cases of NS. The added concentration of CSF-CXCL13 above 62.8 pg/mL plus CSF-FTA-ABS reactivity agreed with diagnosis of NS in 88.9% of People Living with HIV (PLWHs) and plus CSF-TPHA reactivity agreed with the diagnosis of NS in 100% of HIV-uninfected patients.

Conclusion

The study suggests that the clinical use of CSF-CXCL13 is useful for supplementary biomarker for NS and as monitoring the effectiveness of NS therapy, especially in PLWHs with nonreactive CSF-VDRL, excluded other neurologic diseases.
A-314 Comparison of Calibrated Calculated Osmolality to Measured Osmolality by Different Equations: A Study using Pediatric Specimens
Authors: Garg U C , Wiebold A , Knoll M , McDonough R , Stickle D F , Ferguson A M
Published: September 2023

Background

American Diabetes Association recommends using serum osmolality to aid in differentiating between hyperosmolar hyperglycemia state (HHS) and Diabetic Ketoacidosis (DKA). Unfortunately, measured osmolality is unavailable in many small hospitals. Calculated osmolality is used commonly to evaluate the gap between calculated and measured osmolality. Using pediatric samples, we investigated whether calculated osmolality when calibrated against measured osmolality might serve as a surrogate for the measured osmolality.

Methods

Primary data were 441 samples having measured osmolality along with coincident measurements of Na, K, BUN and glucose. Calculated osmolality (α) was obtained using six equations from the literature: A: α = 2*Na+(Glu/18); B: α = 2*Na+(Glu/18)+(BUN/2.8); C: α = 2*(Na+K)+(Glu/18)+(BUN/2.8); D: α = 1.86*Na+(Glu/18)+(BUN/2.8)+9; E: α = 1.86*(Na+K)+(Glu/18)+(BUN/2.8)+10; F: α = 1.89*Na+1.38*K+(1.08*Glu/18)+(1.03*BUN/2.8)+7.45. For each equation, α was correlated with measured osmolality (M) by linear regression: α = slope*M+intercept. Calibrated values (β) were obtained as follows: β = (α-intercept)/slope. This procedure produces a linear regression for β vs M having slope = 1 and intercept = 0. The best calculated osmolality equation was the one for which the standard deviation (sd) of the distribution of errors for the calibrated data (the distribution of e = (β-M) across all points) was least.

Results

Measured osmolality (M) ranged from 232–462 mOsm/kg. The best relationship between β and M was for equation D. For D, calculated osmolality α = 0.77*M+49.2 mOsm/kg; r2 = 0.945. Calibrated β vs M is shown in Figure (r2 = 0.945). Errors (e) for β were normally distributed: e = 0 ± 8.9(1sd) mOsmol/kg. Thus, the 95% confidence interval (±2sd) for calibrated calculated osmolality using D was ±17.8 mOsm/kg. In our database, 18 specimens (4.1%) were outside of this boundary.

Conclusions

Calculated osmolality when calibrated to measured osmolality may be reasonable to report in pediatric hospitals when measured osmolality is not available, so long as physicians are fully informed and in agreement with what is being reported.
A-316 Suboptimal Compliance to Postpartum Glucose Monitoring in a High-risk Pregnancy Population - A Single Center Study
Authors: Olayinka L , Fox K , Aagaard K M , Devaraj S
Published: September 2023

Background

Gestational diabetes mellitus (GDM) is a predictive factor in developing type 2 diabetes mellitus (T2DM) in affected mothers and their offspring. Its prevalence is increasing proportionally with the obesity epidemic, affecting 10% of pregnant women and 50% of which are likely to develop T2DM. Current guidelines by the American Diabetes Association and the American College of Obstetricians and Gynecologists recommend screening at 4–12 weeks with a 2-hour postpartum glucose tolerance test (OGTT) in patients with a history of GDM. However, several studies have reported suboptimal test ordering and completion rates attributable to the busy postpartum period and provider role confusion between primary care physicians and obstetricians. Due to the complex maternal-fetal cases encountered at our institution, the aim of this study is to evaluate the ordering and test completion rates amongst care providers and patients to ensure compliance with stipulated guidelines.

Method

We conducted a retrospective audit of women diagnosed with GDM who delivered at our institution from Jan 2019–Oct 2022. We abstracted data from electronic health records. Gestational diabetes was defined by one or more of the following: abnormal 3hr OGTT or 1-hour OGTT of >/=200 mg/dL at >/= 24 weeks. We excluded patients with pre-existing diabetes defined by diagnosis code or by an abnormal 1st trimester 3hr GTT or HbA1C and patients who did not return for a postpartum visit. We compared the proportions of patients with postpartum glucose monitoring orders (glucose tolerance tests or Hemoglobin A1C) to those without orders. Factors such as race, GDM management, provider type and insurance carrier were assessed as potential barriers to non-compliance.

Results

We identified 356 patients who were diagnosed with GDM during the study period. Of these, 158 patients were excluded who had pre-existing diabetes or did not return for postpartum care. The mean (SD) maternal age was 33.2 (6.0) years. Seventy-four percent (147/198) of patients had a postpartum glucose tolerance test order (Group A), and 26% (51/198) had no laboratory order for glucose monitoring (Group B). The proportion of patients with a completed test order was 24% (35/147), of which four results were abnormal (indicated for diabetes or pre-diabetes). There was no difference in parity, ethnicity, insurance type, diabetes management and provider type between the two groups. Poor compliance was observed in patients with glucose tolerance laboratory orders, while patients with an HbA1c order were 100% compliant.

Conclusion

Overall, this report demonstrates poor patient compliance with postpartum glucose tolerance testing. Although HbA1C is not recommended for postpartum glucose monitoring, patients were more likely to complete this test.
A-326 Argininosuccinic Acid - is it Routinely Detectable in the Urine of Healthy Individuals?
Authors: Karger K M , Ogilvie G , Tsai M Y
Published: September 2023

Background

Argininosuccinic aciduria is a genetic disorder that results in elevated levels of argininosuccinic acid (ASA) in urine and blood. While there is seemingly a consensus within the clinical literature that any detectable amount of ASA in blood/plasma is diagnostic for argininosuccinic aciduria, yet there is conflict as to whether ASA in urine can be found in unaffected individuals. Some literature states that ASA should not be found in the urine of a healthy individual, while other literature reports low levels of ASA in the urine of healthy individuals. Additionally, many laboratories do not have a normal range for ASA within urine, which implies that any level of ASA found within urine is indicative of argininosuccinic aciduria. This conflict may in part be due to differences in the methods used to determine ASA levels. Newer liquid chromatography tandem mass spectrometry (LCMSMS) methods have been shown to be more sensitive than ion-exchange chromatography (IEC) based amino acid methods for detection of ASA. Additionally, the detection of ASA via IEC requires the heating and acidification of the sample to convert ASA into a single peak for quantitation. Heating and acidification is not routinely done for urine amino acid analysis with IEC; with routine IEC urine amino acid analysis, ASA migrates as three small peaks that may go unnoticed. In our clinical laboratory, which utilizes the less sensitive IEC method, our procedure describes the presence of any ASA in urine as diagnostic for argininosuccinic aciduria. Given the conflicting literature, we set forth to determine whether low levels can be detected in unaffected individuals with an IEC method, and if so, establish a normal range of ASA levels in urine with IEC.

Methods

Twenty waste urine samples from patients with no prior diagnoses of argininosuccinic aciduria were evaluated. ASA levels within the samples were determined via high performance ion exchange chromatography for separation of compounds followed by derivatization with ninhydrin for spectrophotometric detection with a Hitachi Amino Acid analyzer. The samples were acidified and heated, which converts ASA into a single anhydride peak for accurate quantitation, and the results were normalized to urine creatinine.

Results

ASA was detected in all twenty urine samples, with an average ASA concentration of 27.2 μmol/g Cr and a range of 11.3–47.7 μmol/g Cr.

Conclusion

Given these findings, our clinical laboratory procedure has been updated to include the information that ASA can be present in the urine of healthy individuals up to a concentration of 50 μmol/g Cr. Other clinical laboratories that analyze urine to identify argininosuccinic aciduria should be aware of the misinformation in the literature that claims that ASA is not present in the urine of healthy individuals.
A-347 Performance Evaluation of Standard Q COVID/FLU Ag Combo for Detection of SARS-CoV-2 and Influenza A and B Antigens from the Patients with Suspected Respiratory Infections
Authors: Kim S , Choi W
Published: September 2023

Background

COVID-19 and influenza are highly contagious respiratory diseases and are sometimes fatal, making them a major concern worldwide. Hence, rapid and accurate detection and differentiation are required as preventive measures to control the further spread of these diseases.

Methods

We evaluated performance of the Standard Q COVID/FLU Ag Combo test (Q Ag combo test) (SD Biosensor, Korea) for detection of SARS-CoV-2, influenza A, or influenza B using a single point-of-care device compared with real-time PCR. A total of 408 individuals: 55 positives of SARS-CoV-2, 90 influenza A, 68 influenza B, and 195 negatives from all viruses investigated.

Results

The Q Ag combo test demonstrated a high sensitivity of up to 92.73% and specificity of up to 99.49% for the detection of SARS-CoV-2. Similarly, a sensitivity of 92.22% and specificity of 100% for influenza A, and a sensitivity of 91.18%, and a specificity of 99.49% for influenza B were observed. When the days from symptom onset (DSO) were restricted to 0<DSO≤6, the sensitivity of the Q Ag combo test to detect SARS-CoV-2 was up to 100%, and when the Ct value of RdRp is ≤ 20, the sensitivity to detect SARS-CoV-2 was up to 93.10%.

Conclusion

The Q Ag combo might be useful to detect and differentiate SARS-CoV-2, and influenza A/B efficiently and rapidly.
A-352 Investigation of the Immunochromatographic Method using 150 nm Gold Colloids (1)-Comparison of Different Types of Gold Colloids
Authors: Hirano A , Asahi M , Otsuka M , Kubota R
Published: September 2023

Background

Gold colloids, which have been extensively used in immunochromatography, are typically 40 nm in particle size. Recently, 150 nm gold colloidal nanoparticles, which are prepared by gold coating a silica nucleus up to a diameter of 150 nm, have attracted considerable attention. These nanoparticles enable high sensitivity in immunochromatography. The purpose of this study is to compare the antibodies labeled with 40 and 150 nm gold colloids using the physisorption and covalent bonding methods, which are applied to the immunochromatography method developed in our laboratory.

Methods

1) For the physisorption method, 40 nm gold colloids (gold colloid AuH2, Morinaga Institute of Biochemistry) and 150 nm gold nanoshells (nanoComposix) were used to physically adsorb the antibody. The covalent gold conjugation kit (nanoComposix) was used to prepare 40 nm gold colloid-labeled antibodies by covalent bonding, and the high sensitivity gold conjugation kit was used to perform covalent bonding of the antibody and gold colloid after buffer displacement of the antibody.2) Anti-human albumin monoclonal antibody (abcam) was applied as the solid-phase antibody onto a nitrocellulose membrane (HF075, Merck Millipore) and dried. A human serum albumin sample (Fujifilm Wako Pure Chemicals) was diluted to a concentration of 1 mg/mL using phosphate-buffered saline (PBS). The sample was mixed with the gold colloid-labeled antibodies and a blocking solution (EZBlock Chemi, ATTO). Subsequently, 90 μL of the mixture was added dropwise and allowed to expand for 15 min before analysis.

Results

1) Comparison of detection linesA red line was detected in the judgment zone for the 40 nm gold colloid, whereas a black line was detected in the judgment zone for the 150 nm gold colloid. The background of the detection area for the physisorption method was higher than that for the covalent bonding method. 2) Comparison of detection sensitivitiesUsing the physisorption method, the 40 nm gold colloid detected up to 10 ng/mL. In contrast, using the covalent bonding method, the 40 nm gold colloid detected up to 100 ng/mL. Using the physisorption method, the 150 nm gold colloid detected up to 3 ng/mL when tested at 100, 10, and 3 ng/mL. In contrast, using the covalent bonding method, the 150 nm gold colloid detected up to 3 ng/mL.

Conclusion

Currently, 40 nm gold colloids are extensively used as a labeling material in immunochromatography. However, the use of 150 nm gold colloids, which have better detection sensitivity, may increase sensitivity and lead to more accurate detection.