bluuebunny/crossref_metadata_2025 huggingface dataset:
B-313 Assessment of β2-microglobulin concentration in pleural effusions
Authors: Bérgamo Vázquez S , Trapé Pujol J , Rives Jimenez J , González Fernández C , González García L
Published: October 2024

Background

β2-microglobulin (β2-m) is a biomarker used in serum for different types of pathologies. It has been described that lymphocyte activation processes us tuberculosis infections, AIDS virus or cytomegalovirus infections, can produce an increase in the concentration of this marker. As a tumor marker is useful in lymphomas diagnosis. In the bibliography has reported that processes involving renal failure lead to a significant increase in its concentration. In patients with renal failure and treated with hemodialysis, have been described medians twenty times the upper reference limit. The objective is to assess whether the concentration of (β2-m) in pleural fluid is affected by the same factors as in serum.

Methods

We analyzed 303 pleural effusions (PE) samples from undiagnosed patients with pleural effusion. β2-microglobulin levels were prospectively measured by electrochemiluminescence (ECLIA) assays (Cobas c702, Roche Diagnostics®). Glomerular filtration rate (GFR) was calculated by CKD-EPI equation. The diagnostic performance of β2-microglobulin was evaluated by receiver operating characteristic (ROC) curve analysis. Statistical analyses were performed using SPSS software.

Results

Pleural fluid of 303 patients (104 female, 204 male) were collected. The median age was 72 ± 10,6 years. For all samples β2-m median concentration was 5,85 mg/L (IQR:3.4 -6.45).When we compared all results according to kidney failure values; GFR >60mL/min β2-m median concentration was 4,12mg/L and if GFR <60 mL/min, β2-m was 8,62g/L significant difference have found (p<0,001). Comparing results between malignant pleural effusions (MPE) (n=96) and benign pleural effusions (BPE) (n=207), MPE median concentration was 5.38 mg/L and 6.07mg/L significant difference (p<0,001). Benign pathologies associated with pleural effusions, tuberculosis samples had the highest concentration of β2-m. Tuberculosis samples (n=6) had a normal distribution, obtaining a value [mean (SD)] of 7.28 mg/mL (2,13) mg/mL. For tuberculosis samples and patients without renal failure (n=5) (GFR>60 mL/min), the area under the ROC curve was 0.98 (95% CI: 0.88-0.98) (p<0.005). For β2-m cut-off point was 5.150 mg/L, a sensitivity of 100%, specificity of 16%, positive predictive value (PPV) of 14% and negative predictive value (NPV) of 100% were obtained. Patients with lymphomas present the highest concentration in the group of malignant pleural effusions, but further investigations could not be performed due to the small sample size.

Conclusions

Based on the results obtained from our present study, it can be concluded that β2-microglobulin marker in pleural effusions has significant association with glomerular filtration rate, as well as occurs in serum. Higher concentrations were found in patients with GFR>60 mL/min and tuberculosis. Using 5,15 mg/L cut-off point, 100% of NPV was obtained.
B-316 Evaluation of an FDA-cleared Chromogranin A Assay on an Automated Analyzer
Authors: Boyert N , Schroeder G , Dee M , Colon-Franco J M
Published: October 2024

Background

Chromogranin A (CgA) is a hydrophilic and acidic protein, present in the chromaffin granules of neuroendocrine cells. It is the preferred tumor marker for the monitoring of neuroendocrine tumors (NETS), which are often found in the lungs, appendix, pancreas, and gastrointestinal tract. Previous CgA assays were performed by manual ELISA testing, and were not FDA-approved, leading to a longer, more rigorous validation process and longer run times. The introduction of an automated, FDA-cleared CgA assay allows the laboratory to process patient samples more quickly and reliably, shortening a multiple hour process to minutes. The objective of this study was to evaluate the performance of an automated CgA assay recently cleared by the FDA.

Methods

We validated the the B·R·A·H·M·S™ Chromogranin A II (CGAII) assay on the automated B·R·A·H·M·S KRYPTOR Compact PLUS (Thermo Fisher Scientific Inc.). The CGAII assay is an immunofluorescent assay, which uses Time-Resolved Amplified Cryptate Emission (TRACE) to quantitate CGA in human serum. Assay performance characteristics were evaluated including measuring range (MR) and maximum dilution, precision, method comparison, stability, reference interval, stability, and carryover.

Results

The MR for CGAII was established with triplicate analysis of serum at 8 levels, ranging from 25.8 - 2,700 ng/mL. Linearity was demonstrated with a slope of 0.907, intercept of 1.948 and observed error of 2.54 ng/mL. Recovery at each point ranged from 83.3-110.3%. Carryover (<5.0 ng/mL) was not observed at a concentration approximately 2 times the upper limit of the MR. A 1:25 or 1:500 automatic dilution was determined to be acceptable (% bias <16%). Intraday precision coefficient of variation (CV) ranged from 4.1-1.7% (SDs from 2.32-6.64 ng/mL) at concentrations of 56.7 and 393.0 ng/mL. The interday CVs ranged from 6.0-7.1% (SDs from 3.43 - 28.84 ng/mL) at concentrations of 57.5 and 403.8 ng/mL. Twenty samples with concentrations ranging from 56.4-2,907 ng/mL were compared to a reference laboratory utilizing a similar methodology. The correlation coefficient was 0.9934, with a slope of 1.014, and intercept of -32.95. An additional twenty samples with concentrations ranging from 67.0-2,446 ng/mL were compared to a CgA ELISA kit (CGA-ELISA-NG, CISBIO) to determine the bias between the two methodologies. The correlation coefficient was 0.9902, with a slope of 0.845, and intercept of -15.31, and a bias of -19.9%. The serum samples were stable for 3 days when stored at 2-8°C. Recovered CgA concentrations fell outside of the 95% confidence interval after day 3 at 2-8°C. The manufacturer provided reference interval of <187 ng/mL was verified by testing 20 healthy adult samples, all of which fell within this range.

Conclusions

This assay has been validated and shown to be an accurate and precise method for monitoring CgA. Further, the method was validated on an automated analyzer to allow expeditious turnaround time in a core laboratory.
B-317 Novel prognostic marker TGFBI affects the migration and invasion function of ovarian cancer cells via integrin αvβ3-PI3K-Akt signaling pathway
Authors: Guo Y , Wang H , Xu Y
Published: October 2024

Background

Patients with ovarian cancer show remarkably different prognosis. Present prognostic models for ovarian cancer mainly focus on clinico-pathological parameters, so quantifiable prognostic markers at molecular level are urgently needed. Platelets contribute to ovarian cancer progression, but have not been considered as biomarkers likely due to their instability. Therefore, we aimed to screened out stable prognostic markers from platelet-treated ovarian cancer cells, and explored mechanisms by which they promote ovarian cancer metastasis.

Methods

Microarrays analysis was done with platelet-treated SKOV-3 ovarian cancer cells, and similar studies were searched in the Gene Expression Omnibus (GEO) database. The candidate genes were determined by analyzing differentially expressed genes (DEGs), protein-protein interaction (PPI) network, Cox proportional hazard models and Kaplan-Meier curves. The expression of TGFBI in the tissue microarray was assessed by immunehistochemical staining (IHC), and its prognostic efficiency was evaluated by univariate and multivariate analysis. The functions of TGFBI were predicted using data from TCGA, and validated by in vitro and in vivo experiments. The mechanism exploration was performed based on proteomic analysis, molecular docking and intervention study.

Results

TGFBI was significantly higher expressed in the platelet-treated ovarian cancer cells. Tissue microarray showed that increased expression of TGFBI led to significant decrease of overall survival (OS), progression-free survival (PFS), and TGFBI was proved to be an independent prognostic factor for ovarian cancer. Functionally, TGFBI affected the migration and invasion of ovarian cancer cells by regulation of epithelial mesenchymal transition (EMT) markers (CDH1 and CDH2) and extracellular matrix (ECM) degradation proteins (MMP-2). Mechanistically, TGFBI phosphorylated PI3K and Akt by combining integrin αvβ3.

Conclusions

We found out TGFBI as a novel prognostic indicator for ovarian cancer patients. TGFBI could promote metastasis in ovarian cancer by EMT induction and ECM remodeling, which might be associated with the activation of integrin αvβ3-PI3K-Akt signaling pathway.
B-319 Kappa and Lambda Free Light Chains Quantification in Serum Samples with 3 or 4 Monoclonal Components Detected by Serum Immunofixation
Authors: Loureiro G , Rocha L , Siciliano S , Benini M , Martins M , Souza G , Pelegrini A , Facchin M , de Sá V , Sumita N
Published: October 2024

Background

Serum free light chain (FLC) quantification is a diagnostic criterion for monoclonal gammopathy. Oligoclonal expansion is defined when two or more small bands are detected in the gamma region of serum protein electrophoresis (SPEP) or immunofixation (SIFE) within the context of infectious diseases, autoimmune diseases, or some lymphoproliferative processes. This study aims to investigate the frequency of FLC disturbances in samples with oligoclonal pattern of 3 or 4 monoclonal bands observable in SIFE.

Methods

We have analyzed 7553 consecutive samples during the period of January to December 2023 in which both determination of FLC and SIFE were ordered in a large central laboratory at São Paulo, Brazil. FLC quantification and SIFE analysis were performed with FreeLite assay and Optilite system (The Binding Site, UK) and SPIFE 3000 (Helena Laboratories, USA), respectively.

Results

In our analysis, 119 samples (50 males, 69 females, median age 69 years (range 37-90)), with 3 or 4 monoclonal bands were identified, constituting 1.57% of the overall study population. These samples were then categorized into two groups. The first group had normal FLC Ratio (range 0.26 to 1.65) and the second group had altered FLC Ratio (outside 0.26-1.65 range). Seventy-seven samples (65%) had altered FLC ratio, with kappa elevation being the most common alteration (51 samples). Within these samples, median FLC ratio was 2.99 (range 1.72-719.05). Lambda elevation was present in 26 samples, with median FLC ratio 0.04 (range 0.005-0.16).

Conclusions

Presence of 3 or more oligoclonal bands in SIFE analysis may be indicative of various pathological processes (benign and malignant) and also be observed in post-transplantation. In this study, we have observed that most of these samples present altered FLC ratio, which indicate monoclonal disturbances in the production of free light chains. Those disturbances may be associated with a lymphoproliferative disease (e.g. multiple myeloma) or may be transient. Clinicians should be aware of the need for follow-up of these cases.
B-321 Enhancing Early Detection of Prostate Cancer Using PSA-Guided Screening in High-Risk Men Under 50
Authors: Chen L , Meng Q
Published: October 2024

Background

Prostate Cancer remains a significant global public health concern. It is the most common cancer and the second leading cause of cancer death among men in the United States. Current guidelines, including those by the USPSTF, ACS and ASCO offer varying recommendations on PSA screening. Present clinical practice, primarily targeting men aged 50-69. Our study aimed to assess the feasibility and validity of using PSA for targeted screening in men under 50 who are at high risk, enhancing early detection of prostate cancer.

Methods

This retrospective analysis utilized data from our hospital's prostate cancer screening program collected from 2022 to 2023, including104 individuals under 50. Participants were categorized based on PSA levels 4-10 ng/mL (n=71) and over10 ng/mL (n=33). We analyzed the number of cases diagnosed with prostate cancer and the correlation with PSA levels, Gleason Scores (GS), family history, and ethnicity/race.

Results

In the104 participants, 88 of them were diagnosed with prostate cancer, highlighting an 84.6% detection rate. Among PSA levels 4-10 ng/mL group, 36 out of 43 White or Caucasian and 13 out of 13 Black or African American men were identified as GS 6-10. In the group PSA over 10 ng/mL, 18 White or Caucasian and 6 Black or African American individuals with more aggressive disease (GS 6-10). Importantly, a substantial fraction of these cases had a first-degree relative with prostate cancer, emphasizing the influence of family history on PSA screening decision.

Conclusions

Our findings suggest that PSA-guided screening in men under 50 at high risk can enhance the early detection of prostate cancer. The significant presence of intermediate-risk prostate cancer (GS 6 or 7) in populations at higher risk due to ethnicity/race and family history. Our study highlights the potential benefits of revisiting current screening guidelines to lower the age threshold for high-risk populations.
B-323 Measurement of PIVIKA II Blood Level in Patients with Liver Diseases by Immunoassays
Authors: TAMIMI W , AlBagaei N , Alhamad A , Altwaijry A , Alkhidhr A , Alhuwayshil S , Alasam H A , Almaiman S , Althubiti F M , AlAjlan A
Published: October 2024

Background

Liver diseases are the most common diseases globally and can be complicated to cirrhosis and cancer and lead to death if not managed. It is crucial to prevent patients with liver diseases to reach the level of complications in particular liver cancer or hepatocellular Carcinoma (HCC). There are many screening lab tests to monitor and evaluate patients with liver disease such as alpha fetoprotein (AFP), however, it lacks optimal sensitivity and specificity. Another promising screening test is Prothrombin Induced by Vitamin K deficiency or antagonist- II (PIVKA-II) to complements AFP in screening of HCC. The aim of this study was to evaluate two PIVKA-II immunoassays and compare it to AFP in blood samples of patients with liver diseases.

Methods

Blood samples were collected from 56 patients with liver diseases, chronic hepatitis B (n=14), chronic hepatitis C (n=18), liver cirrhosis (n=14), and HCC (n=10) at King Abdulaziz medical city, Riyadh, SA. Measurement of PIVKA-II levels were performed on all samples by Snibe and Abbott analyzers. Clinical data was collected from the HIS BestCare. AFP was performed on Abbott analyzer. Statistical analysis was carried by Excel sheet Microsoft and p value was set at 0.05.

Results

There was an excellent correlation (R2= 0.9327) between the PIVKA-II two immunoassays from Snibe and Abbott among patients with HCC (p=0.1384). The diagnostic sensitivity PIVKA-II for Abbott and Snibe were calculated to be 78% and 90% respectively among HCC patients at cutoff 32 mAU/mL with specificity of 16% and 44.4% respectively. This was corresponding to sensitivity of 90% and specificity of 67% on AFP at cutoff 10 ng/mL.

Conclusions

The two PIVKA-II two immunoassays were perfectly correlated among the samples of HCC patients. The sensitivity of both assays was high but with lower specificity. Snibe assay has superior sensitivity and specificity among patients with HCC.
B-328 A Novel Pathway of Akt-Dependent PARP1 Activation Through the Nuclear Localization of EPRS1
Authors: Zin I , China A , Gogonea V , Fox P
Published: October 2024

Background

Glutamyl-prolyl-tRNA synthetase (EPRS1) is the only bifunctional aminoacyl-tRNA synthetase (aaRS) and is essential for interpreting the genetic code. EPRS1, along with seven other aaRSs, forms the multi-tRNA synthetase complex (MSC). EPRS1 consists of two catalytic domains, GluRS and ProRS, connected by a linker region. Several aaRSs within the MSC, including EPRS1, can dissociate from the MSC in response to specific stimuli. This dissociation enables non-canonical activities distinct from their primary role in protein synthesis. Breast cancer cells harboring a loss-of-function mutation in phosphatase and tensin homolog (PTEN) are known to have more activity in the serine/threonine kinase Akt. Poly-(ADP)-ribose polymerase 1 (PARP1), plays a vital role in DNA damage repair (DDR). PARP1 deposits one or more ADP-Ribose moieties onto damaged DNA or other proteins in a process referred to as PARylation. We hope to connect Akt activation and PARP1 activity through the nuclear localization and noncanonical function of EPRS1. We hypothesize, that when Akt is activated, either through the loss of PTEN function or through stimuli such as heat shock or H2O2 treatment, will stimulate the nuclear localization of EPRS1 and modulate PARP1 activity.

Methods

To test our hypothesis, we evaluate Akt activation, EPRS1 localization, and PARP1 activity. Using pharmacological activators and inhibitors of Akt, we test if inhibitors and activators alone are sufficient to cause the nuclear localization of EPRS1. Biochemically, we isolate nuclear and cytosolic fractions used in various western blot analysis. We use a variety of assays for PARP1 activity and DDR that include immobilized histones, calculating IC50s of PARP1 inhibitors, comet assay, and confocal microscopy. To ascertain the connection between PARP1 and EPRS1 we use LC-MS/MS analysis and immunoprecipitation.

Results

We show, in both patient-derived and cultured breast cancer cells, elevated levels of EPRS1 not only in the cytoplasm, but also within the nucleus. We find that nuclear localization EPRS1 is facilitated by a nuclear localization sequence (NLS) located within the linker region of the protein. Breast cancer cells harboring a loss-of-function in PTEN exhibit higher levels of EPRS1 in the nucleus compared to PTEN-positive cells. In EPRS1 knockdown cells, there is diminished expression of multiple tumor-related transcription factors, DNA-damage repair, tumor cell survival, and PARP1 auto-PARylation. We demonstrate that nuclear EPRS1 binds to and shares an interactome with PARP1.

Conclusions

EPRS1-mediated regulation of PARP1 activity provides a new mechanistic link between PTEN loss in breast cancer cells, PARP1 activation, and cell survival and tumor growth. Targeting the non-canonical activity of EPRS1, without inhibiting canonical tRNA ligase activity, might provide a new therapeutic approach in breast and other forms of cancer, potentially supplementing existing cancer therapeutics.
B-332 Use of urinary volatile organic compounds in monitoring prostate cancer after radical prostatectomy
Authors: Badmos S , Lee W
Published: October 2024

Background

Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer among males and the second cause of cancer-related deaths. PCa treatment involves different methods, and most common is radical prostatectomy (RP), which entails removal of prostate-gland from men who have been diagnosed with PCa. Prostatic-specific-antigen (PSA) has been used for detection of recurrent disease for years. After its introduction as biochemical recurrence (BCR) marker, men with distinct diseases were treated similarly. Overtime, it has been observed that PSA relapse presents several meanings according to clinicopathological features, like Gleason score, PSA-doubling-time, clinical stage, surgical margin status. Despite this, PSA remains main tool to assess disease progression after RP. RP remains primary treatment for localized PCa and has been performed for years with excellent oncologic control. However, approximately 20-40% of patients with clinically localized PCa will present biochemical-recurrence (BCR) after RP, while some with recurrent-metastasis. The study aims to investigate potential volatile organic compounds (VOCs) associated with men who have undergone RP but still abhor the disease.

Methods

Urine samples were collected from 110 male adults with biopsy-proven PCa-positive results before and after RP. VOCs in urine were extracted by stir-bar-sorptive-extraction and analyzed using thermal-desorption with gas chromatography-mass spectrometry. Metabolomics and machine-learning tools used to develop and evaluate models for PCa diagnosis before and after RP.

Results

PLS-DA and VIP loading plots identified potential VOC panels that could be used to differentiate PCa patients before and after RP and those with BCR and recurrent metastasis. Furthermore, logistic-regression results with validation provide a promising diagnostic model for PCa diagnosis after RP.

Conclusions

This novel method using urinary VOCs was developed to fill gaps in PCa monitoring after RP. These research findings could aid and fast-track the provision of rapid point of care to the treated PCa patients who still abhor the disease.
B-333 Optimizing AFP Cutoffs for Hepatocellular Carcinoma Screening: Insights from the National Cancer Screening Program in Korea
Authors: Choi Y , Kim S , Kim H , Jeong H , Lee H , Lee W , Chun S
Published: October 2024

Background

The incidence rate and mortality rate of liver cancer were 11.6 (ranked 8th among cancers) and 10.7 (4th) per 100,000 individuals respectively globally in 2020, whereas in Korea, they were higher at 29.5 (7th) and 20.6 (2nd) per 100,000 individuals. The National Cancer Screening Program (NCSP) in Korea conducts biannual concurrent liver ultrasound and serum alpha-fetoprotein (AFP) measurement for hepatocellular carcinoma (HCC) surveillance in high-risk groups, including those with chronic hepatitis B and C, and liver cirrhosis. The effectiveness of surveillance is impacted by varying AFP cutoffs; however, within the NCSP, different cutoffs are being used, and it is not clear which cutoffs are being employed. Harmonization of AFP test results by major reagent manufacturers have been achieved, enabling the adoption of a uniform threshold. This study aims to assess the variation of AFP cutoffs among institutions within the NCSP and suggest a unified and optimal AFP threshold.

Methods

This study examined HCC screening results from the NCSP between 2018 and 2020, investigating unit and cutoff usage for AFP test across institutions each year (number of institutions were 4452 for 2018, 4754 for 2019, and 4847 for 2020). To determine the optimal AFP cutoff for HCC screening, datasets comprised unique patient results from 2018 to 2020 (number of patients = 819,644). Receiver operating characteristic (ROC) curve analyses were conducted for determine best AFP cutoffs. Cancer diagnosis was defined by billing records indicating HCC within one year post-screening.

Results

More than 96% of institutions used ng/mL as a unit of AFP test. Among institutions using ng/mL, the most frequently used AFP cutoff was 7 ng/mL, with frequency percentages of 75.7%, 72.2%, and 62.2% in 2018, 2019, 2020, respectively. The percentiles (1st, 10th, 90th, 99th) of AFP cutoff usage for the years 2018, 2019, and 2020 were (7, 7, 8.8, 15), (7, 7, 8.9, 15), and (7, 7, 9, 15) respectively. The AUC of ROC was 0.824 and some cut-off points with their sensitivity and specificity values were as follows: 5 ng/mL (0.648, 0.874); 10 (0.457, 0.976); 20 (0.327, 0.993); 40 (0.246, 0.997); 100 (0.169, 0.998); 200 (0.123, 0.999); 400 (0.084, 1).

Conclusions

Different cutoffs observed across institutions in NCSP. Our study cautiously suggests that the optimal AFP value for screening HCC in NCSP may range from 10 to 20 ng/mL, considering sensitivity and specificity when AFP is combined with ultrasound in regions with a high prevalence of HCC. For a more suitable AFP cutoff recommendation, additional analyses based on ultrasound findings and underlying diseases should be considered.
B-340 Evaluation of the Analytical Performance of Three Major Immunoglobulins Assays on the Atellica CI Analyzer
Authors: Carter R H , Gupta P , Tyler C , Micklitsch C , Arrode-Bruses G , Snyder J
Published: October 2024

Background

The Atellica® CI Analyzer is an automated, high-throughput integrated chemistry and immunoassay analyzer utilizing both Atellica® CH and Atellica® IM Assays. This study evaluated the analytical performance of the the Atellica CH Immunoglobulin A_2 (IgA_2), Immunoglobulin G_2 (IgG_2), and Immunoglobulin M_2 (IgM_2) Assays on the Atellica CI Analyzer.

Methods

Precision studies were performed according to CLSI EP05-A3 using native and contrived human serum samples. One aliquot of each sample was tested in duplicate in two runs per day ≥2 hours apart on each analyzer for ≥20 days. Precision was evaluated using three reagent lots on one system. Method comparison studies were performed using three reagent lots according to CLSI EP09c. Individual native and contrived human serum samples were analyzed using the Atellica CH IgA_2, IgG_2, and IgM_2 Assays on the Atellica CH Analyzer and the Atellica CI Analyzer. LoB and LoD were determined as described in CLSI EP17-A2.

Results

Representative precision and method comparison results for each assay are listed in the table. For the three assays tested, repeatability and within-lab %CVs were <1.8% and <3.9%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1. Detection capability for the Atellica CH IgA_2 Assay on the Atellica CI Analyzer was estimated at 1.6 mg/dL (0.02 g/L) and 3.6 mg/dL (0.04 g/L) for LoB, and LoD. For the Atellica CH IgG_2 Assay, LoB and LoD were determined at 7 mg/dL (0.07 g/L) and 21 mg/dL (0.21 g/L). For the Atellica CH IgM_2 Assay, LoB and LoD were determined at 5.0 mg/dL (0.05 g/L) and 8.0 mg/dL (0.08 g/L).

Conclusions

Evaluation of the Atellica CH IgA_2, IgG_2, and IgM_2 Assays using the Atellica CI Analyzer demonstrated good precision and equivalent performance compared to the same assays on the Atellica CH Analyzer.
B-347 Analytical Performance Evaluation of the High Sensitivity PSA Assay and the Free PSAII Assay on the Atellica IM Analyzer
Authors: Olson Nissen K , Ngbokoli M , Snyder J , Pagano M , Owusu A , Patibandla S
Published: October 2024

Background

Measurement of serum prostate specific antigen (PSA) levels may be used in prostate cancer (PC) screening, but elevated PSA levels also are observed in patients with other etiologies such as benign prostatic hypertrophy. Studies suggest that measuring PSA with or before digital rectal examination (DRE) provides a better method of detecting PC than DRE alone. The free prostate specific antigen (fPSA) assay is an aid for distinguishing PC from benign prostate conditions in men 50 years or older with PSA values 4.0-10.0 ng/mL (µg/L) and DRE findings nonsuspicious for PC. The goal of this study was to evaluate the analytical performance of the high sensitivity PSA (hsPSA)* and free PSA (fPSAII)* assays on the Atellica® IM Analyzer.

Methods

Detection capability studies were performed per CLSI EP17-A2. Precision testing was performed per CLSI EP05-A3 with native human serum and QC samples, 3 reagent lots, 1 analyzer, 2 runs/day, 2 replicates/run for 20 days. For Atellica® hsPSA and fPSAII assays a multi-site reproducibility study was conducted per CLSI EP-05 A3 using native and contrived serum samples, 3 reagent lots, and 3 different sites and analyzers; samples were assayed in triplicate for five days, two runs/day ∼2 hours apart. Linearity testing was performed per CLSI EP06-A on a dilution series made from a high PSA sample (native human male serum pool) and a low sample (native human female serum), 4 replicates, 3 reagent lots, and 1 analyzer. Specimen equivalency was determined by Weighted Deming regression model per CLSI EP09c-ed3.

Results

Results are presented in the table.

Conclusions

The Atellica IM hsPSA assay and fPSAII assays detection capability, precision, linearity, and specimen equivalency were acceptable.

*CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.
B-348 Performance of the Atellica IM Analyzer’s HighSensitivity PSA Assay as an Aid for Monitoring Prostate Cancer Recurrence
Authors: Olson Nissen K , Snyder J , Pagano M , Owusu A , Grosett M , Birmingham N , Christenson R , deFilippi C
Published: October 2024

Background

Prostate specific antigen (PSA) is a suitable marker for monitoring men with prostate cancer (PC), and for detecting recurrence after therapy in conjunction with other diagnostic measures. Studies were performed to evaluate performance of the Atellica® IM High-Sensitivity PSA assay (hsPSA)* versus the Atellica® IM PSA assay in patients undergoing management (monitoring) of PC.

Methods

A total of 868 serum samples from 170 subjects with PC (92 [54%] subjects had a radical prostatectomy (RP) before enrollment) were collected at 7 sites across the United States. Subjects had baseline and >2 follow-up visits during treatment (average 5.106 visits, SD=1.414). Samples were tested using the Atellica IM hsPSA assay and the commercially available Atellica IM PSA assay (comparative method). For RP and non-RP combined, 644 paired samples for each assay were tested. Subjects were designated “No Progression” (responding, stable, and no evidence of disease subjects) or “Progression” at each visit based on clinical classification.

Results

In this study the Atellica IM hsPSA assay demonstrated equivalent performance as commercial Atellica IM PSA in predicting disease status (table). The PPA between the assays was 95.5% and the NPA was 98.9%. Concordance to clinician classification was similar for both assays (∼80% PPA and 90% NPA).

Conclusions

Preliminary results demonstrated equivalent performance of the Atellica IM hsPSA assay as the commercially available Atellica IM PSA assay in terms of predicting disease status. This hsPSA assay can detect very low levels of PSA, which is particularly important for the monitoring of RP patients.

*CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.
B-351 Genotoxic Producing Escherichia coli Protects and Promotes Breast Adenocarcinoma
Authors: Heaton L , Figard S D , Garcia R A
Published: October 2024

Background

Recent studies have linked certain colibactin producing subphylas of E. coli to colorectal cancer. The bacterium synthesizes colibactin via the pks genomic island containing a series of clbA to clbS genes. The genotoxin causes inter-strand DNA cross-links, which lead to double strand breaks and promotion of colorectal adenocarcinoma. The published studies have prioritized the colorectal regions of the body where E. coli is commonly found, but none have identified the same genotoxic relationship with other types of adenocarcinoma. In this study, we evaluate DNA damage and cellular changes of mammary breast tissue based on high and low levels of colibactin producing E. coli exposure. The goal is to evaluate if colibactin can affect cells in the mammary breast tissue promoting breast adenocarcinoma growth.

Methods

Two cell lines were acquired from ATCC: primary mammary epithelial cells (PCS-600-010) and MCF-7 breast adenocarcinoma cells (HTB-22). Both cell lines were split into six culture flasks and maintained until ∼80% confluence was reached using the ATCC cell culture protocols. Once all the flasks had reached the target confluence, they were divided into exposure groups of high and low concentrations of colibactin producing E. coli, a group of non-colibactin producing E. coli, a group exposed only to phosphate buffered saline, and a control group with no exposure. Cellular morphology was observed using light microscopy before, after exposure, and every 5 minutes up to 15 minutes. E. coli and colibactin DNA concentrations were quantified using quantitative polymerase chain reaction. Genomic DNA was extracted from each group of cells. The DNA from each group was whole genome sequenced and analyzed for genomic variation.

Results

The normal cells exposed to E. coli showed immediate lysing and continued to lyse after a 5 minute incubation; however, the adenocarcinoma positive cells showed no lysing up to 30 minutes incubation. Sequencing results show genomic variation between the groups and specific break points associated with the E. coli exposed groups.

Conclusions

Our results show that the presence of E. coli with mammary breast tissue can destroy normal tissue, promote lysis resistance, and allow adenocarcinoma cells to continue to grow. The colibactin producing E. coli does cause double stranded breaks and can lead to cell death. This new information points out a critical need to monitor the microbiome and infection levels of people at risk or in early stages of cancer to prevent adenocarcinoma growth and destruction of normal tissue. This study indicates that colibactin producing E. coli may play a larger role in tissue damage and promotion of other types of cancer. More research is needed to elucidate the molecular pathway and mechanisms of colibactin, which will lead to new diagnostics or therapeutics that monitor E. coli levels or inhibit colibactin’s toxic effects.
B-356 Siemens CYFRA 21-1: an assay for measurement of cytokeratin fragment 21-1
Authors: Cline D J , Khokhar S , Benina N , Thorne G
Published: October 2024

Background

Cytokeratins are structural proteins forming the subunits of epithelial intermediary filaments. The soluble fragment of cytokeratin 19, cytokeratin fragment 21-1 (CYFRA 21-1), can be found in the blood of lung cancer patients, primarily those with non-small cell lung cancer (NSCLC). CYFRA 21-1 is the preferred biomarker in the management of NSCLC, particularly squamous cell and large cell carcinoma subtypes. An assay for CYFRA 21-1 on Siemens ADVIA Centaur® XPT and Siemens Atellica® IM (Siemens CYFRA) is being developed and analytical performance is being presented.

Methods

The Siemens CYFRA 21-1 assay (in development) is a one-step chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of CYFRA 21-1 in human serum and plasma. The specimen is incubated with paramagnetic microparticles coated with the monoclonal antibody (mAb) BM19.21 and acridinium-labeled mAb KS19.1 conjugate on the Siemens ADVIA Centaur XPT System and Siemens Atellica IM System. After incubation and washing, Acid and Base reagents are added. The resulting relative light units (RLUs) are directly proportional to the amount of CYFRA 21-1 in the sample allowing for the quantitative determination of CYFRA 21-1 in the specimen.

Results

The following performance were determined using 3 unique lots of reagents and calibrators with the calibration range for the assay being 0.00 to 100.00 ng/mL. For the ADVIA Centaur XPT and Atellica IM systems were shown to be equivalent within 4%. The limit of blank (LoB), limit of detection (LoD), and limit of quantitation at 20% CV (LoQ) were determined and met the goal of ≤ 1.00 ng/mL. Linearity according to CLSI EP06 Ed2 was demonstrated for a range of 0.66 through 100.00 ng/mL. A Precision study of 2 controls and 5 panels spanning the range of the assay demonstrated a total %CV ≤ 8% at all levels. In the sample tube type study, a matrix comparison of 61 matched serum and plasma samples were evaluated. Passing-Bablock slopes of < 5% and r > 0.99 were observed when evaluating samples within the measurement range for plasma (LiHep, LiHep separator, K2EDTA and K3EDTA) tubes and serum separator tubes (SST) compared to the Red Top serum samples. Six endogenous substances were evaluated for interference in the CYFRA 21-1 assay. The average percent difference between test and control samples for all endogenous interferents was < 10%. Percent difference in the presence of 20 potentially interfering drugs was ≤ 4.0%.

Conclusions

The Siemens CYFRA 21-1 assay currently in development is a sensitive and precise assay for the quantitative determination of CYFRA 21-1 in human serum and plasma.
B-357 Siemens CA 72-4: an assay for measurement of Tumor Associated Glycoprotein (TAG) 72
Authors: Cline D J , Glass E , Benina N , Thorne G
Published: October 2024

Background

The tumor associated glycoprotein (TAG) 72, also known as CA 72-4 is a mucin protein of high molecular weight. CA 72-4 is found on the surface of many cancer cells, including stomach (gastric), ovary, breast, colon and pancreatic cells. CA 72-4 is currently one of the primary markers for the diagnosis of gastric cancer and monitoring the course and efficacy of gastric cancer. In ovarian cancer, it has a higher sensitivity for mucin- type ovarian cancer, and its combination with CA125 for detection can significantly improve the clinical sensitivity. In colorectal cancer, CA 72-4 combined with CEA detection was also found to significantly improve the sensitivity of the initial diagnosis. An assay for CA 72-4 on Siemens Atellica IM (Siemens CA 72-4) is being developed and analytical performance is being presented.

Methods

The Siemens CA 72-4 assay (in development) is a one-step chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of CA 72-4 in human serum and plasma. The specimen is incubated with paramagnetic microparticles coated with the monoclonal antibody (mAb) B72.3 and acridinium-labeled mAb CC49 conjugate on the Siemens Atellica IM® System. After incubation and washing, Acid and Base reagents are added. The resulting relative light units (RLUs) are directly proportional to the amount of CA 72-4 in the sample allowing for the quantitative determination of CA 72-4 in the specimen.

Results

The following performance were determined using 3 unique lots of reagents and calibrators with the calibration range for the assay being 0.00 to 200.00 U/mL. The limit of blank (LoB), limit of detection (LoD), and limit of quantitation at 20% CV (LoQ) were determined and met the goal of ≤ 1.00 U/mL. Linearity according to CLSI EP06 Ed2 was demonstrated for a range of 1.00 through 200.00 U/mL. A Precision study of 2 controls and 5 panels spanning the range of the assay demonstrated a total %CV ≤ 6% for samples ≥ 5.00 U/mL and ≤ 0.25 SD for samples <5.00 U/mL. In the sample tube type study, a matrix comparison of 23 matched serum and plasma samples were evaluated. Passing-Bablock slopes of < 8% and r > 0.99 were observed when evaluating samples within the measurement range for plasma (LiHep, LiHep separator, K2EDTA and K3EDTA) tubes and serum separator tubes (SST) compared to the Red Top serum samples. Five endogenous substances were evaluated for interference in the CA 72-4 assay. The average percent difference between test and control samples for all endogenous interferents was < 10%. Percent difference in the presence of 28 potentially interfering drugs was ≤ 4.0%.

Conclusions

The Siemens CA 72-4 assay currently in development is a sensitive and precise assay for the quantitative determination of CA 72-4 in human serum and plasma.
B-358 Siemens NSE: an assay for measurement of human Neuron-Specific Enolase
Authors: Cline D J , Khokhar S , Benina N , Thorne G
Published: October 2024

Background

Neuron-specific enolase (NSE), a glycolytic enzyme (2-phospho-D-Glycerate hydrolase) can be found in a variety of non-neuroendocrine cells. Determination of NSE is used for monitoring response to therapy and detection of recurrent disease, such as SCLC and neuroendocrine tumors. An assay for NSE on Siemens ADVIA Centaur® XPT System and Siemens Atellica® IM system (Siemens NSE) is being developed and analytical performance is being presented.

Methods

The Siemens NSE assay (in development) is a one-step chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of NSE in human serum. The specimen is incubated with paramagnetic microparticles coated with the monoclonal antibody (mAb) NSE21, and acridinium-labeled mAb NSE17 conjugate on the Siemens ADVIA Centaur XPT system and Siemens Atellica IM system. After incubation and washing, Acid and Base reagents are added. The resulting relative light units (RLUs) are directly proportional to the amount of NSE in the sample allowing for the quantitative determination of NSE in serum.

Results

The following performance were determined using 3 unique lots of reagents and calibrators with the calibration range for the assay being 0.0 to 400.0 ng/mL. For the ADVIA Centaur XPT and Atellica IM systems were shown to be equivalent within 2%. The limit of blank (LoB), limit of detection (LoD), and limit of quantitation at 20% CV (LoQ) were determined and met the goal of ≤ 1.6 ng/mL. Linearity according to CLSI EP06 Ed2 was demonstrated for a range of 1.6 through 400.0 ng/mL. A Precision study of 2 controls and 6 panels spanning the range of the assay demonstrated a total %CV ≤ 7% at all levels. Comparison of 50 specimens collected in Red Top serum and Serum Separator Tubes (SST) had a Passing-Bablock slope of < 2% and r of > 0.99 when evaluating samples within the measurement range. Five endogenous substances were evaluated for interference in the Siemens NSE assay. The average percent difference between test and control samples for all endogenous interferents was < 10%. Percent difference in the presence of 38 potentially interfering drugs was ≤ 10.0%. The potential cross-reactant αα enolase was evaluated at concentration of 900 ng/mL and the percent cross-reactivity was ≤ 2%.

Conclusions

The Siemens NSE assay currently in development is a sensitive and precise assay for the quantitative determination of NSE in human serum.
Uncovering the first-infall history of the LMC through its dynamical impact in the Milky Way halo
Authors: Sheng Yanjun , Ting Yuan-Sen , Xue Xiang-Xiang , Chang Jiang , Tian Hao
Published: October 2024

The gravitational interactions between the LMC and the Milky Way cause dynamical perturbations in the MW halo, leading to biased distributions of stellar density and kinematics. We run 50 high-resolution N-body simulations exploring varying masses and halo shapes of the MW and LMC to study the evolution of LMC-induced perturbations. By measuring mean velocities of simulated halo stars, we identify a discontinuity between the first-infall and second-passage scenarios of the LMC’s orbital history. In the first-infall, the Galactocentric latitudinal velocity hovers around 16 km s$^{-1}$ for stars at 50–100 kpc, while it subsides to about 8 km s$^{-1}$ in the second-passage scenario. We demonstrate that, this reduced perturbation magnitude in the second-passage scenario is mainly due to the short dynamical times of the Galactic inner halo and the lower velocity of the LMC during its second infall into the MW. Using a subset of $\sim 1100$ RR Lyrae stars located in the outer halo (50 kpc $\le R_{\mathrm{GC}}\lt $ 100 kpc) with precise distance estimates from Gaia, we find the mean latitudinal velocity ($v_{b}$) in the Galactocentric frame to be $\langle v_{b} \rangle =18.1 \pm 4.1$ km s$^{-1}$. The observation supports the first-infall scenario with a massive LMC ($\sim$$2.1 \times 10^{11} \, \mathrm{M}_{\odot }$) at infall, an oblate MW halo with a virial mass $M_{200}\lt 1.4\times 10^{12}\,\mathrm{M}_{\odot }$ and a flattening parameter $q\gt 0.7$. Our study indicates that LMC-induced kinematic disturbances can reveal its orbital history and key characteristics, as well as those of the MW. This approach shows promise in helping determine fundamental parameters of both galaxies.
MTAS-01 UPDATES ON BRAIN METASTASIS MANAGEMENT AND OUTCOMES IN LMICS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Dokponou Yao Christian Hugues , Badirou Omar Boladji Adébayo , Mustapha Mubarak Jolayemi , Obame Fresnel Lutèce Ontsi , Nyalundja Arsene Daniel , Agada Nicaise Kpègnon , Lawson Late Dzidoula , Gbenou Ferol Baudelaire Babatoundé , Bankole Nourou Dine Adeniran
Published: October 2024

BACKGROUND

Brain Metastases (BM) occur in the natural course of malignant tumors and cause a high rate of morbidity and mortality. The approaches to their management have changed considerably over the past decade. We aimed to give an update regarding the current means of diagnosis, management, and the outcomes of brain metastases in LMIC.

METHODS

We searched PubMed, ScienceDirect, Medline, Embase, Global Index Medicus, African Journals Online, and Google Scholar for studies reporting data on Brain metastasis diagnosis, management, and outcomes in LMICs from inception to October 23rd, 2022. The systematic review was conducted using the PRISMA principles.

RESULTS

A total of 7916 unique studies were identified, of which, 48 were included. The most studied (21, 43.75%) and common cause of metastases was lung tumors (1602, 51.43%). A subtotal resection (STR) was archived in the majority of reported cases in the frequency of 56.2% (n = 1751), gross total resection (GTR) in 37.5% (n = 1169) of cases, while only biopsy was possible in 6.3% (n = 195). The reported adjuvant treatments were radiotherapy 39.9% (n = 1036), radiosurgery 22.5% (n = 585), and radiosurgery + radiotherapy 37.5% (N = 974). Management of the primary tumor was reported in 13 (27.08%) studies. Half (24, 50%) of the studies reported the overall survival time to be 4-52 months.

CONCLUSION

Lung, breast, and GI tumors were the most common primary tumors for the MB. Whole-brain radiotherapy is the most common management method in LMICs.
OTHR-08 ANALYSIS OF INCIDENCE AND TRENDS IN NEUROLOGICAL MALIGNANCIES IN BULAWAYO FROM 2012 TO 2021
Authors: Rukwava Godfrey
Published: October 2024

OBJECTIVES

We aim to quantify the incidence of neurological malignancies in Bulawayo from 2012 to 2021, to Identify any significant changes in the incidence rates over the decade, to explore the demographic, geographic, and socioeconomic factors that may influence the incidence of these malignancies and to compare the incidence trends with national and international data to understand the regional context.,as well as to identify any potential risk factors or preventive measures that could be targeted to reduce the incidence of neurological malignancies in Bulawayo.

METHODS

A retrospective observational study with analysis of primary data for 139 patients with neurological malignancies, collected from Cancer Registry for Zimbabwe’s southern region(Bulawayo being the center) over a decade will be done using SPSS and trends in terms of type of malignancy, distribution between sex and among different age groups as well as incidence for each year will be identified.

RESULTS

The results will quantify the incidence,as well as show the changes in incidence rates over the decade.it will also show the epidemiology of different neurological malignancies in the sample population and trends according to age and sex.

CONCLUSION

The key findings include trends of incidence for the given 10 years as well as variation in pattern of different malignancies across sex and age. The findings of the study will contribute to the understanding of neurological malignancies in Bulawayo as well as the Zimbabwe at large, however more evidence should be assessed in larger trials or by using national data.