ADVIA Centaur Research Articles

Evaluation of R-FIND SARS-CoV-2 Neutralizing Antibody ELISA and FREND COVID-19 SP Rapid Fluorescence Immunoassay.

Serology testing is useful to determine the past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the comparative performance of a newly developed neutralizing antibody test (R-FIND SARS-CoV-2 Neutralizing Antibody ELISA, SG Medical, Seoul, Korea) and a rapid fluorescence immunoassay (FREND™ COVID-19 SP, NanoEntek, Hwaseong, Korea) for the detection of SARS-CoV-2 spike protein antibody. They were compared with cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit (Genscript Biotech, Piscataway, NJ, USA) and ADVIA Centaur SARS-CoV-2 Total (COV2T) (Siemens Healthineers, Erlangen, Germany). Forty COVID-19 samples and 80 negative samples were collected after nucleic acid tests. The positive percent agreement (%) of the kit in samples from 6 - 7 days, 8 - 14 days, and 15 - 45 days after symptom onset were as follows: R-FIND (83.3, 76.9, 95.2), cPass (83.3, 69.2, 90.5), FREND (66.6, 84.6, 100), and COV2T (66.6, 69.2, 76.2). The negative percent agreement (%) was 100, 97.5, 92.5, and 100 for R-FIND, cPass, FREND, and COV2T. The total agreement rate between the neutralizing antibody kits (R-FIND and cPass) was 96.7%. FREND showed high agreement with two neutralizing antibody kits (96.7% for R-FIND and 93.3% for cPass). R-FIND Neutralizing Antibody and FREND COVID-19 SP showed comparable detecting ability to commercial tests.

Safety and Immunogenicity Outcomes of an Inactivated Viral Vaccine against SARS-CoV-2 (Covaxin®)

Introduction: Bharat Biotech International Ltd in partnership with National Institute of Virology (NIV), has developed an indigenous whole virion inactivated Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) viral vaccine BBV-152 (Covaxin®), formulated with Toll Like Receptors 7/8 agonist Imidazoquinoline (IMDG) molecule adsorbed to alum (Algel). Variety of factors other than environmental ones can affect vaccines efficiency outside the strict setting of clinical trials, like how the vaccine is stored or transported, and even how patients are vaccinated. In addition, the intrinsic capacity of the recipient to respond to a vaccine which is determined by sex, genetic factors, age, psychological stress, nutrition and other diseases are also likely to have an impact. Aim: To determine the safety, reactogenicity and immunogenicity of the inactivated whole virus vaccine (Covaxin®) amongst hospital-based population groups. Materials and Methods: The prospective analytical study was conducted in the Department of Microbiology, Sawai Man Singh Medical College, Jaipur, Rajasthan, India, from January 2021 to March 2021.The study primarily included Healthcare Workers (HCWs) employed at SMS Medical college and attached hospitals. In-vitro quantitative IgG antibodies against SARSCoV-2 spike Receptor Binding Domain (RBD) were measured using Chemiluminescence Immunoassay (CLIA) based Advia centaur SARS-CoV-2 IgG, manufactured by Siemens Pvt Ltd, Munich, Germany, as per manufacture’s instructions. Results: Out of total 223 individuals, 61.88 % (138/223) showed neutralising antibody titre of >1 index value by CLIA, rest 38.12% (85/223) were non reactive i.e., titre <1 index value, after four weeks of receiving first dose of Covaxin®. After 2 to 4 weeks of receiving second dose 84.30% (188/223) showed neutralising antibody titre of >1 index value by CLIA, rest 15.70% (35/223) were non reactive i.e., titre <1 index value. After receiving first dose, 100% (223/223) of the participants developed localised pain and bodyache 33.63% (75/223). None of the participants showed any anaphylactic reaction or any emergency condition just after vaccination. Conclusion: Covaxin® is a well-tolerated vaccine, and induces good humoral response against SARS-CoV-2 with a significant rise in the neutralising antibody titres.

Thyroid Dysfunction and its Effect on Red Blood Cell Parameters

Background: Thyroid hormones are necessary for the growth and development, cellular differentiation, physiological function and metabolic regulation of almost all tissues in our body. Thyroid disorders are accompanied by alteration in hematological profile. This study aims to evaluate the effect of thyroid dysfunction on red blood cell parameters.
 Materials and Methods: This case-control observational study was conducted in the Department of Clinical Biochemistry, KIST Medical College and Teaching Hospital (KISTMCTH), Lalitpur, Nepal from January 2021 to June 2021.Total number of recruited subjects was 248, out of which 67 were labeled as hypothyroid, 7 were hyperthyroid and 174 were euthyroid as control. Subjects for all three groups were between 16-93 years old. Thyroid hormone profile of patients was determined by Siemens ADVIA Centaur CP immunoassay analyzer and hematological parameters by automated hematology analyzer Sysmex XN-550. Results were analyzed by SPSS 21 software and a chi-square test was applied to see significant differences among the groups.
 Results: The mean age of all study participants was 42.08±17.27 years and female constituted 74.6% of total subjects. Analysis of the data obtained a statistically significant difference in the mean hemoglobin (p<0.001) between hypothyroid and euthyroid groups. The difference was not significant for hemoglobin (p=0.252) among hyperthyroid and euthyroid groups. There was no statistical significant difference between thyroid cases and control for MCV, MCH and MCHC.
 Conclusion: The current study concluded that thyroid dysfunction have a significant effect on red blood cell parameters. Hematological parameters should be evaluated in patient with thyroid dysfunction.

Serum Ferritin Concentration in Corona Virus Disease 19

Introduction: Coronavirus disease 19 (COVID-19) is a complex disease responsible for the development of exacerbated inflammatory response (cytokine storm) that ultimately leads to multiorgan failure and death. Serum ferritin has been recently identified as one of the inflammatory markers responsible for the pro-inflammatory effects. Small amount of ferritin is present in plasma (15-150 ng/mL) which might increase with the severity of COVID-19. Therefore, measurement of ferritin is essential in identifying disease severity and predict disease prognosis. Objective: This study aims to assess the ferritin level in COVID-19 patients. Methods: A cross-sectional study was carried out on 259 COVID-19 patients visiting KIST Medical College and Teaching Hospital (KISTMCTH), Lalitpur, Nepal from November 2020 to April 2021. Serum ferritin was estimated in the automated Siemens ADVIA Centaur CP Chemiluminescence Immunoassay system. All the patients visiting KISTMCTH referred by clinician for ferritin assessment were included in this study. Data collected using the proforma tool was tabulated in SPSS 21 and statistical analysis was done by inferential statistical test. Results: Out of total 259 COVID-19 patients, 58.7% were male and the majority of patients (82.6%) were below 70 years of age. The mean age for all participants was 52.11±16.59 years. Hyperferritinemia was seen in 218 (84.16%) COVID -19 patients. The mean value of serum ferritin was 767.1±789.86 (IQR: 12.8-4590) ng/mL and was significantly higher in males (p<0.001). Comparing the mean values of ferritin between the patients below and above 70 years, no statistical difference was observed (p=0.872). Conclusions: In our study, serum ferritin levels were greatly increased in patients with COVID-19 infection. Keywords: Coronavirus disease 19; cytokine storm; inflammatory marker; serum ferritin.

Anti-CCP Antibody and Rheumatoid Factor among Clinically Diagnosed Rheumatoid Arthritis Patients Attending a Tertiary Hospital at Chitwan, Nepal

INTRODUCTION: Rheumatoid Arthritis (RA) is a common, chronic inflammatory multisystem autoimmune disorder of undetermined aetiology involving primarily the synovial membranes and articular structures of many joints. Rheumatoid factor (RF) is most frequently used serum biomarkers for the diagnosis of RA; however, these antibodies are detectable in many other pathological conditions and even in 5% in healthy population. Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibodies is another serological biomarker having high sensitivity and specificity than RF which present in pre-clinical stage and seronegative rheumatoid arthritis patients. MATERIALS AND METHODS: This is a cross-sectional study conducted among the confirmed RA patients visiting orthopaedic OPD. Anti-CCP antibody was determined quantitively by CLIA on Siemen ADVIA Centaur CP immunoassay system and RA-factor were determined quantitively by Nephelometry assay on MISPA I3 and comparison was done between two serological tests, i.e., Anti-CCP and RF. RESULTS: Out of 112 clinically diagnosed RA patients, 23 (20.5%) were males and 89(79.5%) were females with the ratio of 1:3.9 and the mean age ± SD of the patients was 50 ± 14.56. Out of 112 clinically diagnosed RA patients, 55 patients, i.e., 49.1% were RF antibodies positive and 57 patients, i.e., 50.9% were RF antibodies negative. Among RF positive, 32 (58.2%) patients were positive for anti-CCP antibody and among RF negative, 10 (17.5%) patients were positive for anti-CCP antibody and the differences between Anti-CCP and RF groups was statistically highly significant (p<0.001). CONCLUSIONS: Females are at high risk of developing Rheumatoid arthritis than males because male to female ratio is found to be 1:3.9. This study also showed that Anti-CCP antibody is more beneficial and better marker than RF for the diagnosis of Rheumatoid arthritis.

Classification of maternal thyroid function in early pregnancy using repeated blood samples.

Objective The assessment of maternal thyroid function in early pregnancy is debated. It is well-established that pregnancy-specific reference ranges preferably should be used. We speculated if the use of repeated blood samples drawn in early pregnancy would influence the classification of maternal thyroid function.MethodsPregnant women with repeated early pregnancy blood samples were identified in the North Denmark Region Pregnancy Cohort. Each sample was used for the measurement of TSH, free T4 (fT4), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers). Method- and pregnancy week-specific reference ranges were used for the classification of maternal thyroid function.ResultsAmong 1466 pregnancies included, 89 women had TSH above the upper reference limit in the first sample (median pregnancy week 8) and 44 (49.4%) of these similarly had high TSH in the second sample (median week 10). A total of 47 women had TSH below the lower reference limit in the first sample and 19 (40.4%) of these similarly had low TSH in the second sample. Regarding women classified with isolated changes in fT4 in the first sample, less than 20% were similarly classified as such in the second sample. The percentage agreement between the samples was dependent on the level of TSH in the first sample and the presence of TPO- and Tg-Ab.ConclusionIn a large cohort of pregnant women, the classification of maternal thyroid function varied considerably with the use of repeated blood samples. Results emphasize a focus on the severity of thyroid function abnormalities in pregnant women.

Fully automated immunoassays for measuring beta‐amyloid peptide (1‐42) and total tau in cerebral spinal fluid

AbstractBackgroundBeta‐amyloid1‐42 (Aβ42) and tau protein are cerebral spinal fluid (CSF) biomarkers for progression to AD. The sensitivity requirements for Aβ42 and total tau assays are in the pg/mL range, a challenge for any methodology. The use of these biomarkers for clinical purposes requires assays that can reliably deliver accurate and reproducible results.MethodNew prototype immunoassays for Aβ42 and total tau on a fully automated clinical analyzer [Siemens Healthineers ADVIA Centaur® XPT Immunoassay System] are under development to enable routine testing of AD biomarkers in clinical laboratories. Each assay uses an antigen/antibody sandwich format and chemiluminescence detection. Standard curves from 0 to 4000 pg/mL and 0 to 6500 pg/mL were generated for the Aβ42 and Tau assays, respectively. Synthetic Aβ42 and recombinant tau‐441 were spiked into an immunodepleted (ID) CSF pool and tested. Precision was evaluated over 6 days by testing a CSF pool and buffer controls on two analyzers. Functional sensitivity was estimated using the precision data. Clinical utility was evaluated by testing 30 clinical CSF samples from subjects with and without AD.ResultRecoveries of spiked Aβ42 from CSF ranged from ‐13% to +0.7% over 113 to 3179 pg/mL. Recoveries of spiked tau‐441 from CSF ranged from ‐11% to +13% over 35 to 3826 pg/mL. The repeatability and within‐laboratory precision of the Aβ42 assay ranged from 1.3% to 8.6% and 1.9% to 9.9%, respectively, over 107 to 2005 pg/mL. The repeatability and within‐laboratory precision of the total tau assay ranged from 1.2% to 10.8% and 1.6% to 12.5%, respectively, over 108 to 3300 pg/mL. The functional sensitivities of the Aβ42 and total tau assays were estimated to be < 200 pg/mL and < 80 pg/mL, respectively. Using ROC analysis, a ratio of Aβ42 and total tau results was able to differentiate AD from non‐AD subjects with 90% sensitivity and 95% specificity (AUC 0.95).ConclusionWhen finalized, the fully automated Aβ42 and total tau assays will have performance characteristics suitable for routine use in a clinical laboratory. The performance of the assays in combination with automation will make testing for these important biomarkers more reliable and routine.

Reference interval for type III procollagen (PIIINP) using the Advia centaur PIIINP assay in adults and elderly

Objective The amino-terminal peptide of type III procollagen (PIIINP) is a byproduct of type III collagen synthesis that exhibits promise as a biomarker of fibrosis, specifically in monitoring hepatic fibrosis in methotrexate treated patients. The Advia Centaur® PIIINP assay is developed for track-based automated laboratory systems and is suitable for large volume analysis. Reference intervals in children and younger adults have been published previously. Here we measured PIIINP to determine reference ranges, specifically including elderly patients, for whom such are currently lacking. Methods Samples were collected from subjects ranging from 20 to 98 years of age. Blood donors and clinical samples from primary care patients were used for reference interval calculation. Samples were analysed using the Advia Centaur® PIIINP assay. After exclusion of samples high in alanine transaminase (AST), aspartate transaminase (ALT), and C-reactive protein (CRP) 386 samples were used in the reference interval calculation. Results and conclusion We determined the following reference interval for the Advia Centaur® PIIINP assay: the lower limit of the reference interval (2.5% percentile with 95% CI) was 4.42 (4.20–4.65) µg/L and the upper limit of the reference interval (97.5% percentile 95% CI) 16.0 (15.04–17.02) µg/L.No significant differences in mean PIIINP concentrations were found between men and women. While differing mean PIIINP concentrations were seen among subjects in different age groups, the differences were small and partitioning of reference range was determined not to be necessary.

Comparative evaluation of ADVIA Centaur® XP chemiluminescence system for screening of HBV, HCV, HIV and syphilis in Indian blood donors

BackgroundThe introduction of chemiluminescent immunoassay (CLIA) in blood donor screening has led to a gradual replacement of enzyme-linked-immunosorbent assay (ELISA) as the former offers automation, higher sensitivity and lower turn-around-time. However, only a few CLIA platforms are used for blood donor screening in India. The present study evaluated one such newer platform viz., Adiva Centaur XP CLIA for screening of HBV, HCV, HIV and syphilis. Material and methodsProspective comparative study wherein 4843 whole blood donors were screened for HBsAg, Anti-HCV, HIV Ag-Ab and Anti-treponemal antibodies in both Advia Centaur XP and Architect i2000SR platforms. Additional tests were performed in samples which were reactive in only one of the platforms. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, false positive rate and false negative rate of both the platforms were compared. Kappa coefficient was calculated to determine the agreement between the testing platforms. ResultsThe sensitivity of Advia Centaur platform for HBV, HCV, HIV and syphilis detection were 94.9 %, 100 %, 100 % and 100 % respectively as compared to 96.6 %, 100 %, 100 % and 100 % in Architect i2000SR platform. The specificity of both the platforms were 99.8−99.9 % for all the four tests. The agreement between the two platforms was almost perfect for HBV, HCV and syphilis testing; and fair for HIV testing. ConclusionThe Advia Centaur CLIA platform was found to be comparable with the Architect CLIA platform for blood donor screening. Unexpected finding was the occurrence of HBV false negatives in both the platforms, possibly due to HBsAg mutations.

First-Trimester Reference Intervals for Thyroid Function Testing among Women Screened at a Tertiary Care Hospital in India.

Objectives Due to differences in the method of assay and population-specific factors, each laboratory needs to establish its own gestation-specific reference intervals (GRIs) for thyroid hormones. Materials and Methods Three-hundred forty-one women with less than 14 weeks gestation were screened at a tertiary care hospital in Chhattisgarh, India. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and thyroid peroxidase antibody (anti-TPO) were measured using an ADVIA Centaur XP immunoassay. GRIs (2.5th and 97.5th percentiles) were determined for TSH and fT4. TSH and fT4 concentrations were converted to multiples of the median (MoM) values. Effect of maternal age, gestational age, and maternal weight was analyzed.Statistical Analysis Quantitative variables were expressed as means and standard deviations (SD), and qualitative variables were expressed as frequencies and percentages. Normality of the data was checked using the Kolmogorov–Smirnov test. Values that were normally distributed were expressed only as means and SD. Those that were not normally distributed were expressed as medians and interquartile range. For all statistical analysis, p < 0.05 was considered as statistically significant. Results First-trimester GRI was 0.245 to 4.971 mIU/L for TSH, 10.2 to 18.9 pmol/L for fT4, and 27.0 to 56.89 kIU/L for anti-TPO. There was no significant difference in the mean serum TSH ( p = 0.920), fT4 ( p = 0.714), or anti-TPO ( p = 0.754) values among women in 4 to 7th week and 7 to 14th week of gestation. The 1st and 99th centile MoMs were 0.03 and 4.09 for TSH and 0.66 and 1.39 for fT4. There was a significant positive correlation between the maternal weight and TSH MoM values ( p = 0.027, r = 0.120). Conclusion These laboratory- and first-trimester-specific GRI for TSH and fT4 shall help in proper diagnosis and treatment of subclinical thyroid dysfunctions. TSH and fT4 MoM values can be used to indicate high or low values in a quantitative manner independent of the reference ranges and may be used by other laboratories.

Immunogenicity of SARS-CoV-2 Vaccine in Dialysis.

Patients receiving maintenance dialysis represent a high-risk, immune-compromised population with 15%-25% COVID-19 mortality rate who were unrepresented in clinical trials of mRNA vaccines. All patients receiving maintenance dialysis who received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021, were included. Response was on the basis of levels of Ig-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike-antigen (seropositive ≥2 U/L) using an FDA-approved semiquantitative chemiluminescent assay (ADVIA Centaur XP/XPT COV2G). Among 186 patients on dialysis from 30 clinics in eight states tested 23±8 days after receiving two vaccine doses, there were 165 (88.7%) responders with 70% at maximum titer. There was no significant difference between BNT162b2/Pfizer (148 out of 168, 88.1%) and mRNA-1273/Moderna (17 out of 18, 94.4%), P=0.42. All 38 patients with COVID-19 history were responders, with 97% at maximum titer. Among patients without COVID-19, 127 out of 148 (85.8%) were responders, comparable between BNT162b2/Pfizer (113 out of 133) and mRNA-1273/Moderna (14 out of 15) vaccines (85.0% versus 93.3%, P=0.38). Most patients receiving maintenance dialysis responded after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine, suggesting the short-term development of antispike antibody is good, giving hope that most of these patients who are vulnerable, once immunized, will be protected from COVID-19. Longer-term evaluation is needed to determine antibody titer durability and if booster dose(s) are warranted. Further research to evaluate the approach to patients without a serologic response is needed, including benefits of additional dose(s) or administration of alternate options.

Factors Affecting Side Effects, Seroconversion Rates and Antibody Response After Inactivated SARS-CoV-2 Vaccination in Healthcare Workers

In this study, it was aimed to prospectively evaluate the efficacy, side effects and seroconversion data of inactive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), CoronaVac® (Sinovac, China) vaccine in healthcare workers. A total of 1053 healthcare workers who were initially seronegative (COV2T® SARS-CoV-2 Total Siemens, USA) and vaccinated with inactivated SARS-CoV-2 were included in the study. Quantitative IgG antibodies (ADVIA Centaur® SARS-CoV-2 IgG, Siemens, USA) were investigated 28 days after the first vaccine (n= 939) and the second vaccine (n= 771). In addition, neutralizing antibodies were evaluated via "enzyme linked immunosorbent assay (ELISA)" test (ACE2-RBD Neutralization Assay, Dia-Pro, Italy) 28 days after the first vaccine. Antibody response of the vaccine was evaluated statistically by univariate (Chi-square, Fisher's exact test, Student's t test, Mann-Whitney U, one-way ANOVA and Kruskall Wallis ANOVA tests) analysis and linear regression models. The consistency between quantitative IgG test and neutralizing antibody test was also evaluated in blood samples taken 28 days after second vaccination. Statistical analysis was determined in logarithmically transformed data with statistical analysis with SPSS 23.0 and Stata, and type 1 error level was accepted as 0.05. At least one side effect was reported by 31.3% and 26.8% of the participants after the first and second vaccine, respectively. The most frequent side effect was pain at the injection site with a frequency of 20.4% vs 21.7%. The frequency of applying to a health center due to side effects was 1.0% after the first vaccine and 0.8% after the second vaccine. The percentage of those who produced sufficient quantitative IgG was found as 25.3% (95% CI= 22.5-28.1) 28 days after the first vaccine and 97.9% (95% CI= 96.91- 98.93) after the second vaccine. Neutralizing test antibody positivity was found as 97.7% 28 days after the second vaccine. In univariate analysis, the characteristics that significantly increased the quantitative IgG response against inactivated SARS-CoV-2 vaccine were young age (p<0.01), female gender (p<0.01), being a non smoker (p<0.001), not having a chronic disease (p= 0.019), having had the flu vaccine this year (p= 0.012), not being overweight or obese (p= 0.020), and having a SARS-CoV2 infection prior to vaccination (p<0.001). In addition, allied health personnel showed significantly lower antibody responses than the other workers (p<0.001). Multiple linear regression models revealed that, female gender, younger age, smoking and previous COVID-19 polymerase chain reaction test positivity significantly affected the quantitative IgG response after vaccination. A 99% agreement was found between the ELISA-based neutralizing antibody test and the quantitative IgG test (Kappa p= 0.783) performed on the 28th day after the second vaccination. CoronaVac® provides adequate antibody response in 25% of healthcare workers aged 18-64, after 28 days from a single vaccine, and 97% after 28 days from the second vaccine. Antibody response was significantly higher in younger ages, women, non-smokers, and those who had previously encountered SARS-CoV-2. Phase 3 and phase 4 results are needed to Show effectiveness of this vaccine in real life.

Sensitive and quantitative detection of cardiac troponin I with upconverting nanoparticle lateral flow test with minimized interference

Measurement of cardiac troponin I (cTnI) should be feasible for point-of-care testing (POCT) to diagnose acute myocardial infarction (AMI). Lateral flow immunoassays (LFIAs) have been long implemented in POCT and clinical settings. However, sensitivity, matrix effect and quantitation in lateral flow immunoassays (LFIAs) have been major limiting factors. The performance of LFIAs can be improved with upconverting nanoparticle (UCNP) reporters. Here we report a new methodological approach to quantify cTnI using UCNP-LFIA technology with minimized plasma interference. The performance of the developed UCNP-LFIA was evaluated using clinical plasma samples (n = 262). The developed UCNP-LFIA was compared to two reference assays, the Siemens Advia Centaur assay and an in-house well-based cTnI assay. By introducing an anti-IgM scrub line and dried EDTA in the LFIA strip, the detection of cTnI in plasma samples was fully recovered. The UCNP-LFIA was able to quantify cTnI concentrations in patient samples within the range of 30–10,000 ng/L. The LoB and LoD of the UCNP-LFIA were 8.4 ng/L and 30 ng/L. The method comparisons showed good correlation (Spearman’s correlation 0.956 and 0.949, p < 0.0001). The developed UCNP-LFIA had LoD suitable for ruling in AMI in patients with elevated cTnI levels and was able to quantify cTnI concentrations in patient samples. The technology has potential to provide simple and rapid assay for POCT in ED setting

Indirect estimation of reference intervals for thyroid parameters using advia centaur XP analyzer.

BackgroundThe aim of this study was to determine the reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and FT3/FT4 ratio using indirect methods.MethodsWe analyzed 1256 results TSH, FT4 and FT3 collected from a laboratory information system between 2017 and 2021. All measurements were performed on a Siemens ADVIA Centaur XP analyzer using the chemiluminescent immunoassay. We calculated the values of the 2.5th and 97.5th percentiles as recommended by the IFCC (CLSI C28-A3).ResultsThe RIs derived for TSH, FT4, FT3 and FT3/FT4 ratio were 0.34-4.10 mIU/L, 11.3-20.6 pmol/L, 3.5-6.32 pmol/L and 0.21-0.47, respectively. We found a significant difference between calculated RIs for the TSH and FT4 and those recommended by the manufacturer. Also, FT3 values were significantly higher in the group younger than 30 years relative to the fourth decade (5.26 vs. 5.02, p=0.005), the fifth decade (5.26 vs. 4.94, p=0.001), the sixth decade (5.26 vs. 4.87, p<0.001), the seventh decade (5.26 vs. 4.79, p<0.001) and the group older than 70 years old (5.26 vs. 4.55, p<0.001). Likewise, we found for TSH values and FT3/FT4 ratio a significant difference (p <0.001) between different age groups.ConclusionsThe establishing RIs for the population of the Republic of Srpska were significantly differed from the recommended RIs by the manufacturer for TSH and FT4. Our results encourage other laboratories to develop their own RIs for thyroid parameters by applying CLSI recommendations.

Clinical characteristics and prognostic implications of diabetes and myocardial injury in patients admitted to the emergency room

BackgroundThis study aimed to investigate the clinical features and prognosis of diabetes and myocardial injury in patients admitted to the emergency department.MethodsWe analyzed the clinical data of all consecutive patients admitted to the emergency department during the years 2012 and 2013 with at least 1 cardiac Troponin I (cTnI Ultra Siemens, Advia Centaur) determination, and were classified according to the status of diabetes mellitus (DM) and myocardial injury (MI). Clinical events were evaluated in a 4-year follow-up.ResultsA total of 3622 patients were classified according to the presence of DM (n = 924 (25.55%)) and MI (n = 1049 (28.96%)). The proportion of MI in patients with DM was 40% and 25% in patients without DM. Mortality during follow-up was 10.9% in non-DM patients without MI, 21.3% in DM patients without MI, 40.1% in non-DM patients with MI, and 52.8% in DM patients with MI. A competitive risk model was used to obtain the Hazard Ratio (HR) for readmission for myocardial infarction or heart failure. There was a similar proportion of readmission for myocardial infarction and heart failure at a four-year follow-up in patients with DM or MI, which was much higher when DM was associated with MI, with respect to patients without DM or MI. The HR (95% Coefficient Interval) for myocardial infarction in the DM without MI, non-DM with MI, and DM with MI groups with respect to the non-DM without MI group was 2511 (1592–3960), 2682 (1739–4138), and 5036 (3221–7876), respectively. The HR (95% CI) for the risk of readmission for heart failure in the DM without MI, non-DM with MI, and DM with MI groups with respect to the non-DM without MI group was 2663 (1825–3886), 2562 (1753–3744) and 4292 (2936–6274), respectively.ConclusionsThe association of DM and MI in patients treated in an Emergency Service identifies patients at very high risk of mortality and cardiovascular events.

Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay

The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the assay performance using samples from seven sites in Germany, Austria, and Switzerland. For specificity and sensitivity analyses, 7880 presumed negative pre-pandemic samples and 827 SARS-CoV-2 PCR-confirmed single or sequential samples from 272 different patients were tested, respectively. The overall specificity and sensitivity (≥14 days post-PCR) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87–99.99; 7876/7880) and 97.92% (95% CI: 95.21–99.32; 235/240), respectively. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON® SARS-CoV-2 S1/S2 IgG (99.95% [2032/2033] vs 98.82% [2009/2033]), ADVIA Centaur® SARS-CoV-2 Total (100% [928/928] vs 86.96% [807/928]), ARCHITECT SARS-CoV-2 IgG (99.97% [2931/2932] vs 99.69% [2923/2932]), iFlash-SARS-CoV-2 IgM (100.00% [928/928] vs 99.57% [924/928]), and EUROIMMUN Anti-SARS-CoV-2 IgG (100.00% [903/903] vs 97.45% [880/903]) and IgA (100.00% [895/895] vs 95.75% [857/895]) assays. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher sensitivity (≥14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG (98.70% [76/77] vs 87.01% [67/77]), iFlash-SARS-CoV-2 IgG (100.00% [76/76] vs 93.42% [71/76]) and IgM (100.00% [76/76] vs 35.53% [27/76]), and EUROIMMUN Anti-SARS-CoV-2 IgG (98.26% [113/115] vs 93.91% [108/115]) assays. Therefore, the Elecsys Anti-SARS-CoV-2 S assay demonstrated a reliable performance across various sample populations for the detection of anti-S antibodies.

Relationship between CA-125 Levels and Extrauterine Spread in Endometrial Cancer Endometrioid Type at Dr. Soetomo General Hospital Surabaya

Background: Endometrial cancer is the sixth most common malignancy incidence in women worldwide. The surgical staging in endometrial cancer management such as bilateral salpingooophorectomy and lymphadenectomy is not a routine procedure for all endometrial cancer patients. Therefore, a biomarker to estimate the presence of endometrial cancer metastases to adnexa and lymph nodes is needed. This study aims to find out the level of cancer antigen 125 (CA-125) in endometrial cancer endometrioid type and the relationship between the level of CA-125 and the incidence of adnexal metastases, lymph node metastases, clinical stage, and myometrial invasion.Methods: This observational analytic study used a direct observational design. The in-vitro quantitative examination was performed to measure CA-125 levels using CA-125 Advia Centaur CA-125 Kit. Fischer exact test used to analyzed CA-125 levels with the subject characteristics. All the statistical analyses were performed using SPSS v. 21.0.Results: Of the 30 research subjects with the characteristics of the most age groups of 51–60 years (60%), with the most multiparous parity (73.3%), grade III (43.3%), myometrial invasion &gt; 50% by 66.7%, early-stage (63.3%), the incidence of adnexal metastases (30%), and the incidence of lymph node (LN) metastases (10%), a significant relationship between CA-125 levels and lymph node (LN) metastases was found with a p = 0.041 and the phi association of 0.016 and between CA-125 levels and adnexal metastases with a p = 0.035 and the phi association of 0.026. There was also a significant relationship between CA-125 levels and the clinical stage (advanced stage) with p = 0.004 and the phi association of 0.002. There is no significant relationship with a p = 0.702 and a phi association value of -0.098.Conclusions: CA-125 can be used as a tumor marker to predict the presence of extrauterine metastases (adnexa &amp; lymph nodes).

External validation of a high-sensitive troponin I algorithm for rapid evaluation of acute myocardial infarction in a Danish cohort.

An accelerated diagnostic algorithm for ruling-in or ruling-out myocardial infarction (MI) after 1 hour (1 h) has recently been derived and internally validated for the Siemens ADVIA Centaur TNIH assay. We aimed to validate the diagnostic performance of the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in a Danish cohort. Patients with chest pain suggestive of MI were prospectively enrolled. High-sensitive troponin I (TNIH) was measured at admission (0 h) and after 30 minutes (30 m), 1 h, and 3 hours (3 h). We externally validated the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in Danish patients. Moreover, we applied the algorithm using the second TNIH measurement at 30 m instead of 1 h. We enrolled 1003 patients: median (Q1-Q3) age 64 (52-74) years, 42% female, and 23% with previous MI. Myocardial infarction was the final diagnosis in 9% of patients. Median (Q1-Q3) times from admission to 30 m and 1 h blood draw were 35 min (30-37 min) and 67 min (62-75 min), respectively. Using the 0 h and 1 h results, 468 (47%) patients were assigned to rule-out, 104 (10%) to rule-in, and 431 (43%) to the observational zone. This resulted in a negative predictive value of 100% (95% confidence interval: 99.2-100%), sensitivity of 100% (95.9-100%), positive predictive value of 79.8 (70.8-87.0%), and specificity of 97.7% (96.5-98.6%). The diagnostic performance after 30 m was similar. The TNIH 0 h/1 h algorithm ad modum Boeddinghaus performed excellently for rule-out of MI in a Danish cohort. The Boeddinghaus algorithm also performed excellently after only 30 m. NCT03634384. Rapid Use of High-Sensitive Cardiac Troponin I for Ruling-in and Ruling-out Acute Myocardial Infarction (RACING-MI), https://clinicaltrials.gov/ct2/show/NCT03634384.

Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers.

Anti-SARS-CoV-2 spike RBD (receptor-binding domain) IgG antibody levels were monitored in 1643 volunteer healthcare workers of Eginition, Evangelismos, and Konstantopoulio General Hospitals (Athens, Greece), who underwent vaccination with two doses of COVID-19 BNT162b2 mRNA vaccine (Pfizer) and had no history of SARS-CoV-2 infection. Venous blood was collected 20–30 days after the second vaccine dose and anti-RBD IgG levels were determined using CMIA SARS-CoV-2 IgG II Quant (Abbott) on ARCHITECT i System or ADVIA Centaur SARS-CoV-2 IgG (Siemens) on Centaur XP platform. From the total population of 1643 vaccinees (533 M/1110 F; median age = 49; interquartile range-IQR = 40–56), 1636 (99.6%) had anti-SARS-CoV-2 IgG titers above the positivity threshold of the assay used. One-Way ANOVA Kruskal-Wallis H test showed a statistically significant difference in the median of antibody titers between the different age groups (p < 0.0001). Consistently, Spearman’s correlation coefficient (r) for IgGs and age as continuous variables was −0.2380 (p = 1.98 × 10−17). Moreover, antibody titers were slightly higher by 1.2-mean fold (p = 3 × 10−6) in the total female population of the three hospitals (median = 1594; IQR = 875–2584) as compared to males (median = 1292; IQR = 671.9–2188). The present study supports that BNT162b2 vaccine is particularly effective in producing high anti-SARS-CoV-2 IgG levels in healthy individuals, and this humoral response is age- and gender-dependent.

Single troponin measurement to rule-out acute myocardial infarction in early presenters

BackgroundA single high-sensitive cardiac troponin (hs-cTn) can be used to rule-out acute myocardial infarction (MI) in patients presenting >3 hours (3 h) after chest pain onset to the emergency department. This study aimed to investigate the safety of ruling-out MI in early presenters with chest pain ≤3 h using a single hs-cTnI at admission. MethodsWe prospectively enrolled patients presenting with chest pain suggestive of MI. Hs-cTnI (Siemens ADVIA Centaur TNIH, Limit of detection: 2.2 ng/L) was measured at admission. Two physicians adjudicated final diagnosis. A diagnostic cut-off value <3 ng/L was used to rule-out MI. Patients were classified as early (chest pain ≤3 h) or late presenters (>3 h). ResultsWe included 1370 patients with available admission hs-cTnI results: median (Q1–Q3) age 65 (52–74), female sex: 43%, previous MI: 22%. We confirmed MI in 118 (8.6%) patients. Overall, 470 (34%) patients were classified as early, 770 (56%) as late presenters, and 130 (9%) patients had unknown onset. When applying the diagnostic cut-off value, MI was correctly ruled-out at admission in 370 (27%) patients: 134 (29%) early presenters, 206 (27%) late presenters and 30 (23%) patients with unknown onset. This resulted in an overall negative predictive value of 100% (95% CI: 99.0–100%), with both 100% (97.3–100%) for early and 100% (98.2–100%) for late presenters, respectively. Sensitivity was similarly high in the two groups. ConclusionMI could be safely ruled-out in all patients presenting with chest pain ≤3 h when using a single hs-cTnI value <3 ng/L as diagnostic cut-off. Trial registration numberNCT03634384.