sFlt-1 and CA 15.3 are indicators of endothelial damage and pulmonary fibrosis in SARS-CoV-2 infection

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p < 0.001 Sens. 83.9% and Spec. 86.7%) with presence, extent and severity of the disease. Moreover, CA 15.3 appeared significantly increased in COVID-19 severe lung fibrosis (ICU vs NON-ICU patients 42.6 ± 3.3 vs 25.7 ± 1.5 U/mL, p < 0.0001) and was associated with lung damage severity grade (ROC AUC 0.958, decision threshold > 24.8 U/mL, p < 0.0001, Sens. 88.4% and Spec. 91.8%). In conclusion, serum levels of sFlt-1 and CA 15.3 appeared useful tools for categorizing COVID-19 clinical stage and may represent a valid aid for clinicians to better personalise treatment.

Prognostic role of neoplastic markers in Takotsubo syndrome

Takotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic biomarkers [CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)] as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL, p = 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank p < 0.01, HR = 5.3, 95% CI 1.9–14.8, HR = 7.8 95% CI 2.4–25.1, respectively, p < 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank p < 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6–52.5, p = 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE.

Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy

Circulating tumor DNA (ctDNA) levels may predict response to anticancer drugs, including CDK4/6 inhibitors and endocrine therapy combinations (CDK4/6i+ET); however, critical questions remain unanswered such as which assay or statistical method to use. Here, we obtained paired plasma samples at baseline and week 4 in 45 consecutive patients with advanced breast cancer treated with CDK4/6i+ET. ctDNA was detected in 96% of cases using the 74-gene Guardant360 assay. A variant allele fraction ratio (VAFR) was calculated for each of the 79 detected mutations between both timepoints. Mean of all VAFRs (mVAFR) was computed for each patient. In our dataset, mVAFR was significantly associated with progression-free survival (PFS). Baseline VAF, on-treatment VAF or absolute changes in VAF were not associated with PFS, nor were CA-15.3 levels at baseline, week 4 or the CA-15.3 ratio. These findings demonstrate that ctDNA dynamics using a standardized multi-gene panel and a unique methodological approach predicts treatment outcome. Clinical trials in patients with an unfavorable ctDNA response are needed.

Biotin interference in several electrochemiluminescence immunoassays (eclia)

– Background: The aim of this study is to define the interference of biotin in several endocrine, tumor marker, and vitamin assays performed by an electrochemiluminescence method, trying to determinate the critical level that causes biotin interference. – Material and methods: Working biotin solutions were prepared in phosphate-buffered saline (PBS) at different concentrations (10000, 7500, 5000, 2500, 1250, 625, and 312.5 ng/mL), which were spiked on the samples to obtain final concentrations ten-fold lower. Each serum biotin dilution was tested in triplicate, using at least two levels of analytes. Determinations of several endocrine, vitamins, tumor and bone markers were carried-out with eletrochemilumenescent immunoassays on the cobas e801 and cobas e411. Comparison between the results obtained by analyzing the biotin-spiked samples and the reference PBS-spiked samples was performed using Microsoft Excel. The relative bias with the interfering-free specimen was calculated for each biotin concentration. Interference was considered significant when the relative bias exceeded 10%. Glick´s interferographs were performed plotting the percentage of change vs. biotin concentration. – Results: Analyte concentrations were spuriously decreased in 12 sandwich immunoassays and falsely increased in 11 competitive immunoassays. However thyrotropin and CA 15.3 antigen were not significantly affected. – Conclusions: Except CA 15.3 and TSH, the methods tested were susceptible to biotin interference. Falsely low values occurred in sandwich assays and high bias in competitive assays. Clinicians and laboratorians should be aware of the medical importance of biotin interference as a cause of misdiagnosis and incorrect treatment.

Neoplastic markers in Takotsubo syndrome. Results from a prospective registry

Background Takotsubo syndrome (TTS) is an acute heart failure syndrome with significant rate of in and out-of hospital mayor cardiac adverse events (MACE). Aim of this study Evaluate the possible role of neoplastic biomarkers (CA 15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)) as prognostic marker at short- and long-term follow-up in subjects with TTS. Methods Ninety consecutive subjects with TTC were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9, CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Results Forty-three (46%) patients experienced MACE during hospitalization. These patients were older (78±9 vs 72±12 p=0.01), had lower LVEF (32±7 vs 38±8 p=0,01) and increased levels of CEA (4.3±6.2 vs 2.2±1.5 ng/ml p=0.03). CEA and CA 19.9 levels at admission were statistically correlated with CRP and NT-proBNP levels (both p&lt;0.05). At long term follow-up CEA and CA 19.9 levels (higher than median) were associated with increased risk of death (log rank p&lt;0.01 (both) RR=5.3 CI 95% 1.9–14.8 p&lt;0.01; RR=7.8 CI 95% 2.4–25.1 p&lt;0.01 respectively). At multivariate analysis including age, sex and admission LVEF, CEA and CA 19.9 levels higher than median were an independent predictor of MACE at long term (p&lt;0.01 RR 3.5 CI 1.6–7.3). Conclusion CEA and CA 19.9 serum levels are associated with higher risk of in-hospital MACE and death at long-term. Funding Acknowledgement Type of funding source: None

Marcadores tumorales y su valor en ginecología

Los marcadores tumorales (MT) son moléculas que pueden estar elevadas en presencia de un cáncer, bien como reacción del huésped ante el tumor o bien como producto del propio tumor. Los MT no son específicos de las neoplasias, y pueden encontrarse concentraciones apreciables en un gran número de situaciones fisiológicas o patológicas tumorales. Son útiles para la detección precoz de un cáncer, para establecer el estadiaje, la respuesta a la terapia, predecir las recurrencias, presentar una elevada sensibilidad, especificidad y valor predictivo positivo y ser órgano-específicos y tumor-específicos. Dentro de los que representan más relevancia y valor en ginecología se destacan: el CEA, AFP, betaHCG, CA125, CA 15.3, CA 19.9, SCC, Citoqueratinas y LDH. Los marcadores biológicos son cambios medibles, ya sean bioquímicos, fisiológicos o morfológicos que se asocian a la exposición a algún tóxico. En las patologías oncológicas-gineco-lógicas son referidos con frecuencia los BRCA1, BCRA2 y el Her2; también pueden mencionarse: los receptores hormonales (ER y PR). El verdadero valor clínico en ginecología reside en el segui-miento de las pacientes, tanto para detectar una recidiva temprana como para evaluar la efectividad del tratamiento. En general, los marcadores tumorales y los marcadores biológicos pueden ser la clave para reducir la mortalidad por cáncer a nivel mundial. Por lo que, nos proponemos esta revisión bibliográfica para realzar los MT más utili-zados en la práctica clínica en el área de ginecología.