Tumour markers are a very heterogeneous group of molecules that are generally found in very small concentrations in the plasma and serum of healthy individuals. In the process of neoplastic differentiation the cell can synthesize, release, or induce synthesis of other cells, thus increasing their concentration in plasma and serum. These substances may also increase their plasma concentration in patients without cancer due to processes that increase the release or reduce catabolism, and so give rise to false positives. An understanding of the main physiopathological processes that increase the concentrations of these substances could improve our interpretation of tumour markers and their clinical application. In this study we review the physiopathological processes that may increase the plasma concentrations of tumour markers. We performed a bibliography review in PubMed, searching for causes of false positives for the following tumour markers: α-Fetoprotein, CA 125, CA 15-3, CA 19-9, CA 72-4, carcinoembryonic antigen, CYFRA 21-1, squamous cell carcinoma, prostatic specific antigen, β(2)-microglobulin, choriogonadotropin (β chain), chromogranin A, neuron specific enolase, HER2-neu, progastrin releasing peptide, S-100, and thyroglobulin. The results favour the use of tests which can identify pathological processes that may increase tumour marker concentrations.

Pleural effusions present a diagnostic challenge. Approximately 20% are associated with cancer and some 50% require invasive procedures to perform diagnosis. Determination of tumour markers may help to identify patients with malignant effusions. Two strategies are used to obtain high specificity in the differential diagnosis of malignant pleural effusions: a) high cut-off, and b) fluid/serum (F/S) ratio and low cut-off. The aim of this study is to compare these two strategies and to establish whether the identification of possible false positives using benign biomarkers – ADA, CRP and % of polymorphonuclear cells – improves diagnostic accuracy. We studied 402 pleural effusions, 122 of them malignant. Benign biomarkers were determined in pleural fluid, and CEA, CA72-4, CA19-9 and CA15-3 in pleural fluid and serum. Establishing a cut-off value for each TM for a specificity of 100%, a joint sensitivity of 66.5% was obtained. With the F/S strategy and low cut-off points, sensitivity was 77% and specificity 98.2%, Subclassifying cases with negative benign biomarkers, both strategies achieved a specificity of 100%; sensitivity was 69.9% for single determination and 80.6% for F/S ratio. The best interpretation of TM in the differential diagnosis of malignant pleural effusions is obtained using the F/S ratio in the group with negative benign biomarkers.

With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.

In Long COVID, dysfunction in the pituitary–adrenal axis and alterations in immune cells and inflammatory status are warned against. We performed a prospective study in a cohort of 42 patients who suffered COVID-19 at least 6 months before attending the Long COVID unit at Althaia Hospital. Based on Post-COVID Functional Status, 29 patients were diagnosed with Long COVID, while 13 were deemed as recovered. The hormones of the pituitary–adrenal axis, adrenocorticotropin stimulation test, and immune cell profiles and inflammatory markers were examined. Patients with Long COVID had significantly lower EuroQol and higher mMRC scores compared to the recovered individuals. Their symptoms included fatigue, myalgia, arthralgia, persistent coughing, a persistent sore throat, dyspnoea, a lack of concentration, and anxiety. We observed the physiological levels of cortisol and adrenocorticotropin in individuals with or without Long COVID. The results of the adrenocorticotropin stimulation test were similar between both groups. The absolute number of neutrophils was lower in the Long COVID patients compared to recovered individuals (p < 0.05). The total count of B lymphocytes remained consistent, but Long COVID patients had a higher percentage of mature B cells compared to recovered participants (p < 0.05) and exhibited a higher percentage of circulating resident memory CD8+ T cells (p < 0.05) and Treg-expressing exonucleases (p < 0.05). Our findings did not identify adrenal dysfunction related to Long COVID, nor an association between adrenal function and clinical symptoms. The data indicated a dysregulation in certain immune cells, pointing to immune activation. No overt hyperinflammation was observed in the Long COVID group.

Aims: The objective of the present study is to determine the prognostic value of clinical variables and biomarkers in patients with advanced stages of NSCLC and establish a prognostic classification of these patients. Methods: For 135 patients with advanced NSCLC we determined their clinical variables and their levels of CEA, CA 125, CYFRA 21–1, albumin, LDH, erythrosedimentation and leukocytes. Results: Multivariate analysis identified PS (ECOG) >1, metastases, no anti-neoplastic treatment, CA 125 >35 U/mL, CYFRA 21–1 >3.3 ng/mL and leukocytes >10'000/μL, as independent prognostic factors for survival. Patients were classified into 3 groups according to the number of adverse prognostic factors (APF). One point was assigned for each APF, except for chemotherapy treatment. Patients with 0–1 APF represented our reference group: patients with 2–3 APF had HR=2.7 (95% CI: 1.5–4.6), while patients with 4–5 APF had HR=8.8 (95% CI: 4.6–16.8). This “score” maintained the differences between risk groups both in patients who received antineoplastic treatment and in those who did not. Conclusion: The application of a score that includes clinical data and biomarkers may improve the prognostic classification of NSCLC patients.