Will 14-3-3η Be a New Diagnostic and Prognostic Biomarker in Rheumatoid Arthritis? A Prospective Study of Its Utility in Early Diagnosis and Response to Treatment

Aim of the Work. To evaluate diagnostic and prognostic capacity of 14-3-3η protein in early RA, investigate its pathogenic and theragnostic role, and find its correlations with disease activity and severity in established RA patients. Subjects and Methods: 80 patients with early RA, 80 patients with established RA, and 80 healthy controls were included in this study. ROC curve analysis of RF, ACCP, and 14-3-3η in early disease was conducted, and serum levels of 14-3-3η were assessed by ELISA and reassessed in early RA patients 6 months after anti-TNF therapy. Correlation of 14-3-3η with parameters of disease activity and severity was analyzed. Results. Serum14-3-3η levels were significantly higher in all RA patients than in controls P < 0.001 , its sensitivity was 86.7% and 88.3% in early and established RA patients with a significant difference with RF and ACCP at early disease, and the specificity was 96.7%. There was a significant reduction of 14-3-3η levels 6 months after treatment in the first group p = 0.004 , and there was a significant positive correlation between serum 14-3-3η levels and parameters of disease activity and severity. Conclusion. 14-3-3η could be a novel, potent, and efficacious diagnostic, and prognostic marker for RA with high sensitivity, that may become a new therapeutic target for RA.

COMPARATIVE ANALYSIS OF ANTIBODY RESPONSES FROM COVID-19 CONVALESCENTS RECEIVING VARIOUS VACCINES REVEALS CONSISTENT HIGH NEUTRALIZING ACTIVITY FOR SARS-CoV-2 VARIANT OF CONCERN OMICRON.

The novel SARS-CoV-2 Omicron variant of concern (VOCs), with its escape from unboosted vaccines and monoclonal antibodies, is demanding for a return to COVID19 convalescent plasma therapies. Lessons learnt from previous usage of CCP suggests focusing on outpatients and using high nAb-titer units in early disease stages. In this systematic analysis, we show that CCP from unvaccinated donors is not effective against Omicron, while CCP from vaccinees convalescents from previous VOCs or third-dose uninfected vaccinees is likely to remain effective against Omicron. countries. CCP remains the only antibody-based therapy that keeps up with the variants and provides an effective tool to combat the emergence of variants that defeat monoclonal antibodies. Consequently, there is a need for continue study of the variables that determine CCP efficacy.

Extracellular Vesicles as Intercellular Communication Vehicles in Regenerative Medicine

Extracellular vesicles (EVs) represent cell-specific carriers of bioactive cargos that can be of importance in either physiological or pathological processes. Frequently, EVs are seen as intercellular communication vehicles, but it has become more and more evident that their usefulness can vary from circulating biomarkers for an early disease diagnosis to future therapeutic carriers for slowing down the evolution of different afflictions and their ability to restore damaged tissue/organs. Here, we summarize the latest progress of EVs classification, biogenesis, and characteristics. We also briefly discuss their therapeutic potential, with emphasis on their potential application in regenerative medicine.

P-OGC45 Could lymphatic, vascular or perineural invasion status improve clinical staging prior to oesophagectomy?

Background Unimodal treatment of oesophagogastric cancer (OGC) with surgery only is currently reserved for patients with early disease. Presence of vascular (VI), perineural (PNI) or lymphatic vessel invasion (LI) in pathological samples have been shown to be negative prognostic indicators of survival. These factors have been found to be associated with more advanced disease. Staging of OGC has limitations and in neoadjuvant naive populations it has been shown to be imperfect. It is unknown whether VI, PNI or LI could play any role during the staging process. Methods Patients with early disease (cT2 or less and cN0) who underwent unimodal treatment of their oesophageal or junctional cancer with oesophagectomy between 2010 and 2019 in a single centre were included in this study. Therelationship between presence of LI, VI and PNI on pathological samples with incorrect staging/upstaging indicating locally advanced disease (defined as pT3+ or pN+) was studied using logistic regression model. Results There were 128 patients included. 26 patients (20%) were upstaged to pT3+ or pN+. LI, VI and PNI were present in 18%, 11% and 8% respectively. The presence of LI and clinical T stage were independently predictive of incorrect staging/upstaging in multivariable logistic regression analysis. LI (OR 12.5 95%CI 3.7-42.8, p &lt; 0.001) and cT2 (OR 5.9 95%CI 1.5-23.2, p = 0.01). Conclusions These results indicate that the presence of LI from pathological samples is a strong independent prognostic factor of incorrect staging which would normally favour neoadjuvant treatment. The presence of LI suggests aggressive disease. Further studies should concentrate on the possibility of obtaining LI status from preoperative biopsies or endoscopic mucosal resection samples. This staging information could play an important role in deciding whether neoadjuvant therapy is indicated in patients staged as early disease.

Exploring Serum NMR-Based Metabolomic Fingerprint of Colorectal Cancer Patients: Effects of Surgery and Possible Associations with Cancer Relapse

Background: Colorectal cancer (CRC) is the fourth most commonly diagnosed and third most deadly cancer worldwide. Surgery is the main treatment option for early disease; however, a relevant proportion of CRC patients relapse. Here, variations among preoperative and postoperative serum metabolomic fingerprint of CRC patients were studied, and possible associations between metabolic variations and cancer relapse were explored. Methods: A total of 41 patients with stage I-III CRC, planned for radical resection, were enrolled. Serum samples, collected preoperatively (t0) and 4–6 weeks after surgery before the start of any treatment (t1), were analyzed via NMR spectroscopy. NMR data were analyzed using multivariate and univariate statistical approaches. Results: Serum metabolomic fingerprints show differential clustering between t0 and t1 (82–85% accuracy). Pyruvate, HDL-related parameters, acetone, and 3-hydroxybutyrate appear to be the major players in this discrimination. Eight out of the 41 CRC patients enrolled developed cancer relapse. Postoperative, relapsed patients show an increase of pyruvate and HDL-related parameters, and a decrease of Apo-A1 Apo-B100 ratio and VLDL-related parameters. Conclusions: Surgery significantly alters the metabolomic fingerprint of CRC patients. Some metabolic changes seem to be associated with the development of cancer relapse. These data, if validated in a larger cohort, open new possibilities for risk stratification in patients with early-stage CRC.