Methotrexate & rheumatoid arthritis associated atherosclerosis: A narrative review of multidisciplinary approach for risk modification by the international board of experts.

Rheumatoid arthritis (RA) is an idiopathic, autoimmune connective tissue disorder that primarily affects the synovial joints, causing symmetric, erosive-deforming polyarthritis. It is also associated with extra-articular manifestations, particularly cardiovascular (CV) diseases (CVD). CV risk modification in RA remains unsolved despite recent advances in the management of RA. RA is an independent risk factor for atherosclerosis. RA and atherosclerosis share similar pathophysiological features (such as the pro-inflammatory cascade activation including interleukin-6) and risk factors (such as microflora dysbacteriosis and smoking). Patients with RA experience an exacerbation of atherogenesis, with atheromas destabilization, endothelial dysfunction, vasculitis, and hypercytokinemia. Consequently, the inflammatory response associated with RA is the basis for CVD development. The treat-to-target strategy not only improved RA control but also had a favorable effect on the morpho-functional state of the CV system in patients living with RA. Thus, disease-modifying antirheumatic drugs (DMARDs) - in particular methotrexate - may have a beneficial effect on the prevention of CV events in RA. It must be mentioned that RA is a serious multi-system disease, not only because of a window period during which the course of RA can be reversed, but also due to early damage to the heart and blood vessels. For this reason, a thorough cardiological assessment must be performed for all patients with RA, regardless of sex, age, disease stage, and disease activity score.

Diabetic Cardiomyopathy: 2023 Update by the International Multidisciplinary Board of Experts.

Diabetes mellitus (DM) is considered by many the pandemic of the 21st century and is associated with multiple organ damages. Among these, cardiovascular complications are responsible for an incredible burden of mortality and morbidity in Western Countries. The study of the pathological mechanisms responsible for the cardiovascular complications in DM patients is key for the development of new therapeutic strategies. The metabolic disorders caused by hyperglycemia, insulin resistance, and dyslipidemia, results in a cascade of pathomorphological changes favoring the atherosclerotic process and leading to myocardial remodeling. Parallel to this, oxidative stress, calcium overload, mitochondrial dysfunction, activation of protein kinase C signaling pathways, myocardial lipomatosis, and low-grade inflammation of the myocardium - are the main pathways responsible for the diabetic cardiomyopathy development. This review aims to appraise and discuss the pathogenetic mechanisms behind the diabetic cardiomyopathy development.

Pathomorphological Features of the Novel Coronavirus Disease in Patients with Systemic Amyloidosis.

Amyloidosis is one of the rare systemic illnesses characterized by the deposition of amyloid fibrils in various organs and tissues. There is a common point between COVID-19 and systemic amyloidosis regarding the multiorgan involvement in the pathological process which leads to a heightened risk for severe morbidity and mortality in amyloidosis patients who contracted COVID-19. We performed a pathomorphological analysis of the autopsy records of 22 patients who had COVID-19 and pre-existing systemic amyloidosis. The premortem diagnosis of systemic amyloidosis was established in 55% of patients, and in other 45% of cases, amyloidosis was found at autopsy. Based on the results of immunohistochemical amyloid typing, amyloid A (AA) amyloidosis was detected in 23%, amyloid light chain (AL) lambda in 32%, AL kappa-in 9%, and transthyretin (ATTR) amyloidosis-in 36% of observations. Immunohistochemical staining with an antibody against SARS-CoV-2 Spike (S) protein revealed positive immune reactions in type II alveolocytes in 59% of deceased persons. The analysis of autopsy findings indicates that patients with systemic amyloidosis are more likely to experience an aggressive clinical course of COVID-19 which leads to a multiorgan failure and a higher risk of fatal outcome.

Signaling Pathways in the Pathogenesis of Barrett's Esophagus and Esophageal Adenocarcinoma.

Barrett's esophagus (BE) is a premalignant lesion that can develop into esophageal adenocarcinoma (EAC). The development of Barrett's esophagus is caused by biliary reflux, which causes extensive mutagenesis in the stem cells of the epithelium in the distal esophagus and gastro-esophageal junction. Other possible cellular origins of BE include the stem cells of the mucosal esophageal glands and their ducts, the stem cells of the stomach, residual embryonic cells and circulating bone marrow stem cells. The classical concept of healing a caustic lesion has been replaced by the concept of a cytokine storm, which forms an inflammatory microenvironment eliciting a phenotypic shift toward intestinal metaplasia of the distal esophagus. This review describes the roles of the NOTCH, hedgehog, NF-κB and IL6/STAT3 molecular pathways in the pathogenesis of BE and EAC.

Colorectal Serrated Lesions: A Current View on Clinical, Morphological, Molecular, and Genetic Diagnostic Criteria.

OBJECTIVE: Serrated colorectal lesions are a group of colonic lesions with a serrated (saw-tooth) profile of the surface epithelium and crypts, and peculiar molecular and genetic developmental mechanisms that are incompletely understood. These formations cause concern due to their premalignant potential. AIM: The review is dedicated to serrated lesions of colon and appendix. We focused on modern classification, role in carcinogenesis, as well as new approaches to morphological diagnosis. METHODS: A literature search was performed using PubMed, Scopus, ResearchGate, Google, MEDLINE, and ScienceDirect databases to find studies of serrated colorectal lesions related cancer published between 2000 and 2020 that address epidemiological risk factors, underlying pathophysiological mechanism and enable our review of these factors as well as molecular, genetics, and structural patterns. RESULTS: Serrated colorectal lesions take one third of all benign neoplasms of the colon in the pathologist's practice. The active study of serrated lesions began in the 1900s. Terminology and diagnostic criteria changed in the updated classification in 2019. Morphological criteria, immunohistochemical and molecular profile, endoscopic and clinical characteristics are reviewed. CONCLUSION: Although significant efforts were made in attempt to improve our understanding and diagnostic criteria of serrated polyps of colorectum, very little has changed since the original morphologic description of preneoplastic serrated lesions in early 2000s. There remains a need for more research in order to develop more definitive immuophenotypic and molecular biomarkers in order to distinguish between non-neoplastic and neoplastic serrated lesions.