Molecular Markers for Bladder Cancer Screening: An Insight into Bladder Cancer and FDA-Approved Biomarkers.

Bladder cancer is one of the most financially burdensome cancers globally, from its diagnostic to its terminal stages. The impact it imposes on patients and the medical community is substantial, exacerbated by the absence of disease-specific characteristics and limited disease-free spans. Frequent recurrences, impacting nearly half of the diagnosed population, require frequent and invasive monitoring. Given the advancing comprehension of its etiology and attributes, bladder cancer is an appealing candidate for screening strategies. Cystoscopy is the current gold standard for bladder cancer detection, but it is invasive and has the potential for undesired complications and elevated costs. Although urine cytology is a supplementary tool in select instances, its efficacy is limited due to its restricted sensitivity, mainly when targeting low-grade tumors. Although most of these assays exhibit higher sensitivity than urine cytology, clinical guidelines do not currently incorporate them. Consequently, it is necessary to explore novel screening assays to identify distinctive alterations exclusive to bladder cancer. Thus, integrating potential molecular assays requires further investigation through more extensive validation studies. Within this article, we offer a comprehensive overview of the critical features of bladder cancer while conducting a thorough analysis of the FDA-approved assays designed to diagnose and monitor its recurrences.

Results Obtained from a Pivotal Validation Trial of a Microsatellite Analysis (MSA) Assay for Bladder Cancer Detection through a Statistical Approach Using a Four-Stage Pipeline of Modern Machine Learning Techniques.

Several studies have shown that microsatellite changes can be profiled in urine for the detection of bladder cancer. The use of microsatellite analysis (MSA) for bladder cancer detection requires a comprehensive analysis of as many as 15 to 20 markers, based on the amplification and interpretations of many individual MSA markers, and it can be technically challenging. Here, to develop fast, more efficient, standardized, and less costly MSA for the detection of bladder cancer, we developed three multiplex-polymerase-chain-reaction-(PCR)-based MSA assays, all of which were analyzed via a genetic analyzer. First, we selected 16 MSA markers based on 9 selected publications. Based on samples from Johns Hopkins University (the JHU sample, the first set sample), we developed an MSA based on triplet, three-tube-based multiplex PCR (a Triplet MSA assay). The discovery, validation, and translation of biomarkers for the early detection of cancer are the primary focuses of the Early Detection Research Network (EDRN), an initiative of the National Cancer Institute (NCI). A prospective study sponsored by the EDRN was undertaken to determine the efficacy of a novel set of MSA markers for the early detection of bladder cancer. This work and data analysis were performed through a collaboration between academics and industry partners. In the current study, we undertook a re-analysis of the primary data from the Compass study to enhance the predictive power of the dataset in bladder cancer diagnosis. Using a four-stage pipeline of modern machine learning techniques, including outlier removal with a nonlinear model, correcting for majority/minority class imbalance, feature engineering, and the use of a model-derived variable importance measure to select predictors, we were able to increase the utility of the original dataset to predict the occurrence of bladder cancer. The results of this analysis showed an increase in accuracy (85%), sensitivity (82%), and specificity (83%) compared to the original analysis. The re-analysis of the EDRN study results using machine learning statistical analysis proved to achieve an appropriate level of accuracy, sensitivity, and specificity to support the use of the MSA for bladder cancer detection and monitoring. This assay can be a significant addition to the tools urologists use to both detect primary bladder cancers and monitor recurrent bladder cancer.

Risk of Stroke With Mitral Stenosis: The Underlying Mechanism, Treatment, and Prevention.

Mitral stenosis (MS), a valvular heart disease, is defined by the narrowing of the mitral valve orifice. The common risk factors for stroke include mitral annular calcification (MAC), diabetes mellitus (DM), male gender, hypertension (HTN), hyperlipidemia, and obesity. Endothelial damage, hypercoagulability, and blood stasis in the left atrium promote the development of the thrombus. Among all the risk factors described, MAC is the independent predictor of stroke. The complicated mechanisms responsible for thromboembolism, predisposing factors for thromboembolism, the risk of cerebrovascular accident (CVA) in MS patients, advanced standardized assessment models for identifying those at risk for stroke, and the possible advantages and disadvantages of available therapies have all been discussed in this review article. We have also discussed newer oral anticoagulants (NOACs) like dabigatran, edoxaban, apixaban, and rivaroxaban. Non-pharmacological therapies are also highlighted such as left atrial appendage ligation and occlusion devices. We also conducted a thorough review of the literature on the efficacy and safety of various NOACs in reducing the risk of stroke.

Cirrhosis and Coagulopathy: Mechanisms of Hemostasis Changes in Liver Failure and Their Management.

Cirrhosis is an end-stage liver disease that can cause changes in any component of the hemostatic system. The net effects of the complicated hemostatic changes have long been unknown due to concurrent changes in pro-and antihemostatic drivers. Coagulation disorders are caused by various factors, including decreased clotting and inhibitor factor synthesis, reduced clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis, and increased intravascular coagulation. This review discusses the pathogenesis of coagulopathy and multiple studies related to its clinical presentations. This article also highlights an additional problem in the diagnostic and therapeutic approach to this group of patients: the fact that traditional coagulation tests and transfusional strategies may not be reliable for assessing and managing bleeding or thrombotic risks. Hence, multiple management options have been assessed for bleeding and thrombosis in liver disease.

Ulcerative Colitis-Induced Colorectal Carcinoma: A Deleterious Concatenation.

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal ailment that encompasses Crohn's disease (CD) and ulcerative colitis (UC). UC is an idiopathic, chronic inflammatory condition of the colonic mucosa that begins in the rectum and progresses proximally in a continuous way over a portion of the entire colon. Chronic inflammation is linked to cancer, and IBD-related chronic colonic inflammation raises the risk of colorectal cancer. Chronic inflammation has been linked to cancer, and chronic colonic inflammation caused by IBD increases the risk of colorectal cancer (CRC). When CRC arises in people with IBD, unlike sporadic CRC, the lesions are difficult to identify due to mucosal alterations produced by inflammation. The total prevalence of IBD-associated CRC is increasing due to the rapidly increasing frequency of IBD. Screening and surveillance colonoscopy in IBD patients is considered to allow for the early diagnosis of dysplasia and cancer, improving the prognosis of IBD-related CRC by giving patients proactive therapy. This article has reviewed literature pertaining to the mechanisms related to CRC development in UC and its clinical and therapeutic implications.

Tiny Toes to Tau Tangles: Down's Syndrome and Its Association With Alzheimer's Disease.

Down's syndrome (DS) is a common genetic condition caused by the trisomy of chromosome 21, which leads to the development of many multisystemic complications, early-onset Alzheimer's disease (AD) being one of its most common complications. In this article, we have performed an intensive literature review that established a strong relationship between AD and DS. These two conditions are clubbed pathologically, clinically, and diagnostically to understand the association between AD and DS. This article focuses on understanding the impact of AD on a DS patient on both clinical and pathological levels and exploring some advanced treatment modalities. It has also emphasized the importance of early screening and diagnosis for AD in this group of patients to prevent AD development. Regular monitoring, early diagnosis, and a proper treatment plan can slow the AD occurrence in DS patients.

Systemic Lupus Erythematosus and Cardiovascular Disease.

Systemic lupus erythematosus (SLE) is a condition in which autoimmune inflammation affects nearly every organ in the human body; it is characterized by a relapsing-remitting pattern. Systemic inflammation and tissue damage can arise from autoantibodies, the creation of immune complexes, and the deposition of autoantibodies, all defined as autoimmune diseases. Women of reproductive age are at a high risk of developing lupus, a chronic systemic condition. Among women between the ages of 15 and 44 years, the female-to-male ratio for the occurrence of lupus is as high as 13:1, while it is only 2:1 in children and in the elderly. In addition to accelerated atherosclerosis, SLE is associated with an increased risk of cardiovascular (CV) events such as coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular accident (CVA). Several SLE-specific processes, including impaired immunological regulation, impaired endothelial cell (EC) function, impaired vascular repair, hyperleptinemia, and traditional risk factors, contribute to early atherosclerosis in the disease. CAD can occur at any stage of the disease's progression, with younger individuals being much more at risk than their age-matched counterparts. This review article aims to provide a unique insight into the relationship between SLE and cardiovascular disease (CVD) by discussing the pathophysiological role of CVD in SLE, outlining screening criteria, and highlighting the treatment options for CVD in connection with SLE.