Project description:Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo.
Project description:Lynch syndrome (LS) is caused by mutations in mismatch repair genes and is characterized by a high cumulative risk for the development of mainly colorectal carcinoma and endometrial carcinoma. Early detection of LS is important since surveillance can reduce morbidity and mortality. However, the diagnosis of LS is complicated by the absence of a pre-morbid phenotype and germline mutation analysis is expensive and time consuming. Therefore it is standard practice to precede germline mutation analysis by a molecular diagnostic work-up of tumours, guided by clinical and pathological criteria, to select patients for germline mutation analysis. In this review we address these molecular analyses, the central role for the pathologist in the selection of patients for germline diagnostics of LS, as well as the molecular basis of LS.
Project description:Turnaround time is an important quality indicator in surgical pathology. Retrospective analysis of three data points in September 2014, January 2015, and February 2015 showed that on average, about a quarter (24%) of routine surgical pathology cases (26%, 19%, and 27% respectively) are not reported on time and do not meet the accepted level of the College of American Pathologists' (CAP) standard turnaround time, which states at least 90% of routine surgical pathology cases should be reported and verified within two days. Our daily observation supported by a root cause analysis exercise revealed that subprocesses including slide allocation and delivery to pathologists, slide review by pathologists, report editing by transcriptionists, and report verification by pathologists are where most delays occur. Thus, to tackle these process issues we developed a quality improvement project using the model of improvement methods to streamline the sample flow process and avoid unjustified reporting delay. The improvement ideas included developing a time log sheet to be attached with all pathology requests, and sending a daily reminder email followed by a phonecall to all pathologists to verify completed reports on the same day. These intervention elements were tested using multiple PDSA cycles resulting in a very noticeable improvement, with more than 94% of all routine cases reported in less than two days, meeting and exceeding the CAP standards. Such noticeable improvement in turnaround of surgical pathology reports will eventually lead to improving the quality and safety of patient care outcome, including diagnosing patients on time, developing the appropriate treatment plan, and avoiding unjustified complications resulting in morbidity and mortality due to delayed reports.
Project description:Molecular pathology as applied to neoplasia is a rapidly expanding component of the discipline of pathology that uses molecular biology tools in addition to conventional morphologic, immunohistochemical and chemical analyses of abnormalities in tissues and cells to understand the etiology and pathogenesis of tumors, establish their diagnosis, and contribute to prognostication and therapeutic decisions for cancer patient care. Biomarkers are a fundamental component of personalized cancer care, and the discipline of molecular pathology therefore contributes throughout the continuum from biomarker research to use in standard-of-care personalized cancer therapy. This brief review addresses some of the specific roles of molecular pathology in that continuum.