Hepatic Epithelioid Hemangioendothelioma.

Epithelioid hemangioendothelioma is a rare vascular tumor, composed of epithelioid and histiocytoid vascular endothelial cells in myxoid or fibrotic stroma, which can arise in multiple locations throughout the body. In the liver, this neoplasm usually presents on imaging as an incidental finding of multifocal, heterogeneously enhancing nodules in both lobes or presents clinically with nonspecific abdominal symptoms. Histologically, the tumor has been mistaken for metastatic carcinoma, angiosarcoma, hepatocellular carcinoma, and cholangiocarcinoma. The neoplasm usually stains positive for vascular markers, such as factor VIII-related antigen, CD31, and CD34, and negative for cytokeratins. The translocation t(1;3)(p36.3;q25), resulting in the CAMTA1- WWTR1 fusion product, is the most commonly identified genetic abnormality with this tumor. Although hepatic epithelioid hemangioendothelioma can have a varied clinical course, it is generally considered less aggressive than angiosarcoma. There is no consensus treatment protocol and techniques including liver transplantation, liver resection, chemotherapy and/or radiation therapy, and surveillance have all been used with varying outcomes.

Needs and workflow assessment prior to implementation of a digital pathology infrastructure for the US Air Force Medical Service.

BACKGROUND: Advances in digital pathology are accelerating integration of this technology into anatomic pathology (AP). To optimize implementation and adoption of digital pathology systems within a large healthcare organization, initial assessment of both end user (pathologist) needs and organizational infrastructure are required. Contextual inquiry is a qualitative, user-centered tool for collecting, interpreting, and aggregating such detailed data about work practices that can be employed to help identify specific needs and requirements. AIM: Using contextual inquiry, the objective of this study was to identify the unique work practices and requirements in AP for the United States (US) Air Force Medical Service (AFMS) that had to be targeted in order to support their transition to digital pathology. SUBJECTS AND METHODS: A pathology-centered observer team conducted 1.5 h interviews with a total of 24 AFMS pathologists and histology lab personnel at three large regional centers and one smaller peripheral AFMS pathology center using contextual inquiry guidelines. Findings were documented as notes and arranged into a hierarchal organization of common themes based on user-provided data, defined as an affinity diagram. These data were also organized into consolidated graphic models that characterized AFMS pathology work practices, structure, and requirements. RESULTS: Over 1,200 recorded notes were grouped into an affinity diagram composed of 27 third-level, 10 second-level, and five main-level (workflow and workload distribution, quality, communication, military culture, and technology) categories. When combined with workflow and cultural models, the findings revealed that AFMS pathologists had needs that were unique to their military setting, when compared to civilian pathologists. These unique needs included having to serve a globally distributed patient population, transient staff, but a uniform information technology (IT) structure. CONCLUSIONS: The contextual inquiry method helped reveal similarities and key differences with civilian pathologists. Such an analysis helped identify specific instances that would benefit from implementing digital pathology in a military environment. Employing digital pathology to facilitate workload distribution, secondary consultations, and quality assurance (over-reads) could help the AFMS deliver more accurate, efficient, and timely AP services at a global level.

Neonatal chlamydial pneumonia induces altered respiratory structure and function lasting into adult life.

Respiratory dysfunction in adults has been correlated with neonatal Chlamydia trachomatis pneumonia in several studies, but a causal association has not been clearly demonstrated. In this study, we examined radial alveolar counts (RACs) by microscopy, and airway and parenchymal lung function using a small animal ventilator in juvenile (5 weeks age) and adult (8 weeks age) BALB/c mice challenged as neonates with Chlamydia muridarum (C. mur) on day 1 or day 7 after birth, representing saccular (human pre-term neonates) and alveolar (human term neonates) stages of lung development, respectively. Pups challenged with C. mur on either day 1 or 7 after birth demonstrated significantly enhanced airway hyperreactivity and lung compliance, both as juveniles (5 weeks age) and adults (8 weeks age), compared with mock-challenged mice. Moreover, mice challenged neonatally with Chlamydia displayed significantly reduced RACs, suggesting emphysematous changes. Antimicrobial treatment during the neonatal infection induced early bacterial clearance and partially ameliorated the Chlamydia-induced lung dysfunction as adults. These results suggest that neonatal chlamydial pneumonia, especially in pre-term neonates, is a cause of respiratory dysfunction continuing into adulthood, and that antimicrobial administration may be partially effective in preventing the adverse respiratory sequelae in adulthood. The results of our studies also emphasize the importance of prenatal screening and treatment of pregnant women for C. trachomatis in order to prevent the infection of neonates.

The contribution of interleukin-12/interferon-gamma axis in protection against neonatal pulmonary Chlamydia muridarum challenge.

Neonatal Chlamydia trachomatis pneumonia has been associated with respiratory sequelae in later life. We recently established a mouse model of neonatal pulmonary Chlamydia muridaum infection and found an important contribution of IFN-gamma to protective immunity. In this study, we further characterized the role of Th1-type cytokines; IL-12, IFN-gamma, and IFN-gamma signaling using mice genetically deficient in IL-12, IFN-gamma, or IFN-gamma receptor 1. All 3 knockout (KO) mice challenged intranasally with C. muridarum 1 day after birth exhibited 100% mortality by day 17 post-challenge whereas wild-type (WT) animals survived the monitoring period of 1 month. The KO mice exhibited greater lung bacterial burdens and enhanced dissemination to the liver, compared to WT animals. The inflammatory cellular infiltration in C. muridarum-challenged KO animals was significantly reduced in the lungs, but markedly enhanced in the livers of the KO mice compared to similarly challenged WT mice. It was also found that a deficiency in IL-12 or IFN-gamma resulted in correspondingly reduced IFN-gamma or IL-12 production, respectively, suggesting an intricate interdependence in the induction of these cytokines. Collectively, these results suggest that the IL-12/ IFN-gamma axis induces pulmonary cellular infiltration, induces bacterial clearance from the lung, reduces dissemination to other organs, and promotes the survival of the host during neonatal pulmonary chlamydial infection.

Oral live vaccine strain-induced protective immunity against pulmonary Francisella tularensis challenge is mediated by CD4+ T cells and antibodies, including immunoglobulin A.

Francisella tularensis is an intracellular gram-negative bacterium and the etiological agent of pulmonary tularemia. Given the high degrees of infectivity in the host and of dissemination of bacteria following respiratory infection, immunization strategies that target mucosal surfaces are critical for the development of effective vaccines against this organism. In this study, we have characterized the efficacy of protective immunity against pneumonic tularemia following oral vaccination with F. tularensis LVS (live vaccine strain). Mice vaccinated orally with LVS displayed colocalization of LVS with intestinal M cells, with subsequent enhanced production of splenic antigen-specific gamma interferon and of systemic and mucosal antibodies, including immunoglobulin A (IgA). LVS-vaccinated BALB/c mice were highly protected against intranasal (i.n.) SCHU S4 challenge and exhibited significantly less bacterial replication in the lungs, liver, and spleen than mock-immunized animals. Depletion of CD4(+) T cells significantly abrogated the protective immunity, and mice deficient in B cells or IgA displayed partial protection against SCHU S4 challenge. These results suggest that oral vaccination with LVS induces protective immunity against i.n. challenge with F. tularensis SCHU S4 by a process mediated cooperatively by CD4(+) T cells and antibodies, including IgA.