Venetian Rule and Control of Plague Epidemics on the Ionian Islands during 17th and 18th Centuries

One-sentence summary for tables of contents: Measures taken by the Venetian administration to combat plague were successful

Acute myelogenous leukemia switch lineage upon relapse to acute lymphoblastic leukemia: a case report

Acute leukemia, the most common form of cancer in children, accounts for approximately 30% of all childhood malignancies, with acute lymphoblastic leukemia being five times more frequent than acute myeloid leukemia. Lineage switch is the term that has been used to describe the phenomenon of acute leukemias that meet the standard French-American-British system criteria for a particular lineage (either lymphoid or myeloid) upon initial diagnosis, but meet the criteria for the opposite lineage at relapse. Many reports have documented conversions of acute lymphoblastic leukemia to acute myeloid leukemia

Osteosarcoma microenvironment: whole-slide imaging and optimized antigen detection overcome major limitations in immunohistochemical quantification.

BACKGROUND: In osteosarcoma survival rates could not be improved over the last 30 years. Novel biomarkers are warranted to allow risk stratification of patients for more individual treatment following initial diagnosis. Although previous studies of the tumor microenvironment have identified promising candidates, novel biomarkers have not been translated into routine histopathology. Substantial difficulties regarding immunohistochemical detection and quantification of antigens in decalcified and heterogeneous osteosarcoma might largely explain this translational short-coming. Furthermore, we hypothesized that conventional hot spot analysis is often not representative for the whole section when applied to heterogeneous tissues like osteosarcoma. We aimed to overcome these difficulties for major biomarkers of the immunovascular microenvironment. METHODS: Immunohistochemistry was systematically optimized for cell surface (CD31, CD8) and intracellular antigens (FOXP3) including evaluation of 200 different antigen retrieval conditions. Distribution patterns of these antigens were analyzed in formalin-fixed and paraffin-embedded samples from 120 high-grade central osteosarcoma biopsies and computer-assisted whole-slide analysis was compared with conventional quantification methods including hot spot analysis. RESULTS: More than 96% of osteosarcoma samples were positive for all antigens after optimization of immunohistochemistry. In contrast, standard immunohistochemistry retrieved false negative results in 35-65% of decalcified osteosarcoma specimens. Standard hot spot analysis was applicable for homogeneous distributed FOXP3+ and CD8+ cells. However, heterogeneous distribution of vascular CD31 did not allow reliable quantification with hot spot analysis in 85% of all samples. Computer-assisted whole-slide analysis of total CD31- immunoreactive area proved as the most appropriate quantification method. CONCLUSION: Standard staining and quantification procedures are not applicable in decalcified formalin-fixed and paraffin-embedded samples for major parameters of the immunovascular microenvironment in osteosarcoma. Whole-slide imaging and optimized antigen retrieval overcome these limitations

The potential utility of B cell-directed biologic therapy in autoimmune diseases

Increasing awareness of the importance of aberrant B cell regulation in autoimmunity has driven the clinical development of novel B cell-directed biologic therapies with the potential to treat a range of autoimmune disorders. The first of these drugs—rituximab, a chimeric monoclonal antibody against the B cell-specific surface marker CD20—was recently approved for treating rheumatoid arthritis in patients with an inadequate response to other biologic therapies. The aim of this review is to discuss the potential use of rituximab in the management of other autoimmune disorders. Results from early phase clinical trials indicate that rituximab may provide clinical benefit in systemic lupus erythematosus, Sjögren’s syndrome, vasculitis, and thrombocytopenic purpura. Numerous case reports and several small pilot studies have also been published reporting the use of rituximab in conditions such as myositis, antiphospholipid syndrome, Still’s disease, and multiple sclerosis. In general, the results from these preliminary studies encourage further testing of rituximab therapy in formalized clinical trials. Based on results published to date, it is concluded that rituximab, together with other B cell-directed therapies currently under clinical development, is likely to provide an important new treatment option for a number of these difficult-to-treat autoimmune disorders

Clinical presentation of zygomycosis

AbstractZygomycetes are filamentous fungi with a worldwide distribution. This class of fungi encompasses two orders, i.e. the Mucorales and the Entomophthorales. Members of the latter are associated with chronic cutaneous and subcutaneous infections that are limited to the tropics and rarely disseminate to internal organs. The order Mucorales includes several species involved in rhinocerebral, pulmonary, cutaneous, gastrointestinal and other less frequent infections in immunocompetent and immunocompromised individuals, and is characterized by a tendency to disseminate. Portals of entry of zygomycetes are usually the lungs, skin, and gastrointestinal tract. A characteristic property of zygomycetes is their tendency to invade blood vessels and to cause thrombosis—processes that result in subsequent necrosis of involved tissues. Risk factors associated with zygomycosis include prolonged neutropenia and use of corticosteroids, solid organ or haematopoietic stem cell transplantation, AIDS, poorly controlled diabetes mellitus, iron chelation with deferoxamine, burns, wounds, malnutrition, extremes of age, and intravenous drug abuse. Recently, the widespread use of voriconazole for prophylaxis or treatment of aspergillosis in patients with haematological malignancies has been linked with a rise in the numbers of cases of invasive zygomycosis. As the symptoms, clinical signs and imaging findings of these infections are non-specific, a high index of suspicion is required for timely diagnosis. Early diagnosis, correction of the underlying predisposing factors, aggressive surgical debridement of all infected tissues and lengthy administration of antifungals are the only potentially curative options for this rare but emerging invasive fungal infection