Rapid recovery of postnivolumab vemurafenib-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome after tocilizumab and infliximab administration

Background Immune checkpoint inhibitors such as nivolumab and targeted BRAF inhibitors have dramatically altered the treatment outcomes of metastatic melanoma over the past few years. Skin toxicity is the most common adverse event (AE) related to the commonly used BRAF inhibitor vemurafenib, affecting more than 90% of patients. Vemurafenib-related severe AEs with early onset are reported in patients who were previously treated with anti-programmed cell death-1 (anti PD-1) antibodies. A prolonged administration of systemic steroids is the firstline treatment of severe or life-threatening AEs. We report the case of a woman suffering from vemurafenib-related severe, rapidly worsening Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, resolved in a few hours after single-dose administration of a combination of TNF-α antagonist infliximab with interleukin (IL)-6 receptor antagonist tocilizumab. Case presentation A 41-year-old woman treated with single-agent nivolumab presented with a melanoma progression. Biopsy samples were revised, revealing a BRAF V600E mutation. The patient was started on vemurafenib and cobimetinib treatment only 10 days after the last administration of nivolumab. On the third day of anti-BRAF therapy, profound lymphopenia was detected, and maculopapular eruption appeared afterward. Subsequently, the clinical conditions deteriorated further, and the woman was admitted on an emergency basis with high fever, respiratory and cardiocirculatory failure, diffuse rash, generalized edema, and lymphadenopathy. Diagnosis of DRESS syndrome with overexpressed capillary leakage was made. A single dose of tocilizumab was administered with an improvement of cardiocirculatory and renal function in a few hours. Because of worsening of liver function, skin lesions and mucositis, a single dose of infliximab was prescribed, and dramatic improvement was noted over the next 24 hours. Dabrafenib and trametinib were initiated, and coinciding with washout of infliximab from the patient’s blood, the drug toxicity recurred. Conclusion Anti-IL-6 and anti-TNF-α target treatment of very severe AEs may afford an immediate resolution of potentially life-threatening symptoms and reduce the duration and the costs of hospitalization. Maintenance of therapeutic infliximab blood concentrations permits an early switch to dabrafenib after vemurafenib-related AEs

Organisation design and adaptability of the organisation

The article builds upon the thesis that developing an adaptive organisation is strongly determined by the choice of organisational design. By reviewing design components and their importance for organisational adaptability, we outline the organisational features that design choice is to ensure for adaptability to be achieved. The benefits of using project organisational structure, adhocracy and networks in ensuring adaptability are discussed. Beside the requirements regarding “organisational hardware”, arguments for the significance of softer organisational components are given. Results of our own and others’ empirical studies on the role of soft organisational elements such as managerial philosophy, trust- and loyalty-based relationships with contracting parties and staff and aptitude to continuous innovation in building agility are also reported

Applications for people with health disabilities

There are such diseases that people had to live with all their lives. Such simple actions as talking on the phone, going downstairs or even determining the expiration date of milk can become difficult for people with disabilities. We present a selection of mobile applications that make life of people with disabilities easie

Agile organisations – features and agility enablers

Building organisations with a high degree of agility is becoming a more and more relevant and key issue as the dynamicity and unpredictability of the environment grow. A number of studies offer lists of characteristics outlining the profile of an agile organisation. The influence of numerous organisational resources and managerial practices for enhancing agility is focused upon by researchers as well. By reviewing and comparatively analysing the features of agile organisations as formulated by other researchers, the aim of this article is to outline the main features of agile organisations, as well as differentiate the markers of agility from the factors and practices which enable it. The role of knowledge in achieving agility is emphasised and centred around in the logical framework which describes the link between agility enablers and agility features. Thus, the necessity to acquire and develop knowledge and employ it in achieving agility justifies the choice of practices and resources pointed out in this article as key agility enablers

The EU Green Deal and the necessity for organizational changes in Bulgarian apparel and textile companies

The paper discusses the expected textile and apparel regulations intended in the EU Strategy for Sustainable and Circular Textiles, as well as the necessary changes which the organizations in said industry should consider in order to adapt to the new requirements. Based on an overview of publicly released policies and scholarly reports and analyses, there are formulated two main approaches to ensuring circularity within the industry – slowing down the loop and closing the loop. After a brief analysis of the situation in the Bulgarian textile and apparel industry, possible changes in strategies, processes, organizational structures and systems which may be considered, are proposed. Building new partnerships along the entire extended value chain, changes in the customer communication strategy in order to establish trust in the brand, the development of new values within and outside of the organization, and increasing innovation potential are among the essential steps towards realizing the necessary changes

THREE ESSAYS ON POPULATION DYNAMICS, TRADE AND GROWTH

Changes in immigration patterns and differential fertility choices shape the economies of both developed and developing countries. However, these changes affect the economies of developed and developing nations in different ways. This study aims to understand the changes in population dynamics, brought about by differences in cross--country differential fertility choices and migration patterns, and how these changes affect economic development via the channels of international trade and cross--country human capital accumulation. Chapter 1 discusses the background, data and literature on the patterns and composition of immigration and international trade, which are further explored in Chapter 2 for the world sample and in Chapter 3 for the U.S. and its trade partners. Chapter 2 employs data on refugee and immigrant stocks for the years 1990--2005, and compares the extent to which refugees and immigrants differentially affect trade (exports and imports) with their home countries. The main contributions of Chapter 2 are: the high--dimensional fixed effect estimation of the immigrants\u27 and refugees\u27 effect on trade---a technique not previously applied within the immigration and trade literature; differentiation between the effect of immigrants and refugees on trade in commodity and differentiated product types for the world sample; and, finally, expanding the sample size beyond the countries and years considered in the previous studies. Chapter 2 provides the first evidence of the differential refugee--immigrant trade effect for the world sample, using the high--dimensional fixed effect estimation, which controls for unobserved events correlated with both trade and migration decisions over time. I find that immigrants have a small positive (1.27%) effect on differentiated exports to their home country, while refugees do not affect trade. I find no evidence of immigrants or refugees affecting imports. These findings are different from the previous research, which relied on using the augmented gravity approach and estimated the effect of immigrants on trade to be anywhere between 4--6 percent on exports and 5--7 percent on imports, respectively. Controlling for time--varying multilateral resistance terms is one of the main contributions of the paper, as it allows for a better estimation of the effect of immigration on trade, and, contrary to previous research, finds little evidence of immigrants\u27 and refugees\u27 effect on trade with their home countries. Chapter 3 analyzes the effect of immigrants and refugees on U.S. trade with their home countries. More specifically, it explores the relationship between U.S. exports to 125 and imports from 100 immigrant and refugee countries of origin for the years 1990--2005. I find that immigrants have a positive effect on differentiated exports (0.3%) and have a negative effect on imports (affecting imports in differentiated products more). I do to find an effect of refugees on either U.S. exports or imports from their home countries. Finally, Chapter 4 explores the cross–country differences in educational attainments, taking differential fertility rates into account. Differential fertility rate is the difference between fertility rates of women with high educational attainment and women with low educational attainment. In a country where differential fertility is high, lower-educated women have more children than highly educated women but, due to the highly persistent intergenerational transmission of human capital, the many children born to lower--educated women also tend to have less education, decreasing the future aggregate educational attainment and, potentially, reducing growth. In contrast, in a country with initially lower differential fertility, the children of less educated women still receive less education (compared to the children of highly educated women), but since they do not represent a large enough fraction of the population, the decrease in the future aggregate level of human capital is not as stark. We document that and increase in differential fertility has a positive effect on future primary enrollment ratios, and is negatively correlated to the total average years of schooling

The Landscape: Italy and Russia

The paper presents the results of the PhD research of author supported by the Erasmus Mundus Action 2 Programme of the European Union. The paper is dedicated to the landscape planning after European Landscape Convention, in particularly to the Italian experience, demonstrates the differences of understanding the landscape related to social, linguistic, economic, environmental aspects and its interrelationship. European Landscape Convention (Florence, 2000) defined that landscape has “an important public interest role in the cultural, ecological, environmental and social fields”. These intends various possibilities for new programs, for new tools, for new process and activity in regard the city as a landscape. The research investigates the theme of landscaping planning in Italy to answer the main question of the thesis: how can the ELC's addresses be applied to the Russian case through experience of Italian landscape planning. To achieve this goal, has been verified: the process of integrating the European Landscape Convention, the Italian legislative system and landscape planning tools