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Systemic steroids are still the first-line approach in acute graft-versus-host disease (aGvHD), and the backbone of chronic GvHD management. Refractoriness to steroid represent a major cause of morbidity and non-relapse mortality after hematopoietic stem cell transplantation (HSCT). In both backgrounds, several second-line immunosuppressive agents have been tested with variable results in terms of efficacy and toxicity. Solid evidence regarding these approaches is still lacking in the pediatric setting where results are mainly derived from adult experiences. Furthermore, the number of treated patients is limited and the incidence of acute and chronic GvHD is lower, resulting in a very heterogeneous approach to this complication by pediatric hematologists. Some conventional therapies and anti-cytokine monoclonal antibodies used in the adult setting have been evaluated in children. In recent years, the increasing understanding of the biological mechanisms underpinning the pathogenesis of GvHD justified the efforts toward the adoption of targeted therapies and non-pharmacologic approaches, with higher response rates and lower immunosuppressive effects. Moreover, many questions regarding the precise timing and setting in which to integrate these new approaches remain unanswered. This Review aims to critically explore the current evidence regarding novel approaches to treat SR-GvHD in pediatric HSCT recipients.

Treatment of refractory autoimmune cytopenias (AICs) and Evans syndrome (ES) represent a great challenge in pediatric setting, where an underlying primary immunodeficiency is recurrent. Frequently, second or third line treatments are employed, with an increased risk of toxicity and infections. The advent of novel drugs is the object of research in order to modify the management of these patients. We report a case of successful use of bortezomib in a child with 22q11.2 deletion syndrome and CVID-like phenotype with a multi-refractory severe ES. Last flares were prolonged and dominated by severe and symptomatic ITP, refractory to different courses of high dose steroid and IVIG, mofetil mycophenolate, thrombopoietin receptor agonists, sirolimus, and rituximab. Persistence of AICs in subjects with depletion of CD20 + B-cells and IgG strengthens the hypothesis about the production of autoantibodies by terminally differentiated plasma-cells, not targetable from immunosuppressants and rituximab. In the attempt to enhance plasma-cells inhibition, the child was addressed to bortezomib, with a good response at 6 month follow-up without side effects. Nowadays, the use of bortezomib in ES/AICs is based only on small retrospective studies and case reports. Despite the lack of long term follow-up, our work highlights the potential role of bortezomib in the management of pediatric patients with multi-resistant AICs secondary to immune-system impairment.

Historically, Indigenous women have been the target of violence at an alarming rate compared to the non-Indigenous population. This work explores how Indigenous women have used the United Nations Declaration on the Rights of Indigenous Peoples (UNDRIP) to call for the end of this abuse. The United States and Canada are two North American Federal governments with a strong presence of Indigenous Peoples. Even though Canada and the United States have signed UNDRIP, in North America as many as four in five Indigenous women experience violence in their lifetime. This work looks at how and why there is still such a significant rate of violence against Indigenous women in the U.S. and Canada. In addition, this article surveys the current extent of Indigenous women's participation in the policymaking process. It then explores what changes in law and policy should flow from Indigenous women's activism and in what ways Indigenous women can and should become more involved in the decision-making process. This work also aims to reflect on how the law and policies in the U.S., in Canada and at an international level could more efficiently address the issue. Indigenous women have historically been absent from the decision-making process and even when they are given a voice and their rights are emphasized, for instance with UNDRIP, countries are not complying with their responsibilities on the matter. Consequently, Indigenous women are de facto denied the possibility to participate in the debate, and their claims are left unheard. This article concludes that they should be empowered to advocate for enhanced accountability of the individual countries and the international community alike. In fact, increased participation of Indigenous women in the decision-making process increases the opportunity for Indigenous voices to be heard, in a quest to fight the widespread issue of violence against Indigenous women.

How do we guarantee dignity and quality of life to individuals with Down syndrome? If a family cannot commit to granting a dignified life, or if there are other health concerns at issue, how do we balance the right of the mother, parents, and unborn child? This article offers a comparative perspective of the disability legal framework in the U.S. and Italy, focusing on Down syndrome. In Italy, healthcare is public and universal, while in the United States healthcare is mostly privatized. In this context, in the U.S. people with mental and physical disabilities are particularly vulnerable due to the high costs of healthcare, stigma, and the need for additional advocacy. This work compares the Americans with Disabilities Act (ADA) in the U.S., the Legge 104/1992 in Italy, and the Convention on the Rights of Persons with Disabilities (CRPD) internationally. Numerous policy considerations impact the lives of individuals with Down syndrome, from conception to delivery, and from early childhood throughout development. There is a controversial legal debate concerning abortion if the fetus has an identified genetic abnormality. Additionally, once individuals with Down syndrome are born, how does the legal framework support these children and their families? Law and policy regarding access to care make a big difference in the quality of life of people with Down syndrome. At first glance, the standpoint of protecting and supporting a child with Down syndrome, and that of protecting the parents' right to terminate a pregnancy, might seem antithetical. However, they are, in fact, part of the same (difficult) conversation. By adopting a person-centered approach, paired with a relationship-centered care approach, we can pursue the holistic and humanistic ideals that our society aspires to achieve.

Religion and public policy are interconnected across a variety of issues. One aspect where this linkage has been understudied is religion and Indigenous sacred sites protection. This article aims to address this gap by analyzing how Indigenous women’s activism advances this cause. The focus is on how Indigenous Peoples, specifically women, use grassroots activism to provoke change on public policy in the context of the protection of Indigenous sacred sites. Two case studies are used to illustrate this concept: the American “Women of Standing Rock” and the Canadian “Idle No More” grassroots social movements. My analysis draws from interpretative methods. Interpretative research revolves around the concept of individuals as active producers of meaning. The women-led grassroots social movements at issue highlight a fundamental lack of awareness of the historical and current struggles of Indigenous Peoples, both in the US and Canada. Modern technologies and social media provide democratic means for grassroots social movements to be heard and empowered. The growing movement by Indigenous women to assert their rights, and their quest for self-determination in land use and sacred sites protection create a positive discourse that advances Indigenous women’s position in crossing the obstacles onto “institutional places of privilege,” hence influencing public policy.

Dengue is a mosquito-borne disease frequently imported in Europe, where autochthonous outbreaks are potential since recent spreading of the vector. Primary infections usually produce a selflimited febrile syndrome. Secondary infections with different serotype, especially in children, may lead to a severe shock syndrome with plasma leakage and hemorrhagic features. We report a case series of 4 children infected with viral serotype 3 during a journey to the Maldive Islands, who developed symptoms after returning to Italy. Once diagnosed, they were admitted to hospital, followed with clinical and laboratory monitoring and treated supportively; they developed no complications. Dengue endemic areas are popular touristic destinations. Vector eradication may be incomplete where tourist resorts share water tanks with local dwellings. Diagnostic tests should be available in our hospitals for early recognition of cases. Awareness of a primary infection may help prevent re-exposure, avoiding a reinfection with a potentially severe clinical course.