More than half of children with idiopathic nephrotic syndrome develop frequent relapses or steroid dependence and require chronic use of immune suppressants, such as cyclosporin, mycophenolate mofetil, or B cell-depleting therapies, to maintain disease in remission (1). Loss of endogenous antibodies in the nephrotic urines and pharmacologic immune suppression contribute to a higher risk for upper respiratory viral infections and influenza in children with steroiddependent nephrotic syndrome. These infectious episodes may cause or induce relapse of nephrotic syndrome.This formed the background for the 2012 Kidney Disease Improving Global Outcomes guidelines that recommend pneumococcal, annual influenza, and inactivated vaccines, whereas they contraindicate live attenuated vaccines (measles, mumps, rubella, varicella, rotavirus, and yellow fever), especially in patients on immunosuppressive or cytotoxic agents (2). Pathogenic mechanisms of nephrotic syndrome are still not fully elucidated, but increasing evidence points at a dysregulation of the immune system, involving both B and T cells. This also raises the intriguing hypothesis that vaccines, by eliciting an immune response, promote disease relapses (3). Overall, previous retrospective analysis reported that influenza virus vaccination in children with nephrotic syndrome is not associated with a higher risk of relapse (4). Similar data are reported for immunization against Streptococcus pneumoniae (3). However, no data from prospective studies are available that test the risk of nephrotic syndrome relapse after vaccines (4,5).We have prospectively followed up a cohort of 140 pediatric and young adult patients on chronic immunosuppression due to multidrug-dependent nephrotic syndrome. These patients were part of a single-center, randomized controlled trial comparing the safety/efficacy profile of two B cell-depleting antibodies: rituximab and ofatumumab (NCT02394119). After randomization, no other immune-suppressive treatments were allowed. Further anti-B cell-depleting therapy administrations were allowed, but only after disease relapse (i.e., after patients reached their primary end point). Common vaccinations, recommended by the Italian Ministry of Health according to age, were allowed

Autophagy is an evolutionarily conserved and tightly regulated process that plays an important role in maintaining cellular homeostasis. It involves regulation of various genes that function to degrade unnecessary or dysfunctional cellular components, and to recycle metabolic substrates. Autophagy is modulated by many factors, such as nutritional status, energy level, hypoxic conditions, endoplasmic reticulum stress, hormonal stimulation and drugs, and these factors can regulate autophagy both upstream and downstream of the pathway. In cancer, autophagy acts as a double-edged sword depending on the tissue type and stage of tumorigenesis. On the one hand, autophagy promotes tumor progression in advanced stages by stimulating tumor growth. On the other hand, autophagy inhibits tumor development in the early stages by enhancing its tumor suppressor activity. Moreover, autophagy drives resistance to anticancer therapy, even though in some tumor types, its activation induces lethal effects on cancer cells. In this review, we summarize the biological mechanisms of autophagy and its dual role in cancer. In addition, we report the current understanding of autophagy in some cancer types with markedly high incidence and/or lethality, and the existing therapeutic strategies targeting autophagy for the treatment of cancer.

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Organizations continuously need to adapt and respond to ever-present technology advancements. Proactivity is a necessity; only those organizations who can pivot when presented with change gain a competitive edge in their respective industry. The most invaluable strategic weapon organizations will have in the face of change is a method to streamline initiatives, conserve resources, and have seamless communication. The modern benefits of cloud-based project-portfolio management (PPM) tools are the solution. This study identifies a gap in the research and knowledge about these modern tools. Extant literature is focused on what cloud-based PPM tools provide, but there doesn’t exist research on how to diagnose an organization’s specific needs and select the appropriate tool to maximize business value. Through a two-phase research approach, this study fills the lack of research on the topic and provides a framework for tool selection which is applicable to multiple industries.