Recent advances in sepsis therapy exclusively involve improvements in supportive care, while sepsis mortality rates remain disturbingly high at 30%. These persistently high sepsis mortality rates arise from the absence of sepsis specific therapies. However with improvements in supportive care, patients with septic shock commonly partially recover from the infection that precipitated their initial illness, yet they frequently succumb to subsequent health care associated infections. Remarkably today the pathophysiology of sepsis in humans, a common disease in western society, remains largely a conundrum. Conventionally sepsis was regarded as primarily a disorder of inflammation. More recently the importance of immune compromise in the pathophysiology of sepsis and health care associated infection has now become more widely accepted. Accordingly a review of the human evidence for this novel sepsis paradigm is timely. Septic patients appear to exhibit a complex and long-lasting immune deficiency state, involving lymphocytes of both the innate and adaptive immune responses that have been linked with mortality and the occurrence of health care associated infection. Such is the pervasive nature of immune compromise in sepsis that ultimately immune modulation will play a crucial role in sepsis therapies of the future.

ObjectiveThe role of Th1 and Th17 lymphocyte responses in human infection and sepsis of elderly patients has yet to be clarified.DesignA prospective observational study of patients with sepsis, infection only and healthy controls.SettingThe acute medical wards and intensive care units in a 1000 bed university hospital.Patients32 patients with sepsis, 20 patients with infection, and 20 healthy controls. Patients and controls were older than 65 years of age. Patients with recognised underlying immune compromise were excluded.MethodsPhenotype, differentiation status and cytokine production by T lymphocytes were determined by flow cytometry.MeasurementsThe differentiation states of circulating CD3+, CD4+, and CD8+ T cells were characterised as naive (CD45RA+, CD197+), central memory (CD45RA-, CD197+), effector memory (CD45RA-, CD197-), or terminally differentated (CD45RA+, CD197-). Expression of IL-12 and IL-23 receptors, and the transcription factors T-bet and RORγt, was analysed in circulating T lymphocytes. Expression of interferon- γ and IL-17A were analysed following stimulation in vitro.ResultsCD4+ T cells from patients with infection predominantly expressed effector-memory or terminally differentiated phenotypes but CD4+ T cells from patients with severe sepsis predominantly expressed naive phenotypes (p<0.0001). CD4+ T cells expressing IL-23 receptor were lower in patients with sepsis compared to patients with infection alone (p = 0.007). RORγt expression by CD4+ T cells was less frequent in patients with sepsis (p<0.001), whereas T-bet expressing CD8+ T cells that do not express RORγt was lower in the sepsis patients.HLA-DR expression by monocytes was lower in patients with sepsis. In septic patients fewer monocytes expressed IL-23.ConclusionPersistent failure of T cell activation was observed in patients with sepsis. Sepsis was associated with attenuated CD8+Th1 and CD4+Th17 based lymphocyte response.

This study examines the international activist movement known as Sleeping Giants, a social-media “campaign to make bigotry and sexism less profitable” (Sleeping Giants, n.d.). The campaign originated in the US with an anonymous Twitter account that enlisted followers in encouraging brands to pull their online advertising from <em>Breitbart News</em>. The campaign achieved dramatic success and rapidly spread to regions outside the US, with other anonymously run and loosely allied chapters emerging in 15 different nations (as well as a regional chapter for the EU). Many of these were initially created to take on <em>Breitbart</em> advertisers in their home countries, but in a number of cases they subsequently turned their attention to disrupting financial support for other far-right news media in—or impacting—their home countries. Based on interviews with leaders of eight Sleeping Giants chapters, as well as the related UK-based Stop Funding Hate campaign, this study examines the Sleeping Giants campaign with respect to its continuity with media activism of previous eras, while also seeking to understand its potential as one of the first high-profile activist campaigns to grapple with the impacts of programmatic advertising on the news ecosystem. In particular, we consider how the campaign’s interventions speak to the larger debate around the normative relationship between advertising and the performance of the news ecosystem.

Right ventricular failure is common in children with severe pneumonia, and it is probably caused by pulmonary hypertension rather than septic toxemia. The clinical signs of heart failure are unreliable. There is no evidence that digoxin is effective treatment for right ventricular failure secondary to pulmonary hypertension.

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