Dysregulated Cytokine Expression by CD4+ T cells from Post-Septic Mice Modulates both Th1 and Th2-Mediated Granulomatous Lung Inflammation

Previous epidemiological studies in humans and experimental studies in animals indicate that survivors of severe sepsis exhibit deficiencies in the activation and effector function of immune cells. In particular, CD4+ T lymphocytes can exhibit reduced proliferative capacity and improper cytokine responses following sepsis. To further investigate the cell-intrinsic defects of CD4+ T cells following sepsis, splenic CD4+ T cells from sham surgery and post-septic mice were transferred into lymphopenic mice. These recipient mice were then subjected to both TH1-(purified protein derivative) and TH2-(Schistosoma mansoni egg antigen) driven models of granulomatous lung inflammation. Post-septic CD4+ T cells mediated smaller TH1 and larger TH2 lung granulomas as compared to mice receiving CD4+ T cells from sham surgery donors. However, cytokine production by lymph node cells in antigen restimulation assays indicated increased pan-specific cytokine expression by post-septic CD4+ T cell recipient mice in both TH1 and TH2 granuloma models. These include increased production of TH2 cytokines in TH1 inflammation, and increased production of TH1 cytokines in TH2 inflammation. These results suggest that cell-intrinsic defects in CD4+ T cell effector function can have deleterious effects on inflammatory processes post-sepsis, due to a defect in the proper regulation of TH-specific cytokine expression

Factors associated with posttraumatic stress symptoms in a prospective cohort of patients after abdominal sepsis: a nomogram

Objective: To determine to what extent patients who have survived abdominal sepsis suffer from symptoms of posttraumatic stress disorder (PTSD) and depression, and to identify potential risk factors for PTSD symptoms. Design and setting: PTSD and depression symptoms were measured using the Impact of Events Scale-Revised (IES-R), the Post-Traumatic Symptom Scale 10 (PTSS-10) and the Beck Depression Inventory II (BDI-II). Patients and participants: A total of 135 peritonitis patients were eligible for this study, of whom 107 (80%) patients completed the questionnaire. The median APACHE-II score was 14 (range 12-16), and 89% were admitted to the ICU. Measurements and results: The proportion of patients with "moderate" PTSD symptom scores was 28% (95% CI 20-37), whilst 10% (95% CI 6-17) of patients had "high" PTSD symptom scores. Only 5% (95% CI 2-12) of the patients expressed severe depression symptoms. Factors associated with increased PTSD symptoms in a multivariate ordinal regression model were younger age (0.74 per 10 years older, p = 0.082), length of ICU stay (OR = 1.4 per doubling of duration, p = 0.003) and having some (OR = 4.9, p = 0.06) or many (OR = 55.5, p < 0.001) traumatic memories of the ICU or hospital stay. Conclusion: As many as 38% of patients after abdominal sepsis report elevated levels of PTSD symptoms on at least one of the questionnaires. Our nomogram may assist in identifying patients at increased risk for developing symptoms of PTSD

Year in review 2007: Critical Care – multiple organ failure and sepsis

Several research papers published in Critical Care throughout 2007 examined the pathogenesis, diagnosis, treatment and prognosis of sepsis and multiorgan failure. The present review summarizes the findings and implications of the papers published on sepsis and multiorgan failure and places the research in the context of other work in the field

Exploring Cosmic Origins with CORE: Survey requirements and mission design

Future observations of cosmic microwave background (CMB) polarisation havethe potential to answer some of the most fundamental questions of modernphysics and cosmology. In this paper, we list the requirements for a future CMBpolarisation survey addressing these scientific objectives, and discuss thedesign drivers of the CORE space mission proposed to ESA in answer to the "M5"call for a medium-sized mission. The rationale and options, and themethodologies used to assess the mission's performance, are of interest toother future CMB mission design studies. CORE is designed as a near-ultimateCMB polarisation mission which, for optimal complementarity with ground-basedobservations, will perform the observations that are known to be essential toCMB polarisation scienceand cannot be obtained by any other means than adedicated space mission