Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity*

Cohen, Jérémy; Pretorius, Carel J.; Ungerer, Jacobus P.J.; Cardinal, John; Blumenthal, Antje; Presneill, Jeffrey; Gatica-Andrades, Marcela; Jarrett, Paul; Lassig-Smith, Melissa; Stuart, Janine; Dunlop, Rachel; Starr, Therese; Venkatesh, Balasubramanian

doi:10.1097/ccm.0000000000001633

Cited by 41 publications

(35 citation statements)

References 23 publications

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“…All these changes are likely to contribute to corticosteroid resistance at a tissue level. Tissue resistance to corticosteroid is highly variable and correlates with severity of illness and mortality [85].…”

Section: Tissue Resistance To Glucocorticoidsmentioning

confidence: 99%

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

et al. 2017

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Section: Tissue Resistance To Glucocorticoidsmentioning

confidence: 99%

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

et al. 2017

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“…Inclusion and exclusion criteria were previously published. 27 Clinical patient management was at the discretion of the treating physician. Demographic data, Acute Physiology and Chronic Health Evaluation Score (APACHE) II, and white blood cell differentials were recorded on study entry.…”

Section: Human Study Subjectsmentioning

confidence: 99%

“…Two milliliters blood were collected (PaxGene Blood RNA tubes, Applied Biosystems) from 23 patients with septic shock within 72 hours of diagnosis in a prospective, observational study at a tertiary referral intensive care unit, 27 approved by the Royal Brisbane and Women's Hospital Ethics Committee (HREC/11/QRBW/201). Patients or their next of kin provided informed consent.…”

Section: Human Study Subjectsmentioning

confidence: 99%

WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice

et al. 2017

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Key Points• Differential expression of WNT ligands in patients with septic shock and a mouse model of endotoxemia correlates with inflammatory cytokines.• WNT ligands and WNT/b-catenin signaling positively regulate lipopolysaccharideinduced proinflammatory cytokines without impairing IL-10. IL-12/23p40 in serum of LPS-challenged mice and cultured splenocytes, whereas IL-10 production remained largely unaffected. Taken together, our data support the conclusion that the concerted action of WNT proteins during severe infection and septic shock promotes inflammation, and that this is, at least in part, mediated by WNT/b-catenin signaling.

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“…Glucocorticoids are a class of corticosteroids that are prescribed for numerous diseases, including rheumatoid arthritis (19), septic shock (20) and IgA nephropathy (21). However, high-dose or abnormal use of glucocorticoids results in bone disease.…”

Section: Discussionmentioning

confidence: 99%

Overactivated autophagy contributes to steroid-induced avascular necrosis of the femoral head

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Steroid-induced avascular necrosis of the femoral head (SANFH) is a mainly bilateral complication of steroid therapy that involves extensive necrosis, and frequently occurs in young and middle-aged individuals, with a high disability rate. Autophagy is an intracellular lysosomal degradation process occurring in numerous diseases. However, the effect of dexamethasone (DXM)-induced autophagy on osteoblasts is unclear. The aim of the present study was to investigate the effects of autophagy on SANFH. In the present study, femoral head of SANFH patients was collected, and the autophagy in the samples was evaluated. In addition, cell proliferation, membrane integrity and differentiation of osteoblasts were also detected to confirm the effect of DXM on a mouse osteoblasts cell MC3T3-E1 in vitro. Beclin 1 and microtubule-associated protein 1 light chain 3 were used as the markers of autophagy, while the autophagy inhibitor 3-methyladenine (3-MA) was used to investigate the role of autophagy in DXM-challenged osteoblasts. Immunohistochemistry results demonstrated that Beclin1 was markedly increased in the femoral head of SANFH patients. Furthermore, the treatment of osteoblasts with DXM decreased cell viability, increased lactate dehydrogenase activity in the cell culture supernatant, and reduced the alkaline phosphatase activity and bone morphogenetic protein-2 expression in osteoblasts in vitro. By contrast, 3-MA treatment attenuated the cell injury induced by DXM. The present study indicates that overactivated autophagy may be an important factor contributing to SANFH, and autophagy may be a potential target for the prevention of SANFH.

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Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity*

Cited by 41 publications

References 23 publications

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice

Overactivated autophagy contributes to steroid-induced avascular necrosis of the femoral head

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