Characterization of Sepsis and Sepsis-Associated Encephalopathy

Feng, Qing; Ai, Yuhang; Gong, Hua; Long, Wenyong; Ai, Meilin; Deng, Songyun; Huang, Li; Peng, Qianyi; Zhang, Lina

doi:10.1177/0885066617719750

Cited by 78 publications

(78 citation statements)

References 28 publications

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“…This result was consistent with similar findings in studies by Yamaguchi, et al [9] and Svenningsen et al [24]. Our previous study also came up with similar results [6], patients with sepsis associated delirium have higher short-term (28-day) and long-term (6-month) mortality rates. The possibility reason is that the primary disease is relatively serious.…”

Section: Discussionsupporting

confidence: 93%

“…Delirium is an acute neurological disorder that is frequently observed in Intensive Care Unit (ICU) patients with an incidence ranging from 11-80% [1,2,3]. It is characterized by transitory changes of consciousness and cognition, generally for a short period of time [4].patients that developed this disorder performed worst in the clinical outcomes, contributing to extended length of ICU stay, higher mortality rate, neurological sequelae such as cognitive impairment and significant risk of death after six months which represents a significant burden for patients and relatives, as well as to the health care system [5,6,7].…”

Section: Introductionmentioning

confidence: 99%

“…the prognosis of delirium was different in different disease types, among them, patients with sepsis/septic shock have the worst prognosis.First, the overall incidence of ICU delirium of this study was 45.8%, and the incidence of different diseases is different, from 15-68%. Our earlier studies showed that the incidence of delirium in septic populations range between 17.7-42.3%[6,19]. Takako Yamaguchi, R.N.…”

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confidence: 99%

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ICU delirium:what is different between the type of diseases?

Feng

Yu-hang

et al. 2020

Preprint

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Background: Delirium is an acute neurological disorder that is quite common complication in intensive care unit (ICU) patients. However, there are no studies to focus on risk factors vary from disease to disease. The purpose of our study was to identify the risk factors and prognosis of delirium in patients with different disease types. Method: We conducted an observed study of consecutive patients from September to November 2016, who underwent surgical operation or with poor conservative treatment were admitted to the ICU. The patients were screened for delirium by using the diagnostic tools of Richmond Agitation Sedation Scale (RASS score) and the Confusion Assessment Method ICU (CAM-ICU). Results: A total of 406 patients met the inclusion criteria in our study. The overall incidence of ICU delirium was 45.8% (186/406), the delirium was highest in patients with brain disease (68%), followed by pulmonary disease (63%) and sepsis/shock (49%). The risk factors are different for different types of disease, for heart and vascular disease subgroup, only sleep quality (OR=0.236, p＜0.001) was independent risk factor for delirium. For abdominal disease subgroup, age (OR=2.514, p=0.002), vasoactive drugs (OR=13.799, p=0.002), and sleep quality (OR=0.114, p＜0.001) were risk factors for the delirium. And for sepsis and septic shock subgroup, age(OR=1.100, p=0.022), APACHE II scores(OR=1.255, p＜0.001) and sleep quality (OR=0.090, p=0.034) were risk factors for the delirium. ICU delirium is associated with worse outcomes including ICU stays(P<0.001) and 28-day mortality(P=0.001). The difference of ICU stays between delirium and non-delirium groups in the subgroup of heart and vascular disease(P<0.001), pulmonary disease(P=0.011), sepsis/septic shock(P<0.001) and cerebral disease(P=0.011) were consistent with the general population. But subgroup of sepsis/septic shock was the only one whom has the significant difference in the 28-day mortality (P=0.006) between delirium and non-delirium groups. Conclusion: The incidence and risk factors of delirium varied greatly with the type of disease. Age and sleep quality were independent risk factors for the development of delirium in most subgroup diseases. The prognosis of delirium was different in different disease types, among them, patients with sepsis/septic shock associated delirium have the worst prognosis.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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ICU delirium:what is different between the type of diseases?

Feng

Yu-hang

et al. 2020

Preprint

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“…Its pathophysiological mechanism is complex and not fully resolved. It may involve brain microvascular endothelial cell dysfunction, destruction of the BBB, cerebral local inflammatory cell infiltration, inflammation medium, reduced cerebral perfusion, cerebral microvascular adjustment disorder, astrocyte and neuron dysfunction, neurotransmitter disorders, mitochondrial dysfunction, apoptosis, oxidative stress, calcium disorders, and so on [1,13,15]. Compelling evidence indicates that oxidative stress, mitochondrial dysfunction, and apoptosis play critical roles in the pathogenesis of SAE [16].…”

Section: Discussionmentioning

confidence: 99%

Omi/HtrA2 Regulates a Mitochondria-Dependent Apoptotic Pathway in a Murine Model of Septic Encephalopathy

Wang

Yao

et al. 2018

Cell Physiol Biochem

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Background/Aims: the pathogenesis of sepsis-associated encephalopathy (SAE) is multifactorial, involving neurotransmitter alterations, inflammatory cytokines, oxidative damage, mitochondrial dysfunction, apoptosis, and other factors. Mitochondria are major producers of reactive oxygen species, resulting in cellular injury. Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent cell death; it is translocated from mitochondria to the cytosol after an apoptotic insult. We previously found that UCF-101, a specific inhibitor of Omi/HtrA2, has neuroprotective effects on cerebral oxidative injury and cognitive impairment in septic rats. In this study, the mechanisms and molecular pathways underlying these effects were investigated. Methods: Male Sprague–Dawley rats were subjected to cecal ligation and puncture (CLP) or sham-operated laparotomy and were administered vehicle or UCF-101 (10 µmol/kg). The hippocampus was isolated for subsequent analysis. Omi/HtrA2 expression in the mitochondria or cytosol was evaluated by immunofluorescence or western blotting. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was utilized to evaluate levels of apoptosis, and western blotting was used to evaluate apoptosis-related proteins, such as cleaved caspase-3, caspase-9, and poly (ADP-ribose) polymerase (PARP). Tight junction expression was assessed by immunofluorescence and western blotting. Mitochondrial function, inflammatory cytokines, and oxidative stress were also assayed. In addition, a wet/dry method was used to evaluate brain edema and Evans blue extravasation was used to evaluate blood–brain barrier (BBB) integrity. Results: After CLP treatment, the hippocampus exhibited a mild increase in Omi/HtrA2 expression; cytosolic Omi/HtrA2 expression increased significantly, whereas mitochondrial Omi/HtrA2 expression was reduced, indicating that CLP-induced oxidative stress resulted in the translocation of Omi/HtrA2 from mitochondria to the cytosol. Hippocampal cleaved caspase-3, caspase-9, and PARP levels were significantly higher in animals treated with CLP than in sham-operated animals, while XIAP expression was lower. Treatment with UCF-101 prevented the mobilization of Omi/HtrA2 from mitochondria to the cytosol, attenuated XIAP degradation, and decreased cleaved caspase-3, caspase-9, and PARP expression as well as apoptosis. UCF-101 also reversed the decreased mitochondrial complex I, II, and III respiration and the reduced ATP caused by CLP. In addition, UCF-101 treatment resulted in a significant improvement in BBB integrity, as demonstrated by increased occludin, claudin-5, and zonula occludens 1 levels and reduced Evans blue extravasation. No significant effects of UCF-101 on brain edema were found. Inflammatory cytokines and oxidative stress were significantly higher in the CLP-treated group than in the sham-operated group. However, the inhibition of Omi/HtrA2 by UCF-101 significantly alleviated these responses. Conclusion: Our data indicated that Omi/ HtrA2 regulates a ...

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“…To date, aside from the combined use of early and appropriate antimicrobial therapy, restoration of adequate tissue/organ perfusion and timely source control at the early stage of sepsis, no specific method has been available to prevent post-sepsis cognitive impairment [2,3]. Occurrence of post-sepsis sequelae is significantly associated with decreased life quality and decreased life independence [3,4]. Thus, high prevalence of post-sepsis cognitive impairment remains an important problem in sepsis survivors, calling for new, simple and effective prevention methods.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous administration of β-hydroxybutyrate improves learning and memory of sepsis surviving mice

et al. 2020

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Post-sepsis cognitive impairment is one of the major sequelae in sepsis survivors. Its prevention remains clinically challenging. Here we tested the effects and underlying mechanisms of exogenous β-hydroxybutyrate (BHB) on post-sepsis cognitive impairment. We found that subcutaneous administration of BHB increased survival and body weight recovery of sepsis mice and improved learning and memory of sepsis surviving mice in a cecal ligation and perforation-induced sepsis model. Additionally, the improvement of learning and memory of sepsis surviving mice was still detected even if BHB was administrated at the late stage of sepsis. In contrast, glucose solution did not show similar effects. Mechanistically, subcutaneous administration of BHB increased the BHB level of hippocampus, and limited neuroinflammation and neuroplasticity damage in sepsis mice. Intracerebroventricular administration of BHB also alleviated neuroinflammation and cognitive impairment of sepsis surviving mice. In the coculture of neurons, astrocytes, and BV2 cells (a microglial cell line), knocking down the expression of microglial HCA2 (BHB receptor) via a specific shRNA reduced the protection of BHB to lipopolysaccharide-induced inflammatory response and neuron damage more significantly than knocking down neuronal MCT2 (BHB transporter). These data showed that (1) BHB was a potential pharmacological adjunct treatment for prevention of post-sepsis cognitive impairment and (2) inhibiting neuroinflammation via HCA2 was an important mechanism.

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Characterization of Sepsis and Sepsis-Associated Encephalopathy

Cited by 78 publications

References 28 publications

ICU delirium:what is different between the type of diseases?

ICU delirium:what is different between the type of diseases?

Omi/HtrA2 Regulates a Mitochondria-Dependent Apoptotic Pathway in a Murine Model of Septic Encephalopathy

Subcutaneous administration of β-hydroxybutyrate improves learning and memory of sepsis surviving mice

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