Sequential Organ Failure Assessment Score for Prediction of Mortality of Patients With Rhabdomyolysis Following Exertional Heatstroke: A Longitudinal Cohort Study in Southern China

Wu, Ming; Wang, Conglin; Liu, Zheying; Liu, Zhifeng

doi:10.3389/fmed.2021.724319

Cited by 12 publications

(13 citation statements)

References 30 publications

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“… 29 Recent studies have reported that the content of the CK and MB levels were powerfully elevated in the nonsurvival group of EHS patients within 24 h in ICU, which indicated that RM has an important contribution to the mortality of EHS patients. 30 , 31 Fer‐1 was identified as a small molecule inhibitor of ferroptosis. 11 In the current study, the treatment of Fer‐1 significantly attenuated the skeletal muscle injury in RM following EHS compared with other forms of cell death inhibitors, which is manifested by diminishing the increased serum CK and MB levels induced by EHS.…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that the standard mortality ratio, a key element in intensive care unit (ICU), is calculated based on the data available within the first 24 h of ICU stay 29 . Recent studies have reported that the content of the CK and MB levels were powerfully elevated in the nonsurvival group of EHS patients within 24 h in ICU, which indicated that RM has an important contribution to the mortality of EHS patients 30,31 . Fer‐1 was identified as a small molecule inhibitor of ferroptosis 11 .…”

Section: Discussionmentioning

confidence: 99%

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ACSL4 contributes to ferroptosis‐mediated rhabdomyolysis in exertional heat stroke

Peng

et al. 2022

J cachexia sarcopenia muscle

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Background Rhabdomyolysis (RM) is a common complication of exertional heat stroke (EHS) and constitutes a direct cause of death. However, the mechanism underlying RM following EHS remains unclear. Methods The murine EHS model was prepared by our previous protocol. RNA sequencing is applied to identify the pathological pathways that contribute to RM following EHS. Inhibition of the acyl‐CoA synthetase long‐chain family member 4 (ACSL4) was achieved by RNA silencing in vitro prior to ionomycin plus heat stress exposure or pharmacological inhibitors in vivo prior to heat and exertion exposure. The histological changes, the iron accumulation, oxidized phosphatidylethanolamines species, as well as histological evaluation and levels of lipid metabolites in skeletal muscle tissues were measured. Results We demonstrated that ferroptosis contributes to RM development following EHS. Ferroptosis inhibitor ferrostatin‐1 administration once EHS onset significantly ameliorated the survival rate of EHS mice from 35.357% to 52.288% within 24 h after EHS (P = 0.0028 compared with control) and markedly inhibited RM development induced by EHS. By comparing gene expression of between sham heat rest (SHR) (n = 3) and EHS (n = 3) mice in the gastrocnemius (Gas) muscle tissue, we identified that Acsl4 mRNA expression is elevated in Gas muscle tissue of EHS mice (P = 0.0038 compared with SHR), so as to its protein levels (P = 0.0001 compared with SHR). Followed by increase in creatine kinase (CK) and myoglobin (MB) levels, the labile iron accumulation, decrease in glutathione peroxidase 4 (GPX4) expression, and elevation of lipid peroxidation products. From in vivo and in vitro experiments, inhibition of Acsl4 significantly improves muscle cell death caused by EHS, thereby ameliorating RM development, followed by reduction in CK and MB levels by 30–40% (P < 0.0001; n = 8–10) and 40% (P < 0.0001; n = 8–10), restoration of GPX4 expression, and decrease in lipid peroxidation products. Mechanistically, ACSL4‐mediated RM seems to be Yes‐associated protein (YAP) dependent via TEA domain transcription factor1/TEA domain transcription factor4. Conclusions These findings demonstrate an important role of ACSL4 in mediating ferroptosis activation in the development of RM following EHS and suggest that targeting ACSL4 may represent a novel therapeutic strategy to limit the skeletal muscle cell death and prevent RM after EHS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ACSL4 contributes to ferroptosis‐mediated rhabdomyolysis in exertional heat stroke

Peng

et al. 2022

J cachexia sarcopenia muscle

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“…Some reports have revealed the potential usefulness of the SOFA score 3 – 7 , 9 , 10 . Here, we have also shown an advantage of using SOFA score for predicting the outcome of patients included in the heatstroke database.…”

Section: Discussionmentioning

confidence: 99%

“…Internationally, the Sequential Organ Failure Assessment (SOFA) score is widely used to assess multiple organ dysfunction or failure as the main causes of death in critically ill patients 8 . Prior studies have suggested that the SOFA score is also useful for predicting mortality in patients with heatstroke 3 – 7 , 9 , 10 . However, those studies exhibited some weaknesses, including the use of populations comprising only exertional heatstroke, and single-center designs.…”

Section: Introductionmentioning

confidence: 99%

Sequential organ failure assessment score as a predictor of the outcomes of patients hospitalized for classical or exertional heatstroke

Yokoyama

Kaneko

Ito

et al. 2022

Sci Rep

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Heatstroke is a life-threatening event that affects people worldwide. Currently, there are no established tools to predict the outcomes of heatstroke. Although the Sequential Organ Failure Assessment (SOFA) score is a promising tool for judging the severity of critically ill patients. Therefore, in this study, we investigated whether the SOFA score could predict the outcome of patients hospitalized with severe heatstroke, including the classical and exertional types, by using data from a Japanese nationwide multicenter observational registry. We performed retrospective subanalyses of the Japanese Association for Acute Medicine heatstroke registry, 2019. Adults with a SOFA score ≥ 1 hospitalized for heatstroke were analyzed. We analyzed data for 225 patients. Univariate and multivariable analyses showed a significant difference in the SOFA score between non-survivors and survivors in classical and exertional heatstroke cases. The area under the receiver operating characteristic curve were 0.863 (classical) and 0.979 (exertional). The sensitivity and specificity of SOFA scores were 50.0% and 97.5% (classical), 66.7% and 97.5% (exertional), respectively, at a cutoff of 12.5, and 35.0% and 98.8% (classical), 33.3% and 100.0% (exertional), respectively, at a cutoff of 13.5. This study revealed that the SOFA score may predict mortality in patients with heatstroke and might be useful for assessing prognosis.

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“…ALI was also found in mouse and rat models of heatstroke (21,99,158,(177)(178)(179)(180)(181)(182)(183). Rhabdomyolysis is more common in patients with EHS, and several possible mechanisms cause such phenomenon (3,166,(184)(185)(186)(187)(188)(189)(190)(191)(192)(193). One potential mechanism is the elevated muscle tension caused by strenuous activity, which increases the chance of tissue injury (184).…”

Section: Tissue Injury Responsesmentioning

confidence: 99%

ZBP1 and heatstroke

Deng²,

He³

et al. 2023

Front. Immunol.

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Heatstroke, which is associated with circulatory failure and multiple organ dysfunction, is a heat stress-induced life-threatening condition characterized by a raised core body temperature and central nervous system dysfunction. As global warming continues to worsen, heatstroke is expected to become the leading cause of death globally. Despite the severity of this condition, the detailed mechanisms that underlie the pathogenesis of heatstroke still remain largely unknown. Z-DNA-binding protein 1 (ZBP1), also referred to as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1, was initially identified as a tumor-associated and interferon (IFN)-inducible protein, but has recently been reported to be a Z-nucleic acid sensor that regulates cell death and inflammation; however, its biological function is not yet fully understood. In the present study, a brief review of the main regulators is presented, in which the Z-nucleic acid sensor ZBP1 was identified to be a significant factor in regulating the pathological characteristics of heatstroke through ZBP1-dependent signaling. Thus, the lethal mechanism of heatstroke is revealed, in addition to a second function of ZBP1 other than as a nucleic acid sensor.

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Sequential Organ Failure Assessment Score for Prediction of Mortality of Patients With Rhabdomyolysis Following Exertional Heatstroke: A Longitudinal Cohort Study in Southern China

Cited by 12 publications

References 30 publications

ACSL4 contributes to ferroptosis‐mediated rhabdomyolysis in exertional heat stroke

ACSL4 contributes to ferroptosis‐mediated rhabdomyolysis in exertional heat stroke

Sequential organ failure assessment score as a predictor of the outcomes of patients hospitalized for classical or exertional heatstroke

ZBP1 and heatstroke

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