Serum procalcitonin levels are associated with rhabdomyolysis following exertional heatstroke: an over 10-year intensive care survey

BACKGROUND:Heatstroke has become a common emergency event in hospitals.Procalcitonin(PCT)is used as a biomarker of infection in the emergency department(ED),but its role in rhabdomyolysis(RM)following exertional heatstroke(EHS)remains unclear.METHODS:A retrospective cohort study enrolled patients with EHS from the intensive care unit(ICU).We collected RM biomarkers,inflammation markers,critical disease scores at admission,24 h,48 h,and discharge,and 90-day mortality.Correlation analysis,linear regression and curve fi tting were used to identify the relationship between PCT and RM.RESULTS:A total of 162 patients were recruited and divided into RM(n=56)and non-RM(n=106)groups.PCT was positively correlated with myoglobin(Mb),acute hepatic injury,disseminated intravascular coagulation(DIC),Sequential Organ Failure Assessment(SOFA)score,and Acute Physiology and Chronic Health Evaluation II(APACHE II)score,with correlation coefficients of 0.214,0.237,0.285,0.454,and 0.368,respectively(all P<0.05).Interestingly,the results of curve fi tting revealed a nonlinear relationship between PCT and RM,and a two-piecewise linear regression model showed that PCT was related to RM with an odds ratio of 1.3 and a cut-off of<4.6 ng/mL.Survival analysis revealed that RM was associated with higher mortality compared to non-RM cases(P=0.0093).CONCLUSION:High serum PCT concentrations are associated with RM after EHS in critically ill patients.Elevated PCT concentrations should be interpreted cautiously in patients with EHS in the ED.

Risk factors for brain injury in patients with exertional heatstroke:A 5-year experience

Purpose:Minimal data exist on brain injury in patients with exertional heatstroke(EHS)in developing country.In this study,we explored the risk factors for brain injury induced by EHS 90-day after onset.Methods:A retrospective cohort study of patients with EHS was conducted in the intensive care unit of the General Hospital of Southern Theater Command of PLA in China from April 2014 to June 2019.Patients were divided into non-brain injury(fully recovered)and brain injury groups(comprising deceased patients or those with neurological sequelae).The brain injury group was further subdivided into a death group and a sequela group for detailed analysis.General information,neurological performance and information on important organ injuries in the acute stage were recorded and analysed.Multivariable logistic regression was used to identify risk factors for brain injury after EHS and mortality risk factors for brain injury,and Kaplan-Meier survival curve was used to evaluate the effect of the neurological dysfunction on survival.Results:Out of the 147 EHS patients,117 were enrolled,of which 96(82.1%)recovered,13(11.1%)died,and 8(6.8%)experienced neurological sequelae.Statistically significant differences were found between non-brain injury and brain injury groups in age,hypotension,duration of consciousness disorders,time to drop core body temperature below 38.5℃,lymphocyte counts,platelet counts,procalcitonin,alanine aminotransferase,aspartate aminotransferase,creatinine,cystatin C,coagulation parameters,international normalized ratio,acute physiology and chronic health evaluation II scores,sequential organ failure assessment(SOFA)scores,and Glasgow coma scale scores(all p<0.05).Multivariate logistic regression showed that age(OR=1.090,95%CI:1.02-1.17,p=0.008),time to drop core temperature(OR=8.223,95%CI:2.30-29.40,p=0.001),and SOFA scores(OR=1.676,95%CI:1.29-2.18,p<0.001)are independent risk factors for brain injury induced by EHS.The Kaplan-Meier curves suggest significantly prolonged survival(p<0.001)in patients with early Glasgow coma scale score>8 and duration of consciousness disorders≤24 h.Conclusions:Advanced age,delayed cooling,and higher SOFA scores significantly increase the risk of brain injury post-EHS.These findings underscore the importance of rapid cooling and early assessment of organ failure to improve outcomes in EHS patients.

Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke

With the escalating prevalence of global heat waves,heat stroke has become a prominent health concern,leading to substantial liver damage.Unlike other forms of liver injury,heat strokeinduced damage is characterized by heat cytotoxicity and heightened inflammation,directly contributing to elevated mortality rates.While clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction,their specific correlation with heat stroke liver injury remains unclear.Our hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke,initiating IL-1bmediated inflammation.Using single-cell RNA sequencing of murine macrophages,a distinct and highly susceptible Kupffer cell subtype,Clec4Ft/CD206t,emerged,with heme oxygenase 1(HMOX-1)playing a pivotal role.Mechanistically,heat-induced HMOX-1,regulated by early growth response factor 1,mediated ferroptosis in Kupffer cells,specifically in the Clec4F t/CD206 t subtype(KC2),activating phosphatidylinositol 4-kinase beta and promoting PI4P production.This cascade triggered NLRP3 inflammasome activation and maturation of IL-1b.These findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells,particularly in Clec4F t/CD206 t KCs.Such an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke,offering a promising avenue for future therapeutic interventions.