Glucose metabolic reprogramming-related parameters for the prediction of 28-day neurological prognosis and all-cause mortality in patients after cardiac arrest: a prospective single-center observational study.

BACKGROUND: We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation (ROSC). METHODS: Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1, 2017, to May 30, 2021, were enrolled. According to 28-day survival, the patients were divided into a non-survival group (n=82) and a survival group (n=38). Healthy adult volunteers (n=40) of similar ages and sexes were selected as controls. The serum levels of glucose metabolic reprogramming-related parameters (lactate dehydrogenase [LDH], lactate and pyruvate), neuron-specific enolase (NSE) and interleukin 6 (IL-6) were measured on days 1, 3, and 7 after ROSC. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score were calculated. The Cerebral Performance Category (CPC) score was recorded on day 28 after ROSC. RESULTS: Following ROSC, the serum LDH (607.0 U/L vs. 286.5 U/L), lactate (5.0 mmol/L vs. 2.0 mmol/L), pyruvate (178.0 µmol/L vs. 70.9 µmol/L), and lactate/pyruvate ratio (34.1 vs. 22.1) significantly increased and were higher in the non-survivors than in the survivors on admission (all P<0.05). Moreover, the serum LDH, pyruvate, IL-6, APACHE II score, and SOFA score on days 1, 3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality (all P<0.05). The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve (AUC) of 0.904 [95% confidence interval [95% CI]: 0.851-0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950 (95% CI: 0.911-0.989) with 94.7% specificity for predicting 28-day all-cause mortality, which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION: Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC. Increased serum LDH and pyruvate levels, and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC, and the predictive efficacy of LDH during the first week was superior to others.

Mild Hypothermia Alleviates Complement C5a-Induced Neuronal Autophagy During Brain Ischemia-Reperfusion Injury After Cardiac Arrest.

After restoration of spontaneous circulation (ROSC) following cardiac arrest, complements can be activated and excessive autophagy can contribute to the brain ischemia-reperfusion (I/R) injury. Mild hypothermia (HT) protects against brain I/R injury after ROSC, but the mechanisms have not been fully elucidated. Here, we found that HT significantly inhibited the increases in serum NSE, S100ß, and C5a, as well as neurologic deficit scores, TUNEL-positive cells, and autophagic vacuoles in the pig brain cortex after ROSC. The C5a receptor 1 (C5aR1) mRNA and the C5a, C5aR1, Beclin 1, LC3-II, and cleaved caspase-3 proteins were significantly increased, but the P62 protein and the PI3K/Akt/mTOR pathway-related proteins were significantly reduced in pigs after ROSC or neuronal oxygen-glucose deprivation/reoxygenation. HT could significantly attenuate the above changes in NT-treated neurons. Furthermore, C5a treatment induced autophagy and apoptosis and reduced the PI3K/Akt/mTOR pathway-related proteins in cultured neurons, which could be reversed by C5aR1 antagonist PMX205. Our findings demonstrated that C5a could bind to C5aR1 to induce neuronal autophagy during the brain I/R injury, which was associated with the inhibited PI3K/Akt/mTOR pathway. HT could inhibit C5a-induced neuronal autophagy by regulating the C5a-C5aR1 interaction and the PI3K/Akt/mTOR pathway, which might be one of the neuroprotective mechanisms underlying I/R injury. The C5a receptor 1 (C5aR1) mRNA and the C5a, C5aR1, Beclin 1, LC3-II, and cleaved caspase-3 proteins were significantly increased, but the P62 protein and the PI3K/Akt/mTOR pathway-related proteins were significantly reduced in pigs after ROSC or neuronal oxygen-glucose deprivation/reoxygenation. Mild hypothermia (HT) could significantly attenuate the above changes in NT-treated neurons. Furthermore, C5a treatment induced autophagy and apoptosis and reduced the PI3K/Akt/mTOR pathway-related proteins in cultured neurons, which could be reversed by C5aR1 antagonist PMX205. Proposed mechanism by which HT protects against brain I/R injury by repressing C5a-C5aR1-induced excessive autophagy. Complement activation in response to brain I/R injury generates C5a that can interact with C5aR1 to inactivate mTOR, probably through the PI3K-AKT pathway, which can finally lead to autophagy activation. The excessively activated autophagy ultimately contributes to cell apoptosis and brain injury. HT may alleviate complement activation and then reduce C5a-induced autophagy to protect against brain I/R injury. HT, mild hypothermia; I/R, ischemia reperfusion.

Risk factors associated with 28-day all-cause mortality in older severe COVID-19 patients in Wuhan, China: a retrospective observational study.

We aimed to analyse clinical characteristics and identify risk factors predicting all-cause mortality in older patients with severe coronavirus disease 2019 (COVID-19). A total of 281 older patients with severe COVID-19 were categorized into two age groups (60-79 years and ≥ 80 years). Epidemiological, clinical, and laboratory data, and outcome were obtained. Patients aged ≥ 80 years had higher mortality (63.6%) than those aged 60-79 years (33.5%). Anorexia and comorbidities including hypertension, diabetes and COPD, higher levels of lactate dehydrogenase (LDH), osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I and procalcitonin, and higher SOFA scores were more common in patients aged > 80 years than those aged 60-79 years and also more common and higher in non-survivors than survivors. LDH, osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I, and procalcitonin were positively correlated with age and sequential organ failure assessment (SOFA), whereas CD8+ and lymphocyte counts were negatively correlated with age and SOFA. Anorexia, comorbidities including hypertension, diabetes, and chronic obstructive pulmonary disease (COPD), LDH, osmotic pressure, and SOFA were significantly associated with 28-day all-cause mortality. LDH, osmotic pressure and SOFA were valuable for predicting 28-day all-cause mortality, whereas the area under the receiver operating characteristic curve of LDH was the largest, with sensitivity of 86.0% and specificity of 80.8%. Therefore, patients with severe COVID-19 aged ≥ 80 years had worse condition and higher mortality than did those aged 60-79 years, and anorexia and comorbidities including hypertension, diabetes, COPD, elevated plasma osmotic pressure, LDH, and high SOFA were independent risk factors associated with 28-day all-cause mortality in older patients with severe COVID-19. LDH may have the highest predictive value for 28-day all-cause mortality in all examined factors.