Lactate combined with SOFA score for improving the predictive efficacy of SOFA score in patients with severe heatstroke.

BACKGROUND: The relationship between lactate levels and multiple organ dysfunction in patients with severe heatstroke remains unclear. In this study, we aimed to elucidate the clinical significance of lactate in severe heatstroke prognosis and assess whether incorporating lactate in the SOFA score improves its predictive efficacy. METHODS: This study was a multicenter retrospective cohort investigation included 275 patients. Logistic regression analysis was performed to examine the relationship between lactate levels and patient outcomes and complications, including acute kidney injury (AKI), disseminated intravascular coagulation (DIC), and myocardial injury. Further, receiver operating characteristic (ROC) curves and clinical decision curve analysis (DCA) were used to evaluate the predictive power of lactate and SOFA scores in severe heatstroke-associated death. Lastly, the Kaplan-Meier survival curve was employed to differentiate the survival rates among the various patient groups. RESULTS: After adjusting for confounding factors, lactate was demonstrated as an independent risk factor for death (OR = 1.353, 95% CI [1.170, 1.569]), AKI (OR = 1.158, 95% CI [1.007, 1.332]), DIC (OR = 1.426, 95% CI [1.225, 1.659]), and myocardial injury (OR = 2.039, 95% CI [1.553, 2.679]). The area under the curve (AUC) of lactate for predicting death from severe heatstroke was 0.7540, with a cutoff of 3.35. The Kaplan-Meier survival curve analysis showed that patients with elevated lactate levels had higher mortality rates. Additionally, the ROC curves demonstrated that combining lactate with the SOFA score provided better predictive efficacy than the SOFA score alone in patients with severe heatstroke (AUC: 0.9025 vs. 0.8773, DeLong test, P < 0.001). Finally, the DCA curve revealed a higher net clinical benefit rate for lactate combined with the SOFA score. CONCLUSIONS: Lactate is an independent risk factor for severe heatstroke-related death as well as a risk factor for AKI, DIC, and myocardial injury associated with severe heatstroke. Thus, combining lactate with the SOFA score can significantly improve its predictive efficacy in patients with severe heatstroke.

Clinical relevance of neutrophil/lymphocyte ratio combined with APACHEII for prognosis of severe heatstroke.

We evaluated clinical implication of neutrophil-lymphocyte ratio (NLR) for severe heatstroke and predictive value of combined acute physiology and chronic health evaluation (APACHEII) score for prognosis of severe heatstroke. Retrospectively, we studied 185 individuals that have been admitted at emergency department for severe heatstroke. On the basis of their prognosis, we sorted the patients into two categories, namely non-survival (n = 43) and survival groups (n = 142). The primary outcome was 30-day mortality. A considerably higher NLR was observed among the non-survivors compared to survivors (P < 0.05). After correction for confounders, statistical analysis using multi-variable Cox regression indicated NLR as an independent risk factor for patient death (HR = 1.167, 95%CI = 1.110-1.226, P < 0.001). Through receiver-operating characteristics (ROC) curve, we estimated area-under the curve (AUC) of NLR to be 0.7720 (95% CI [0.6953, 0.8488]). Also, transformation of NLR into a profile type analysis showed that the marker remained a risk factor for death, which showed trend variation (P for trend <0.001). Subgroup forest plot analysis showed robustness in the predictive ability of NLR after exclusion of confounders. Besides, we demonstrated through Kaplan-Meier (KM) survival analysis curve that high risk NLR mortality substantially exceeded low risk NLR. The combined prediction of NLR and APACHEII achieved higher efficacy than NLR and APACHEII alone (AUC = 0.880, 95% CI [0.8280, 0.9290]). Additionally, Delong test indicated that the combined prediction demonstrated a significantly greater ROC than NLR and APACHEII alone, while DCA showed a considerably higher clinical net benefit rate. Increased NLR is a high risk factor and has predictive value for death in individuals with severe heatstroke. Suggestively, combination of NLR and APACHEII have greater predictive value.

[Clinical significance of early troponin I levels on the prognosis of patients with severe heat stroke].

OBJECTIVE: To investigate the clinical significance of early troponin I (TnI) level in the prognosis of severe heat stroke. METHODS: Clinical data of 131 patients with severe heat stroke in the intensive care unit (ICU) of the Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University (study dataset) and ICU 67 patients with severe heat stroke in Jintan First People's Hospital of Changzhou (validation dataset) were retrospectively analyzed from June 2013 to September 2022. The patients were divided into survival group and death group according to 30-day outcomes. TnI was collected within 24 hours after admission to the emergency department. Cox regression analysis was performed to analyze the risk factors of severe heat stroke death. Spearman correlation test was used to analyze the correlation between TnI and heart rate, and peripheral systolic blood pressure. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of TnI for death in patients with severe heat stroke. Decision curve analysis (DCA) was conducted to assess the clinical net benefit rate of TnI prediction. Grouping by TnI cut-off value, Kaplan-Meier survival curve was used to analyze 30-day cumulative survival. Sensitivity analysis included modified Possion regression, E-value, and subgroup forest map was used to evaluate the mortality risk of TnI in different populations. External dataset was used to verify the predictive value of TnI. RESULTS: The death group had significantly higher TnI compared to the survival group [µg/L: 0.623 (0.196, 1.510) vs. 0.084 (0.019, 0.285), P < 0.01]. Multivariate Cox regression analysis after adjusting for confounding factors showed that TnI was an independent risk factor for death [hazard ratio (HR) = 1.885, 95% confidence interval (95%CI) was 1.528-2.325,P < 0.001]. Spearman correlation test showed that TnI was positively correlated with heart rate (r = 0.537, P < 0.001) and negatively correlated with peripheral systolic blood pressure (r = -0.611, P < 0.001). ROC curve showed that the area under the curve (AUC) of the TnI (0.817) was better than that of the acute physiology and chronic health evaluation II (APACHE II, 0.756). The DCA curve showed that the range of clinical net benefit rate of TnI (6.21%-20.00%) was higher than that of APACHE II score (5.14%-20.00%). Kaplan-Meier survival curve showed that patients in the low-risk group (TnI ≤ 0.106) had a significantly higher 30-day survival rate than that in the high-risk group (TnI > 0.106) group (Log-Rank test: χ2 = 17.350, P < 0.001). Modified Possion regression with adjustment for confounding factors showed that TnI was still an independent risk factor for death in patients with severe heat stroke [relative risk (RR) = 1.425, 95%CI was 1.284-1.583, P < 0.001]. The E-value was 2.215. The subgroup forest plot showed that the risk factors of TnI were obvious in male patients and patients ≤ 60 years old (male: HR = 1.731, 95%CI was 1.402-2.138, P < 0.001; ≤ 60 years old: HR = 1.651, 95%CI was 1.362-2.012, P < 0.001). In the validation dataset, ROC curve analysis showed that the AUC (0.836) of TnI predicting the prognosis of severe heat stroke was still higher than the APACHE II score (0.763). CONCLUSIONS: Early elevation of TnI is a high-risk factor for death in patients with severe heat stroke, and it has a good predictive value for death.

A sandwich-type electrochemical immunosensor based on spherical nucleic acids-templated Ag nanoclusters for ultrasensitive detection of tumor biomarker.

The accurate determination of tumor biomarkers in blood is of vital significance in the diagnosis and therapy of tumor disease. In this research, an innovative sandwich-type electrochemical immunosensor is designed for the ultrasensitive determination of tumor biomarker AFP using spherical nucleic acids-templated silver nanoclusters (AgNCs) sensing platform. For this purpose, on one hand, DNA functionalized gold nanoparticles (AuNPs@DNA) is selected not only as the cross-linker to immobilize the primary antibody (anti-AFP antibody 1, Ab1) to obtain AuNPs@DNA-Ab1, but also as the template for synthesizing AgNCs on AuNPs to form AuNPs@DNA-AgNCs. On the other hand, p-sulfonated calix[4]arene (pSC4) modified Au is chosen to immobilize the secondary antibody (anti-AFP antibody 2, Ab2) through host-guest recognition between Ab2 and pSC4. When AFP is encountered, the immunoreaction signal can be significantly amplified by the electrochemical reduction of AgNCs. Under optimal circumstances, the sandwich-type electrochemical immunosensor exhibits broad limit of linearity from 0.001 to 100 ng mL-1 (R2 = 0.997) and low detection limit of 7.74 fg mL-1 (S/N = 3). The immunosensor possesses excellent repeatability and selectivity, offering a novel method for sensitive clinical diagnosis of tumor markers in human hepatocellular carcinoma.

A NOMOGRAM FOR PREDICTING PATIENTS WITH SEVERE HEATSTROKE.

ABSTRACT: Background: No predictive models are currently available to predict poor prognosis in patients with severe heatstroke. We aimed to establish a predictive model to help clinicians identify the risk of death and customize individualized treatment. Methods: The medical records and data of 115 patients with severe heatstroke hospitalized in the intensive care unit of Changzhou No. 2 People's Hospital between June 2013 and September 2019 were retrospectively analyzed for modeling. Furthermore, data of 84 patients with severe heatstroke treated at Jintan No. 1 People's Hospital from June 2013 to 2021 were retrospectively analyzed for external verification of the model. We analyzed the hematological parameters of the patients recorded within 24 h of admission, which included routine blood tests, liver function, renal function, coagulation routine, and myocardial enzyme levels. Risk factors related to death in patients with severe heatstroke were screened using Least Absolute Shrinkage and Selection Operator regression. The independent variable risk ratio for death was investigated using the Cox univariate and multivariate regression analyses. The nomogram was subsequently used to establish a suitable prediction model. A receiver operating characteristic curve was drawn to evaluate the predictive power of the prediction model and the Acute Physiology and Chronic Health Evaluation (APACHE II) score. In addition, decision curve analysis was established to assess the clinical net benefit. The advantages and disadvantages of both models were evaluated using the integrated discrimination improvement and Net Reclassification Index. A calibration curve was constructed to assess predictive power and actual conditions. The external data sets were used to verify the predictive accuracy of the model. Results: All independent variables screened by Least Absolute Shrinkage and Selection Operator regression were independent risk factors for death in patients with severe heatstroke, which included neutrophil/lymphocyte ratio, platelet (PLT), troponin I, creatine kinase myocardial band, lactate dehydrogenase, human serum albumin, D-dimer, and APACHE-II scores. On days 10 and 30, the integrated discrimination improvement of the prediction model established was 0.311 and 0.364 times higher than that of the APACHE-II score, respectively; and the continuous Net Reclassification Index was 0.568 and 0.482 times higher than that of APACHE-II, respectively. Furthermore, we established that the area under the curve (AUC) of the prediction model was 0.905 and 0.918 on days 10 and 30, respectively. Decision curve analysis revealed that the AUC of this model was 7.67% and 10.67% on days 10 and 30, respectively. The calibration curve showed that the predicted conditions suitably fit the actual requirements. External data verification showed that the AUC on day 10 indicated by the prediction model was 0.908 (95% confidence interval, 82.2-99.4), and the AUC on day 30 was 0.930 (95% confidence interval, 0.860-0.999). Conclusion: The survival rate of patients with severe heatstroke within 24 h of admission on days 10 and 30 can be effectively predicted using a simple nomogram; additionally, this nomogram can be used to evaluate risks and make appropriate decisions in clinical settings.

An ultrasensitive immunosensor based on cellulose nanofibrils/polydopamine/Cu-Ag nanocomposite for the detection of AFP.

In this work, an ultrasensitive immunosensor for amperometric determination of alpha-fetoprotein (AFP) was developed utilizing Ag and Cu nanoparticles on polydopamine (PDA) functionalized cellulose nanofibrils (CNFs) composite (CNFs/PDA/Cu-Ag) as signal amplifier. PDA was first prepared by self-polymerizing of dopamine, and then was adsorbed on CNFs. The obtained CNFs/PDA was applied as substrate to electrolessly deposit Cu-Ag nanoparticles, using NaBH4 as reducing agent. The structure and morphology of the synthesized CNFs/PDA/Cu-Ag nanocomposite were analyzed through Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray powder diffraction, scanning electron microscopy, particle size analyzer and transmission electron microscopy. The CNFs/PDA/Cu-Ag modified glassy carbon electrode can fix AFP antibody (Ab), and further capture AFP specifically. Electrochemical impedance spectroscopy and cyclic voltammetry were used to characterize the assembly process of immunosensor. The immunoreaction was amplified by electrocatalytical reduction of H2O2 on Cu-Ag nanoparticles, through which AFP was quantitatively detected. The developed sensor exhibits wide linear range of 0.01-100 ng mL-1 (R2 = 0.9963) with low detection limit of 4.27 pg mL-1 (S/N = 3). In addition, it has been used for the detection of AFP in human serum, manifesting its preeminent application prospect in early liver cancer diagnosis.

Emodin alleviates sepsis-mediated lung injury via inhibition and reduction of NF-kB and HMGB1 pathways mediated by SIRT1.

Inflammation plays an important role during sepsis, and excessive inflammation can result in organ damage, chronic inflammation, fibrosis, and scarring. The study aimed to investigate the specific mechanism of emodin by constructing in vivo and in vitro septic lung injury models via inhibition and reduction of NF-kB and high mobility group box 1 (HMGB1) pathways. A cecal ligation and puncture (CLP) model was built for adult male Sprague-Dawley rats. Concentrations of TNF-α, IL-1ß, and IL-6 in bronchoalveolar lavage fluid were determined using commercially available ELISA kits. Hematoxylin and eosin staining was used for the right lung inferior lobes. Myeloperoxidase (MPO) activity of the lung tissue was detected by using the MPO kit. Murine alveolar epithelial cell line (MLE-12) cells were used for flow cytometry and Western blot to analyze the apoptosis rate and protein expression. Emodin significantly decreased CLP-induced cell apoptosis, upregulated expression of sirtuin 1 (SIRT1), and inhibited p-p65/p65 and HMGB1. In lipopolysaccharide (LPS) treated cell model, emodin treatment markedly decreased LPS-induced release of IL-1, IL-6, and tumor necrosis factor (TNF)-α, inhibited LPS-induced cell apoptosis and suppressed protein levels of P-P65/P65 and HMGB1. However, science of SIRT1 reversed the above effects by treatment of emodin. In summarize, this study found that emodin can alleviate sepsis-induced lung injury in vivo and in vitro through regulation of SIRT1.

Anionic heptadecanuclear silver(I) cluster constructed from in situ generated 2-mercaptobenzoic acid and a sulfide anion.

A novel anionic heptadecanuclear silver(I) cluster, (NH(4))(17)[(µ(6)-S)@Ag(17)(mba)(16)]·22H(2)O (1; H(2)mba = 2-mercaptobenzoic acid), was obtained by the reaction of equivalent molar silver oxide and 2,2'-dithiodibenzoic acid (H(2)dtba) under ultrasonic conditions at 50 °C. Complex 1 is a discrete cluster comprised of unexpected mba ligands on the shell and a µ(6)-S(2-) ion in the core, suggesting the occurrence of in situ S-S and S-C(sp(2)) bond cleavages of the H(2)dtba ligand. This novel cluster displays moderate orange-red emission in the solid state at room temperature.

Capture and activation of aerial CO2 by carbamoylation of L-threonine in a Ag(I) supramolecular framework.

An ultrasonic reaction of Ag(2)O, 4,4'-bipyridine (bipy) and (2S, 3R)-3-amino-2-hydroxybutanoic acid (L-Thr) gives an unexpected Ag(I) supramolecular framework, {[Ag(3)(bipy)(3)(cahba)]·HCO(3)·10H(2)O}(n) (1), in which the (2S, 3R)-3-(carboxyamino)-2-hydroxybutanoic acid (H(2)cahba) is a carbamate derivative of L-Thr, obtained via in situ transformation of amino group of L-Thr into carbamate by means of CO(2) uptake.