Erratum to "Relationship between PaO2/FiO2 and delirium in intensive care: A cross-sectional study" [Journal of Intensive Medicine volume 3 (2023) 73-78.].

[This corrects the article DOI: 10.1016/j.jointm.2022.08.002.].

Inhibition of the glutamatergic PVT-NAc projections attenuates local anesthetic-induced neurotoxic behaviors.

INTRODUCTION: Local anesthetic-induced neurotoxicity contributes to perioperative nerve damage; however, the underlying mechanisms remain unclear. Here, we investigated the role of the paraventricular thalamus (PVT)-nucleus accumbens (NAc) projections in neurotoxicity induced by ropivacaine, a local anesthetic agent. METHODS: Ropivacaine (58 mg/kg, intraperitoneal administration) was used to construct the local anesthetic systemic toxicity (LAST) mice model. We first identified neural projections from the PVT to the NAc through the expression of a retrograde tracer and virus. The inhibitory viruses (rAAV-EF1α-DIO-hm4D(Gi)-mCherry-WPREs: AAV2/retro and rAAV-CaMKII-CRE-WPRE-hGh: AAV2/9) were injected into the mice model to assess the effects of the specific inhibition of the PVT-NAc pathway on neurological behaviors in the presence of clozapine-N-oxide. The inhibition of the PVT-NAc pathway was evaluated by immunofluorescence staining of c-Fos-positive neurons and Ca2+ signals in CaMKIIa neurons. RESULTS: We successfully identified a circuit connecting the PVT and NAc in C57BL/6 mice. Ropivacaine administration induced the activation of the PVT-NAc pathway and seizures. Specific inhibition of NAc-projecting CaMKII neurons in the PVT was sufficient to inhibit the neuronal activity in the NAc, which subsequently decreased ropivacaine-induced neurotoxicity. CONCLUSION: These results reveal the presence of a dedicated PVT-NAc circuit that regulates local anesthetic-induced neurotoxicity and provide a potential mechanistic explanation for the treatment and prevention of LAST.

Chemogenetic activation of the HPC-mPFC pathway improves cognitive dysfunction in lipopolysaccharide -induced brain injury.

Rationale: Although sepsis-associated encephalopathy (SAE) is a common psychiatric complication in septic patients, the underlying mechanisms remain unclear. Here, we explored the role of the hippocampus (HPC) - medial prefrontal cortex (mPFC) pathway in cognitive dysfunction in lipopolysaccharide-induced brain injury. Methods: Lipopolysaccharide (LPS, 5 mg/kg, intraperitoneal) was used to induce an animal model of SAE. We first identified neural projections from the HPC to the mPFC via a retrograde tracer and virus expression. The activation viruses (pAAV-CaMKIIα-hM3Dq-mCherry) were injected to assess the effects of specific activation of mPFC excitatory neurons on cognitive tasks and anxiety-related behaviors in the presence of clozapine-N-oxide (CNO). Activation of the HPC-mPFC pathway was evaluated via immunofluorescence staining of c-Fos-positive neurons in mPFC. Western blotting was performed to determine protein levels of synapse- associated factors. Results: We successfully identified a structural HPC-mPFC connection in C57BL/6 mice. LPS-induced sepsis induces cognitive impairment and anxiety-like behaviors. Chemogenetic activation of the HPC-mPFC pathway improved LPS-induced cognitive dysfunction but not anxiety-like behavior. Inhibition of glutamate receptors abolished the effects of HPC-mPFC activation and blocked activation of the HPC-mPFC pathway. The glutamate receptor-mediated CaMKII/CREB/BDNF/TrKB signaling pathway influenced the role of the HPC-mPFC pathway in sepsis-induced cognitive dysfunction. Conclusions: HPC-mPFC pathway plays an important role in cognitive dysfunction in lipopolysaccharide-induced brain injury. Specifically, the glutamate receptor-mediated downstream signaling appears to be an important molecular mechanism linking the HPC-mPFC pathway with cognitive dysfunction in SAE.

Effect of ß-blockers on mortality in patients with sepsis: A propensity-score matched analysis.

Objectives: We aimed to evaluate the association between ß-blocker therapy and mortality in patients with sepsis. Methods: Patients with sepsis were selected from the Medical Information Mart for Intensive Care (MIMIC)-III. Propensity score matching (PSM) was used to balance the baseline differences. A multivariate Cox regression model was used to assess the relationship between ß-blocker therapy and mortality. The primary outcome was the 28-day mortality. Results: A total of 12,360 patients were included in the study, involving 3,895 who received ß-blocker therapy and 8,465 who did not. After PSM, 3,891 pairs of patients were matched. The results showed that ß-blockers were associated with improved 28- (hazards ratio (HR) 0.78) and 90-day (HR 0.84) mortality. Long-acting ß-blockers were associated with improved 28-day survival (757/3627 [20.9%] vs. 583/3627 [16.1%], P < 0.001, HR0.76) and 90-day survival (1065/3627 [29.4%] vs.921/3627 [25.4%], P < 0.001, HR 0.77). Short-acting ß-blocker treatment did not reduce the 28-day and 90-day mortality (61/264 [23.1%] vs. 63/264 [23.9%], P = 0.89 and 83/264 [31.4%] vs. 89/264 [31.7%], P = 0.8, respectively). Conclusions: ß-blockers were associated with improved 28- and 90-day mortality in patients with sepsis and septic shock. Long-acting ß-blocker therapy may have a protective role in patients with sepsis, reducing the 28-day and 90-day mortality. However, short-acting ß-blocker (esmolol) treatment did not reduce the mortality in sepsis.

Effect of basal metabolic rate on osteoporosis: A Mendelian randomization study.

Purpose: Basal metabolic rate may play a key role in the pathogenesis and progression of osteoporosis. We performed Mendelian random analysis to evaluate the causal relationship between basal metabolic rate and osteoporosis. Methods: Instrumental variables for the basal metabolic rate were selected. We used the inverse variance weighting approach as the main Mendelian random analysis method to estimate causal effects based on the summary-level data for osteoporosis from genome-wide association studies. Results: A potential causal association was observed between basal metabolic rate and risks of osteoporosis (odds ratio = 0.9923, 95% confidence interval: 0.9898-0.9949; P = 4.005e - 09). The secondary MR also revealed that BMR was causally associated with osteoporosis (odds ratio = 0.9939, 95% confidence interval: 0.9911-0.9966; P = 1.038e - 05). The accuracy and robustness of the findings were confirmed using sensitivity tests. Conclusion: Basal metabolic rate may play a causal role in the development of osteoporosis, although the underlying mechanisms require further investigation.

Relationship between PaO2/FiO2 and delirium in intensive care: A cross-sectional study.

Background: To investigate the relationship between partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) and the probability of delirium in intensive care units (ICUs). Methods: The investigation was a cross-sectional study that involved the collection of data from patients admitted to the Xiang Ya Hospital Cardiothoracic Surgical Care Unit and Comprehensive Intensive Care Unit from 01 September 2016 to 10 December 2016. Delirium was diagnosed using the simplified version of the Chinese Confusion Assessment Method (CAM) for the ICU. Demographic and medical data were obtained within 24 h of each patient admitted in the ICU. The PaO2/FiO2 of each patient was recorded 24 h after admission in the ICU. The patients were divided into three groups according to PaO2/FiO2 data : normal (PaO2/FiO2 ≥300 mmHg), slightly low (200 ≥PaO2/FiO2 <300 mmHg), and severely low (PaO2/FiO2 <200 mmHg). Baseline characteristics were compared in the three groups. Results of the unadjusted model, minimally adjusted model, and fully adjusted model are presented. Results: A total of 403 participants were included in the study, of which 184 (45.7%) developed delirium. Age (P <0.001), Sequential Organ Failure Assessment (SOFA) score (P <0.001), Acute Physiology and Chronic Health Evaluation (APACHE) II score (P <0.001), mechanical ventilation time (P <0.001), history of hypertension (P=0.040), heart disease (P=0.040), sedation (P=0.001), and PaO2/FiO2 (P=0.006) were significantly associated with delirium in univariate analysis. Multivariate regression analysis models were used to further analyze the associations between PaO2/FiO2 and delirium. In the crude model, for 1 standard deviation (SD) increase in PaO2/FiO2, the odds ratio (OR) of delirium was 0.8 (95% confidence interval [CI]: 0.6-0.9), but there was no significant correlation in the fully adjusted model. There was a non-linear relationship between the PaO2/FiO2 and delirium in a generalized additive model. A two-piecewise linear regression model was used to calculate a PaO2/FiO2 threshold of 243 mmHg. On the left side of the threshold, the OR was 0.9 and the 95% CI was 0.9-1.0 (P=0.013) when PaO2/FiO2 increased by 1 SD. Conclusions: PaO2/FiO2 was negatively associated with delirium when PaO2/FiO2 was below the identified threshold. As a readily available laboratory indicator, PaO2/FiO2 has potential value in the clinical evaluation of risk of delirium in ICU patients.

An Extension Network of Dendritic Neurons.

Deep learning (DL) has achieved breakthrough successes in various tasks, owing to its layer-by-layer information processing and sufficient model complexity. However, DL suffers from the issues of both redundant model complexity and low interpretability, which are mainly because of its oversimplified basic McCulloch-Pitts neuron unit. A widely recognized biologically plausible dendritic neuron model (DNM) has demonstrated its effectiveness in alleviating the aforementioned issues, but it can only solve binary classification tasks, which significantly limits its applicability. In this study, a novel extended network based on the dendritic structure is innovatively proposed, thereby enabling it to solve multiple-class classification problems. Also, for the first time, an efficient error-back-propagation learning algorithm is derived. In the extensive experimental results, the effectiveness and superiority of the proposed method in comparison with other nine state-of-the-art classifiers on ten datasets are demonstrated, including a real-world quality of web service application. The experimental results suggest that the proposed learning algorithm is competent and reliable in terms of classification performance and stability and has a notable advantage in small-scale disequilibrium data. Additionally, aspects of network structure constrained by scale are examined.

Hippocampus-prefrontal cortex inputs modulate spatial learning and memory in a mouse model of sepsis induced by cecal ligation puncture.

AIMS: Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments. However, the pathophysiology of SAE is complex and unclear. Here, we investigated the role of hippocampus (HPC)-prefrontal cortex (PFC) in cognitive dysfunction in sepsis induced by cecal ligation puncture (CLP) in mice. METHODS: The neural projections from the HPC to PFC were first identified via retrograde tracing and viral expression. Chemogenetic activation of the HPC-PFC pathway was shown via immunofluorescent staining of c-Fos-positive neurons in PFC. Morris Water Maze (MWM) and Barnes maze (BM) were used to evaluate cognitive function. Western blotting analysis was used to determine the expression of glutamate receptors and related molecules in PFC and HPC. RESULTS: Chemogenetic activation of the HPC-PFC pathway enhanced cognitive dysfunction in CLP-induced septic mice. Glutamate receptors mediated the effects of HPC-PFC pathway activation in CLP mice. The activation of the HPC-PFC pathway resulted in significantly increased levels of NMDAR, AMPAR, and downstream signaling molecules including CaMKIIa, pCREB, and BDNF in PFC. However, inhibition of glutamate receptors using 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F)quinoxaline (NBQX), which is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR inhibitor), or D-2-amino-5-phosphonopentanoate (D-AP5), which is an NMDA receptor antagonist abolished this increase. CONCLUSION: Our study reveals the important role of the HPC-PFC pathway in improving cognitive dysfunction in a mouse model of CLP sepsis and provides a novel pathogenetic mechanism for SAE.

Association between albumin infusion and septic patients with coronary heart disease: A retrospective study based on medical information mart for intensive care III database.

Coronary heart disease (CHD) is a common comorbidity in intensive care unit (ICU) patients, particularly in the elderly. This particular population may have worse conditions during sepsis, and it presents an overwhelming challenge for clinical practice. Previous studies suggested that patients with CHD have an increased risk of cardiovascular events, and low albumin concentration worsens the prognosis of patients with stable CHD. Hypoalbuminemia in patients with sepsis is common due to nutritional disorders, excessive consumption, and leakage. Albumin is a fluid often used for resuscitation in patients with sepsis. However, albumin infusion in patients with sepsis and CHD has rarely been studied. The effects and safety of albumin infusion in patients with sepsis and CHD remain unclear. Therefore, we collected medical information from Mimic-III (Mimic-III) and compared the all-cause mortality and cardiovascular mortality at 28- or 90-day between the albumin and non-albumin groups in septic patients with CHD. A total of 2,027 patients with sepsis and CHD were included in our study, with 405 in the albumin group and 1,622 in the non-albumin group. After propensity score matching (PSM), 350 pairs were included in our study. Improved survival benefits were found in the albumin group at the 28-day all-cause mortality compared with the non-albumin group (hazard ratio [HR], 0.54; 95% CI: 0.38-0.78; p = 0.0009). However, no difference was detected in the 90-day survival benefits (HR, 0.80, 95% CI: 0.60-1.06, p = 0.1207). Albumin infusion did not reverse cardiovascular mortality neither at 28th day nor at 90th day (cardiovascular mortality: 28 days, HR, 0.52, 95% CI: 0.23-1.19, p = 0.1218; 90 days, HR, 0.66, 95% CI: 0.33-1.33, p = 0.2420).

Machine learning for early prediction of sepsis-associated acute brain injury.

Background: Sepsis-associated encephalopathy (SAE) is defined as diffuse brain dysfunction associated with sepsis and leads to a high mortality rate. We aimed to develop and validate an optimal machine-learning model based on clinical features for early predicting sepsis-associated acute brain injury. Methods: We analyzed adult patients with sepsis from the Medical Information Mart for Intensive Care (MIMIC III) clinical database. Candidate models were trained using random forest, support vector machine (SVM), decision tree classifier, gradients boosting machine (GBM), multiple layer perception (MLP), extreme gradient boosting (XGBoost), light gradients boosting machine (LGBM) and a conventional logistic regression model. These methods were applied to develop and validate the optimal model based on its accuracy and area under curve (AUC). Results: In total, 12,460 patients with sepsis met inclusion criteria, and 6,284 (50.4%) patients suffered from sepsis-associated acute brain injury. Compared other models, the LGBM model achieved the best performance. The AUC for both train set and test set indicated excellent validity (Trainset AUC 0.91, Testset AUC 0.87). Feature importance analysis showed that glucose, age, mean arterial pressure, heart rate, hemoglobin, and length of ICU stay were the top 6 important clinical factors to predict occurrence of sepsis-associated acute brain injury. Conclusion: Almost half of patients admitted to ICU with sepsis had sepsis-associated acute brain injury. The LGBM model better identify patients with sepsis-associated acute brain injury than did other machine-learning models. Glucose, age, and mean arterial pressure were the three most important clinical factors to predict occurrence of sepsis-associated acute brain injury.

Relationship Between Cerebral Hemodynamics, Tissue Oxygen Saturation, and Delirium in Patients With Septic Shock: A Pilot Observational Cohort Study.

Background: Septic shock patients have tendencies toward impairment in cerebral autoregulation and imbalanced cerebral oxygen metabolism. Tissue Oxygen Saturation (StO2) and Transcranial Doppler (TCD) monitoring were undertaken to observe the variations of cerebral hemodynamic indices and cerebral/peripheral StO2 to find risk factors that increase the sepsis-associated delirium (SAD). Materials and Methods: The research cohort was chosen from septic shock patients received in the Department of Critical Care Medicine, Xiangya Hospital, Central South University between May 2018 and March 2019. These patients were separated into two groups, SAD and non-SAD as assessed by using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Comparisons were made between the two groups in terms of peripheral StO2, fluctuations in regional cerebral oxygen saturation (rSO2), cerebral vascular automatic regulation function [Transient Hyperemic Response Ratio (THRR) index], cerebral hemodynamic index, organ function indicators, blood gas analysis indices, and patient characteristics. Results: About 39% of the patients (20/51) suffered from SAD. Nearly 43% of the patients died within 28 days of admission (22/51). Individuals in the SAD cohort needed a longer period of mechanical ventilation [5 (95% CI 2, 6) vs. 1 days (95% CI 1, 4), p = 0.015] and more time in ICU [9 (95% CI 5, 20) vs. 5 days (95% CI 3, 9), p = 0.042]; they also experienced more deaths over the 28-day period (65 vs. 29%, p = 0.011). The multivariate regression analysis indicated that independent variables associated with SAD were THRR index [odds ratio (OR) = 5.770, 95% CI: 1.222-27.255; p = 0.027] and the mean value for rSO2 was < 55% (OR = 3.864, 95% CI: 1.026-14.550; p = 0.046). Conclusion: Independent risk factors for SAD were mean cerebral oxygen saturation below 55% and cerebrovascular dysregulation (THRR < 1.09).

Clinical values of cerebral oxygen saturation monitoring in patients with septic shock. / è„‘æ°§é¥±å’Œåº¦ç›‘æµ‹åœ¨è„“æ¯’ç—‡ä¼‘å ‹æ‚£è€ ä¸­çš„ä¸´åºŠåº”ç”¨ä»·å€¼.

OBJECTIVES: Sepsis associated encephalopathy (SAE) is a common neurological complication of sepsis. Delirium is a common symtom of SAE. The pathophysiology of SAE is still unclear, but several likely mechanisms have been proposed, such as mitochondrial and endothelial dysfunction, neurotransmission disturbances, derangements of calcium homeostasis, cerebral microcirculation dysfunction, and brain hypoperfusion. Near-infrared spectroscopy (NIRS) is a non-invasive measure for regional cerebral oxygen saturation (rSO2), which has attracted more attention these years. Previous studies have reported that abnormal NIRS values were associated with delirium in critically ill patients. Blood pressure management according to NIRS monitoring improved the organ perfusion and prognosis of patients. This study aimed to observe the dynamic changes of rSO2 using NIRS in septic shock patients, and analyze the relationship between them. METHODS: A total of 48 septic patients who admitted to the intensive care unit (ICU) of Xiangya Hospital, Central South University from August 2017 to May 2018, were retrospectively study. Septic shock was diagnosed according to the criteria of sepsis 3.0 defined by the American Association of Critical Care Medicine and the European Society of Critical Care Medicine. NIRS monitoring was performed during the first 6 hours admitted to ICU with sensors placed on the bilateral forehead of patients. The maximum (rSO2max), minimum (rSO2min), mean value, and the variation rate during the first 6 hours of monitor were recorded. The following data were collected upon the first 24 h after admission to the ICU: The baseline data of patients, laboratory examination results (routine blood test, liver and renal function, blood gas analysis, indicators of infection, and coagulation function), scoring system results [Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)]. Delirium was screened with the Confusion Assessment Method for ICU (CAM-ICU). The length of time on mechanical ventilation (MV), length of ICU-stay, length of hospital-stay, and 28-day mortality were also recorded. The primary outcome was 28-day mortality, and the secondary outcomes were the incidence of delirium, length of ICU-stay, and length of hospital-stay. The differences between survivors and non-survivors, and patients with or without delirium were analyzed, and the risk factors for delirium were assessed. The performance of rSO2-related indexes (rSO2max, rSO2min, the mean value, and the variation rate of rSO2) in predicting 28-day mortality and delirium was analyzed and the cutoff values were determined. RESULTS: The overall 28-day mortality of septic shock patients was 47.92% (23/48), and the incidence of delirium was 18.75% (9/48). The rSO2min was significantly lower in the non-survivors than the survivors (P=0.042). The variation rate of rSO2 was higher in patients with delirium than those without delirium (P=0.006). The independent risk factors for delirium were rSO2max, the level of direct bilirubin (DBIL), and whether achieved the 6-hour bundle. To predict the 28-day mortality of septic shock patients, the area under the receiver operating characteristic curve (AUROC) for rSO2max, rSO2min, the mean value and the variation rate of rSO2 were 0.616, 0.606, 0.623, and 0.504, respectively. To predict the incidence of delirium, AUROC for rSO2max, rSO2min, the mean value and the variation rate of rSO2 were 0.682, 0.617, 0.580, and 0.501, respectively. The best cutoff value for rSO2max in predicting delirium was 77.5% (sensitivity was 0.444, specificity was 0.897). The best cutoff value for rSO2min in predicting delirium was 65.5% (sensitivity was 0.556, specificity was 0.744). CONCLUSIONS: Cerebral anoxia and hyperoxia, as well as the large fluctuation of cerebral oxygen saturation are important factors that affect the outcomes and the incidence of delirium in septic shock patients, which should be paid attention to in clinical practice. Dynamic monitoring of cerebral oxygen saturation and maintain its stability may be of great significance in patients with septic shock.

Association between albumin infusion and outcomes in patients with acute kidney injury and septic shock.

Septic shock with acute kidney injury (AKI) is common in critically ill patients. Our aim was to evaluate the association between albumin infusion and outcomes in patients with septic shock and AKI. Medical Information Mart for Intensive Care (MIMIC)-III was used to identify patients with septic shock and AKI. Propensity score matching (PSM) was employed to balance the baseline differences. Cox proportional hazards model, Wilcoxon rank-sum test, and logistic regression were utilized to determine the associations of albumin infusion with mortality, length of stay, and recovery of kidney function, respectively. A total of 2861 septic shock patients with AKI were studied, including 891 with albumin infusion, and 1970 without albumin infusion. After PSM, 749 pairs of patients were matched. Albumin infusion was associated with improved 28-day survival (HR 0.72; 95% CI 0.59-0.86; P = 0.002), but it was not difference in 90-day mortality between groups (HR 0.94; 95% CI 0.79-1.12; P = 0.474). Albumin infusion was not associated with the renal function recovery (HR 0.91; 95% CI 0.73-1.13; P = 0.393) in either population. Nevertheless, subgroup analysis showed that albumin infusion was distinctly associated with reduced 28-day mortality in patients with age > 60 years. The results need to be validated in more randomized controlled trials.

NU9056, a KAT 5 Inhibitor, Treatment Alleviates Brain Dysfunction by Inhibiting NLRP3 Inflammasome Activation, Affecting Gut Microbiota, and Derived Metabolites in LPS-Treated Mice.

Background: The pathogenesis of sepsis-associated encephalopathy (SAE) is complicated, while the efficacy of current treatment technologies is poor. Therefore, the discovery of related targets and the development of new drugs are essential. Methods: A mouse model of SAE was constructed by intraperitoneal injection of lipopolysaccharide (LPS). LPS treatment of microglia was used to build an in vitro model of inflammation. Nine-day survival rates, behavioral testing, transmission electron microscopy (TEM), immunohistochemical (IHC), immunofluorescence (IF), and ELISA were performed. The expression levels of Occludin, Claudin 5, NLRP3, caspase-1, and ASC genes and proteins were detected by RT-qPCR or Western blot. Caspase-1 P10 (Casp-1 P10) protein expression was detected. 16S rDNA sequencing and gas chromatography-mass spectrometer (GC-MS) were used to analyze the gut microbiota and metabolism. Flow cytometric experiment and Cell Counting Kit-8 (CCK8) assay were performed. Results: NU9056 improved the survival rate of mice and alleviated LPS-induced cognitive impairment, anxiety, and depression in vivo. The tight junctions were thickened via NU9056 treatment. Further, the mRNAs and proteins expression levels of Occludin and Claudin 5 were up-regulated by NU9056. NU9056 increased the expression level of DCX. The expression levels of Iba-1, NLRP3, IL-1ß, ASC, and Casp-1 P10 were down-regulated by NU9056. The composition of the gut microbiota changed. Kyoto Encyclopedia of Genes and Genomes data predicted that the effects of NU9056 might be related to apoptosis and tight junction pathways. NU9056 up-regulated the concentration of acetate, propionate, and butyrate. NU9056 significantly reduced LPS-induced apoptosis of microglia, the average fluorescence intensity of ROS, and the release of IL-1ß and IL-18, while improving cell viability in vitro. Conclusions: NU9056 might effectively alleviate LPS-induced cognitive impairment and emotional disorder in experimental mice by inhibiting the NLRP3 inflammasome. The therapeutic effects may be related to gut microbiota and derived metabolites. NU9056 might be a potential drug of SAE prevention.

Lung ultrasound score based on the BLUE-plus protocol is associated with the outcomes and oxygenation indices of intensive care unit patients.

PURPOSE: The primary objective was to demonstrate the relationship between lung ultrasound (LUS) manifestations and the outcomes of intensive care unit (ICU) patients. The secondary objective was to determine the characteristics of LUS manifestations in different subgroups of ICU patients. METHODS: This prospective multi-center cohort study was conducted in 17 ICUs. A total of 1702 patients admitted between August 31, 2017 and February 16, 2019 were included. LUS was performed according to the bedside lung ultrasound in emergency (BLUE)-plus protocol, and LUS scores were calculated. Data on the outcomes and oxygenation indices were analyzed and compared between different primary indication groups. RESULTS: The LUS scores were significantly higher for non-survivors than for survivors and were significantly different between the oxygenation index groups, with higher scores in the lower oxygenation index groups. The LUS score was an independent risk factor for the 28-day mortality. The area under the receiver operating characteristic curve was 0.663 for prediction of the 28-day mortality and 0.748 for prediction of an oxygenation index ≤100. CONCLUSIONS: The LUS score based on the BLUE-plus protocol was an independent risk factor for the 28-day mortality and was important for the prediction of an oxygenation index ≤100. An early LUS score within 24 hours of ICU admission helps predicting the outcome of ICU patients.

Effect of focused cardiopulmonary ultrasonography on clinical outcome of septic shock: a randomized study.

OBJECTIVE: To investigate the effect of focused ultrasonography on clinical outcomes of septic shock. METHODS: Patients with septic shock were randomized into an integrated cardiopulmonary ultrasonography (ICUS) group and conventional (CON) group. Within 1 hour of admission, the ICUS group underwent ICUS examination for hemodynamic decision-making, while the CON group received standard treatment. The primary endpoint was 28-day mortality after admission. The secondary endpoints were cumulative fluid administration in the first 6, 24, and 72 hours; use of vasoactive drugs; lactate clearance; duration of ventilation; and ICU stay. RESULTS: Ninety-four qualified patients were enrolled (ICUS group, 49; CON group, 45). ICUS showed no significant effect on 28-day mortality. Within the initial 6 hours, the ICUS group tended to have a higher fluid balance and fluid intake than the CON group. The duration of vasopressor support was shorter in the ICUS group. There were no differences in the cumulative fluid infusion within 24 or 72 hours, lactate clearance, ICU stay, or duration of ventilation. CONCLUSIONS: The initially focused ICUS did not affect the clinical outcomes of septic shock, but it tended to be associated with a higher fluid balance within the initial 6 hours and shorter duration of vasopressor support.

S100B/RAGE/Ceramide signaling pathway is involved in sepsis-associated encephalopathy.

AIMS: Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis, and it might lead to long-term cognitive dysfunction and disability. This study aimed to explore the role of S100 calcium binding protein B (S100B)/RAGE/ceramide signaling pathway in SAE. MAIN METHODS: FPS-ZM1 (an inhibitor of RAGE), myriocin and GW4869 (an inhibitor of ceramide) were used to explore the role of S100B/RAGE/ceramide in acute brain injury and long-term cognitive impairment in sepsis. In addition, Mdivi-1 (inhibitor of Drp1) and Drp1 siRNA were utilized to assess the effects of C2-ceramide on neuronal mitochondria, and to explore the specific underlying mechanism in C2 ceramide-induced death of HT22 mouse hippocampal neuronal cells. KEY FINDINGS: Western blot analysis showed that sepsis significantly up-regulated S100B and RAGE. Nissl staining and Morris water maze (MWM) test revealed that inhibition of RAGE with FPS-ZM1 markedly attenuated cecal ligation and puncture (CLP)-induced brain damage and cognitive dysfunction. Furthermore, FPS-ZM1 relieved sepsis-induced C2-ceramide accumulation and abnormal mitochondrial dynamics. Moreover, inhibition of ceramide also showed similar protective effects both in vivo and in vitro. Furthermore, Mdivi-1 and Drp1 siRNA significantly reduced C2-ceramide-induced neuronal mitochondrial fragmentation and cell apoptosis in vitro. SIGNIFICANCE: This study confirmed that S100B regulates mitochondrial dynamics through RAGE/ceramide pathway, in addition to the role of this pathway in acute brain injury and long-term cognitive impairment during sepsis.

MicroRNA-125b alleviates hydrogen-peroxide-induced abnormal mitochondrial dynamics in HT22 cells by inhibiting p53.

Micro-RNA125b (miR-125b) and tumor protein p53 (p53) are involved in the regulation of mitochondrial dynamics; however, the mechanism of their possible interaction during oxidative stress remains unclear. In this study, we investigated the role and mechanism of miR-125b and p53 in oxidative stress-induced mitochondrial damage in immortalized mouse hippocampal HT22 cells. Following stimulation with H2O2, we observed downregulation of miR-125b expression, upregulation of p53 expression, mitochondria were damaged and increased cell death. Overexpression of miR-125b alleviated mitochondrial damage and inhibited p53 expression. Furthermore, confocal and electron microscopy showed that overexpression of p53 eliminated the protective effect of miR-125b on the mitochondria. Thus, miR-125b alleviates abnormal mitochondrial homeostasis in H2O2-treated HT22 cells by suppressing p53 expression. Our data reveal a new model by which miR-125b influences mitochondrial dynamics.

Differences in clinical characteristics between younger and older patients with COVID-19 and their relationship with the length of hospital stay.

Background: The coronavirus disease 2019 (COVID-19) pandemic is currently threatening the health of individuals worldwide. We compared the clinical characteristics between younger patients (aged <60 years) and older patients (aged ≥60 years) with COVID-19, detected the risk factors associated with a prolonged hospital stay, and examined the treatments commonly used with a particular focus on antiviral therapies. Methods: This retrospective study was conducted at the West Campus, Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology (Wuhan, China). The sample consisted of 123 patients admitted to the hospital between 9th February, 2020, and 3rd March, 2020. The data related to the demographics, laboratory findings, and treatment were analyzed to identify discrepancies between younger and older patients and those with and without primary diseases. The risk factors that contribute to a prolonged hospital stay were subsequently identified. Results: Patients aged ≥60 years required longer hospital stay than younger patients (P=0.001). The percentage of lymphocytes was significantly lower in older patients and those with primary diseases (P=0.016 and P=0.042, respectively). The findings revealed that the risk factors that contributed to the length of hospital stay were age, the number of days of illness before hospitalization, white blood cell (WBC) count and albumin levels at admission, a neutrophil fraction at discharge, and antibiotic treatment. Analysis using a model that consisted of the above five risk factors for predicting prolonged hospital stay (>14 days) yielded an area under the ROC (AuROC) curve of 0.716. Antiviral and antibiotic treatments were administered to 97.6% and 39.0% of patients, respectively. The antiviral drugs most commonly administered were traditional Chinese medicine (83.7%) and arbidol (75.6%). Conclusions: In this study, older patients and those with primary diseases were at a higher risk of worse clinical manifestations. The physicians who treat the patients should pay close attention to the risk factors that contribute to the length of hospital stay, which could be used for predicting prolonged hospital stay. Traditional Chinese medicine and arbidol were the most frequently used antiviral drugs. Nevertheless, the extent to which these medications can effectively treat COVID-19 warrants further investigation.

Can bioimpedance cardiography assess hemodynamic response to passive leg raising in critically ill patients: A STROBE-compliant study.

ABSTRACT: Passive leg raising (PLR) is a convenient and reliable test to predict fluid responsiveness. The ability of thoracic electrical bioimpedance cardiography (TEB) to monitor changes of cardiac output (CO) during PLR is unknown.In the present study, we measured CO in 61 patients with shock or dyspnea by TEB and transthoracic echocardiography (TTE) during PLR procedure. Positive PLR responsiveness was defined as the velocity-time integral (VTI) ≥10% after PLR. TTE measured VTI in the left ventricular output tract. The predictive value of TEB parameters in PLR responders was tested. Furthermore, the agreement of absolute CO values between TEB and TTE measurements was assessed.Among the 61 patients, there were 28 PLR-responders and 33 non-responders. Twenty-seven patients were diagnosed with shock and 34 patients with dyspnea, with 55.6% (15/27) and 54.6% (18/34) non-responders, respectively. A change in TEB measured CO (ΔCO) ≥9.8% predicted PLR responders with 75.0% sensitivity and 78.8% specificity, the area under the receiver operating characteristic curve (AUROC) was 0.79. The Δd2Z/dt2 (a secondary derivative of the impedance wave) showed the best predictive value with AUROC of 0.90, the optimal cut point was -7.1% with 85.7% sensitivity and 87.9% specificity. Bias between TEB and TTE measured CO was 0.12 L/min, and the percentage error was 65.8%.TEB parameters had promising performance in predicting PLR responders, and the Δd2Z/dt2 had the best predictive value. The CO values measured by TEB were not interchangeable with TTE in critically ill settings.