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Background: Coronavirus disease 2019 (COVID-19) is the etiology of acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) is used to support gas exchange in patients who have failed conventional mechanical ventilation. However, there is no clear consensus on the timing of ECMO use in severe COVID-19 patients. Objective: The aim of this study is to compare the differences in pre-ECMO time and ECMO duration between COVID-19 survivors and non-survivors and to explore the association between them. Methods: PubMed, the Cochrane Library, Embase, and other sources were searched until 21 October 2022. Studies reporting the relationship between ECMO-related time and COVID-19 survival were included. All available data were pooled using random-effects methods. Linear regression analysis was used to determine the correlation between pre-ECMO time and ECMO duration. The meta-analysis was registered with PROSPERO under registration number CRD42023403236. Results: Out of the initial 2473 citations, we analyzed 318 full-text articles, and 54 studies were included, involving 13,691 patients. There were significant differences between survivors and non-survivors in the time from COVID-19 diagnosis (standardized mean difference (SMD) = −0.41, 95% confidence interval (CI): [−0.53, −0.29], p < 0.00001), hospital (SMD = −0.53, 95% CI: [−0.97, −0.09], p = 0.02) and intensive care unit (ICU) admission (SMD = −0.28, 95% CI: [−0.49, −0.08], p = 0.007), intubation or mechanical ventilation to ECMO (SMD = −0.21, 95% CI: [−0.32, −0.09], p = 0.0003) and ECMO duration (SMD = −0.18, 95% CI: [−0.30, −0.06], p = 0.003). There was no statistical association between a longer time from symptom onset to ECMO (hazard ratio (HR) = 1.05, 95% CI: [0.99, 1.12], p = 0.11) or time from intubation or mechanical ventilation (MV) and the risk of mortality (highest vs. lowest time groups odds ratio (OR) = 1.18, 95% CI: [0.78, 1.78], p = 0.42; per one-day increase OR = 1.14, 95% CI: [0.86, 1.52], p = 0.36; HR = 0.99, 95% CI: [0.95, 1.02], p = 0.39). There was no linear relationship between pre-ECMO time and ECMO duration. Conclusion: There are differences in pre-ECMO time between COVID-19 survivors and non-survivors, and there is insufficient evidence to conclude that longer pre-ECMO time is responsible for reduced survival in COVID-19 patients. ECMO duration differed between survivors and non-survivors, and the timing of pre-ECMO does not have an impact on ECMO duration. Further studies are needed to explore the association between pre-ECMO and ECMO time in the survival of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Acute Respiratory Distress Syndrome (ARDS) is a sudden onset of lung injury characterized by bilateral pulmonary edema, diffuse inflammation, hypoxemia, and a low P/F ratio. Epithelial injury and endothelial injury are notable in the development of ARDS, which is more severe under mechanical stress. This review explains the role of alveolar epithelial cells and endothelial cells under physiological and pathological conditions during the progression of ARDS. Mechanical injury not only causes ARDS but is also a side effect of ventilator-supporting treatment, which is difficult to model both in vitro and in vivo. The development of lung organoids has seen rapid progress in recent years, with numerous promising achievements made. Multiple types of cells and construction strategies are emerging in the lung organoid culture system. Additionally, the lung-on-a-chip system presents a new idea for simulating lung diseases. This review summarizes the basic features and critical problems in the research on ARDS, as well as the progress in lung organoids, particularly in the rapidly developing microfluidic system-based organoids. Overall, this review provides valuable insights into the three major factors that promote the progression of ARDS and how advances in lung organoid technology can be used to further understand ARDS. [ABSTRACT FROM AUTHOR]

Background: In the process of mechanical ventilation, the problem of patient-ventilator asynchrony (PVA) is faced. This study proposes a self-developed remote mechanical ventilation visualization network system to solve the PVA problem. Method: The algorithm model proposed in this study builds a remote network platform and achieves good results in the identification of ineffective triggering and double triggering abnormalities in mechanical ventilation. Result: The algorithm has a sensitivity recognition rate of 79.89% and a specificity of 94.37%. The sensitivity recognition rate of the trigger anomaly algorithm was as high as 67.17%, and the specificity was 99.92%. Conclusions: The asynchrony index was defined to monitor the patient's PVA. The system analyzes real-time transmission of respiratory data, identifies double triggering, ineffective triggering, and other anomalies through the constructed algorithm model, and outputs abnormal alarms, data analysis reports, and data visualizations to assist or guide physicians in handling abnormalities, which is expected to improve patients' breathing conditions and prognosis. [ABSTRACT FROM AUTHOR]

Background: To investigate the optimal target e of lactate kinetics at different time during the resuscitation, the factors that influence whether the kinetics achieve the goals, and the clinical implications of different clinical phenotypes. Methods: Patients with hyperlactatemia between May 1, 2013 and December 31, 2018 were retrospectively analyzed. Demographic data, basic organ function, hemodynamic parameters at ICU admission (T0) and at 6 h, 12 h, 24 h, 48 h, and 72 h, arterial blood lactate and blood glucose levels, cumulative clinical treatment conditions at different time points and final patient outcomes were collected. Results: A total of 3298 patients were enrolled, and the mortality rate was 12.2%. The cutoff values of lactate kinetics for prognosis at 6 h, 12 h, 24 h, 48 h, and 72 h were 21%, 40%, 57%, 66%, and 72%. The APACHE II score, SOFA score, heart rate (HR), and blood glucose were risk factors that correlated with whether the lactate kinetics attained the target goal. Based on the pattens of the lactate kinetics, eight clinical phenotypes were proposed. The odds ratios of death for clinical phenotypes VIII, IV, and II were 4.39, 4.2, and 5.27-fold of those of clinical phenotype I, respectively. Conclusion: Stepwise recovery of lactate kinetics is an important resuscitation target for patients with hyperlactatemia. The APACHE II score, SOFA score, HR, and blood glucose were independent risk factors that influenced achievement of lactate kinetic targets. The cinical phenotypes of stepwise lactate kinetics are closely related to the prognosis. [ABSTRACT FROM AUTHOR]

Background: Although protective mechanical ventilation (MV) has been used in a variety of applications, lung injury may occur in both patients with and without acute respiratory distress syndrome (ARDS). The purpose of this study is to use machine learning to identify clinical phenotypes for critically ill patients with MV in intensive care units (ICUs).Methods: A retrospective cohort study was conducted with 5013 patients who had undergone MV and treatment in the Department of Critical Care Medicine, Peking Union Medical College Hospital. Statistical and machine learning methods were used. All the data used in this study, including demographics, vital signs, circulation parameters and mechanical ventilator parameters, etc., were automatically extracted from the electronic health record (EHR) system. An external database, Medical Information Mart for Intensive Care III (MIMIC III), was used for validation.Results: Phenotypes were derived from a total of 4009 patients who underwent MV using a latent profile analysis of 22 variables. The associations between the phenotypes and disease severity and clinical outcomes were assessed. Another 1004 patients in the database were enrolled for validation. Of the five derived phenotypes, phenotype I was the most common subgroup (n = 2174; 54.2%) and was mostly composed of the postoperative population. Phenotype II (n = 480; 12.0%) led to the most severe conditions. Phenotype III (n = 241; 6.01%) was associated with high positive end-expiratory pressure (PEEP) and low mean airway pressure. Phenotype IV (n = 368; 9.18%) was associated with high driving pressure, and younger patients comprised a large proportion of the phenotype V group (n = 746; 18.6%). In addition, we found that the mortality rate of Phenotype IV was significantly higher than that of the other phenotypes. In this subgroup, the number of patients in the sequential organ failure assessment (SOFA) score segment (9,22] was 198, the number of deaths was 88, and the mortality rate was higher than 44%. However, the cumulative 28-day mortality of Phenotypes IV and II, which were 101 of 368 (27.4%) and 87 of 480 (18.1%) unique patients, respectively, was significantly higher than those of the other phenotypes. There were consistent phenotype distributions and differences in biomarker patterns by phenotype in the validation cohort, and external verification with MIMIC III further generated supportive results.Conclusions: Five clinical phenotypes were correlated with different disease severities and clinical outcomes, which suggested that these phenotypes may help in understanding heterogeneity in MV treatment effects. [ABSTRACT FROM AUTHOR]

Microcirculatory shock is a condition defined by the presence of tissue hypoperfusion despite the normalization of systemic and regional blood flow. Currently, more evidence shows that intrinsic septic shock is microcirculatory shock, which results in septic shock that is difficult to resuscitate. At present, treatments are aimed at recovering macro-circulation functions and include fluid resuscitation, vasoactive drugs, positive inotropic drugs, de-obstruction, and even mechanical assistance to improve oxygen delivery. However, the application of these treatments to more accurately improve microcirculation or avoid further microcirculatory damage is more important in clinics. In this article, we discuss the need for microcirculation protection and microcirculation-guided protection strategies in hemodynamic therapies. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the relationship between the variables of mechanical ventilation and circulatory perfusion and its association with ICU mortality during the first day of mechanical ventilation.Design: Retrospective cohort study.Setting: The Department of Critical Care Medicine, Peking Union Medical College Hospital.Patients: Patients who have undergone mechanical ventilation.Interventions: None.Measurements and Main Results: This study used the main clinical data obtained from the real-time bedside messaging systems of mechanically ventilated patients during their first day in the ICU from May 2013 to May 2016, including data on the variables of mechanical ventilation and circulatory perfusion. An analysis was then performed on the association of the above data with the patient's in-ICU mortality. There were 5,103 patients who received mechanical ventilation during this period, and of these, 309 patients died during their ICU treatment. Peak airway pressure, mean airway pressure, respiratory rate, heart rate, mean arterial pressure, FIO2, blood oxygen saturation, PO2, peripheral perfusion index, and lactate level were correlated with patient outcomes. A Cox logistic regression analysis suggested that mean airway pressure and perfusion index were the most independent risk and protective factors, respectively, for patient ICU mortality. The areas under the curve for a poor prognosis for mean airway pressure and perfusion index were 0.799 (95% CI, 0.77-0.829) and 0.759 (95% CI, 0.729-0.789), respectively. Further, mean airway pressure and perfusion index exhibited a causal interaction. The relative excess risk due to interaction was 2.061 (-0.691 to 4.814), the attributable proportion due to interaction was 0.210 (-0.027 to 0.447), and the synergy index was 1.306 (0.930-1.833).Conclusions: A higher mean airway pressure and lower perfusion index provided a worse prognosis in mechanically ventilated patients, and it appears that these two variables have a casual interaction. [ABSTRACT FROM AUTHOR]

Background: This aim of study was to introduce a diaphragm-based EIT-belt placement method based on diaphragm position by ultrasound, and to evaluate the difference between diaphragm-based EIT-belt placement and conventional EIT-belt placement. Method: The diaphragm position (L0) determined by ultrasound was taken as zero reference level. The direction of headward is defined as positive, and toward feet is negative. For EIT data collection, the electrode belt was placed at 7 different levels, respectively (denoted as L−2 cm, L0, L2cm, L4cm, L6cm, L8cm, L10cm) at supine position in healthy volunteers. The diaphragm-based EIT-belt level (Lxcm) was defined where highest tidal impedance variation (TV) was achieved. Subsequently, EIT measurements were conducted at diaphragm-based EIT-belt levels and traditional EIT-belt level in 50 critically ill patients under mechanical ventilation. Result: The highest TV was achieved at L6cm and the smallest at L−2 cm., so the L6cm were taken as diaphragm-based EIT-belt level by ultrasound in 8 healthy volunteers. In 23 patients, the diaphragm-based EIT-belt plane agreed with the conventional planes (4th–6th ICS), which was defined as the Agreed group. Other patients were classified to the Disagreed group (above 4th ICS). The Disagreed group has a significantly higher BMI and lower global TV at the diaphragm-based EIT-belt plane compared to the Agreed group. Conclusions: The diaphragm-based EIT-belt position by ultrasound was feasible and resulted in different belt positions compared to the conventional position in > 50% of the examined subjects, especially in patients with higher BMI. Further study is required to validate the impact on EIT images with this novel method on clinical management. [ABSTRACT FROM AUTHOR]

Procalcitonin (PCT) has been widely investigated for its prognostic value in septic patients. However, studies have produced conflicting results. The purpose of the present meta-analysis is to explore the diagnostic accuracy of a single PCT concentration and PCT non-clearance in predicting all-cause sepsis mortality. We searched PubMed, Embase, Web of Knowledge and the Cochrane Library. Articles written in English were included. A 2 × 2 contingency table was constructed based on all-cause mortality and PCT level or PCT non-clearance in septic patients. Two authors independently evaluated study eligibility and extracted data. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. We used the Q-test and I2 index to test heterogeneity. Twenty-three studies with 3,994 patients were included. An elevated PCT level was associated with a higher risk of death. The pooled relative risk (RR) was 2.60 (95% confidence interval (CI), 2.05–3.30) using a random-effects model (I2 = 63.5%). The overall area under the summary receiver operator characteristic (SROC) curve was 0.77 (95% CI, 0.73–0.80), with a sensitivity and specificity of 0.76 (95% CI, 0.67–0.82) and 0.64 (95% CI, 0.52–0.74), respectively. There was significant evidence of heterogeneity for the PCT testing time (P = 0.020). Initial PCT values were of limited prognostic value in patients with sepsis. PCT non-clearance was a prognostic factor of death in patients with sepsis. The pooled RR was 3.05 (95% CI, 2.35–3.95) using a fixed-effects model (I2 = 37.9%). The overall area under the SROC curve was 0.79 (95% CI, 0.75–0.83), with a sensitivity and specificity of 0.72 (95% CI, 0.58–0.82) and 0.77 (95% CI, 0.55–0.90), respectively. Elevated PCT concentrations and PCT non-clearance are strongly associated with all-cause mortality in septic patients. Further studies are needed to define the optimal cut-off point and the optimal definition of PCT non-clearance for accurate risk assessment. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies. Methods: Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU) admission, and the serum concentrations of 42 amino acids were measured. Results: The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs), especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively. Conclusions: Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic. Trial Registration: ClinicalTrial.gov identifier . [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary arterial pressure and vascular resistance. Despite advances in therapy for PAH, its treatment and prognosis remain poor. We aimed to investigate whether the transplantation of bone marrow mesenchymal stem cells (MSCs) overexpressing hepatocyte growth factor (HGF), alone or in combination with granulocyte colony-stimulating factor (G-CSF), attenuates the development of experimental monocrotaline (MCT)-induced PAH. Three weeks after MCT administration, rats were divided into the following groups: (1) untreated (PAH); (2) HGF treated; (3) MSCs administered; (4) HGF-MSCs treated; and (5) HGF-MSCs plus G-CSF treated. After 3 weeks, hemodynamic changes, histomorphology, and angiogenesis were evaluated. To elucidate the molecular mechanisms of vascular remodeling and angiogenesis, serum levels of transforming growth factor (TGF)-β and endothelin-1 (ET-1) were measured, and the gene and protein expression levels of vascular cell adhesion molecule-1 (VCAM-1) and matrix metalloproteinase-9 (MMP-9) were determined. Compared with the PAH, MSC, and G-CSF groups, the HGF and HGF+G-CSF groups exhibited significantly reduced right ventricular hypertrophy and mean pulmonary arterial pressure ( P < 0.05). Histologically, vessel muscularization or thickening and collagen deposition were also significantly decreased ( P < 0.05). The number of vessels in the HGF+G-CSF group was higher than that in the other groups ( P < 0.05). The TGF-β and ET-1 concentrations in the plasma of pulmonary hypertensive rats were markedly lower in the HGF and HGF+G-CSF groups ( P < 0.05). Furthermore, HGF induced the expression of VCAM-1, and HGF treatment together with G-CSF synergistically stimulated MMP-9 expression. Transplanted HGF-MSCs combined with G-CSF potentially offer synergistic therapeutic benefit for the treatment of PAH. [ABSTRACT FROM AUTHOR]

Abstract: The environment in space could affect microorganisms by changing a variety of features, including proliferation rate, cell physiology, cell metabolism, biofilm production, virulence, and drug resistance. However, the relevant mechanisms remain unclear. To explore the effect of a space environment on Bacillus cereus, a strain of B. cereus was sent to space for 398h by ShenZhou VIII from November 1, 2011 to November 17, 2011. A ground simulation with similar temperature conditions was simultaneously performed as a control. After the flight, the flight and control strains were further analyzed using phenotypic, genomic, transcriptomic and proteomic techniques to explore the divergence of B. cereus in a space environment. The flight strains exhibited a significantly slower growth rate, a significantly higher amikacin resistance level, and changes in metabolism relative to the ground control strain. After the space flight, three polymorphic loci were found in the flight strains LCT-BC25 and LCT-BC235. A combined transcriptome and proteome analysis was performed, and this analysis revealed that the flight strains had changes in genes/proteins relevant to metabolism. In addition, certain genes/proteins that are relevant to structural function, gene expression modification and translation, and virulence were also altered. Our study represents the first documented analysis of the phenotypic, genomic, transcriptomic, and proteomic changes that occur in B. cereus during space flight, and our results could be beneficial to the field of space microbiology. [Copyright &y& Elsevier]

This study explored the association of sepsis prognosis with dynamic changes in serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and its polymorphisms. We enrolled 80 subjects with sepsis and 80 controls. Serum sTREM-1 was tested on days 1, 3, 5, 7, 10, and 14. PCR sequencing was performed to detect TREM-1 genetic variation on its four exons. sTREM-1 levels were significantly higher in the nonsurvivor than in the survivor group ( p < 0.001), and those at each time point were the same ( p ≤ 0.001). Of the three tested TREM-1 SNPs (rs144672509, rs2234237, and rs2234246), only rs2234237 (Ser25Thr) was significantly associated with sepsis prognosis in three inheritance models ( p < 0.05). However, there was no relationship between TREM-1 polymorphism and dynamic concentration of sTREM-1. Logistic regression showed that sTREM-1, APACHE II, and rs2234237 polymorphism are risk factors for prognosis. Dynamic changes in serum sTREM-1 and rs2234237 polymorphism could be used in sepsis prognosis assessment. [ABSTRACT FROM AUTHOR]

New diagnostic biomarkers or therapeutic targets for sepsis have substantial significance for critical care medicine. In this study, 192 differentially expressed proteins were selected through iTRAQ. Based on cluster analysis of protein expression dynamics and protein-protein interactions, hemopexin, vimentin, and heat shock protein 90 were selected for further investigation. It was demonstrated that serum vimentin (VIM) levels were significantly increased in patients with sepsis and septic shock compared to controls and that VIM expression was significantly increased in lymphocytes isolated from septic shock and sepsis patients compared to controls. Moreover, a nonsurvivor group had higher serum VIM levels and VIM expression in lymphocytes. Caspase-3 was significantly upregulated in Jurkat T cells lacking VIM and when exposed to LPS compared to control cells. In contrast, caspase-3 was reduced nearly 40% in cells over-expressing VIM. IL-2, IL-10 and IFN-α levels were significantly decreased in cells lacking VIM compared to control cells, whereas they were not significantly altered in cells over-expressing VIM. These findings suggest that VIM modulates lymphocyte apoptosis and inflammatory responses and that VIM could be a new target for the diagnosis and prognostic prediction of patients with sepsis or septic shock. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. Methods: In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. Main results: In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value < 0.001). In terms of comorbidities, septic patients with hypertension and atrial fibrillation were prone to DVT (p value 0.045 and 0.048). Inflammatory cytokines, such as procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, had no significant correlation with DVT in patients with sepsis (p value 0.364, 0.882, 0.912, 0.789, 0.245, and 0.780). Levels of serum albumin correlated with DVT in patients with sepsis (p value 0.003). The SOFA total score had no relationship with DVT formation (p value 0.254). Coagulation and respiration function were negatively correlated with DVT (p value 0.018). Liver function was positively correlated with DVT (p value 0.020). Patients in the DVT group had longer duration of mechanical ventilation and longer intensive care unit (ICU) stays (p value < 0.001 and 0.006). There was no significant difference in survival in septic patients with and without DVT (p value 0.868). Conclusions: The SOFA total score had no relationship with DVT formation. The function of each organ had different effects on DVT formation. Better coagulation and respiration function, easier DVT formation. Poorer liver function, easier DVT formation. DVT was associated with longer duration of mechanical ventilation and longer ICU stays. [ABSTRACT FROM AUTHOR]

To explore a machine learning model for the early prediction of acute kidney injury (AKI) and to screen the related factors affecting new-onset AKI in the ICU. A retrospective analysis was performed used the MIMIC-III data source. New onset of AKI defined based on the serum creatinine changed. We included 19 variables for AKI assessment using four machine learning models: support vector machines, logistic regression, and random forest. and XGBoost, using accuracy, specificity, precision, recall, F1 score, and AUROC (area under the ROC curve) to evaluate model performance. The four models predicted new-onset AKI 3–6–9–12 h ahead. The SHapley Additive exPlanation (SHAP) value is used to evaluate the feature importance of the model. We finally respectively extracted 1130 AKI patients and non-AKI patients from the MIMIC-III database. With the extension of the early warning time, the prediction performance of each model showed a downward trend, but the relative performance was consistent. The prediction performance comparison of the four models showed that the XGBoost model performed the best in all evaluation indicators in all the time point at new-onset AKI 3–6–9–12 h ahead (accuracy 0.809 vs 0.78 vs 0.744 vs 0.741, specificity 0.856 vs 0.826 vs 0.797 vs 0.787, precision 0.842 vs 0.81 vs 0.775 vs 0.766, recall 0.759 vs 0.734 vs 0.692 vs 0.694, Fl score 0.799 vs 0.769 vs 0.731 vs 0.729, AUROC 0.892 vs 0.857 vs 0.827 vs 0.818). In the prediction of AKI 6, 9 and 12 h ahead, the importance of creatinine, platelets, and height was the most important based on SHapley. The machine learning model described in this study can predict AKI 3–6–9–12 h before the new-onset of AKI in ICU. In particular, platelet plays an important role. The new-onset of AKI in ICU is a common and important problem, which early be identified the risk of AKI can improve patients' outcomes. We explored MIMIC-III and determined the exact time point of occurrence of AKI as the basis for the new-onset of AKI in ICU. XGBoost model performed the best prediction in all the time point at new-onset AKI 3–6–9–12 h ahead. For patients with the new-onset of AKI in ICU, platelets become an important factor associated with AKI. [ABSTRACT FROM AUTHOR]

Platelets are highly involved in inflammation and organ injury under pathological conditions. The mitophagy in platelets may restrict hyperactivation of the inflammasome and relieve acute kidney injury (AKI). Cecal ligation puncture (CLP)/LPS‐induced AKI Triggering receptor expressed on myeloid cells (TREM‐1)‐knockout mice models were established. Additionally, septic patients with AKI were also included. TREM‐1 expression in platelets and inflammasome activation were examined. Platelet transfer assays were performed to investigate the contribution of platelet TREM‐1 to renal injury. Mitophagy was evaluated in the context of inflammation. BNIP3L/Nix knockout mice were used to examine the relationship between platelet mitophagy and inflammatory activation. The results showed that the level of TREM‐1 was increased and the platelet inflammasome was hyperactivated in CLP mice and septic patients, and TREM‐1 activated platelet inflammasomes. TREM‐1 deletion significantly abrogated hyperactivation of the platelet inflammasome and dramatically reduced AKI, whereas ablation of the mitophagy receptor BNIP3L/Nix induced the accumulation of damaged mitochondria and hyperactivation of platelet inflammasomes in CLP mice. BNIP3L/Nix controlled platelet inflammasome activation, and an amplification loop of platelet inflammasome activation and dysfunctional mitochondria controlled sepsis‐related AKI. Therefore, targeting TREM‐1 and NLRP3/BNIP3L in platelets may represent a novel therapeutic strategy for treating septic AKI. [ABSTRACT FROM AUTHOR]

Background: Serum lactate has long been used to evaluate hypoxia and predict prognosis in critically ill patients, however, discrepancy in lactate measurements between different sites have not been recognized as a useful tool for monitoring hypoxia and evaluating outcome. Methods: Data were obtained from the clinical information system of the intensive care unit (ICU) in a tertiary academic hospital for 1582 ICU patients with vasoactive drug requirement and valid paired blood gas. The mortality rates were compared between patients with sustained negative venous to arterial lactate gradient (VALac) and the others using the Cox proportional hazard model. Predictive factors associated with negative VALac were searched. Results: A sustained negative VALac was significantly associated with higher 30 day ICU mortality [Adjusted hazard ratio (HR) = 2.31, 95% confidence interval (CI), 1.07–4.99; p = 0.032. Propensity score- weighted HR: 2.57; 95% CI, 1.17–5.64; p = 0.010]. Arterial lactate in the first blood gas pair, 24-h arterial lactate clearance, use of epinephrine, mean positive end-expiratory pressure level, and extracorporeal membrane oxygenation initiation showed statistically significant association with sustained negative VALac during the first 24 h. Conclusion: The sustained negative VALac in the early stage of treatment may suggest additional information about tissue hypoxia than arterial lactate alone. Critical care physicians should pay more attention to the lactate discrepancy between different sites in their clinical practice. [ABSTRACT FROM AUTHOR]

Background: With the global spread of COVID-19, detecting high-risk countries/regions timely and dynamically is essential; therefore, we sought to develop automatic, quantitative and scalable analysis methods to observe and estimate COVID-19 spread worldwide and further generate reliable and timely decision-making support for public health management using a comprehensive modeling method based on multiple mathematical models. Methods: We collected global COVID-19 epidemic data reported from January 23 to September 30, 2020, to observe and estimate its possible spread trends. Countries were divided into three outbreak levels: high, middle, and low. Trends analysis was performed by calculating the growth rate, and then country grouping was implemented using group-based trajectory modeling on the three levels. Individual countries from each group were also chosen to further disclose the outbreak situations using two predicting models: the logistic growth model and the SEIR model. Results: All 187 observed countries' trajectory subgroups were identified using two grouping strategies: with and without population consideration. By measuring epidemic trends and predicting the epidemic size and peak of individual countries, our study found that the logistic growth model generally estimated a smaller epidemic size than the SEIR model. According to SEIR modeling, confirmed cases in each country would take an average of 9–12 months to reach the outbreak peak from the day the first case occurred. Additionally, the average number of cases at the peak time will reach approximately 10–20% of the countries' populations, and the countries with high trends and a high predicted size must pay special attention and implement public health interventions in a timely manner. Conclusions: We demonstrated comprehensive observations and predictions of the COVID-19 outbreak in 187 countries using a comprehensive modeling method. The methods proposed in this study can measure COVID-19 development from multiple perspectives and are generalizable to other epidemic diseases. Furthermore, the methods also provide reliable and timely decision-making support for public health management. [ABSTRACT FROM AUTHOR]

Background. Sepsis-induced myocardial dysfunction is a severe clinical problem. Recent studies have indicated that autophagy and myocardial energy depletion play a major role in myocardial dysfunction during sepsis, a mechanistic target of rapamycin (mTOR) as a master sensor of energy status and autophagy mediator; however, there are little data describing its role during sepsis in the heart. Methods. Cecal ligation and puncture (CLP) or sham operation (SHAM) was performed in rats. After treatment, pathological changes were determined by H&E staining, cardiac functions by echocardiography, the distribution of microtubule-associated protein light chain 3 (LC-3) type II and hypoxia-inducible factor 1α (HIF-1a) by immunohistochemical staining, and autophagic vacuoles by transmission electron microscopy. Moreover, the mTOR signaling pathway and LC3II, p62, and HIF-1a expression were measured by western blotting. Results. Rapamycin alleviated the pathological damage of myocardial tissue, attenuated cardiac dysfunction (left ventricular ejection fraction (LVEF), p<0.05; fractional shortening (FS), p<0.05), and reduced HIF-1a expression (p<0.05). Expectedly, rapamycin decreased the activity of the mTOR pathway in both sham-operated rats (p<0.0001) and CLP rats (p<0.01). Interestingly, we also found inhibition of the mTOR pathway in CLP rats compared with sham-operated rats; phosphorylation of both mTOR (p<0.001) and pS6K1 (p<0.01) was significantly suppressed following CLP challenge. Furthermore, autophagic processes were elevated by CLP; the ratio of LC3II/LC3I (p<0.05) was increased while p62 expression (p<0.001) was decreased significantly; there were also more autophagic vacuoles in CLP rats; and rapamycin could further elevate the autophagic processes compared with CLP rats (LC3II/LC3I, p<0.05; P62, p<0.05). Conclusion. Inhibition of the mTOR pathway has cardioprotective effects on myocardial dysfunction during sepsis induced by CLP, which is partly mediated through autophagy. [ABSTRACT FROM AUTHOR]

To explore the mechanism of mitochondrial uncoupling protein 2 (UCP2) mediating the protective of melatonin when septic cardiomyopathy. UCP2 knocked out mice and cardiomyocytes were used to study the effect of melatonin in response to LPS. Indicators of myocardial and mitochondria injury including mitochondrial membrane potential, mitochondrial permeability transition pore, calcium loading, ROS, and ATP detection were assessed. In addition cell viability and apoptosis as well as autophagy-associated proteins were evaluated. Melatonin was able to protect heart function from LPS, which weakened in the UCP2-knockout mice. Consistently, genipin, a pharmacologic inhibitor of UCP2, augmented LPS-induced damage of AC16 cells. In contrast, melatonin upregulated UCP2 expression and protected the cells from the changes in morphology, mitochondrial membrane potential loss, mitochondrial Ca2+ overload, the opening of mitochondrial permeability transition pore, and subsequent increased ROS generation as well as ATP reduction. Mitophagy proteins (Beclin-1 and LC-3β) were increased while apoptosis-associated proteins (cytochrome C and caspase-3) were decreased when UCP2 was up-regulated. In conclusion, UCP2 may play a protecting role against LPS by regulating the balance between autophagy and apoptosis of cardiomyocytes, and by which mechanisms, it may contribute to homeostasis of cardiac function and cardiomyocytes activity. Melatonin may protect cardiomyocytes through modulating UCP2. [ABSTRACT FROM AUTHOR]

Objective: Neuroinflammation is a major etiology of cognitive dysfunction due to sepsis. Maresin1 (MaR1), identified as a docosahexaenoic acid (DHA)-derived metabolite from macrophages, has been demonstrated to exhibit potent neuroprotective and anti-inflammatory effects. Nevertheless, detailed functions and molecular mechanism of MaR1 in sepsis-induced cognitive dysfunction has not been fully elucidated. Here, we aimed to investigate potential neuroprotective effects of MaR1 on microglia-induced neuroinflammation in sepsis-induced cognitive impairment and to explore its anti-inflammatory mechanism. Methods: Different doses of MaR1 were administered to septic rats by via tail vein injection. The optimal dose was determined based on the 7-day survival rate of rats from each group. derived from macrophages with both anti-inflammatory to observe the ameliorative effects of MaR1 at optimal doses on cognitive dysfunction in septic rats. The effects of MaR1 on neuroinflammation-mediated microglial activation, neuronal apoptosis, and pro-inflammatory cytokine productions were in vivo and in vitro assayed, using Western blot, ELISA, TUNEL staining, Nissl staining, and the immunofluorescence method. To further elucidate anti-inflammatory machinery of MaR1, protein expressions of NLRP3 inflammatory vesicles and TLR4-NF-κB pathway-related proteins were subjected to Western blot assay. Results: After tail vein injection of MaR1 with different doses (2 ng/g, 4 ng/g, 8 ng/g), the results showed that 4 ng/g MaR1 treatment significantly increased the rats' 7-day survival rate compared to the CLP controls. Therefore, subsequent experiments set 4 ng/g MaR1 as the optimal dose. Morris water maze experiments confirmed that MaR1 significantly reduced space memory dysfunction in rats. In addition, in CLP rats and LPS-stimulated BV2 microglia, MaR1 significantly reduced activated microglia and pro-inflammatory cytokines levels and neuronal apoptosis. Mechanically, MaR1 inhibits microglia-induced neuroinflammation through suppressing activations of NLRP3 inflammatory vesicles and TLR4-NF-κB signal pathway. Conclusion: Collectively, our findings suggested that MaR1 might be a prospective neuroprotective compound for prevention and treatment in the sepsis process. [ABSTRACT FROM AUTHOR]

Septic shock, largely caused by intestinal perforation, is a common critical disease in intensive care unit (ICU). For hospitals and health systems, a performance improvement program for sepsis was strong recommended in guidelines. Numerous studies have shown that improved quality control improves outcomes in patients with septic shock. Nevertheless, association between quality control and outcomes of septic shock caused by intestinal perforation are not fully revealed. Thus we designed this study to investigate effects of quality control on septic shock caused by intestinal perforation in China. This was a multicenter observational study. A total of 463 hospitals were enrolled in this survey, led by the China National Critical Care Quality Control Center (China-NCCQC) from January 1, 2018 to December 31, 2018. In this study, the indicators of quality control included the proportion of ICU patient bed occupancy to total inpatient bed occupancy, the proportion of ICU patients with APACHE II score ≥ 15, and the microbiology detection rate before antibiotic use. The outcome indicators included hospital stays, hospitalization costs, complications, and mortality. Generalized linear mixed models were used to analyse the association between quality control and septic shock caused by intestinal perforation. The proportion of ICU patient bed occupancy to total inpatient bed occupancy is positively correlated with hospital stays, incidence of complications (ARDS, AKI) and costs in septic shock caused by intestinal perforation (p < 0.05). The proportion of ICU patients with APACHE II score ≥ 15 was not associated with hospital stays and incidence of ARDS and AKI (p < 0.05). Increasing of the proportion of ICU patients with APACHE II score ≥ 15 decreased the costs of patients with septic shock caused by intestinal perforation (p < 0.05). The microbiology detection rate before antibiotic use was not associated with hospital stays, incidence of AKI and costs of patients with septic shock caused by intestinal perforation (p < 0.05). Surprisingly, the increase of microbiology detection rate before antibiotic use increased the incidence of ARDS in patients with septic shock caused by intestinal perforation (p < 0.05). The above three indicators of quality control were not associated with mortality of the patients with septic shock caused by intestinal perforation. On the one hand, the number of ICU patients admitted should be controlled to reduce the proportion of ICU patients out of total inpatient bed occupancy. On the other hand, intensive care unit admission of severe patients (patients with APACHE II score ≥ 15) should be encouraged to improve the proportion of patients with APACHE II score ≥ 15 in the ICU, so that ICU can focus more on the treatment of severe patients and promote the professionalization of severe patient management. It is not advisable to collect sputum specimens too frequently for patients without pneumonia. [ABSTRACT FROM AUTHOR]

This study was performed to visualize the hemodynamic effects of pulmonary microcirculation and ventilation/perfusion (V/Q) matching after mechanical ventilation under different cardiac outputs and positive end-expiratory pressures (PEEPs). Ten experimental pigs were randomly divided into high and low tidal volume groups, and ventilation/perfusion were measured by electrical impedance tomography (EIT) at different PEEPs. Then, all the pigs were redivided into high cardiac output (CO) and low CO groups and measured by EIT at different PEEP levels with a low tidal volume. Additionally, sidestream dark field (SDF) was used to measure pulmonary microcirculation. Hemodynamic parameters and respiratory mechanics parameters were recorded. As PEEP increased at high tidal volume, blood flow was impaired at a higher PEEP (20 cmH2O) compared with low tidal volume (shunt: 30.01 ± 0.69% vs. 17.95 ± 0.72%; V/Q ratio: 65.12 ± 1.97% vs. 76.57 ± 1.25%, p < 0.01). Low tidal volume combined with an appropriate PEEP is the best option from the match between ventilation and pulmonary blood flow. Increasing PEEP can solve the problem of excessive shunt at high CO, and the V/Q ratio tends to match. At low CO, the increased dead space can reach as high as 64.64 ± 7.13% when PEEP = 20 cmH2O. With increasing PEEP, the microcirculation index deteriorates, including total vessel density (TVD), proportion of perfused vessel (PPV), perfused vessel density (PVD), and microcirculatory flow index (MFI). The periodic collapse of pulmonary capillaries or interruption of blood flow obviously occurred with high PEEP. The hemodynamic parameters indicated that the transpulmonary capillary wall pressure (Pcap) of the low CO group was negative at PEEP = 5 cmH2O, which determines the opening and closing of the pulmonary microcirculation and controls lung perfusion and the production of extravascular lung water. Therefore, it is essential to couple macrocirculation and pulmonary microcirculation during mechanical ventilation by improving shunting and optimizing Pcap. [ABSTRACT FROM AUTHOR]

Background: The prevalence of carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) is increasing worldwide. CRKP-BSI is associated with high rates of morbidity and mortality due to limited antibiotic choices. Here, we aim to identify the prevalence and risk factors for infection and mortality of CRKP BSI. Methods: This was a retrospective study of the past data from January 1st, 2012 to December 31st, 2019 of adult patients with KP-BSI in Xiangya Hospital, China. Results: Among the 706 incidences included in this study, 27.4% of them (212/753) being CR-KP strains. The occurrence of CRKP-BSI was increased from 20.69 to 37.40% from 2012 to 2019. Hematologic malignancies and ICU acquired infection were identified to be substantial risk factors of carbapenem resistance. The overall 28-day mortality rates of CRKP-BSI patients was significantly higher than that of CSKP-BSI (P < 0.001). Logistic regression analysis identified severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset as the independent predictors of 28-day mortality of CRKP-BSI patients. However, high dose carbapenem combination therapy was identified as anticipated factors of low 28-day mortality. Conclusion: The occurrence of CRKP-BSI was significantly increased during the study period. Hematologic malignancies and ICU acquired infection were associated with the development of CRKP BSI. Severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset caused significant increase of mortality rates in CRKP-BSI patients. High dose carbapenem combination therapy was associated with better outcome. [ABSTRACT FROM AUTHOR]

Background: The prevalence of carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) is increasing worldwide. CRKP-BSI is associated with high rates of morbidity and mortality due to limited antibiotic choices. Here, we aim to identify the prevalence and risk factors for infection and mortality of CRKP BSI. Methods: This was a retrospective study of the past data from January 1st, 2012 to December 31st, 2019 of adult patients with KP-BSI in Xiangya Hospital, China. Results: Among the 706 incidences included in this study, 27.4% of them (212/753) being CR-KP strains. The occurrence of CRKP-BSI was increased from 20.69 to 37.40% from 2012 to 2019. Hematologic malignancies and ICU acquired infection were identified to be substantial risk factors of carbapenem resistance. The overall 28-day mortality rates of CRKP-BSI patients was significantly higher than that of CSKP-BSI (P < 0.001). Logistic regression analysis identified severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset as the independent predictors of 28-day mortality of CRKP-BSI patients. However, high dose carbapenem combination therapy was identified as anticipated factors of low 28-day mortality. Conclusion: The occurrence of CRKP-BSI was significantly increased during the study period. Hematologic malignancies and ICU acquired infection were associated with the development of CRKP BSI. Severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset caused significant increase of mortality rates in CRKP-BSI patients. High dose carbapenem combination therapy was associated with better outcome. [ABSTRACT FROM AUTHOR]

• Effects of the hospital care capacity for septic shock on the patient mortality at the overall hospital management. • Hospitals with higher care capacity for septic shock, showed a lower hospital mortality in China. • Percentage of patients with severe pneumonia was positively correlating with the mortality of septic shock. Hospitals with higher septic shock case volume demonstrated lower hospital mortality. We conducted this study to investigate whether this phenomenon was only caused by the increase in the number of admissions or the need to improve the medical care capacity in septic shock at the same time. Seven-hundred and eighty-seven hospitals from China collected in a survey from January 1, 2021 to December 31, 2021. Medical care capacity for septic shock was explored by patients with septic shock in intensive care units (ICU) divided into beds, intensivists, and nurses respectively. The proportion of ICU patients with septic shock was negatively associated with the patient mortality of septic shock (Estimate [95%CI], −0.2532 [-0.5038, -0.0026]) (p -value 0.048). The ratios of patients with septic shock to beds, intensivists, and nurses were negatively associated with mortality of septic shock (Estimate [95%CI], −0.370 [−0.591, −0.150], −0.136 [−0.241, −0.031], and −0.774 [−1.158, −0.389]) (p -value 0.001, 0.011 and < 0.001). Severe pneumonia, the most common infection that caused a septic shock, correlated positively with its mortality (Estimate [95%CI], 0.1002 [0.0617, 0.1387]) (p -value < 0.001). Hospitals with higher medical care capacity for septic shock were associated with lower hospital mortality. [ABSTRACT FROM AUTHOR]

Circulating lymphocyte number was significantly decreased in patients with sepsis. However, it remains unknown which severity phase (sepsis, severe sepsis, and septic shock) does it develop and what happen on each subpopulation. Eight patients with differing severities of sepsis (31 sepses, 33 severe sepses, and 16 septic shocks) were enrolled. Quantitative real-time polymerase chain reaction (RT-PCR) of Th1, Th2, and Th17; regulatory T (Treg) cell-specific transcription factor T-bet; GATA-3; RORgammat (RORγt); forkhead box P3 (FOXP3); and IL-17 mRNA were performed, and the enzyme-linked immunosorbent assay (ELISA) was used to detect serum interferon (IFN)-γ, IL-4, and IL-10. In this study, the Th1, Th2, Treg transcription factors, and related cytokines IFN-γ, IL-4, and IL-10 levels of sepsis and severe sepsis patients in peripheral blood were significantly higher than those of the normal controls. Except for IL-17, the T-bet, GATA-3, and IFN-γ levels of septic shock patients were lower than those of sepsis patients. We also observed that the proportions of Th17/Treg in the sepsis and septic shock groups were inversed. From the above, the inflammatory response especially the adaptive immune response is still activated in sepsis and severe sepsis, but significant immunosuppression was developed in septic shock. In addition, the proportion of Th17/Treg inversed may be associated with the illness aggravation of patients with sepsis. [ABSTRACT FROM AUTHOR]

Sepsis-associated encephalopathy (SAE) is a prevalent complication of sepsis, with hippocampal neuroinflammation playing a crucial role in SAE-induced cognitive impairment. Maresin1 (MaR1), a bioactive docosahexaenoic acid (DHA) metabolite, demonstrates comprehensive anti-inflammatory and neuroprotective attributes. Yet, its protective efficacy against SAE-induced cognitive decline remains unexplored. In this investigation, we implemented a rat SAE model via cecal ligation and puncture (CLP), while lipopolysaccharide (LPS) stimulation of HT22 cells simulated an in vitro SAE model; both models were pre-treated with MaR1. We evaluated rat learning and memory using a water maze, assessed hippocampal neuron damage via Nissl and FJC staining, and observed mitochondrial alterations through TEM. In vivo and in vitro assays gauged levels of Fe2+, MDA, GSH, and SOD. Additionally, Iba1 expression in the hippocampus was examined via immunofluorescence, while SLC7A11 and GPX4 protein expression levels were determined using western blot. Our findings indicated CLP-induced learning and memory impairment in rats, along with heightened ROS, Fe2+, and MDA levels in hippocampal neurons, diminished GSH and SOD levels, and down-regulated ferroptosis-related proteins (GPX4 and SLC7A11). Remarkably, MaR1 treatment attenuated these adverse effects. In LPS-stimulated HT22 cells, MaR1 lowered lipid ROS and bolstered mitochondrial membrane potential. Nonetheless, the ferroptosis inducer Erastin reversed MaR1′s protective effects. Transwell experiments further showed MaR1′s potential to inhibit microglia activation triggered by ferroptosis in HT22 cells. Consequently, MaR1 may mitigate hippocampal neuroinflammation via activating the SLC7A11/GPX4 ferroptosis signaling pathway, thus ameliorating SAE-related cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Analgesia and sedation therapy are commonly used for critically ill patients, especially mechanically ventilated patients. From the initial nonsedation programs to deep sedation and then to on-demand sedation, the understanding of sedation therapy continues to deepen. However, according to different patient's condition, understanding the individual patient's depth of sedation needs remains unclear.Methods: The public open source critical illness database Medical Information Mart for Intensive Care III was used in this study. Latent profile analysis was used as a clustering method to classify mechanically ventilated patients based on 36 variables. Principal component analysis dimensionality reduction was used to select the most influential variables. The ROC curve was used to evaluate the classification accuracy of the model.Results: Based on 36 characteristic variables, we divided patients undergoing mechanical ventilation and sedation and analgesia into two categories with different mortality rates, then further reduced the dimensionality of the data and obtained the 9 variables that had the greatest impact on classification, most of which were ventilator parameters. According to the Richmond-ASS scores, the two phenotypes of patients had different degrees of sedation and analgesia, and the corresponding ventilator parameters were also significantly different. We divided the validation cohort into three different levels of sedation, revealing that patients with high ventilator conditions needed a deeper level of sedation, while patients with low ventilator conditions required reduction in the depth of sedation as soon as possible to promote recovery and avoid reinjury.Conclusion: Through latent profile analysis and dimensionality reduction, we divided patients treated with mechanical ventilation and sedation and analgesia into two categories with different mortalities and obtained 9 variables that had the greatest impact on classification, which revealed that the depth of sedation was limited by the condition of the respiratory system. [ABSTRACT FROM AUTHOR]

Background: Regional citrate anticoagulation (RCA) is an important local anticoagulation method during bedside continuous renal replacement therapy. To improve patient safety and achieve computer assisted dose monitoring and control, we took intensive care units patients into cohort and aiming at developing a data-driven machine learning model to give early warning of citric acid overdose and provide adjustment suggestions on citrate pumping rate and 10% calcium gluconate input rate for RCA treatment.Methods: Patient age, gender, pumped citric acid dose value, 5% NaHCO3 solvent, replacement fluid solvent, body temperature value, and replacement fluid PH value as clinical features, models attempted to classify patients who received regional citrate anticoagulation into correct outcome category. Four models, Adaboost, XGBoost, support vector machine (SVM) and shallow neural network, were compared on the performance of predicting outcomes. Prediction results were evaluated using accuracy, precision, recall and F1-score.Results: For classifying patients at the early stages of citric acid treatment, the accuracy of neutral networks model is higher than Adaboost, XGBoost and SVM, the F1-score of shallow neutral networks (90.77%) is overall outperformed than other models (88.40%, 82.17% and 88.96% for Adaboost, XGBoost and SVM). Extended experiment and validation were further conducted using the MIMIC-III database, the F1-scores for shallow neutral networks, Adaboost, XGBoost and SVM are 80.00%, 80.46%, 80.37% and 78.90%, the AUCs are 0.8638, 0.8086, 0.8466 and 0.7919 respectively.Conclusion: The results of this study demonstrated the feasibility and performance of machine learning methods for monitoring and adjusting local regional citrate anticoagulation, and further provide decision-making recommendations to clinicians point-of-care. [ABSTRACT FROM AUTHOR]

• Significant negative correlation between IL-6 and platelet parameters was discovered. • Correlation between multiple cytokines and coagulation indicators was found. • Pro-inflammatory factors were found to be more associated to coagulation parameters. • Cytokines play an important role in the pathogenesis and evaluation of the condition of COVID-19. The novel SARS-CoV-2 caused a large number of infections and deaths worldwide. Thus, new ideas for an appropriated assessment of patients' condition and clinical treatment are of utmost importance. Therefore, in this study, the laboratory parameters of patients with coronavirus disease 2019 (COVID-19) were evaluated to identify the correlation between cytokine expression and other laboratory parameters. A retrospective and single-center study was performed in Wuhan, involving 83 severe or critical COVID-19 patients admitted to the intensive care unit (ICU). Laboratory parameters in ICU patients with laboratory-confirmed infection of SARS-CoV2 were collected. The association between parameters was assessed by Spearman's rank correlation. Patients' median age was 66 years (IQR, 57–73), and 55 (66%) were men. Among the 83 patients, 61 (73%) had 1 or more coexisting medical condition. The median concentration of IL-2R, IL-6, IL8, IL10, and TNFα were above the normal range, without IL-1β. A significant negative correlation between IL-6 and platelet count was discovered (r2 = −0.448, P < 0.001) as well as a significant correlation between IL-6 and other platelet parameters. Finally, a correlation between multiple cytokines and coagulation indicators was found, pro-inflammatory factors were found to be more associated to coagulation parameters, with the highest correlation between IL-6 and the International normalized ratio (INR) (r2 = 0.444, P < 0.001). Our results suggested that cytokines play an important role in the pathogenesis of COVID-19. In addition, IL-6 seems more relevant in the evaluation of the condition of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Objectives: The relationship between respiratory mechanical parameters and hemodynamic variables remains unclear. This study was performed to determine whether mean airway pressure and central venous pressure in the first day of mechanical ventilation are associated with patient outcomes.Design: Retrospective first 24-hour comparison during ICU stay.Setting: The Department of Critical Care Medicine of Peking Union Medical College Hospital.Patients: Patients with mechanical ventilation.Interventions: None.Measurements and Main Results: The clinical data of patients who received mechanical ventilation, especially respiratory and hemodynamic data, were collected and analyzed. In terms of the hemodynamic and perfusion data, the nonsurvivors group (177/2,208) had higher heart rate, respiratory rate, central venous pressure, and lactates and a lower perfusion index and P(v-a)CO2 (p < 0.05). In terms of respiratory condition, mean airway pressure, peak airway pressure, positive end-expiratory pressure, driving pressure, and inspiratory time/total respiration time of nonsurvivors were significantly higher, and arterial oxygen pressure and dynamic compliance worsened and were lower than the survivors (p < 0.05). Increased central venous pressure (odds ratio, 1.125; 95% CI, 1.069-1.184; p < 0.001) and elevated mean airway pressure (odds ratio, 1.125; 95% CI, 1.069-1.184; p < 0.001) were independently associated with 28-day mortality. The area under receiver operating characteristic demonstrated that central venous pressure and mean airway pressure were measured at 0.795 (95% CI, 0.654-0.757) and 0.833 (95% CI, 0.608-0.699), respectively. Based on the cutoff of central venous pressure and mean airway pressure, all of the participants were divided into the following groups: low central venous pressure and mean airway pressure, only high central venous pressure or mean airway pressure, or high central venous pressure and mean airway pressure. Post hoc tests showed significant differences among these three groups based on 28-day survival (log rank [Mantel-Cox], 131.931; p < 0.001).Conclusions: During the first 24 hours of mechanical ventilation, patients with elevated mean airway pressure and elevated central venous pressure had worse outcomes. [ABSTRACT FROM AUTHOR]

Background: To investigate the impact of initial antifungal therapeutic strategies on the prognosis of invasive Candida infections (ICIs) in intensive care units (ICUs) in China.Methods: A total of 306 patients with proven ICIs in the China-SCAN study were analyzed retrospectively. Empiric, pre-emptive, and targeted therapy were adopted based on starting criteria including clinical, microbiological, and other conventional prediction rules. The primary outcome was hospital mortality and the secondary endpoints were duration days in ICU and duration days in hospital. The global responses (clinical and microbiological) at the end of the empirical therapy were also assessed.Results: A total of 268/306 (87.6%) ICI patients received antifungal therapy, including 142/268 (53.0%) initial empirical therapy, 53/268 (19.8%) initial pre-emptive therapy, and 73/268 (27.2%) initial targeted therapy. Compared with the initial empirical antifungal therapy and targeted antifungal therapy, patients with initial pre-emptive antifungal therapy had significantly less clinical remission [11/53 (21.2%) vs. 61/142 (43.3%) vs. 22/73 (30.1%), P = 0.009], higher ICU [26/53 (57.8%) vs. 42/142 (32.2%) vs. 27/73 (43.5%), P = 0.008] and hospital mortality [27/53 (60.0%) vs. 43/142 (32.8%) vs. 29/73 (46.8%), P = 0.004] and more microbiological persistence [9/53 (17.0%) vs. 6/142 (4.2%) vs. 9/73 (12.3%), P = 0.011]. Kaplan-Meier survival analysis revealed that ICI patients with initial pre-emptive antifungal therapy and targeted antifungal therapy were associated with reduced hospital duration compared with patients with initial empirical antifungal therapy after confirmation of fungal infection (log-rank test: P = 0.021). Multivariate regression analysis provided evidence that initial empirical antifungal therapy was an independent predictor for DECREASING the hospital mortality in ICI patients on ICU admission and at ICI diagnosis (odds ratio 0.327, 95% confidence interval 0.160-0.667, P = 0.002; odds ratio 0.351, 95% confidence interval 0.168-0.735, P = 0.006).Conclusions: The initial therapeutic strategy for invasive candidiasis was independently associated with hospital mortality. Prompt empirical antifungal therapy could be critical to decrease early hospital mortality.Trial Registration: Clinicaltrials.gov NCT01253954 (retrospectively registration date: December 3, 2010). [ABSTRACT FROM AUTHOR]

Background and Aims Bacteremia is a common serious manifestation of disease in the intensive care unit (ICU), which requires quick and accurate determinations of pathogens to select the appropriate antibiotic treatment. To overcome the shortcomings of traditional bacterial culture (BC), we have adapted next-generation sequencing (NGS) technology to identify pathogens from cell-free plasma DNA. Methods In this study, 78 plasma samples from ICU patients were analyzed by both NGS and BC methods and verified by PCR amplification/Sanger sequencing and ten plasma samples from healthy volunteers were analyzed by NGS as negative controls to define or calibrate the threshold of the NGS methodology. Results Overall, 1578 suspected patient samples were found to contain bacteria or fungi by NGS, whereas ten patients were diagnosed by BC. Seven samples were diagnosed with bacterial or fungal infection both by NGS and BC. Among them, two samples were diagnosed with two types of bacteria by NGS, whereas one sample was diagnosed with two types of bacteria by BC, which increased the detectability of bacteria or fungi from 11 with BC to 17 with NGS. Most interestingly, 14 specimens were also diagnosed with viral infection by NGS. The overall diagnostic sensitivity was significantly increased from 12.82% (10/78) by BC alone to 30.77% (24/78) by NGS alone for ICU patients, which provides more useful information for establishing patient treatment plans. Conclusion NGS technology can be applied to detect bacteria in clinical blood samples as an emerging diagnostic tool rich in information to determine the appropriate treatment of septic patients. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli 055:B5, 10 mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS injection). Both activities and protein levels of MMP-2 p<0.001 and MMP-9 p<0.001 were significantly upregulated in aortic homogenates from LPS-treated rats, associated with decreased ZO-1 p<0.001 and syndecan-1 p=0.011 protein contents. Both dexamethasone and doxycycline could significantly inhibit MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition of MMPs by dexamethasone was significantly lower than that by doxycycline, while the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic aorta was significantly higher in the dexamethasone-treated compared to the doxycycline-treated p=0.03. In conclusion, activation of MMPs plays important role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that may contribute to the rescue of ZO-1 and syndecan-1 expression. [ABSTRACT FROM AUTHOR]

The extreme environment of space could affect microbial behavior and may increase the risk of infectious disease during spaceflight. However, the molecular genetic changes of methicillin-resistant Staphylococcus aureus (MRSA) in response to the spaceflight environment have not been fully clarified. In the present study, we determined the draft genome sequences for an ancestral S. aureus strain (LCT-SAO) isolated from a clinical sample and three derivative strains, LCT-SAS, LCT-SAM and LCT-SAG, cultured in parallel during the spaceflight Shenzhou-X, under simulated microgravity and on the ground, respectively. To evaluate the impact of short-term spaceflight on the MRSA strains, comparative genomic analysis was implemented. Genome-based mapping of toxin genes and antibiotic resistance genes confirmed that these strains have the conventional pathogenicity and resistance to drugs, as none of the strains showed significant changes in these regions after culturing in the three different environments; this result suggests that spaceflight may not change bacterial virulence or drug resistance. Thirty-nine strain-specific sequence variants (SVs) were identified throughout the genomes, and the three derivatives exhibited almost the same mutation rates. Fifty-nine percent of SVs were located in the intergenic regions of the genomes, indicating that S. aureus may have an extremely robust repair mechanism responsible for recognizing and repairing DNA replication mismatches. It is noteworthy that strain LCT-SAS, cultured in space, presented the most unique SVs ( n = 9) and shared the fewest SVs with LCT-SAM ( n = 5) and LCT-SAG ( n = 4). Furthermore, we identified 10 potential deletion regions and 2 potential insertion regions, with LCT-SAS appearing more fragile than other strains by this measure. These results suggest that the environment of space is inherently complicated, with multiple variables, and cannot be simulated in a simple manner. Our results represent the first analysis of nucleotide structure variation of S. aureus strains in a spaceflight environment and also provide a valuable insight for understanding the mutation strategies of MRSA on earth. [ABSTRACT FROM AUTHOR]

Abstract: The microgravity environment of spaceflight expeditions has been associated with altered microbial responses. This study explores the characterization of Serratia marcescensis grown in a spaceflight environment at the phenotypic, transcriptomic and proteomic levels. From November 1, 2011 to November 17, 2011, a strain of S. marcescensis was sent into space for 398h on the Shenzhou VIII spacecraft, and ground simulation was performed as a control (LCT-SM213). After the flight, two mutant strains (LCT-SM166 and LCT-SM262) were selected for further analysis. Although no changes in the morphology, post-culture growth kinetics, hemolysis or antibiotic sensitivity were observed, the two mutant strains exhibited significant changes in their metabolic profiles after exposure to spaceflight. Enrichment analysis of the transcriptome showed that the differentially expressed genes of the two spaceflight strains and the ground control strain mainly included those involved in metabolism and degradation. The proteome revealed that changes at the protein level were also associated with metabolic functions, such as glycolysis/gluconeogenesis, pyruvate metabolism, arginine and proline metabolism and the degradation of valine, leucine and isoleucine. In summary S. marcescens showed alterations primarily in genes and proteins that were associated with metabolism under spaceflight conditions, which gave us valuable clues for future research. [Copyright &y& Elsevier]

The aim of this study was to investigate the space mutagenesis of genetically engineered bacteria expressing recombinant human interferon α1b. The genetically engineered bacteria expressing the recombinant interferon α1b were sent into outer space on the Chinese Shenzhou VIII spacecraft. After the 17 day space flight, mutant strains that highly expressed the target gene were identified. After a series of screening of spaceflight-treated bacteria and the quantitative comparison of the mutant strains and original strain, we found five strains that showed a significantly higher production of target proteins, compared with the original strain. Our results support the notion that the outer space environment has unique effects on the mutation breeding of microorganisms, including genetically engineered strains. Mutant strains that highly express the target protein could be obtained through spaceflight-induced mutagenesis. [ABSTRACT FROM AUTHOR]

The species in family Planctomycetaceae are ideal groups for investigating the origin of eukaryotes. Their cells are divided by a lipidic intracytoplasmic membrane and they share a number of eukaryote-like molecular characteristics. However, their genomic structures, potential abilities, and evolutionary status are still unknown. In this study, we searched for common protein families and a core genome/pan genome based on 11 sequenced species in family Planctomycetaceae. Then, we constructed phylogenetic tree based on their 832 common protein families. We also annotated the 11 genomes using the Clusters of Orthologous Groups database. Moreover, we predicted and reconstructed their core/pan metabolic pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes) orthology system. Subsequently, we identified genomic islands (GIs) and structural variations (SVs) among the five complete genomes and we specifically investigated the integration of two Planctomycetaceae plasmids in all 11 genomes. The results indicate that Planctomycetaceae species share diverse genomic variations and unique genomic characteristics, as well as have huge potential for human applications. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients' outcome. Methods: This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. Results: The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P < 0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. Conclusions: IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients. [ABSTRACT FROM AUTHOR]