Possible pharmacological targets and mechanisms of sivelestat in protecting acute lung injury.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening syndrome induced by various diseases, including COVID-19. In the progression of ALI/ARDS, activated neutrophils play a central role by releasing various inflammatory mediators, including elastase. Sivelestat is a selective and competitive inhibitor of neutrophil elastase. Although its protective effects on attenuating ALI/ARDS have been confirmed in several models of lung injury, clinical trials have presented inconsistent results on its therapeutic efficacy. Therefore, in this report, we used a network pharmacology approach coupled with animal experimental validation to unravel the concrete therapeutic targets and biological mechanisms of sivelestat in treating ALI/ARDS. In bioinformatic analyses, we found 118 targets of sivelestat against ALI/ARDS, and identified six hub genes essential for sivelestat treatment of ALI/ARDS, namely ERBB2, GRB2, PTK2, PTPN11, ESR1, and CCND1. We also found that sivelestat targeted several genes expressed in human lung microvascular endothelial cells after lipopolysaccharide (LPS) treatment at 4 h (ICAM-1, PTGS2, RND1, BCL2A1, TNF, CA2, and ADORA2A), 8 h (ICAM-1, PTGS2, RND1, BCL2A1, MMP1, BDKRB1 and SLC40A1), and 24 h (ICAM-1). Further animal experiments showed that sivelestat was able to attenuate LPS-induced ALI by inhibiting the overexpression of ICAM-1, VCAM-1, and PTGS2 and increasing the phosphorylation of PTK2. Taken together, the bioinformatic findings and experimentative data indicate that the therapeutic effects of sivelestat against ALI/ARDS mainly focus on the early stage of ALI/ARDS by pharmacological modulation of inflammatory reaction, vascular endothelial injury, and cell apoptosis-related molecules.

Influence of Appropriate Empirical Antibiotic Treatment on the Prognosis of ICU Patients with HAP Caused by Carbapenem-Resistant Gram-Negative Bacteria.

Purpose: In patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infection, the impact of appropriate empirical antibiotic treatment (AEAT) initialized before culture results were available remains controversial. We aimed to investigate the effect of AEAT on the prognosis of critically ill patients with hospital-acquired pneumonia (HAP) caused by CRGNB. Patients and Methods: Patients with CRGNB-infected HAP and received empirical antibiotic treatment (EAT) for at least 3 days in the intensive care unit (ICU) of a tertiary teaching hospital in China from February 2017 to September 2021 were included in the retrospective cohort study. Patients were categorized into AEAT and inappropriate empirical antibiotic treatment (IEAT) groups based on whether they received EAT covering CRGNB. The associations of AEAT with ICU and 28-day mortality were assessed using multivariable logistic regression model. Results: A total of 94 patients were enrolled, including 29 patients in AEAT group and 65 patients in IEAT group. Patients in AEAT group had a higher Sequential Organ Failure Assessment (SOFA) score (P = 0.003), levels of procalcitonin (PCT) (P = 0.001), and lactic acid (LAC) (P = 0.026); while patients in the IEAT group had a higher platelet count (PLT) (P = 0.001). There was no significant difference in the length of ICU stay between the two groups (P = 0.051). Compared with IEAT, AEAT was associated with an increased risk of 28-day mortality in the univariable logistic regression model (OR: 2.618, 95% CI: 1.063-6.448). However, after adjusted for SOFA score, PLT, PCT, and LAC level, the association between AEAT and 28-day mortality diminished (OR: 1.028, 95% CI: 0.353-2.996). AEAT showed no significant association with ICU mortality in neither univariable (OR: 1.167, 95% CI: 0.433-3.142) nor multivariable (OR: 0.357, 95% CI: 0.097-1.320) models. Conclusion: AEAT showed no significant influence on ICU or 28-day mortality in critically ill patients with HAP caused by CRGNB infection.

Systematic investigation of the underlying mechanisms of GLP-1 receptor agonists to prevent myocardial infarction in patients with type 2 diabetes mellitus using network pharmacology.

Background: Several clinical trials have demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) reduce the incidence of non-fatal myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. In this study, we applied a network pharmacology method to investigate the mechanisms by which GLP-1RAs reduce MI occurrence in patients with T2DM. Methods: Targets of three GLP-1RAs (liraglutide, semaglutide, and albiglutide), T2DM, and MI were retrieved from online databases. The intersection process and associated targets retrieval were employed to obtain the related targets of GLP-1RAs against T2DM and MI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) enrichment analyses were performed. The STRING database was used to obtain the protein-protein interaction (PPI) network, and Cytoscape was used to identify core targets, transcription factors, and modules. Results: A total of 198 targets were retrieved for the three drugs and 511 targets for T2DM with MI. Finally, 51 related targets, including 31 intersection targets and 20 associated targets, were predicted to interfere with the progression of T2DM and MI on using GLP-1RAs. The STRING database was used to establish a PPI network comprising 46 nodes and 175 edges. The PPI network was analyzed using Cytoscape, and seven core targets were screened: AGT, TGFB1, STAT3, TIMP1, MMP9, MMP1, and MMP2. The transcription factor MAFB regulates all seven core targets. The cluster analysis generated three modules. The GO analysis for 51 targets indicated that the terms were mainly enriched in the extracellular matrix, angiotensin, platelets, and endopeptidase. The results of KEGG analysis revealed that the 51 targets primarily participated in the renin-angiotensin system, complement and coagulation cascades, hypertrophic cardiomyopathy, and AGE-RAGE signaling pathway in diabetic complications. Conclusion: GLP-1RAs exert multi-dimensional effects on reducing the occurrence of MI in T2DM patients by interfering with targets, biological processes, and cellular signaling pathways related to atheromatous plaque, myocardial remodeling, and thrombosis.

BiT-MAC: Mortality prediction by bidirectional time and multi-feature attention coupled network on multivariate irregular time series.

Mortality prediction is crucial to evaluate the severity of illness and assist in improving the prognosis of patients. In clinical settings, one way is to analyze the multivariate time series (MTSs) of patients based on their medical data, such as heart rates and invasive mean arterial blood pressure. However, this suffers from sparse, irregularly sampled, and incomplete data issues. These issues can compromise the performance of follow-up MTS-based analytic applications. Plenty of existing methods try to deal with such irregular MTSs with missing values by capturing the temporal dependencies within a time series, yet in-depth research on modeling inter-MTS couplings remains rare and lacks model interpretability. To this end, we propose a bidirectional time and multi-feature attention coupled network (BiT-MAC) to capture the temporal dependencies (i.e., intra-time series coupling) and the hidden relationships among variables (i.e., inter-time series coupling) with a bidirectional recurrent neural network and multi-head attention, respectively. The resulting intra- and inter-time series coupling representations are then fused to estimate the missing values for a more robust MTS-based prediction. We evaluate BiT-MAC by applying it to the missing-data corrupted mortality prediction on two real-world clinical datasets, i.e., PhysioNet'2012 and COVID-19. Extensive experiments demonstrate the superiority of BiT-MAC over cutting-edge models, verifying the great value of the deep and hidden relations captured by MTSs. The interpretability of features is further demonstrated through a case study.

Ultrafast Synthesis of Metal-Layered Hydroxides in a Dozen Seconds for High-Performance Aqueous Zn (Micro-) Battery.

Efficient synthesis of transition metal hydroxides on conductive substrate is essential for enhancing their merits in industrialization of energy storage field. However, most of the synthetic routes at present mainly rely on traditional bottom-up method, which involves tedious steps, time-consuming treatments, or additional alkaline media, and is unfavorable for high-efficiency production. Herein, we present a facile, ultrafast and general avenue to synthesize transition metal hydroxides on carbon substrate within 13 s by Joule-heating method. With high reaction kinetics caused by the instantaneous high temperature, seven kinds of transition metal-layered hydroxides (TM-LDHs) are formed on carbon cloth. Therein, the fastest synthesis rate reaches ~ 0.46 cm2 s-1. Density functional theory calculations further demonstrate the nucleation energy barriers and potential mechanism for the formation of metal-based hydroxides on carbon substrates. This efficient approach avoids the use of extra agents, multiple steps, and long production time and endows the LDHs@carbon cloth with outstanding flexibility and machinability, showing practical advantages in both common and micro-zinc ion-based energy storage devices. To prove its utility, as a cathode in rechargeable aqueous alkaline Zn (micro-) battery, the NiCo LDH@carbon cloth exhibits a high energy density, superior to most transition metal LDH materials reported so far.

Association between body mass index change and mortality in critically ill patients: A retrospective observational study.

OBJECTIVE: Previous studies have emphasized the association between baseline body mass index (BMI) and mortality in patients during a stay in the intensive care unit (ICU). However, to our knowledge, few studies have focused on BMI change during an ICU stay. The aim of this study was to explore the prognostic value of BMI change during ICU hospitalization. METHODS: This was a multicenter, retrospective cohort study with data extracted from the eICU Collaborative Research Database. Logistic regression models were used to explore the relationship between BMI change and mortality in ICU patients. BMI change was calculated as follows: {[discharge ICU weight (kg) - admission ICU weight (kg)] / height (m)2]}. Interaction and subgroup analyses were conducted for patients grouped with baseline BMI on ICU admission (≥30 versus 25-29.9 versus <25 kg/m2), Acute Physiology and Chronic Health Evaluation (APACHE) IV score (<53 versus ≥53), and ICU length of stay (≥3 versus <3 d). RESULTS: Compared with those with weight loss (n = 17 134), patients with weight gain during ICU hospitalization (n = 17 436) were associated with higher hospital mortality (odds ratio [OR], 1.251; 95% confidence interval [CI], 1.155-1.356; P < 0.001) and ICU mortality (OR, 1.360; 95% CI, 1.227-1.506; P < 0.001) after multivariable adjustment. The associations remained robust in patients with different baseline BMI levels and were especially remarkable among those with higher APACHE IV score and the longer ICU stay. CONCLUSIONS: The present study exposed the potential hazard of increasing BMI for hospital and ICU mortalities during ICU hospitalization and indicating that patients in the ICU may benefit from a more balanced nutritional strategy.

Relationship of Admission Serum Anion Gap and Prognosis of Critically Ill Patients: A Large Multicenter Cohort Study.

Background: There were controversies over the relationship between Anion gap (AG) and mortality in critically ill patients. Therefore, a large multicenter cohort study was conducted to evaluate the association of AG and mortality in large-scale intensive care units (ICUs) patients. Methods: This retrospective cohort study included adult ICU patients enrolled from eICU Collaborative Research Database. According to initial serum AG upon ICU admission, patients were divided into three groups: AG < 8 mmol/L, 8 ≤ AG ≤ 16 mmol/L, and AG > 16 mmol/L. Logistic regression models were built to investigate the association between serum AG and ICU and hospital mortalities. Serum AG was added into Acute Physiology and Chronic Health Evaluation (APACHE) IV score and the model discrimination was assessed by the area under the curve (AUC) of receiver operating characteristic curves. The relationship between serum AG and mortalities in patients with different acid-base status and serum lactate were also evaluated. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People's Hospital. Results: A total of 8520 patients entered the final cohort. There are 42 patients with serum AG < 8 mmol/L, 3238 patients with 8 ≤ AG ≤ 16 mmol/L, and 5240 patients with AG > 16 mmol/L. Serum AG > 16 mmol/L is related with increased ICU mortality (odds ratio [OR], 1.530; 95% confidence interval [CI], 1.305-1.794) and hospital mortality (OR, 1.618; 95% CI, 1.415-1.849), compared with 8 ≤ AG ≤ 16 mmol/L. Adding Serum AG to APACHE IV score could statistically improve the prediction of ICU (0.770 [0.761-0.779] to 0.774 [0.765-0.783], P = 0.001) and hospital mortalities (0.756 [0.747-0.765] to 0.761 [0.751-0.770], P = 0.012). The associations between serum AG and mortalities remain robust in patients with different acid-base statuses and serum lactate. The findings are validated in the external cohort. Conclusions: Initial serum AG > 16 mmol/L after ICU admission is associated with increased mortality in critically ill patients.

Fast constructing polarity-switchable zinc-bromine microbatteries with high areal energy density.

Microbatteries (MBs) are promising candidates to provide power for various miniaturized electronic devices, yet they generally suffer from complicated fabrication procedures and low areal energy density. Besides, all cathodes of current MBs are solid state, and the trade-off between areal capacity and reaction kinetics restricts their wide applications. Here, we propose a dual-plating strategy to facilely prepare zinc-bromine MBs (Zn-Br2 MBs) with a liquid cathode to achieve both high areal energy density and fast kinetics simultaneously. The Zn-Br2 MBs deliver a record high areal energy density of 3.6 mWh cm-2, almost an order of magnitude higher than available planar MBs. Meanwhile, they show a polarity-switchable feature to tolerate confusion of cathode and anode. This strategy could also be extended to other battery systems, such as Zn-I2 and Zn-MnO2 MBs. This work not only proposes an effective construction method for MBs but also enriches categories of microscale energy storage devices.

Prognostic Value of Serum Albumin Level in Critically Ill Patients: Observational Data From Large Intensive Care Unit Databases.

Background: Decreased serum albumin level (SAL) is associated with adverse clinical outcomes. We designed the present study to further assess the prognostic value of SAL in critically ill patients based on data from large intensive care unit (ICU) databases. Methods: This retrospective cohort study recruited 18,353 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Restricted cubic splines (RCS) were performed to visualize the association of SAL at admission with ICU and hospital mortalities. The prognostic value of SAL was analyzed using logistic regression models and receiver operating characteristic (ROC) curves in overall patients and subgroups. Results: Restricted cubic splines revealed rapid increasing risks in ICU and hospital mortalities when SAL declined to below 30 g/l. Patients with SAL <30 g/l (n = 6,069) had higher ICU (13.7% vs. 6.4%, p < 0.001) and hospital (23.9% vs. 10.7%, p < 0.001) mortalities than those with SAL ≥30 g/l. Multivariable logistic regression model revealed that SAL <30 g/l independently correlated with higher risks of both ICU (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07-1.36) and hospital (OR: 1.51, 95% CI: 1.37-1.66) mortalities. However, the association diminished in patients with cirrhosis (OR: 1.16, 95% CI: 0.91-1.49 for ICU mortality; OR: 1.21, 95% CI: 1.00-1.48 for hospital mortality). ROC curves revealed a poor performance of SAL in predicting mortalities, both in overall patients and in those with cirrhosis. Conclusions: Decreased SAL is associated with increased risk of mortality. However, it possesses low sensitivity and specificity for outcome prediction in critically ill patients, especially in those with cirrhosis.

Fixture-free omnidirectional prestretching fabrication and integration of crumpled in-plane micro-supercapacitors.

Multidimensional folded structures with elasticity could provide spatial charge storage capability and shape adaptability for micro-supercapacitors (MSCs). Here, highly crumpled in-plane MSCs with superior conformality are fabricated in situ and integrated by a fixture-free omnidirectional elastic contraction strategy. Using carbon nanotube microelectrodes, a single crumpled MSC holds an ultrahigh volumetric capacitance of 9.3 F cm-3, and its total areal capacitance is 45 times greater than the initial state. Experimental and theoretical simulation methods indicate that strain-induced improvements of adsorption energy and conductance for crumpled microelectrodes are responsible for the prominent enhancement of electrochemical performance. With outstanding morphological randomicity, the integrated devices can serve as smart coatings in moving robots, withstanding extreme mechanical deformations. Notably, integration on a spherical surface is possible by using a spherical mask, in which a small area of the microdevice array (3.9 cm2) can produce a high output voltage of 100 V.

Global burden of gallbladder and biliary diseases: A systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND AND AIM: Gallbladder and biliary diseases (GBDs) are one of the most prevalent medical issues in the digestive system. This study was designed to describe the characteristics of prevalence, death, and disability-adjusted life years (DALYs) of GBDs during 1990-2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. METHODS: Prevalence, death, and DALYs for GBDs in different locations, years, sex, and age groups were estimated using DisMod-MR 2.1 and a generic Cause of Death Ensemble Modeling approach. Countries and territories were categorized according to socio-demographic index (SDI) quintiles. RESULTS: The prevalence cases (127 345 732 to 193 493 378), death cases (82 430 to 124 941), and DALYs (4 604 821 to 6 352 738) of GBDs increased from 1990 to 2019. However, the age-standardized rates of indicators decreased over the 30-year period (prevalence, 2851.84 to 2350.78 per 100 000 population; death, 2.40 to 1.65 per 100 000 population; DALYs, 106.76 to 78.25 per 100 000 population). In 2019, the high and middle-high SDI regions had higher age-standardized prevalence rates, the low SDI region had the highest age-standardized death rate, and the middle SDI region had the highest DALYs and age-standardized DALYs rate of GBDs. Being female, older age, and high body mass index were important risk factors for the burden of GBDs. CONCLUSIONS: Globally, there were improvements in overall health with regard to GBDs over the 30 years. However, the prevention of GBDs should be promoted in middle, middle-high, and high SDI regions, while more medical resources should be provided to improve treatment levels in low SDI region.

Association of platelet count with mortality in patients with infectious diseases in intensive care unit: a multicenter retrospective cohort study.

Platelets play important roles in thrombosis, hemostasis, inflammation, and infection. We aimed to evaluate the association between platelet count and its variation trend and prognosis of patient with infectious diseases in intensive care units (ICUs). This retrospective cohort study extracted 4,251 critically ill adult patients with infectious diseases from the eICU Collaborative Research Database, whose platelet counts were measured daily during the first 7 days after admission. In the survivors, platelet counts decreased in the first days after admission, reached a nadir on day 3, and then returned and continued to rise above the admission value. In non-survivors, the platelet counts decreased after admission, without a subsequent upturn. We defined three subgroups according to the nadir platelet counts within 7 days: ≤50, 50-130, and ≥130 × 109/L, corresponding to high, intermediate, and low ICU mortality. A decreased platelet count was associated with increased ICU mortality (intermediate vs. low: 1.676 [1.285-2.187]; high vs. low: 3.632 [2.611-5.052]). In conclusion, during the first 7 days, platelet counts decreased after ICU admission, while increased subsequently in the survivors but not in the non-survivors. ICU mortality risk increased as nadir platelet count decreased below 130 × 109/L, and further boosted when it reached below 50 × 109/L.

Enabling fast-charging selenium-based aqueous batteries via conversion reaction with copper ions.

Selenium (Se) is an appealing alternative cathode material for secondary battery systems that recently attracted research interests in the electrochemical energy storage field due to its high theoretical specific capacity and good electronic conductivity. However, despite the relevant capacity contents reported in the literature, Se-based cathodes generally show poor rate capability behavior. To circumvent this issue, we propose a series of selenium@carbon (Se@C) composite positive electrode active materials capable of delivering a four-electron redox reaction when placed in contact with an aqueous copper-ion electrolyte solution (i.e., 0.5 M CuSO4) and copper or zinc foils as negative electrodes. The lab-scale Zn | |Se@C cell delivers a discharge voltage of about 1.2 V at 0.5 A g-1 and an initial discharge capacity of 1263 mAh gSe-1. Interestingly, when a specific charging current of 6 A g-1 is applied, the Zn | |Se@C cell delivers a stable discharge capacity of around 900 mAh gSe-1 independently from the discharge rate. Via physicochemical characterizations and first-principle calculations, we demonstrate that battery performance is strongly associated with the reversible structural changes occurring at the Se-based cathode.

The global burden of peptic ulcer disease in 204 countries and territories from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Peptic ulcer disease is one of the most common diseases in gastroenterology clinics. However, reported data about the global burden of peptic ulcer disease are still scarce. METHODS: This was a secondary data analysis on the prevalence, mortality and disability-adjusted life years (DALYs) due to peptic ulcer disease by sex, age group and socio-demographic index (SDI) at the global level in 21 regions and 204 countries and territories between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. RESULTS: Globally, the prevalence cases of peptic ulcer disease increased from 6 434 103 (95% uncertainty interval 5 405 963 to 7 627 971) in 1990 to 8 090 476 (6 794 576 to 9 584 000) in 2019. However, the age-standardized prevalence rate decreased from 143.4 (120.5 to 170.2) per 100 000 population in 1990 to 99.4 (83.9 to 117.5) per 100 000 population in 2019. Moreover, the age-standardized mortality rate decreased by 59.4% (55.3 to 63.1) and the DALYs rate fell by 60.6% (56.8 to 63.9) from 1990 to 2019. Across SDI quintiles, low-middle and low SDI quintiles had the highest age-standardized prevalence, mortality and DALYs rates from 1990 to 2019. CONCLUSION: The age-standardized prevalence, mortality and DALYs estimates of peptic ulcer disease decreased from 1990 to 2019 globally, but more efforts are needed for the prevention, early diagnosis and treatment of peptic ulcer disease in low SDI and low-middle SDI groups of countries.

Association between circadian variation of heart rate and mortality among critically ill patients: a retrospective cohort study.

BACKGROUND: Heart rate (HR) related parameters, such as HR variability, HR turbulence, resting HR, and nighttime mean HR have been recognized as independent predictors of mortality. However, the influence of circadian changes in HR on mortality remains unclear in intensive care units (ICU). The study is designed to evaluate the relationship between the circadian variation in HR and mortality risk among critically ill patients. METHODS: The present study included 4,760 patients extracted from the Multiparameter Intelligent Monitoring in Intensive Care II database. The nighttime mean HR/daytime mean HR ratio was adopted as the circadian variation in HR. According to the median value of the circadian variation in HR, participants were divided into two groups: group A (≤ 1) and group B (> 1). The outcomes included ICU, hospital, 30-day, and 1-year mortalities. The prognostic value of HR circadian variation was investigated by multivariable logistic regression models and Cox proportional hazards models. RESULTS: Patients in group B (n = 2,471) had higher mortality than those in group A (n = 2,289). Multivariable models revealed that the higher circadian variation in HR was associated with ICU mortality (odds ratio [OR], 1.393; 95% confidence interval [CI], 1.112-1.745; P = 0.004), hospital mortality (OR, 1.393; 95% CI, 1.112-1.745; P = 0.004), 30-day mortality (hazard ratio, 1.260; 95% CI, 1.064-1.491; P = 0.007), and 1-year mortality (hazard ratio, 1.207; 95% CI, 1.057-1.378; P = 0.005), especially in patients with higher SOFA scores. CONCLUSIONS: The circadian variation in HR might aid in the early identification of critically ill patients at high risk of associated with ICU, hospital, 30-day, and 1-year mortalities.

A Flexible Aqueous Zinc-Iodine Microbattery with Unprecedented Energy Density.

Currently, reported aqueous microbatteries (MBs) only show unsatisfactory electrochemical performance (≤120 mWh cm-3 volumetric energy density and <1000 µWh cm-2 areal energy density) and it remains challenging to develop durable aqueous MBs that can simultaneously offer both high volumetric and areal energy density. Herein, an in situ electrodeposition strategy is adopted to construct a flexible aqueous zinc-iodine MB (ZIDMB). Notably, the fabrication process well avoids the use of common additives (such as binders, conductive agents, and toxic solvent) and also bypasses subsequent time-consuming procedures such as grinding, coating, drying, etc., thus greatly simplifying the manufacture of the ZIDMB. Meanwhile, owing to the suppression of the shuttle effect of triiodide ions and the high ionic conductivity of the polyelectrolyte, the ZIDMB can simultaneously deliver record-high volumetric and areal energy densities of 1647.3 mWh cm-3 and 2339.1 µWh cm-2 , thus achieving values at least 13.5- and 2.3-fold better than those of best available aqueous MBs, respectively. This work affords an innovative strategy to construct an ideal micro-power-source for future miniaturized and integrated electronics.

Effect of initial serum chloride level on the association between intravenous chloride load and mortality in critically ill patients: A retrospective cohort study.

PURPOSE: To assess the effect of intravenous chloride load on prognosis in intensive care unit (ICU) patients with different initial serum chloride levels. MATERIALS AND METHODS: Participants from the Medical Information Mart for Intensive Care IV database were divided into low, normal (>100 and ≤110 mEq/L), and high chloride groups according to initial chloride levels. Records of intravenous fluids were extracted to calculated the volume adjusted chloride load (VACL) and VACL per body weight (VACL-W). The associations of VACL, VACL-W, and changes in serum chloride concentration (ΔCl) with mortalities were investigated in different initial chloride groups. RESULTS: Respectively, 4593 (20.9%), 13,364 (60.9%), and 3978 (18.1%) patients had a low, normal, and high initial chloride level. Interactions were found between initial chloride levels and VACL, VACL-W, and ΔCl on mortality risks. In normal and high chloride groups, increased VACL, VACL-W, and ΔCl were associated with higher ICU and hospital mortalities. However, in the low chloride group, multivariable models found no associations between VACL, VACL-W, or ΔCl with mortalities. CONCLUSIONS: High chloride load and increased serum chloride level were associated with poor outcomes in patients with normal or high initial chloride levels, but not in those with a low initial chloride level.

A Cascade Battery: Coupling Two Sequential Electrochemical Reactions in a Single Battery.

Currently, rechargeable electrochemical batteries generally operate on one reversible electrochemical reaction during discharging and charging cycles. Here, a cascade battery that couples two sequential electrochemical reactions in a single battery is proposed. Such a concept is demonstrated in an aqueous Zn-S hybrid battery, where solid sulfur serves as the cathode in the first discharge step and the generated Cu2 S catalyzes Cu2+ reduce to Cu/Cu2 O to provide the second discharge step. The cascade battery shows many merits compared to traditional batteries. First, it integrates two batteries internally, eliminating the use of additional inactive connecting materials required for external integration. Second, it can more fully utilize the inactive reaction chamber of the battery than traditional batteries. Third, cascade battery can bypass the challenges of thick solid electrode to access high areal capacity. An ultrahigh areal capacity of 48 mAh cm-2 is achieved even at a low solid cathode loading (9.6 mg cm-2 ). The cascade battery design breaks the stereotype of conventional battery configuration, providing a paradigm for constructing two-in-one batteries.

Relationship Between Mean Vancomycin Trough Concentration and Mortality in Critically Ill Patients: A Multicenter Retrospective Study.

Background: It remains unclear whether the mean vancomycin trough concentration (VTC) derived from the entire course of therapy is of potential benefit for critically ill patients. This study was conducted to explore the association between mean serum VTC and mortality in intensive care units (ICUs). Methods: 3,603 adult patients with two or more VTC records after receiving vancomycin treatment in the eICU Collaborative Research Database were included in this multicenter retrospective cohort study. Mean VTC was estimated using all measured VTCs and investigated as a continuous and categorical variable. Patients were categorised into four groups according to mean VTC: <10, 10-15, 15-20, and >20 mg/L. Multivariable logistic regression and subgroup analyses were performed to investigate the relationship of mean VTC with mortality. Results: After adjusting for a series of covariates, logistic regression analyses indicated that mean VTC, as a continuous variable, was positively correlated with ICU (odds ratio, 1.038, 95% confidence interval, [1.014-1.063]) and hospital (1.025 [1.005-1.046]) mortalities. As a categorical variable, mean VTC of 10-15 mg/L was not associated with reduced ICU (1.705 [0.975-2.981]) and hospital (1.235 [0.829-1.841]) mortalities. Mean VTC of 15-20 mg/L was not correlated with a lower risk of hospital mortality (1.370 [0.924-2.029]). Moreover, mean VTCs of 15-20 and >20 mg/L were significantly associated with higher ICU mortality (1.924 [1.111-3.332]; 2.428 [1.385-4.258]), and mean VTC of >20 mg/L with higher hospital mortality (1.585 [1.053-2.387]) than mean VTC of <10 mg/L. Similar results were observed in patients with different Acute Physiology and Chronic Health Evaluation IV score, creatinine clearance, age, and body mass index subgroups. Conclusion: Mean VTC was not associated with reduced ICU/hospital related mortality. Our results suggested that VTC monitoring might not guarantee vancomycin efficacy for ICU patients.

Global burden of upper respiratory infections in 204 countries and territories, from 1990 to 2019.

BACKGROUND: Upper respiratory infections (URIs) are among the most common diseases. However, the related burden has not been comprehensively evaluated. Thus, we designed the present study to describe the global and regional burden of URIs from 1990 to 2019. METHODS: A secondary analysis was performed on the incidence, mortality, and disability-adjusted life years (DALYs) of URIs in different sex and age groups, from 21 geographic regions, 204 countries and territories, between 1990 and 2019, using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Countries and territories were categorized according to Socio-demographic Index (SDI) quintiles. FINDINGS: Globally, the incident cases of URIs reached 17·2 (95% uncertainty interval: 15·4 to 19·3) billion in 2019, which accounted for 42·83% (40·01% to 45·77%) cases from all causes in the GBD 2019 study. The age-standardized incidence rate remained stable from 1990 to 2019, while significant decreases were found in the mortality and DALY rate. The highest age-standardized incidence rates from 1990 to 2019 and the highest age-standardized DALY rates after 2011 were observed in high SDI regions. Among all the age groups, children under five years old suffered from the highest incidence and DALY rates, both of which were decreased with increasing age. Fatal consequences of URIs occurred mostly in the elderly and children under five years old. INTERPRETATION: The present study provided comprehensive estimates of URIs burden for the first time. Our findings, highlighting the substantial incidence and considerable DALYs due to URIs, are expected to attract more attention to URIs and provide future explorations in the prevention and treatment with epidemiological evidence. FUNDING: The study was funded by the National Natural Science Foundation of China (81770057).