Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

OBJECTIVES: To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV). DESIGN: A multicenter, single-blind, randomized, noninferiority trial. SETTING: Twenty-one centers across China from December 2020 to June 2021. PATIENTS: A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6-24 hours. INTERVENTIONS: One hundred thirty-five ICU patients were randomly allocated into ciprofol ( n = 90) and propofol ( n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to -2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5-1 µg/kg, maintenance dose: 0.02-0.15 µg/kg/min). MEASUREMENTS AND MAIN RESULTS: Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of -5.98% and -4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time ( p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05). CONCLUSIONS: Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6-24 hours.

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.

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.

Association between coronary dominance and acute inferior myocardial infarction: a matched, case-control study.

BACKGROUND: Previous studies have found a connection between left coronary artery dominance and worse prognoses in patient with acute coronary syndrome, which remains a predominant cause of morbidity and mortality globally. The aim of this study was to investigate whether coronary dominance is associated with the incidence of acute inferior myocardial infarction (MI). METHODS: Between January 2011 and November 2014, 265 patients with acute inferior MI and 530 age-matched and sex-matched controls were recruited for a case-control study in the Second Affiliated Hospital of Xi'an Jiaotong University in Xi'an, China. All participants underwent coronary angiography. The exclusion criteria included history of coronary artery bypass graft surgery, chronic or systemic diseases (including hepatic failure, kidney failure, hypothyroidism and Grave's disease), ventricular fibrillation, and known allergy to iodinated contrast agent. Patients with left- or co-dominant anatomies were placed into the LD group and those with right-dominant anatomy were included in the RD group. The association of acute inferior MI and coronary dominant anatomy were assessed using multivariable conditional logistic regression, and to estimate the odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: Distributions of right dominance were significantly different between the acute inferior MI group and control group (94.0% vs. 87.9%, P = 0.018). Univariable conditional logistic regression revealed that right dominance may be a risk factor for the incident acute inferior MI (OR: 2.137; 95% CI: 1.210-3.776; P = 0.009). After adjusting for baseline systolic blood pressure, heart rate, smoking status, diabetes mellitus, hypertension, hyperlipidaemia, and family history of coronary artery disease, results of multivariate conditional logistic regression showed that right dominance was associated with the incidence of acute inferior MI (OR: 2.396; 95% CI: 1.328-4.321; P = 0.004). CONCLUSIONS: Right coronary dominance may play a disadvantageous role in the incidence of acute inferior MI. However, further studies are needed to verify our findings, especially with regard to the underlying mechanisms.

Clinical Efficacy and Safety of Mechanical Ventilation Combined with Fiberoptic Bronchoalveolar Lavage in Patients with Severe Pulmonary Infection.

BACKGROUND The aim of this study was to assess the clinical efficacy and safety of mechanical ventilation combined with fiberoptic bronchoalveolar lavage in patients with severe pulmonary infection. MATERIAL AND METHODS We randomly divided 81 patients with severe pulmonary infection into a control group (n=40) and an observation group (n=41). Both groups were treated using mechanical ventilation, and observation group additionally received assistive fiberoptic bronchoalveolar lavage. RESULTS The cure rate and effectiveness rate in the observation group were higher than in the control group (P<0.05, χ²=3.2), and the incidence of ventilator-associated pneumonia in the observation group was significantly lower than that in the control group (P<0.05, χ²=9.4). The partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) were higher in the observation group than in the control group (P<0.05, t=3.862, t=33.595), whereas the partial pressure of carbon dioxide (PaCO2) and respiratory rate were lower in the observation group than in the control group (P<0.05, t=3.307, t=5.043). The levels of C-reactive protein (CRP), tumor necrosis factor-a (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8) in the 2 groups were lower after treatment than before treatment (all P<0.05), and the levels in the observation group were lower than those in the control group (all P<0.05). Hospital stay, infection control window appearance time, invasive mechanical ventilation time, and total mechanical ventilation time in the observation group were shorter than those in the control group (P<0.05, t=13.990, t=8.643, t=9.717, t=8.980). CONCLUSIONS Mechanical ventilation combined with fiberoptic bronchoalveolar lavage can effectively improve the curative effects and the blood gas and inflammation indicators in patients.

Inhibition of Notch3 prevents monocrotaline-induced pulmonary arterial hypertension.

It has been shown that activation of Notch3 signaling is involved in the development of pulmonary arterial hypertension (PAH) by stimulating pulmonary arteries remodeling, while the molecular mechanisms underlying this are still largely unknown. The aims of this study are to address these issues. Monocrotaline dramatically increased right ventricle systolic pressure to 39.0 ± 2.6 mmHg and right ventricle hypertrophy index to 53.4 ± 5.3% (P < 0.05 versus control) in rats, these were accompanied with significantly increased proliferation and reduced apoptosis of pulmonary vascular cells as well as pulmonary arteries remodeling. Treatment of PAH model with specific Notch inhibitor DAPT significantly reduced right ventricle systolic pressure to 26.6 ± 1.3 mmHg and right ventricle hypertrophy index to 33.5 ± 2.6% (P < 0.05 versus PAH), suppressed proliferation and enhanced apoptosis of pulmonary vascular cells as well as inhibited pulmonary arteries remodeling. Our results further indicated that level of Notch3 protein and NICD3 were increased in MCT-induced model of PAH, this was accompanied with elevation of Skp2 and Hes1 protein level and reduction of P27Kip1. Administration of rats with DAPT-prevented MCT induced these changes. Our results suggest that Notch3 signaling activation stimulated pulmonary vascular cells proliferation by Skp2-and Hes1-mediated P27Kip1 reduction, and Notch3 might be a new target to treat PAH.

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.

A causal relationship between educational attainment and risk of infectious diseases: A Mendelian randomisation study.

Background: Previous observational studies have investigated the association between educational attainment and sepsis, pneumonia, and urinary tract infections (UTIs). However, their findings have been susceptible to reverse causality and confounding factors. Furthermore, no study has examined the effect of educational level on the risk of infections of the skin and subcutaneous tissue (SSTIs). Thus, we aimed to evaluate the causal relationships between educational level and the risk of four infectious diseases using Mendelian randomisation (MR) techniques. Methods: We used univariable MR analysis to investigate the causal associations between educational attainment (years of schooling (n = 766 345) and holding college or university degree (n = 334 070)) and four infectious diseases (sepsis (n = 486 484), pneumonia (n = 486 484), UTIs (n = 463 010), and SSTIs (n = 218 792)). We included genetic instrumental variables with a genome-wide significance (P < 5 × 10-8) in the study. We used inverse variance-weighted estimation in the primary analysis and explored the stability of the results using multivariable MR analysis after adjusting for smoking, alcohol consumption, and body mass index. Results: Genetically predicted years of schooling were associated with a reduced risk of sepsis (odds ratio (OR) = 0.763; 95% confidence interval (CI) = 0.668-0.870, P = 5.525 × 10-5), pneumonia (OR = 0.637; 95% CI = 0.577-0.702, P = 1.875 × 10-19), UTIs (OR = 0.995; 95% CI = 0.993-0.997, P = 1.229 × 10-5), and SSTIs (OR = 0.696; 95% CI = 0.605-0.801, P = 4.034 × 10-7). We observed consistent results for the correlation between qualifications and infectious diseases. These findings remained stable in the multivariable MR analyses. Conclusions: Our findings suggest that increased educational attainment may be causally associated with a decreased risk of sepsis, pneumonia, UTIs, and SSTIs.

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.

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.

Cerebrospinal fluid protein levels are elevated 100 times in a Leptomeningeal metastasis patient: a case report and literature review.

Leptomeningeal metastasis (LM) has a high degree of malignancy and high mortality. We describe a patient admitted to hospital with acute lower extremity weakness, dysuria, and high intracranial pressure. Enhanced magnetic resonance imaging (MRI) showed extensive enhancement of the leptomeningeal and spinal meninges with multiple nodular changes and extensive fusion. His cerebrospinal fluid (CSF) was yellow and cloudy, the Pandy test was strongly positive (++++), the protein was 46 g/L (normal range 0.15-0.45 g/L), which attracted our attention. Initially, miliary TB with associated tuberculous meningitis (TBM) was diagnosed, and neurosarcoidosis cannot be ruled out. After poor therapeutic effect of standard antituberculosis (anti-TB) therapy, further inspection found that malignant cells were detected by cerebrospinal fluid (CSF) cytology. PET/CT suggested the diagnosis of LM. The purpose of this paper is to describe the characteristics of atypical diffuse LM. In conclusion, when patient with unexplained high levels of CSF protein, it is necessary to be alert to the diagnosis of LM. Multiple examinations of fresh CSF are helpful to increase the positive detection rate of tumor cells. Early diagnosis and active treatment are conducive to improving survival rate.

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.

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.

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.

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.

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.

Increasing serum ammonia level is a risk factor for the prognosis of critically ill patients: A multicenter retrospective cohort study.

PURPOSE: To assess the association between serum ammonia level upon admission during the initial intensive care unit (ICU) stay and mortality. MATERIALS AND METHODS: This retrospective cohort study included 2703 adult patients in eICU Collaborative Research Database. The ICU mortality within ammonia deciles were assessed. Logistic regression analyses were performed to analyze the relationship between ammonia and mortality. RESULTS: We defined three ammonia categories: <47, 47-111, and ≥111 µg/dL, corresponding to low, intermediate, and high ICU mortality. Increased ammonia was significantly associated with increased ICU mortality (per 10 µg/dL increase: odds ratio, 1.070 [95% confidence intervals, 1.05-1.09]; intermediate vs. low: 1.90 [1.41-2.56]; high vs. low: 4.38 [2.99-6.41]) and in-hospital mortality (1.06 [1.04-1.08]; 1.45 [1.13-1.87]; 3.41 [2.43-4.79]). Adding ammonia to the Acute Physiology and Chronic Health Evaluation (APACHE) IV score improved the area under the curve from 0.826 to 0.839 (P < 0.001) and from 0.806 to 0.813 (P = 0.001) for ICU and in-hospital mortality, respectively. Interaction and subgroup analyses demonstrated consistent results in patients with different APACHE IV scores, with or without hepatic diseases. CONCLUSIONS: Elevated serum ammonia level in critically ill patients upon admission was an early risk factor for higher ICU and in-hospital mortality.

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.