Protectin Conjugates in Tissue Regeneration 1 Inhibits Macrophage Pyroptosis by Restricting NLRP3 Inflammasome Assembly to Mitigate Sepsis via the cAMP-PKA Pathway.

Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1ß release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases.

The risk factors for deep venous thrombosis in critically ill older adult patients: a subgroup analysis of a prospective, multicenter, observational study.

BACKGROUND: Older adult patients mainly suffer from multiple comorbidities and are at a higher risk of deep venous thrombosis (DVT) during their stay in the intensive care unit (ICU) than younger adult patients. This study aimed to analyze the risk factors for DVT in critically ill older adult patients. METHODS: This was a subgroup analysis of a prospective, multicenter, observational study of patients who were admitted to the ICU of 54 hospitals in Zhejiang Province from September 2019 to January 2020 (ChiCTR1900024956). Patients aged > 60 years old on ICU admission were included. The primary outcome was DVT during the ICU stay. The secondary outcomes were the 28- and 60-day survival rates, duration of stay in ICU, length of hospitalization, pulmonary embolism, incidence of bleeding events, and 60-day coagulopathy. RESULTS: A total of 650 patients were finally included. DVT occurred in 44 (2.3%) patients. The multivariable logistic regression analysis showed that age (≥75 vs 60-74 years old, odds ratio (OR) = 2.091, 95% confidence interval (CI): 1.308-2.846, P = 0.001), the use of analgesic/sedative/muscarinic drugs (OR = 2.451, 95%CI: 1.814-7.385, P = 0.011), D-dimer level (OR = 1.937, 95%CI: 1.511-3.063, P = 0.006), high Caprini risk score (OR = 2.862, 95%CI: 1.321-2.318, P = 0.039), basic prophylaxis (OR = 0.111, 95%CI: 0.029-0.430, P = 0.001), and physical prophylaxis (OR = 0.322, 95%CI: 0.109-0.954, P = 0.041) were independently associated with DVT. There were no significant differences in 28- and 60-day survival rates, duration of stay in ICU, total length of hospitalization, 60-day pulmonary embolism, and coagulation dysfunction between the two groups, while the DVT group had a higher incidence of bleeding events (2.6% vs. 8.9%, P < 0.001). CONCLUSION: In critically ill older adult patients, basic prophylaxis and physical prophylaxis were found as independent protective factors for DVT. Age (≥75 years old), the use of analgesic/sedative/muscarinic drugs, D-dimer level, and high Caprini risk score were noted as independent risk factors for DVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024956).URL: http://www.chictr.org.cn/listbycreater.aspx .

Increased neutrophil percentage-to-albumin ratio is associated with all-cause mortality in patients with severe sepsis or septic shock.

There has been no study exploring the prognostic values of neutrophil percentage-to-albumin ratio (NPAR). We hypothesised that NPAR is a novel marker of inflammation and is associated with all-cause mortality in patients with severe sepsis or septic shock. Patient data were extracted from the MIMIC-III V1.4 database. Only the data for the first intensive care unit (ICU) admission of each patient were used and baseline data were extracted within 24 h after ICU admission. The clinical endpoints were 30-, 90- and 365-day all-cause mortality in critically ill patients with severe sepsis or septic shock. Cox proportional hazards models and subgroup analyses were used to determine the relationship between NPAR and these clinical endpoints. A total of 2166 patients were eligible for this analysis. In multivariate analysis, after adjustments for age, ethnicity and gender, higher NPAR was associated with increased risk of 30-, 90- and 365-day all-cause mortality in critically ill patients with severe sepsis or septic shock. Furthermore, after adjusting for more confounding factors, higher NPAR remained a significant predictor of all-cause mortality (tertile 3 vs. tertile 1: HR, 95% CI: 1.29, 1.04-1.61; 1.41, 1.16-1.72; 1.44, 1.21-1.71). A similar trend was observed in NPAR levels stratified by quartiles. Higher NPAR was associated with increased risk of all-cause mortality in critically ill patients with severe sepsis or septic shock.

Red Blood Cell Distribution Width Is Associated with All-Cause Mortality in Critically Ill Patients with Cardiogenic Shock.

BACKGROUND There is no previously published epidemiological study exploring the association between red blood cell distribution width (RDW) and mortality in patients with cardiogenic shock (CS). The aim of this study was to examine the association between RDW and the risk of all-cause mortality in these patients. MATERIAL AND METHODS We analyzed clinical data from the MIMIC-III V1.4 database. We collected data on each patient's demographic parameters, vital signs, laboratory parameters, vital signs, comorbidities, and scoring systems on ICU admission. Cox proportional hazards models were used to assess the association between RDW levels and the 30-day, 90-day, and 365-day mortality in patients with CS. RESULTS There were 1131 patients meeting inclusion criteria in our study. In multivariate analysis, following adjustment for age, sex, and ethnicity, higher RDW in tertiles and quintiles were all associated with increased risk of 30-day, 90-day, and 365-day all-cause mortality. Furthermore, after adjusting for more relevant confounders, RDW remained a significant predictor of risk of 30-day, 90-day, and 365-day mortality (tertile 3 versus tertile 1: HR, 95% CI: 1.66, 1.19-2.31; 1.73, 1.28-2.33; 1.80, 1.38-2.34). Similarly significant robust associations were found in RDW levels stratified by quintiles. CONCLUSIONS Higher RDW is associated with increased risk of all-cause mortality in critically ill patients with CS.

Paramedian Thalamic Ischemic Infarction: A Retrospective Clinical Observation.

BACKGROUND: The study aimed to evaluate the clinical features in patients with bilateral and unilateral paramedian thalamic infarcts. METHODS: Twenty-one patients with paramedian thalamic infarcts were included, and their case records were reviewed. We focused on the patients' neuroimaging and neurological symptoms including the duration of coma, vertical gaze palsy, and memory impairment. The causes of bilateral and unilateral paramedian thalamic infarcts were also investigated. RESULT: Nine patients had bilateral paramedian thalamic infarcts and 12 patients had unilateral lesions. As an initial symptom, coma had occurred in 5 patients with bilateral lesions and 4 patients with unilateral lesions. Bilateral vertical gaze palsy and memory impairment were found in both groups. Most of them recovered well, except 1 patient who died due to bilateral thalamic paramedian infarction. CONCLUSIONS: Our results show that both bilateral and unilateral paramedian thalamic infarcts can cause coma, vertical gaze palsy, and memory impairment. This may promote our understanding of paramedian thalamic infarction.

Imperatorin acts as a cisplatin sensitizer via downregulating Mcl-1 expression in HCC chemotherapy.

Acquisition of cisplatin resistance is the common and critical limitation for hepatocellular carcinoma (HCC) therapy. Our study was aimed to determine whether there were conditions under which the addition of imperatorin would reverse the resistance of HCC cells to cisplatin-based therapy. In this study, we found that addition of imperatorin significantly enhanced the cytotoxicity of cisplatin to HCC cells. Since the Mcl-1 was overexpressed in HCC cell lines (HepG2, HepG3B, PLC, Huh7) compared with normal liver cell line (L-O2), we found that the Mcl-1 expression was downregulated by imperatorin but not influenced by cisplatin in HCC cells. In addition, our results showed the combination of imperatorin and cisplatin induced apoptosis and ∆Ψm collapse more significantly compared with treatment of imperatorin or cisplatin alone. Furthermore, the imperatorin-induced sensitization for cisplatin-cytotoxicity to HCC cells was abolished by the transfection of Mcl-1 expression plasmid. Finally, we found that the addition of imperatorin significantly reversed the resistance to cisplatin in cisplatin-resistant HCC cells, which was Mcl-1 dependent. In summary, our study revealed that combination with imperatorin could enhance the antitumor activity of cisplatin via targeting Mcl-1 and reverse the resistance to cisplatin in HCC.

[Effect of Curcumin on Cerebral Ischemia-reperfusion Injury in Rats].

OBJECTIVE: To investigate the effect of curcumin on cerebral ischemia-reperfusion injury in rats and its mechanism. METHODS: 250 male SD rats were randomly divided into five groups:sham group (Sham group), ischemia-reperfusion group (I/R group), curcumin groups with dosage of 30 mg/kg (Cur30 group), 100 mg/kg (Cur100 group) and 300 mg/kg (Cur300 group). The brain tissue damage degree, leukocyte cells infiltration, levels of TNF-α and MMP-9 expressions, and blood-brain barrier permeability were detected. RESULTS: At the same time point,the score of brain tissue injury,number of leukocyte, expression of MMP-9 and TNF-α, and Evans blue dye of I/R group and Curs group were higher than those of Sham group (P < 0.05). The score of brain tissue damage degree, number of leukocyte, expression of MMP-9 and TNF-α, and Evans blue dye of Cur groups were lower than those of I/R group (P < 0.05). The Cur100 group had the best effect. CONCLUSION: Curcumin can decrease cerebral ischemia reperfusion pathological damage significantly and suppressed the expression of MMP-9 and TNF-α, and Evans blue dye, brain tissue damage, leukocyte infiltration, which may be involved in protective mechanisms of curcumin.

Prognostic Value of the Red Blood Cell Distribution Width-to-Albumin Ratio in Critically Ill Older Patients with Acute Kidney Injury: A Retrospective Database Study.

Background: There is no evidence suggesting that red blood cell distribution width-to-albumin ratio (RA) predicts outcomes in severely ill older individuals with acute kidney injury (AKI). We hypothesized that RA is associated with all-cause mortality in critically ill older patients with AKI. Methods: We recorded demographics, laboratory tests, comorbidities, vital signs, and other clinical information from the MIMIC-III V1.4 dataset. The primary endpoint was 90-day all-cause mortality, and the secondary endpoints were 30-day mortality, one-year mortality, renal replacement treatment (RRT), duration of stay in the intensive care unit (ICU), sepsis, and septic shock. We generated Cox proportional hazards and logistic regression models to determine RA's prognostic values and subgroup analyses to determine the subgroups' mortality. We conducted a Pearson correlation analysis on RA and C-reactive protein (CRP) in the cohort of patients from the Second Affiliated Hospital of Wenzhou Medical University. Results: A total of 6,361 patients were extracted from MIMIC-III based on the inclusion and exclusion criteria. RA levels directly and linearly correlated with 90-day all-cause mortality. After controlling for ethnicity, gender, age, and other confounding variables in multivariate analysis, higher RA was significantly associated with an increased risk of 30-day, 90-day, and one-year all-cause mortality as opposed to the reduced levels of RA (tertile 3 vs. tertile 1: hazard ratios (HRs), 95% confidence intervals (CIs): 1.70, 1.43-2.01; 1.90, 1.64-2.19; and 1.95, 1.72-2.20, respectively). These results suggested that elevated levels of RA were linked to an elevated risk of 30-day, 90-day, and one-year all-cause death. There was a similar trend between RA and the use of RRT, length of stay in ICUs, sepsis, and septic shock. The subgroup analysis did not reveal any considerable interplay among strata. When areas under the curve were compared, RA was a weaker predictor than the SAPS II score but a stronger predictor than red blood cell distribution width (RDW) or albumin alone (P < 0.001); RA combined with SAPS II has better predictive power than SAPS II alone (P < 0.001). The Second Affiliated Hospital of Wenzhou Medical University cohort showed that CRP positively correlated with RA, with a coefficient of 0.2607 (P < 0.001). Conclusions: RA was an independent prognostic predictor in critically ill older patients with AKI, and greater RA was linked to a higher probability of death. The risk of AKI is complicated when RRT occurs; sepsis and septic shock increase with RA levels.

Body Mass Index Is Associated with the Severity and All-Cause Mortality of Acute Kidney Injury in Critically Ill Patients: An Analysis of a Large Critical Care Database.

BACKGROUND: Acute kidney injury (AKI) is a common clinical syndrome carrying high morbidity and mortality. Body mass index (BMI) is a common health indicator, and a high BMI value-obesity has been shown to be associated with the outcomes of several diseases. However, the relationship between different BMI categories and mortality in all critically ill patients with AKI is unclear and needs further investigation. Therefore, we evaluated the ability of BMI to predict the severity and all-cause mortality of AKI in critically ill patients. METHODS: We extracted clinical data from the MIMIC-III v1.4 database. All adult patients with AKI were initially screened. The baseline data extracted within 24 hours after ICU admission were presented according to WHO BMI categories. Logistic regression models and the Cox proportional hazards models were, respectively, constructed to assess the relationship between BMI and the severity and all-cause mortality of AKI. The generalized additive model (GAM) was used to identify nonlinear relationships as BMI was a continuous variable. The subgroup analyses were performed to further analyze the stability of the association between BMI category and 365-day all-cause mortality of AKI. RESULT: A total of 15,174 patients were extracted and were divided into four groups according to BMI. Obese patients were more likely to be young and male. In the fully adjusted logistic regression model, we found that overweight and obesity were significant predictors of AKI stage III (OR, 95 CI: 1.17, 1.05-1.30; 1.32, 1.18-1.47). In the fully adjusted Cox proportional hazards model, overweight and obesity were associated with significantly lower 30-day, 90-day, and 365-day all-cause mortality. The corresponding adjusted HRs (95 CIs) for overweight patients were 0.87 (0.77, 0.99), 0.84 (0.76, 0.93), and 0.80 (0.74, 0.88), and for obese patients, they were 0.87 (0.77, 0.98), 0.79 (0.71, 0.88), and 0.73 (0.66, 0.80), respectively. The subgroup analyses further presented a stable relationship between BMI category and 365-day all-cause mortality. CONCLUSIONS: BMI was independently associated with the severity and all-cause mortality of AKI in critical illness. Overweight and obesity were associated with increased risk of AKI stage III; however, they were predictive of a relatively lower mortality risk in these patients.

Prevention, treatment, and risk factors of deep vein thrombosis in critically ill patients in Zhejiang province, China: a multicenter, prospective, observational study.

PURPOSE: The aim of this study is to investigate the prevention and treatment patterns of deep vein thrombosis (DVT) in critically ill patients and to explore the risk factors for DVT in people from Zhejiang Province, China. MATERIALS AND METHODS: This study prospectively enrolled patients admitted in intensive care units (ICUs) of 54 hospitals from 09/16/2019 to 01/16/2020. The risk of developing DVT and subsequent prophylaxis was evaluated. The primary outcome was DVT occurrence during ICU hospitalisation. Univariate and multivariate logistic regression were performed to determine the risk factors for DVT. RESULTS: A total of 940 patients were included in the study. Among 847 patients who received prophylaxis, 635 (75.0%) patients received physical prophylaxis and 199 (23.5%) patients received drug prophylaxis. Fifty-eight (6.2%) patients were diagnosed with DVT after admission to the ICU, and 36 patients were treated with anticoagulants (all patients received low molecular weight heparin [LMWH]). D-dimer levels (OR = 1.256, 95% CI: 1.132-1.990), basic prophylaxis (OR = 0.092, 95% CI: 0.016-0.536), and physical prophylaxis (OR = 0.159, 95% CI: 0.038-0.674) were independently associated with DVT in ICU patients. The short-term survival was similar between DVT and non-DVT patients. CONCLUSIONS: DVT prophylaxis is widely performed in ICU patients. Prophylaxis is an independent protective factor for DVT occurrence. The most common treatment of DVT patients is LMWH, although it might increase the rate of bleeding.Key messagesThis is the only multicenter and prospective study of DVT in ICUs in China.d-dimer levels were independently associated with DVT in ICU patients.Prophylaxis was an independent protective factor for DVT occurrence in ICU.

The Neutrophil Percentage-to-Albumin Ratio Is Associated with All-Cause Mortality in Critically Ill Patients with Acute Kidney Injury.

BACKGROUND: There is no evidence to suggest the predictive power of neutrophil percentage-to-albumin ratio (NPAR) in patients with acute kidney injury (AKI). We hypothesized that NPAR would correlate with all-cause mortality in critically ill patients with AKI. METHODS: From the MIMIC-III V1.4 database, we extracted demographics, vital signs, comorbidities, laboratory tests, and other clinical data. The clinical endpoints were 30-, 90- and 365-day all-cause mortality in critically ill patients with AKI. Cox proportional hazards models were used to evaluate the prognostic values of NPAR, and subgroup analyses were performed to measure mortality across various subgroups. RESULTS: A total of 7,481 eligible subjects were enrolled. In multivariate analysis, after adjustments for age, ethnicity, gender, and other confounding factors, higher NPARs were associated with an increased risk of 30-, 90- and 365-day all-cause mortality in critically ill patients with AKI (tertile 3 versus tertile 1: adjusted HR, 95% CI: 1.48, 1.30-1.69; 1.47, 1.31-1.66; 1.46, 1.32-1.62, respectively; P trend <0.01). A similar trend was observed in the NPAR group division by quintiles. Subgroup analysis revealed no significant interactions in most strata. CONCLUSIONS: Increased NPAR correlates with increased risk of all-cause mortality in critically ill patients with AKI.

Serum Anion Gap Predicts All-Cause Mortality in Critically Ill Patients with Acute Kidney Injury: Analysis of the MIMIC-III Database.

BACKGROUND: No epidemiological study has investigated the effect of anion gap (AG) on the prognosis of critically ill patients with acute kidney injury (AKI). Therefore, we aimed to determine the association between serum AG and all-cause mortality in these patients. METHODS: From MIMIC III, we extracted demographics, vital signs, laboratory tests, comorbidities, and scoring systems from the first 24 h after patient ICU admission. A generalized additive model was used to identify a nonlinear association between anion gap and 30-day all-cause mortality. We also used the Cox proportional hazards models to measure the association between AG levels and 30-day, 90-day, and 365-day mortality in patients with AKI. RESULTS: A total of 11,573 eligible subjects were extracted from the MIMIC-III. The relationship between AG levels and 30-day all-cause mortality in patients with AKI was nonlinear, with a U-shaped curve. In multivariate analysis, after adjusting for potential confounders, higher AG was a significant predictor of 30-day, 90-day, and 365-day all-cause mortality compared with lower AG (HR, 95% CI: 1.54, 1.33-1.75; 1.55, 1.38-1.73; 1.46, 1.31-1.60). CONCLUSIONS: The relationship between AG levels and 30-day all-cause mortality described a U-shaped curve. High-AG levels were associated with increased risk 30-day, 90-day, and 365-day all-cause mortality in critically ill patients with AKI.

Correlation Study of Short-Term Mental Health in Patients Discharged After Coronavirus Disease 2019 (COVID-19) Infection without Comorbidities: A Prospective Study.

OBJECTIVE: The WHO has upgraded the status of coronavirus disease 2019 (COVID-19) from epidemic to global pandemic. The psychometric properties aspects of COVID-19 patients without comorbidities in the short term after discharge have not been reported. In this study, the Short Form 36 (SF-36) was used to evaluate the psychometric properties and to find relevant risk factors. METHODS: The study was conducted in seven hospitals from January 2020 to April 2020. The SF-36 questionnaire was administered one month after discharge. Univariate analysis and multivariate regression model were used to analyze the risk factors of psychometric properties impairment. RESULTS: In univariate analysis of independent risk factors, according to the comparison of whether the duration of positive nucleic acid was greater than 20 days, the positive nucleic acid duration was independently related to the decreased role-emotional value [100, IQR (66-100) vs 100, IQR (0, 100); p = 0.0156]. In addition, multivariable linear regression model showed that male sex and positive nucleic acid duration were related to decreased role-emotional value (p = 0.03< 0.05; p = 0.01< 0.05, respectively). Mental health was associated with age (p= 0.0435). Subsequently, we divided into three subgroups: less than seven days, 7 to 14 days and more than 14 days according to the positive nucleic acid duration. The results revealed that there were significant differences in the vitality value and mental health value of patients aged 46 to 69 in the subgroup where the positive nucleic acid duration longer than 14 days (p= 0.0472; p= 0.0311< 0.05, respectively). Similarly, there are also significant differences in role-emotional value in different genders (p= 0.0316). CONCLUSION: The study described the psychometric properties of COVID-19 patients without comorbidities shortly after discharge. Risk factors for psychometric properties damage included age, male sex, and nucleic acid duration.

Suppression of NLRP3 Inflammasome by Erythropoietin via the EPOR/JAK2/STAT3 Pathway Contributes to Attenuation of Acute Lung Injury in Mice.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. An excessive inflammatory response results in the progression of ALI/ARDS, and the NLRP3 inflammasome is a key participant in inflammation. Erythropoietin (EPO), which is clinically used for anemia, reportedly exerts pleiotropic effects in ALI. However, whether EPO could protect against lipopolysaccharide (LPS)-induced ALI by regulating the NLRP3 inflammasome and its underlying mechanisms remain poorly elucidated. This study aimed to explore whether the therapeutic effects of EPO rely on the suppression of the NLRP3 inflammasome and the specific mechanisms in an LPS-induced ALI mouse model. ALI was induced in C57BL/6 mice by intraperitoneal (i.p.) injection of LPS (15 mg/kg). EPO was administered intraperitoneally at 5 U/g after LPS challenge. The mice were sacrificed 8 h later. Our findings indicated that application of EPO markedly diminished LPS-induced lung injury by restoring histopathological changes, lessened lung wet/dry (W/D) ratio, protein concentrations in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) levels. Meanwhile, EPO evidently decreased interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) secretion, the expression of NLRP3 inflammasome components including pro-IL-1ß, NLRP3, and cleaved caspase-1 as well as phosphorylation of nuclear factor-κB (NF-κB) p65, which may be associated with activation of EPO receptor (EPOR), phosphorylation of Janus-tyrosine kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). However, all the beneficial effects of EPO on ALI and modulation NLRP3 inflammasome were remarkably abrogated by the inhibition of EPOR/JAK2/STAT3 pathway and knockout (KO) of NLRP3 gene. Taken together, this study indicates that EPO can effectively attenuate LPS-induced lung injury in mice by suppressing the NLRP3 inflammasome, which is dependent upon activation of EPOR/JAK2/STAT3 signaling and inhibition of the NF-κB pathway.

Association of serum total and ionized calcium with all-cause mortality incritically ill patients with acute kidney injury.

BACKGROUND: There have been no epidemiological studies exploring the prognostic ability of serum total and ionized calcium (tCa and iCa) in critically ill patients with acute kidney injury (AKI). We assessed the association of admission tCa and iCa concentrations with all-cause mortality in these patients. METHODS: We extracted clinical data from the MIMIC-III V1.4 database. Only the data for the first intensive care unit (ICU) admission of each patient were used and baseline data were extracted within 24 h after ICU admission. Cox proportional hazards models and subgroup analyses were used to determine the relationship between tCa and iCa concentrations and 30, 90 and 365-day all-cause mortality in critically ill patients with AKI. A total of 10,207 eligible patients were studied. In multivariate analysis, adjusted for age, ethnicity and gender, both low-tCa (< 7.9 mg/dl) and low-iCa (<1.06 mmol/l) concentrations were significant predictors of risk of all-cause mortality. Furthermore, after adjusting for more confounding factors, low-iCa concentrations remained a significant predictor of all-cause mortality at 30 days, 90 days, 365 days (HR, 95% CI: 1.19, 1.06-1.33; 1.15, 1.05-1.27; 1.10, 1.01-1.20). CONCLUSIONS: Low-iCa concentrations were independent predictors of all-cause mortality in critically ill patients with AKI.

Relation between Red Cell Distribution Width and Mortality in Critically Ill Patients with Acute Respiratory Distress Syndrome.

BACKGROUND: Currently, evidence regarding the predictive significance of red blood cell distribution width (RDW) among patients with acute respiratory distress syndrome (ARDS) remains scarce. The aim of this study was to determine the prognostic value of RDW for critically ill patients with ARDS. METHODS: We studied all patients with ARDS from the Multiparameter Intelligent Monitoring in Intensive Care Database III (MIMIC-III) for whom RDW was available. The clinical outcomes were 30-day and 90-day mortality. Analyses included logistic multivariate regression model, Receiver Operating Characteristic (ROC) analysis, and subgroup analysis. RESULTS: A total of 404 eligible ARDS patients were included. After adjustment for several clinical characteristics related to 30-day mortality, the adjusted OR (95% CIs) for RDW levels ≥14.5% was 1.91 (1.08, 3.39). A similar trend was observed for 90-day mortality. The RDW levels ≥14.5% were also an independent predictor of 90-day mortality (OR, 2.56; 95% CI, 1.50 to 4.37; P = 0.0006) compared with the low RDW levels (<14.5%). In subgroup analyses, RDW showed no significant interactions with other relevant risk factors for 30-day mortality. CONCLUSIONS: RDW appeared to be a novel, independent predictor of mortality in critically ill patients with ARDS.

Correlations of IL-17 and NF-κB gene polymorphisms with susceptibility and prognosis in acute respiratory distress syndrome in a chinese population.

The present study was performed to investigate the association between interleukin-17 (IL-17) and nuclear factor κB (NF-κB) gene polymorphisms and the risk and prognosis of acute respiratory distress syndrome (ARDS) in a Chinese population. A total of 210 Chinese patients with ARDS were selected as the study group, 210 individuals who were identified as at-risk patients but did not meet criteria for ARDS were recruited as the control group. Three single nucleotide polymorphisms (SNPs) of IL-17, including rs763780 (A>G), rs2275913 (G>A), rs8193036 (C>T) and NF-κB1 gene rs3774934 (G>A) loci were examined by Sanger sequencing technique in the peripheral blood of all subjects. Patients were followed for 30-day survival. The IL-17 rs763780 and NF-κB1 rs3774934 SNPs had no impact on ARDS risk and prognosis of ARDS (P>0.05). Compared with individuals carrying the wild-type GG genotype of rs2275913 at IL-17, the AA-homozygous and GA- heterozygous individuals were protected from the development of ARDS. Consistently, a decreased 30-day mortality risk was found among A-allele carriers of rs2275913 at IL-17 (p<0.05). For IL-17 rs8193036 SNP, the homozygote TT genotype and heterozygote CT genotypes were associated with increased ARDS susceptibility and 30-day mortality risk (P<0.05). Besides, decreased IL-17 levels were found in A-allele carriers of IL-17 rs2275913, whereas individuals carrying T-allele of IL-17 rs8193036 were found to have significantly increased levels of IL-17 (P<0.05). Our results suggested that two functional polymorphisms of IL-17, rs2275913 and rs8193036 were associated with ARDS risk and prognosis, indicating that the two genetic variants might act as possible markers for the prediction of ARDS risk and development.

Association of Initial Serum Total Calcium Concentration with Mortality in Critical Illness.

BACKGROUND: Several studies have suggested that serum ionized calcium (iCa) is associated with mortality in critical illness. However, evidence regarding the predictive significance of serum total calcium (tCa) in critical illness remains scarce. The aim of this study was to assess the association of tCa levels with mortality in critical illness. METHODS: We employed the MIMIC-III v1.3 database. tCa was measured upon ICU admission and its relationship with mortality was determined using smooth curve fitting. The association between admission tCa levels and hospital mortality was determined using logistic regression. RESULTS: Inclusion criteria were met by 44,886 critically ill patients. A U-shaped pattern was observed between tCa and hospital mortality. Similar trends were observed for hospital mortality when quintiles were used to group patients according to tCa. In multivariate analysis, adjusted for age and sex, the model indicated that admission tCa levels ⩽7.6mg/dl, 7.7-8.1mg/dl, and ⩾9.0mg/dl were associated with an increase in mortality when compared to the reference level (8.6-9.0mg/dl). However, adjusted for more clinical characteristics, tCa was not associated with hospital mortality. CONCLUSIONS: The relationship between tCa and hospital mortality followed a ''U" shaped curve. tCa had certain prognostic value in critically ill patients, but it had no independent association with hospital mortality.

Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery: An Update Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: Recent studies suggest that levosimendan does not provide mortality benefit in patients with low cardiac output syndrome undergoing cardiac surgery. These results conflict with previous findings. The aim of the current study is to assess whether levosimendan reduces postoperative mortality in patients with impaired left ventricular function (mean EF ≤ 40%) undergoing cardiac surgery. METHODS: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library Database through November 20, 2017. Inclusion criteria were random allocation to treatment with at least one group receiving levosimendan and another group receiving placebo or other treatments and cardiac surgery patients with a left ventricular ejection fraction of 40% or less. The primary endpoint was postoperative mortality. Secondary outcomes were cardiac index, pulmonary capillary wedge pressure (PCWP), length of intensive care unit (ICU) stay, postoperative atrial fibrillation, and postoperative renal replacement therapy. We performed trial sequential analysis (TSA) to evaluate the reliability of the primary endpoint. RESULTS: Data from 2,152 patients in 15 randomized clinical trials were analyzed. Pooled results demonstrated a reduction in postoperative mortality in the levosimendan group [RR = 0.53, 95% CI (0.38-0.73), I2 = 0]. However, the result of TSA showed that the conclusion may be a false positive. Secondary outcomes demonstrated that PCWP, postoperative renal replacement therapy, and length of ICU stay were significantly reduced. Cardiac index was greater in the levosimendan group. No difference was found in the rate of postoperative atrial fibrillation. CONCLUSIONS: Levosimendan reduces the rate of death and other adverse outcomes in patients with low ejection fraction who were undergoing cardiac surgery, but results remain inconclusive. More large-volume randomized clinical trials (RCTs) are warranted.