Nomogram predictive model for in-hospital mortality risk in elderly ICU patients with urosepsis.

BACKGROUND: Urinary tract infection (UTI) is a common cause of sepsis. Elderly patients with urosepsis in intensive care unit (ICU) have more severe conditions and higher mortality rates owing to factors such as advanced age, immunosenescence, and persistent host inflammatory responses. However, comprehensive studies on nomograms to predict the in-hospital mortality risk in elderly patients with urosepsis are lacking. This study aimed to construct a nomogram predictive model to accurately assess the prognosis of elderly patients with urosepsis and provide therapeutic recommendations. METHODS: Data of elderly patients with urosepsis were extracted from the Medical Information Mart for Intensive Care (MIMIC) IV 2.2 database. Patients were randomly divided into training and validation cohorts. A predictive nomogram model was constructed from the training set using logistic regression analysis, followed by internal validation and sensitivity analysis. RESULTS: This study included 1,251 patients. LASSO regression analysis revealed that the Glasgow Coma Scale (GCS) score, red cell distribution width (RDW), white blood count (WBC), and invasive ventilation were independent risk factors identified from a total of 43 variables studied. We then created and verified a nomogram. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) of the nomogram were superior to those of the traditional SAPS-II, APACHE-II, and SOFA scoring systems. The Hosmer-Lemeshow test results and calibration curves suggested good nomogram calibration. The IDI and NRI values showed that our nomogram scoring tool performed better than the other scoring systems. The DCA curves showed good clinical applicability of the nomogram. CONCLUSIONS: The nomogram constructed in this study is a convenient tool for accurately predicting in-hospital mortality in elderly patients with urosepsis in ICU. Improving the treatment strategies for factors related to the model could improve the in-hospital survival rates of these patients.

Correlation between early intracranial pressure and cerebral perfusion pressure with 28-day intensive care unit mortality in patients with hemorrhagic stroke.

INTRODUCTION: Hemorrhagic stroke may cause changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP), which may influence the prognosis of patients. The aim of this study was to investigate the relationship between early ICP, CPP, and 28-day mortality in the intensive care unit (ICU) of patients with hemorrhagic stroke. PATIENTS AND METHODS: A retrospective study was performed using the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD), including hemorrhagic stroke patients in the ICU with recorded ICP monitoring. The median values of ICP and CPP were collected for the first 24 h of the patient's monitoring. The primary outcome was 28-day ICU mortality. Multivariable Cox proportional hazards models were used to analyze the relationship between ICP, CPP, and 28-day ICU mortality. Restricted cubic regression splines were used to analyze nonlinear relationships. RESULTS: The study included 837 patients with a 28-day ICU mortality rate of 19.4%. Multivariable analysis revealed a significant correlation between early ICP and 28-day ICU mortality (HR 1.08, 95% CI 1.04-1.12, p < 0.01), whereas early CPP showed no correlation with 28-day ICU mortality (HR 1.00, 95% CI 0.98-1.01, p = 0.57), with a correlation only evident when CPP < 60 mmHg (HR 1.99, 95% CI 1.14-3.48, p = 0.01). The study also identified an early ICP threshold of 16.5 mmHg. DISCUSSION AND CONCLUSION: Early ICP shows a correlation with 28-day mortality in hemorrhagic stroke patients, with a potential intervention threshold of 16.5 mmHg. In contrast, early CPP showed no correlation with patient prognosis.

Interpretable machine learning model for early prediction of 28-day mortality in ICU patients with sepsis-induced coagulopathy: development and validation.

OBJECTIVE: Sepsis-induced coagulopathy (SIC) is extremely common in individuals with sepsis, significantly associated with poor outcomes. This study attempted to develop an interpretable and generalizable machine learning (ML) model for early predicting the risk of 28-day death in patients with SIC. METHODS: In this retrospective cohort study, we extracted SIC patients from the Medical Information Mart for Intensive Care III (MIMIC-III), MIMIC-IV, and eICU-CRD database according to Toshiaki Iba's scale. And the overlapping in the MIMIC-IV was excluded for this study. Afterward, only the MIMIC-III cohort was randomly divided into the training set, and the internal validation set according to the ratio of 7:3, while the MIMIC-IV and eICU-CRD databases were considered the external validation sets. The predictive factors for 28-day mortality of SIC patients were determined using recursive feature elimination combined with tenfold cross-validation (RFECV). Then, we constructed models using ML algorithms. Multiple metrics were used for evaluation of performance of the models, including the area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), accuracy, sensitivity, specificity, negative predictive value, positive predictive value, recall, and F1 score. Finally, Shapley Additive Explanations (SHAP), Local Interpretable Model-Agnostic Explanations (LIME) were employed to provide a reasonable interpretation for the prediction results. RESULTS: A total of 3280, 2798, and 1668 SIC patients were screened from MIMIC-III, MIMIC-IV, and eICU-CRD databases, respectively. Seventeen features were selected to construct ML prediction models. XGBoost had the best performance in predicting the 28-day mortality of SIC patients, with AUC of 0.828, 0.913 and 0.923, the AUPRC of 0.807, 0.796 and 0.921, the accuracy of 0.785, 0.885 and 0.891, the F1 scores were 0.63, 0.69 and 0.70 in MIMIC-III (internal validation set), MIMIC-IV, and eICU-CRD databases. The importance ranking and SHAP analyses showed that initial SOFA score, red blood cell distribution width (RDW), and age were the top three critical features in the XGBoost model. CONCLUSIONS: We developed an optimal and explainable ML model to predict the risk of 28-day death of SIC patients 28-day death risk. Compared with conventional scoring systems, the XGBoost model performed better. The model established will have the potential to improve the level of clinical practice for SIC patients.

Protective effect of canagliflozin on post-resuscitation myocardial function in a rat model of cardiac arrest.

BACKGROUND: Currently, most patients with cardiac arrest (CA) show reversible myocardial dysfunction, hemodynamic instability, systemic inflammation and other pathophysiological state in early stage of resuscitation, some patients may eventually progress to multiple organ failure. There is evidence that heart failure is the terminal stage in the development of various cardiovascular diseases. Although the cardio-protective effect of canagliflozin (CANA) has been confirmed in large clinical studies and recommended in domestic and international heart failure-related guidelines, the effectiveness of CANA after resuscitation remains unclear. In this study, we constructed a modified CA/CPR rat model to investigate whether CANA administered on post-resuscitation improves myocardial function. METHODS: Twenty-fourth healthy male Sprague-Dawley rats were randomized into four groups: (1) Sham + placebo group, (2) Sham + CANA group, (3) CPR + placebo group, and (4) CPR + CANA group. Ventricular fibrillation was induced by transcutaneous electrical stimulation on epicardium. After 6 min untreated ventricular fibrillation, chest compressions was initiated. The rats were received an injection of placebo or canagliflozin (3 ug/kg) randomly 15 min after restore of spontaneous circulation (ROSC). Electrocardiogram (ECG) and blood pressure were continuously detected in each group throughout the experiment. The rats were killed 6 h after ROSC to collected the arterial serum and myocardial tissue. Myocardial injury was estimated with concentrations of inflammatory factors, oxidative stress indexes and, apoptosis index, myocardial injury markers, echocardiography and myocardial pathological slices. RESULTS: After resuscitation, mean arterial pressure (MAP) were significantly increased after cardiopulmonary resuscitation in CANA group rats when compared with placebo group. Heart rate, body lactate returned and left ventricular ejection fraction (LVEF) to normal levels in a shorter time and the myocardial injury was obviously attenuated in CPR + CANA group. Inflammatory factors (IL-6, TNF-α) and oxidative stress indexes (MAD, SOD, CAT) were dramatically decreased with the administration of CANA. The expression of apoptosis index (BAX, caspase-3) were higher in CPR + placebo group and the expression of anti-apoptosis index (Bcl-2) was lower (P < 0.05). CONCLUSIONS: The administration of CANA effectively reduces myocardial ischaemia/reperfusion (I/R) injury after cardiac arrest and cardiopulmonary resuscitation (CPR), and the underlying mechanism may be related to anti-inflammation, oxidative stress and apoptosis.

Early persistent exposure to high CVP is associated with increased mortality and AKI in septic shock: A retrospective study.

PURPOSE: This study's objective was to investigate the association between exposure to different intensities of central venous pressure (CVP) over time in patients with septic shock with 28-day mortality and acute kidney injury (AKI). MATERIALS AND METHODS: We obtained data from the AmsterdamUMCdb, which includes data on patients ≥18 years old with septic shock undergoing CVP monitoring. The primary outcome was mortality by day 28. Piecewise exponential additive mixed models were used to estimate the strength of the association over time. RESULTS: 9668 patients were included in the study. They exhibited 8.2% overall mortality at 28 days and 41.1% AKI incidence. Daily time-weighted average CVP was strongly associated with increased mortality at 28 days, primarily within 24 h of ICU admission. The mortality rate of patients was lowest when the CVP was 6-12 cmH2O. When the time of high CVP (TWA-CVP >12 cmH2O) exposure within the first 24 h was >5 h, the risk of death increased by 2.69-fold. Additionally, patients exposed to high CVP had a significantly increased risk of developing AKI. CONCLUSIONS: The optimal CVP range for patients with septic shock within 24 h of ICU admission is 6-12 cmH2O. Mortality increased when patients were exposed to high CVP for >5 h.

Development of a machine learning-based prediction model for sepsis-associated delirium in the intensive care unit.

Septic patients in the intensive care unit (ICU) often develop sepsis-associated delirium (SAD), which is strongly associated with poor prognosis. The aim of this study is to develop a machine learning-based model for the early prediction of SAD. Patient data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the eICU Collaborative Research Database (eICU-CRD). The MIMIC-IV data were divided into a training set and an internal validation set, while the eICU-CRD data served as an external validation set. Feature variables were selected using least absolute shrinkage and selection operator regression, and prediction models were built using logistic regression, support vector machines, decision trees, random forests, extreme gradient boosting (XGBoost), k-nearest neighbors and naive Bayes methods. The performance of the models was evaluated in the validation set. The model was also applied to a group of patients who were not assessed or could not be assessed for delirium. The MIMIC-IV and eICU-CRD databases included 14,620 and 1723 patients, respectively, with a median time to diagnosis of SAD of 24 and 30 h. Compared with Non-SAD patients, SAD patients had higher 28-days ICU mortality rates and longer ICU stays. Among the models compared, the XGBoost model had the best performance and was selected as the final model (internal validation area under the receiver operating characteristic curves (AUROC) = 0.793, external validation AUROC = 0.701). The XGBoost model outperformed other models in predicting SAD. The establishment of this predictive model allows for earlier prediction of SAD compared to traditional delirium assessments and is applicable to patients who are difficult to assess with traditional methods.

Acetaldehyde dehydrogenase 2 activation attenuates sepsis-induced brain injury through NLRP3 inflammasome regulation.

OBJECTIVE: Acetaldehyde dehydrogenase 2 (ALDH2) plays an important part in neuroprotection; however, its effect on sepsis-induced brain injury is nuclear. Our aim is to investigate the potential effect and mechanism of ALDH2 in this condition. METHODS: We established an animal model using cecal ligation and perforation (CLP). Twenty-four rats were divided into sham group (n = 6), CLP group (n = 6), CLP + Alda-1 group (n = 6) and CLP + Cyanamide (CYA) group (n = 6). Vital signs were monitored, and arterial blood gas analysis, hippocampal histological staining and ALDH2 activity analysis were conducted. Western blot analysis and enzyme-linked immunosorbent assays were also carried out. Lipopolysaccharide (LPS)-treated HT22 cells were employed as an in vitro model of sepsis-induced brain injury, with and without pretreatment with Alda-1 or CYA, to further examine the potential mechanisms. Real-time quantitative polymerase chain reaction and western blot were used to determine the levels of pyrin domain-containing 3 (NLRP3) inflammasome. RESULTS: We found hippocampal cell injury in the CLP group (p < 0.05), with decreased ALDH2 activity (p < 0.05) and suspected overexpression of NLRP3/caspase-1 axis (p < 0.05). In the group pretreated with Alda-1, there were increased ALDH2 activity (p < 0.05), decreased hippocampal cell damage (p < 0.05), and reduced protein levels of NLRP3, apoptosis-associated speck like protein containing a caspase recruitment domain (ASC), cleaved caspase-1 and Gasdermin D (GSDMD) (p < 0.05). The levels of interleukin 18 (IL-18) and interleukin 1ß (IL-1ß) were also reduced (p < 0.05). In the group pretreated with CYA, ALDH2 activity was further declined, the cell injury grade increased, and the elevated levels of pyroptosis-related proteins aggravated (p < 0.05). LPS treatment decreased the cell viability and ALDH2 activity of the HT22 cells (p < 0.05), along with increased mRNA levels of the NLRP3 inflammasome, as well as IL-1ß and IL-18 (p < 0.05). Western blot further revealed elevated levels of NLRP3, ASC, cleaved caspase-1 and GSDMD (p < 0.05). In the LPS+Alda-1 group, there were increased cell viability (p < 0.05), elevated ALDH2 activity (p < 0.05), and reduced levels of NLRP3 inflammasome and pyroptosis-related proteins (p < 0.05). In the CYA+LPS group, cell viability and ALDH2 activity were further declined (p < 0.05), while levels of NLRP3 /caspase-1 axis were increased (p < 0.05). CONCLUSIONS: The activation of ALDH2 can attenuate sepsis-induced brain injury, hypothetically through regulation of the NLRP3/caspase-1 signaling pathway. Therefore, ALDH2 could potentially be considered as a new therapeutic target for the treatment of sepsis-induced brain injury.

The association of diastolic arterial pressure and heart rate with mortality in septic shock: a retrospective cohort study.

BACKGROUND: The effects of diastolic arterial pressure (DAP) and heart rate (HR) on the prognosis of patients with septic shock are unclear, and whether these effects persist over time is unknown. We aimed to investigate the relationship between exposure to different intensities of DAP and HR over time and mortality at 28 days in patients with septic shock. METHODS: In this cohort study, we obtained data from the Medical Information Mart for Intensive Care IV, which includes the data of adult patients (≥ 18 years) with septic shock who underwent invasive blood pressure monitoring. We excluded patients who received extracorporeal membrane oxygenation (ECMO) or glucocorticoids within 48 h of ICU admission. The primary outcome was mortality at 28 days. Piece-wise exponential additive mixed models were used to estimate the strength of the associations over time. RESULTS: In total, 4959 patients were finally included. The median length of stay in the ICU was 3.2 days (IQR: 1.5-7.1 days), and the mortality in the ICU was 12.9%, with a total mortality at 28 days of 15.9%. After adjustment for baseline and time-dependent confounders, both daily time-weighted average (TWA) DAP and HR were associated with increased mortality at 28 days and strong association, mainly in the early to mid-stages of the disease. The results showed that mortality in patients with septic shock was lowest at a DAP of 50-70 mm Hg and an HR of 60-90 beats per minute (bpm). Throughout, a significant increase in the risk of death was found with daily exposure to TWA-DAP ≤ 40 mmHg (hazard ratio 0.99, 95% confidence interval (CI) 0.94-1.03) or TWA-HR ≥ 100 bpm (hazard ratio 1.16, 95% CI 1.1-1.21). Cumulative and interactive effects of harmful exposure (TWA-DAP ≤ 40 mmHg and TWA-HR ≥ 100 bpm) were also observed. CONCLUSION: The optimal ranges for DAP and HR in patients with septic shock are 50-70 mmHg and 60-90 bpm, respectively. The cumulative and interactive effects of exposure to low DAP (≤ 40 mmHg) and tachycardia (≥ 100 bpm) were associated with an increased risk of death.

Influence of the Initial Neutrophils to Lymphocytes and Platelets Ratio on the Incidence and Severity of Sepsis-Associated Acute Kidney Injury: A Double Robust Estimation Based on a Large Public Database.

Background: Acute kidney injury (AKI) is a frequent consequence of sepsis and has been linked to poor prognosis. In critically ill patients, the ratio of neutrophils to lymphocytes and platelets (N/LP) has been confirmed as an inflammation-related marker connected with the development of renal dysfunction. However, the effect of the N/LP ratio on the initiation and development of AKI in patients with sepsis remained unclear. The purpose of this study was to determine if the N/LP ratio on intensive care unit (ICU) admission was associated with the occurrence of sepsis-associated AKI (S-AKI) and severe AKI. Methods: Adult septic patients from the Medical Information Mart for Intensive Care-IV database were screened and classified into three categories (low, middle, or high) based on their N/LP ratio quartiles. The Cox proportional hazard and competing risk models were used to determine the risk of S-AKI in various N/LP groups, whilst the logistic regression model and restricted cubic splines (RCS) analysis were employed to investigate the link between N/LP ratios and the occurrence of severe AKI. Finally, we did a doubly robust estimation, a subgroup analysis, and a sensitivity analysis to determine the findings' robustness. Results: We categorized 485, 968, and 485 septic patients into three groups based on their N/LP ratios: low, intermediate, and high. According the Cox proportional hazard model, the hazard rate (95% CI) for those in the middle and high N/LP groups on the incidence of S-AKI were 1.30(1.07, 1.58) and 1.27(1.02, 1.59), respectively, as compared to those in the low N/LP group. And the Fine-Gray proportional subdistribution hazards model indicated that mortality was not a substantial competing risk for S-AKI. Additionally, multivariate logistic regression revealed that the risk of severe AKI increased 1.83 fold in the high group compared to the low group. The RCS result also suggested that the probability of severe AKI rose significantly when N/LP > 9.5. The consistency of these findings was confirmed using doubly robust estimation. However, subgroup and sensitivity analyses revealed that the association between N/LP and the incidence of S-AKI, severe AKI varied considerably between different populations and diagnostic criteria. Conclusion: A raised initial N/LP level may induce the development of S-AKI and severe AKI within 7 days after ICU admission in septic patients. These influences were enhanced in elder, male, septic shock, and those with poor health condition. Furthermore, high NLP was more strongly connected to the risk of S-AKI and severe AKI in sepsis patients on the urine output-based AKI criteria than on the serum creatinine-based criteria.

Association of Blood Glucose Level and Glycemic Variability With Mortality in Sepsis Patients During ICU Hospitalization.

Background: There was considerable debate regarding the effect of mean blood glucose (MBG) and glycemic variability (GV) on the mortality of septic patients. This retrospective cohort study aimed to assess the association between MBG and GV with ICU mortality of sepsis patients and to explore the optimal MBG range. Methods: Sepsis patients were enrolled from the Medical Information Mart for Intensive Care IV database (MIMIC-IV). MBG and glycemic coefficient of variation (GluCV) were, respectively, calculated to represent the overall glycemic status and GV during ICU stay. The associations between MBG, GluCV, and ICU mortality of the septic patients were assessed by using multivariate logistic regression in different subgroups and the severity of sepsis. Restricted cubic splines evaluated the optimal MBG target. Results: A total of 7,104 adult sepsis patients were included. The multivariate logistic regression results showed that increased MBG and GluCV were significantly correlated with ICU mortality. The adjusted odds ratios were 1.14 (95% CI 1.09-1.20) and 1.05 (95% CI 1.00-1.12). However, there was no association between hyperglycemia and ICU mortality among diabetes, liver disease, immunosuppression, and hypoglycemia patients. And the impact of high GluCV on ICU mortality was not observed in those with diabetes, immunosuppression, liver disease, and non-septic shock. The ICU mortality risk of severe hyperglycemia (≧200 mg/dl) and high GluCV (>31.429%), respectively, elevated 2.30, 3.15, 3.06, and 2.37, 2.79, 3.14-folds in mild (SOFA ≦ 3), middle (SOFA 3-7), and severe group (SOFA ≧ 7). The MBG level was associated with the lowest risk of ICU mortality and hypoglycemia between 120 and 140 mg/dl in the subgroup without diabetes. For the diabetic subset, the incidence of hypoglycemia was significantly reduced when the MBG was 140-190 mg/dl, but a glycemic control target effectively reducing ICU mortality was not observed. Conclusion: MBG and GluCV during the ICU stay were associated with all-cause ICU mortality in sepsis patients; however, their harms are not apparent in some particular subgroups. The impact of hyperglycemia and high GV on death increased with the severity of sepsis. The risk of ICU mortality and hypoglycemia in those with no pre-existing diabetes was lower when maintaining the MBG in the range of 120-140 mg/dl.

A Nomogram With Six Variables Is Useful to Predict the Risk of Acquiring Carbapenem-Resistant Microorganism Infection in ICU Patients.

Background: Carbapenem-resistant microorganism (CRO) transmission in the medical setting confers a global threat to public health. However, there is no established risk prediction model for infection due to CRO in ICU patients. This study aimed to develop a nomogram to predict the risk of acquiring CRO infection in patients with the first ICU admission and to determine the length of ICU stay (ICU-LOS) and 28-day survival. Methods: Patient data were retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV) database based on predetermined inclusion and exclusion criteria. A CRO was defined as a bacterium isolated from any humoral microbial culture that showed insensitivity or resistance to carbapenems. The characteristics of CRO and non-CRO patients in the first ICU admission were compared. Propensity score matching was applied to balance the differences between the CRO and non-CRO cohorts. Kaplan-Meier curves were constructed to determine the 28-day survival rate and ICU-LOS. Furthermore, after randomization of the CRO cohort into the training and validation sets, a predictive nomogram was constructed based on LASSO regression and Logistic regression analysis, and its performance was verified by internal validation. Results: Overall, 4531 patients who had first ICU admission as recorded in MIMIC-IV were enrolled, 183 (4.04%) of whom were diagnosed with CRO infection. Moreover, CRO infection was independently associated with 28-day survival and ICU-LOS in ICU patients. Parameters eligible for inclusion in this nomogram were male sex, hemoglobin-min, temperature-max, use of a peripherally inserted central catheter line, dialysis treatment, and use of carbapenems. This nomogram showed a better performance as indicated by the area under the receiver operating characteristic curve values of 0.776 (95% confidence interval [CI] 0.667-0.750) and 0.723 (95% CI 0.556-0.855) in the training and validation sets, respectively, in terms of predicting the risk of acquiring CRO infection. Conclusions: CRO infection was independently associated with ICU-LOS and 28-day survival in patients with first ICU admission. The nomogram showed the best prediction of the risk of acquiring CRO infection in ICU patients. Based on the nomogram-based scoring, we can management the risk factors and guide individualized prevention and control of CRO.

Calcitonin gene-related peptide alleviates hypertrophic scar formation by inhibiting the inflammation.

The present study aims to explore the roles of calcitonin gene-related peptide (CGRP) in the hypertrophic scar and its underlying mechanism. The levels of CGRP were determined in human hypertrophic scar and mouse cutaneous scar using ELISA and Western blot. In in vivo studies, A cutaneous excision mouse model was established and treated with exogenous CGRP or CGRP antagonist. In in vitro studies, bone marrow-derived macrophages (BMDMs) were isolated and treated with exogenous CGRP in the presence of lipopolysaccharide (LPS). qRT-PCR and Western blot were applied to determine the mRNA and protein levels of scar formation and inflammation-related genes, respectively. Flow cytometry was operated to determine the populations of macrophages in the scar. Elevated levels of CGRP were observed in the hypertrophic scar. In the cutaneous excision mouse model, treatment of exogenous CGRP or CGRP antagonist-affected scar formation-related genes including Col1, Tgfb1, and α-SMA, inflammation-related genes including Il1b, Il6, Tnfa, and Ccl2, and CD45+F4/80+ macrophage. In LPS-induced BMDMs, treatment of exogenous CGRP also altered inflammation-related genes by regulating NF-κB and ERK signaling pathways. The ameliorated effects of CGRP on inflammation in hypertrophic scar formation are associated with its regulative effects on NF-κB and ERK signaling pathways.

Efficacy and safety of abdominal paracentesis drainage on patients with acute pancreatitis: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis of the efficacy and safety of abdominal paracentesis drainage (APD) in patients with acute pancreatitis (AP) when compared with conventional 'step-up' strategy based on percutaneous catheter drainage (PCD). DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library, MEDLINE (OVID), China National Knowledge Infrastructure and Wanfang Database were electronically searched to collect cohort studies and randomised controlled trials (RCTs) from inception to 25 July 2020. Studies related to comparing APD with conventional 'step-up' strategy based on PCD were included. OUTCOMES: The primary outcome was all-cause mortality. The secondary outcomes were the rate of organ dysfunction, infectious complications, hospitalisation expenses and length of hospital stay. RESULTS: Five cohort studies and three RCTs were included in the analysis. Compared with the conventional 'step-up' method, pooled results suggested APD significantly decreased all-cause mortality during hospitalisation (cohort studies: OR 0.48, 95% CI 0.26 to 0.89 and p=0.02), length of hospital stay (cohort studies: standard mean difference (SMD) -0.31, 95% CI -0.53 to -0.10 and p=0.005; RCTs: SMD -0.45, 95% CI -0.64 to -0.26 and p<0.001) and hospitalisation expenses (cohort studies: SMD -2.49, 95% CI -4.46 to -0.51 and p<0.001; RCTs: SMD -0.67, 95% CI -0.89 to -0.44 and p<0.001). There was no evidence to prove that APD was associated with a higher incidence of infectious complications. However, the incidence of organ dysfunction between cohort studies and RCTs subgroup slightly differed (cohort studies: OR 0.66, 95% CI 0.34 to 1.28 and p=0.22; RCTs: OR 0.58, 95% CI 0.35 to 0.98 and p=0.04). CONCLUSIONS: The findings suggest that early application of APD in patients with AP is associated with reduced all-cause mortality, expenses during hospitalisation and the length of stay compared with the 'step-up' strategy without significantly increasing the risk of infectious complications. These results must be interpreted with caution because of the limited number of included studies as well as a larger dependence on observational trials. PROSPERO REGISTRATION NUMBER: CRD42020168537.

Development of a Nomogram to Predict 28-Day Mortality of Patients With Sepsis-Induced Coagulopathy: An Analysis of the MIMIC-III Database.

Background: Sepsis-induced coagulopathy (SIC) is a common cause for inducing poor prognosis of critically ill patients in intensive care unit (ICU). However, currently there are no tools specifically designed for assessing short-term mortality in SIC patients. This study aimed to develop a practical nomogram to predict the risk of 28-day mortality in SIC patients. Methods: In this retrospective cohort study, we extracted patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Sepsis was defined based on Sepsis 3.0 criteria and SIC based on Toshiaki Iba's criteria. Kaplan-Meier curves were plotted to compare the short survival time between SIC and non-SIC patients. Afterward, only SIC cohort was randomly divided into training or validation set. We employed univariate logistic regression and stepwise multivariate analysis to select predictive features. The proposed nomogram was developed based on multivariate logistic regression model, and the discrimination and calibration were verified by internal validation. We then compared model discrimination with other traditional severity scores and machine learning models. Results: 9432 sepsis patients in MIMIC III were enrolled, in which 3280 (34.8%) patients were diagnosed as SIC during the first ICU admission. SIC was independently associated with the 7- and 28-day mortality of ICU patients. K-M curve indicated a significant difference in 7-day (Log-Rank: P < 0.001 and P = 0.017) and 28-day survival (Log-Rank: P < 0.001 and P < 0.001) between SIC and non-SIC groups whether the propensity score match (PSM) was balanced or not. For nomogram development, a total of thirteen variables of 3,280 SIC patients were enrolled. When predicted the risk of 28-day mortality, the nomogram performed a good discrimination in training and validation sets (AUROC: 0.78 and 0.81). The AUROC values were 0.80, 0.81, 0.71, 0.70, 0.74, and 0.60 for random forest, support vector machine, sequential organ failure assessment (SOFA) score, logistic organ dysfunction score (LODS), simplified acute physiology II score (SAPS II) and SIC score, respectively, in validation set. And the nomogram calibration slope was 0.91, the Brier value was 0.15. As presented by the decision curve analyses, the nomogram always obtained more net benefit when compared with other severity scores. Conclusions: SIC is independently related to the short-term mortality of ICU patients. The nomogram achieved an optimal prediction of 28-day mortality in SIC patient, which can lead to a better prognostics assessment. However, the discriminative ability of the nomogram requires validation in external cohorts to further improve generalizability.

A Simple Weaning Model Based on Interpretable Machine Learning Algorithm for Patients With Sepsis: A Research of MIMIC-IV and eICU Databases.

BACKGROUND: Invasive mechanical ventilation plays an important role in the prognosis of patients with sepsis. However, there are, currently, no tools specifically designed to assess weaning from invasive mechanical ventilation in patients with sepsis. The aim of our study was to develop a practical model to predict weaning in patients with sepsis. METHODS: We extracted patient information from the Medical Information Mart for Intensive Care Database-IV (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Kaplan-Meier curves were plotted to compare the 28-day mortality between patients who successfully weaned and those who failed to wean. Subsequently, MIMIC-IV was divided into a training set and an internal verification set, and the eICU-CRD was designated as the external verification set. We selected the best model to simplify the internal and external validation sets based on the performance of the model. RESULTS: A total of 5020 and 7081 sepsis patients with invasive mechanical ventilation in MIMIC-IV and eICU-CRD were included, respectively. After matching, weaning was independently associated with 28-day mortality and length of ICU stay (p < 0.001 and p = 0.002, respectively). After comparison, 35 clinical variables were extracted to build weaning models. XGBoost performed the best discrimination among the models in the internal and external validation sets (AUROC: 0.80 and 0.86, respectively). Finally, a simplified model was developed based on XGBoost, which included only four variables. The simplified model also had good predictive performance (AUROC:0.75 and 0.78 in internal and external validation sets, respectively) and was developed into a web-based tool for further review. CONCLUSIONS: Weaning success is independently related to short-term mortality in patients with sepsis. The simplified model based on the XGBoost algorithm provides good predictive performance and great clinical applicablity for weaning, and a web-based tool was developed for better clinical application.

[Progress of intensive care unit delirium research from 2010 to 2020: analysis based on knowledge visualization].

OBJECTIVE: To explored the progress of intensive care unit (ICU) delirium between 2010 and 2020 based on knowledge visualization analysis. METHODS: The literatures related to ICU delirium included in Web of Sciences (WOS) and China National Knowledge Infrastructure (CNKI) databases from 2010 to 2020 were collected. A bibliometric analysis was performed. The growth trend was showed by Excel 2019 software. The information about country, institution and author were extracted by VOSviewer 1.6.15 for generating cooperative network, to find the main research power and each cooperative relation. At the same time, Citespace 5.0.R1 was used to analyze those high frequency keywords and bursting keywords and build the map of co-citation reference, in order to explore the evolution of research in the field of ICU delirium and the hotspots about this field in recent 10 years. RESULTS: A total of 1 102 Chinese journal articles and 2 422 English "Articles" or "Reviews" from 2010 to 2020 were collected preliminarily, and the number of published literatures increased steadily. In the respect of quality, the impact factors of most articles were concentrated between 2 and 3, and the literatures with impact factor over 5 accounted for 27.9% (337/1 209). According to the knowledge visualization analysis, the United States published most of the related articles (total 1 152) in this field, while the England and Canada ranked second and third respectively, totaling 220 and 204. In terms of the distribution of research institutions, the Vanderbilt University School of Medicine was not only far ahead in the number of publication (n = 149), but more importantly, top three high-impact authors located in this institution. The amount of domestic publications was lower than developed countries, however, the burst index, which reflected the sudden increase, ranked first (7.09), suggesting that the interest and investment of Chinese researchers was increasing recently. The most productive institution in China was Capital Medical University School of Nursing with totaling 23 articles. Wu Ying, who published most Chinese papers (n = 14), belongs to this institution. However, it was a pity that there was no large scientific community be constructed in China, and the cooperation between institutions was deficient. By generating the co-occuring keyword mapping, the research hotpots mainly focused on the prevention, treatment and prevention of delirium in mechanically ventilated patients, the effect of dexmedetomidine and exploring the risk factor of ICU delirium. Finally, the results of co-citation reference analysis showed that Cluster 4 (risk assessment) was still in the process of development, in hence it was the frontier in this domain. CONCLUSIONS: There was a big gap between China and leading countries in the field of ICU delirium research. The main research power was located in the United States, and the trending of future studies mainly focus on delirium-related risk assessment.

[Translation and interpretation of the Telecommunicator cardiopulmonary resuscitation: a policy statement from the American Heart Association].

Out-of-hospital cardiac arrest (OHCA) is a global medical challenge. Early case recognition and initiating the chain of survival is associated with good prognosis of these patients. On the basis of former research, American Heart Association (AHA) published a policy statement related to telecommunicator cardiopulmonary resuscitation (T-CPR) in March 2020, and introduced its specific procedures, standards and precautions. To assist Chinese doctors in better understanding of the T-CPR, and give a reference for the emergency curing of OHCA, the guideline was translated and interpreted in this paper.

Efficacy and Safety of Recombinant Human Thrombopoietin on Sepsis Patients With Thrombocytopenia: A Systematic Review and Meta-Analysis.

BACKGROUND: The efficacy and safety of the administration of recombinant human thrombopoietin (rhTPO) in sepsis patients with thrombocytopenia were still inconclusive. OBJECTIVES: To investigate whether rhTPO is a benefit for sepsis patients with thrombocytopenia. METHODS: PubMed, Cochrane library, Embase, China National Knowledge Infrastructure, and Wanfang Database were electronically searched to the randomized controlled trials (RCTs) from inception to March 4, 2020. The primary outcome was the level of platelet (PLT) on the 7th day of treatment, and secondary outcomes were 28-d mortality, the level of coagulation indicators, hepatic and renal function indicators, blood transfusion, and length of intensive care unit (ICU) stay. RESULTS: Ten RCTs involving 681 patients were included. For compared with conventional antibiotic therapy, rhTPO could significantly increase platelet counts (PCs) [standardized mean difference (SMD), 2.61; 95% confidence interval (CI), 1.28-3.94; P < 0.001], decreased 28-d mortality [relative risk (RR), 0.66; 95%CI, 0.46-0.97; P=0.03], transfusion volume of blood products and length of ICU stay. Additionally, for compared with conventional antibiotic therapy combined with intravenous immunoglobulin, the pooled results shown that rhTPO also associated with an improvement of PCs on 7th of treatment (SMD, 0.86; 95%CI, 0.54-1.17; P < 0.001), and a reduced transfusion volume of blood products. However, there were no differences in 28-d mortality and the length of ICU stay. CONCLUSIONS: Current evidence shown that rhTPO could increase PCs on 7th day of treatment and reduce the transfusion volume of blood products in sepsis-related thrombocytopenia during hospitalization. The conclusions are needed to be verified indeed by more multicenter RCTs due to the limitation of the included studies.

[Progress of microcirculation research in shock and sepsis from 2000 to 2019 based on knowledge visualization analysis].

OBJECTIVE: To explore the progress of microcirculation research in shock and sepsis from 2000 to 2019 based on knowledge visualization analysis. METHODS: The literatures related to microcirculation of shock and sepsis published in Web of Science and Wanfang databases were collected from 2000 to 2019. Then, data collected was sorted out and used to make bar charts and curves reflecting the growth trend of the literatures using Excel software. The information about country, institution and author were extracted by CiteSpace 5.0 R1 for generating co-occurring network, to find the main research power and each cooperative relation. This software was also used to analyze the related-keywords and cited reference, so that the map of co-citation reference was drawn subsequently to explore the frontiers and hot spots in this field. RESULTS: There were a total of 2 000 Chinese "papers" or "dissertations", 1 823 English "articles" or "reviews", collected preliminarily. The Chinese literatures were only statistically described for the amounts, institutions and authors, however, all retrieved English literatures were enrolled in the visualization analysis eventually. From 2009 to 2019, the number of English literatures rose steadily; however, the number of Chinese literatures had been sliding since 2011. On terms of quality, the impact factors of most literatures were under 6, lacking high quality ones, and the number remained stable every year. According to the analysis of English literatures, the top three countries that published related papers around the world were Germany (n = 430), the United States (n = 401) and Netherlands (n = 223). In the aspect of research institutions, the University of Amsterdam (Netherlands) ranked first in the Web of Science (n = 113), while the institution in China with the most publications was the Southern Medical University (n = 71). According to the analysis of co-occurring author network, there were three major globe scientific groups in which Can Ince, Daniel De Backer and Jean-Louis Vincent contributed most to this research field. The top three authors who published most Chinese papers were Niu Chunyu (n = 20), Zhao Zigang (n = 18) and Duan Meili (n = 13). By generating the co-occurring keyword mapping, the research hot spots mainly focused on "blood flow", "nitric oxide", "hemorrhagic shock" and "perfusion". However, these burst keywords, including "cardiogenic shock", "acute kidney injury", "fluid resuscitation", "sublingual microcirculation", "mortality", "oxidative stress", and "critically ill patient", represented the frontiers in microcirculation research of shock and sepsis field. Finally, the results of co-citation reference analysis showed that "sublingual microcirculation" and "mottling score" were most active, indicating that the research of microcirculation monitoring technology could be considered as a hot spot and also the frontier in this field, which was consistent with the results of co-occurring keywords network. CONCLUSIONS: Knowledge visualization analysis can visually exhibit the hot spot and trend of microcirculation research in shock and sepsis. The power was mainly focused on a few developed countries in Europe, and the trend was more inclined to the related microcirculation monitoring technology.