Utility of paired plasma and drainage fluid mNGS in diagnosing acute intra-abdominal infections with sepsis.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has been increasingly applied in sepsis. We aimed to evaluate the diagnostic and therapeutic utility of mNGS of paired plasma and peritoneal drainage (PD) fluid samples in comparison to culture-based microbiological tests (CMTs) among critically ill patients with suspected acute intra-abdominal infections (IAIs). METHODS: We conducted a prospective study from October 2021 to December 2022 enrolling septic patients with suspected IAIs (n = 111). Pairwise CMTs and mNGS of plasma and PD fluid were sent for pathogen detection. The mNGS group underwent therapeutic regimen adjustment based on mNGS results for better treatment. The microbial community structure, clinical features, antibiotic use and prognoses of the patients were analyzed. RESULTS: Higher positivity rates were observed with mNGS versus CMTs for both PD fluid (90.0% vs. 48.3%, p < 0.005) and plasma (76.7% vs. 1.6%, p < 0.005). 90% of enrolled patients had clues of suspected pathogens combining mNGS and CMT methods. Gram-negative pathogens consist of most intra-abdominal pathogens, including a great variety of anaerobes represented by Bacteroides and Clostridium. Patients with matched plasma- and PD-mNGS results had higher mortality and sepsis severity. Reduced usage of carbapenem (30.0% vs. 49.4%, p < 0.05) and duration of anti-MRSA treatment (5.1 ± 3.3 vs. 7.0 ± 8.4 days, p < 0.05) was shown in the mNGS group in our study. CONCLUSIONS: Pairwise plasma and PD fluid mNGS improves microbiological diagnosis compared to CMTs for acute IAI. Combining plasma and PD mNGS could predict poor prognosis. mNGS may enable optimize empirical antibiotic use.

Effect of Improved Nursing Strategy on Prognosis of Immunosuppressed Patients With Pneumonia and Sepsis: A Prospective Cohort Study.

Objectives: To investigate the effect of our improved nursing strategy on prognosis in immunosuppressed patients with pneumonia and sepsis. Methods: Immunosuppressed patients (absolute lymphocyte count <1000 cells/mm3) with pneumonia and sepsis were enrolled and divided into a control group and treatment group. The treatment group received the improved nursing strategy. The primary outcome in this study was 28-day mortality. Results: In accordance with the study criteria, 1019 patients were finally enrolled. Compared with patients in the control group, those in the treatment group had significantly fewer days on mechanical ventilation [5 (4, 7) versus 5 (4, 7) days, P = .03] and lower intensive care unit (ICU) mortality [21.1% (132 of 627) vs 28.8% (113 of 392); P = .005] and 28-day mortality [22.2% (139 of 627) vs 29.8% (117 of 392); P = .006]. The treatment group also had a shorter duration of ICU stay [9 (5, 15) vs 11 (6, 22) days, P = .0001] than the control group. The improved nursing strategy acted as an independent protective factor in 28-day mortality: odds ratio 0.645, 95% confidence interval: 0.449-0.927, P = .018. Conclusion: Our improved nursing strategy shortened the duration of mechanical ventilation and the ICU stay and decreased ICU mortality and 28-day mortality in immunosuppressed patients with pneumonia and sepsis. Trial registration: ChiCTR.org.cn, ChiCTR-ROC-17010750. Registered 28 February 2017.

[Effect of improved nursing strategy on prognosis of older immunosuppressed patients with pneumonia and sepsis].

OBJECTIVE: To investigate the effect of improved nursing strategy on prognosis of older immunosuppressed patients with pneumonia and sepsis. METHODS: A prospective study was conducted. The older immunosuppressed patients with pneumonia and sepsis admitted to the department of intensive care medicine and emergency intensive care unit (ICU) of Peking Union Medical College Hospital from January 2017 to July 2022 were enrolled. In the first stage (from January 2017 to December 2019), patients received the original nursing strategy (original nursing strategy group), including: (1) nurses were randomly assigned; (2) routine terminal cleaning; (3) ICU environmental cleaning twice a day; (4) oral care was performed with chlorhexidine twice a day; (5) original lung physiotherapy [head of bed elevated at 30 degree angle-45 degree angle, maintaining a Richmond agitation-sedation scale (RASS) -2 to 1, sputum aspiration as needed]. After 1 month of learning and training of the modified nursing treatment strategy for nurses and related medical staff, the patients in the second stage (from February 2020 to July 2022) received the improved nursing strategy (improved nursing strategy group). The improved nursing strategy improved the hospital infection prevention and control strategy and lung physical therapy strategy on the basis of the original nursing strategy, including: (1) nurses were fixed assigned; (2) patients were placed in a private room; (3) enhanced terminal cleaning; (4) ICU environmental cleaning four times a day; (5) education and training in hand hygiene among health care workers was improved; (6) bathing with 2% chlorhexidinegluconate was performed once daily; (7) oral care with a combination of chlorhexidine and colistin was provided every 6 hours; (8) surveillance of colonization was conducted; (9) improved lung physiotherapy (on the basis of the original lung physiotherapy, delirium score was assessed to guide early mobilization of the patients; airway drainage was enhanced, the degree of airway humidification was adjusted according to the sputum properties, achieving sputum viscosity grade II; lung ultrasound was also used for lung assessment, and patients with atelectasis were placed in high lateral position and received the lung recruitment maneuver). Baseline patient information were collected, including gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, pathogens and drug therapy. The primary outcome was 28-day mortality, and the secondary outcomes were duration of mechanical ventilation, length of ICU stay, and ICU mortality. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in older immunosuppressed patients with pneumonia and sepsis. RESULTS: Finally, 550 patients were enrolled, including 199 patients in the original nursing strategy group and 351 patients in the improved nursing strategy group. No significant differences were found in gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, coexisting pathogens or drug therapy between the two groups. Compared with patients in the original nursing strategy group, those in the improved nursing strategy group had significantly fewer duration of mechanical ventilation and length of ICU stay [duration of mechanical ventilation (days): 5 (4, 7) vs. 5 (4, 9), length of ICU stay (days): 11 (6, 17) vs. 12 (6, 23), both P < 0.01], and lower ICU mortality and 28-day mortality [ICU mortality: 23.9% (84/351) vs. 32.7% (65/199), 28-day mortality: 23.1% (81/351) vs. 33.7% (67/199), both P < 0.05]. Multivariate Logistic regression analysis showed that the improved nursing strategy acted as an independent protective factor in 28-day death of older immunosuppressed patients with pneumonia and sepsis [odds ratio (OR) = 0.543, 95% confidence interval (95%CI) was 0.334-0.885, P = 0.014]. CONCLUSIONS: Improved nursing strategy shortened the duration of mechanical ventilation and the length of ICU stay, and decreased ICU mortality and 28-day mortality in older immunosuppressed patients with pneumonia and sepsis, significantly improving the short-term prognosis of such patients.

Multisite Metagenomic Next-Generation Sequencing Improved Diagnostic Performance for Sepsis-Associated Lymphopenia Patients.

A precise and efficient microbiological diagnosis is essential for sepsis. Metagenomic next-generation sequencing (mNGS) is a novel technique for the diagnosis of infectious diseases, but its current application in multisite sampling and interpretation remains controversial. Therefore, this study was undertaken to evaluate the reliability of multisite mNGS tests and the efficiency of plasma mNGS based on lymphocyte subset counts. A prospective observational study was performed on the intubated patients with sepsis-associated lymphopenia from January 2020 to February 2022. During the study period, data on 71 patients with sepsis-induced lymphopenia were collected. Among the 125 mNGS tests, 95 were positive for pathogens, whereas of the 166 conventional microbiological tests (CMTs), 91 were positive. The comparison showed that 38 patients (53.5%) had at least one matched pair of plasma mNGS and CMT results, while for multisite sampling, 47 patients (66.2%) had at least one. Lymphocyte subset analysis showed that T lymphocyte (577 ± 317 versus 395 ± 207, P = 0.005) and CD4+ T lymphocyte (333 ± 199 versus 230 ± 120, P = 0.009) counts were lower in the matched group. According to receiver operating characteristic (ROC) analysis, a CD4+ T lymphocyte count lower than 266 cells/mm3 was predictive of a match result. For sepsis-associated lymphopenia patients, we found that multisite mNGS tests showed a higher positivity rate. With plasma mNGS, a lower CD4+ T lymphocyte count predicted a better match result with CMT. The lymphocyte subset analysis may promote the clinical interpretation of mNGS results. IMPORTANCE This study was undertaken to evaluate the reliability of pathogenic diagnoses based on multisite mNGS detection at the clinically suspected sites and to analyze the efficiency of plasma mNGS detection based on lymphocyte subset counts in patients with sepsis-associated lymphopenia.

Exploring dynamic change in arterial base excess with patient outcome and lactate clearance in the intensive care unit by hierarchical time-series clustering.

Background: Hyperlactatemia is common in the intensive care unit (ICU) and relevant to prognosis, while the process of lactate normalization requires a relatively long period. We hypothesized that the dynamic change in base excess (BE) would be associated with ICU mortality and lactate clearance. Methods: We performed a retrospective cohort study of adult patients with hyperlactatemia admitted to the ICU from 2016 to 2021. The patients were divided into two groups according to whether the peak BE in 12 h was reached in the first 6 h. We compared ICU mortality and lactate clearance at 6 and 12 h after ICU admission. Results: During the study period, 1,608 patients were admitted to the ICU with a lactate concentration of >2.0 mmol/L and stayed in the ICU for >24 h. The mortality rate was 11.2%. The patients were divided into two groups according to whether the peak BE was reached in the first 6 h following ICU admission: Peak BE12h ≤ 6h and Peak BE12h > 6h. The patients were also recorded as whether bicarbonate treatment was received (bicarbonate group, CRRT included) or not (non-bicarbonate group). Furthermore, lactic acid clearance patterns were identified by time-series clustering (TSC) using various algorithms and distance measures. We compared ICU mortality and lactate clearance at 6 and 12 h after ICU admission with logistic regression. After adjustment for other confounding factors, we found that Peak BE12h > 6h was independently associated with ICU mortality with an odds ratio of 2.231 (p = 0.036) in the bicarbonate group and 2.359 (p < 0.005) in the non-bicarbonate group. In addition, based on the definition of >10% lactate clearance at 6 h or >30% at 12 h, we found that Peak BE12h ≤ 6h had 85.2% sensitivity and 38.1% specificity for effective lactate clearance. In time-series clustering analysis, four categories were discriminated, and pattern of lactic acid clearance reveals the early prognostic value of BE in clearance of lactic acid. Conclusion: A prolonged time to reaching the peak BE was independently associated with ICU mortality. In patients with hyperlactatemia, Peak BE12h ≤ 6h could be used as an indicator to predict effective lactate clearance.

Nonlinear optical properties and photoexcited carrier dynamics of MnPS3 nanosheets.

Here, we systematically report on the preparation of high-quality few-layered MnPS3 nanosheets (NSs) by chemical vapor transport (CVT) and mechanical stripping method, and its carrier dynamics and third-order nonlinear optical properties were studied. Using the classical technique of open aperture Z-scan, a typical phenomenon of saturable absorption (SA) was observed at 475 nm, which indicates that the material is expected to be used as a saturable absorber in ultrafast lasers. The typical phenomenon of reverse saturation absorption (RSA) is observed at 800 and 1550 nm, which shows its potential in the field of broadband optical limiting. Compared with graphene, BP, MXene, MoS2 and other typical two-dimensional materials, MnPS3 NSs has a higher modulation depth. Using the non-degenerate transient absorption spectroscopy technology at room temperature, a slower cooling process of thermal carrier of MnPS3 was observed. Moreover, the carrier lifetime can be tuned according to the wavelength. This work is of great significance to the improvement of MnPS3 based devices, and lays a foundation for the application of MnPS3 in short-wavelength photovoltaic cell, photoelectric detection and other fields.

Early alteration of peripheral blood lymphocyte subsets as a risk factor for delirium in critically ill patients after cardiac surgery: A prospective observational study.

Objective: There is a high incidence of delirium among patients with organ dysfunction undergoing cardiac surgery who need critical care. This study aimed to explore the risk factors for delirium in critically ill patients undergoing cardiac surgery and the predictive value of related risk factors. Methods: We conducted a prospective observational study on adult critically ill patients who underwent cardiac surgery between January 2019 and August 2021. Patients were consecutively assigned to delirium and non-delirium groups. Univariate analysis and multivariate logistic analysis were used to determine the risk factors for delirium. Receiver operating characteristic curves and a nomogram were used to identify the predictive value of related risk factors. Results: Delirium developed in 242 of 379 (63.9%) participants. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were 14.2 ± 5.6 and 18 ± 8.4, respectively. Patients with delirium had longer cardiopulmonary bypass time (149.6 ± 59.1 vs. 126.7 ± 48.5 min, p < 0.001) and aortic cross-clamp time (98.7 ± 51.5 vs. 86.1 ± 41.6 min, p = 0.010) compared with the non-delirium group. The area under the curve was 0.824 for CD4+ T cell count and 0.862 for CD4/CD8 ratio. Multivariate analysis demonstrated that age [odds ratio (OR) 1.030, p = 0.038], duration of physical restraint (OR 1.030, p < 0.001), interleukin-6 (OR 1.001, p = 0.025), CD19+ B cell count (OR 0.996, p = 0.016), CD4+ T cell count (OR 1.005, p < 0.001) and CD4/CD8 ratio (OR 5.314, p < 0.001) were independent risk factors for delirium. A nomogram revealed that age, cardiopulmonary bypass duration, CD4+ T cell count and CD4/CD8 ratio were independent predictors of delirium. Conclusion: Age, duration of physical restraint, CD4+ T cell count and CD4/CD8 ratio were reliable factors for predicting delirium in critically ill patients after cardiac surgery. The receiver operating characteristic curves and nomogram suggested a potential role for CD4+ T cells in mediating potential neuroinflammation of delirium.

Development and Validation of a Risk Score for Predicting Invasive Candidiasis in Intensive Care Unit Patients by Incorporating Clinical Risk Factors and Lymphocyte Subtyping.

Objective: To develop and validate a rapid invasive candidiasis (IC)-predictive risk score in intensive care unit (ICU) patients by incorporating clinical risk factors and parameters of lymphocyte subtyping. Methods: A prospective cohort study of 1054 consecutive patients admitted to ICU was performed. We assessed the clinical characteristics and parameters of lymphocyte subtyping at the onset of clinical signs of infection and their potential influence on IC diagnosis. A risk score for early diagnosis of IC was developed and validated based on a logistic regression model. Results: Sixty-nine patients (6.5%) had IC. Patients in the cohort (N=1054) were randomly divided into a development (n=703) or validation (n=351) cohorts. Multivariate logistic regression identified that CD8+ T-cell count ≤143 cells/mm3, receipt of high-dose corticosteroids (dose ≥50 mg prednisolone equivalent), receipt of carbapenem/tigecycline, APACHE II score≥15, (1,3)-ß-D-glucan (BDG) positivity and emergency gastrointestinal/hepatobiliary (GIT/HPB) surgery were significantly related with IC. IC risk score was calculated using the following formula: CD8+ T-cell count ≤143 cells/mm3 + receipt of high-dose corticosteroids + receipt of carbapenem/tigecycline + APACHE II score ≥15 + BDG positivity + emergency GIT/HPB surgery ×2. The risk scoring system had good discrimination and calibration with area under the receiver operating characteristic (AUROC) curve of 0.820 and 0.807, and a non-significant Hosmer-Lemeshow test P=0.356 and P=0.531 in the development and validation cohorts, respectively. We categorized patients into three groups according to risk score: low risk (0-2 points), moderate risk (3-4 points) and high risk (5-7 points). IC risk was highly and positively associated with risk score (Pearson contingency coefficient=0.852, P for trend=0.007). Candida score had a moderate predicting efficacy for early IC diagnosis. The AUROC of the risk score was significantly larger than that of Candida score (0.820 versus 0.711, Z=2.013, P=0.044). Conclusions: The predictive scoring system, which used both clinical factors and CD8+ T cell count, served as a clinically useful predictive model for rapid IC diagnosis in this cohort of ICU patients. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR-ROC-17010750.

Role of Intensified Lung Physiotherapy Bundle on the Occurrence of Pneumonia After Cardiac Surgery.

Objective: The role of intensified lung physiotherapy bundle after cardiac surgery was investigated. Methods: A before- and after-surgery comparison was conducted between the study from January 1, 2018 to December 31, 2019 (control group), when traditional lung physiotherapy bundle was used, and from January 1, 2020 to May 1, 2021 (study group), when the intensified bundle was used. The baseline data, clinical features, incidence of postoperative pneumonia, and prognoses of all the enrolled cardiac surgery patients were analyzed. Results: In accordance with the study criteria, 358 patients were enrolled. The incidence rate of postoperative pneumonia was significantly lower in the study group than in the control group (14.2 vs. 22.7%, P = 0.037), as was in-hospital mortality (1.5 vs. 5.2%, P = 0.043). Patients receiving the intensified lung physiotherapy bundle had much shorter mechanical ventilation time (92 vs. 144 h, P < 0.0001), much shorter intensive care unit (ICU) stay (5 vs. 7 days, P < 0.001), and much shorter hospital stay (17 vs. 18.5 days, P = 0.022). The intensified lung physiotherapy bundle was an independent protective factor enabling the reduced occurrence of pneumonia (P = 0.007). On univariate analysis, this bundle significantly improved in-hospital mortality (P = 0.043). Conclusions: Our intensified lung physiotherapy bundle potentially reduces the rate of postoperative pneumonia after cardiac surgery. This bundle might also be adopted as a suitable reference guide for the prevention of other postoperative pulmonary complications.

Metagenomic Next-Generation Sequencing for the Microbiological Diagnosis of Abdominal Sepsis Patients.

OBJECTIVES: For patients with intra-abdominal infection (IAI), the rapid and accurate identification of pathogens remains a challenge. Metagenomic next-generation sequencing (mNGS) is a novel technique for infectious diseases, but its application in IAI is limited. In this study, we compared the microbiological diagnostic ability of plasma mNGS with that of conventional peritoneal drainage (PD) culture in critical care settings. METHODS: From January 2018 to December 2020, a prospective observational study was performed at a tertiary teaching hospital in China and data on 109 abdominal sepsis patients were collected. The pathogen detection performance of plasma mNGS and PD culture method were compared. MEASUREMENTS AND RESULTS: Ninety-two positive cases detected on PD culture, while plasma mNGS detected 61 positive cases. Forty-five patients (44.0%) had at least one matched pair of plasma mNGS and PD culture results. Compared with PD culture, the plasma mNGS was more rapid (27.1 ± 4.0 vs. 68.9 ± 22.3 h, p < 0.05). The patients received initial antibiotic treatment matched with mNGS detection showed better clinical outcomes. CONCLUSION: For abdominal sepsis patients, plasma mNGS can provide early, noninvasive, and rapid microbiological diagnosis. Compared with conventional PD smear, culture, and blood culture methods, plasma mNGS promote the rapid detection of pathogenic bacteria.

Early Alterations of Lymphocyte Subsets in Acute Respiratory Distress Syndrome Caused by Acinetobacter baumannii Pneumonia: A Prospective Observational Study.

Background: To prospectively observe the early alterations of lymphocyte subsets in ARDS caused by Acinetobacter baumannii. Methods: ARDS patients admitted to our ICU between January 1, 2017 and May 30, 2020 were selected. We enrolled all the pulmonary ARDS caused by Acinetobacter baumannii pneumonia who required mechanical ventilation or vasopressors. All the available clinical data, follow up information and lymphocyte subsets were recorded. Results: Eighty-seven of all the 576 ARDS patients were enrolled. The 28-day mortality of the enrolled patients was 20.7% (18/87). The T lymphocyte count (452 vs. 729 cells/ul, P = 0.004), especially the CD8+ T lymphocyte count (104 vs. 253 cells/ul, P = 0.002) was significantly lower in non-survivors, as were counts of the activated T cell subsets (CD8+CD28+ and CD8+CD38+). The CD8+ T cell count was an independent risk factor for 28-day mortality, and a cutoff value of 123 cells/ul was a good indicator to predict the prognosis of ARDS caused by Acinetobacter baumannii pneumonia, with sensitivity of 74.6% and specificity of 83.3% (AUC 0.812, P < 0.0001). Conclusions: Lower CD8+ T cell count was associated with higher severity and early mortality in ARDS patients caused by Acinetobacter baumannii pneumonia, which could be valuable for outcome prediction.

Early Prediction of Mortality, Severity, and Length of Stay in the Intensive Care Unit of Sepsis Patients Based on Sepsis 3.0 by Machine Learning Models.

Background: Early prediction of the clinical outcome of patients with sepsis is of great significance and can guide treatment and reduce the mortality of patients. However, it is clinically difficult for clinicians. Methods: A total of 2,224 patients with sepsis were involved over a 3-year period (2016-2018) in the intensive care unit (ICU) of Peking Union Medical College Hospital. With all the key medical data from the first 6 h in the ICU, three machine learning models, logistic regression, random forest, and XGBoost, were used to predict mortality, severity (sepsis/septic shock), and length of ICU stay (LOS) (>6 days, ≤ 6 days). Missing data imputation and oversampling were completed on the dataset before introduction into the models. Results: Compared to the mortality and LOS predictions, the severity prediction achieved the best classification results, based on the area under the operating receiver characteristics (AUC), with the random forest classifier (sensitivity = 0.65, specificity = 0.73, F1 score = 0.72, AUC = 0.79). The random forest model also showed the best overall performance (mortality prediction: sensitivity = 0.50, specificity = 0.84, F1 score = 0.66, AUC = 0.74; LOS prediction: sensitivity = 0.79, specificity = 0.66, F1 score = 0.69, AUC = 0.76) among the three models. The predictive ability of the SOFA score itself was inferior to that of the above three models. Conclusions: Using the random forest classifier in the first 6 h of ICU admission can provide a comprehensive early warning of sepsis, which will contribute to the formulation and management of clinical decisions and the allocation and management of resources.

A Clinical Prediction Model to Predict Heparin Treatment Outcomes and Provide Dosage Recommendations: Development and Validation Study.

BACKGROUND: Unfractionated heparin is widely used in the intensive care unit as an anticoagulant. However, weight-based heparin dosing has been shown to be suboptimal and may place patients at unnecessary risk during their intensive care unit stay. OBJECTIVE: In this study, we intended to develop and validate a machine learning-based model to predict heparin treatment outcomes and to provide dosage recommendations to clinicians. METHODS: A shallow neural network model was adopted in a retrospective cohort of patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database and patients admitted to the Peking Union Medical College Hospital (PUMCH). We modeled the subtherapeutic, normal, and supratherapeutic activated partial thromboplastin time (aPTT) as the outcomes of heparin treatment and used a group of clinical features for modeling. Our model classifies patients into 3 different therapeutic states. We tested the prediction ability of our model and evaluated its performance by using accuracy, the kappa coefficient, precision, recall, and the F1 score. Furthermore, a dosage recommendation module was designed and evaluated for clinical decision support. RESULTS: A total of 3607 patients selected from MIMIC III and 1549 patients admitted to the PUMCH who met our criteria were included in this study. The shallow neural network model showed results of F1 scores 0.887 (MIMIC III) and 0.925 (PUMCH). When compared with the actual dosage prescribed, our model recommended increasing the dosage for 72.2% (MIMIC III, 1240/1718) and 64.7% (PUMCH, 281/434) of the subtherapeutic patients and decreasing the dosage for 80.9% (MIMIC III, 504/623) and 76.7% (PUMCH, 277/361) of the supratherapeutic patients, suggesting that the recommendations can contribute to clinical improvements and that they may effectively reduce the time to optimal dosage in the clinical setting. CONCLUSIONS: The evaluation of our model for predicting heparin treatment outcomes demonstrated that the developed model is potentially applicable for reducing the misdosage of heparin and for providing appropriate decision recommendations to clinicians.

Noninvasive Real-Time Mortality Prediction in Intensive Care Units Based on Gradient Boosting Method: Model Development and Validation Study.

BACKGROUND: Monitoring critically ill patients in intensive care units (ICUs) in real time is vitally important. Although scoring systems are most often used in risk prediction of mortality, they are usually not highly precise, and the clinical data are often simply weighted. This method is inefficient and time-consuming in the clinical setting. OBJECTIVE: The objective of this study was to integrate all medical data and noninvasively predict the real-time mortality of ICU patients using a gradient boosting method. Specifically, our goal was to predict mortality using a noninvasive method to minimize the discomfort to patients. METHODS: In this study, we established five models to predict mortality in real time based on different features. According to the monitoring, laboratory, and scoring data, we constructed the feature engineering. The five real-time mortality prediction models were RMM (based on monitoring features), RMA (based on monitoring features and the Acute Physiology and Chronic Health Evaluation [APACHE]), RMS (based on monitoring features and Sequential Organ Failure Assessment [SOFA]), RMML (based on monitoring and laboratory features), and RM (based on all monitoring, laboratory, and scoring features). All models were built using LightGBM and tested with XGBoost. We then compared the performance of all models, with particular focus on the noninvasive method, the RMM model. RESULTS: After extensive experiments, the area under the curve of the RMM model was 0.8264, which was superior to that of the RMA and RMS models. Therefore, predicting mortality using the noninvasive method was both efficient and practical, as it eliminated the need for extra physical interventions on patients, such as the drawing of blood. In addition, we explored the top nine features relevant to real-time mortality prediction: invasive mean blood pressure, heart rate, invasive systolic blood pressure, oxygen concentration, oxygen saturation, balance of input and output, total input, invasive diastolic blood pressure, and noninvasive mean blood pressure. These nine features should be given more focus in routine clinical practice. CONCLUSIONS: The results of this study may be helpful in real-time mortality prediction in patients in the ICU, especially the noninvasive method. It is efficient and favorable to patients, which offers a strong practical significance.

Stepwise lactate kinetics in critically ill patients: prognostic, influencing factors, and clinical phenotype.

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

The effects of UCP2 on autophagy through the AMPK signaling pathway in septic cardiomyopathy and the underlying mechanism.

BACKGROUND: Mitochondrial dysfunction plays an important role in the development of septic cardiomyopathy. This study aimed to reveal the protective role of uncoupling protein 2 (UCP2) in mitochondria through AMP-activated protein kinase (AMPK) on autophagy during septic cardiomyopathy. METHODS: UCP2 knockout mice via a cecal ligation and puncture (CLP) model and the H9C2 cardiomyocyte cell line in response to lipopolysaccharide (LPS) in vitro were used to study the effect. The myocardial morphological alterations, indicators of mitochondrial injury and levels of autophagy-associated proteins (pAMPK, pmTOR, pULK1, pTSC2, Beclin-1, and LC3-I/II) were assessed. In addition, the mechanism of the interaction between UCP2 and AMPK was further studied through gain- and loss-of-function studies. RESULTS: Compared with the wild-type mice, the UCP2 knockout mice exhibited more severe cardiomyocyte injury after CLP, and the AMPK agonist AICAR protected against such injury. Consistent with this result, silencing UCP2 augmented the LPS-induced pathological damage and mitochondrial injury in the H9C2 cells, limited the upregulation of autophagy proteins and reduced AMPK phosphorylation. AICAR protected the cells from morphological changes and mitochondrial membrane potential loss and promoted autophagy. The silencing and overexpression of UCP2 led to correlated changes in the AMPK upstream kinases pLKB1 and CAMKK2. CONCLUSIONS: UCP2 exerts cardioprotective effects on mitochondrial dysfunction during sepsis via the action of AMPK on autophagy.

Plasma mitochondrial DNA levels are associated with acute lung injury and mortality in septic patients.

BACKGROUND: Mitochondrial DNA (mtDNA) is a critical activator of inflammation. Circulating mtDNA released causes lung injury in experimental models. We hypothesized that elevated plasma mtDNA levels are associated with acute lung injury (ALI) in septic patients. METHODS: We enrolled 66 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between January 2019 and October 2019. Respiratory, hemodynamic and bedside echocardiographic parameters were recorded. Plasma mtDNA, procalcitonin, interleukin 6, and interleukin 8 levels were examined. RESULTS: Plasma mtDNA levels within 24 h after admission were significantly increased in the group of septic patients with ALI [5.01 (3.38-6.64) vs 4.13 (3.20-5.07) log copies/µL, p 0.0172]. mtDNA levels were independently associated with mortality (hazard ratio, 3.2052; 95% CI 1.1608-8.8500; p 0.0253) and ALI risk (odds ratio 2.7506; 95% CI 1.1647-6.4959; p 0.0210). Patients with high mtDNA levels had worse outcomes, and post hoc tests showed significant differences in 28-day survival rates. Increased mtDNA levels were seen in patients with abdominal infection. CONCLUSIONS: Increased plasma mtDNA levels within 24 h after admission were significantly associated with ALI incidence and mortality in septic patients.

Fluctuations of driving pressure during mechanical ventilation indicates elevated central venous pressure and poor outcomes.

Inappropriate mechanical ventilation may induce hemodynamic alterations through cardiopulmonary interactions. The aim of this study was to explore the relationship between airway pressure and central venous pressure during the first 72 h of mechanical ventilation and its relevance to patient outcomes. We conducted a retrospective study of the Department of Critical Care Medicine of Peking Union Medical College Hospital and a secondary analysis of the MIMIC-III clinical database. The relationship between the ranges of driving pressure and central venous pressure during the first 72 h and their associations with prognosis were investigated. Data from 2790 patients were analyzed. Wide range of driving airway pressure (odds ratio, 1.0681; 95% CI, 1.0415-1.0953; p < 0.0001) were independently associated with mortality, ventilator-free time, intensive care unit and hospital length of stay. Furthermore, wide range of driving pressure and elevated central venous pressure exhibited a close correlation. The area under receiver operating characteristic demonstrated that range of driving pressure and central venous pressure were measured at 0.689 (95% CI, 0.670-0.707) and 0.681 (95% CI, 0.662-0.699), respectively. Patients with high ranges of driving pressure and elevated central venous pressure had worse outcomes. Post hoc tests showed significant differences in 28-day survival rates (log-rank (Mantel-Cox), 184.7; p < 0.001). In conclusion, during the first 72 h of mechanical ventilation, patients with hypoxia with fluctuating driving airway pressure have elevated central venous pressure and worse outcomes.

Evaluation of the updated "Candida score" with Sepsis 3.0 criteria in critically ill patients.

BACKGROUND: The Candida score proposed in 2009 was calculated on the definition of "severe sepsis", which was removed in the Sepsis 3.0 definition. This study investigated the clinical relevance of Candida score with the updated Sepsis 3.0 definition (CS-3.0) instead of severe sepsis (CS-2009) in the new admitted critically ill patients. METHODS: We performed a retrospective analysis on a single center public database. All patients with ICU stay ≥72 hours were included in this study. The Candida score was calculated based on the data collected on ICU admission. The incidence of invasive candidiasis was determined and its relationship with the CS-2009 and CS-3.0 was studied. RESULTS: A total of 17,666 patients were identified after screening 58,976 hospital admissions, and 436 cases (2.5%) were diagnosed with invasive candidiasis. In the infection group, the number of patients who met the Sepsis 3.0 criteria was greater than the number of patients with severe sepsis (81.2% vs. 78.4%, P<0.005). The area under curve of the CS-2009 was 0.789 (95% CI: 0.765-0.813) and the CS-3.0 was 0.804 (95% CI: 0.782-0.827). CONCLUSIONS: Our study confirmed the clinical relevance and comparative superiority of the updated Candida score model, using the Sepsis 3.0 definition, compared with the classic sepsis/severe sepsis model, in assessment of critically ill patients. Considering the clinical importance of organ dysfunction in ICI, the Sepsis 3.0 should be used as the basis for prediction of invasive candidiasis.

Pulmonary hypertension with adult respiratory distress syndrome: prevalence, clinical impact, and association with central venous pressure.

Pulmonary hypertension (PH) occurs in patients with acute respiratory distress syndrome (ARDS); the most severe form comprises acute cor pulmonale (ACP). Here, we investigated the prevalence of PH in patients with ARDS to evaluate its correlation with ACP risk, ARDS severity and central venous pressure (CVP). We conducted a secondary analysis using data from the MIMIC-III open-source clinical database. The prevalence of PH associated with new-onset ARDS during the first 72 h after intensive care unit admission was investigated; moreover, the association between ACP risk score and PH was validated. We also evaluated the association between elevated CVP (mean CVP > 10 mmHg) and PH and other clinical outcomes. Among 2434 patients who met the ARDS Berlin criteria and underwent echocardiography or pulmonary artery catheterization evaluation, a total of 583 (24.0%) patients were diagnosed with moderate or severe PH, of which 418 had low and 165 had high ACP risk. After adjustment for disease/ARDS severity, ACP risk score, and other demographic variables, elevated CVP was independently associated with the occurrence of PH (odds ratio, 2.239 (1.674, 2.993), p < 0.005). Among patients with PH, higher mean CVP was associated with prolonged hospital stay (13.4 vs. 15.2 days, p = 0.041) and duration of ventilation (116.5 vs. 150.5 h, p = 0.023). Incidence of PH was 24.0% in patients with new-onset ARDS in this retrospective study. Elevated CVP is relevant with higher incidence of PH and worse clinical outcome; these highlighted the importance of hemodynamic monitoring in the management of ARDS.