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Abstract Background No reliable clinical tools exist to predict acute kidney injury (AKI) progression. We aim to explore a scoring system for predicting the composite outcome of progression to severe AKI or death within seven days among early AKI patients after cardiac surgery. Methods In this study, we used two independent cohorts, and patients who experienced mild/moderate AKI within 48 h after cardiac surgery were enrolled. Eventually, 3188 patients from the MIMIC-IV database were used as the derivation cohort, while 499 patients from the Zhongshan cohort were used as external validation. The primary outcome was defined by the composite outcome of progression to severe AKI or death within seven days after enrollment. The variables identified by LASSO regression analysis were entered into logistic regression models and were used to construct the risk score. Results The composite outcome accounted for 3.7% (n = 119) and 7.6% (n = 38) of the derivation and validation cohorts, respectively. Six predictors were assembled into a risk score (AKI-Pro score), including female, baseline eGFR, aortic surgery, modified furosemide responsiveness index (mFRI), SOFA, and AKI stage. And we stratified the risk score into four groups: low, moderate, high, and very high risk. The risk score displayed satisfied predictive discrimination and calibration in the derivation and validation cohort. The AKI-Pro score discriminated the composite outcome better than CRATE score, Cleveland score, AKICS score, Simplified renal index, and SRI risk score (all P

Abstract Background Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. Methods Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. Results Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p

Abstract Background Patients receiving surgical treatment of acute type A Aortic Dissection (aTAAD) are common to suffer organ dysfunction in the intensive care unit due to overwhelming inflammation. Previous studies have revealed that glucocorticoids may reduce complications in certain patient groups, but evidence between postoperative glucocorticoids administration and improvement in organ dysfunction after aTAAD surgery are lacking. Methods This study will be an investigator-initiated, prospective, single-blind, randomized, single-center study. Subjects with confirmed diagnosis of aTAAD undergoing surgical treatment will be enrolled and 1:1 randomly assigned to receive either glucocorticoids or normal treatment. All patients in the glucocorticoids group will be given methylprednisolone intravenously for 3 days after enrollment. The primary endpoint will be the amplitude of variation of Sequential Organ Failure Assessment score on post-operative day 4 compared to baseline. Discussion The trial will explore the rationale for postoperative application of glucocorticoids in patients after aTAAD surgery. Trial registration This study has been registered on ClinicalTrials.gov (NCT04734418).

Abstract Background Sepsis is an abnormal immune response after infection, wherein the lung is the most susceptible organ to fail, leading to acute lung injury. To overcome the limitations of current therapeutic strategies and develop more specific treatment, the inflammatory process, in which T cell-derived extracellular vesicles (EVs) play a central role, should be explored deeply. Methods Liquid chromatography–tandem mass spectrometry was performed for serum EV protein profiling. The serum diacylglycerol kinase kappa (DGKK) and endotoxin contents of patients with sepsis-induced lung injury were measured. Apoptosis, oxidative stress, and inflammation in A549 cells, bronchoalveolar lavage fluid, and lung tissues of mice were measured by flow cytometry, biochemical analysis, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and western blot. Results DGKK, the key regulator of the diacylglycerol (DAG)/protein kinase C (PKC) pathway, exhibited elevated expression in serum EVs of patients with sepsis-induced lung injury and showed strong correlation with sepsis severity and disease progression. DGKK was expressed in CD4+ T cells under regulation of the NF-κB pathway and delivered by EVs to target cells, including alveolar epithelial cells. EVs produced by CD4+ T lymphocytes exerted toxic effects on A549 cells to induce apoptotic cell death, oxidative cell damage, and inflammation. In mice with sepsis induced by cecal ligation and puncture, EVs derived from CD4+ T cells also promoted tissue damage, oxidative stress, and inflammation in the lungs. These toxic effects of T cell-derived EVs were attenuated by the inhibition of PKC and NOX4, the downstream effectors of DGKK and DAG. Conclusions This approach established the mechanism that T-cell-derived EVs carrying DGKK triggered alveolar epithelial cell apoptosis, oxidative stress, inflammation, and tissue damage in sepsis-induced lung injury through the DAG/PKC/NOX4 pathway. Thus, T-cell-derived EVs and the elevated distribution of DGKK should be further investigated to develop therapeutic strategies for sepsis-induced lung injury.

Abstract Purpose This national study aimed to investigate the lung ultrasound (LUS) training and practice of respiratory therapists (RTs) in mainland China. Methods A cross-sectional multicenter survey was conducted from May 22, 2021 to August 12, 2021, through online platforms. This survey included RTs in mainland China. The survey was divided into four sections: (1) demographic characteristics and basic information; (2) basic information about LUS training and practice; (3) LUS practice details; and (4) Other ultrasound training and practice. Results A total of 514 responses were received, and 494 valid responses were included in the analysis. 81.2% (401/494) participants’ highest degree of education was a bachelor’s degree, and 43.1% (213/494) participants were at level II in terms of job ranking. 99.2%(490/494) participants agreed that the RTs needed to learn lung ultrasound, but only 12.3% (61/494) participants had received a LUS training course. Further, 66.2% (327/494) experienced participants responded to Sect. 3. Most of RTs used LUS when the patient had hypoxia (265/327, 81%) or dyspnea (260/317, 79.5%); they also used it during spontaneous breathing trial(SBT) (191/327, 58.4%) or in prone position (177/327, 54.1%). The A-line (302/327, 92.4%), B-line (299/327, 91.4%), lung slide (263/327, 80.4%), and bat sign (259/327, 79.2%) were well known as LUS signs. Also, 30.6% (100/327) participants did not use the LUS protocol in their clinical practice, and only 25.4%(83/327) participants said they had used LUS scores. Moreover, 55.7% (182/327) participants frequently changed the respiratory therapy strategy according to LUS results. Conclusions We should improve the number and workplace of RTs in mainland China in the future. We should also standardize the application of LUS practice and training for RTs in mainland China and establish corresponding certification pathways.

Abstract Background Noninvasive ventilation (NIV) has been widely used in critically ill patients after extubation. However, NIV failure is associated with poor outcomes. This study aimed to determine early predictors of NIV failure and to construct an accurate machine-learning model to identify patients at risks of NIV failure after extubation in intensive care units (ICUs). Methods Patients who underwent NIV after extubation in the eICU Collaborative Research Database (eICU-CRD) were included. NIV failure was defined as need for invasive ventilatory support (reintubation or tracheotomy) or death after NIV initiation. A total of 93 clinical and laboratory variables were assessed, and the recursive feature elimination algorithm was used to select key features. Hyperparameter optimization was conducted with an automated machine-learning toolkit called Neural Network Intelligence. A machine-learning model called Categorical Boosting (CatBoost) was developed and compared with nine other models. The model was then prospectively validated among patients enrolled in the Cardiac Surgical ICU of Zhongshan Hospital, Fudan University. Results Of 929 patients included in the eICU-CRD cohort, 248 (26.7%) had NIV failure. The time from extubation to NIV, age, Glasgow Coma Scale (GCS) score, heart rate, respiratory rate, mean blood pressure (MBP), saturation of pulse oxygen (SpO2), temperature, glucose, pH, pressure of oxygen in blood (PaO2), urine output, input volume, ventilation duration, and mean airway pressure were selected. After hyperparameter optimization, our model showed the greatest accuracy in predicting NIV failure (AUROC: 0.872 [95% CI 0.82–0.92]) among all predictive methods in an internal validation. In the prospective validation cohort, our model was also superior (AUROC: 0.846 [95% CI 0.80–0.89]). The sensitivity and specificity in the prediction group is 89% and 75%, while in the validation group they are 90% and 70%. MV duration and respiratory rate were the most important features. Additionally, we developed a web-based tool to help clinicians use our model. Conclusions This study developed and prospectively validated the CatBoost model, which can be used to identify patients who are at risk of NIV failure. Thus, those patients might benefit from early triage and more intensive monitoring. Trial registration: NCT03704324. Registered 1 September 2018, https://register.clinicaltrials.gov .

Abstract Aims Recombinant human brain natriuretic peptide (rh‐BNP) is commonly used as a decongestive therapy. This study aimed to investigate the instant effects of rh‐BNP on cardiac output and venous return function in post‐cardiotomy patients with congestive heart failure (CHF). Methods and results Twenty‐four post‐cardiotomy heart failure patients were enrolled and received a standard loading dose of rh‐BNP. Haemodynamic monitoring was performed via a pulmonary artery catheter before and after the administration of rh‐BNP. The cardiac output and venous return functions were estimated by depicting Frank‐Starling and Guyton curves. After rh‐BNP infusion, variables reflecting cardiac congestion and venous return function, such as pulmonary artery wedge pressure, mean systemic filling pressure (Pmsf) and venous return resistance index (VRRI), reduced from 15 ± 3 to 13 ± 3 mmHg, from 32 ± 7 to 28 ± 7 mmHg and from 6.7 ± 2.6 to 5.7 ± 1.8 mmHg min m2/L, respectively. Meanwhile, cardiac index, stroke volume index, and the cardiac output function curve remained unchanged per se. The decline in Pmsf [−13% (−22% to −8%)] and VRRI [−12% (−25% to −5%)] was much greater than that in the systemic vascular resistance index [−7% (−14% to 0%)]. In the subgroup analysis of reduced ejection fraction (

Abstract Background Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19. Methods Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3–7 days); Stage 3 (8–14 days); Stage 4 (15–21 days); and Stage 5 (22–31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, − 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders. Results Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (− 3.27% [95% CI, − 5.86 to − 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P

Low left ventricular ejection fraction (LVEF) was always considered a high-risk factor for surgery. A growing number of patients with preoperative low LVEF have undergone cardiac surgery in recent years. The transition of postoperative LVEF and its correlation with short-term outcomes is not yet clear. We retrospectively collected the clinical data of cardiac surgery patients with low preoperative LVEF (≤40%). LVEF measurements were collected preoperatively and at least twice postoperatively. The primary endpoint was the composite endpoint of hospital mortality or length of intensive care unit (ICU) stay ≥7 days. Univariate logistic regression was used to evaluate the association of each indicator with the outcomes, including calculation of the area under the receiver operating characteristic (ROC) curve. A two-piecewise linear regression model was applied to examine the threshold effect of the LVEF on the composite endpoint using a smoothing function. From 1 January to 31 December 2018, a total of 123 patients had low LVEF preoperatively, of whom 35 (28.5%) met the composite endpoint. LVEF was 35% [interquartile range (IQR) 30%–42%] at first measurement and increased to 40% (IQR 35%–45%) at final measurement during their hospitalization. There was a linear relationship between composite endpoint and lowest level of postoperative LVEF. The base e logarithm of odds ratio [Ln(OR)] of composite endpoint decreased with increasing LVEF (OR = 0.83, 95% confidence interval 0.76–0.91, p < 0.01). Most patients with low preoperative LVEF will benefit from cardiac surgery. The lowest measurement of postoperative LVEF can be used to evaluate the short-term outcome of patients after cardiac surgery.

The cardiac function reserve is crucial for the successful weaning of V-A ECMO. During the V-A ECMO weaning phase, the gradual reduction in pump flow converts the blood flow originally driven by the pump to native cardiac output and also transforms afterload (caused by retrograde flow) into ventricular preload, thus introducing a “flow challenge” to the native heart. In this perspective, we propose to use this flow challenge as a test to simulate the preload-to-afterload conversion to assess cardiac functional reserve quantitatively. With this short article we offer the hemodynamic and clinical aspects regarding the flow challenge test.

Abstract Background Evaluation of fluid responsiveness during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support is crucial. The aim of this study was to investigate whether changes in left ventricular outflow tract velocity–time integral (ΔVTI), induced by a Trendelenburg maneuver, could predict fluid responsiveness during VA-ECMO. Methods This prospective study was conducted in patients with VA-ECMO support. The protocol included four sequential steps: (1) baseline-1, a supine position with a 15° upward bed angulation; (2) Trendelenburg maneuver, 15° downward bed angulation; (3) baseline-2, the same position as baseline-1, and (4) fluid challenge, administration of 500 mL gelatin over 15 min without postural change. Hemodynamic parameters were recorded at each step. Fluid responsiveness was defined as ΔVTI of 15% or more, after volume expansion. Results From June 2018 to December 2019, 22 patients with VA-ECMO were included, and a total of 39 measurements were performed. Of these, 22 measurements (56%) met fluid responsiveness. The R 2 of the linear regression was 0.76, between ΔVTIs induced by Trendelenburg maneuver and the fluid challenge. The area under the receiver operating characteristic curve of ΔVTI induced by Trendelenburg maneuver to predict fluid responsiveness was 0.93 [95% confidence interval (CI) 0.81–0.98], with a sensitivity of 82% (95% CI 60–95%), and specificity of 88% (95% CI 64–99%), at a best threshold of 10% (95% CI 6–12%). Conclusions Changes in VTI induced by the Trendelenburg maneuver could effectively predict fluid responsiveness in VA-ECMO patients. Trial registration ClinicalTrials.gov, NCT 03553459 (the TEMPLE study). Registered on May 30, 2018

BackgroundSeptic myocardial depression has been associated with increased morbidity and mortality. miR-885-5p has been shown to regulate cell growth, senescence, and/or apoptosis. Published studies demonstrated that Homeobox-containing protein 1 (HMBOX1) inhibits inflammatory response, regulates cell autophagy, and apoptosis. However, the role of miR-885-5p/HMBOX1 in sepsis and septic myocardial depression and the underlying mechanism is not fully understood.Materials and MethodsExosomes (exos) derived from sepsis patients (sepsis-exos) were isolated using ultracentrifugation. Rats were subjected to cecal ligation and puncture surgery and treated with sepsis-exos. HMBOX1 was knocked down or overexpressed in AC16 cells using lentiviral plasmids carrying short interfering RNAs targeting human HMBOX1 or carrying HMBOX1 cDNA. Cell pyroptosis was measured by flow cytometry. The secretion of IL-1β and IL-18 was examined by ELISA kits. Quantitative polymerase chain reaction (PCR) or western blot was used for gene expression.ResultsSepsis-exos increased the level of miR-885-5p, decreased HMBOX1, elevated IL-1β and IL-18, and promoted pyroptosis in AC16 cells. Septic rats treated with sepsis-exos increased the serum inflammatory cytokines is associated with increased pyroptosis-related proteins of hearts. MiR-885-5p bound to the three prime untranslated regions of HMBOX1 to negatively regulate its expression. Overexpressing HMBOX1 reversed miR-885-5p-induced elevation of inflammatory cytokines and upregulation of NLRP3, caspase-1, and GSDMD-N in AC16 cells. The mechanistic study indicated that the effect of HMBOX1 was NF-κB dependent.ConclusionSepsis-exos promoted the pyroptosis of AC16 cells through miR-885-5p via HMBOX1. The results show the significance of the miR-885-5p/HMBOX1 axis in myocardial cell pyroptosis and provide new directions for the treatment of septic myocardial depression.

Abstract Background The present study aimed at comparing the success rate and safety of proximal versus distal approach for ultrasound (US)-guided axillary vein catheterization (AVC) in cardiac surgery patients susceptible to bleeding. Methods In this single-center randomized controlled trial, cardiac surgery patients susceptible to bleeding and requiring AVC were randomized to either the proximal or distal approach group for US-guided AVC. Patients susceptible to bleeding were defined as those who received oral antiplatelet drugs or anticoagulants for at least 3 days. Success rate, catheterization time, number of attempts, and mechanical complications within 24 h were recorded for each procedure. Results A total of 198 patients underwent randomization: 99 patients each to the proximal and distal groups. The proximal group had the higher first puncture success rate (75.8% vs. 51.5%, p

Background: Hypoperfusion, a common manifestation of many critical illnesses, could lead to abnormalities in body surface thermal distribution. However, the interpretation of thermal images is difficult. Our aim was to assess the mortality risk of critically ill patients at risk of hypoperfusion in a prospective cohort by infrared thermography combined with deep learning methods. Methods: This post-hoc study was based on a cohort at high-risk of hypoperfusion. Patients’ legs were selected as the region of interest. Thermal images and conventional hypoperfusion parameters were collected. Six deep learning models were attempted to derive the risk of mortality (range: 0 to 100%) for each patient. The area under the receiver operating characteristic curve (AUROC) was used to evaluate predictive accuracy. Results: Fifty-five hospital deaths occurred in a cohort consisting of 373 patients. The conventional hypoperfusion (capillary refill time and diastolic blood pressure) and thermal (low temperature area rate and standard deviation) parameters demonstrated similar predictive accuracies for hospital mortality (AUROC 0.73 and 0.77). The deep learning methods, especially the ResNet (18), could further improve the accuracy. The AUROC of ResNet (18) was 0.94 with a sensitivity of 84% and a specificity of 91% when using a cutoff of 36%. ResNet (18) presented a significantly increasing trend in the risk of mortality in patients with normotension (13 [7 to 26]), hypotension (18 [8 to 32]) and shock (28 [14 to 62]). Conclusions: Interpreting infrared thermography with deep learning enables accurate and non-invasive assessment of the severity of patients at risk of hypoperfusion.

Background: Enteral nutrition (EN) is recommended within the first 24–48 h for patients with hemodynamic stability, following admission to an intensive care unit (ICU). However, for patients with approximate stable hemodynamics requiring mechanical circulatory support and vasoactive drugs, the application of early EN remains controversial. We sought to evaluate the tolerance of early EN in patients with cardiogenic shock who required vasoactive drugs and mechanical circulatory support after cardiac surgery.Methods: This single-center, prospective observational study included patients with cardiogenic shock, requiring vasoactive drugs and mechanical circulatory support after cardiac surgery, undergoing EN. The primary endpoint was EN tolerance and secondary endpoints were mortality, length of mechanical ventilation, and length of ICU stay.Results: From February 2019 to December 2020, 59 patients were enrolled, of which 25 (42.37%) developed intolerance within 3 days of starting EN. Patients in the EN intolerant group had a longer median length of mechanical ventilation (380 vs. 128 h, p = 0.006), a longer median ICU stay (20 vs. 11.5 days, p = 0.03), and a higher proportion of bloodstream infections (44 vs. 14.71%, p = 0.018). The median EN calorie levels for all patients in the first 3 days of EN were 4.00, 4.13, and 4.28 kcal/kg/day, respectively. Median protein intake levels of EN in the first 3 days were 0.18, 0.17, and 0.17 g/kg/day, respectively. No significant difference was observed in the median dose of vasoactive drugs between the groups (0.035 vs. 0.05 μg/kg/min, p = 0.306).Conclusions: Patients with cardiogenic shock after cardiac surgery had a high proportion of early EN intolerance, and patients with EN intolerance had a worse prognosis, but no significant correlation was identified between EN tolerance and the dose of vasoactive drugs.

Objective: Primary graft dysfunction (PGD) is the leading cause of early death after heart transplantation. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide temporary mechanical circulatory support and time for functional recovery of the transplanted heart. The purpose of this study was to analyze the timing and prognoses of VA-ECMO in patients with severe PGD after heart transplantation.Methods: A total of 130 patients underwent heart transplantation at the Zhongshan Hospital Affiliated with Fudan University between January 2014 and December 2020. All patients received basiliximab immunoinduction and a classic double vena cava anastomosis orthotopic heart transplantation. Among them, 29 patients (22.3%) developed severe PGD in the early postoperative period. VA-ECMO was performed in patients with difficulty weaning from cardiopulmonary bypass (CPB) or postoperative refractory cardiogenic shock. Patients were divided into two groups according to whether or not they were successfully weaned from VA-ECMO (patients who survived for 48 h after weaning and did not need VA-ECMO assistance again). The perioperative clinical data were recorded, and all patients were followed up until discharge. Early outcomes were compared between groups.Results: A total of 29 patients with VA-ECMO support after heart transplantation were included in this study. The proportion of patients receiving VA-ECMO was 22.3% (29/130). Nineteen patients (65.5%) needed VA-ECMO due to difficulty with weaning from CPB, and 10 patients required VA-ECMO for postoperative cardiogenic shock. Nineteen patients (65.5%) were successfully weaned from VA-ECMO. Overall, in-hospital mortality of VA-ECMO support patients was 55.2%. The main causes of death were ventricular fibrillation (four cases), major bleeding (three cases), infection (four cases), and graft failure (five cases).Conclusion: Despite advances in heart transplantation, severe PGD remains a lethal complication after heart transplantation. At present, the treatment for severe PGD after heart transplantation is a challenge. VA-ECMO provides an effective treatment for severe PGD after heart transplantation, which can promote graft function recovery.

Background: Cardiopulmonary support, as extracorporeal membrane oxygenation (ECMO) or mechanical ventilation (MV), is crucial for ICU patients. However, some of these patients are difficult to wean. Therefore, we aimed to assess the efficacy and safety of levosimendan in facilitating weaning from cardiorespiratory support in this patient population.Methods: We searched for potentially relevant articles in PubMed, Embase, China National Knowledge Infrastructure, Wanfang, and the Cochrane database from inception up to Feb 30, 2021. Studies focusing on weaning data in MV/ECMO adult patients who received levosimendan compared to controls were included. We used the Cochrane risk of bias tool or the Newcastle-Ottawa Quality Assessment Scale to evaluate the study quality. The primary outcome was the weaning rate from MV/ECMO. Secondary outcomes were mortality, duration of MV, and ICU stay. Subgroup analysis, sensitivity analysis, and publication bias were also conducted.Results: Eighteen studies with 2,274 patients were included. The quality of the included studies was low to moderate. Overall, levosimendan effectively improved weaning rates from MV/ECMO [odds ratio (OR) = 2.32; 95%CI, 1.60–3.36; P < 0.00001, I2 = 68%]. Subgroup analyses confirmed the higher successful weaning rates in ventilated patients with low left ventricular ejection fractions (OR = 4.06; 95%CI, 2.16–7.62), patients with ECMO after cardiac surgery (OR = 2.04; 95%CI, 1.25–3.34), and patients with ECMO and cardiogenic shock (OR = 1.98; 95%CI, 1.34–2.91). However, levosimendan showed no beneficial effect on patients with MV weaning difficulty (OR = 2.28; 95%CI, 0.72–7.25). Additionally, no differences were found concerning the secondary outcomes between the groups.Conclusions: Levosimendan therapy significantly increased successful weaning rates in patients with cardiopulmonary support, especially patients with combined cardiac insufficiency. Large-scale, well-designed RCTs will be needed to define the subgroup of patients most likely to benefit from this strategy.

Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.

Acute or chronic kidney disease can cause micronutrient deficiency. Patients with end-stage renal disease, kidney transplantation or on dialysis have reduced circulating levels of folate, an essential B vitamin. However, the molecular mechanism is not well understood. Reabsorption of folate in renal proximal tubules through folate transporters is an important process to prevent urinary loss of folate. The present study investigated the impact of acute kidney injury (AKI) on folate transporter expression and the underlying mechanism. AKI was induced in Sprague-Dawley rats that were subjected to kidney ischemia (45 min)-reperfusion (24 h). Both male and female rats displayed kidney injury and low plasma folate levels compared with sham-operated rats. The plasma folate levels were inversely correlated to plasma creatinine levels. There was a significant increase in neutrophil gelatinase-associated lipocalin (NGAL) and IL-6 mRNA expression in the kidneys of rats with ischemia-reperfusion, indicating kidney injury and increased inflammatory cytokine expression. Ischemia-reperfusion decreased mRNA and protein expression of folate transporters including folate receptor 1 (FOLR1) and reduced folate carrier (RFC); and inhibited transcription factor Sp1/DNA binding activity in the kidneys. Simulated ischemia-reperfusion through hypoxia-reoxygenation or Sp1 siRNA transfection in human proximal tubular cells inhibited folate transporter expression and reduced intracellular folate levels. These results suggest that ischemia-reperfusion injury downregulates renal folate transporter expression and decreases folate uptake by tubular cells, which may contribute to low folate status in AKI. In conclusion, ischemia-reperfusion injury can downregulate Sp1 mediated-folate transporter expression in tubular cells, which may reduce folate reabsorption and lead to low folate status.

Objectives: Acute type A aortic dissection (aTAAD) is usually lethal without emergency surgery. Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in patients with cardiogenic shock following cardiac surgery, VA-ECMO support following aTAAD surgery has not been well-described. Based on our 6-year experience, we aimed to retrospectively analyze risk factors, application and timing of VA-ECMO, and outcomes in aTAAD patients.Methods: In this retrospective, single-center study, we enrolled adult patients who underwent aTAAD surgery from January 2014 to December 2019 and were supported with VA-ECMO. Patients were divided into two groups according to whether or not they were successfully weaned from VA-ECMO. Preoperative, intraoperative and postoperative variables were assessed and analyzed. Outcomes of the patients were followed up until discharge.Results: Twenty-seven patients who received aTAAD surgery with VA-ECMO support were included in the study. Nine patients (33.3%) were successfully weaned from VA-ECMO. The median VA-ECMO support time and length of hospital stay in the successfully weaned group were significantly longer than in the group could not be successfully weaned (192 [111–327] vs. 55 [23–95] h, p < 0.01; 29 [18–40] vs. 4 [3–8] days, p < 0.01). Overall in-hospital mortality was 81.5%. The main causes of death were bleeding (37%), neurological complications (15%), and multiple organ dysfunction syndrome (15%). Preoperative levels of creatine kinase-MB (CK-MB) were lower in patients who were successfully weaned from VA-ECMO than in the failed group (14 [6–30] vs. 55 [28–138] U/L, p < 0.01). Postoperative peak levels of CK-MB, cardiac troponin T, lactate dehydrogenase, and lactate were significantly lower in the successful group than in the failed group.Conclusion: Postoperative VA-ECMO support was rarely used in aTAAD patients. Our study showed that VA-ECMO can be considered as a salvage treatment in aTAAD patients, despite the high rate of complications and mortality.

Background: Extubation failure (EF) can lead to an increased chance of ventilator-associated pneumonia, longer hospital stays, and a higher mortality rate. This study aimed to develop and validate an accurate machine-learning model to predict EF in intensive care units (ICUs).Methods: Patients who underwent extubation in the Medical Information Mart for Intensive Care (MIMIC)-IV database were included. EF was defined as the need for ventilatory support (non-invasive ventilation or reintubation) or death within 48 h following extubation. A machine-learning model called Categorical Boosting (CatBoost) was developed based on 89 clinical and laboratory variables. SHapley Additive exPlanations (SHAP) values were calculated to evaluate feature importance and the recursive feature elimination (RFE) algorithm was used to select key features. Hyperparameter optimization was conducted using an automated machine-learning toolkit (Neural Network Intelligence). The final model was trained based on key features and compared with 10 other models. The model was then prospectively validated in patients enrolled in the Cardiac Surgical ICU of Zhongshan Hospital, Fudan University. In addition, a web-based tool was developed to help clinicians use our model.Results: Of 16,189 patients included in the MIMIC-IV cohort, 2,756 (17.0%) had EF. Nineteen key features were selected using the RFE algorithm, including age, body mass index, stroke, heart rate, respiratory rate, mean arterial pressure, peripheral oxygen saturation, temperature, pH, central venous pressure, tidal volume, positive end-expiratory pressure, mean airway pressure, pressure support ventilation (PSV) level, mechanical ventilation (MV) durations, spontaneous breathing trial success times, urine output, crystalloid amount, and antibiotic types. After hyperparameter optimization, our model had the greatest area under the receiver operating characteristic (AUROC: 0.835) in internal validation. Significant differences in mortality, reintubation rates, and NIV rates were shown between patients with a high predicted risk and those with a low predicted risk. In the prospective validation, the superiority of our model was also observed (AUROC: 0.803). According to the SHAP values, MV duration and PSV level were the most important features for prediction.Conclusions: In conclusion, this study developed and prospectively validated a CatBoost model, which better predicted EF in ICUs than other models.

Abstract Background Three-dimensional color flow Doppler (3DCF) is a new convenient technique for cardiac output (CO) measurement. However, to date, no one has evaluated the accuracy of 3DCF echocardiography for CO measurement after cardiac surgery. Therefore, this single-center, prospective study was designed to evaluate the reliability of three-dimensional color flow and two-dimensional pulse wave Doppler (2D-PWD) transthoracic echocardiography for estimating cardiac output after cardiac surgery. Methods Post-cardiac surgical patients with a good acoustic window and a low dose or no dose of vasoactive drugs (norepinephrine

Background: Early Warning Scores (EWS), including the National Early Warning Score 2 (NEWS2) and Modified NEWS (NEWS-C), have been recommended for triage decision in patients with COVID-19. However, the effectiveness of these EWS in COVID-19 has not been fully validated. The study aimed to investigate the predictive value of EWS to detect clinical deterioration in patients with COVID-19.Methods: Between February 7, 2020 and February 17, 2020, patients confirmed with COVID-19 were screened for this study. The outcomes were early deterioration of respiratory function (EDRF) and need for intensive respiratory support (IRS) during the treatment process. The EDRF was defined as changes in the respiratory component of the sequential organ failure assessment (SOFA) score at day 3 (ΔSOFAresp = SOFA resp at day 3–SOFAresp on admission), in which the positive value reflects clinical deterioration. The IRS was defined as the use of high flow nasal cannula oxygen therapy, noninvasive or invasive mechanical ventilation. The performances of EWS including NEWS, NEWS 2, NEWS-C, Modified Early Warning Scores (MEWS), Hamilton Early Warning Scores (HEWS), and quick sepsis-related organ failure assessment (qSOFA) for predicting EDRF and IRS were compared using the area under the receiver operating characteristic curve (AUROC).Results: A total of 116 patients were included in this study. Of them, 27 patients (23.3%) developed EDRF and 24 patients (20.7%) required IRS. Among these EWS, NEWS-C was the most accurate scoring system for predicting EDRF [AUROC 0.79 (95% CI, 0.69–0.89)] and IRS [AUROC 0.89 (95% CI, 0.82–0.96)], while NEWS 2 had the lowest accuracy in predicting EDRF [AUROC 0.59 (95% CI, 0.46–0.720)] and IRS [AUROC 0.69 (95% CI, 0.57–0.81)]. A NEWS-C ≥ 9 had a sensitivity of 59.3% and a specificity of 85.4% for predicting EDRF. For predicting IRS, a NEWS-C ≥ 9 had a sensitivity of 75% and a specificity of 88%.Conclusions: The NEWS-C was the most accurate scoring system among common EWS to identify patients with COVID-19 at risk for EDRF and need for IRS. The NEWS-C could be recommended as an early triage tool for patients with COVID-19.

Background: Sepsis-induced coagulopathy (SIC) denotes an increased mortality rate and poorer prognosis in septic patients.Objectives: Our study aimed to develop and validate machine-learning models to dynamically predict the risk of SIC in critically ill patients with sepsis.Methods: Machine-learning models were developed and validated based on two public databases named Medical Information Mart for Intensive Care (MIMIC)-IV and the eICU Collaborative Research Database (eICU-CRD). Dynamic prediction of SIC involved an evaluation of the risk of SIC each day after the diagnosis of sepsis using 15 predictive models. The best model was selected based on its accuracy and area under the receiver operating characteristic curve (AUC), followed by fine-grained hyperparameter adjustment using the Bayesian Optimization Algorithm. A compact model was developed, based on 15 features selected according to their importance and clinical availability. These two models were compared with Logistic Regression and SIC scores in terms of SIC prediction.Results: Of 11,362 patients in MIMIC-IV included in the final cohort, a total of 6,744 (59%) patients developed SIC during sepsis. The model named Categorical Boosting (CatBoost) had the greatest AUC in our study (0.869; 95% CI: 0.850–0.886). Coagulation profile and renal function indicators were the most important features for predicting SIC. A compact model was developed with an AUC of 0.854 (95% CI: 0.832–0.872), while the AUCs of Logistic Regression and SIC scores were 0.746 (95% CI: 0.735–0.755) and 0.709 (95% CI: 0.687–0.733), respectively. A cohort of 35,252 septic patients in eICU-CRD was analyzed. The AUCs of the full and the compact models in the external validation were 0.842 (95% CI: 0.837–0.846) and 0.803 (95% CI: 0.798–0.809), respectively, which were still larger than those of Logistic Regression (0.660; 95% CI: 0.653–0.667) and SIC scores (0.752; 95% CI: 0.747–0.757). Prediction results were illustrated by SHapley Additive exPlanations (SHAP) values, which made our models clinically interpretable.Conclusions: We developed two models which were able to dynamically predict the risk of SIC in septic patients better than conventional Logistic Regression and SIC scores.

Background: Respiratory failure is one of the most common complications following cardiac surgery. Although noninvasive ventilation (NIV) has been an effective treatment, it has a high rate of intolerance. Both remifentanil and dexmedetomidine are used as sedatives in cardiac surgery (CS) patients with NIV intolerance. However, no randomized controlled trials have compared the effects of these drugs in relieving the intolerance. Methods: REDNIVI will be a multicenter, prospective, single-blind, randomized controlled trial carried out in six clinical sites in China. Subjects with NIV intolerance will be randomized to receive remifentanil or dexmedetomidine in a ratio of 1:1. Primary outcomes of intolerance remission rate at different timings (15 minutes, 1, 3, 6, 12, 24, 36, 48, 60, 72 hours after initiation of treatment) and 72 h average remission rate will be determined. In addition, secondary outcomes such as mortality, duration of intensive care unit (ICU) stay, duration of mechanical ventilation (MV), the need for endotracheal intubation, hemodynamic changes, and delirium incidence will also be determined. Conclusions: This trial will provide evidence to determine the effects of remifentanil and dexmedetomidine in patients with NIV intolerance after cardiac surgery. Clinical Trial Registration: This study has been registered on ClinicalTrials.gov (NCT04734418).

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful cardiac biomarker that is associated with acute kidney injury (AKI) and mortality after cardiac surgery. However, its prognostic value in cardiac surgical patients receiving renal replacement therapy (RRT) remains unclear.Objectives: Our study aimed to assess the prognostic value of NT-proBNP in patients with established AKI receiving RRT after cardiac surgery.Methods: A total of 163 cardiac surgical patients with AKI requiring RRT were enrolled in this study. Baseline characteristics, hemodynamic variables at RRT initiation, and NT-proBNP level before surgery, at RRT initiation, and on the first day after RRT were collected. The primary outcome was 28-day mortality after RRT initiation.Results: Serum NT-proBNP levels in non-survivors was markedly higher than survivors before surgery (median: 4,096 [IQR, 962.0–9583.8] vs. 1,339 [IQR, 446–5,173] pg/mL; P < 0.01), at RRT initiation (median: 10,366 [IQR, 5,668–20,646] vs. 3,779 [IQR, 1,799–11,256] pg/mL; P < 0.001), and on the first day after RRT (median: 9,055.0 [IQR, 4,392–24,348] vs. 5,255 [IQR, 2,134–9,175] pg/mL; P < 0.001). The area under the receiver operating characteristic curve of NT-proBNP before surgery, at RRT initiation, and on the first day after RRT for predicting 28-day mortality was 0.64 (95% CI, 0.55–0.73), 0.71 (95% CI, 0.63–0.79), and 0.68 (95% CI, 0.60–0.76), respectively. Consistently, Cox regression revealed that NT-proBNP levels before surgery (HR: 1.27, 95% CI, 1.06–1.52), at RRT initiation (HR: 1.11, 95% CI, 1.06–1.17), and on the first day after RRT (HR: 1.17, 95% CI, 1.11–1.23) were independently associated with 28-day mortality.Conclusions: Serum NT-proBNP was an independent predictor of 28-day mortality in cardiac surgical patients with AKI requiring RRT. The prognostic role of NT-proBNP needs to be confirmed in the future.

Abstract Background To evaluate the efficacy of using internal jugular vein variability (IJVV) as an index of fluid responsiveness in mechanically ventilated patients after cardiac surgery. Methods Seventy patients were assessed after cardiac surgery. Hemodynamic data coupled with ultrasound evaluation of IJVV and inferior vena cava variability (IVCV) were collected and calculated at baseline, after a passive leg raising (PLR) test and after a 500-ml fluid challenge. Patients were divided into volume responders (increase in stroke volume ≥ 15%) and non-responders (increase in stroke volume

Abstract Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung diseases. Methylprednisolone (MP) is a common drug against inflammation in clinic. In this study, we aim to investigate the protective effect of MP on ALI and potential mechanisms. Methods Male BABL/c mice were injected through tail vein using lipopolysaccharide (LPS, 5 mg/kg) with or without 5 mg/kg MP. Lung mechanics, tissue injury and inflammation were examined. Macrophage subsets in the lung were identified by flow cytometry. Macrophages were cultured from bone marrow of mice with or without MP. Then, we analyzed and isolated the subsets of macrophages. These isolated macrophages were then co-cultured with CD4+ T cells, and the percentage of regulatory T cells (Tregs) was examined. The expression of IL-10 and TGF-β in the supernatant was measured. The Tregs immunosuppression function was examined by T cell proliferation assay. To disclose the mechanism of the induction of Tregs by M2c, we blocked IL-10 or/and TGF-β using neutralizing antibody. Results Respiratory physiologic function was significantly improved by MP treatment. Tissue injury and inflammation were ameliorated in the MP-treated group. After MP treatment, the number of M1 decreased and M2 increased in the lung. In in vitro experiment, MP promoted M2 polarization rather than M1. We then induced M1, M2a and M2c from bone marrow cells. M1 induced more Th17 while M2 induced more CD4+CD25+Fxop3+ Tregs. Compared with M2a, M2c induced more Tregs, and this effect could be blocked by anti-IL-10 and anti-TGF-β antibodies. However, M2a and M2c have no impact on Tregs immunosuppression function. Conclusion In conclusion, MP ameliorated ALI by promoting M2 polarization. M2, especially M2c, induced Tregs without any influence on Tregs immunosuppression function.

Abstract Background To investigate the impact of timing the initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI), focusing on the randomized controlled trials (RCTs) in this field. Methods The PubMed, EMBASE and Cochrane databases were searched between January 1, 1985, and June 30, 2016, to identify randomized trials that assessed the timing of initiation of RRT in patients with AKI. Results Nine RCTs, with a total of 1636 patients, were enrolled in this meta-analysis. A pooled analysis of the studies indicated no mortality benefit with “early” RRT, with an RR of 0.98 (95% CI 0.78 to 1.23, P = 0.84). There was no significant difference in intensive care unit (ICU) length of stay (LOS) or hospital LOS between the early and late RRT groups for survivors or nonsurvivors. Pooled analysis also demonstrated no significant change in renal function recovery (RR 1.02, 95% CI 0.88 to 1.19, I2 = 59%), RRT dependence (RR 0.76, 95% CI 0.42 to 1.37, I2 = 0%), duration of RRT (Mean difference 1.43, 95% CI -1.75 to 4.61, I2 = 78%), renal recovery time (Mean difference 0.73, 95% CI -2.09 to 3.56, I2 = 70%) or mechanical ventilation time (Mean difference − 0.95, 95% CI -3.54 to 1.64, I2 = 64%) between the early and late RRT groups. We found no significant differences in complications between the groups. Conclusions Our meta-analysis revealed that the “early” initiation of RRT in critically ill patients did not result in reduced mortality. Pooled analysis of secondary outcomes also showed no significant difference between the early and late RRT groups. More well-designed and large-scale trials are expected to confirm the result of this meta-analysis.

Background: In cardiac surgery, elevation of procalcitonin (PCT) could be observed postoperatively in the absence of any evidence of infection and also seems to be a prognostic marker. PCT levels measured in patients undergoing Type A aortic dissection (TAAD) were used to determine prognostic values for complications and surgical outcomes. Methods: Measurements of PCT, C-reactive protein (CRP), and leukocyte count were observed in TAAD surgery patients (n = 251; average age: 49.02 ± 12.83 years; 78.5% male) at presurgery (T0) and 24 h (T1), 48 h (T2), and 7 days (T3) postsurgery. PCT clearance (PCTc) on days 2 and 7 was calculated: (PCTday1− PCTday2/day7)/PCTday1 × 100%. Endotracheal intubation duration, length of stay (LOS) in the Intensive Care Unit (ICU)/hospital, and complications were recorded. Results: PCT peaked 24 h postsurgery (median 2.73 ng/ml) before decreasing. Correlation existed between PCT levels at T1 and duration of cardiopulmonary bypass (P = 0.001, r = 0.278). Serum PCT concentrations were significantly higher in nonsurvivor and multiple organ dysfunction syndrome groups on all postoperative days. PCT levels at T1 correlated with length of time of ventilation support and ICU/hospital LOS. Comparing PCT values of survivors versus nonsurvivors, a PCT cutoff level of 5.86 ng/ml at T2 had high sensitivity (70.6%) and specificity (74.3%) in predicting in-hospital death. PCTc-day 2 and 7 were significantly higher in survivor compared with nonsurvivor patients (38% vs. 8%, P= 0.012, 83% vs. −39%, P< 0.001). A PCTc-day 7 cutoff point of 48.7% predicted survival with high sensitivity (77.8%) and specificity (81.8%). Conclusions: PCT level and PCTc after TAAD surgery might serve as early prognostic markers to predict postoperative outcome. PCT measurement may help identify high-risk patients.

Mortality of renal transplant recipients with severe community-acquired pneumonia (CAP) remains high, despite advances in critical care management. There is still a lack of biomarkers for predicting prognosis of these patients. The present study aimed to investigate the association between neutrophil-to-lymphocyte ratio (NLR) and mortality in renal transplant recipients with severe CAP. A total of 111 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility between 1 January 2009 and 30 November 2018. Patient characteristics and laboratory test results at ICU admission were retrospectively collected. There were 18 non-survivors (22.2%) among 81 patients with severe CAP who were finally included. Non-survivors had a higher NLR level than survivors (26.8 vs. 12.3, p < 0.001). NLR had the greatest power to predict mortality as suggested by area under the curve (0.88 ± 0.04; p < 0.0001) compared to platelet-to-lymphocyte ratio (0.75 ± 0.06; p < 0.01), pneumonia severity index (0.65 ± 0.08; p = 0.05), CURB-65 (0.65 ± 0.08; p = 0.05), and neutrophil count (0.68 ± 0.07; p < 0.01). Multivariate logistic regression models revealed that NLR was associated with hospital and ICU mortality in renal transplant recipients with severe CAP. NLR levels were independently associated with mortality and may be a useful biomarker for predicting poor outcome in renal transplant recipients with severe CAP.