Early pathophysiology-driven airway pressure release ventilation versus low tidal volume ventilation strategy for patients with moderate-severe ARDS: study protocol for a randomized, multicenter, controlled trial.

BACKGROUND: Conventional Mechanical ventilation modes used for individuals suffering from acute respiratory distress syndrome have the potential to exacerbate lung injury through regional alveolar overinflation and/or repetitive alveolar collapse with shearing, known as atelectrauma. Animal studies have demonstrated that airway pressure release ventilation (APRV) offers distinct advantages over conventional mechanical ventilation modes. However, the methodologies for implementing APRV vary widely, and the findings from clinical studies remain controversial. This study (APRVplus trial), aims to assess the impact of an early pathophysiology-driven APRV ventilation approach compared to a low tidal volume ventilation (LTV) strategy on the prognosis of patients with moderate to severe ARDS. METHODS: The APRVplus trial is a prospective, multicenter, randomized clinical trial, building upon our prior single-center study, to enroll 840 patients from at least 35 hospitals in China. This investigation plans to compare the early pathophysiology-driven APRV ventilation approach with the control intervention of LTV lung-protective ventilation. The primary outcome measure will be all-cause mortality at 28 days after randomization in the intensive care units (ICU). Secondary outcome measures will include assessments of oxygenation, and physiology parameters at baseline, as well as on days 1, 2, and 3. Additionally, clinical outcomes such as ventilator-free days at 28 days, duration of ICU and hospital stay, ICU and hospital mortality, and the occurrence of adverse events will be evaluated. TRIAL ETHICS AND DISSEMINATION: The research project has obtained approval from the Ethics Committee of West China Hospital of Sichuan University (2019-337). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION: The study was registered at Clinical Trials.gov (NCT03549910) on June 8, 2018.

A Fast-Track Respiratory Protocol for High Cervical Spine Injury: A Case Report.

BACKGROUND: Cervical spinal cord injury can greatly affect pulmonary function, resulting in complications, including respiratory failure with prolonged mechanical ventilation, ultimately leading to increased mortality and high health care costs. Weaning from mechanical ventilation is particularly challenging in patients with complete high spinal cord injury. CASE PRESENTATION: We present the case of a 42-year-old man who suffered a complete cervical 5-6 spinal cord injury following a rollover motor vehicle crash and subsequently developed postoperative pneumonia and severe hypoxemic respiratory failure. He received a novel approach to fast-track respiratory care, including early and aggressive secretion clearance management, moderate pressure level of airway pressure release ventilation, timely transition to spontaneous mode, early tracheostomy and humane care, and high-flow oxygenation via tracheotomy after weaning off the ventilator. As a result, the patient experienced significant improvement in pulmonary function and was successfully liberated from the ventilator within a 2-week period. CONCLUSION: This case highlights the potential effectiveness of fast-track respiratory care in promoting lung function restoration and expediting liberation from mechanical ventilation in patients with severe hypoxemic respiratory failure following a complete cervical spinal cord injury. However, further research is warranted to validate these findings and expand our understanding in this area.

Noncanonical JAK1/STAT3 interactions with TGF-ß modulate myofibroblast transdifferentiation and fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited survival. Janus kinases (JAKs), tyrosine kinases that transduce cytokine-mediated signals, are known to be involved, but their specific roles in lung fibrosis are not well defined. In this study, the interactions between JAK1/signal transducers and activators of transcription (STAT)3 signaling and transforming growth factor-beta (TGF-ß)-induced fibroblast responses were investigated using both pharmacological and siRNA approaches in human normal and IPF-derived lung fibroblasts. We found that JAK1 directly interacts with the TGF-ß receptor I subunit (TßRI), and silencing JAK1 promotes myofibroblast transdifferentiation. However, the suppression of JAK1 signaling in vitro and in vivo using an inhibitor (upadacitinib) did not alter lung fibroblast activation or fibrosis development. STAT3 was constitutively active in cultured primary lung fibroblasts; this STAT3 activation required JAK1 and repressed myofibroblast transdifferentiation. Loss of phosphorylated STAT3 following transcriptional JAK1 silencing promoted myofibroblast transdifferentiation. In contrast, transcriptional silencing of unphosphorylated STAT3 suppressed TGF-ß signaling, decreased SMAD3 activation, and reduced myofibroblast transdifferentiation and ECM production. Taken together, these observations support a role for JAK1/STAT3 as a direct regulator of TGF-ß signaling in lung fibroblasts. Modulation of JAK1/STAT3 signaling in lung fibroblasts represents a noncanonical approach to regulating TGF-ß-induced fibrosis and suggests the potential for a novel approach to treat pulmonary fibrosis.

Lumican is elevated in the lung in human and experimental acute respiratory distress syndrome and promotes early fibrotic responses to lung injury.

BACKGROUND: Fibroproliferative repair starts early in the inflammatory phase of acute respiratory distress syndrome (ARDS) and indicates a poor prognosis. Lumican, a small leucine-rich proteoglycan, is implicated in homeostasis and fibrogenesis, but its role in ARDS is unclear. METHODS: Bronchoalveolar lavage fluid (BALF) samples were obtained from ARDS patients (n = 55) enrolled within 24 h of diagnosis and mechanically ventilated (n = 20) and spontaneously breathing (n = 29) control subjects. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse models were intratracheally administered an adeno-associated virus (AAV) vector expressing lumican shRNA. Primary human lung fibroblasts (HLF) and small airway epithelial cells (SAECs) were cultured with tumour necrosis factor (TNF)-α or lumican. Luminex/ELISA, histochemistry/immunohistochemistry, immunofluorescence microscopy, quantitative real-time PCR, and western blotting were performed. RESULTS: Lumican levels were significantly higher in the BALF of ARDS patients than in that of ventilated or spontaneously breathing controls (both p < 0.0001); they were correlated with the PaO2/FiO2 ratio and levels of proinflammatory cytokines (interleukin-6, interleukin-8, and TNF-α) and profibrotic factors (fibronectin, alpha-1 type I collagen [COL1A1], and alpha-1 type III collagen [COL3A1]). Lumican expression was enhanced in the alveolar walls and airway epithelium in the ALI mouse model. Murine lumican levels were also linked to proinflammatory and profibrotic cytokine levels in the BALF. In vitro, TNF-α induced the synthesis and secretion of lumican in HLF. In turn, lumican increased the expression of alpha-smooth muscle actin (α-SMA), COL1A1, and COL3A1 in HLF, upregulated α-SMA and COL3A1, downregulated E-cadherin, and caused spindle-shaped morphological changes in SAECs. Moreover, increased ERK phosphorylation and Slug were noted in both HLF and SAECs treated with lumican. In vivo, AAV-mediated knockdown of lumican inhibited the pulmonary production of fibronectin and COL3A1 and alleviated lung fibrotic lesions in LPS-challenged mice. CONCLUSIONS: Pulmonary lumican levels were increased early in human and experimental ARDS and linked to disease severity and inflammatory fibrotic processes. Lumican triggers the transdifferentiation of lung fibroblasts into myofibroblasts and epithelial-mesenchymal transition in SAECs, possibly via the ERK/Slug pathway. Knockdown of pulmonary lumican attenuated extracellular matrix deposition in ALI mice. Overall, lumican promotes fibrotic responses in the early phase of ARDS, suggesting its potential as a therapeutic target.

Sequential use of midazolam and dexmedetomidine for long-term sedation may reduce weaning time in selected critically ill, mechanically ventilated patients: a randomized controlled study.

BACKGROUND: Current sedatives have different side effects in long-term sedation. The sequential use of midazolam and dexmedetomidine for prolonged sedation may have distinct advantages. We aimed to evaluate the efficacy and safety of the sequential use of midazolam and either dexmedetomidine or propofol, and the use of midazolam alone in selected critically ill, mechanically ventilated patients. METHODS: This single-center, randomized controlled study was conducted in medical and surgical ICUs in a tertiary, academic medical center. Patients enrolled in this study were critically ill, mechanically ventilated adult patients receiving midazolam, with anticipated mechanical ventilation for ≥ 72 h. They passed the spontaneous breathing trial (SBT) safety screen, underwent a 30-min-SBT without indication for extubation and continued to require sedation. Patients were randomized into group M-D (midazolam was switched to dexmedetomidine), group M-P (midazolam was switched to propofol), and group M (sedation with midazolam alone), and sedatives were titrated to achieve the targeted sedation range (RASS - 2 to 0). RESULTS: Total 252 patients were enrolled. Patients in group M-D had an earlier recovery, faster extubation, and more percentage of time at the target sedation level than those in group M-P and group M (all P < 0.001). They also experienced less weaning time (25.0 h vs. 49.0 h; HR1.47, 95% CI 1.05 to 2.06; P = 0.025), and a lower incidence of delirium (19.5% vs. 43.8%, P = 0.002) than patients in group M. Recovery (P < 0.001), extubation (P < 0.001), and weaning time (P = 0.048) in group M-P were shorter than in group M, while the acquisition cost of sedative drug was more expensive than other groups (both P < 0.001). There was no significant difference in adverse events among these groups (all P > 0.05). CONCLUSIONS: The sequential use of midazolam and dexmedetomidine was an effective and safe sedation strategy for long-term sedation and could provide clinically relevant benefits for selected critically ill, mechanically ventilated patients. TRIAL REGISTRATION: NCT02528513 . Registered August 19, 2015.

Increased diaphragm echodensity correlates with postoperative pulmonary complications in patients after major abdominal surgery: a prospective observational study.

BACKGROUND: Associated with increased morbidity and mortality, postoperative pulmonary complications (PPCs) often occur after major abdominal surgery. Diaphragmatic dysfunction is suggested to play an important role in the development of PPCs and diaphragm echodensity can be used as an indicator of diaphragm function. This study aimed to determine whether diaphragm echodensity could predict the occurrence of PPCs in patients after major abdominal surgery. METHODS: Diaphragm ultrasound images of patients after major abdominal surgery were collected during spontaneous breathing trials. Echodensity was quantified based on the right-skewed distribution of grayscale values (50th percentile, ED50; 85th percentile, ED85; mean, EDmean). Intra- and inter-analyzer measurement reproducibility was determined. Outcomes including occurrence of PPCs, reintubation rate, duration of ventilation, and length of ICU stay were recorded. RESULTS: Diaphragm echodensity was measured serially in 117 patients. Patients who developed PPCs exhibited a higher ED50 (35.00 vs. 26.00, p < 0.001), higher ED85 (64.00 vs. 55.00, p < 0.001) and higher EDmean (39.32 vs. 33.98, p < 0.001). In ROC curve analysis, the area under the curve of ED50 for predicting PPCs was 0.611. The optimal ED50 cutoff value for predicting the occurrence of PPCs was 36. According to this optimal ED50 cutoff value, patients were further divided into a high-risk group (ED50 > 36, n = 35) and low-risk group (ED50 ≤ 36, n = 82). Compared with the low-risk group, the high-risk group had a higher incidence of PPCs (unadjusted p = 0.003; multivariate-adjusted p < 0.001). CONCLUSION: Diaphragm echodensity can be feasibly and reproducibly measured in mechanically ventilated patients. The increase in diaphragm echodensity during spontaneous breathing trials was related to an increased risk of PPCs in patients after major abdominal surgery.

Effects of airway pressure release ventilation on multi-organ injuries in severe acute respiratory distress syndrome pig models.

BACKGROUND: Extra-pulmonary multi-organ failure in patients with severe acute respiratory distress syndrome (ARDS) is a major cause of high mortality. Our purpose is to assess whether airway pressure release ventilation (APRV) causes more multi-organ damage than low tidal volume ventilation (LTV). METHODS: Twenty one pigs were randomized into control group (n = 3), ARDS group (n = 3), LTV group (n = 8) and APRV group (n = 7). Severe ARDS model was induced by repeated bronchial saline lavages. Pigs were ventilated and monitored continuously for 48 h. Respiratory data, hemodynamic data, serum inflammatory cytokines were collected throughout the study. Histological injury and apoptosis were assessed by two pathologists. RESULTS: After severe ARDS modeling, pigs in ARDS, LTV and APRV groups experienced significant hypoxemia and reduced lung static compliance (Cstat). Oxygenation recovered progressively after 16 h mechanical ventilation (MV) in LTV and APRV group. The results of the repeated measures ANOVA showed no statistical difference in the PaO2/FiO2 ratio between the APRV and LTV groups (p = 0.54). The Cstat showed a considerable improvement in APRV group with statistical significance (p < 0.01), which was significantly higher than in the LTV group since 16 h (p = 0.04). Histological injury scores showed a significantly lower injury score in the middle and lower lobes of the right lung in the APRV group compared to LTV (pmiddle = 0.04, plower = 0.01), and no significant increase in injury scores for extra-pulmonary organs, including kidney (p = 0.10), small intestine (p = 1.0), liver (p = 0.14, p = 0.13) and heart (p = 0.20). There were no significant differences in serum inflammatory cytokines between the two groups. CONCLUSION: In conclusion, in the experimental pig models of severe ARDS induced by repetitive saline lavage, APRV improved lung compliance with reduced lung injury of middle and lower lobes, and did not demonstrate more extra-pulmonary organ injuries as compared with LTV.

Mitochondrial Damage-Associated Molecular Patterns Exacerbate Lung Fluid Imbalance Via the Formyl Peptide Receptor-1 Signaling Pathway in Acute Lung Injury.

OBJECTIVES: To investigate the effect of mitochondrial damage-associated molecular patterns on the lung fluid homeostasis in experimental acute lung injury. DESIGN: Experimental study. SETTING: Research laboratory. SUBJECTS: Patients with acute respiratory distress syndrome and control subjects, wild-type C57BL/6 and formyl peptide receptor-1 gene knockout mice, and primary rat alveolar epithelial type II cells. INTERVENTIONS: Samples of bronchoalveolar lavage fluid and serum were obtained from patients and control subjects. Mice were intratracheally instilled with lipopolysaccharide and mitochondrial damage-associated molecular patterns. The primary rat alveolar epithelial type II cells were isolated and incubated with mitochondrial damage-associated molecular patterns. MEASUREMENTS AND MAIN RESULTS: Patients were divided into direct (pulmonary) and indirect (extrapulmonary) injury groups based on etiology. The release of mitochondrial peptide nicotinamide adenine dinucleotide dehydrogenase 1 in both bronchoalveolar lavage fluid and serum was induced in patients and was associated with etiology. In the lipopolysaccharide-induced lung injury, administration of mitochondrial damage-associated molecular patterns exacerbated the lung fluid imbalance, which was mitigated in formyl peptide receptor-1 knockout mice. Proteomic analysis of mouse lung tissues revealed the involvement of ion channels and tight junction proteins in this process. Treatment with mitochondrial damage-associated molecular patterns decreased the expression of epithelial sodium channel α, zonula occludens-1, and occludin via the formyl peptide receptor-1/p38 pathway in the primary rat alveolar epithelial type II cells. CONCLUSIONS: Mitochondrial damage-associated molecular patterns exacerbate lung fluid imbalance in the experimental acute lung injury model through formyl peptide receptor-1 signaling, the inhibition of which may prevent exacerbation of lung fluid imbalance induced by mitochondrial damage-associated molecular patterns. Thus, formyl peptide receptor-1 is a potential therapeutic target for acute respiratory distress syndrome.

Compare the effect of noninvasive ventilation and tracheotomy in critically ill mechanically ventilated neurosurgical patients: a retrospective observe cohort study.

OBJECTIVE: Patients with severe brain injury is usual at high risk of extubation failure, despite of those with no/minor primary respiratory problem, majority of them still needs long term respiratory support and has severe pulmonary complications. This retrospective study aimed to compare the effect of noninvasive ventilation (NIV) and tracheotomy on the prognosis in critically ill mechanically ventilated neurosurgical patients. METHODS: This is a single center, retrospective observe cohort study. Postoperative patients with brain injury consecutively admitted to ICU from November 1st, 2015 through February 28th, 2017, who had received invasive mechanical ventilation more than 48 h were screened, those who received NIV or tracheotomy procedure, meanwhile with Glasgow Coma Scale (GCS) score between 8 and 13 points before using NIV or undergoing tracheotomy, were retrospectively included in this study. The demographic data and clinical main outcomes such as ICU and hospital mortality, time of mechanical ventilation, length of ICU and hospital were collected. The primary outcome was the incidence of postoperative pulmonary infection between two groups. RESULTS: 77 patients were included in this study. 33 patients received NIV, and 44 patients received tracheotomy through the ICU duration. The incidence of postoperative pulmonary infection in NIV group was significantly lower than that in tracheotomy group (54.5% VS 84.1%, P < 0.05), Application of NIV was associated with shorter duration of invasive mechanical ventilation ([median 123.0 h VS 195.0 h, P < 0.05). Moreover, GCS score at ICU discharge, as well as the difference of GCS score between at admission to ICU and ICU discharge were also better than the tracheotomy group (P < 0.001). CONCLUSION: Compared with tracheotomy, use of NIV after extubation in critically ill mechanically ventilated neurosurgical patients may be associated with lower incidence of postoperative pulmonary infection, shorter duration of invasive mechanical ventilation and better improvement in brain function. Further studies need to verify the effect of NIV in this kind of patients.

Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study.

INTRODUCTION: Midazolam and propofol used alone for long-term sedation are associated with adverse effects. Sequential use may reduce the adverse effects, and lead to faster recovery, earlier extubation and lower costs. This study evaluates the effects, safety, and cost of midazolam, propofol, and their sequential use for long-term sedation in critically ill mechanically ventilated patients. METHODS: A total of 135 patients who required mechanical ventilation for >3 days were randomly assigned to receive midazolam (group M), propofol (group P), or sequential use of both (group M-P). In group M-P, midazolam was switched to propofol until the patients passed the spontaneous breathing trial (SBT) safety screen. The primary endpoints included recovery time, extubation time and mechanical ventilation time. The secondary endpoints were pharmaceutical cost, total cost of ICU stay, and recollection to mechanical ventilation-related events. RESULTS: The incidence of agitation following cessation of sedation in group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean percentage of adequate sedation and duration of sedation were similar in the three groups. The recovery time, extubation time and mechanical ventilation time of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5) hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly longer than the other groups, while they were similar between the other two groups. In the treatment-received analysis, ICU duration was longer in group M than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment-received analysis, respectively, the pharmaceutical cost of group M-P was lower than group P (P <0.01) and its ICU cost was lower than group M (P <0.01; P = 0.015). The proportion of group M-P with unbearable memory of the uncomfortable events was lower than in group M (11.7% versus 25.0%, P <0.01), while the proportion with no memory was similar (P >0.05). The incidence of hypotension in group M-P was lower than group (P = 0.01). CONCLUSION: Sequential use of midazolam and propofol was a safe and effective sedation protocol, with higher clinical effectiveness and better cost-benefit ratio than midazolam or propofol used alone, for long-term sedation of critically ill mechanically ventilated patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN01173443. Registered 25 February 2014.

Cystatin C Attenuates Perihematomal Secondary Brain Injury by Inhibiting the Cathepsin B/NLRP3 Signaling Pathway in a Rat Model of Intracerebral Hemorrhage.

Secondary brain injury (SBI) is a noticeable contributor to the high mortality and morbidity rates associated with intracerebral hemorrhage (ICH), and effective treatment options remain limited. Cystatin C (CysC) emerges as a novel candidate for SBI intervention. The therapeutic effects and underlying mechanisms of CysC in mitigating SBI following ICH were explored in the current research. An in vivo ICH rat model was established by injecting autologous blood into the right caudate nucleus. Western blotting (WB) was utilized to assess the levels of CysC, cathepsin B (CTSB), and the NLRP3 inflammasome. Subsequently, the ICH rat model was treated with exogenous CysC supplementation or CysC knockdown plasmids. Various parameters, including Evans blue (EB) extravasation, brain water content, and neurological function in rats, were examined. RT-qPCR and WB were employed to determine the expression levels of CTSB and the NLRP3 inflammasome. The co-expression of CTSB, CysC, and NLRP3 inflammasome with GFAP, NeuN, and Iba1 was assessed through double-labeled immunofluorescence. The interaction between CysC and CTSB was investigated using double-labeled immunofluorescence and co-immunoprecipitation. The findings revealed an elevation of CysC expression level, particularly at 24 h after ICH. Exogenous CysC supplementation alleviated severe brain edema, neurological deficit scores, and EB extravasation induced by ICH. Conversely, CysC knockdown produced opposite effects. The expression levels of CTSB and the NLRP3 inflammasome were significantly risen following ICH, and exogenous CysC supplement attenuated their expression levels. Double-labeled immunofluorescence illustrated that CysC, CTSB, and the NLRP3 inflammasome were predominantly expressed in microglial cells, and the interaction between CysC and CTSB was evidenced. CysC exhibited potential in ameliorating SBI following ICH via effectively suppressing the activation of the NLRP3 inflammasome mediated by CTSB specifically in microglial cells. These findings underscore the prospective therapeutic efficacy of CysC in the treatment of ICH-induced complications.

A Retrospective Cohort Study: Predicting 90-Day Mortality for ICU Trauma Patients with a Machine Learning Algorithm Using XGBoost Using MIMIC-III Database.

Objective: The aim of this study was to develop and validate a machine learning-based predictive model that predicts 90-day mortality in ICU trauma patients. Methods: Data of patients with severe trauma were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The performances of mortality prediction models generated using nine machine learning extreme gradient boosting (XGBoost), logistic regression, random forest, AdaBoost, multilayer perceptron (MLP) neural networks, support vector machine (SVM), light gradient boosting machine (GBM), k nearest neighbors (KNN) and gaussian naive bayes (GNB). The performance of the model was evaluated in terms of discrimination, calibration and clinical application. Results: We found that the accuracy, sensitivity, specificity, PPV, NPV and F1 score of our proposed XGBoost model were 82.8%, 79.7%, 77.6%, 51.2%, 91.5% and 0.624, respectively. Among the nine models, the XGBoost model performed best. Compared with traditional logistic regression, the calibration curves of the XGBoost model and decision curve analysis (DCA) performed well. Conclusion: Our study shows that the XGBoost model outperforms other machine learning models in predicting 90-day mortality in trauma patients. It can be used to assist clinicians in the early identification of mortality risk factors and early intervention to reduce mortality.

Lower serum cystatin C level predicts poor functional outcome in patients with hypertensive intracerebral hemorrhage independent of renal function.

We explored the association between the serum level of cystatin C (CysC) at admission and short-term functional outcome in patients with hypertensive intracerebral hemorrhage (HICH) without chronic kidney disease (CKD). A total of 555 patients with HICH were consecutively recruited after admission and were followed-up for 3 months after admission. The primary outcome was poor functional outcome (modified Rankin Scale [mRS] score ≥ 3). The median serum CysC level in our cohort was 1.03 mg/L (interquartile range, .89-1.20). Patients were categorized into four groups according to the serum CysC quartiles. Multivariate logistic regression analysis revealed a negative association between serum CysC and poor functional outcome at 3-month follow-up (quartile [Q]1 vs. Q4: adjusted odds ratio [OR] = .260, 95% confidence interval [CI] = .098, .691, p < .001). The negative association between serum CysC and poor functional outcome at 3 months was more pronounced in subgroups with smaller hematoma volume (≤ 30 mL), and absence of secondary intraventricular hemorrhage (IVH). Addition of serum CysC to a model containing conventional risk factors improved the model performance with net reclassification index (NRI) of .426% (p < .001) and integrated discrimination improvement (IDI) of .043% (p < .001) for poor functional outcome. Serum CysC was found to be a negative predictor of poor short-term functional outcome in HICH patients independent of renal function.

[Time-related association between fluid balance and prognosis in sepsis patients: a cohort study based on MIMIC-IV database].

OBJECTIVE: To investigate time-related association between fluid balance and prognosis in sepsis patients. METHODS: A retrospective cohort study was conducted based on the data of sepsis patients in the Medical Information Database for Intensive Care-IV 2.0 (MIMIC-IV 2.0) from 2008 to 2019. Sepsis patients aged ≥ 18 years who were admitted to intensive care unit (ICU) for at least 2 days were included. The daily fluid balance and cumulative fluid balance (CFB) were calculated from days 1 to 7 after ICU admission. According to CFB,the patients were divided into negative fluid balance group (CFB% < 0%), fluid balance group (0% ≤ CFB% ≤ 10%), and fluid overload group (CFB% > 10%). In-hospital mortality was the primary outcome. Multifactorial Logistic regression was used to analyze time-related association between different CFB and the risk of in-hospital mortality in patients with sepsis during 7 days after ICU admission. In addition, subgroup analysis was performed on patients with septic shock and patients with sepsis who stayed in the ICU for 7 days or longer. RESULTS: A total of 11 437 patients with sepsis were included, of which 6 595 were male and 4 842 were female. The mean age was (64.4±16.4) years. A total of 10 253 patients (89.6%) survived and 1 184 patients (10.4%) died during hospitalization. Compared with the survival group, patients in the death group were older, lighter, had higher sequential organ failure assessment (SOFA), simplified acute physiology score II (SAPS II), longer ICU stay, higher incidence of septic shock, and higher proportion of invasive mechanical ventilation, renal replacement therapy (RRT) and vasoactive drugs. In terms of comorbidities, congestive heart failure, renal disease, liver disease, and malignancy were more common in the death group. The death group had a higher daily fluid balance than the survival group during 7 days after ICU admission, the CFB in the two groups gradually increased with length of ICU stay. After adjusting variables such as age, gender, race, SOFA score, SAPS II score, comorbidities, and the use of invasive mechanical ventilation, RRT and vasoactive drugs, multivariate Logistic regression analysis showed that fluid overload on day 1 after ICU admission was a protective factor for the reduced risk of in-hospital mortality in sepsis patients [odds ratio (OR) = 0.74, 95% confidence interval (95%CI) was 0.64-0.86, P = 0.001]. However, fluid overload on day 3 was a risk factor for in-hospital mortality in sepsis patients (OR = 1.70, 95%CI was 1.47-1.97, P < 0.001) and the risk of in-hospital mortality was significantly increased from day 4 to day 7. Furthermore, the same results were obtained in patients with septic shock and sepsis patients who stayed in the ICU for 7 days or longer. CONCLUSIONS: Fluid overload on day 1 was associated with reduced in-hospital mortality. However, from the third day, fluid overload increases the risk of in-hospital mortality. Thus, managing fluid balance at different times may improve prognosis.

A high-throughput phenotyping method for sugarcane rind penetrometer resistance and breaking force characterization by near-infrared spectroscopy.

BACKGROUND: Sugarcane (Saccharum spp.) is the core crop for sugar and bioethanol production over the world. A major problem in sugarcane production is stalk lodging due to weak mechanical strength. Rind penetrometer resistance (RPR) and breaking force are two kinds of regular parameters for mechanical strength characterization. However, due to the lack of efficient methods for determining RPR and breaking force in sugarcane, genetic approaches for improving these traits are generally limited. This study was designed to use near-infrared spectroscopy (NIRS) calibration assay to accurately assess mechanical strength on a high-throughput basis for the first time. RESULTS: Based on well-established laboratory measurements of sugarcane stalk internodes collected in the years 2019 and 2020, considerable variations in RPR and breaking force were observed in the stalk internodes. Following a standard NIRS calibration process, two online models were obtained with a high coefficient of determination (R2) and the ratio of prediction to deviation (RPD) values during calibration, internal cross-validation, and external validation. Remarkably, the equation for RPR exhibited R2 and RPD values as high as 0.997 and 17.70, as well as showing relatively low root mean square error values at 0.44 N mm-2 during global modeling, demonstrating excellent predictive performance. CONCLUSIONS: This study delivered a successful attempt for rapid and precise prediction of rind penetrometer resistance and breaking force in sugarcane stalk by NIRS assay. These established models can be used to improve phenotyping jobs for sugarcane germplasm on a large scale.

Association of IL-10-1082 G/G genotype with lower mortality of acute respiratory distress syndrome in a Chinese population.

We aimed to investigate whether interleukin-10 (IL-10) -1082 G/G genotype is associated with lower mortality of acute respiratory distress syndrome (ARDS) in a Chinese population. A hospital-based case-control study was conducted in 314 cases of ARDS and 210 controls who were admitted to an intensive care unit with sepsis, trauma, aspiration or massive transfusions. Cases were followed for 30-day mortality. The -1082G/G genotype was associated with lower development of ARDS (OR=0.51; 95% CI 0.34-0.76; P=0.001). Among patients with ARDS, the -1082G/G genotype was associated with lower 30-day mortality (OR=0.44; 95% CI 0.25-0.76; P=0.003). In conclusion, IL-10-1082 G/G genotype is associated with lower development and mortality of ARDS in a Chinese population.

The Effects of Airway Pressure Release Ventilation on Pulmonary Permeability in Severe Acute Respiratory Distress Syndrome Pig Models.

Objective: The aim of the study was to compare the effects of APRV and LTV ventilation on pulmonary permeability in severe ARDS. Methods: Mini Bama adult pigs were randomized into the APRV group (n = 5) and LTV group (n = 5). A severe ARDS animal model was induced by the whole lung saline lavage. Pigs were ventilated and monitored continuously for 48 h. Results: Compared with the LTV group, CStat was significantly better (p < 0.05), and the PaO2/FiO2 ratio showed a trend to be higher throughout the period of the experiment in the APRV group. The extravascular lung water index and pulmonary vascular permeability index showed a trend to be lower in the APRV group. APRV also significantly mitigates lung histopathologic injury determined by the lung histopathological injury score (p < 0.05) and gross pathological changes of lung tissues. The protein contents of occludin (p < 0.05), claudin-5 (p < 0.05), E-cadherin (p < 0.05), and VE-cadherin (p < 0.05) in the middle lobe of the right lung were higher in the APRV group than in the LTV group; among them, the contents of occludin (p < 0.05) and E-cadherin (p < 0.05) of the whole lung were higher in the APRV group. Transmission electron microscopy showed that alveolar-capillary barrier damage was more severe in the middle lobe of lungs in the LTV group. Conclusion: In comparison with LTV, APRV could preserve the alveolar-capillary barrier architecture, mitigate lung histopathologic injury, increase the expression of cell junction protein, improve respiratory system compliance, and showed a trend to reduce extravascular lung water and improve oxygenation. These findings indicated that APRV might lead to more profound beneficial effects on the integrity of the alveolar-capillary barrier architecture and on the expression of biomarkers related to pulmonary permeability.

Does airway pressure release ventilation offer new hope for treating acute respiratory distress syndrome?

Mechanical ventilation (MV) is an essential life support method for patients with acute respiratory distress syndrome (ARDS), which is one of the most common critical illnesses with high mortality in the intensive care unit (ICU). A lung-protective ventilation strategy based on low tidal volume (LTV) has been recommended since a few years; however, as this did not result in a significant decrease of ARDS-related mortality, a more optimal ventilation mode was required. Airway pressure release ventilation (APRV) is an old method defined as a continuous positive airway pressure (CPAP) with a brief intermittent release phase based on the open lung concept; it also perfectly fits the ARDS treatment principle. Despite this, APRV has not been widely used in the past, rather only as a rescue measure for ARDS patients who are difficult to oxygenate. Over recent years, with an increased understanding of the pathophysiology of ARDS, APRV has been reproposed to improve patient prognosis. Nevertheless, this mode is still not routinely used in ARDS patients given its vague definition and complexity. Consequently, in this paper, we summarize the studies that used APRV in ARDS, including adults, children, and animals, to illustrate the settings of parameters, effectiveness in the population, safety (especially in children), incidence, and mechanism of ventilator-induced lung injury (VILI) and effects on extrapulmonary organs. Finally, we found that APRV is likely associated with improvement in ARDS outcomes, and does not increase injury to the lungs and other organs, thereby indicating that personalized APRV settings may be the new hope for ARDS treatment.