The accuracy of simplified calculation of mechanical power: a simulation study.

Background: Mechanical ventilation (MV) is an important life-saving method in the intensive care unit (ICU). A lower mechanical power (MP) is associated with a better MV strategy. However, traditional MP calculating methods are complicated, and algebraic formulas seem to be rather practical. The aim of the present study was to compare the accuracy and application of different algebraic formulas calculating MP. Methods: A lung simulator, TestChest, was used to simulate pulmonary compliance variations. Using the TestChest system software, the parameters, including compliance and airway resistance, were set to simulate various acute respiratory distress syndrome (ARDS) lungs. Ventilator was also set to volume- and pressure-controlled modes with various parameter values (respiratory rate, RR, time of inspiration, Tinsp, positive end-expiratory pressure, PEEP) to ventilate the simulated lung of ARDS (with various respiratory system compliance, Crs). For the lung simulator, resistance of airway (Raw) was fixed to 5 cmH2O/L/s. Crs below lower inflation point (LIP) or above upper inflation point (UIP) was set to 10 mL/cmH2O. The reference standard geometric method was calculated offline with a customized software. Three algebraic formulas for volume-controlled and three for pressure-controlled were used to calculate MP. Results: The performances of the formulas were different, although the derived MP were significantly correlated with that derived from the reference method (R2>0.80, P<0.001). Under volume-controlled ventilation, medians of MP calculated with one equation was significantly lower than that with the reference method (P<0.001). Under pressure-controlled ventilation, median of MP calculated with two equations were significantly higher (P<0.001). The maximum difference was over 70% of the MP value calculated with the reference method. Conclusions: The algebraic formulas may introduce considerably large bias under the presented lung conditions, especially in moderate to severe ARDS. Cautious is required when selecting adequate algebraic formulas to calculate MP based on the formula's premises, ventilation mode, and patients' status. In clinical practice, the trend rather than the value of MP calculated by formulas should require more attention.

Weaning critically ill patients from mechanical ventilation: a protocol from a multicenter retrospective cohort study.

BACKGROUND: Mechanical ventilation (MV) is an important lifesaving method in intensive care unit (ICU). Prolonged MV is associated with ventilator associated pneumonia (VAP) and other complications. However, premature weaning from MV may lead to higher risk of reintubation or mortality. Therefore, timely and safe weaning from MV is important. In addition, identification of the right patient and performing a suitable weaning process is necessary. Although several guidelines about weaning have been reported, compliance with these guidelines is unknown. Therefore, the aim of this study is to explore the variation of weaning in China, associations between initial MV reason and clinical outcomes, and factors associated with weaning strategies using a multicenter cohort. METHODS: This multicenter retrospective cohort study will be conducted at 17 adult ICUs in China, that included patients who were admitted in this 17 ICUs between October 2020 and February 2021. Patients under 18 years of age and patients without the possibility for weaning will be excluded. The questionnaire information will be registered by a specific clinician in each center who has been evaluated and qualified to carry out the study. DISCUSSION: In a previous observational study of weaning in 17 ICUs in China, weaning practices varies nationally. Therefore, a multicenter retrospective cohort study is necessary to be conducted to explore the present weaning methods used in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) (No. ChiCTR2100044634).

Optimal Positive End Expiratory Pressure Levels in Ventilated Patients Without Acute Respiratory Distress Syndrome: A Bayesian Network Meta-Analysis and Systematic Review of Randomized Controlled Trials.

Background: To find the optimal positive end expiratory pressure (PEEP) in mechanical ventilated patients without Acute Respiratory Distress Syndrome (ARDS), we conducted a Bayesian network meta-analysis and systematic review of randomized controlled trials (RCTs) comparing different level of PEEP based on a novel classification of PEEP level: ZEEP group (PEEP = 0 cm H2O); lower PEEP group (PEEP = 1-6 cm H2O); intermediate PEEP group (PEEP = 7-10 cm H2O); higher PEEP group (PEEP > 10 cm H2O). Result: Twenty eight eligible studies with 2,712 patients were included. There were no significant differences in the duration of mechanical ventilation between higher and intermediate PEEP (MD: 0.020, 95% CI: -0.14, 0.28), higher and lower PEEP (MD: -0.010, 95% CI: -0.23, 0.22), higher PEEP and ZEEP (MD: 0.010, 95% CI: -0.40, 0.22), intermediate and lower PEEP (MD: -0.040, 95% CI: -0.18, 0.040), intermediate PEEP and ZEEP (MD: -0.010, 95% CI: -0.42, 0.10), lower PEEP and ZEEP (MD: 0.020, 95% CI: -0.32, 0.13), respectively. Higher PEEP was associated with significantly higher PaO2/FiO2 ratio(PFR) when compared to ZEEP (MD: 73.24, 95% CI: 11.03, 130.7), and higher incidence of pneumothorax when compared to intermediate PEEP, lower PEEP and ZEEP (OR: 2.91e + 12, 95% CI: 40.3, 1.76e + 39; OR: 1.85e + 12, 95% CI: 29.2, 1.18e + 39; and OR: 1.44e + 12, 95% CI: 16.9, 8.70e + 38, respectively). There was no association between PEEP levels and other secondary outcomes. Conclusion: We identified higher PEEP was associated with significantly higher PFR and higher incidence of pneumothorax. Nonetheless, in terms of other outcomes, no significant differences were detected among four levels of PEEP. Systematic Review Registration: The study had registered on an international prospective register of systematic reviews, PROSPERO, on 09 April 2021, identifier: [CRD42021241745].

Reverse Trigger in Ventilated Non-ARDS Patients: A Phenomenon Can Not Be Ignored!

INTRODUCTION: The role of reverse trigger (RT) was unknown in ventilated non-acute respiratory distress syndrome (ARDS) patients. So we conducted a retrospective study to evaluate the incidence, characteristics and physiologic consequence of RT in such population. METHOD: Six ventilated non-ARDS patients were included, the esophageal balloon catheter were placed for measurements of respiratory mechanics in all patients. And the data were analyzed to identified the occurrence of RT, duration of the entrainment, the entrainment pattern or ratio, the phase difference (dP) and the phase angle (θ), phenotypes, Effects and clinical correlations of RT. RESULT: RT was detected in four patients of our series (66.7%), and the occurrence of RT varying from 19 to 88.6% of their recording time in these 4 patients. One patient (No.2) showed a stable 1:1 ratio and Mid-cycle RT was the most common phenotype. However, the remained patients showed a mixed ratios, and Late RT was the most common phenotype, followed by RT with breath stacking. The average values of mean phase delay and phase angles were 0.39s (0.32, 0.98) and 60.52° (49.66, 102.24). Mean phase delay and phase angles were shorter in early reverse triggering with early and delayed relaxation, and longer in mid, late RT and RT with breath stacking. Pmus was variable between patients and phenotypes, and larger Pmus was generated in Early RT, Delayed Relaxation and mid cycle RT. When the RT occurred, the Peso increased 17.27 (4.91, 19.71) cmH2O compared to the controlled breathing, and the average value of incremental ΔPeso varied widely inter and intra patients (Table 3B and Figure 1). Larger ΔPeso was always generated in Early RT, Delayed Relaxation and mid cycle RT, accompanied by an significant increase of PL with 19.12 (0.75) cmH2O and 16.10 (6.23) cmH2O. CONCLUSION: RT could also be observed in ventilated non-ARDS patients. The characteristics of pattern and phenotype was similar to RT in ARDS patients to a large extent. And RT appeared to alter lung stress and delivered volumes.

Translational Nanotherapeutics Reprograms Immune Microenvironment in Malignant Pleural Effusion of Lung Adenocarcinoma.

Malignant pleural effusion (MPE) remains a treatment bottleneck in advanced lung cancer, due to its complicated microenvironments and "cold" immunity. Therefore, the search for therapeutic drugs to transform MPE to functionally "hot" one could advance the development of effective immunotherapeutic strategy. Herein, translational selenium nanoparticles coated with immune-modulating macromolecule lentinan (SeNPs@LNT) are designed to restore the dysfunctional immune cells in patient-derived MPE microenvironment. Internalization of the SeNPs@LNT can effectively reduce the immunosuppressive status by enhancing the proliferation of CD4+ T cells and natural killer cells, and remodeling the tumor associated macrophages into tumoricidal M1 phenotype in MPE derived from patients presenting low Se levels in blood and pleural effusion. Th1, cytotoxic T cell, γδ T, and B cell functions are upregulated, and Th2, Th17, and Treg cells activity is downregulated. Furthermore, SeNPs@LNT can be gradually metabolized into SeCys2 to promote the production of metabolites associated with tumor growth inhibition and immune response activation in MPE microenvironment. In contrast, lung cancer markers and vitamin B6 metabolism are decreased. The translational SeNP-based nanotherapeutic strategy restores functional "cold" MPE to "hot" MPE to activate the immune responses of various immune cells in MPE of lung cancer patients.

The Prevalence, Risk Factors, and Prognosis of Acute Kidney Injury After Lung Transplantation: A Single-Center Cohort Study in China.

PURPOSE: The aim of this study is to evaluate the incidence, risk factors, and prognosis of acute kidney injury (AKI) after lung transplantation (LTx). METHODS: Records of patients who underwent LTx in a single center were retrospectively reviewed. The prevalence of post-transplant AKI, the use of continuous renal replacement therapy (CRRT), and the risk factors for AKI were investigated. The effects of AKI and CRRT on short-term outcomes and long-term survival were measured. RESULTS: This study included 148 patients, 67 of which developed postoperative AKI. Of these, 31 patients underwent CRRT; the percentage of cases with no AKI was 6.2%, and the percentage of cases with stage 1, 2, and 3 who used CRRT was 0%, 10%, and 86.2%, respectively. Patients with AKI had significantly higher intensive care unit mortality and in-hospital mortality. The 1-year post-LTx survival rate of patients with AKI was 47.8%, significantly lower than those without AKI (74.1%). There was no difference in 1-year survival rate of those with stage 1 and stage 2 AKI, but patients with stage 3 AKI showed the worst survival. Patients who underwent CRRT had an inferior survival outcome (9.7% vs 76.1%, P < .05). We found that higher acute physiologic assessment and chronic health evaluation (APACHE) II scores (odds ratio [OR] 1.082, P = .009) and higher intraoperative fluid balance (OR 1.001, P = .012) were independent risk factors, and female sex (OR 2.539) and pulmonary hypertension (OR 2.869) were potential risk factors for post-LTx AKI. A prediction model integration of the above factors showed a good concordance with actual risks and had a concordance index (C-index) of 0.76 (95% confidence interval [CI], 0.66-0.87). CONCLUSION: Severe AKI requiring CRRT had a negative impact on the short-term and long-term outcomes of patients.

Clinical Findings of COVID-19 Patients Admitted to Intensive Care Units in Guangdong Province, China: A Multicenter, Retrospective, Observational Study.

Background: Information about critically ill patients with coronavirus disease 2019 (COVID-19) in China but outside of Wuhan is scarce. We aimed to describe the clinical features, treatment, and outcomes of patients with COVID-19 admitted to the intensive care unit (ICU) in Guangdong Province. Methods: In this multicenter, retrospective, observational study, we enrolled consecutive patients with COVID-19 who were admitted to seven ICUs in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatment, and outcomes were collected. Data were compared between patients with and without intubation. Results: A total of 45 COVID-19 patients required ICU admission in the study hospitals [mean age 56.7 ± 15.4 years, 29 males (64.4%)]. The most common symptoms at onset were fever and cough. Most patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all patients. Thirty-six patients (80%) developed acute respiratory distress syndrome at ICU admission, and 15 (33.3%) septic shock. Twenty patients (44.4%) were intubated, and 10 (22.2%) received extracorporeal membrane oxygenation. The 60-day mortality was 4.4% (2 of 45). Conclusion: COVID-19 patients admitted to ICU were characterized by fever, lymphopenia, acute respiratory failure, and multiple organ dysfunction. The mortality of ICU patients in Guangdong Province was relatively low with a small sample size.

Ghrelin attenuates sepsis-induced acute lung injury by inhibiting the NF-κB, iNOS, and Akt signaling in alveolar macrophages.

Ghrelin has proven to be protective against sepsis-induced acute lung injury (ALI) via anti-inflammatory effects. However, its mechanisms remain poorly understood. Alveolar macrophages (AMs) play a key role in mediating inflammatory responses during sepsis-induced ALI by secretion of cytokines and chemokines. This study was undertaken to investigate whether ghrelin suppresses inflammatory effects of AMs and therefore may help to attenuate sepsis-induced ALI. A sepsis model in rats was achieved using cecal ligation and puncture. Ghrelin treatment markedly improved histopathological changes in the lungs and reduced pulmonary inflammation in septic rats. NF-κB translocation and p-Akt and inducible nitric oxide synthase (iNOS) activities in AMs from septic rats were suppressed by ghrelin. In vitro data indicated that ghrelin decreased the levels of LPS-induced IL-1ß, TNF-α, and IL-6, NF-κB translocation, and iNOS and Akt activities of AMs. Furthermore, the NF-κB/iNOS pathway or Akt signaling was positively correlated with LPS-induced inflammatory production of AMs in vitro. In conclusion, ghrelin exerts a protective role against sepsis-induced ALI probably by reducing the production of inflammatory cytokines from AMs via inhibition of the NF-κB/iNOS pathway or Akt signaling.

Effects of Ghrelin on iNOS-Derived NO Promoted LPS-Induced Pulmonary Alveolar Epithelial A549 Cells Apoptosis.

BACKGROUND/AIMS: In the process of abnormal apoptosis of pulmonary alveolar type II epithelial A549 cells in acute respiratory distress syndrome (ARDS), inducible nitric oxide synthase (iNOS) activity in the lung, nitric oxide (NO) production, and the level of protein S-nitrosylation were increased. However, the role of excessive NO production in sepsis-induced ARDS is controversial. Additionally, ghrelin is a growth hormone that exerts an inhibitory role in cell apoptosis. We examined the effect of NO and S-nitrosylation on apoptosis of A549 cells induced by Lipopolysaccharide (LPS) and molecular mechanism underlying the anti-apoptotic effect of ghrelin in this process. METHODS: Flow cytometry and qPCR were used to detect lentiviral infection efficiency and iNOS gene level, respectively. Extracellular and intracellular NO levels were observed by Griess assay kit and DAF-FM DA. Mitochondrial transmembrane potential, apoptosis rate and SNO levels were determined by flow cytometry, Biotin-Switch method and immunofluoresence staining. The expression of iNOS, apoptotic proteins and JNK were assessed by immunoblot analysis. RESULTS: The results showed about two times increase in iNOS expression and intracellular NO levels response to LPS exposure at 24 hours (P< 0.05), while not in extracellular NO levels. NO donors, S-nitroso-N-acetylpenicillamine (SNAP) significantly raised (36.7%, P< 0.05; 38.4%, P< 0.05; 41.8%, P< 0.05) extracellular NO levels without influencing the intracellular NO levels. LPS increased the apoptosis rate (42.4%±2.6% vs 2.8%±1%, P< 0.05) of A549 accompanied by increased Bax levels and decreased Bcl-2 levels through activating JNK signaling, which was reversed when we diminished the iNOS expression in A549 cells using lentiviral vectors encoding iNOS shRNA in the presence of LPS (24.8%±3.8% vs 42.4%±2.6%, P< 0.05). However, the apoptosis rate was increased when SNAP was added (38.8%±1.3% vs 24.8%±3.8%, P< 0.05). Furthermore, we investigated whether ghrelin exert a protective role against LPS-induced apoptosis and the potential mechanism involved in. Ghrelin alone appeared to decrease iNOS expression (32.3%, P< 0.05; 42.3%, P< 0.05), which showed no signifiant difference between LPS+ghrelin group and LPS group. However, this study showed that ghrelin decreased the intracellular NO production (38.9%, P< 0.05), protein S-nitrosylation levels (33.5%, P< 0.05), Bax protein expression (70.2%, P< 0.05), whereas increasing Bcl-2 protein expression (14.1%, P< 0.05) and mitochondrial transmembrane potential (∆ΨM) (20.7%, P< 0.05) in the presence of LPS. CONCLUSION: The data suggested that NO derived from iNOS induced by LPS stimulation exerts an important role in promoting apoptosis of A549 cells, and ghrelin abolished intracellular NO production and protein S-nitrosylation levels, abrogating the apoptosis of A549 cells partly through inhibiting mitochondrial-dependent pathways.

Lentiviral vector delivery of short hairpin RNA to NgR1 promotes nerve regeneration and locomotor recovery in injured rat spinal cord.

Nogo receptor 1 (NgR1) is a high-affinity receptor of myelin-associated inhibitors (MAIs), and suppresses neurogenesis. Lentiviral vector are commonly used to alter the expression of targeted genes. However, little is known about the potential function of lentiviral vector harboring NgR1 shRNA (LV-NgR1 shRNA) on neurogenesis in spinal cord injury (SCI). In this study, the rats were randomly divided into three groups: including the LN (LV-NgR1 shRNA injection), LC (LV-control shRNA injection) and Sham (laminectomy only). Eight weeks post-injection of LV, spinal cords were examined by histology for changes in cavity size and by immunohistochemistry for changes in expression of NgR1, cell apoptosis, astrocytes, neurons and myelination. Motor function was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor scale. Animals that received LV-NgR1 shRNA remarkably improved the motor function. These animals also showed an increase in levels of nerve fibers, synapses and myelination, a decrease in levels of lesion cavity and cell apoptosis at 8 weeks post-treatment. These findings give evidence that NgR1 may be a promising target for SCI treatment.

Predictive value of ADAMTS-13 on concealed chronic renal failure in COPD patients.

BACKGROUND: Impaired renal function is often neglected in COPD patients. Considering that COPD patients usually have an ongoing prothrombotic state and systemic inflammation status, we investigated the association among them and explored the predictive value of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), on concealed chronic renal failure (CRF) in COPD patients. METHODS: COPD patients were recruited from the First Affiliated Hospital of Sun Yat-Sen University between January 2015 and December 2016. Control was selected from contemporaneous hospitalized patients without COPD and matched by age and gender at a ratio of 1:1. Estimated glomerular filtration rate (eGFR) was calculated by using the Chronic Kidney Disease Epidemiology Collaboration formula, and all subjects were categorized as having normal renal function (eGFR ≥60 mL min-1 1.73 m-2) and having concealed CRF (normal serum creatinine while eGFR <60 mL min-1 1.73 m-2). Independent correlates of concealed CRF were investigated by logistic regression analysis, and receiver operating characteristic (ROC) curves were used to determine the predictive value of ADAMTS-13. RESULTS: In total, 106 COPD and 106 non-COPD patients were finally recruited, and the incidences of concealed CRF were 19.81% and 7.55%, respectively. ADAMTS-13 (odds ratio [OR] =0.858, 95% CI =0.795-0.926), D-dimer (OR =1.095, 95% CI =1.027-1.169), and C-reactive protein (OR =1.252, 95% CI =1.058-1.480) were significantly associated with concealed CRF. Sensitivity and specificity at an ADAMTS-13 cutoff of 318.72 ng/mL were 100% and 81.2%, respectively. The area under the ROC curve was 0.959. CONCLUSION: Prothrombotic state and systemic inflammation status might contribute to explaining the high incidence of concealed CRF in COPD, and plasma ADAMTS-13 levels may serve as a strong predictor.

Effects of ghrelin on the apoptosis of human neutrophils in vitro.

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and the diffuse infiltration of neutrophils into the alveolar space. Neutrophils are abundant, short-lived leukocytes that play a key role in immune defense against microbial infections. These cells die via apoptosis following the activation and uptake of microbes, and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter pathogens. Apoptosis is essential for the removal of neutrophils from inflamed tissues and for the timely resolution of neutrophilic inflammation. Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue receptor, produced and secreted mainly from the stomach. Previous studies have reported that ghrelin exerts anti-inflammatory effects in lung injury through the regulation of the apoptosis of different cell types; however, the ability of ghrelin to regulate alveolar neutrophil apoptosis remains largely undefined. We hypothesized that ghrelin may have the ability to modulate neutrophil apoptosis. In this study, to examine this hypothesis, we investigated the effects of ghrelin on freshly isolated neutrophils in vitro. Our findings demonstrated a decrease in the apoptotic ratio (as shown by flow cytometry), as well as in the percentage of cells with decreased mitochondrial membrane potential (ΔΨm) and in the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick­end labeling-positive rate, accompanied by an increased B-cell lymphoma 2/Bax ratio and the downregulation of cleaved caspase-3 in neutrophils following exposure to lipopolysaccharide (100 ng/ml). However, pre-treatment with ghrelin at a physiological level (100 nM) did not have a notable influence on the neutrophils in all the aforementioned tests. Our findings suggest that ghrelin may not possess the ability to modulate the neutrophil lifespan in vitro.

Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide.

Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI.

Clinical value of soluble urokinase-type plasminogen activator receptor in the diagnosis, prognosis, and therapeutic guidance of sepsis.

OBJECTIVES: The level of soluble urokinase-type plasminogen activator receptor (suPAR) is significantly increased in sepsis. We investigated whether suPAR could be a valuable biomarker in sepsis. METHODS: We measured suPAR and procalcitonin (PCT) levels, recorded the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores of engaged subjects, and drew Receiver Operating Characteristics curves. RESULTS: The plasma suPAR and serum PCT levels of the sepsis group were higher than those of the systemic inflammatory response syndrome and control groups. Using suPAR to distinguish systemic inflammatory response syndrome from sepsis on day 1, the area under the curve (AUC) curve was 0.817, and when suPAR and PCT were used in combination to diagnose sepsis, the AUC was 0.927. At a cutoff point of 9.52 ng/mL, the sensitivity and specificity for diagnosis of sepsis using suPAR were 71.93% and 95.46%, respectively. At a cutoff point of 12.01 ng/mL, the sensitivity and specificity for distinguishing survival and mortality by suPAR were 87.1% and 72.5%, respectively. When suPAR and the APACHE II score were combined to distinguish survival from mortality, the AUC was 0.857. The plasma suPAR level was positively correlated with the serum PCT level (r = 0.326, P < .001), APACHE II score (r = 0.492, P < .001), and Sequential Organ Failure Assessment score (r = 0.386, P < .001). CONCLUSIONS: Use of both plasma suPAR and PCT levels enhanced the efficiency of sepsis diagnosis, and the combination of plasma suPAR and APACHE II score improved mortality prediction.