Use of pressure muscle index to predict the contribution of patient's inspiratory effort during pressure support ventilation: a prospective physiological study.

Background: The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support. Methods: In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort. Results: A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H2O (p < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H2O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] (p < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort. Conclusion: Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation.Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393.

Characterization of three lamp genes from largemouth bass (Micropterus salmoides): molecular cloning, expression patterns, and their transcriptional levels in response to fast and refeeding strategy.

Lysosomes-associated membrane proteins (LAMPs), a family of glycosylated proteins and major constituents of the lysosomal membranes, play a dominant role in various cellular processes, including phagocytosis, autophagy and immunity in mammals. However, their roles in aquatic species remain poorly known. In the present study, three lamp genes were cloned and characterized from Micropterus salmoides. Subsequently, their transcriptional levels in response to different nutritional status were investigated. The full-length coding sequences of lamp1, lamp2 and lamp3 were 1251bp, 1224bp and 771bp, encoding 416, 407 and 256 amino acids, respectively. Multiple sequence alignment showed that LAMP1-3 were highly conserved among the different fish species, respectively. 3-D structure prediction, genomic survey, and phylogenetic analysis were further confirmed that these genes are widely existed in vertebrates. The mRNA expression of the three genes was ubiquitously expressed in all selected tissues, including liver, brain, gill, heart, muscle, spleen, kidney, stomach, adipose and intestine, lamp1 shows highly transcript levels in brain and muscle, lamp2 displays highly expression level in heart, muscle and spleen, but lamp3 shows highly transcript level in spleen, liver and kidney. To analyze the function of the three genes under starvation stress in largemouth bass, three experimental treatment groups (fasted group and refeeding group, control group) were established in the current study. The results indicated that the expression of lamp1 was significant induced after starvation, and then returned to normal levels after refeeding in the liver. The expression of lamp2 and lamp3 exhibited the same trend in the liver. In addition, in the spleen and the kidney, the transcript level of lamp1 and lamp2 was remarkably increased in the fasted treatment group and slightly decreased in the refed treatment group, respectively. Collectively, our findings suggest that three lamp genes may have differential function in the immune and energetic organism in largemouth bass, which is helpful in understanding roles of lamps in aquatic species.

Corrigendum: Study on the pathogenesis of MiR-6324 regulating diarrheal irritable bowel syndrome and bioinformatics analysis.

[This corrects the article DOI: 10.3389/fphar.2023.1044330.].

Use of airway pressure-based indices to detect high and low inspiratory effort during pressure support ventilation: a diagnostic accuracy study.

BACKGROUND: Assessment of the patient's respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (Paw)-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation. METHODS: In this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH2O to 2 cmH2O at a 2 cmH2O interval. By performing an end-expiratory airway occlusion maneuver, the negative Paw generated during the first 100 ms (P0.1) and the maximal negative swing of Paw (∆Pocc) were measured. After an end-inspiratory airway occlusion, Paw reached a plateau, and the magnitude of change in plateau from peak Paw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (Pmus) and Pmus-time product per minute (PTPmus/min) were used as the reference standard for the patient's effort. High and low effort was defined as Pmus > 10 and < 5 cmH2O, or PTPmus/min > 200 and < 50 cmH2O s min-1, respectively. RESULTS: A total of 246 levels of PS were tested. The low inspiratory effort was diagnosed in 145 (59.0%) and 136 (55.3%) PS levels using respective Pmus and PTPmus/min criterion. The receiver operating characteristic area of the three Paw-based indices by the respective two criteria ranged from 0.87 to 0.95, and balanced sensitivity (0.83-0.96), specificity (0.74-0.88), and positive (0.80-0.91) and negative predictive values (0.78-0.94) were obtained. The high effort was diagnosed in 34 (13.8%) and 17 (6.9%) support levels using Pmus and PTPmus/min criterion, respectively. High receiver operating characteristic areas of the three Paw-based indices by the two criteria were found (0.93-0.95). A high sensitivity (0.80-1.00) and negative predictive value (0.97-1.00) were found with a low positive predictive value (0.23-0.64). CONCLUSIONS: By performing simple airway occlusion maneuvers, the Paw-based indices could be reliably used to detect low inspiratory efforts. Non-invasive and easily accessible characteristics support their potential bedside use for avoiding over-assistance. More evaluation of their performance is required in cohorts with high effort.

Development of a Prediction Score for Evaluation of Extubation Readiness in Neurosurgical Patients with Mechanical Ventilation.

BACKGROUND: There is no widely accepted consensus on the weaning and extubating protocols for neurosurgical patients, leading to heterogeneity in clinical practices and high rates of delayed extubation and extubation failure-related health complications. METHODS: In this single-center prospective observational diagnostic study, mechanically ventilated neurosurgical patients with extubation attempts were consecutively enrolled for 1 yr. Responsive physicians were surveyed for the reasons for delayed extubation and developed the Swallowing, Tongue protrusion, Airway protection reflected by spontaneous and suctioning cough, and Glasgow Coma Scale Evaluation (STAGE) score to predict the extubation success for neurosurgical patients already meeting other general extubation criteria. RESULTS: A total of 3,171 patients were screened consecutively, and 226 patients were enrolled in this study. The rates of delayed extubation and extubation failure were 25% (57 of 226) and 19% (43 of 226), respectively. The most common reasons for the extubation delay were weak airway-protecting function and poor consciousness. The area under the receiver operating characteristics curve of the total STAGE score associated with extubation success was 0.72 (95% CI, 0.64 to 0.79). Guided by the highest Youden index, the cutoff point for the STAGE score was set at 6 with 59% (95% CI, 51 to 66%) sensitivity, 74% (95% CI, 59 to 86%) specificity, 90% (95% CI, 84 to 95%) positive predictive value, and 30% (95% CI, 21 to 39%) negative predictive value. At STAGE scores of 9 or higher, the model exhibited a 100% (95% CI, 90 to 100%) specificity and 100% (95% CI, 72 to 100%) positive predictive value for predicting extubation success. CONCLUSIONS: After a survey of the reasons for delayed extubation, the STAGE scoring system was developed to better predict the extubation success rate. This scoring system has promising potential in predicting extubation readiness and may help clinicians avoid delayed extubation and failed extubation-related health complications in neurosurgical patients.

Study on the pathogenesis of MiR-6324 regulating diarrheal irritable bowel syndrome and bioinformatics analysis.

Objective: To investigate the pathogenesis of IBS-D by bioinformatics analysis of the differential microRNAs in rat colon tissue and to analyze and predict the function of their target genes. Methods: Twenty male Wistar rats of SPF class were randomly divided into two groups, the model group was manipulated using the colorectal dilatation method + chronic restraint stress method to establish the IBS-D model; while the blank group stroked the perineum at the same frequency. Screening of differential miRNAs after High-throughput sequencing of rat colon tissue. GO and KEGG analysis of target genes using the DAVID website, further mapping using RStudio software; the STRING database and the Cytoscape software were used to obtain the protein interaction network (PPI) of the target genes as well as the core genes. Finally, qPCR was used to detect the expression of target genes in the colon tissue of two groups of rats. Results: After the screening, miR-6324 was obtained as the key of this study. The GO analysis of target genes of miR-6324 is mainly involved in protein phosphorylation, positive regulation of cell proliferation, and intracellular signal transduction; it affects a variety of cellular components such as cytoplasm, nucleus, and organelles on the intracellular surface; it is also involved in molecular functions such as protein binding, ATP binding, and DNA binding. KEGG analysis showed that the intersecting target genes were mainly enriched in cancer pathways, proteoglycans in cancer, neurotrophic signaling pathway, etc. The protein-protein interaction network screened out the core genes mainly Ube2k, Rnf41, Cblb, Nek2, Nde1, Cep131, Tgfb2, Qsox1, and Tmsb4x. The qPCR results showed that the expression of miR-6324 decreased in the model group, but the decrease was not significant. Conclusion: miR-6324 may be involved in the pathogenesis of IBS-D as a potential biological target and provide further ideas for research on the pathogenesis of the disease or treatment options.

Ineffective Effort in Patients With Acute Brain Injury Undergoing Invasive Mechanical Ventilation.

BACKGROUND: Ineffective effort (IE) is a frequent patient-ventilator asynchrony in invasive mechanical ventilation. This study aimed to investigate the incidence of IE and to explore its relationship with respiratory drive in subjects with acute brain injury undergoing invasive mechanical ventilation. METHODS: We retrospectively analyzed a clinical database that assessed patient-ventilator asynchrony in subjects with acute brain injury. IE was identified based on airway pressure, flow, and esophageal pressure waveforms collected at 15-min intervals 4 times daily. At the end of each data set recording, airway-occlusion pressure (P0.1) was determined by the airway occlusion test. IE index was calculated to indicate the severity of IE. The incidence of IE in different types of brain injuries as well as its relationship with P0.1 was determined. RESULTS: We analyzed 852 data sets of 71 subjects with P0.1 measured and undergoing mechanical ventilation for at least 3 d after enrollment. IE was detected in 688 (80.8%) data sets, with a median index of 2.2% (interquartile range 0.4-13.1). Severe IE (IE index ≥ 10%) was detected in 246 (28.9%) data sets. The post craniotomy for brain tumor and the stroke groups had higher median IE index and lower P0.1 compared with the traumatic brain injury group (2.6% [0.7-9.7] vs 2.7% [0.3-21] vs 1.2% [0.1-8.5], P = .002; 1.4 [1-2] cm H2O vs 1.5 [1-2.2] cm H2O vs 1.8 [1.1-2.8] cm H2O, P = .001). Low respiratory drive (P0.1 < 1.14 cm H2O) was independently associated with severe IE in the expiratory phase (IEE) even after adjusting for confounding factors by logistic regression analysis (odds ratio 5.18 [95% CI 2.69-10], P < .001). CONCLUSIONS: IE was very common in subjects with acute brain injury. Low respiratory drive was independently associated with severe IEE.

A Highly Sensitive Urinary Exosomal miRNAs Biosensor Applied to Evaluation of Prostate Cancer Progression.

Prostate cancer is the most common cancer in the male population, carrying a significant disease burden. PSA is a widely available screening tools for this disease. Current screen-printed carbon electrode (SPCE)-based biosensors use a two-pronged probe approach to capture urinary miRNA. We were able to successfully detect specific exosomal miRNAs (exomiRs) in the urine of patients with prostate cancer, including exomiR-451 and exomiR-21, and used electrochemistry for measurement and analysis. Our results significantly reaffirmed the presence of exomiR-451 in urine and that a CV value higher than 220 nA is capable of identifying the presence of disease (p-value = 0.005). Similar results were further proven by a PAS greater than 4 (p-value = 0.001). Moreover, a higher urinary exomiR-21 was observed in the high-T3b stage; this significantly decreased following tumor removal (p-values were 0.016 and 0.907, respectively). According to analysis of the correlation with tumor metastasis, a higher exomiR-21 was associated with lymphatic metastasis (p-value 0.042), and higher exomiR-461 expression was correlated with tumor stage (p-value 0.031), demonstrating that the present exomiR biosensor can usefully predict tumor progression. In conclusion, this biosensor represents an easy-to-use, non-invasive screening tool that is both sensitive and specific. We strongly believe that this can be used in conjunction with PSA for the screening of prostate cancer.

Comparative genomic analysis of carboxylesterase genes in Tenebrio molitor and other four tenebrionids.

Carboxylesterases (COEs) have various functions in wide taxons of organisms. In insects, COEs are important enzymes involved in the hydrolysis of a variety of ester-containing xenobiotics, neural signal transmission, pheromone degradation, and reproductive development. Understanding the diversity of COEs is basic to illustrate their functions. In this study, we identified 53, 105, 37, and 39 COEs from the genomes of Tenebrio molitor, Asbolus verucosus, Hycleus cichorii, and H. phaleratus in the superfamily of Tenebrionidea, respectively. Phylogenetic analysis showed that 234 COEs from these four species and those reported in Tribolium castaneum (63) could be divided into 12 clades and three major classes. The α-esterases significantly expanded in T. molitor, A. verucosus, and T. castaneum compared to dipteran and hymenopteran insects. In T. molitor, most COEs showed tissue and stage-specific but not a sex-biased expression. Our results provide insights into the diversity and evolutionary characteristics of COEs in tenebrionids, and lay a foundation for the functional characterization of COEs in the yellow mealworm.

Validation of the flow index to detect low inspiratory effort during pressure support ventilation.

BACKGROUND: Bedside assessment of low levels of inspiratory effort, which are probably insufficient to prevent muscle atrophy, is challenging. The flow index, which is derived from the analysis of the inspiratory portion of the flow-time waveform, has been recently introduced as a non-invasive parameter to evaluate the inspiratory effort. The primary objective of the present study was to provide an external validation of the flow index to detect low inspiratory effort. METHODS: Datasets containing flow, airway pressure, and esophageal pressure (Pes)-time waveforms were obtained from a previously published study in 100 acute brain-injured patients undergoing pressure support ventilation. Waveforms data were analyzed offline. A low inspiratory effort was defined by one of the following criteria, work of breathing (WOB) less than 0.3 J/L, Pes-time product (PTPes) per minute less than 50 cmH2O•s/min, or inspiratory muscle pressure (Pmus) less than 5 cmH2O, adding "or occurrence of ineffective effort more than 10%" for all criteria. The flow index was calculated according to previously reported method. The association of flow index with Pes-derived parameters of effort was investigated. The diagnostic accuracy of the flow index to detect low effort was analyzed. RESULTS: Moderate correlations were found between flow index and WOB, Pmus, and PTPes per breath and per minute (Pearson's correlation coefficients ranged from 0.546 to 0.634, P < 0.001). The incidence of low inspiratory effort was 62%, 51%, and 55% using the definition of WOB, PTPes per minute, and Pmus, respectively. The area under the receiver operating characteristic curve for flow index to diagnose low effort was 0.88, 0.81, and 0.88, for the three respective definition. By using the cutoff value of flow index less than 2.1, the diagnostic performance for the three definitions showed sensitivity of 0.95-0.96, specificity of 0.57-0.71, positive predictive value of 0.70-0.84, and negative predictive value of 0.90-0.93. CONCLUSIONS: The flow index is associated with Pes-based inspiratory effort measurements. Flow index can be used as a valid instrument to screen low inspiratory effort with a high probability to exclude cases without the condition.

Incidence, Risk Factors and Outcomes of Sepsis in Critically Ill Post-craniotomy Patients: A Single-Center Prospective Cohort Study.

Background: Data concerning the epidemiology of sepsis in critically ill post-craniotomy patients are scarce. This study aimed to assess the incidence, risk factors, and outcomes of sepsis in this population. Methods: This was a single-center prospective cohort study. Post-craniotomy patients admitted to the intensive care unit (ICU) were screened daily for the presence of infection and sepsis. Results: Of the 900 included patients, 300 developed sepsis. The cumulative incidence of sepsis was 33.3% [95% confidence interval (CI), 30.2-36.4%]. Advanced age, male, hypertension, trauma, postoperative intracranial complications, and lower Glasgow Coma Scale (GCS) on the first postoperative day were independent risk factors of sepsis. Septic patients had higher hospital mortality (13.7 vs. 8.3%, P = 0.012), longer ICU length of stay (LOS) (14 vs. 4 days, P < 0.001), longer hospital LOS (31 vs. 19 days, P < 0.001), and higher total medical cost (CNY 138,394 vs. 75,918, P < 0.001) than patients without sepsis. Conclusion: Sepsis is a frequent complication in critically ill post-craniotomy patients. Advanced age, male, hypertension, trauma, postoperative intracranial complications, and lower GCS on the first postoperative day were independent risk factors of sepsis.

A U-shaped association of tracheostomy timing with all-cause mortality in mechanically ventilated patients admitted to the intensive care unit: A retrospective cohort study.

Objectives: To evaluate the association of tracheostomy timing with all-cause mortality in patients with mechanical ventilation (MV). Method: It's a retrospective cohort study. Adult patients undergoing invasive MV who received tracheostomy during the same hospitalization based on the Medical Information Mart for Intensive Care-III (MIMIC-III) database, were selected. The primary outcome was the relationship between tracheostomy timing and 90-day all-cause mortality. A restricted cubic spline was used to analyze the potential non-linear correlation between tracheostomy timing and 90-day all-cause mortality. The secondary outcomes included free days of MV, incidence of ventilator-associated pneumonia (VAP), free days of analgesia/sedation in the intensive care unit (ICU), length of stay (LOS) in the ICU, LOS in hospital, in-ICU mortality, and 30-day all-cause mortality. Results: A total of 1,209 patients were included in this study, of these, 163 (13.5%) patients underwent tracheostomy within 4 days after intubation, while 647 (53.5%) patients underwent tracheostomy more than 11 days after intubation. The tracheotomy timing showed a U-shaped relationship with all-cause mortality, patients who underwent tracheostomy between 5 and 10 days had the lowest 90-day mortality rate compared with patients who underwent tracheostomy within 4 days and after 11 days [84 (21.1%) vs. 40 (24.5%) and 206 (31.8%), P < 0.001]. Conclusion: The tracheotomy timing showed a U-shaped relationship with all-cause mortality, and the risk of mortality was lowest on day 8, but a causal relationship has not been demonstrated.

Feasibility of low-dose dexmedetomidine for prevention of postoperative delirium after intracranial operations: a pilot randomized controlled trial.

BACKGROUND: Clinical trials have shown that dexmedetomidine might decrease the occurrence of postoperative delirium after major surgery, but neurosurgical patients were excluded from these studies. We aimed to determine the feasibility of conducting a full-scale randomized controlled trial of the effect of prophylactic low-dose dexmedetomidine on postoperative delirium in patients after elective intracranial operation for brain tumors. METHODS: In this single-center, parallel-arm pilot randomized controlled trial, adult patients who underwent an elective intracranial operation for brain tumors were recruited. Dexmedetomidine (0.1 µg/kg/hour) or placebo was continuously infused from intensive care unit (ICU) admission on the day of surgery until 08:00 AM on postoperative day one. Adverse events during the study-drug administration were recorded. The primary feasibility endpoint was the occurrence of study-drug interruption. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU during the first five postoperative days. The assessable rate of delirium evaluation was documented. RESULTS: Sixty participants were randomly assigned to receive either dexmedetomidine (n = 30) or placebo (n = 30). The study-drug was stopped in two patients (6.7%) in the placebo group due to desaturation after new-onset unconsciousness and an unplanned reoperation for hematoma evacuation and in one patient (3.3%) in the dexmedetomidine group due to unplanned discharge from the ICU. The absolute difference (95% confidence interval) of study-drug interruption between the two groups was 3.3% (- 18.6 to 12.0%), with a noninferiority P value of 0.009. During the study-drug infusion, no bradycardia occurred, and hypotension occurred in one patient (3.3%) in the dexmedetomidine group. Dexmedetomidine tended to decrease the incidence of tachycardia (10.0% vs. 23.3%) and hypertension (3.3% vs. 23.3%). Respiratory depression, desaturation, and unconsciousness occurred in the same patient with study-drug interruption in the placebo group (3.3%). Delirium was evaluated 600 times, of which 590 (98.3%) attempts were assessable except in one patient in the placebo group who remained in a coma after an unplanned reoperation. CONCLUSIONS: The low rate of study-drug interruption and high assessable rate of delirium evaluation supported a fully powered trial to determine the effectiveness of low-dose dexmedetomidine on postoperative delirium in patients after intracranial operation for brain tumors. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT04494828) on 31/07/2020.

Role of a successful spontaneous breathing trial in ventilator liberation in brain-injured patients.

BACKGROUND: Spontaneous breathing trials (SBTs) have been shown to improve outcomes in critically ill patients. However, in patients with brain injury, indications for intubation and mechanical ventilation are different from those of non-neurological patients, and the role of an SBT in patients with brain injury is less established. The aim of the present study was to compare key respiratory variables acquired during a successful SBT between patients with successful ventilator liberation versus failed ventilator liberation. METHODS: In this prospective study, patients with brain injury (≥18 years of age), who completed a 30-min SBT, were enrolled. Airway pressure, flow, esophageal pressure, and diaphragm electrical activity (ΔEAdi) were recorded before (baseline) and during the SBT. Respiratory rate (RR), tidal volume, inspiratory muscle pressure (ΔPmus), ΔEAdi, and neuromechanical efficiency (ΔPmus/ΔEAdi) of the diaphragm were calculated breath by breath and compared between the liberation success and failure groups. Failed liberation was defined as the need for invasive ventilator assistance within 48 h after the SBT. RESULTS: In total, 46 patients (51.9±13.2 years, 67.4% male) completed the SBT. Seventeen (37%) patients failed ventilator liberation within 48 h. Another 11 patients required invasive ventilation within 7 days after completing the SBT. There were no differences in baseline characteristics between the success and failed groups. In-depth analysis showed similar changes in patterns and values of respiratory physiological parameters between the groups. CONCLUSIONS: In patients with brain injury, ventilator liberation failure was common after successful SBT. In-depth physiological analysis during the SBT did not provide data to predict successful liberation in these patients. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (No. NCT02863237).

A gap existed between physicians' perceptions and performance of pain, agitation-sedation and delirium assessments in Chinese intensive care units.

BACKGROUND: Pain, agitation-sedation and delirium management are crucial elements in the care of critically ill patients. In the present study, we aimed to present the current practice of pain, agitation-sedation and delirium assessments in Chinese intensive care units (ICUs) and investigate the gap between physicians' perception and actual clinical performance. METHODS: We sent invitations to the 33 members of the Neuro-Critical Care Committee affiliated with the Chinese Association of Critical Care Physicians. Finally, 24 ICUs (14 general-, 5 neuroscience-, 3 surgical-, and 2 emergency-ICUs) from 20 hospitals participated in this one-day point prevalence study combined with an on-site questionnaire survey. We enrolled adult ICU admitted patients with a length of stay ≥24 h, who were divided into the brain-injured group or non-brain-injured group. The hospital records and nursing records during the 24-h period prior to enrollment were reviewed. Actual evaluations of pain, agitation-sedation and delirium were documented. We invited physicians on-duty during the 24 h prior to the patients' enrollment to complete a survey questionnaire, which contained attitude for importance of pain, agitation-sedation and delirium assessments. RESULTS: We enrolled 387 patients including 261 (67.4%) brain-injured and 126 (32.6%) non-brain-injured patients. There were 19.9% (95% confidence interval [CI]: 15.9-23.9%) and 25.6% (95% CI: 21.2-29.9%) patients receiving the pain and agitation-sedation scale assessment, respectively. The rates of these two types of assessments were significantly lower in brain-injured patients than non-brain-injured patients (p = 0.003 and < 0.001). Delirium assessment was only performed in three patients (0.8, 95% CI: 0.1-1.7%). In questionnaires collected from 91 physicians, 70.3% (95% CI: 60.8-79.9%) and 82.4% (95% CI: 74.4-90.4%) reported routine use of pain and agitation-sedation scale assessments, respectively. More than half of the physicians (52.7, 95% CI: 42.3-63.2%) reported daily screening for delirium using an assessment scale. CONCLUSIONS: The actual prevalence of pain, agitation-sedation and delirium assessment, especially delirium screening, was suboptimal in Chinese ICUs. There is a gap between physicians' perceptions and actual clinical practice in pain, agitation-sedation and delirium assessments. Our results will prompt further quality improvement projects to optimize the practice of pain, agitation-sedation and delirium management in China. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03975751 . Retrospectively registered on 2 June 2019.

Patient-ventilator asynchrony in acute brain-injured patients: a prospective observational study.

BACKGROUND: Patient-ventilator asynchrony is common in mechanically ventilated patients and may be related to adverse outcomes. Few studies have reported the occurrence of asynchrony in brain-injured patients. We aimed to investigate the prevalence, type and severity of patient-ventilator asynchrony in mechanically ventilated patients with brain injury. METHODS: This prospective observational study enrolled acute brain-injured patients undergoing mechanical ventilation. Esophageal pressure monitoring was established after enrollment. Flow, airway pressure, and esophageal pressure-time waveforms were recorded for a 15-min interval, four times daily for 3 days, for visually detecting asynchrony by offline analysis. At the end of each dataset recording, the respiratory drive was determined by the airway occlusion maneuver. The asynchrony index was calculated to represent the severity. The relationship between the prevalence and the severity of asynchrony with ventilatory modes and settings, respiratory drive, and analgesia and sedation were determined. Association of severe patient-ventilator asynchrony, which was defined as an asynchrony index ≥ 10%, with clinical outcomes was analyzed. RESULTS: In 100 enrolled patients, a total of 1076 15-min waveform datasets covering 330,292 breaths were collected, in which 70,156 (38%) asynchronous breaths were detected. Asynchrony occurred in 96% of patients with the median (interquartile range) asynchrony index of 12.4% (4.3%-26.4%). The most prevalent type was ineffective triggering. No significant difference was found in either prevalence or asynchrony index among different classifications of brain injury (p > 0.05). The prevalence of asynchrony was significantly lower during pressure control/assist ventilation than during other ventilatory modes (p < 0.05). Compared to the datasets without asynchrony, the airway occlusion pressure was significantly lower in datasets with ineffective triggering (p < 0.001). The asynchrony index was significantly higher during the combined use of opioids and sedatives (p < 0.001). Significantly longer duration of ventilation and hospital length of stay after the inclusion were found in patients with severe ineffective triggering (p < 0.05). CONCLUSIONS: Patient-ventilator asynchrony is common in brain-injured patients. The most prevalent type is ineffective triggering and its severity is likely related to a long duration of ventilation and hospital stay. Prevalence and severity of asynchrony are associated with ventilatory modes, respiratory drive and analgesia/sedation strategy, suggesting treatment adjustment in this particular population. Trial registration The study has been registered on 4 July 2017 in ClinicalTrials.gov (NCT03212482) ( https://clinicaltrials.gov/ct2/show/NCT03212482 ).

Derecruitment volume assessment derived from pressure-impedance curves with electrical impedance tomography in experimental acute lung injury.

OBJECTIVE: To investigate the accuracy of derecruitment volume (VDER) assessed by pressure-impedance (P-I) curves derived from electrical impedance tomography (EIT). METHODS: Six pigs with acute lung injury received decremental positive end-expiratory pressure (PEEP) from 15 to 0 in steps of 5 cmH2O. At the end of each PEEP level, the pressure-volume (P-V) curves were plotted using the low constant flow method and release maneuvers to calculate the VDER between the PEEP of setting levels and 0 cmH2O (VDER-PV). The VDER derived from P-I curves that were recorded simultaneously using EIT was the difference in impedance at the same pressure multiplied by the ratio of tidal volume and corresponding tidal impedance (VDER-PI). The regional P-I curves obtained by EIT were used to estimate VDER in the dependent and nondependent lung. RESULTS: The global lung VDER-PV and VDER-PI showed close correlations (r = 0.948, P<0.001); the mean difference was 48 mL with limits of agreement of -133 to 229 mL. Lung derecruitment extended into the whole process of decremental PEEP levels but was unevenly distributed in different lung regions. CONCLUSIONS: P-I curves derived from EIT can assess VDER and provide a promising method to estimate regional lung derecruitment at the bedside.

Effect of positive end-expiratory pressure on functional residual capacity in two experimental models of acute respiratory distress syndrome.

OBJECTIVE: Measurement of positive end-expiratory pressure (PEEP)-induced recruitment lung volume using passive spirometry is based on the assumption that the functional residual capacity (FRC) is not modified by the PEEP changes. We aimed to investigate the influence of PEEP on FRC in different models of acute respiratory distress syndrome (ARDS). METHODS: A randomized crossover study was performed in 12 pigs. Pulmonary (n = 6) and extra-pulmonary (n = 6) ARDS models were established using an alveolar instillation of hydrochloric acid and a right atrium injection of oleic acid, respectively. Low (5 cmH2O) and high (15 cmH2O) PEEP were randomly applied in each animal. FRC and recruitment volume were determined using the nitrogen wash-in/wash-out technique and release maneuver. RESULTS: FRC was not significantly different between the two PEEP levels in either pulmonary ARDS (299 ± 92 mL and 309 ± 130 mL at 5 and 15 cmH2O, respectively) or extra-pulmonary ARDS (305 ± 143 mL and 328 ± 197 mL at 5 and 15 cmH2O, respectively). The recruitment volume was not significantly different between the two models (pulmonary, 341 ± 100 mL; extra-pulmonary, 351 ± 170 mL). CONCLUSIONS: PEEP did not influence FRC in either the pulmonary or extra-pulmonary ARDS pig model.

Status, challenges, and future prospects of stem cell therapy in pelvic floor disorders.

Pelvic floor disorders (PFDs) represent a group of common and frequently-occurring diseases that seriously affect the life quality of women, generally including stress urinary incontinence and pelvic organ prolapse. Surgery has been used as a treatment for PFD, but almost 30% of patients require subsequent surgery due to a high incidence of postoperative complications and high recurrence rates. Therefore, investigations of new therapeutic strategies are urgently needed. Stem cells possess strong multi-differentiation, self-renewal, immunomodulation, and angiogenesis abilities and they are able to differentiate into various cell types of pelvic floor tissues and thus provide a potential therapeutic approach for PFD. Recently, various studies using different autologous stem cells have achieved promising results by improving the pelvic ligament and muscle regeneration and conferring the tissue elasticity and strength to the damaged tissue in PFD, as well as reduced inflammatory reactions, collagen deposition, and foreign body reaction. However, with relatively high rates of complications such as bladder stone formation and wound infections, further studies are necessary to investigate the role of stem cells as maintainers of tissue homeostasis and modulators in early interventions including therapies using new stem cell sources, exosomes, and tissue-engineering combined with stem cell-based implants, among others. This review describes the types of stem cells and the possible interaction mechanisms in PFD treatment, with the hope of providing more promising stem cell treatment strategies for PFD in the future.

Use of Electrical Impedance Tomography (EIT) to Estimate Global and Regional Lung Recruitment Volume (VREC) Induced by Positive End-Expiratory Pressure (PEEP): An Experiment in Pigs with Lung Injury.

BACKGROUND Electrical impedance tomography (EIT) is a real-time tool used to monitor lung volume change at the bedside, which could be used to measure lung recruitment volume (VREC) for setting positive end-expiratory pressure (PEEP). We assessed and compared the agreement in VREC measurement with the EIT method versus the flow-derived method. MATERIAL AND METHODS In 12 Bama pigs, lung injury was induced by tracheal instillation of hydrochloric acid and verified by an arterial partial pressure of oxygen to inspired oxygen fraction ratio below 200 mmHg. During the end-expiratory occlusion, an airway release maneuver was conduct at 5 and 15 cmH2O of PEEP. VREC was measured by flow-integrated PEEP-induced lung volume change (flow-derived method) and end-expiratory lung impedance change (EIT-derived method). Linear regression and Bland-Altman analysis were used to test the correlation and agreement between these 2 measures. RESULTS Lung injury was successfully induced in all the animals. EIT-derived VREC was significantly correlated with flow-derived VREC (R²=0.650, p=0.002). The bias (the lower and upper limits of agreement) was -19 (-182 to 144) ml. The median (interquartile range) of EIT-derived VREC was 322 (218-469) ml, with 110 (59-142) ml and 194 (157-307) ml in dependent and nondependent lung regions, respectively. Global and regional respiratory system compliance increased significantly at high PEEP compared to those at low PEEP. CONCLUSIONS Close correlation and agreement were found between EIT-derived and flow-derived VREC measurements. The advantages of EIT-derived recruitability assessment included the avoidance of ventilation interruption and the ability to provide regional recruitment information.