Background The use of extracorporeal membrane oxygenation (ECMO) has expanded significantly, especially during the COVID-19 pandemic, but membrane lung (ML) function at high altitudes remains unexplored. This study aimed to determine whether ML oxygen delivery (V’O2ML) capacity during ECMO is lower in high-altitude Xining than at low-altitude Beijing in China. Methods In this prospective observational study, patients who received ECMO were categorized into the Xining or Beijing group based on treatment center. Patients were monitored for ML gas transfer on the third day of ECMO, and clinical outcomes were compared between the two groups. Results Sixty patients were enrolled, 30 in each group. V'O2ML was significantly lower in the Xining group than in the Beijing group (171 [130-203] ml/min vs. 210 [178-255] ml/min, p = 0.002). Mortality at 60 days showed no significant difference, but ML failure was higher in the Xining group (26.7% vs 6.7%, p = 0.038). V'O2ML was positively correlated with post-ML arterial partial pressure of oxygen (PaO2), hemoglobin, and fibrinogen and negatively correlated with D-dimer (all p < 0.001). Older age (OR, 1.075; 95% CI, 1.020-1.132, p = 0.007) and lower V’O2ML capacity (OR, 0.984; 95% CI, 0.974-0.995, p = 0.005) were independent risk factors for 60-day mortality. The optimal V'O2ML cutoff for survival was ≥205ml/min, with higher V'O2ML associated with better outcomes (p < 0.001). Conclusions High altitude is associated with lower V’O2ML capacity during ECMO, although it does not appear to increase short-term mortality. V'O2ML is an essential prognostic factor, and further research with larger cohorts and dynamic monitoring of V'O2ML across different altitudes is recommended. Trial Registration ClinicalTrials.Gov: NCT06152744. Registered 22 November 2023

Background Flexible bronchoscopy (FB) is commonly performed in patients with acute respiratory failure (ARF), but the procedure can exacerbate hypoxemia and increase the need for respiratory support. The impact of high-flow nasal oxygen (HFNO) therapy during nasal FB in patients with ARF remains uncertain, as prior studies have focused primarily on oxygenation rather than clinical outcomes. We aimed to evaluate whether HFNO therapy via a single-prong cannula interface (HFNO-SPC) could reduce the need for respiratory support escalation within 24 h after FB compared to standard oxygen therapy (SOT). Methods We conducted a two-center, open-label, randomized controlled trial comparing HFNO-SPC to SOT in patients undergoing FB. The primary outcome was escalation of respiratory support within 24 h after FB, defined as the requirement for invasive mechanical ventilation (IMV), noninvasive ventilation (NIV), or HFNO, or as increases in support parameters without changing the mode of respiratory support. The secondary outcome was a hierarchical composite of these escalation events. Electrical impedance tomography (EIT) monitoring was performed during FB to assess tidal volume and end-expiratory lung volume changes. Results A total of 160 patients were randomized to either the HFNO-SPC group (n = 80) or the SOT group (n = 80), and all were included in the intention-to-treat analysis. HFNO-SPC significantly reduced the incidence of respiratory support escalation compared to SOT (15.0% vs. 33.8%, P = 0.006). Hierarchical analysis of the composite secondary outcome supported the primary findings (31.6% vs 12.1%, P = 0.004). Additionally, HFNO-SPC resulted in a lower intubation rate within 24 h (7.5% vs. 20.0%, P = 0.022). EIT measurements showed smaller reductions in tidal impedance variation (TIV) during FB and less pronounced changes in end-expiratory lung impedance (ΔEELI) during and after FB in the HFNO-SPC group. Conclusions In patients with ARF, HFNO-SPC significantly reduced the proportion of patients requiring respiratory support escalation within 24 h after FB compared with SOT. This finding was consistent across a hierarchical analysis of clinically ranked outcomes. Trial Registration ClinicalTrials.Gov: NCT 05759832. Registered 27 February 2023.

Objective: High glycemic variability (GV) often indicates a poor prognosis. Our aim is to investigate the relationship between GV and short and long-term mortality in critically ill heart failure (HF) patients. Methods: We extracted data from the Medical Information Mart for Intensive Care IV database. The risks of inhospital and 1-year mortality were calculated using Logistic and COX regression. In addition, mediation analysis was used to investigate the indirect effect of ventricular arrhythmias (VA) on in-hospital mortality. Results: Among 8,980 critically ill HF patients, the multifactorial regression analysis showed that high GV was associated with an increased risk of in-hospital and 1-year mortality (OR 1.69, 95 % CI 1.47-1.93; HR 1.12, 95 % CI 1.02-1.22). The Kaplan-Meier survival curve and restricted cubic spline plot also emphasized this association. Furthermore, the impact of GV on in-hospital mortality was partially mediated by VA (4.98%). And the increased risk of 1-year mortality associated with high GV was more significant in person with diabetes (p for interaction =0.018). Conclusion: Our Study indicates that high GV may be an independent risk factor for short and long-term mortality in critically ill HF patients. Maintaining the stability of blood glucose can reduce adverse outcomes in critically ill HF patients.

The frameshifting element (FSE) comprises a slippery heptanucleotide sequence followed by a downstream RNA structure, such as a pseudoknot or stem-loop. Found in various RNA viruses, FSE regulates viral replication via programmed -1 ribosomal frameshifting (-1 PRF), making it a potential broad-spectrum antiviral target. Advances in RNA structural analysis have elucidated the dynamic conformations and cross-viral diversity of FSE, with the SARS-CoV-2 outbreak further highlighting its role in viral replication. Efforts to develop antiviral drugs targeting FSE have progressed through virtual and phenotypic screening. In this review, we explore the evolution, structure, and function of FSE in coronaviruses, evaluate recent advances in FSE-targeted drug development, and discuss their design advantages, efficacy, and challenges, providing insights for future antiviral strategies.

Introduction:Although recent research suggests that alterations in gut microbiota play a critical role in the pathophysiology of kidney diseases, the causal relationship between specific intestinal flora and the risk of kidney diseases remains unclear. Here, we investigated the causal relationship between gut microbiota and different kidney diseases through mendelian randomization analysis. Methods:Gut microbiota and three types of kidney diseases, including diabetic nephropathy, IgA nephropathy, and membranous nephropathy, were identified from large-scale genome-wide association studies summary data. Inverse variance weighted method was employed to estimate causal relationships. Cochran's Q test was utilized to uncover any heterogeneity. The mendelian randomization-Egger intercept test was employed to detect horizontal pleiotropy, and the leave-one-out method was used for testing the stability. In addition, the reverse, multivariable, and two-step mendelian randomization analysis was conducted to assess the causation possibilities. Furthermore, the associations between three types of kidney diseases and immune infiltration were determined. Results:We identified 1,531 single-nucleotide polymorphisms. There were 6 positive and 9 negative causal effects between gut microbiota and three types of kidney diseases. Specifically, Dialister was a protective factor for diabetic nephropathy while Lachnospiraceae UCG-008 was a risk factor. Clostridium innocuum was a protective factor for IgA nephropathy, while Christensenellaceae R.7, Clostridium sensu stricto1, Lachnospiraceae UCG-004, Lachnospiraceae UCG-010, Oscillospira, Ruminococcaceae UCG-010, and Terrisporobacter were risk factors for IgA nephropathy. Butyricicoccus, Catenibacterium, Flavonifractor, and Lachnospira were associated with an increased risk of membranous nephropathy, while Ruminococcaceae UCG-011 was associated with a decreased risk of membranous nephropathy. Sensitivity analysis indicated the results were robust. No significant pleiotropy or heterogeneity was identified. Notably, the reverse mendelian randomization analysis did not reveal any causal relationship. After adjusting for environmental confounders, including CO, PM 2.5, PM 10, and exposure to tobacco smoke at home, these causal relationships still exist. Additionally, immune infiltration analysis indicated unique immune cell distribution in each type of kidney disease, which are largely consistent with later two-step approach, emphasizing the significance of immunological processes in the diseases. Conclusion:This study uncovered the causal relationship between gut microbiota and three types of kidney diseases. This discovery provides fresh perspectives on how microbes contribute to kidney diseases, paving the way for more in-depth clinical studies.

ABSTRACT Objective In thoracic posterior decompression surgery, the traditional pedicle‐to‐pedicle (PTP) approach may have limitations in achieving complete decompression and may also pose potential risks of injury to the spinal cord. Through comparative analysis with the PTP method, the study explored the safety of posterior thoracic decompression via the pedicle‐ossification tunnel (POT), aiming to provide a more scientific and safer clinical surgical pathway selection. Methods Combined with preoperative image data and intraoperative operation images, the POT decompression method was deeply analyzed. In this study, the thoracic vertebrae of sheep were taken as experimental specimens. The water sac was placed close to the joint level of the articular process to simulate the spinal cord, and the experiment was carried out by the surgical methods of PTP and POT respectively with a high‐speed bur. The laser displacement sensor (LDS) was used to monitor the vibration displacement of the water sac, and the collected vibration data was divided into 0.1 s/frame (500 vibration signal data points), which were used to calculate the curvature change of the vibration displacement curve. The Wilcoxon rank sum test was used for statistical analysis. Milling parameters for the high‐speed bur were set to: milling depth 0.5 mm, milling speed 0.5 mm/s, milling angle 45 ° , and spherical bit size 4 mm. Results Combining the detailed preoperative image data and intraoperative images of key operations, the study first provides a detailed description of the surgical steps for safe posterior thoracic decompression via the POT. Then, based on Euler–Bernoulli beam theory, the vibration of the “spinal cord” under different surgery pathways (POT and PTP) in posterior thoracic decompression was further studied. The statistical analysis showed that the vibration amplitude and curvature value of the vibration curve of POT and PTP were significantly different ( p < 0.05). As the milling position approached POT, the amplitude and curvature values also decreased gradually. Conclusion Through theoretical analysis and experimental verification, the safety and effectiveness of posterior thoracic decompression via POT was thoroughly investigated. The milling pathway via POT could not only achieve the surgical purpose of complete decompression, but also avoid the contact area between OLF and dura as much as possible, thus reducing the irritation to the spinal cord.

Objective To verify the accuracy of a Non-Contact Sleep Monitoring Mattress(NCSMM)based on body movement during sleep in assessing sleep quality of patients before neurosurgery in order to provide a more portable and efficient assessment tool for clinical staff.Methods A single-arm trial was conducted on 114 inpatients admitted in our department selected with convenience sampling.Sleep quality data of 1 night were collected through 5 sleep quality assessment tools,including NCSMM,polysomnography(PSG),Patient-Reported Outcome Measurement Information System(PROMIS)Sleep Disturbance scale,Richards-Campbell Sleep Scale(RCSQ),and a wearable device(smart watch for body movements and sleep quality monitoring).The sleep efficiency(≤85%)obtained by PSG was used as the diagnostic standard for sleep disorders.The area under the receiver operating characteristic curve(AUC),sensitivity,specificity,positive predictive value,negative predictive value,and Youden index were calculated for the other 4 tools to evaluate and compare their diagnostic effectiveness.Results The AUC value for NCSMM,PROMIS,RCSQ and smart watch was 0.788(95%CI:0.687～0.888,P<0.001),0.664(95%CI:0.543～0.784,P=0.02),0.723(95%CI:0.600～0.846,P=0.001)and 0.750(95%CI:0.654～0.846,P<0.001),respectively.The diagnostic accuracy rate was 0.774,0.559,0.742 and 0.602,with corresponding Youden index value of 0.488,0.321,0.456,and 0.459.NCSMM demonstrated the best AUC value,sensitivity and Youden index when compared with the other 3 tools.Conclusion NCSMM shows high accuracy in assessing sleep quality in pre-neurosurgery inpatients,and it is a viable portable and efficient assessment tool in clinical practice.

Prone positioning (PP) is widely used in patients with moderate to severe acute respiratory distress syndrome (ARDS) to reduce mortality by mitigating the risk of ventilation-induced lung injury (VILI) and enhancing ventilation-perfusion (V/Q) matching. However, patient responses to PP are variable, and the relationship between V/Q matching improvement during PP and clinical outcomes remains unclear. This study aimed to test the hypothesis that improvements in V/Q matching 4 h within the first PP are associated with reduced intensive care unit (ICU) mortality. In this two-center, prospective, observational study, regional ventilation and perfusion changes in patients with moderate to severe ARDS were evaluated using electrical impedance tomography (EIT) during the first PP session. Patients were categorized as responders or non-responders based on whether V/Q matching improved by ≥ 10

Antifungal persistence is the phenomenon that occurs when a subpopulation of fungal cells can survive in the presence of high concentrations of antifungal drugs, which is different from the concepts of antifungal resistance and tolerance. Fungal persisters are not mutants but phenotypic variants of normal cells, entering a dormant state with low metabolism and proliferation. Previous studies have shown that antifungal persistence may lead to therapeutic failure, as well as chronic or recurrent fungal infections in clinical settings. This review provides a comprehensive overview of antifungal persistence covering its definition, distinctions from other related concepts, detection methods, and molecular mechanisms of formation. Importantly, we discuss relevant in vivo experiments and clinical observations to assess clinical relevance of antifungal persistence.

Background: Adjuvant corticosteroids are effective in patients with human immunodeficiency virus (HIV)-associated Pneumocystis jirovecii pneumonia (PCP) patients, but the effectiveness of adjuvant corticosteroids in non-HIV PCP remained controversial. This study aimed to evaluate the effectiveness of standard-dose compared with low-dose steroids in non-HIV PCP patients with acute respiratory distress syndrome (ARDS). Methods: This retrospective observational study included non-HIV PCP patients with ARDS admitted to the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital from 2015 to 2022. Demographics, clinical characteristics, and outcomes were compared between patients receiving standard-dose and those receiving low-dose steroids. Survival times were assessed using Kaplan-Meier curves and compared with the Log rank test. Cox proportional hazards regression analysis was conducted to identify independent risk factors for 28-day and 60-day mortality. Results: A total of 105 non-HIV PCP with ARDS were included, with 48 patients in the standard-dose steroid group (66.7% male, 50.5 +/- 12.6 years) and 57 in the low-dose steroid group (61.4% male, 55.5 +/- 14.2 years). The 60-day mortality was lower in the standard-dose group than in the low-dose group (63.2% vs 48.3%, p=0.04), while 28-day mortality showed no significant difference (50.8% vs 35.4%, p=0.11). After adjusting for confounders, standard-dose steroids reduced 28-day mortality (aHR: 0.339, 95% CI: 0.147- 0.780) and 60-day mortality (aHR: 0.328, 95% CI: 0.152- 0.709), particularly in patients aged < 65 years, non-smokers, those requiring mechanical ventilation, with albumin< 30 g/L, or a PaO2/FiO(2) ratio < 150 mmHg. No differences in co-infections or gastrointestinal bleeding were observed. Conclusion: The standard-dose steroid therapy significantly reduced 28-day and 60-day mortality without major complications in the non-HIV immunocompromised population with severe PCP with ARDS. These findings highlight the potential survival benefit of standard-dose corticosteroid regimen in this population.

Abstract Objective To verify whether the bleeding risk assessment guidelines from the 9th American College of Chest Physicians (ACCP) are prognostic for respiratory intensive care unit (RICU) patients and to explore risk factors for hemorrhages, we conducted a secondary data analysis based on our previously published cohort study of venous thromboembolism. Patients and methods We performed a secondary data analysis on the single-center prospective cohort from our previous study. Patients admitted to the RICU at Beijing Chao-Yang Hospital from August 1, 2014 to December 31, 2020 were included and followed up until discharge. Results The study enrolled 931 patients, of which 715 (76.8%) were at high risk of bleeding, while the remaining were at low risk. Of the total, 9.2% (86/931) suffered major bleeding, and no significant difference was found between the two risk groups (p = 0.601). High-risk patients had poor outcomes, including higher mortality and longer stays. Independent risk factors for major bleeding were APACHE II score ≥ 15; invasive pulmonary aspergillosis; therapeutic dose of anticoagulants; extracorporeal membrane oxygenation; and continuous renal replacement therapy. Blood transfusion not related to bleeding appeared to be an independent protective factor for major bleeding (OR 0.099, 95% CI 0.045–0.218, p < 0.001). Conclusion Bleeding risk assessment models from the 9th ACCP guidelines may not be suitable for patients in RICU. Building a bleeding risk assessment model that is suitable for patients in all RICUs remains a challenge. Trial registration ClinicalTrials.gov: NCT02213978.

Background Adjuvant corticosteroids are effective in patients with human immunodeficiency virus (HIV)-associated Pneumocystis jirovecii pneumonia (PCP) patients, but the effectiveness of adjuvant corticosteroids in non-HIV PCP remained controversial. This study aimed to evaluate the effects of steroids in non-HIV PCP patients with acute respiratory distress syndrome (ARDS). Methods This retrospective observational study included non-HIV PCP patients with ARDS admitted to the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital from 2015 to 2022 were included. We compared demographics, clinical characteristics, and outcomes between patients who received a 21-day course of standard-dose steroids and those who received low-dose steroids. Kaplan-Meier curve and log-rank test were performed to compare the survival time between standard-dose steroid and low-dose steroid patients. Cox regression analysis was performed to identify risk factors for 28- and 60-day mortality. Results A total of 105 non-HIV PCP with ARDS were identified, 48 in the 21-day course of standard-dose steroid group (66.7% male, 50.5±12.6 years) and 57 in the low-dose steroid group(61.4% male, 55.5±14.2 years). 60-day mortality was significantly different between the two groups (63.2% vs 48.3%, p=0.04), but 28-day mortality was not (50.8% vs 35.4%, p=0.11). After adjustment for confounders, 60-day mortality (adjusted hazard ratio: 0.415, 95% confidence interval: 0.227-0.760) was lower in the 21-day standard-dose steroid group compared with those in the low-dose steroid group. 21-day standard-dose steroids were associated with lower 60-day mortality in patients aged<65 years, no smokers, requiring mechanical ventilation, lactic dehydrogenase≥ 495U/L, and PaO2/FiO2 ratio<150mmHg. There were no differences in co-infections and gastrointestinal bleeding between the two groups. Conclusions In conclusion, the 21-day standard-dose steroids therapy significantly reduced 60-day mortality without major complications in the non-HIV immunocompromised population with severe PCP with ARDS.

IntroductionSystematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS).MethodThis was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument.ResultA total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn’t continue improving after 3 months. Health-related quality of life didn’t change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening.ConclusionThe improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

Abstract Background A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO. Methods In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching. Results A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035). Conclusions Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO. Trial Registration ClinicalTrials.Gov: NCT04139733. Registered 23 October 2019.

Introduction Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). Methods This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. Results This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO 2 /FiO 2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. Conclusion Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

Abstract Background Critically ill patients in intensive care units (ICUs) are at high risk of venous thromboembolism (VTE). This study aimed to explore the prophylaxis effect under a guideline-based thromboprophylaxis protocol among critically ill patients in a respiratory ICU. Methods For this single-center prospective cohort study, we followed the thromboprophylaxis protocol, which was drawn up based on relevant guidelines and Chinese experts’ advice. Clinical data were entered into an electronic case report form and analyzed. Multivariate logistic regression was conducted to explore independent risk factors of VTE event under this protocol. Results From August 1, 2014, to December 31, 2020, 884 patients underwent thromboprophylaxis according to this protocol; 10.5% of them received mechanical prophylaxis, 43.8% received pharmacological prophylaxis, and 45.7% received pharmacological combined with mechanical prophylaxis. The proportion of VTE events was 14.3% for patients who received the thromboprophylaxis protocol, of which 0.1% had pulmonary thromboembolism (PTE), 2.0% had proximal deep vein thrombosis (DVT), and 12.1% had isolated distal DVT. There was no significant difference between different thromboprophylaxis measures. Cirrhosis (OR 5.789, 95% CI [1.402, 23.894], P = 0.015), acute asthma exacerbation (OR 39.999, 95% CI [4.704, 340.083], P = 0.001), and extracorporeal membrane oxygenation treatment (OR 22.237, 95%CI [4.824, 102.502], P < 0.001) were independent risk factors for proximal DVT under thromboprophylaxis. Conclusions The thromboprophylaxis protocol based on guidelines applied in the ICU was practicable and could help decrease the proportion of PTE and proximal DVT events. The risk factors of VTE events happening under the thromboprophylaxis protocol require more attention. Trial registration ClinicalTrials.gov: NCT02213978.

OBJECTIVE:To evaluate the safety and efficacy of argatroban applied as alternative anticoagulant in critical illness patients underwent extracorporeal membrane oxygenation (ECMO) with contraindications of unfractionated heparin (UFH), and to further explore the effective dose of argatroban. METHODS:From July 1, 2013 to February 28, 2022, there were 14 patients who admitted in the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital received ECMO and used argatroban for anticoagulation (argatroban group). Two of them received argatroban as the initial anticoagulant. The remaining 12 patients used UFH at first, and then switched to argatroban. UFH group included 28 patients who received UFH for anticoagulation after matching the demographic characteristics. Primary endpoint was the prevalence of ECMO-related thrombotic events. Secondary endpoints included the type of thrombotic events, prevalence of ECMO-related major bleeding events, bleeding sites, ICU mortality, mortality during ECMO, liver and kidney function, thrombelastogram, blood transfusion, dosage of argatroban, the dynamic changes of coagulation variables 4 days before and 7 days after argatroban treatment. RESULTS:In argatroban group, there were 8 patients received veno-venous ECMO (VV-ECMO), 2 patients with veno-arterial ECMO (VA-ECMO), and 4 patients with veno-arterio-venous ECMO (VAV-ECMO). In UFH group, VV-ECMO was applied in 23 patients, VA-ECMO and VAV ECMO was established in 3 patients and 2 patients, respectively. In endpoint events, the incidence of ECMO related thrombotic events in argatroban group was slightly higher than that in UFH group (28.6% vs. 21.4%). The ECMO running time in argatroban group was slightly longer than that in UFH group [days: 16 (7, 21) vs. 13 (8, 17)]. The incidence of ECMO-related bleeding events (28.6% vs. 32.1%) and mortality during ECMO (35.7% vs. 46.4%) in argatroban group were slightly lower than those in UFH group. However, the differences were not statistically significant (all P < 0.05). The platelet transfusion in argatroban group was significantly higher than that in UFH group [U: 7.7 (0, 10.0) vs. 0.8 (0, 1.0)]. The coagulation reaction time (R value) in thrombelastography in argatroban group was significantly longer than that in UFH group [minutes: 9.3 (7.2, 10.8) vs. 8.8 (6.3, 9.7)]. The maximum width value [MA value, mm: 48.4 (40.7, 57.9) vs. 52.6 (45.4, 61.5)] and blood clot generation rate [α-Angle (deg): 54.1 (45.4, 62.0) vs. 57.9 (50.2, 69.0)] in the argatroban group were significantly lower than those in the UFH group (all P < 0.05). The activated partial thromboplastin time (APTT) was prolonged after changing from UFH to argatroban in the argatroban group [seconds: 63.5 (58.4, 70.6) vs. 56.7 (53.1, 60.9)]. The PLT level showed a decreasing trend during UFH anticoagulation therapy, and gradually increased after changing to argatroban. D-dimer level was 19.1 (7.0, 28.7) mg/L after switching to argatroban, and then no longer showed an increasing trend. The level of fibrinogen (FIB) showed a decreasing trend during the anticoagulant therapy of UFH (the lowest was 23.6 g/L), and fluctuated between 16.8 and 26.2 g/L after changing to argatroban. The median initial dose of argatroban was 0.049 (0.029, 0.103) μg×kg-1×min-1, which the highest dose was in VV-ECMO patients of [0.092 (0.049, 0.165) μg×kg-1×min-1]. The initial dose of VAV-ECMO was the lowest [0.026 (0.013, 0.041) μg×kg-1×min-1], but without significant difference (P > 0.05). The maintenance dose of argatroban was 0.033 (0.014, 0.090) μg×kg-1×min-1, VV-ECMO patients was significantly higher than those in VA-ECMO and VAV-ECMO patients [μg×kg-1×min-1: 0.102 (0.059, 0.127) vs. 0.036 (0.026, 0.060), 0.013 (0.004, 0.022), both P < 0.05]. CONCLUSIONS:Argatroban appears to be a feasible, effective and safety alternative anticoagulant for patients with contraindications to UFH who undergoing ECMO support.

BACKGROUND: The cuff leak test (CLT) has been shown to have excellent specificity and moderate sensitivity for predicting postextubation stridor (PES). However, the ventilator flow waveform and the subject position are not uniform in current clinical practice. METHODS: We conducted a prospective cohort study in the respiratory ICU of the Beijing Chaoyang Hospital, Capital Medical University. Prior to extubation, 4 CLTs, combining 2 different postures and ventilator flow waveforms, were conducted, and the diagnostic performance of each test was assessed. RESULTS: Of the 143 included subjects, PES occurred in 13 (9.1%), and 10 (7%) subjects required re-intubation. Initially, an air leak volume of 110 mL was used as the standard to judge performance. The test that involved the square waveform and the subject in semi-recumbent position (test 4) had the best diagnostic performance, with a specificity of 80% and a sensitivity of 67% for predicting PES. After analyzing the receiver operating characteristic curve, an optimal diagnostic threshold of 116 mL for air leak volume was found to result in a specificity of 92% and a sensitivity of 63% for test 4. Additionally, when the air leak ratio of test 4 was 0.32, the area under the curve was 0.76, the specificity was 92%, and the sensitivity was 62%. CONCLUSIONS: In this study, performing the CLT with the subject in semi-recumbent position using the square waveform appeared to allow for the best prediction of PES.

目的: 在模拟海拔6 000 m高原低氧环境中观察人参复方对急性低氧小鼠抗疲劳的作用。方法: 将SPF级昆明小鼠分为正常组、缺氧模型组、阳性对照组(红景天)、人参复方低剂量组(1.0 g/kg)、中剂量组(2.0 g/kg)、高剂量组(3.0 g/kg),正常组和缺氧模型组灌等量生理盐水,按10 ml/kg体质量每天灌胃一次,连续灌胃给药14 d,利用特殊环境人工低压氧舱模拟海拔6 000 m建立小鼠急性低氧模型,除正常组外,其余组小鼠均置于人工低压氧舱中,历时24 h,然后进行负重游泳,记录小鼠负重游泳力竭时间,检测超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、三磷酸腺苷(ATP)、尿素氮(BUN)、肌糖原(MG)、肝糖原(Gly)、乳酸(LA)、乳酸脱氢酶(LDH)含量。结果: 与缺氧模型组相比,人参复方对小鼠负重游泳力竭时间显著延长(P＜0.05);与正常组相比,人参复方低、中、高剂量组血清中LA、Gly含量均显著升高(P＜0.05);与阳性对照组相比,人参复方高剂量组血清中LA含量显著升高(P＜0.05);与缺氧模型组相比,人参复方低、中、高剂量组血清中BUN、LA含量显著降低(P＜ 0.05),肝糖原中Gly含量显著升高(P＜0.05),人参复方中、高剂量组血清中ATP、LDH含量、肌糖原中MG含量显著升高(P＜ 0.05),MDA含量显著降低(P＜0.05),人参复方高剂量组SOD含量显著升高(P＜0.05)。结论: 人参复方可显著提高急性低氧环境中小鼠抗疲劳作用。.