The diaphragmatic electrical activity during spontaneous breathing trial in patients with mechanical ventilation: physiological description and potential clinical utility.

BACKGROUNDS: Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. METHODS: We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. RESULTS: Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p < 0.01). Early increases in EAdi were observed in SBT, which are more prominent in SBT failure group. One minute, changes in EAdi and neuro-discharge per min also predicted weaning outcome (AUROCs 0.944 and 0.918, respectively). CONCLUSIONS: EAdi-based parameters, especially neuro-excursion efficiency and changes in neuro-discharge per min, may detect impending weaning failure earlier than conventional indices. EAdi monitoring provides physiological insights and a more tailored approach to facilitate successful weaning. Further research should validate these findings and explore the utility of combined EAdi and diaphragm ultrasound assessment in weaning ICU patients from mechanical ventilation. TRIAL REGISTRATION: Registered at ClinicalTrials.gov on 20 September 2022 (Identifier: NCT05632822).

Central venous oxygen saturation changes as a reliable predictor of the change of CI in septic shock: To explore potential influencing factors.

PURPOSE: Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO2) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO2 (ΔScvO2) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors. METHODS: In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase of cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO2 and its change before and after fluid challenge. RESULTS: Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO2 (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO2, with R2 = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO2 (R2 = 0.245, p < 0.001). ΔScvO2 had a good discriminatory ability for the responders and non-responders with a threshold of 4.4% (area under the curve = 0.732, p = 0.006). CONCLUSION: ΔScvO2 served as a reliable surrogate marker for ΔCI and could be utilized to assess fluid responsiveness, given that the change of CI was the sole contributing factor to the ΔScvO2. In stable hemoglobin conditions, the absolute value of ScvO2 could serve as a monitoring indicator for adequate oxygen delivery independent of oxygen consumption.

Extracorporeal vs. conventional CPR for out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a significant cause of mortality and morbidity worldwide. Extracorporeal cardiopulmonary resuscitation (ECPR) is a potential intervention for OHCA, but its effectiveness compared to conventional cardiopulmonary resuscitation (CCPR) needs further evaluation. METHOD: We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov for relevant studies from January 2010 to March 2023. Pooled meta-analysis was performed to investigate any potential association between ECPR and improved survival and neurological outcomes. RESULTS: This systematic review and meta-analysis included two randomized controlled trials enrolling 162 participants and 10 observational cohort studies enrolling 4507 participants. The pooled meta-analysis demonstrated that compared to CCRP, ECPR did not improve survival and neurological outcomes at 180 days following OHCA (RR: 3.39, 95% CI: 0.79 to 14.64; RR: 2.35, 95% CI: 0.97 to 5.67). While a beneficial effect of ECPR was obtained regarding 30-day survival and neurological outcomes. Furthermore, ECPR was associated with a higher risk of bleeding complications. Subgroup analysis showed that ECPR was prominently beneficial when exclusively initiated in the emergency department. Additional post-resuscitation treatments did not significantly impact the efficacy of ECPR on 180-day survival with favorable neurological outcomes. CONCLUSIONS: There is no high-quality evidence supporting the superiority of ECPR over CCPR in terms of survival and neurological outcomes in OHCA patients. However, due to the potential for bias, heterogeneity among studies, and inconsistency in practice, the non-significant results do not preclude the potential benefits of ECPR. Further high-quality research is warranted to optimize ECPR practice and provide more generalizable evidence. Clinical trial registration PROSPERO, https://www.crd.york.ac.uk/prospero/, registry number: CRD42023402211.

Impact of Immunosuppressed Status on Prognosis of Carbapenem-Resistant Organisms Bloodstream Infections.

INTRODUCTION: The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. METHODS: This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. RESULTS: A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74-18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60-3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58-3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. CONCLUSION: Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status.

Spinal cord perfusion is associated with microstructural damage in cervical spondylotic myelopathy patients who underwent cervical laminoplasty.

OBJECTIVES: To investigate the association between spinal cord perfusion and microstructural damage in CSM patients who underwent cervical laminoplasty using MR dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) techniques. METHODS: A follow-up cohort study was conducted with 53 consecutively recruited CSM patients who had undergone cervical laminoplasty 12-14 months after the surgery from April 2016 to December 2016. Twenty-one aged-matched healthy volunteers were recruited as controls. For each patient, decompressed spinal cord levels were imaged on a 3.0-T MRI scanner by diffusion and DSC sequences to quantify the degrees of microstructural damage and perfusion conditions, respectively. The diffusion data were analyzed by DTI and NODDI models to produce diffusion metrics. Classic indicator dilution model was used to quantify the DSC metrics. Mann-Whitney U test was performed for comparison of diffusion metrics between patients and healthy controls. Pearson correlation was used to explore the associations between the metrics of spinal cord perfusion and microstructural damage. RESULTS: DTI metrics, neurite density, and isotropic volume fraction had significant differences between postoperative patients and healthy controls. Pearson correlation test showed that SCBV was significantly positively correlated with RD, MD, and ODI, and negatively correlated with FA and NDI. SCBF was found to be significantly positively correlated with RD and MD, and negatively correlated with FA. CONCLUSIONS: Increased spinal cord perfusion quantified by DSC is associated with microstructural damage assessed by diffusion MRI in CSM patients who underwent cervical laminoplasty. CLINICAL RELEVANCE STATEMENT: This study found that the spinal cord perfusion is associated with microstructural damage in postoperative cervical spondylotic myelopathy patients, indicating that high perfusion may play a role in the pathophysiological process of cervical spondylotic myelopathy and deserves more attention. KEY POINTS: • Spinal cord microstructural damage can be persistent despite the compression had been relieved 12-14 months after the cervical laminoplasty in cervical spondylotic myelopathy (CSM) patients. • Spinal cord perfusion is associated with microstructural damage in CSM patients after the cervical laminoplasty. • Inflammation in the decompressed spinal cord may be a cause of increased perfusion and is associated with microstructural damage during the recovery period of CSM.

Temporal trends of sepsis-related mortality in China, 2006-2020: a population-based study.

BACKGROUND: The scarcity of sepsis epidemiologic data from most low- and middle-income countries (LMICs) hampered estimation of regional and global burden of the disease, and provided limited guidance for policy makers. We aimed to characterize and analyze the temporal trends of sepsis-related mortality in China, by population groups, underlying causes of death, geographic regions, and sociodemographic index (SDI) levels. METHODS: Sepsis-related deaths were identified from the National Mortality Surveillance System (NMSS) of China from 2006 to 2020. Trends of sepsis-related mortality and years of life lost (YLLs), stratified by age, sex, underlying diseases, and regions were analyzed using the Jointpoint regression analysis. We investigated the association of SDI with trends of sepsis-related mortality. RESULTS: In 2020, sepsis was estimated to be responsible for 986,929 deaths and 17.1 million YLLs in China. Age-standardized sepsis-related mortality significantly declined from 130.2 (95%CI, 129.4-131) per 100,000 population in 2006 to 76.6 (76.3-76.9) in 2020. Age-standardized YLLs decreased from 2172.7 (2169.4-2176) per 100,000 population in 2006 to 1271 (1269.8-1272.2) in 2020. Substantial variations of sepsis-related mortality and YLLs were observed between population groups and regions, with higher burden in males, the elderly, and western China. An inverse relation was noted between SDI and sepsis-related mortality or YLLs. CONCLUSIONS: Despite declining trends of age-standardized mortality and YLLs of sepsis in China, significant disparities between population groups and regions highlight a need for targeted policies and measures to close the gaps and improve the outcome of sepsis.

Tissue oxygen saturation is predictive of lactate clearance in patients with circulatory shock.

BACKGROUND: Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. METHODS: This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. RESULTS: A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2 in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2 for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2 of masseter (0.65, 95% CI 0.45-0.84; p < 0.01), deltoid (0.77, 95% CI 0.60-0.94; p = 0.04), thenar (0.72, 95% CI 0.55-0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2 (0.85, 0.73-0.98; p = 0.09). Additionally, BSA-weighted StO2 model had continuous net reclassification improvement (NRI) over the knee StO2 and mean StO2 model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2 was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose. CONCLUSIONS: Our results suggested that BSA-weighted StO2 was a strong predictor of 6-hour lactate clearance in patients with shock.

Transient Productivity Analysis and Completion Parameter Optimization of Perforating Herringbone Wells.

Herringbone wells are of great significance in tapping the potential of remaining reservoirs, improving recovery efficiency, and reducing development costs and have been widely used in oilfields, especially offshore oilfields. Due to the complex structure of herringbone wells, there is mutual interference between wellbores during seepage, resulting in complex seepage problems, and it is difficult to analyze the productivity and evaluate the perforating effect. In this paper, considering the mutual interference between branches and perforations, a prediction model of transient productivity of perforated herringbone wells was derived based on the theory of transient seepage, and the complex structure with any number of branches, arbitrary configurations, and orientations in three-dimensional space could be considered in this model. The formation pressure in reservoir points at different production times, IPR curves, and the radial inflow of herringbone well were studied by the line-source superposition method, which directly reflected the process of productivity and pressure change, avoiding the one-sidedness caused by using a point source to replace the line source in the stability analysis. Then, through the productivity calculation of different perforation schemes, the influence curves of perforation density, perforation length, perforation phase angle, and perforation radius on unstable productivity were obtained. Orthogonal tests were performed to obtain the degree of impact of each parameter on productivity. Lastly, the selective completion perforation technology was adopted. When the shot density at the end of the wellbore was increased, the productivity of herringbone wells could be improved economically and effectively. According to the above study, a scientific and reasonable construction scheme is recommended for oil well completion construction, which provides a theoretical basis for the improvement and development of perforation completion technology.

Safety, tolerability, pharmacokinetics, and efficacy of kukoamine B in patients with sepsis: A randomized phase IIa trial.

PURPOSE: To evaluate the safety, tolerability, pharmacokinetics, and efficacy of kukoamine B (KB), an alkaloid compound with high affinity for both lipopolysaccharide (LPS) and oligodeoxynucle-otides containing CpG motifs (CpG DNA), in patients with sepsis-induced organ failure. MATERIALS AND METHODS: This was a multicenter, randomized, double-blind, placebo-controlled phase IIa trial. Patients with sepsis-induced organ failure were randomized to receive either KB (0.06, 0.12, or 0.24 mg/kg) or placebo, every 8 h for 7 days. Primary endpoint was safety, and secondary endpoints included pharmacokinetic (PK) parameters, changes in inflammatory mediators' level, and prognostic parameters. RESULTS: Of 44 patients enrolled, adverse events occurred in 28 patients [n = 20, 66.7% (KB pooled); n = 8, 57.1% (placebo)], while treatment emergent adverse events were reported in 14 patients [n = 10, 33.3% (KB pooled); n = 4, 28.6% (placebo)]. Seven patients died at 28-day follow-up [n = 4, 13.3% (KB pooled); n = 3, 21.4% (placebo)], none was related to study drug. PK parameters suggested dose-dependent drug exposure and no drug accumulation. KB did not affect clinical outcomes such as ΔSOFA score, vasopressor-free days or ventilator-free days. CONCLUSIONS: In patients with sepsis-induced organ failure, KB was safe and well tolerated. Further investigation is warranted. TRIAL REGISTRATION: http://ClinicalTrials.gov, NCT03237728.

National incidence and mortality of hospitalized sepsis in China.

BACKGROUND: Sepsis is a leading cause of preventable death around the world. Population-based estimation of sepsis incidence is lacking in China. In this study, we aimed to estimate the population-based incidence and geographic variation of hospitalized sepsis in China. METHODS: We retrospectively identified hospitalized sepsis from the nationwide National Data Center for Medical Service (NDCMS) and the National Mortality Surveillance System (NMSS) by ICD-10 codes for the period from 2017 to 2019. In-hospital sepsis case fatality and mortality rate were calculated to extrapolate the national incidence of hospitalized sepsis. The geographic distribution of hospitalized sepsis incidence was examined using Global Moran's Index. RESULTS: We identified 9,455,279 patients with 10,682,625 implicit-coded sepsis admissions in NDCMS and 806,728 sepsis-related deaths in NMSS. We estimated that the annual standardized incidence of hospitalized sepsis was 328.25 (95% CI 315.41-341.09), 359.26 (95% CI 345.4-373.12) and 421.85 (95% CI 406.65-437.05) cases per 100,000 in 2017, 2018 and 2019, respectively. We observed 8.7% of the incidences occurred among neonates less than 1 year old, 11.7% among children aged 1-9 years, and 57.5% among elderly older than 65 years. Significant spatial autocorrelation for incidence of hospitalized sepsis was observed across China (Moran's Index 0.42, p = 0.001; 0.45, p = 0.001; 0.26, p = 0.011 for 2017, 2018, 2019, respectively). Higher number of hospital bed supply and higher disposable income per capita were significantly associated with a higher incidence of hospitalized sepsis. CONCLUSION: Our study showed a greater burden of sepsis hospitalizations than previous estimated. The geographical disparities suggested more efforts were needed in prevention of sepsis.

Newly Proposed Diagnostic Criteria for Acute Respiratory Distress Syndrome: Does Inclusion of High Flow Nasal Cannula Solve the Problem?

Acute respiratory distress syndrome (ARDS) is a common life-threatening clinical syndrome which accounts for 10% of intensive care unit admissions. Since the Berlin definition was developed, the clinical diagnosis and therapy have changed dramatically by adding a minimum positive end-expiratory pressure (PEEP) to the assessment of hypoxemia compared to the American-European Consensus Conference (AECC) definition in 1994. High-flow nasal cannulas (HFNC) have become widely used as an effective respiratory support for hypoxemia to the extent that their use was proposed in the expansion of the ARDS criteria. However, there would be problems if the diagnosis of a specific disease or clinical syndrome occurred, based on therapeutic strategies.

The growth-regulating factor PdbGRF1 positively regulates the salt stress response in Populus davidiana × P. bolleana.

Growth-regulating factor (GRF) is a transcription factor unique to plants that plays a crucial role in the growth, development and stress adaptation of plants. However, information on the GRFs related to salt stress in Populus davidiana × P. bolleana is lacking. In this study, we characterized the activity of PdbGRF1 in transgenic Populus davidiana × P. bolleana under salt stress. qRTPCR analyses showed that PdbGRF1 was highly expressed in young leaves and that the pattern of PdbGRF1 expression was significantly changed at most time points under salt stress, which suggests that PdbGRF1 expression may be related to the salt stress response. Moreover, PdbGRF1 overexpression enhanced tolerance to salt stress. A physiological parameter analysis showed that the overexpression of PdbGRF1 significantly decreased the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and increased the activities of antioxidant enzymes (SOD and POD) and the proline content. A molecular analysis showed that PdbGRF1 regulated the expression of PdbPOD17 and PdbAKT1 by binding to the DRE ('A/GCCGAC') in their respective promoters. Together, our results demonstrate that the binding of PdbGRF1 to DRE regulates genes related to stress tolerance and activates the associated physiological pathways, and these effects increase the ROS scavenging ability, reduce the degree of damage to the plasma membrane and ultimately enhance the salt stress response in Populus davidiana × P. bolleana.

A case of disseminated Legionnaires' disease: The value of metagenome next-generation sequencing in the diagnosis of Legionnaires.

Background: Legionella rarely causes hospital-acquired pneumonia (HAP), although it is one of the most common pathogens of community-acquired pneumonia. Hospital-acquired Legionnaires' disease, mainly occurring in immunocompromised patients, is often delayed in diagnosis with high mortality. The use of the metagenome Next-Generation Sequencing (mNGS) method, which is fast and unbiased, allows for the early detection and identification of microorganisms using a culture-independent strategy. Case report: A 52-year-old male, with a past medical history of Goods syndrome, was admitted due to nephrotic syndrome. The patient developed severe pneumonia, rhabdomyolysis, and soft tissue infection after receiving immunosuppressive therapy. He did not respond well to empiric antibiotics and was eventually transferred to the medical intensive care unit because of an acute respiratory failure and septic shock. The patient then underwent a comprehensive conventional microbiological screening in bronchoalveolar lavage fluid (BALF) and blood, and the results were all negative. As a last resort, mNGS of blood was performed. Extracellular cell-free and intracellular DNA fragments of Legionella were detected in plasma and blood cell layer by mNGS, respectively. Subsequent positive results of polymerase chain reaction for Legionella in BALF and soft tissue specimens confirmed the diagnosis of disseminated Legionnaires' disease involving the lungs, soft tissue, and blood stream. The patient's condition improved promptly after a combination therapy of azithromycin and moxifloxacin. He was soon extubated and discharged from ICU with good recovery. Conclusion: Early recognition and diagnosis of disseminated Legionnaires' disease is challenging. The emergence and innovation of mNGS of blood has the potential to address this difficult clinical issue.

Motion detection and correction for carotid MRI using a markerless optical system.

PURPOSE: Motion related artifact is a challenge for MRI, especially when imaging regions like the carotid artery where complex motion (abrupt and bulk motion) may occur. This study aims to develop a non-contact motion detection and correction system for carotid MRI using a markerless optical tracking system. METHODS: The proposed markerless optical tracking system consisted of a cross-line laser, an MRI-compatible camera and plastic holders mounted inside the scanner bore. The neck motion of the subject can be captured by monitoring the change of the projected laser position in real-time. The system was used to correct both abrupt motion and bulk motion for carotid MRI. The abrupt motion (e.g. coughing) was compensated by discarding the corrupted k-space lines and re-estimating the missing lines using SPIRiT algorithm. The bulk motion was corrected by phase adjustment of k-space lines according to the measured 1D-translational bulk motion (along anterior-posterior direction) and optimized in-plane translation parameters. Ten volunteers underwent carotid MRI with real-time neck motion detection and retrospective motion correction. Artery sharpness, vessel wall thickness and overall image quality score were compared between the motion-corrupted image and motion-corrected images of different correction strategies. RESULTS: Both the abrupt motion and the bulk motion during carotid scanning were successfully detected and corrected. The results of ten volunteers demonstrated significant improvement in carotid artery sharpness, vessel wall thickness measurement, and overall image quality score using the proposed markerless optical tracking system and motion correction strategies. CONCLUSION: The proposed markerless structured light based motion detection and correction system can sensitively detect both abrupt and bulk motion during carotid MR scans. By correcting for both abrupt and bulk motion, vessel wall delineation was improved in carotid MR images, which could potentially facilitate carotid plaque identification and atherosclerosis diagnosis in the future.

Construction of two regulatory networks related to salt stress and lignocellulosic synthesis under salt stress based on a Populus davidiana × P. bolleana transcriptome analysis.

KEY MESSAGE: Construction of ML-hGRN for the salt pathway in Populus davidiana × P. bolleana. Construction of ML-hGRN for the lignocellulosic pathway in Populus davidiana × P. bolleana under salt stress. Many woody plants, including Populus davidiana × P. bolleana, have made great contributions to human production and life. High salt is one of the main environmental factors that restricts the growth of poplar. This study found that high salt could induce strong biochemical changes in poplar. To detect the effect of salt treatment on gene expression, 18 libraries were sequenced on the Illumina sequencing platform. The results identified a large number of early differentially expressed genes (DEGs) and a small number of late DEGs, which indicated that most of the salt response genes of poplar were early response genes. In addition, 197 TFs, including NAC, ERF, and other TFs related to salt stress, were differentially expressed during salt treatment, which indicated that these TFs may play an important role in the salt stress response of poplar. Based on the RNA-seq analysis results, multilayered hierarchical gene regulatory networks (ML-hGRNs) of salt stress- and lignocellulosic synthesis-related DEGs were constructed using the GGM algorithm. The lignocellulosic synthesis regulatory network under salt stress revealed that lignocellulosic synthesis might play an important role in the process of salt stress resistance. Furthermore, the NAC family transcription factor PdbNAC83, which was found in the upper layer in both pathways, was selected to verify the accuracy of the ML-hGRNs. DAP-seq showed that the binding site of PdbNAC83 included a "TT(G/A)C(G/T)T" motif, and ChIP-PCR further verified that PdbNAC83 can regulate the promoters of at least six predicted downstream genes (PdbNLP2-2, PdbZFP6, PdbMYB73, PdbC2H2-like, PdbMYB93-1, PdbbHLH094) by binding to the "TT(G/A)C(G/T)T" motif, which indicates that the predicted regulatory network diagram obtained in this study is relatively accurate. In conclusion, a species-specific salt response pathway might exist in poplar, and this finding lays a foundation for further study of the regulatory mechanism of the salt stress response and provides new clues for the use of genetic engineering methods to create high-quality and highly resistant forest germplasms.

ECCO2R in 12 COVID-19 ARDS Patients With Extremely Low Compliance and Refractory Hypercapnia.

Purpose: A phenotype of COVID-19 ARDS patients with extremely low compliance and refractory hypercapnia was found in our ICU. In the context of limited number of ECMO machines, feasibility of a low-flow extracorporeal carbon dioxide removal (ECCO2R) based on the renal replacement therapy (RRT) platform in these patients was assessed. Methods: Single-center, prospective study. Refractory hypercapnia patients with COVID-19-associated ARDS were included and divided into the adjusted group and unadjusted group according to the level of PaCO2 after the application of the ECCO2R system. Ventilation parameters [tidal volume (VT), respiratory rate, and PEEP], platform pressure (Pplat) and driving pressure (DP), respiratory system compliance, arterial blood gases, and ECCO2R system characteristics were collected. Results: Twelve patients with refractory hypercapnia were enrolled, and the PaCO2 was 64.5 [56-88.75] mmHg. In the adjusted group, VT was significantly reduced from 5.90 ± 0.16 to 5.08 ± 0.43 ml/kg PBW; DP and Pplat were also significantly reduced from 23.5 ± 2.72 mmHg and 29.88 ± 3.04 mmHg to 18.5 ± 2.62 mmHg and 24.75 ± 3.41 mmHg, respectively. In the unadjusted group, PaCO2 decreased from 94 [86.25, 100.3] mmHg to 80 [67.50, 85.25] mmHg but with no significant difference, and the DP and Pplat were not decreased after weighing the pros and cons. Conclusions: A low-flow ECCO2R system based on the RRT platform enabled CO2 removal and could also decrease the DP and Pplat significantly, which provided a new way to treat these COVID-19 ARDS patients with refractory hypercapnia and extremely low compliance. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT04340414.

Clinical characteristics and survival analysis in critical and non-critical patients with COVID-19 in Wuhan, China: a single-center retrospective case control study.

Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. The epidemiological and clinical course of COVID-19 patients has been reported, but there have been few analyses about the characteristics, predictive risk factors, and outcomes of critical patients. In this single-center retrospective case-control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory tests, and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP), and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid, and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical course. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application, and anticoagulation may be beneficial for patient survival.

Neurological Manifestations in Critically Ill Patients With COVID-19: A Retrospective Study.

Background: The complications of coronavirus disease 2019 (COVID-19) involved multiple organs or systems, especially in critically ill patients. We aim to investigate the neurological complications in critically ill patients with COVID-19. Methods: This retrospective single-center case series analyzed critically ill patients with COVID-19 at the intensive care unit of Tongji Hospital, Wuhan, China from February 5 to April 2, 2020. Demographic data, clinical and laboratory findings, comorbidities and treatments were collected and analyzed. Results: Among 86 patients with confirmed COVID-19, 54 patients (62.8%) were male, and the mean (SD) age was 66.6 (11.1) years. Overall, 65% patients presented with at least one neurological symptom. Twenty patients (23.3%) had symptoms involving the central nervous system, including delirium, cerebrovascular diseases and hypoxic-ischemic brain injury, while 6 patients (7%) had neuromuscular involvement. Seven of 86 patients exhibited new stroke and 6 (7%) cases were ischemic. A significantly higher prevalence of antiphospholipid antibodies was observed in patients with ischemic stroke than in those without stroke (83.3 vs. 26.9%, p < 0.05). Patients with ischemic stroke were more likely to have a higher myoglobulin level, and a lower hemoglobin level. Conclusions: The clinical spectrum of neurological complications in critically ill patients with COVID-19 was broad. Stroke, delirium and neuromuscular diseases are common neurological complications of COVID-19. Physicians should pay close attention to neurological complications in critically ill patients with COVID-19.

Antiphospholipid Antibodies in Critically Ill Patients With COVID-19.

OBJECTIVE: Coagulopathy is one of the characteristics observed in critically ill patients with coronavirus disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, though their role in COVID-19 remains unclear. This study was undertaken to determine the prevalence and characteristics of aPLs in patients with COVID-19. METHODS: Sera collected from 66 COVID-19 patients who were critically ill and 13 COVID-19 patients who were not critically ill were tested by chemiluminescence immunoassay for anticardiolipin antibodies (aCLs), anti-ß2 -glycoprotein I (anti-ß2 GPI) (IgG, IgM, and IgA), and IgG anti-ß2 GPI-domain 1 (anti-ß2 GPI-D1) and IgM and IgG anti-phosphatidylserine/prothrombin (anti-PS/PT) antibodies were detected in the serum by enzyme-linked immunosorbent assay. RESULTS: Of the 66 COVID-19 patients in critical condition, aPLs were detected in 31 (47% ). Antiphospholipid antibodies were not present among COVID-19 patients who were not in critical condition. The IgA anti-ß2 GPI antibody was the most commonly observed aPL in patients with COVID-19 and was present in 28.8% (19 of 66) of the critically ill patients, followed by IgA aCLs (17 of 66, or 25.8%) and IgG anti-ß2 GPI (12 of 66, or 18.2%). For multiple aPLs, IgA anti-ß2 GPI + IgA aCLs was the most common antibody profile observed (15 of 66, or 22.7%), followed by IgA anti-ß2 GPI + IgA aCL + IgG anti-ß2 GPI (10 of 66, or 15.2%). Antiphospholipid antibodies emerge ~35-39 days after disease onset. A dynamic analysis of aPLs revealed 4 patterns based on the persistence or transient appearance of the aPLs. Patients with multiple aPLs had a significantly higher incidence of cerebral infarction compared to patients who were negative for aPLs (P = 0.023). CONCLUSION: Antiphospholipid antibodies were common in critically ill patients with COVID-19. Repeated testing demonstrating medium to high titers of aPLs and the number of aPL types a patient is positive for may help in identifying patients who are at risk of developing cerebral infarction. Antiphospholipid antibodies may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of an autoimmune condition similar to the antiphospholipid syndrome (APS), referred to as "COVID-19-induced APS-like syndrome." Long-term follow-up of COVID-19 patients who are positive for aPLs would be of great importance in understanding the pathogenesis of this novel coronavirus.