Nursing Care of a Child With Delirium Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Case Report.

INTRODUCTION: Children receiving extracorporeal membrane oxygenation are prone to delirium. This case report describes the nursing care of a child with delirium who received venoarterial extracorporeal membrane oxygenation. Relevant interventions and precautions are also discussed. CLINICAL FINDINGS: A 6-year-old girl was admitted to the pediatric intensive care unit with a 2-day history of vomiting and fever. The child underwent cannulation for venoarterial extracorporeal membrane oxygenation. DIAGNOSIS: The child was diagnosed with acute fulminant myocarditis, cardiac shock, and ventricular arrhythmia. INTERVENTIONS: On the third day of extracorporeal membrane oxygenation, bedside nurses began using the Cornell Assessment of Pediatric Delirium to assess the child for delirium symptoms. The team of physicians and nurses incorporated a nonpharmacologic delirium management bundle into pediatric daily care. Delirium screening, analgesia and sedation management, sleep promotion, and family participation were implemented. OUTCOMES: During the 18 days of pediatric intensive care unit hospitalization, the child had 6 days of delirium: 1.5 days of hypoactive delirium, 1.5 days of hyperactive delirium, and 3 days of mixed delirium. The child was successfully discharged home on hospital day 22. CONCLUSION: Caring for a child with delirium receiving venoarterial extracorporeal membrane oxygenation required multidimensional nursing capabilities to prevent and reduce delirium while ensuring safe extracorporeal membrane oxygenation. This report may assist critical care nurses caring for children under similar circumstances.

Efficacy and safety of proxalutamide (GT0918) in severe or critically ill patients with COVID-19: study protocol for a prospective, open-label, single-arm, single-center exploratory trial.

BACKGROUND: The rapid worldwide spread of COVID-19 has caused a global health challenge with high mortality of severe or critically ill patients with COVID-19. To date, there is no specific efficient therapeutics for severe or critically ill patients with COVID-19. It has been reported that androgen is related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Proxalutamide as an androgen receptor antagonist has shown potential treatment effects on COVID-19 patients. Thus, this trial is designed to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19. METHODS: This single-arm, open-label, single-center prospective exploratory trial is planned to recruit 64 severe or critically ill patients with COVID-19 in China. Recruitment started on 16 May 2022 and is foreseen to end on 16 May 2023. Patients will be followed-up until 60 days or death, whichever comes first. The primary outcome is the 30-day all-cause mortality. Secondary endpoints included 60-day all-cause mortality, rate of clinical deterioration within 30 days after administration, time to sustain clinical recovery (determined using an 8-point ordinal scale), mean change in the Acute Physiology and Chronic Health Evaluation II scores, change in oxygenation index, changes in chest CT scan, percentage of patients confirmed negative for SARS-CoV-2 by nasopharyngeal swab, change in Ct values of SARS-CoV-2 and safety. Visits will be performed on days 1 (baseline), 15 or 30, 22, and 60. DISCUSSION: The trial is the first to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19. The findings of this study might lead to the development of better treatment for COVID-19 and provide convincing evidence regarding the efficacy and safety of proxalutamide. TRIAL REGISTRATION: This study was registered on 18 June 2022 at the Chinese Clinical Trial Registry (ChiCTR2200061250).

Risk factors of delirium in a paediatric intensive care unit: A prospective case series study.

BACKGROUND: Delirium is one of the most common complications in critically ill children. Once delirium occurs, it will cause physical and psychological distress in children and increase the length of their ICU stay and hospitalization costs. Understanding the risk factors for delirium in critically ill children can help develop targeted nursing interventions to reduce the incidence of delirium. AIMS: To investigate the incidence and the risk factors of delirium in the paediatric intensive care unit (PICU). STUDY DESIGN: We performed a prospective observational study in critically ill patients in the PICU between February and July 2020. Delirium was diagnosed by the Cornell Assessment of Paediatric Delirium (CAPD) and the Richmond Agitation Sedation Scale and analysed via univariate analysis and multivariate logistic regression to determine the independent risk factors of delirium in critically ill children. RESULTS: The study enrolled 315 patients ranging in age from 1-202 (65.3-54.3) months, with 56.2% (n = 177) being male. The incidence of delirium was 29.2% (n = 92) according to CAPD criteria. Among them, 33 cases (35.9%) were of hyperactive delirium, 16 cases (17.4%) were of hypoactive delirium, and 43 cases (46.7%) were of mixed delirium. By using stepwise logistic regression, the independent risk factors of delirium included mechanical ventilation (odds ratio [OR], 11.470; 95% confidence interval [CI], 4.283-30.721), nervous system disease (OR, 5.596; 95%CI, 2.445 to 12.809), developmental delay (OR, 5.157; 95% CI, 1.990-13.363), benzodiazepine (OR, 3.359; 95% CI 1.278-8.832), number of catheters (OR, 1.918; 95% CI, 1.425 to 2.582), and age (OR, 0.985; 95% confidence interval CI, 0.976-0.993). CONCLUSIONS: Delirium is a common complication in the PICU. The independent risk factors include mechanical ventilation, nervous system disease, developmental delay, benzodiazepines, higher number of catheters, and younger age. This study may help develop intervention strategies to reduce the incidence of delirium in critically ill children by targeting modifiable risk factors. RELEVANCE TO CLINICAL PRACTICE: Recommendations for practice include paying attention to high-risk children in the ICU who are prone to delirium, removing influencing factors as soon as possible, and providing targeted nursing interventions.

Proxalutamide for the treatment of COVID-19 rebound following Paxlovid treatment: Report of four cases and review of the literature.

BACKGROUND: The pandemic the coronavirus disease 2019 (COVID-19) has created a global health crisis. Although Paxlovid is recommended for the early-stage treatment of mild-to-moderate COVID-19 in patients at increased risk of progression to severe COVID-19, more and more cases are reported a COVID-19 rebound after Paxlovid treatment. Currently, information on the additional treatment for COVID-19 rebound following Paxlovid treatment is limited. CASE REPORT: Here, we present four cases with COVID-19 who were mild on admission. All cases experienced a COVID-19 rebound and progressed to severe COVID-19, following treatment with Paxlovid (300 mg of nirmatrelvir with 100 mg ritonavir, twice daily for 5 days). After being treated with proxalutamide (300 mg/day), all cases finally turned real-time reverse transcription polymerase chain reaction (RT-PCR) negative. CONCLUSION: Our cases suggested that proxalutamide might be an effective remedial treatment option for patients experiencing a COVID-19 rebound after Paxlovid treatment.

The immunomodulation role of Th17 and Treg in renal transplantation.

Kidney transplantation (KT) is an ultimate treatment of end-stage chronic kidney disease, which can meet a lot of complications induced by immune system. With under-controlled immunosuppression, the patient will obtain a good prognosis. Otherwise, allograft disfunction will cause severe organ failure and even immune collapse. Acute or chronic allograft dysfunction after KT is related to Th17, Treg, and Th17/Treg to a certain extent. Elevated Th17 levels may lead to acute rejection or chronic allograft dysfunction. Treg mainly plays a protective role on allografts by regulating immune response. The imbalance of the two may further aggravate the balance of immune response and damage the allograft. Controlling Th17 level, improving Treg function and level, and adjusting Th17/Treg ratio may have positive effects on longer allograft survival and better prognosis of receptors.

The Clinical Impact of Metagenomic Next-Generation Sequencing (mNGS) Test in Hospitalized Patients with Suspected Sepsis: A Multicenter Prospective Study.

Background: Metagenomic Next Generation Sequencing (mNGS) has the potential to detect pathogens rapidly. We aimed to assess the diagnostic performance of mNGS in hospitalized patients with suspected sepsis and evaluate its role in guiding antimicrobial therapy. Methods: A multicenter, prospective cohort study was performed. We enrolled patients with suspected sepsis, collected clinical characteristics and blood samples, and recorded the 30-day survival. Diagnostic efficacy of mNGS test and blood culture was compared, and the clinical impact of mNGS on antibiotic regimen modification was analyzed. Results: A total of 277 patients were enrolled, and 162 were diagnosed with sepsis. The mortality was 44.8% (121/270). The mNGS test exhibited shorter turn-out time (27.0 (26.0, 29.0) vs. 96.0 (72.0, 140.3) hours, p < 0.001) and higher sensitivity (90.5% vs. 36.0%, p < 0.001) compared with blood culture, especially for fungal infections. The mNGS test showed better performance for patients with mild symptoms, prior antibiotic use, and early stage of infection than blood culture, and was capable of guiding antibiotic regimen modification and improving prognosis. Higher reads of pathogens detected by mNGS were related to 30-day mortality (p = 0.002). Conclusions: Blood mNGS testing might be helpful for early etiological diagnosis of patients with suspected sepsis, guiding the antibiotic regimen modification and improving prognosis.

Ginger supplement significantly reduced length of hospital stay in individuals with COVID-19.

BACKGROUND: Evidence from previous studies has suggested that ginger extract exhibits the potential as an alternative treatment for Coronavirus disease 2019 (COVID-19). Here, we want to investigate whether ginger supplement improves the clinical manifestation of hospitalized COVID-19 individuals. METHODS: A total of 227 hospitalized individuals with COVID-19 were randomized to either the control (n = 132) or intervention group (n = 95). The intervention group took ginger supplement orally at the dosage of 1.5 g twice daily, until they were discharged from the hospital. Both groups received the same standard of general medical care during hospitalization, and the length of stay was recorded and compared between groups. RESULTS: Among all participants, a significant reduction in hospitalization time (the difference between the treatment and control groups was 2.4 d, 95% CI 1.6-3.2) was detected in response to the ginger supplement. This effect was more pronounced in men, participants aged 60 years or older, and participants with pre-existing medical conditions, relative to their counterparts (P-interactions < 0.05 for all). CONCLUSION: Ginger supplement significantly shortened the length of stay of hospitalized individuals with COVID-19. TRIAL REGISTRATION: The trial was registered on the Chinese Clinical Trial Registry (ChiCTR2200059824).

Cyclic helix B peptide ameliorated the sepsis-induced injury in human HPMEC cells through regulating NF-κB.

BACKGROUND: Sepsis is a life-threatening condition. The incidence of severe sepsis is increasing. Sepsis is often complicated with organ dysfunctions. Cyclic helix B peptide (CHBP) is a peptide derivant of erythropoietin with powerful tissue-protective efficacies. However, the role of CHBP in sepsis-induced injury remains unclear. MATERIAL AND METHODS: Lyso-phosphatidylserine (LPS) was used to induce sepsis in human pulmonary microvascular endothelial cells (HPMECs). Cell growth was detected using Cell Counting Kit-8. Cell permeability was measured using fluorescein isothiocyanate (FITC)-dextran. Cecal ligation and puncture (CLP) method was applied to induce sepsis and CHBP was provided to test its efficacy. Western blot assays were used to evaluate gene expression. RESULTS: Administration of CHBP ameliorated LPS-induced injury in HPMECs dose-dependently. Administration of CHBP decreased the permeability of LPS-treated HPMEC cells in a same way as well. Furthermore, we identified that recombinant CHBP protein (Re-CHBP) ameliorated CLP-induced injury in vivo. Finally, we found that administration of NF-κB activator, TNF-α, abolished the function of Re-CHBP in LPS-treated HPMEC cells. CONCLUSION: CHBP ameliorated sepsis-induced injury dose dependently both in vitro and in vivo through decreasing the permeability of HPMEC cells via suppressing NF-κB signaling and inflammation. Present findings highlight the importance of CHBP/NF-κB signaling in septic injury and provide new insights into therapeutic strategies for sepsis-induced injury.

Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and NLRP3 Inflammasome.

Background and Aims: The effect of ginsenoside Rb1 on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury (ALI) is unknown. The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms. Methods: Mice were pretreated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment, to induce ALI. The survival rate was monitored every hour for 24 h, and serum biochemical parameters, hepatic index and histopathological analysis were evaluated to measure the degree of liver injury. ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum. Immunohistochemistry staining, RT-PCR and western blotting were performed to evaluate the expression of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and NLR family, pyrin domain-containing 3 protein (NLRP3) in liver tissue and Kupffer cells (KCs). Results: Ginsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%, significantly ameliorated the increased alanine and aspartate transaminase, restored the hepatic pathological changes and reduced the levels of oxidative stress and inflammatory cytokines altered by D-GalN/LPS. Compared to the control group, the KCs were increased in the D-GalN/LPS groups but did not increase significantly with Rb1 pretreatment. D-GalN/LPS could upregulate while Rb1 pretreatment could downregulate the expression of interleukin (IL)-1ß, IL-18, NLRP3, apoptosis associated speck-like protein containing CARD (ASC) and caspase-1 in isolated KCs. Furthermore, ginsenoside Rb1 inhibited activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome induced by D-GalN/LPS administration. Conclusions: Ginsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.

Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

Objective: Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation. Method: 20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group). Results: Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023). Conclusion: The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT04328688).

Usage of compromised lung volume in monitoring steroid therapy on severe COVID-19.

BACKGROUND: Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19. METHODS: Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3-7 days); Stage 3 (8-14 days); Stage 4 (15-21 days); and Stage 5 (22-31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, - 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders. RESULTS: Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (- 3.27% [95% CI, - 5.86 to - 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P < 0.01). Steroid therapy was associated with decrease in %CL after stage 3 (all P < 0.05), but not at stage 2. Similarly, steroid therapy was associated with a more significant decrease in %CL in the high CL group (P < 0.05), but not in the low CL group. CONCLUSIONS: Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process. Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247.

Early Enteral Nutrition Tolerance in Patients With Cardiogenic Shock Requiring Mechanical Circulatory Support.

Background: Enteral nutrition (EN) is recommended within the first 24-48 h for patients with hemodynamic stability, following admission to an intensive care unit (ICU). However, for patients with approximate stable hemodynamics requiring mechanical circulatory support and vasoactive drugs, the application of early EN remains controversial. We sought to evaluate the tolerance of early EN in patients with cardiogenic shock who required vasoactive drugs and mechanical circulatory support after cardiac surgery. Methods: This single-center, prospective observational study included patients with cardiogenic shock, requiring vasoactive drugs and mechanical circulatory support after cardiac surgery, undergoing EN. The primary endpoint was EN tolerance and secondary endpoints were mortality, length of mechanical ventilation, and length of ICU stay. Results: From February 2019 to December 2020, 59 patients were enrolled, of which 25 (42.37%) developed intolerance within 3 days of starting EN. Patients in the EN intolerant group had a longer median length of mechanical ventilation (380 vs. 128 h, p = 0.006), a longer median ICU stay (20 vs. 11.5 days, p = 0.03), and a higher proportion of bloodstream infections (44 vs. 14.71%, p = 0.018). The median EN calorie levels for all patients in the first 3 days of EN were 4.00, 4.13, and 4.28 kcal/kg/day, respectively. Median protein intake levels of EN in the first 3 days were 0.18, 0.17, and 0.17 g/kg/day, respectively. No significant difference was observed in the median dose of vasoactive drugs between the groups (0.035 vs. 0.05 µg/kg/min, p = 0.306). Conclusions: Patients with cardiogenic shock after cardiac surgery had a high proportion of early EN intolerance, and patients with EN intolerance had a worse prognosis, but no significant correlation was identified between EN tolerance and the dose of vasoactive drugs.

Neutrophil-to-Lymphocyte Ratio Predicts Mortality in Adult Renal Transplant Recipients with Severe Community-Acquired Pneumonia.

Mortality of renal transplant recipients with severe community-acquired pneumonia (CAP) remains high, despite advances in critical care management. There is still a lack of biomarkers for predicting prognosis of these patients. The present study aimed to investigate the association between neutrophil-to-lymphocyte ratio (NLR) and mortality in renal transplant recipients with severe CAP. A total of 111 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility between 1 January 2009 and 30 November 2018. Patient characteristics and laboratory test results at ICU admission were retrospectively collected. There were 18 non-survivors (22.2%) among 81 patients with severe CAP who were finally included. Non-survivors had a higher NLR level than survivors (26.8 vs. 12.3, p < 0.001). NLR had the greatest power to predict mortality as suggested by area under the curve (0.88 ± 0.04; p < 0.0001) compared to platelet-to-lymphocyte ratio (0.75 ± 0.06; p < 0.01), pneumonia severity index (0.65 ± 0.08; p = 0.05), CURB-65 (0.65 ± 0.08; p = 0.05), and neutrophil count (0.68 ± 0.07; p < 0.01). Multivariate logistic regression models revealed that NLR was associated with hospital and ICU mortality in renal transplant recipients with severe CAP. NLR levels were independently associated with mortality and may be a useful biomarker for predicting poor outcome in renal transplant recipients with severe CAP.

Cyclic helix B peptide alleviates sepsis-induced acute lung injury by downregulating NLRP3 inflammasome activation in alveolar macrophages.

Acute lung injury (ALI) exhibits high clinical morbidity and mortality rates. Our previous study has indicated that the novel proteolysis-resistant cyclic helix B peptide (CHBP) exerts an anti-inflammatory effect in mice with AKI. In the present study, we evaluated the effect of CHBP in an in vivo sepsis-induced ALI model and in vitro using lipopolysaccharide (LPS) and ATP stimulated bone marrow-derived macrophages (BMDMs). For in vivo experiments, mice were randomly divided into three groups: 1) sham; 2) LPS; and 3) LPS + CHBP (n = 6). All relevant data were collected after 18 h. Following CHBP treatment, the lung function of the mice was significantly improved compared to the LPS group. CHBP administration inhibited interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α production at both the protein and mRNA levels. Additionally, following CHBP treatment, the population of pulmonary macrophages decreased. Simultaneously, the proportion of caspase-1-activated alveolar macrophages was also decreased after CHBP treatment. The protein levels of NLRP3 and cleaved caspase-1 were attenuated in the lung tissue following CHBP treatment. In in vitro experiments, CHBP treatment decreased NLRP3 inflammasome expression and downstream IL-1ß secretion, consistent with the in vivo results. In addition, CHBP reversed nuclear factor (NF)-κB and I-κB phosphorylation with a significant dose-dependent effect. Therefore, these findings suggest the potential of CHBP as a therapeutic agent in sepsis-induced ALI owing to inhibition of the NLRP3 inflammasome via the NF-κB pathway in macrophages.

Neuroprotective Effect of the Inhibitor Salubrinal after Cardiac Arrest in a Rodent Model.

Cardiac arrest (CA) yields poor neurological outcomes. Salubrinal (Sal), an endoplasmic reticulum (ER) stress inhibitor, has been shown to have neuroprotective effects in both in vivo and in vitro brain injury models. This study investigated the neuroprotective mechanisms of Sal in postresuscitation brain damage in a rodent model of CA. In the present study, rats were subjected to 6 min of CA and then successfully resuscitated. Either Sal (1 mg/kg) or vehicle (DMSO) was injected blindly 30 min before the induction of CA. Neurological status was assessed 24 h after CA, and the cortex was collected for analysis. As a result, we observed that, compared with the vehicle-treated animals, the rats pretreated with Sal exhibited markedly improved neurological performance and cortical mitochondrial morphology 24 h after CA. Moreover, Sal pretreatment was associated with the following: (1) upregulation of superoxide dismutase activity and a reduction in maleic dialdehyde content; (2) preserved mitochondrial membrane potential; (3) amelioration of the abnormal distribution of cytochrome C; and (4) an increased Bcl-2/Bax ratio, decreased cleaved caspase 3 upregulation, and enhanced HIF-1α expression. Our findings suggested that Sal treatment improved neurological dysfunction 24 h after CPR (cardiopulmonary resuscitation), possibly through mitochondrial preservation and stabilizing the structure of HIF-1α.

Prognostic Accuracy of Early Warning Scores for Clinical Deterioration in Patients With COVID-19.

Background: Early Warning Scores (EWS), including the National Early Warning Score 2 (NEWS2) and Modified NEWS (NEWS-C), have been recommended for triage decision in patients with COVID-19. However, the effectiveness of these EWS in COVID-19 has not been fully validated. The study aimed to investigate the predictive value of EWS to detect clinical deterioration in patients with COVID-19. Methods: Between February 7, 2020 and February 17, 2020, patients confirmed with COVID-19 were screened for this study. The outcomes were early deterioration of respiratory function (EDRF) and need for intensive respiratory support (IRS) during the treatment process. The EDRF was defined as changes in the respiratory component of the sequential organ failure assessment (SOFA) score at day 3 (ΔSOFAresp = SOFA resp at day 3-SOFAresp on admission), in which the positive value reflects clinical deterioration. The IRS was defined as the use of high flow nasal cannula oxygen therapy, noninvasive or invasive mechanical ventilation. The performances of EWS including NEWS, NEWS 2, NEWS-C, Modified Early Warning Scores (MEWS), Hamilton Early Warning Scores (HEWS), and quick sepsis-related organ failure assessment (qSOFA) for predicting EDRF and IRS were compared using the area under the receiver operating characteristic curve (AUROC). Results: A total of 116 patients were included in this study. Of them, 27 patients (23.3%) developed EDRF and 24 patients (20.7%) required IRS. Among these EWS, NEWS-C was the most accurate scoring system for predicting EDRF [AUROC 0.79 (95% CI, 0.69-0.89)] and IRS [AUROC 0.89 (95% CI, 0.82-0.96)], while NEWS 2 had the lowest accuracy in predicting EDRF [AUROC 0.59 (95% CI, 0.46-0.720)] and IRS [AUROC 0.69 (95% CI, 0.57-0.81)]. A NEWS-C ≥ 9 had a sensitivity of 59.3% and a specificity of 85.4% for predicting EDRF. For predicting IRS, a NEWS-C ≥ 9 had a sensitivity of 75% and a specificity of 88%. Conclusions: The NEWS-C was the most accurate scoring system among common EWS to identify patients with COVID-19 at risk for EDRF and need for IRS. The NEWS-C could be recommended as an early triage tool for patients with COVID-19.

Ulinastatin ameliorates LPS­induced pulmonary inflammation and injury by blocking the MAPK/NF­κB signaling pathways in rats.

Ulinastatin, a urinary trypsin inhibitor (UTI) is commonly used to treat patients with acute inflammatory disease. However, the underlying mechanisms of its anti­inflammatory effect in acute lung injury (ALI) are not fully understood. The present study aimed to investigate the protective effect of UTI and explore its potential mechanisms by using a rat model of lipopolysaccharide (LPS)­induced ALI. Rats were treated with 5 mg/kg LPS by intratracheal instillation. The histological changes in LPS­induced ALI was evaluated using hematoxylin and eosin staining and the myeloperoxidase (MPO) activity was determined using ELISA. The wet/dry ratio (W/D ratio) of the lungs was used to assess the severity of pulmonary edema and Evans blue dye was used to evaluate the severity of lung vascular leakage. The results demonstrated that LPS administration induced histological changes and significantly increased the lung W/D ratio, MPO activity and Evans blue dye extravasation compared with the control group. However, treatment with UTI attenuated LPS­induced ALI in rats by modifying histological changes and reducing the lung W/D ratio, MPO activity and Evans blue dye extravasation. In addition, LPS induced the secretion of numerous pro­inflammatory cytokines in bronchoalveolar lavage fluid (BALF), including tumor necrosis factor­α, interleukin (IL)­6, IL­1ß and interferon­Î³; however, these cytokines were strongly reduced following treatment with UTI. In addition, UTI was able to reduce cellular counts in BALF, including neutrophils and leukocytes. Western blotting demonstrated that UTI significantly blocked the LPS­stimulated MAPK and NF­κB signaling pathways. The results of the present study indicated that UTI could exert an anti­inflammatory effect on LPS­induced ALI by inhibiting the MAPK and NF­κB signaling pathways, which suggested that UTI may be considered as an effective drug in the treatment of ALI.

Understanding Gene Therapy in Acute Respiratory Distress Syndrome.

Acute Respiratory Distress Syndrome (ARDS) and its complications remain lifethreatening conditions for critically ill patients. The present therapeutic strategies such as prone positioning ventilation strategies, nitric oxide inhalation, restrictive intravenous fluid management, and extracorporeal membrane oxygenation (ECMO) do not contribute much to improving the mortality of ARDS. The advanced understanding of the pathophysiology of acute respiratory distress syndrome suggests that gene-based therapy may be an innovative method for this disease. Many scientists have made beneficial attempts to regulate the immune response genes of ARDS, maintain the normal functions of alveolar epithelial cells and endothelial cells, and inhibit the fibrosis and proliferation of ARDS. Limitations to effective pulmonary gene therapy still exist, including the security of viral vectors and the pulmonary defense mechanisms against inhaled particles. Here, we summarize and review the mechanism of gene therapy for acute respiratory distress syndrome and its application.