Background: High-frequency oscillatory ventilation (HFOV) may theoretically provide lung protective ventilation. The negative clinical results may be due to inadequate mean airway pressure (mPaw) settings in HFOV. Our objective was to evaluate the air distribution, ventilatory and hemodynamic effects of individual mPaw titration during HFOV in ARDS animal based on oxygenation and electrical impedance tomography (EIT).Methods: ARDS was introduced with repeated bronchoalveolar lavage followed by injurious mechanical ventilation in ten healthy male pigs (51.2 ± 1.9 kg). Settings of HFOV were 9 Hz (respiratory frequency), 33% (inspiratory time) and 70 cmH 2 O (∆pressure). After lung recruitment, the mPaw was reduced in steps of 3 cmH 2 O every 6 min. Hemodynamics and blood gases were obtained in each step. Regional ventilation distribution was determined with EIT.Results: PaO 2 /FiO 2 decreased significantly during the mPaw decremental phase (p < 0.001). Lung overdistended regions decreased, while recruitable regions increased as mPaw decreased. The optimal mPaw with respect to PaO 2 / FiO 2 was 21 (18.0-21.0) cmH 2 O, that is comparable to EIT-based center of ventilation (EIT-CoV) and EIT-collapse/over, 19.5 (15.0-21.0) and 19.5 (18.0-21.8), respectively (p = 0.07). EIT-CoV decreasing along with mPaw decrease revealed redistribution toward non-dependent regions. The individual mPaw titrated by EIT-based indices improved regional ventilation distribution with respect to overdistension and collapse (p = 0.035). Conclusion:Our data suggested personalized optimal mPaw titration by EIT-based indices improves regional ventilation distribution and lung homogeneity during high-frequency oscillatory ventilation.

IntroductionSepsis is a major challenge with high incidence and is associated with high mortality worldwide. Current management of sepsis remains mainly supportive except for treatment with antibiotics. Both basic research and clinical investigation have shown that the Chinese herbal-derived therapeutic Xuebijing (XBJ) injection is beneficial for patients with sepsis. However, the quality of evidence supporting the therapeutic use of XBJ in sepsis is limited. The aim of this trial is to evaluate the Efficacy of Xuebijing Injection for Sepsis, compared with a placebo, on the outcome of patients with sepsis in the intensive care unit (ICU).Methods and analysisIn this multicentre, blinded randomised controlled trial, we are recruiting a total of 1800 subjects who met Sepsis 3.0 criteria. Subjects will be randomised (1:1) to receive XBJ, every 12 hours for 5 days or a matching placebo and usual care. The primary outcome is 28 days all-cause mortality. Secondary outcomes will be the improvement of Sequential Organ Failure Assessment scores, the improvement of the Acute Physiology and Chronic Health Evaluation II score, duration of mechanical ventilation, mortality in ICU and duration of stay in the ICU. Investigators, participants and statisticians will be blinded to the allocated treatment.Ethics and disseminationThis trial has been approved by all ethics committees of the centres that will participate in this trial. The findings of the study will be disseminated in peer-reviewed journals and present at conferences. Once this study is complete, the results of this trial may help provide evidence-based recommendations for complementary therapeutic options for patients with sepsis.Trial registration numberNCT03238742 and ChiCTR-IPR-17012713.

Background: Coronavirus Disease-2019 (COVID-19) has become a major health event that endangers people health throughout China and the world. Understanding the factors associated with COVID-19 disease severity could support the early identification of patients with high risk for disease progression, inform prevention and control activities, and potentially reduce mortality. This study aims to describe the characteristics of patients with COVID-19 and factors associated with severe or critically ill presentation.Methods: Multicentre retrospective cohort study of all individuals with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections diagnosed at 24 COVID-19-designated hospitals in Jiangsu province between the 10th January and 15th March 2020. Demographic, clinical, laboratory, and radiological data were collected at hospital admission and data on disease severity were collected at from admission. Patients were categorised as asymptomatic/mild/moderate, and severe/critically ill according to the worst level of COVID-19 recorded during hospitalisation.Results: A total of 625 patients, 64 (10.2%) were severe/critically ill and 561 (89.8%) were asymptomatic/mild/moderate. All patients were discharged and no patients died. Patients with severe/critically ill COVID-19 were more likely to be older, to be single onset (i.e. not to a cluster of cases in family/community), to have a medical history of hypertension and diabetes; had higher temperature, faster respiratory rates, lower peripheral capillary oxygen saturation (SpO2), and higher CT image quadrant scores and pulmonary opacity percentage; had increased C-reactive protein, fibrinogen, and D-dimer on admission; and had lower white blood cells, lymphocyte, and platelet counts and albumin on admission than asymptomatic/mild/moderate cases. Multivariable regression showed that odds of being a severe/critically ill case were associated with age (year) (OR 1.06, 95%CI 1.03-1.09), lymphocyte count (109/L) (OR 0.25, 95%CI 0.08-0.74), and pulmonary opacity in CT (per 5%) on admission (OR 1.31, 95%CI 1.15-1.51).Conclusions: Severe or critically ill patients with COVID-19 is about one-tenths of patients in Jiangsu. Age, lymphocyte count, and pulmonary opacity in CT on admission were associated with risk of severe or critically ill COVID-19.

Background PD-1 is an important immune checkpoint expressed on T lymphocytes and is associated with T-cell function in sepsis. However, the role of PD-1 in naive and memory T-cell responses in sepsis is not well understood. We aimed to determine the expression of PD-1 induced on naive and memory T lymphocytes in patients with sepsis and its association with clinical outcome. Methods A prospective observational study was conducted at a general intensive care unit (ICU). Whole blood samples were collected from patients within 48 h after sepsis diagnosis. PD-1 expression on naive and memory T cells was measured by flow cytometry. The levels of IFN-γ, IL-2 and TNF-α released by memory T cells were also determined. All patients were followed up to 28 days, and 28-day mortality was recorded. Results PD-1 expression showed no difference in naive CD4 + T cells ( P =0.617) or naive CD8 + T cells ( P =0.079) between survivors (n = 21) and nonsurvivors (n = 9). Increased PD-1 expression on memory CD4 + T cells was found in nonsurvivors ( P =0.030) and memory CD8 + T cells ( P =0.006) in comparison with survivors. According to the cutoff value of the percentage of PD-1 on memory CD8 + T cells in predicting 28-day mortality of patients with sepsis, patients were divided into two groups. The 28-day mortality rates between the two groups were significantly different ( P =0.009). A Kaplan Meier curve was constructed to derive a hazard ratio of 9.33 (95% CI: 2.52–34.60) for the percentage of PD-1 on memory CD8 + T cells regarding 28-day mortality. In addition, the IFN-γ secretion of memory CD4 + T cells ( P =0.046) and IL-2 secretion of memory CD8 + T cells ( P =0.014) were significantly greater in survivors than nonsurvivors. Conclusion Flow cytometric assessment of PD-1 expression on memory CD8 + T cells identifies patients with poor outcomes during sepsis.

BackgroundTo describe the characteristics of patients with Coronavirus Disease-2019 (COVID-19) and factors associated with severe or critically ill presentation.MethodsMulticentre retrospective cohort study of all individuals with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) infections diagnosed at 24 COVID-19-designated hospitals in Jiangsu province between the 10th January and 15th March 2020. Demographic, clinical, laboratory, and radiological data were collected at hospital admission and data on disease severity were collected at from admission. Patients were categorised as asymptomatic/mild/moderate, and severe/critically ill according to the worst level of COVID-19 recorded during hospitalisation.ResultsA total of 625 patients, 64 (10.2%) were severe/critically ill and 561 (89.8%) were asymptomatic/mild/moderate. All patients were discharged and no patients died. Multivariable regression showed that odds of being a severe/critically ill case were associated with age (year) (OR, 95%CI 1.06, 1.03–1.09), lymphocyte count (109/L) (OR 0.25, 0.08–0.74), and pulmonary opacity in CT (per 5%) on admission (OR 1.31, 95%CI 1.15–1.51).ConclusionsSevere or critically ill patients with COVID-19 is about one-tenths of patients in Jiangsu. Age, lymphocyte count, and pulmonary opacity in CT on admission were associated with risk of severe or critically ill COVID-19.# Songqiao Liu, Huanyuan Luo, Yuancheng Wang contributed equally to this manuscript