Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Erratum for Alveolar Type II Cells Escape Stress Failure Caused By Tonic Stretch Through Transient Focal Adhesion Disassembly.

[This corrects the article DOI: 10.7150/ijbs.7.588.].

Circulating and Pulmonary T-cell Populations Driving the Immune Response in Non-HIV Immunocompromised Patients with Pneumocystis jirovecii Pneumonia.

Background: Previous studies in human subjects have mostly been confined to peripheral blood lymphocytes for Pneumocystis infection. We here aimed to compare circulating and pulmonary T-cell populations derived from human immunodeficiency virus (HIV)-uninfected immunocompromised patients with Pneumocystis jirovecii pneumonia (PCP) in order to direct new therapies. Methods: Peripheral blood and bronchoalveolar lavage samples were collected from patients with and without PCP. Populations of Th1/Tc1, Th2/Tc2, Th9/Tc9, and Th17/Tc17 CD4+ and CD8+ T cells were quantified using multiparameter flow cytometry. Results: No significant differences were found between PCP and non-PCP groups in circulating T cells. However, significantly higher proportions of pulmonary Th1 and Tc9 were observed in the PCP than in the non-PCP group. Interestingly, our data indicated that pulmonary Th1 was negatively correlated with disease severity, whereas pulmonary Tc9 displayed a positive correlation in PCP patients. Conclusions: Our findings suggest that pulmonary expansion of Th1 and Tc9 subsets may play protective and detrimental roles in PCP patients, respectively. Thus, these specific T-cell subsets in the lungs may serve as targeted immunotherapies for patients with PCP.

Expression profiling analysis of long noncoding RNAs in a mouse model of ventilator-induced lung injury indicating potential roles in inflammation.

The key regulators of inflammation underlying ventilator-induced lung injury (VILI) remain poorly defined. Long noncoding RNAs (lncRNAs) have been implicated in the inflammatory response of many diseases; however, their roles in VILI remain unclear. We, therefore, performed transcriptome profiling of lncRNA and messenger RNA (mRNA) using RNA sequencing in lungs collected from mice model of VILI and control groups. Gene expression was analyzed through RNA sequencing and quantitative reverse transctiption polymerase chain reaction. A comprehensive bioinformatics analysis was used to characterize the expression profiles and relevant biological functions and for multiple comparisons among the controls and the injury models at different time points. Finally, lncRNA-mRNA coexpression networks were constructed and dysregulated lncRNAs were analyzed functionally. The mRNA transcript profiling, coexpression network analysis, and functional analysis of altered lncRNAs indicated enrichment in the regulation of immune system/inflammation processes, response to stress, and inflammatory pathways. We identified the lncRNA Gm43181 might be related to lung damage and neutrophil activation via chemokine receptor chemokine (C-X-C) receptor 2. In summary, our study provides an identification of aberrant lncRNA alterations involved in inflammation upon VILI, and lncRNA-mediated regulatory patterns may contribute to VILI inflammation.

Prognostic factors for severe Pneumocystis jiroveci pneumonia of non-HIV patients in intensive care unit: a bicentric retrospective study.

BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) in non-HIV patients is still a challenge for intensivists. The aim of our study was to evaluate mortality predictors of PJP patients requiring Intensive care unit (ICU) admission. METHODS: Retrospectively review medical records of patients with diagnosis of PJP admitted to four ICUs of two academic medical centers from October 2012 to October 2015. RESULTS: Eighty-two patients were enrolled in the study. Overall hospital mortality was 75.6 %. Compared with survivors, the non-survivors had older age (55 ± 16 vs. 45 ± 17, p = 0.014), higher APACHE II score (20 ± 5 vs. 17 ± 5, p = 0.01), lower white blood cell count (7.68 ± 3.44 vs. 10.48 ± 4.62, p = 0.005), less fever (80.6%vs. 100 %, p = 0.033), more hypotension (58.1 % vs. 20 %, p = 0.003), more pneumomediastinum (29 % vs. 5 %, p = 0.027). Logistic regression analysis demonstrated that age [odds ratio (OR)1.051; 95 % CI 1.007-1.097; p = 0.022], white blood cell count [OR 0.802; 95 % CI 0.670-0.960; p = 0.016], and pneumomediastinum [OR 16.514; 95 % CI 1.330-205.027; p = 0.029] were independently associated with hospital mortality. CONCLUSIONS: Mortality rate for non-HIV PJP patients requiring ICU admission was still high. Poor prognostic factors included age, white blood cell count and pneumomediastinum.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

Survey of Prolonged Mechanical Ventilation in Intensive Care Units in Mainland China.

INTRODUCTION: In mainland China, there are no special care centers (long-term acute care, weaning, chronic care facilities) for patients requiring prolonged mechanical ventilation (PMV). Our goal was to characterize the prevalence and outcome of patients undergoing PMV in Chinese intensive care units (ICUs). METHODS: A prospective 1-d prevalence study was performed at 55 ICUs, with 28-d follow-up. RESULTS: On the observation day, 622 adult patients occupied ICU beds. Enrollment criteria were met by 302 subjects receiving invasive mechanical ventilation, of which 109 (36.1%) had received ventilation for more than 21 d (median 51, 21-3,419), which was defined as PMV. During the following 28 d, another 45 subjects were classified as receiving PMV, but only 5% (3/58) of the subjects who were newly admitted to the ICU on the study day received PMV. Thirty-six (22.9%) of the 157 subjects receiving PMV were weaned, and 81 (51.6%) continued ventilation in the ICU. In the logistic regression analysis, age >74 y (odds ratio = 2.78, 95% CI 1.05-7.40, P = .041) and chronic congestive heart failure (odds ratio =12.23, 95% CI 1.48-101.05, P = .020) were associated with failure to wean in 28 d, while acute respiratory distress syndrome (ARDS) as the reason for mechanical ventilation (odds ratio = 0.14, 95% CI 0.04-0.52, P = .003) was associated with successful weaning. CONCLUSION: The number of subjects receiving PMV was surprisingly high in this cross-section of Chinese ICUs. In the following 28 ICU days, only a small proportion of these subjects were weaned. Age and chronic heart dysfunction were high risk factors for weaning failure.

A follow-up study on acute respiratory distress syndrome survivors after extracorporeal membrane oxygenation by pulmonary high-resolution CT.

OBJECTIVE: This study aims to identify morphological changes in the lung parenchyma of acute respiratory distress syndrome (ARDS) survivors after extracorporeal membrane oxygenation  (ECMO) by high-resolution computed tomography (HRCT) follow-up. Factors influencing these changes are also examined. METHODS: Information and lung HRCT scans were collected and studied 1, 3, 6, and 12 months after the withdrawal of severe ARDS survivors rescued by ECMO in the Respiratory Care Unit of Beijing Chaoyang Hospital from November 2009 to August 2012. The observation endpoint was set as the time when the lung lesions were basically absorbed or 12 months after withdrawal. RESULTS: Among nine survivors, one survivor was lost to follow-up. The lesions of two patients, which were attributed to bacterial pneumonia and pneumocystis pneumonia, were basically absorbed 1 month after surgery. Six patients completed the 12 month follow-up. Although initial morphological changes varied, different degrees of absorption improvement were observed in later stages of treatment. Lung HRCT analysis on the sixth month indicated that the degree of involvement of the ventral region was greater than that of the dorsal area. No significant difference was observed in patients in terms of ECMO support time, pre-ECMO Murray score, and APACHE II score, among others. CONCLUSION: Lung HRCT of severe ARDS survivors after ECMO treatment showed various degrees of morphological changes in the lung parenchyma. The severity of these changes may be associated with the disease duration.

Significance of Aspergillus spp. isolation from lower respiratory tract samples for the diagnosis and prognosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary diseases (COPD) is an emerging population at risk for invasive infection of Aspergillus. Isolation of Aspergillus from lower respiratory tract (LRT) samples is important for the diagnosis of invasive pulmonary aspergillosis (IPA). The purpose of this study was to investigate the value of Aspergillus isolation from LRT samples for the diagnosis and prognosis of IPA in COPD population. METHODS: Clinical record with Aspergillus spp. isolation in COPD and immunocompromised patients was reviewed in a retrospective study. Patients were categorized and compared according to their severity of illness (admitted to general ward or ICU) and immunological function (COPD or immunocompromised). RESULTS: Multivariate statistical analysis showed that, combined with Aspergillus spp. isolation, APACHE II scores > 18, high cumulative doses of corticosteroids (> 350 mg prednisone or equivalent dose) and more than four kinds of broad-spectrum antibiotics received in hospital may be predictors of IPA in COPD (OR = 9.076, P = 0.001; OR = 4.073, P = 0.026; OR = 4.448, P = 0.021, respectively). The incidence of IPA, overall mortality, mortality of patients with IPA and mortality of patients with Aspergillus spp. colonization were higher in COPD patients in ICU than in general ward, but were similar between COPD and immunocompromised patients. CONCLUSIONS: Aspergillus spp. isolation from LRT in COPD may be of similar importance as in immunocompromised patients, and may indicate an increased diagnosis possibility of IPA and worse prognosis when these patients received corticosteroids, antibiotics, and need to admit to ICU. Aspergillus spp. isolation from LRT samples combined with certain risk factors may be useful in differentiating colonization from IPA and evaluating the prognosis of IPA in COPD patients.

[Clinical observation of therapeutic effect of extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome].

OBJECTIVE: To investigate the therapeutic effects and safety of extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome (ARDS). METHODS: ECMO were initiated in 6 patients with ARDS, not responding to conventional mechanical ventilation. Oxygenation status, positive end-expiratory pressure (PEEP) level, and fraction of inspired oxygen [FiO(2)] were compared before and after treatment with ECMO, while the adverse effects of ECMO were recorded. RESULTS: In 6 cases, pulse blood oxygen saturation [SpO(2)] was elevated (0.45-0.92 up to 0.94-1.00), PEEP level [cm H(2)O, 1 cm H(2)O=0.098 kPa] and [FiO(2)] were lowered [PEEP: 10.0-22.0 down to 4.0-15.0; FiO(2): 1.00 down to 0.30-0.60] after treatment with ECMO. Of 6 cases, 2 patients with severe influenza A/H1N1 pneumonia finally died of shock; 1 patient with severe influenza A/H1N1 pneumonia and 1 patient with Klebsiella pneumoniae pneumonia were withdrawn from ECMO treatment because of deterioration of the disease. One patient suffering from Cytomegalovirus pneumonia and another with Acinetobacter baumannii pneumonia were successfully discharged from hospital with recovery. The main complications were bleeding and hemolysis. CONCLUSIONS: ECMO could improve gas exchange, oxygenation and partially replace pulmonary function. Patients with ARDS should be treated with ECMO early if artificial ventilation treatment was unresponsive.