Risk factors of in-hospital mortality and discriminating capacity of NIVO score in exacerbations of COPD requiring noninvasive ventilation.

BACKGROUND: Noninvasive mechanical ventilation (NIV) is recommended as the initial mode of ventilation to treat acute respiratory failure in patients with AECOPD. The Noninvasive Ventilation Outcomes (NIVO) score has been proposed to evaluate the prognosis in patients with AECOPD requiring assisted NIV. However, it is not validated in Chinese patients. METHODS: We used data from the MAGNET AECOPD Registry study, which is a prospective, noninterventional, multicenter, real-world study conducted between September 2017 and July 2021 in China. Data for the potential risk factors of mortality were collected and the NIVO score was calculated, and the in-hospital mortality was evaluated using the NIVO risk score. RESULTS: A total of 1164 patients were included in the study, and 57 patients (4.9%) died during their hospital stay. Multiple logistic regression analysis revealed that age ≥75 years, DBP <60 mmHg, Glasgow Coma Scale ≤14, anemia and BUN >7 mmol/L were independent predictors of in-hospital mortality. The in-hospital mortality was associated with an increase in the risk level of NIVO score and the difference was statistically significant (p < .001). The NIVO risk score showed an acceptable accuracy for predicting the in-hospital mortality in AECOPD requiring assisted NIV (AUC: 0.657, 95% CI: 0.584-0.729, p < .001). CONCLUSION: Our findings identified predictors of mortality in patients with AECOPD receiving NIV, providing useful information to identify severe patients and guide the management of AECOPD. The NIVO score showed an acceptable predictive value for AECOPD receiving NIV in Chinese patients, and additional studies are needed to develop and validate predictive scores based on specific populations.

Characteristics, treatments, in-hospital and long-term outcomes among inpatients with acute exacerbation of chronic obstructive pulmonary disease in China: sex differences in a large cohort study.

BACKGROUND: Data related to the characteristics, treatments and clinical outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients in China are limited, and sex differences are still a neglected topic. METHODS: The patients hospitalized for AECOPD were prospectively enrolled from ten medical centers in China between September 2017 and July 2021. Patients from some centers received follow-up for 3 years. Data regarding the characteristics, treatments and in-hospital and long-term clinical outcomes from male and female AECOPD patients included in the cohort were analyzed and compared. RESULTS: In total, 14,007 patients with AECOPD were included in the study, and 11,020 (78.7%) were males. Compared with males, female patients were older (74.02 ± 10.79 vs. 71.86 ± 10.23 years, P < 0.001), and had more comorbidities (2.22 ± 1.64 vs. 1.73 ± 1.56, P < 0.001), a higher frequency of altered mental status (5.0% vs. 2.9%, P < 0.001), lower diastolic blood pressure (78.04 ± 12.96 vs. 79.04 ± 12.47 mmHg, P < 0.001). In addition, there were also significant sex differences in a range of laboratory and radiographic findings. Females were more likely to receive antibiotics, high levels of respiratory support and ICU admission than males. The in-hospital and 3-year mortality were not significantly different between males and females (1.4% vs. 1.5%, P = 0.711; 35.3% vs. 31.4%, P = 0.058), while female smokers with AECOPD had higher in-hospital mortality than male smokers (3.3% vs. 1.2%, P = 0.002) and male smokers exhibited a trend toward higher 3-year mortality compared to female smokers (40.7% vs. 33.1%, P = 0.146). CONCLUSIONS: In AECOPD inpatients, females and males had similar in-hospital and long-term survival despite some sex differences in clinical characteristics and treatments, but female smokers had significantly worse in-hospital outcomes than male smokers. CLINICAL TRIAL REGISTRATION: Retrospectively registered, registration number is ChiCTR2100044625, date of registration 21/03/2021. URL: http://www.chictr.org.cn/showproj.aspx?proj=121626 .

A simple clinical risk score (ABCDMP) for predicting mortality in patients with AECOPD and cardiovascular diseases.

BACKGROUND: The morbidity and mortality among hospital inpatients with AECOPD and CVDs remains unacceptably high. Currently, no risk score for predicting mortality has been specifically developed in patients with AECOPD and CVDs. We therefore aimed to derive and validate a simple clinical risk score to assess individuals' risk of poor prognosis. STUDY DESIGN AND METHODS: We evaluated inpatients with AECOPD and CVDs in a prospective, noninterventional, multicenter cohort study. We used multivariable logistic regression analysis to identify the independent prognostic risk factors and created a risk score model according to patients' data from a derivation cohort. Discrimination was evaluated by the area under the receiver-operating characteristic curve (AUC), and calibration was assessed by the Hosmer-Lemeshow goodness-of-fit test. The model was validated and compared with the BAP-65, CURB-65, DECAF and NIVO models in a validation cohort. RESULTS: We derived a combined risk score, the ABCDMP score, that included the following variables: age > 75 years, BUN > 7 mmol/L, consolidation, diastolic blood pressure ≤ 60 mmHg, mental status altered, and pulse > 109 beats/min. Discrimination (AUC 0.847, 95% CI, 0.805-0.890) and calibration (Hosmer‒Lemeshow statistic, P = 0.142) were good in the derivation cohort and similar in the validation cohort (AUC 0.811, 95% CI, 0.755-0.868). The ABCDMP score had significantly better predictivity for in-hospital mortality than the BAP-65, CURB-65, DECAF, and NIVO scores (all P < 0.001). Additionally, the new score also had moderate predictive performance for 3-year mortality and can be used to stratify patients into different management groups. CONCLUSIONS: The ABCDMP risk score could help predict mortality in AECOPD and CVDs patients and guide further clinical research on risk-based treatment. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trail Registry NO.:ChiCTR2100044625; URL: http://www.chictr.org.cn/showproj.aspx?proj=121626 .

Validation of the Rome Severity Classification of Chronic Obstructive Pulmonary Disease Exacerbation: A Multicenter Cohort Study.

Background: The Rome severity classification is an objective assessment tool for the severity of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on readily measurable variables but has not been widely validated. The aim of this study is to evaluate the validity of the Rome classification in distinguishing the severity of AECOPD based on short-term mortality and other adverse outcomes. Methods: The Rome severity classification was applied to a large multicenter cohort of inpatients with AECOPD. Differences in clinical features, in-hospital and 60-day mortality, intensive care unit (ICU) admission, mechanical ventilation (MV) and invasive mechanical ventilation (IMV) usage were compared among the mild, moderate and severe AECOPD according to the Rome proposal. Moreover, univariate logistic analysis and Kaplan Meier survival analysis were also performed to find the association between the Rome severity classification and those adverse outcomes. Results: A total of 7712 patients hospitalized for AECOPD were included and classified into mild (41.88%), moderate (40.33%), or severe (17.79%) group according to the Rome proposal. The rate of ICU admission (6.4% vs 12.0% vs 14.9%, P <0.001), MV (11.7% vs 33.7% vs 45.3%, P <0.001) and IMV (1.4% vs 6.8% vs 8.9%, P <0.001) increased significantly with the increase of severity classification from mild to moderate to severe AECOPD. The 60-day mortality was higher in the moderate or severe group than in the mild group (3.5% vs 1.9%, 4.3% vs 1.9%, respectively, P <0.05) but showed no difference between the moderate and severe groups (2.6% vs 2.5%, P >0.05), results for in-hospital mortality showed the same trends. Similar findings were observed by univariate logistic analysis and survival analysis. Conclusion: Rome severity classification demonstrated excellent performance in predicting ICU admission and the need for MV or IMV, but how it performs in differentiating short-term mortality still needs to be confirmed.

Lipid metabolism of plasma-derived small extracellular vesicles in COVID-19 convalescent patients.

The coronavirus disease 2019 (COVID-19), which affects multiple organs, is causing an unprecedented global public health crisis. Most COVID-19 patients recover gradually upon appropriate interventions. Viruses were reported to utilize the small extracellular vesicles (sEVs), containing a cell-specific cargo of proteins, lipids, and nucleic acids, to escape the attack from the host's immune system. This study aimed to examine the sEVs lipid profile of plasma of recovered COVID-19 patients (RCs). Plasma sEVs were separated from 83 RCs 3 months after discharge without underlying diseases, including 18 recovered asymptomatic patients (RAs), 32 recovered moderate patients (RMs), and 33 recovered severe and critical patients (RSs), and 19 healthy controls (HCs) by Total Exosome Isolation Kit. Lipids were extracted from sEVs and then subjected to targeted liquid chromatography-mass spectrometry. The size, concentration, and distribution of sEVs did not differ in RCs and HCs as validated by transmission electron microscopy, nanoparticle tracking analysis, and immunoblot analysis. Fifteen subclasses of 508 lipids were detected in plasma sEVs from HCs, RAs, RMs, and RSs, such as phosphatidylcholines (PCs) and diacylglycerols (DAGs), etc. Total lipid intensity displayed downregulation in RCs compared with HCs. The relative abundance of DAGs gradually dropped, whereas PCs, lysophosphatidylcholines, and sphingomyelins were higher in RCs relative to HCs, especially in RSs. 88 lipids out of 241 in sEVs of RCs were significantly different and a conspicuous increase was revealed with disease status. The sEVs lipids alternations were found to be significantly correlated with the clinical indices in RCs and HCs, suggesting that the impact of COVID-19 on lipid metabolism lingered for a long time. The lipid abnormalities bore an intimate link with glycerophospholipid metabolism and glycosylphosphatidylinositol anchor biosynthesis. Furthermore, the lipidomic analysis showed that RCs were at higher risk of developing diabetes and sustaining hepatic impairment. The abnormality of immunomodulation in RCs might still exist. The study may offer new insights into the mechanism of organ dysfunction and help identify novel therapeutic targets in the RCs.

Elevated BUN Upon Admission as a Predictor of in-Hospital Mortality Among Patients with Acute Exacerbation of COPD: A Secondary Analysis of Multicenter Cohort Study.

Background: High blood urea nitrogen (BUN) is observed in a subset of patients with acute exacerbation of COPD (AECOPD) and may be linked to clinical outcome, but findings from previous studies have been inconsistent. Methods: We performed a retrospective analysis of patients prospectively enrolled in the MAGNET AECOPD Registry study (ChiCTR2100044625). Receiver operating characteristic (ROC) was used to determine the level of BUN that discriminated survivors and non-survivors. Univariate and multivariate Cox proportional hazards regression analyses were performed to assess the impact of BUN on adverse outcomes. Results: Overall, 13,431 consecutive inpatients with AECOPD were included in this study, of whom 173 died, with the mortality of 1.29%. The non-survivors had higher levels of BUN compared with the survivors [9.5 (6.8-15.3) vs 5.6 (4.3-7.5) mmol/L, P < 0.001]. ROC curve analysis showed that the optimal cutoff of BUN level was 7.30 mmol/L for in-hospital mortality (AUC: 0.782; 95% CI: 0.748-0.816; P < 0.001). After multivariate analysis, BUN level ≥7.3 mmol/L was an independent risk factor for in-hospital mortality (HR = 2.099; 95% CI: 1.378-3.197, P = 0.001), also for invasive mechanical ventilation (HR = 1.540; 95% CI: 1.199-1.977, P = 0.001) and intensive care unit admission (HR = 1.344; 95% CI: 1.117-1.617, P = 0.002). Other independent prognostic factors for in-hospital mortality including age, renal dysfunction, heart failure, diastolic blood pressure, pulse rate, PaCO2 and D-dimer. Conclusion: BUN is an independent risk factor for in-hospital mortality in inpatients with AECOPD and may be used to identify serious (or severe) patients and guide the management of AECOPD. Clinical Trial Registration: MAGNET AECOPD; Chinese Clinical Trail Registry NO.: ChiCTR2100044625; Registered March 2021, URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.

Low diastolic blood pressure and adverse outcomes in inpatients with acute exacerbation of chronic obstructive pulmonary disease: A multicenter cohort study.

BACKGROUND: Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients. METHODS: Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes. RESULTS: Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality. CONCLUSION: Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trail Registry, No. ChiCTR2100044625.

Liver failure as the initial presentation in cancer of unknown primary: a case report.

BACKGROUND: Liver failure is severe hepatic cellular damage caused by multiple factors that leads to clinical manifestations. Hepatic infiltration by malignancy is rarely reported as a cause of liver failure. CASE PRESENTATION: A 51-year-old male patient was admitted to the Wuhan Union Hospital complaining of bloating and jaundice. He had been diagnosed with polymyositis ten prior and was taking oral glucocorticoids. Physical examination revealed seroperitoneum and icteric sclera; laboratory tests revealed liver dysfunction, a coagulopathy, and negative results for the common causes of liver failure. Moreover, an ascitic tap and bone marrow aspirate and trephine confirmed a metastatic, poorly differentiated adenocarcinoma. These findings indicate that malignant infiltration is the most likely cause of liver failure. Regrettably, the patient refused complete liver and lymph node biopsies and was discharged on day 31. CONCLUSION: Clinicians should consider the possibility of malignant infiltration when approaching a case of liver failure with prodromal symptoms or imaging abnormalities, especially in patients with autoimmune diseases, such as polymyositis.

Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge.

BACKGROUND: Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. METHODS: We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. RESULTS: In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing. Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. CONCLUSION: This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.

Blood Eosinophils and Clinical Outcomes in Inpatients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study.

Purpose: The prognostic value of blood eosinophils in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains controversial. This study aimed to evaluate whether blood eosinophils could predict in-hospital mortality and other adverse outcomes in inpatients with AECOPD. Methods: The patients hospitalized for AECOPD were prospectively enrolled from ten medical centers in China. Peripheral blood eosinophils were detected on admission, and the patients were divided into eosinophilic and non-eosinophilic groups with 2% as the cutoff value. The primary outcome was all-cause in-hospital mortality. Results: A total of 12,831 AECOPD inpatients were included. The non-eosinophilic group was associated with higher in-hospital mortality than the eosinophilic group in the overall cohort (1.8% vs 0.7%, P < 0.001), the subgroup with pneumonia (2.3% vs 0.9%, P = 0.016) or with respiratory failure (2.2% vs 1.1%, P = 0.009), but not in the subgroup with ICU admission (8.4% vs 4.5%, P = 0.080). The lack of association still remained even after adjusting for confounding factors in subgroup with ICU admission. Being consistent across the overall cohort and all subgroups, non-eosinophilic AECOPD was also related to greater rates of invasive mechanical ventilation (4.3% vs 1.3%, P < 0.001), ICU admission (8.9% vs 4.2%, P < 0.001), and, unexpectedly, systemic corticosteroid usage (45.3% vs 31.7%, P < 0.001). Non-eosinophilic AECOPD was associated with longer hospital stay in the overall cohort and subgroup with respiratory failure (both P < 0.001) but not in those with pneumonia (P = 0.341) or ICU admission (P = 0.934). Conclusion: Peripheral blood eosinophils on admission may be used as an effective biomarker to predict in-hospital mortality in most AECOPD inpatients, but not in patients admitted into ICU. Eosinophil-guided corticosteroid therapy should be further studied to better guide the administration of corticosteroids in clinical practice.

Nanopore membrane chip-based isolation method for metabolomic analysis of plasma small extracellular vesicles from COVID-19 survivors.

Multiple studies showed that metabolic disorders play a critical role in respiratory infectious diseases, including COVID-19. Metabolites contained in small extracellular vesicles (sEVs) are different from those in plasma at the acute stage, while the metabolic features of plasma sEVs of COVID-19 survivors remain unknown. Here, we used a nanopore membrane-based microfluidic chip for plasma sEVs separation, termed ExoSEC, and compared the sEVs obtained by UC, REG, and ExoSEC in terms the time, cost, purity, and metabolic features. The results indicated the ExoSEC was much less costly, provided higher purity by particles/proteins ratio, and achieved 205-fold and 2-fold higher sEVs yield, than UC and REG, respectively. Moreover, more metabolites were identified and several signaling pathways were significantly enriched in ExoSEC-sEVs compared to UC-sEVs and REG-sEVs. Furthermore, we detected 306 metabolites in plasma sEVs using ExoSEC from recovered asymptomatic (RA), moderate (RM), and severe/critical COVID-19 (RS) patients without underlying diseases 3 months after discharge. Our study demonstrated that COVID-19 survivors, especially RS, experienced significant metabolic alteration and the dysregulated pathways mainly involved fatty acid biosynthesis, phenylalanine metabolism, etc. Metabolites of the fatty acid biosynthesis pathway bore a significantly negative association with red blood cell counts and hemoglobin, which might be ascribed to hypoxia or respiratory failure in RM and RS but not in RA at the acute stage. Our study confirmed that ExoSEC could provide a practical and economical alternative for high throughput sEVs metabolomic study.

Superior Predictive Value of D-Dimer to the Padua Prediction Score for Venous Thromboembolism in Inpatients with AECOPD: A Multicenter Cohort Study.

Background: The optimal tool for risk prediction of venous thromboembolism (VTE) in inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is still unknown. This study aimed to evaluate whether D-dimer could predict the risk of VTE in inpatients with AECOPD compared to the Padua Prediction Score (PPS). Methods: Inpatients with AECOPD were prospectively enrolled from seven medical centers in China between December 2018 and June 2020. On admission, D-dimer was detected, PPS was calculated for each patient, and the incidence of 2-month VTE was investigated. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of D-dimer and PPS on VTE development, and the best cut-off value for both methods was evaluated through the Youden index. Results: Among the 4468 eligible patients with AECOPD, 90 patients (2.01%) developed VTE within 2 months after admission. The area under the receiver operating characteristic curves (AUCs) of D-dimer for predicting VTE were significantly higher than those of the PPS both in the overall cohort (0.724, 95% CI 0.672-0.776 vs 0.620, 95% CI 0.562-0.679; P<0.05) and the subgroup of patients without thromboprophylaxis (0.747, 95% CI 0.695-0.799 vs 0.640, 95% CI 0.582-0.698; P<0.05). By calculating the Youden Index, the best cut-off value of D-dimer was determined to be 0.96 mg/L with an AUC of 0.689, which was also significantly better than that of the PPS with the best cut-off value of 2 (AUC 0.581, P=0.007). After the combination of D-dimer with PPS, the AUC (0.621) failed to surpass D-dimer alone (P=0.104). Conclusion: D-dimer has a superior predictive value for VTE over PPS in inpatients with AECOPD, which might be a better choice to guide thromboprophylaxis in inpatients with AECOPD due to its effectiveness and convenience. Clinical Trial Registration: Chinese Clinical Trail Registry NO. ChiCTR2100044625; URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.

Metagenomic next-generation sequencing for accurate diagnosis and management of lower respiratory tract infections.

OBJECTIVES: This study aimed to evaluate the clinical value of metagenomic next-generation sequencing (mNGS) in patients with suspected lower respiratory tract infections. METHODS: This retrospective study reviewed patients with suspected lower respiratory tract infections at the Wuhan Union Hospital. Data including demographic, laboratory, and radiological profiles; treatment; and outcomes were recorded and analyzed. RESULTS: mNGS identified pathogenic microbes in 100/140 (71.4%) patients, although 135 (96.4%) had received empiric antibiotic treatment before the mNGS tests. Single bacterial infection (35/100, 35%) was the most common type of infection in patients with positive mNGS results, followed by single fungal infection (14/100, 14%), bacterial-viral coinfection (14/100, 14%), single viral infection (12/100, 12%), bacterial-fungal coinfection (9/100, 9%), fungal-viral coinfection (9/100, 9%), and bacterial-fungal-viral coinfection (7/100, 7%). Moreover, compared with culture test, mNGS showed higher sensitivity (63/85, 74.1% vs 22/85, 25.9% P = 0.001) and lower processing time (24 hours vs 48 hours). Antibiotic treatment was adjusted or confirmed based on the mNGS results in 123 (87.9%) patients, including five (3.6%), 33 (23.6%), and 85 (60.7%) patients, in whom treatment was downgraded, upgraded, and unchanged, respectively. Almost all patients, regardless of escalation, de-escalation, or no change in treatment, showed significant improvement in clinical symptoms and inflammatory indicators. In addition, 17 (12.1%) patients were referred to Wuhan Pulmonary Hospital for further treatment because of confirmed or suspected tuberculosis. CONCLUSION: mNGS could be a promising technique for microbiological diagnosis and antibiotic management, potentially improving outcomes for patients.

Validation of Risk Assessment Models Predicting Venous Thromboembolism in Inpatients with Acute Exacerbation Of Chronic Obstructive Pulmonary Disease: A Multicenter Cohort Study in China.

BACKGROUND: Inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are at increased risk for venous thromboembolism (VTE); however, the prophylaxis for VTE is largely underused in China. Identifying high-risk patients requiring thromboprophylaxis is critical to reduce the mortality and morbidity associated with VTE. This study aimed to evaluate and compare the validities of the Padua Prediction Score and Caprini risk assessment model (RAM) in predicting the risk of VTE in inpatients with AECOPD in China. METHODS: The inpatients with AECOPD were prospectively enrolled from seven medical centers of China between September 2017 and January 2020. Caprini and Padua scores were calculated on admission, and the incidence of 3-month VTE was investigated. RESULTS: Among the 3,277 eligible patients with AECOPD, 128 patients (3.9%) developed VTE within 3 months after admission. The distribution of the study population by the Caprini risk level was as follows: high, 53.6%; moderate, 43.0%; and low, 3.5%. The incidence of VTE increased by risk level as high, 6.1%; moderate, 1.5%; and low, 0%. According to the Padua RAM, only 10.9% of the study population was classified as high risk and 89.1% as low risk, with the corresponding incidence of VTE of 7.9 and 3.4%, respectively. The Caprini RAM had higher area under curve compared with the Padua RAM (0.713 ± 0.021 vs. 0.644 ± 0.023, p = 0.029). CONCLUSION: The Caprini RAM was superior to the Padua RAM in predicting the risk of VTE in inpatients with AECOPD and might better guide thromboprophylaxis in these patients.

Single-cell analysis of diverse immune phenotypes in malignant pleural effusion.

The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4+ T cells compared to CD8+ T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer.

Prolonged SARS-CoV-2 Viral Shedding in Patients with COVID-19 was Associated with Delayed Initiation of Arbidol Treatment and Consulting Doctor Later: A Retrospective Cohort Study.

OBJECTIVE: To study data about SARS-CoV-2 virus shedding and clarify the risk factors for prolonged virus shedding. METHODS: Data were retrospectively collected from adults hospitalized with laboratory-confirmed coronavirus disease-19 (COVID-19) in Wuhan Union Hospital. We compared clinical features among patients with prolonged (a positive SARS-CoV-2 RNA on day 23 after illness onset) and short virus shedding and evaluated risk factors associated with prolonged virus shedding by multivariate regression analysis. RESULTS: Among 238 patients, the median age was 55.5 years, 57.1% were female, 92.9% (221/238) were administered with arbidol, 58.4% (139/238) were given arbidol in combination with interferon. The median duration of SARS-CoV-2 virus shedding was 23 days (IQR, 17.8-30 days) with a longest one of 51 days. The patients with prolonged virus shedding had higher value of D-dimer (P=0.002), IL-6 (P<0.001), CRP (P=0.005) and more lobes lung lesion (P=0.014) on admission, as well as older age (P=0.017) and more patients with hypertension (P=0.044) than in those the virus shedding less than 23 days. Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol >8 days after symptom onset [OR: 2.447, 95% CI (1.351-4.431)], ≥3 days from onset of symptoms to first medical visitation [OR: 1.880, 95% CI (1.035-3.416)], illness onset before Jan. 31, 2020 [OR: 3.289, 95% CI (1.474-7.337)]. Arbidol in combination with interferon was also significantly associated with shorter virus shedding [OR: 0.363, 95% CI (0.191-0.690)]. CONCLUSION: Duration of SARS-CoV-2 virus shedding was long. Early initiation of arbidol and arbidol in combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.

Linking the gut microbiota to persistent symptoms in survivors of COVID-19 after discharge.

Several follow-up studies have found that COVID-19 (coronavirus disease 2019) patients had persistent symptoms after discharge. Gut microbiota play an important role in human health and immune responses. Therefore, this study investigated the gut microbiota of recovered COVID-19 patients and the correlations between gut microbiota and persistent symptoms after discharge. Stool samples were collected from 15 recovered healthcare workers (HCWs) with COVID-19 at three months after discharge, in addition, stool samples were collected from 14 healthy controls (HCs) to perform 16S rRNA gene sequencing between May and July 2020. Compared with HCs, recovered HCWs had reduced bacterial diversity at three months after discharge, with a significantly higher relative abundance of opportunistic pathogens, and a significantly lower relative abundance of beneficial bacteria. In addition, Escherichia unclassified was positively correlated with persistent symptoms at three months after discharge, including fatigue (r = 0.567, p = 0.028), chest tightness after activity (r = 0.687, p = 0.005), and myalgia (r = 0.523, p = 0.045). Intestinibacter bartlettii was positively correlated with anorexia (r = 0.629, p = 0.012) and fatigue (r = 0.545, p = 0.036). However, Faecalibacterium prausnitzii was negatively correlated with chest tightness after activity (r = -0.591, p = 0.02), and Intestinimonas butyriciproducens was negatively correlated with cough (r = -0.635, p = 0.011). In conclusion, the gut microbiota of recovered HCWs with COVID-19 at three months after discharge was different from that of HCs, and altered gut microbiota was correlated with persistent symptoms after discharge, highlighting that gut microbiota may play an important role in the recovery of patients with COVID-19.

Role of Prealbumin in Predicting the Prognosis of Severely and Critically Ill COVID-19 Patients.

Most critically ill patients experience malnutrition, resulting in a poor prognosis. This study aimed to evaluate the association of prealbumin (PAB) with the prognosis for severely and critically ill coronavirus disease 2019 (COVID-19) patients and explore factors related to this association. Patients with laboratory-confirmed COVID-19 from West Campus of Union Hospital in Wuhan from January 29, 2020 to March 31, 2020 were enrolled in this study. Patients were classified into the PAB1 (150-400 mg/L; N = 183) and PAB2 (< 150 mg/L; N = 225) groups. Data collection was performed using the hospital's electronic medical records system. The predictive value of PAB was evaluated by measuring the area under the receiver-operating characteristic (AUROC) curve. Patients were defined as severely or critically ill based on the Guidance for COVID-19 (7th edition) by the National Health Commission of China. During this analysis, 316 patients had severe cases and 65 had critical cases. A reduced PAB level was associated with a higher risk of mortality and a longer hospital stay. The AUROC curve for the prognosis based on the PAB level was 0.93, with sensitivity of 97.2% and specificity of 77.6%. For severe cases, a lower level of PAB was associated with a higher risk of malnutrition, higher NK cell counts, and lower B lymphocyte counts; these factors were not significant in critical cases. C-reactive protein and nutritional status mediated the association between PAB and prognosis. This retrospective analysis suggests that the PAB level on admission is an indicator of the prognosis for COVID-19.

Comparison of Immediate and Sequential Withdrawal of a Systemic Glucocorticoid in the Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Parallel-Controlled, Open-Label Study.

Patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) were treated with immediate or sequential withdrawal after 5 days of systemic glucocorticoids. The effects of the two withdrawal methods on the prognosis of patients were compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, double-blind, parallel-controlled, open-label study was conducted in the respiratory department of tertiary hospitals in Central China. Patients met inclusion criteria for AECOPD and needed to use systemic glucocorticoids. They were randomly assigned to immediate and sequential withdrawal groups at a 1:1 ratio. The study was completed in August 2020 and is registered at the China Clinical Trials Registry (Chictr.org) (ChiCTR1800018894). According to general data and clinical characteristics, there were no statistically significant differences between the 329 patients in the immediate withdrawal group and the 310 patients in the sequential withdrawal group (P > 0.05). At the 30, 90, 180, and 360-days follow-up, the acute exacerbation frequency, rehospitalization rate, mortality, and intensive care unit (ICU) treatment rate were not significantly different between the immediate withdrawal group and sequential withdrawal group (P > 0.05). The modified Medical Research Council (mMRC) and COPD assessment test (CAT) scores were also not significantly different between the two groups. At the 180- and 360-day follow-up, forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (P > 0.05). The time from discharge to first acute exacerbation was significantly lower in the immediate withdrawal group (46.12 days) than in sequential withdrawal group (49.02 days) (P < 0.05). The time of stay in the hospital for the first time after discharge was not significantly different between the two groups (P > 0.05). Adverse events were not significantly different between the immediate withdrawal group and sequential withdrawal group (P < 0.05). Subgroup analysis was performed according to age, degree of disease, and relevant indicators. At the 30-day follow-up, the acute exacerbation frequency of patients with advanced age, high global strategy for chronic obstructive lung disease (GOLD), and high fractional exhaled nitric oxide was significantly higher in the immediate withdrawal group than in the sequential withdrawal group (P < 0.05). In addition, according to receiver operating characteristic (ROC) curve analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly higher in patients with age > 63.5 years or GOLD > 3 in the immediate withdrawal group than in the sequential withdrawal group, suggesting that the short-term efficacy was poor.

Inflammatory Profiles and Clinical Features of Coronavirus 2019 Survivors 3 Months After Discharge in Wuhan, China.

BACKGROUND: Postdischarge immunity and its correlation with clinical features among patients recovered from coronavirus disease 2019(COVID-19) are poorly described. This prospective cross-sectional study explored the inflammatory profiles and clinical recovery of patients with COVID-19 at 3 months after hospital discharge. METHODS: Patients with COVID-19 discharged from 4 hospitals in Wuhan, recovered asymptomatic patients (APs) from an isolation hotel, and uninfected healthy controls (HCs) were recruited. Viral nucleic acid and antibody detection, laboratory examination, computed tomography, pulmonary function assessment, multiplex cytokine assay, and flow cytometry were performed. RESULTS: The72 age-, sex- and body mass index-matched participants included 19 patients with severe/critical COVID-19 (SPs), 20 patients with mild/moderate COVID-19 (MPs), 16 APs, and 17 HCs. At 3 months after discharge, levels of proinflammatory cytokines and factors related to vascular injury/repair in patients recovered from COVID-19 had not returned to those of the HCs, especially among recovered SPs compared with recovered MPs and APs. These cytokines were significantly correlated with impaired pulmonary function and chest computed tomographic abnormalities. However, levels of immune cells had returned to nearly normal levels and were not significantly correlated with abnormal clinical features. CONCLUSION: Vascular injury, inflammation, and chemotaxis persisted in patients with COVID-19 and were correlated with abnormal clinical features 3 months after discharge, especially in recovered SPs.