Search

Background Malignant pleural effusion (MPE) is common in malignant pleural mesothelioma (MPM). The survival of patients with MPM and MPE is heterogeneous. The LENT and BRIMS scores using routine clinical parameters were developed to predict the survival of patients with unselected MPE and MPM, respectively. This study aimed to stratify the survival of selected MPM patients with MPE. Methods Data were collected from subjects diagnosed with MPM and MPE. The LENT and BRIMS scores were applied using a combination of clinical variables to stratify subjects and compare survival characteristics. Results In total, 101 patients with MPM complicated by MPE were included in the study. The median follow‐up time was 71 months (interquartile range: 24–121 months). Overall median survival was 24 (interquartile range: 12–52 months). Based on the LENT score, the low‐, moderate‐, and high‐risk groups accounted for 65.3% (66 cases), 34.7% (35 cases), and 0%, respectively. The cumulative survival rates of the two groups were statistically significant (p = 0.031). The area under the curve (AUC) of the LENT score was 0.662. Based on the BRIMS score, the first, second, third, and fourth risk groups accounted for 1.0% (1 case), 42.9% (35 cases), 28.7% (29 cases), and 19.4% (36 cases), respectively. Survival was significantly higher in patients in the risk groups 1 and 2 than in patients in the risk groups 3 and 4 (p = 0.037). The AUC of the BRIMS score was 0.605. Conclusions Using routinely available clinical variables, both LENT and BRIMS scores could stratify selected MPM and MPE patients into risk groups with statistically different survival., The individual survival of patients with MPM combined with MPE varied greatly in this study. Both LENT and BRIMS scores could help stratify the survival risk of patients with MPM complicated by MPE with fair‐to‐good performance. More effective predictive models should be established in adequately designed prospective studies.

Xin Zhang *, Feng-Shuang Yi *, Huan-Zhong Shi Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huan-Zhong Shi; Feng-Shuang YiDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongti Nanlu, Chao-Yang District, Beijing, 100020, People’s Republic of ChinaTel/Fax +86 10 85231890Email shihuanzhong@ccmu.edu.cn; yifengshuang@ccmu.edu.cnBackground: Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies that leads to a poor quality of life and limits treatment options.Objective: The objective of this study was to identify biomarkers of survival in patients with MPE, which will greatly facilitate the clinical management of this complication.Methods: This retrospective study recruited patients who had been pathologically diagnosed with MPE, regardless of the type of primary cancer, at Beijing Chao-Yang Hospital over 158 months. Demographic, clinical, hematological, and pleural fluid data were collected and analyzed as potential predictors of survival, and a new predictive model was developed based on Cox and logistic regression analyses.Results: In our alternative prognostic model (n = 281), four routinely detected variables, namely, carcinoembryonic antigen (CEA) level, monocyte count, N-terminal pro B-type natriuretic peptide (NT-pro-BNP) level, and pleural effusion chloride level on admission, were identified as predictors (the CONCH prognostic score). Patients were divided into three prognosis subgroups based on risk stratification, with median survival periods of 17, 11, and 5 months, respectively. In comparison with the low-risk group, patients in the medium- and high-risk groups showed significantly poorer survival (medium-risk group: hazard ratio [HR], 1.586; 95% confidence interval [CI], 1.047– 2.402; P = 0.029; high-risk group: HR, 4.389; 95% CI, 2.432– 7.921; P < 0.001).Conclusion: Four routinely detected variables were used to develop the CONCH scoring system, which was confirmed to be an accurate prognostic score for patients with MPE. This system can guide the selection of interventions and management for MPE.Keywords: malignant pleural effusion, prognosis, CEA, monocyte, NT-pro-BNP

Pleural effusion (PE) is prevalent in unselected "real-life" populations of multiple myeloma (MM). However, its prognostic value on MM is currently elusive. This study aimed to explore the role of PE on MM prognosis and to develop a novel prognostic nomogram for a cohort of Chinese patients with MM. Patients diagnosed with MM form 2000 through 2017 were retrospectively enrolled. PE was evaluated by chest computed tomography (CT) scans. Independent predictors of overall survival (OS) were identified using a multivariable Cox regression model performed on variables selected by the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram was constructed based on these variables. The concordance index (C-index) and the calibration curve were used to evaluate the predictive performance of the nomogram. Among 861 patients analyzed, 368 patients developed PE. Multivariate cox regression and restricted mean survival time (RMST) analyses revealed that patients with PE experienced worse OS vs. patients without PE. A nomogram predictive of OS was constructed using PE, plasma cell proportion, international staging system (ISS) stage, Charlson comorbidity index (CCI), 1q21 gain, and autologous hematopoietic stem cell transplantation (HSCT). The nomogram showed satisfactory discrimination in the derivation cohort (C-index=0.729) and the validation cohort (C-index=0.684), outperforming the Durie-Salmon (DS) and ISS staging systems. Moreover, the nomogram accurately classified patients into two distinct high- and low-risk groups. PE is frequently encountered in the disease course for MM patients. We derivated and validated a novel nomogram for MM based on PE, outperforming the DS/ISS staging systems.

Malignant pleural effusion (MPE) is a frequent complication of malignancies and poses a clinical problem. CD4+ T lymphocytes are the most frequent cell population in MPE. Traditionally, CD4+ T cells are classified into two subsets based on cytokine production profiles, type 1 (Th1) and type 2 (Th2) helper T cells, which exhibit distinct functions. Recently, other T-cell subsets have been added to the Th-cell “portfolio”, including regulatory T, Th17, Th9, and Th22 cells. The current review focuses on summarizing the Th-cell phenotypic characteristics, mechanism of Th-cell differentiation, and their pleural space recruitment, based on recent research. We also describe the interplay in MPE among different Th cells, as well as Th cells and lung cancer cells or mesothelial cells. Future research should expand the landscape map of human MPE immune cells, explore the immuno-regulation of B cells, and investigate the communication between macrophages and Th cells in MPE, which may facilitate meaningful advancements in the diagnoses and therapeutics of MPE.

Emerging evidence indicates that Myo9b is a cancer metastasis–related protein and functions in a variety of immune-related diseases. However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing TH1 cells and increasing TH17 cells. CD4+ naive T cells isolated from Myo9b−/− mouse spleens exhibited less TH1 cell differentiation and more TH17 cell differentiation in vitro. mRNA sequencing of nucleated cells showed that T cell–specific adaptor protein (TSAd) was downregulated in Myo9b−/− mouse MPE, and enrichment of the H3K27me3 mark in the TSAd promoter region was found in the Myo9b−/− group. Naive T cells purified from wild type mouse spleens transfected with TSAd-specific small interfering RNAs (siRNAs) also showed less TH1 cell differentiation and more TH17 cell differentiation than those from the siRNA control group. Furthermore, downregulation of TSAd in mice using cholesterol-conjugated TSAd-specific siRNA suppressed MPE development, decreased TH1 cells, and increased TH17 cells in MPE in vivo. Taken together, Myo9b deficiency suppresses MPE development not only by suppressing pleural cancer metastasis but also by regulating TH1/TH17 cell response via a TSAd-dependent pathway. This work suggests Myo9b and TSAd as novel candidates for future basic and clinical investigations of cancer.

Characterization of T cell receptor (TCR) repertoires is essential for understanding the mechanisms of

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., Detailed immune cell subset identification in human lung (malignant pleural effusion) MPE is important for diagnosis and prognosis. Here the authors use single cell RNA sequencing to identify immune cell types within MPE and show differential gene expression compared to circulating immune cells in blood.

IL-10, produced by a wide variety of cells, is a highly pleiotropic cytokine that plays a critical role in the control of immune responses. However, its regulatory activity in tumor immunity remains poorly understood. In this study, we report that IL-10 deficiency robustly suppressed the formation of malignant pleural effusion (MPE) and significantly enhanced miR-7116-5p expression in pleural CD4+ T cells. We demonstrated that miR-7116-5p suppressed IL-10-mediated MPE formation by inhibiting pleural vascular permeability as well as tumor angiogenesis and tumor growth. IL-10 promoted MPE formation by suppressing miR-7116-5p that enhances TH 1 response. We identified G protein-coupled receptor 55 (GPR55) as a potential target of miR-7116-5p, and miR-7116-5p promoted TH 1 cell function by downregulating GPR55. Moreover, GPR55 promoted MPE formation by inhibiting TH 1 cell expansion through the ERK phosphorylation pathway. These results uncover an IL-10-mediated pathway controlling TH 1 cells and demonstrate a central role for miR-7116-5p/GPR55/ERK signaling in the physiological regulation of IL-10-driven pro-malignant responses.

Purpose Peripheral blood eosinophilic counts are susceptible to many factors and have variability over time. There are limited studies on association of blood eosinophilia with long-term mortality of chronic obstructive pulmonary disease (COPD) patients and these results remain controversial. Our aims were to explore the association of blood eosinophilia at index hospitalization and stability of blood eosinophilia stability over 5 years with all-cause mortality of patients hospitalized for acute exacerbation of COPD (AECOPD). Patients and methods Eight hundred twenty-nine patients hospitalized for AECOPD between 2013 and 2014 were included in this study and grouped into two groups according to blood eosinophil with 150 cells/μL used as the cutoff value to form eosinophilic and non-eosinophilic groups. Two hundred forty-one COPD inpatients with at least three blood eosinophils measured from different hospitalizations were used for analysis of longitudinally eosinophilic stability and divided into three groups according to the same cutoff value: predominantly (PE), intermittently (IE) and rarely (RE) eosinophilic groups. Cox regression analysis was used to determine the association of blood eosinophilia and all-cause mortality. Results In patients hospitalized for AECOPD, 261 (31.5%) at baseline and 41 (17%) based on at least three measurements of blood eosinophils had increased blood eosinophils. For all-cause mortality, eosinophilic COPD patients at index hospitalization had a lower all-cause mortality compared with non-eosinophilic COPD patients (hazard ratio 0.77, 95% confidence interval 0.6-0.99, P=0.04). In patients readmitted for AECOPD by longitudinal eosinophil stability, with the RE group used as reference, the PE group was associated with a lower all-cause mortality of AECOPD patients (hazard ratio 0.43, 95% confidence interval 0.22-0.85, P=0.016), compared to the IE group (hazard ratio 0.72, 95% confidence interval 0.47-1.11, P=0.133). Conclusion Patients with increased eosinophils (using eosinophil 150 cells/μL as a cutoff value), especially predominantly increased eosinophil levels based on multiple measurements, had a lower risk of all-cause mortality. Blood eosinophilia can be used as a biomarker in hospitalized COPD exacerbations for predicting the risk of all-cause mortality.

γδT cells are an important source of IL-17A and play an anti- or protumor role depending on the surrounding microenvironment. The precise role of γδT cells in the development of malignant pleural effusions (MPE) remains unknown. Using flow cytometry, we analyzed the distribution and differentiation of γδT cells in wild-type (WT) and IL-10-∕- mice. We carefully elucidated the influence of γδT cells on the formation of MPE by depleting γδT cells from WT, IL-10-∕-, and IL-17a-∕- mice. The distribution of γδT17 cells in human MPE and peripheral blood was also determined. Our data showed that both γδT cells and IL-17A-producing γδT (γδT17) cells accumulated in murine MPE, and IL-10 deficiency enhanced their accumulation. γδT cells were the main source of IL-17A in MPE for both WT and IL-10-∕- mice. IL-10 inhibited the chemotactic response of γδT cells to MPE and the proliferation of these cells. IL-10 suppressed γδT cell secretion of IL-17A via RORγt. The ablation of γδT cells accelerated MPE accumulation in both WT and IL-10-∕- mice, but it did not influence MPE accumulation in IL-17a-∕- mice. Patients with higher frequencies of γδT17 cells had significantly longer survival times than patients with lower frequencies of γδT17 cells. Taken together, our data demonstrate that γδT17 cells play an inhibitory role in the progression of MPE, and the accumulation of γδT17 cells in MPE is suppressed by IL-10.

Background Pleural effusion is a common clinical problem in patients with cancer. We aimed to summarize all the known prognostic indicators of malignant pleural effusion. Methods We did a systematic review and meta-analysis with a systematic literature search. All prospective or retrospective cohort studies that estimated the prognostic factors of malignant pleural effusion were enrolled. Mantel–Haenszel method was used to calculate the pooled hazard ratio (HR) and 95% confidence interval (CI). Results Eventually, we identified 82 studies with a total of 10,748 patients that met our inclusion criteria. The LENT score showed a good prognostic value (HR 1.97, 95% CI 1.67–2.31) so did the LENT score item. In addition, clinical parameters like stage (HR 1.68, 95% CI 1.25–2.25), distant metastasis (HR 1.62, 95% CI 1.38–1.89), EGFR mutation (HR 0.65, 95% CI 0.56–0.74), serum biological parameters like hemoglobin (HR 1.56, 95% CI 1.17–2.06), albumin (HR 1.71, 95% CI 1.25–2.34), C-reaction protein (HR 1.84, 95% CI 1.49–2.29), VEGF (HR 1.70, 95% CI 1.18–2.43) and pleural effusion biological parameters like PH (HR 1.95, 95% CI 1.46–2.60), glucose (HR 1.75, 95% CI 1.18–2.61), VEGF (HR 1.99, 95% CI 1.67–2.37), and survivin (HR 2.90, 95% CI 1.17–7.20) are also prognostic factors for malignant pleural effusion. Conclusions For malignant pleural effusion, LENT score and its items are valuable prognostic biomarkers, so do the clinical parameters like stage, distant metastasis, EGFR mutation, the serum biological parameters like hemoglobin, albumin, C-reaction protein, VEGF and the pleural effusion biological parameters like PH, glucose, VEGF and survivin.

BACKGROUND: There is no standardized system to evaluate pleural effusion size on ultrasound (US). We aimed to explore the role of US in determining the amount of pleural effusion, with an attempt to provide evidence for clinical efficacy evaluation and treatment program selection. METHODS: A total of 98 patients undergoing thoracoscopy at our center were enrolled in this study. The patients take a sitting position, then the maximum depths of the pleural effusion by US at the subscapular line, posterior axillary line, midaxillary line, anterior axillary line, and midclavicular line, as well as the maximum thickness of the pleural effusion at the subscapular line, were measured before pleural effusion drainage. Then, the corresponding values in the lateral position were also measured. The relationships between the actual pleural effusion amounts and the measurements at these lines were analyzed using the multivariate linear regression model (MLRM). RESULTS: The regression equation of the group with a pleural effusion amount of 500–1,000 mL in the sitting position showed statistical significance (P=0.001). The P values of the maximum depths at the subscapular line (X(1)) and midclavicular line (X(5)) and the maximum thickness at the subscapular line (X(6)) were below 0.05. Thus, a final model was established using X(1), X(5), and X(6) as the independent variables. CONCLUSIONS: The combination of US examination and MLRM enables the quantitative determination of pleural effusion.

Background The current outbreak of coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei, China, spreads across national and international borders. Methods We prospectively collected medical records of 14 health care workers (HCWs) who were infected with SARS-CoV-2, in neurosurgery department of Wuhan Union Hospital, China. Results Among the 14 HCWs, 12 were conformed cases, the other 2 were suspected cases. Most of them were either exposed to the two index patients or infected coworkers, without knowing they were COVID-19 patients. There were 4 male and 10 female infected HCWs in this cohort, whose mean age was 36 years (SD, 6 years). The main symptoms included myalgia or fatigue (100%), fever (86%) and dry cough (71%). On admission, 79% of infected HCWs showed leucopenia and 43% lymphopenia. Reduced complement C3 could be seen in 57% of the infected HCWs and IL-6 was significantly elevated in 86% of them. The proportion of lymphocytes subsets, concentrations of immunoglobulins, complement C4, IL-2, IL-4, IL-10, TNF-α and IFN-γ were within normal range in these 14 infected HCWs. The most frequent findings on pulmonary computed tomographic images were bilateral multifocal ground-glass opacifications (86%). Conclusions Human-to-human transmission of COVID-19 pneumonia has occurred among HCWs, and most of these infected HCWs with confirmed COVID-19 are mild cases. Our data suggest that in the epidemic area of COVID-19, stringent and urgent surveillance and infection-control measures should be implemented to protect doctors and nurses from COVID-19 infection.

The role of IL-10 in malignant pleural effusion (MPE) remains unknown. By using murine MPE models, we observed that an increase in pleural IL-10 was a significant predictor of increased risk of death. We noted that TH 1- and TH 17-cell content in MPE was higher in IL-10-/- mice than in WT mice, and IL-10 deficiency promoted differentiation into TH 1 but not into TH 17 cells. A higher fraction of TH 1 and TH 17 cells in the MPE of IL-10-/- mice expressed CXCR3 compared with WT mice. We also demonstrated that Lewis lung cancer and colon adenocarcinoma cells secreted large amounts of CXCL10, a ligand of CXCR3, which induced the migration of TH 1 and TH 17 cells into the MPE, and IFN-γ could promote this signaling cascade. Furthermore, intrapleural injection of mice with CXCL10-deficient tumor cells led to decreased TH 1- and TH 17-cell content in MPE, increased MPE volume, and reduced survival of MPE-bearing mice. Taken together, we demonstrated that IL-10 deficiency promoted T-cell differentiation into TH 1 cells and upregulated the CXCR3-CXCL10 signaling pathway that recruits TH 1 and TH 17 cells into MPE, ultimately resulting in decreased MPE formation and longer survival time of mice-bearing MPE.

Pneumocystis pneumonia (PCP) is a common opportunistic infectious disease that is prevalent in immunosuppressed hosts. Accumulating evidence shows that B cells play an important role in infectious diseases. In the present study, the immune regulatory role of mature B cells in host defense to Pneumocystis was evaluated. Pneumocystis infection resulted in a decrease in B cells in patients and mice, and the Pneumocystis burden in B cell-deficient mice also progressively increased from weeks 1 to 7 after infection. The clearance of Pneumocystis was delayed in B cell-activating factor receptor (BAFF-R)-deficient mice (BAFF-R−/−mice), which had few B cells and Pneumocystis-specific IgG and IgM antibodies, compared with clearance in wild-type (WT) mice. There were fewer effector CD4+T cells and higher percentages of T helper (Th)1/Th17 cells in BAFF-R−/−mice than in WT mice. Adoptive transfer of naive B cells, mRNA sequencing, and IL-1β neutralization experiments indicated that IL-1β is a likely determinant of the IL-10-producing B cell-mediated suppression of Th1/Th17-cell immune responses in BAFF-R−/−PCP mice. Our data indicated that B cells play a vital role in the regulation of Th cells in response to Pneumocystis infection.

Inflammatory signaling networks between tumor cells and immune cells contribute to the development of malignant pleural effusion (MPE). B cells have been found in MPE; however, little is known about their roles there. In the present study, by using mouse MPE models, we noted that although the total B cells in MPE were decreased as compared with the corresponding blood and spleen, the percentage of activated naïve B cells expressing higher levels of CD80, CD86, myosin heavy chain-II, CD44, CD69, and programmed cell death-ligand 1 (PD-L1) molecules were increased in wild-type mouse MPE. Compared with wild-type mice, decreased T helper (TH)1 cells and increased TH17 cells were present in B cell-deficient mouse MPE, which paralleled to the reduced MPE volume and longer survival time. Adoptive transfer of activated naïve B cells into B cell-deficient mice was able to increase TH1 cells and decrease TH17 cells in MPE and shorten the survival of mice bearing MPE. Furthermore, we demonstrated that activated naïve B cells inhibited TH17-cell expansion via the PD-1/PD-L1 pathway and promoted naïve CD4+ T-cell differentiation into TH1/TH17 cells through secreting IL-27/IL-6 independent of the PD-1/PD-L1 pathway. Collectively, our data uncovered a mechanism by which naïve B cells promote MPE formation by regulating TH1/TH17 cell responses, making these B cells an attractive target for therapeutic intervention in the fight against cancer.

Yu Kang,1 Zi-Liang Hou,2 Guang-Zhong Yang,3 Xiao-Juan Wang,1 Wen-Ming Chen,3 Huan-Zhong Shi4 1Department of Internal Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Huan-Zhong Shi; Wen-Ming Chen Email shihuanzhong@sina.com; 13910107759@163.comPurpose: Pleural effusion (PE) is prevalent in “real-life” populations of multiple myeloma (MM), a common hematologic malignancy. Development of PE likely has prognostic implications. The aim of this study was to investigate the characteristics and identify risk factors for occurrence of PE in MM.Patients and Methods: We reviewed electronic medical records of 907 patients diagnosed with MM.Results: Incidence of PE in MM patients was 42.7%. Small and bilateral PE in most cases. PE developed in all MM subtypes, the median time from diagnosis of multiple myeloma to pleural effusion was 6.8 months (range 0.8– 33.6 months). Patients with PE showed worse survival than those without PE (unadjusted hazard ratio with 95% confidence interval: 2.249 [1.774– 2.852]). No difference in survival was found between patients with small PE and those with moderate to large PE (unadjusted HR, 1.402; 95% CI, 1.037– 1.896). Plasma cell proportion (OR, 1.373; 95% CI, 1.153– 1.634; P = 0.009) and amyloidosis (OR, 1.791; 95% CI, 1.408– 2.279; P = 0.024) were risk factors for the occurrence of PE at the initial diagnosis of MM. Plasma cell proportion (OR, 1.853; 95% CI, 1.451– 2.368; P = 0.038), pneumonia (OR, 1.309; 95% CI, 1.143– 1.498; P = 0.008) and heart failure (OR, 1.815; 95% CI, 1.387– 2.374; P = 0.031) were risk factors for the occurrence of PE at relapse of MM.Conclusion: The incidence of PE in MM patients is notable and PE can occur in all MM subtypes. PE indicates a poor prognosis, even small amounts of effusion. PE is a problem worthy of attention, especially in patients with high plasma cell proportion, amyloidosis or complicated with pneumonia and heart failure.Keywords: pleural effusion, multiple myeloma, incidence, risk factors, overall survival

We appreciate the thoughtful comments of H-J. Yang and co-workers in their correspondence addressing the predictors of mortality for patients with coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Their comments are very helpful to improve the expression and increase the quality of our paper [1]., Author response to the correspondence regarding “Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study” https://bit.ly/31X8cal

Background: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. Objective: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. Methods: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. Results: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6–16 days), which was significantly longer than that in the control group (8 days [2–12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). Conclusions: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov, NCT04273321.

Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%. Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia. Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020. Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively. Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.

Emerging evidence indicates that Myo9b is a cancer metastasis-related protein and functions in a variety of immune-related diseases. However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing T

Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses.The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS.This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared.The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P .05). The PaoThere were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

Background Accurately diagnosing pleural effusion is a frequent and significant problem in clinical practice. Combining pleural biomarkers with patients’ age may be a valuable method for diagnosing TPE. We sought to evaluate the influence of age on diagnostic values of pleural adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin 27 (IL-27) for tuberculous pleural effusion (TPE). Methods Two hundred seventy-four consecutive adult patients with pleural effusion were selected from Beijing and Wuhan between January 1, 2014 and June 30, 2015, and their pleural fluid concentrations of ADA, IFN-γ, and IL-27 were tested. Biomarker performance was analyzed by standard receiver operating characteristic (ROC) curves according to different ages. Results Data from the Beijing cohort showed that ADA, IFN-γ, and IL-27 could all accurately diagnose TPE in young patients (≤ 40 years of age). With a cutoff of 21.4 U/L, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ADA for diagnosing TPE were 1.000 (95% confidence interval: 0.884–1.000), 100.0, 100.0%, 100.0, and 100.0, respectively. In older patients (> 40 years of age), IL-27 and IFN-γ were excellent biomarkers for discriminating TPE versus non-TPE cases. With a cutoff of 591.4 ng/L, the AUC, sensitivity, specificity, PPV, and NPV of IL-27 for diagnosing TPE were 0.976 (95% confidence interval: 0.932–0.995), 96.3, 99.0%, 96.3, and 99.0, respectively. Similar diagnostic accuracy among the three pleural biomarkers was validated in the Wuhan cohort. Conclusions Among young patients, ADA is reliable for diagnosing TPE. Conversely, in older patients, IL-27 and IFN-γ are excellent biomarkers to differentiate TPE versus non-TPE cases.

IL-10, produced by a wide variety of cells, is a highly pleiotropic cytokine that plays a critical role in the control of immune responses. However, its regulatory activity in tumor immunity remains poorly understood. In this study, we report that IL-10 deficiency robustly suppressed the formation of malignant pleural effusion (MPE) and significantly enhanced miR-7116-5p expression in pleural CD4

Background: The epidemic outbreak of SARS-CoV-2 infective pneumonia still remains a clinical challenge in China A full understanding of the clinical characteri

In the present study, we were prompted to investigate the effect of NO signaling on the formation of malignant pleural effusion (MPE) and determined whether NO affects Th1/Th17 response in MPE. The development of MPE and survival of MPE mice were compared between wild-type and NOS2 ‒/‒ mice. The effect of NOS2 on vascular permeability of pleura and differentiation of Th1 and Th17 in MPE was also explored. Our current data show that production of NO is significantly enhanced in MPE as compared with peripheral circulation, and that nitric oxide synthase-2 (NOS2) deficiency increases pleural vascular permeability and thus promotes the development of MPE, and reduces the survival of mice bearing MPE. NOS2 deficiency inhibits Th1 cell differentiation and promotes Th17 cell differentiation. Our data provide the first evidence that NO inhibits MPE formation by inhibiting fluid extravasation into the pleural space and by promoting Th1 cell differentiation and suppressing Th17 cell differentiation. Overall, our results shed light on the mechanisms by which NO suppresses MPE formation, providing a promising therapeutic strategy in the management of MPE.