SARS-CoV-2 RNAemia as a reliable predictor of long-term mortality among older adults hospitalized in pulmonary intermediate care units: a prospective cohort study.

BACKGROUND: SARS-CoV-2 viremia is associated with disease severity and high risk for in-hospital mortality. However, the impact of SARS-CoV-2 viremia on long-term outcomes in hospitalized patients with COVID-19 is poorly understood. METHODS: We conducted a prospective cohort study and recruited a group of older adult patients with COVID-19 admitted to pulmonary intermediate care units of Peking University Third Hospital during December 2022 and January 2023. The plasma level of SARS-CoV-2 RNA was determined by a standardized RT-PCR technique, and SARS-CoV-2 RNAemia was defined as a plasma viral load ≥ 50 copies/ml. In-hospital and follow-up (180-day) outcome data were collected. RESULTS: A total of 101 patients with an average of 80.4 years were recruited, and 63.4% of them were severe or very severe cases. Twenty-eight patients (27.7%) had SARS-CoV-2 RNAemia, with a median viral RNA load of 422.1 [261.3, 1085.6] copies/ml. Patients with SARS-CoV-2 RNAemia were more likely to develop critical cases and had a higher incidence of sepsis. Accordingly, they had a higher 180-day mortality (57.1% vs. 19.7%, P < 0.001), as well as in-hospital mortality (50.0% vs. 13.7%, P < 0.001), independent of age, disease severity, sepsis, lymphocyte count and C-Reactive protein. In addition, the risk for 180-day mortality increased with the SARS-CoV-2 RNA load in plasma. Plasma cytokines, including IL-6, IL-8 and IL-10, were higher in patients with SARS-CoV-2 RNAemia. CONCLUSIONS: Our study indicates that SARS-CoV-2 RNAemia serves as a useful biomarker for predicting mortality, especially long-term mortality, in older adult patients hospitalized in pulmonary intermediate care units. TRIAL REGISTRATION: Chinese Clinical Trial Registry website (No. ChiCTR2300067434).

Acute miliary tuberculosis in pregnancy after in vitro fertilization and embryo transfer: a report of seven cases.

BACKGROUND: While miliary tuberculosis (TB) in pregnancy is rare after in vitro fertilization and embryo transfer (IVF-ET), it poses a serious threat to the health of pregnant women and their fetuses. The present study aimed to describe the clinical features of miliary TB and pregnancy outcomes of patients after IVF-ET. METHODS: Data of infertile patients who received IVF-ET at Peking University Third Hospital between January 2012 and December 2017 were retrospectively analyzed. Patients who developed miliary TB during pregnancy were identified, and clinical characteristics of miliary TB were described. RESULTS: Out of 62,755 infertile women enrolled, 7137 (11.4 %) showed signs of prior pulmonary TB on chest X-ray (CXR). Among the 15,136 women (mean age: 33.2 ± 5.0 years) who successfully achieved clinical pregnancy, seven patients aged 28-35 years had miliary TB during pregnancy, with two patients having a complication of TB meningitis. All these patients presented with fever. Notably, old TB lesions were detected on CXR in six patients before IVF-ET; nevertheless, no anti-TB therapy was administered. Furthermore, salpingography revealed oviduct obstruction in all patients (7/7). Patients received anti-TB therapy following a diagnosis of miliary TB and were clinically cured. However, pregnancy was terminated due to spontaneous (4/7) and induced (3/7) abortion. CONCLUSIONS: TB reactivation, mostly as miliary TB and TB meningitis, is severe in pregnant women after IVF-ET and deleterious to pregnancy outcomes. Signs of prior TB on CXR may be risk factors for TB reactivation during pregnancy.

Cigarette smoke-induced HMGB1 translocation and release contribute to migration and NF-κB activation through inducing autophagy in lung macrophages.

High-mobility group box 1 (HMGB1) shows pro-inflammatory activity in various inflammatory diseases and has been found up-regulated in chronic obstructive pulmonary disease (COPD). Lung macrophages play an important role in airway inflammation and lung destruction in COPD, yet whether HMGB1 is involved in cigarette smoke (CS)-induced lung macrophage dysfunction is unknown. We sought to evaluate the intracellular localization and release of HMGB1 in lung macrophages from COPD patients and CS-exposed mice, and to investigate the role of HMGB1 in regulating autophagy in CS extract (CSE)-treated lung macrophages (MH-S cells). Our results showed that HMGB1 was highly expressed in lung tissues and sera of COPD patients and CS-exposed mice, along with predominantly cytoplasmic exporting from nuclei in lung macrophages. In vitro experiments revealed that CSE promoted the expression, nucleocytoplasmic translocation and release of HMGB1 partly via the nicotinic acetylcholine receptor (nAChR). Blockade of HMGB1 with chicken anti-HMGB1 polyclonal antibody (anti-HMGB1) or glycyrrhizin (Gly) attenuated the increase of LC3B-II and Beclin1, migration and p65 phosphorylation, suggesting the involvement of HMGB1 in autophagy, migration and NF-κB activation of lung macrophages. Hydroxychloroquine (CQ), an autophagy inhibitor, enhanced the increase of LC3B-II but not Beclin1 in CSE or rHMGB1-treated MH-S cells, and inhibition of autophagy by CQ and 3-methyladenine (3-MA) abrogated the migration and p65 phosphorylation of CSE-treated cells. These results indicate that CS-induced HMGB1 translocation and release contribute to migration and NF-κB activation through inducing autophagy in lung macrophages, providing novel evidence for HMGB1 as a potential target of intervention in COPD.

ADAM15 expression is increased in lung CD8+ T cells, macrophages, and bronchial epithelial cells in patients with COPD and is inversely related to airflow obstruction.

BACKGROUND: A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro. Whether ADAM15 expression is increased in the lungs of COPD patients is not known. METHODS: ADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavage (BAL) macrophage samples obtained from COPD patients, smokers, and non-smokers. Soluble ADAM15 protein levels were measured in BAL fluid (BALF) and plasma samples from COPD patients and controls. Cells expressing ADAM15 in the lungs were identified using immunostaining. Staining for ADAM15 in different cells in the lungs was related to forced expiratory volume in 1 s (FEV1), ratio of FEV1 to forced vital capacity (FEV1/FVC), and pack-years of smoking history. RESULTS: ADAM15 gene expression and/or protein levels were increased in alveolar macrophages and whole lung samples from COPD patients versus smokers and non-smokers. Soluble ADAM15 protein levels were similar in BALF and plasma samples from COPD patients and controls. ADAM15 immunostaining was increased in macrophages, CD8+ T cells, epithelial cells, and airway α-smooth muscle (α-SMA)-positive cells in the lungs of COPD patients. ADAM15 immunostaining in macrophages, CD8+ T cells and bronchial (but not alveolar) epithelial cells was related inversely to FEV1 and FEV1/FVC, but not to pack-years of smoking history. ADAM15 staining levels in airway α-SMA-positive cells was directly related to FEV1/FVC. Over-expressing ADAM15 in THP-1 cells reduced their release of matrix metalloproteinases and CCL2. CONCLUSIONS: These results link increased ADAM15 expression especially in lung leukocytes and bronchial epithelial cells to the pathogenesis of COPD.

A Disintegrin and Metalloproteinase Domain-8: A Novel Protective Proteinase in Chronic Obstructive Pulmonary Disease.

RATIONALE: ADAM8 (a disintegrin and metalloproteinase domain-8) is expressed by leukocytes and epithelial cells in health, but its contribution to the pathogenesis of chronic obstructive pulmonary disease (COPD) is unknown. OBJECTIVES: To determine whether the expression of ADAM8 is increased in the lungs of patients with COPD and cigarette smoke (CS)-exposed mice, and whether ADAM8 promotes the development of COPD. METHODS: ADAM8 levels were measured in lung, sputum, plasma, and/or BAL fluid samples from patients with COPD, smokers, and nonsmokers, and wild-type (WT) mice exposed to CS versus air. COPD-like lung pathologies were compared in CS-exposed WT versus Adam8-/- mice. MEASUREMENTS AND MAIN RESULTS: ADAM8 immunostaining was reduced in macrophages, and alveolar and bronchial epithelial cells in the lungs of patients with COPD versus control subjects, and CS- versus air-exposed WT mice. ADAM8 levels were similar in plasma, sputum, and BAL fluid samples from patients with COPD and control subjects. CS-exposed Adam8-/- mice had greater airspace enlargement and airway mucus cell metaplasia than WT mice, but similar small airway fibrosis. CS-exposed Adam8-/- mice had higher lung macrophage counts, oxidative stress levels, and alveolar septal cell death rates, but lower alveolar septal cell proliferation rates and soluble epidermal growth factor receptor BAL fluid levels than WT mice. Adam8 deficiency increased lung inflammation by reducing CS-induced activation of the intrinsic apoptosis pathway in macrophages. Human ADAM8 proteolytically shed the epidermal growth factor receptor from bronchial epithelial cells to reduce mucin expression in vitro. Adam8 bone marrow chimera studies revealed that Adam8 deficiency in leukocytes and lung parenchymal cells contributed to the exaggerated COPD-like disease in Adam8-/- mice. CONCLUSIONS: Adam8 deficiency increases CS-induced lung inflammation, emphysema, and airway mucus cell metaplasia. Strategies that increase or prolong ADAM8's expression in the lung may have therapeutic efficacy in COPD.

[Population pharmacokinetics of ciprofloxacin in Chinese elderly patients with lower respiratory tract infection].

OBJECTIVE: To analyse population pharmacokinetic (PPK) parameter values of ciprofloxacin in Chinese elderly patients with lower respiratory tract infection. METHODS: Hospitalized in Respiratory Intensive Care Unit (RICU) due to severe lower respiratory tract infection and at high risks of Pseudomonas aeruginosa. 43 consecutive elderly patients received an intravenous infusion of ciprofloxacin at a dose of 200/400 mg every 12/24 h empirically. Plasma samples were drawn from Day 4 and at 1, 2, 3, 4, 6, 8 and 12 h after infusion. The serum concentrations of ciprofloxacin were determined by high-performance liquid chromatography (HPLC). Ciprofloxacin population pharmacokinetic analysis was conducted by the NONMEM 7.3.0 software. RESULTS: Forty patients aged (78 ± 9) years completed the study. A total of 210 serum concentrations were detected. The mean values of clearance and volume of distribution (V1) were 17.8 L/h and 49.8 L respectively. The serum creatinine level influenced ciprofloxacin according to the equation: Clearance - 17.8 × [1 - 0.001 3 × (serum creatinine - 67)] × e(η1i) × 0.659(n) (at a dose of 200 mg, n - 1, at a dose of 400 mg, n - 0; ηi for inter individual random variation). The values of clearance and V1 were multiplied by 0.659 at a dose of 200 mg. At the doses of 200 and 400 mg, the maximum steady-state concentrations (C(max)) were (4.2 ± 1.1) and (5.3 ± 1.21) mg/L, the minimum steady-state concentrations (C(min)) (1.1 ± 1.1) and (0.8 ± 0.4) mg/L and the area under concentration-time curve measured in steady-state up to 24 h after dosing (AUC(0-24 h)) were (45.5 ± 28.1) and (47.2 ± 11.3) mg · h · L⁻¹ respectively. CONCLUSIONS: The clearance of ciprofloxacin in elderly patients significantly decreases as compared with adult patients. Ciprofloxacin PPK model shows a significant influence of serum creatinine level on ciprofloxacin clearance. A single dose of 400 mg may increase serum drug concentration, but causes no in vivo drug retention.

Tuberculosis in infertility and in vitro fertilization-embryo transfer.

ABSTRACT: Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

Comparative analysis of lysophospholipid metabolism profiles and clinical characteristics in patients with high vs. low C-reactive protein levels in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: The precise role of lysophospholipids (LysoPLs) in the pathogenesis of acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) remains unclear. In this study, we sought to elucidate the differences in serum LysoPL metabolite profiles and their correlation with clinical features between patients with low versus high CRP levels. METHODS: A total of 58 patients with AECOPD were enrolled in the study. Patients were classified into two groups: low CRP group (CRP < 20 mg/L, n = 34) and high CRP group (CRP ≥ 20 mg/L, n = 24). Clinical data were collected, and the LysoPL metabolite profiles were analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS) and identified by matching with the LipidBlast library. RESULTS: Nineteen differential LysoPLs were initially identified through Student's t-test (p < 0.05 and VIP > 1). Subsequently, four LysoPLs, LPC(16:0), LPE(18:2), LPC(22:0), and LPC(24:0), were identified by FDR adjustment (adjusted p < 0.05). These four lysoPLs had a significant negative correlation with CRP. Integrative analysis revealed that LPC (16:0) and LPC (22:0) correlated with less hypercapnic respiratory failure and ICU admission. CONCLUSION: AECOPD patients with high CRP levels demonstrated a distinctive LysoPL metabolism profile, with LPC (16:0), LPE(18:2), LPC(22:0), and LPC(24:0) being the most significantly altered lipid molecules. These alterations were associated with poorer clinical outcomes.

Efficacy of Combination of Antiviral Therapy With Neutralizing Monoclonal Antibodies for Recurrent Persistent SARS-CoV-2 Pneumonia in Patients With Lymphoma.

Despite the potential of neutralizing antibodies in the management of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), clinical research on its efficacy in Chinese patients remains limited. This study is aimed at investigating the therapeutic effect of combination of antiviral therapy with neutralizing monoclonal antibodies for recurrent persistent SARS-CoV-2 pneumonia in patients with lymphoma complicated by B cell depletion. A prospective study was conducted on Chinese patients who were treated with antiviral nirmatrelvir/ritonavir therapy and the neutralizing antibody tixagevimab-cilgavimab (tix-cil). The primary outcome was the rate of recurrent SARS-CoV-2 infection. Five patients with lymphoma experienced recurrent SARS-CoV-2 pneumonia and received tix-cil treatment. All patients had a history of CD20 monoclonal antibody use within the year preceding SARS-CoV-2 infection, and two patients also had a history of Bruton's tyrosine kinase (BTK) inhibitor use. These patients had notably low lymphocyte counts and exhibited near depletion of B cells. All five patients tested negative for serum SARS-CoV-2 IgG and IgM antibodies. None of the patients developed reinfection with SARS-CoV-2 pneumonia after antiviral and tix-cil treatment during the 6-month follow-up period. In conclusion, the administration of antiviral and SARS-CoV-2-neutralizing antibodies showed encouraging therapeutic efficacy against SARS-CoV-2 pneumonia in patients with lymphoma complicated by B cell depletion, along with the potential preventive effect of neutralizing antibodies for up to 6 months.

A robust web-based tool to predict viral shedding in patients with Omicron SARS-CoV-2 variants.

Background: Data on viral kinetics and variants affecting the duration of viral shedding were limited. Our objective was to determine viral shedding in distinct severe acute respiratory syndrome coronavirus 2 variants, including Omicron BA.4/5 and BF.7, and to identify the relevant influencing factors. Methods: We carried out a longitudinal cohort study at Beijing Xiaotangshan Fangcang shelter hospital from May to June 2022 (Omicron BA.4/5) and from November to December 2022 (Omicron BF.7). Nucleocapsid protein (N) and open reading frame (ORF) genes were considered as the target genes of the reverse transcription PCR. The daily results of cycle threshold (CT), including lowest ORF1ab-CT values for days 1-3 post-hospitalisation and lowest N-CT values for days 1-3 post-hospitalisation (CT3minN) and demographic and clinical characteristics were collected. Results: 1433 patients with coronavirus disease 2019 (COVID-19) were recruited from the Fangcang shelter hospital, in which 278 patients were diagnosed with Omicron BA.4/5 and 1155 patients with Omicron BF.7. Patients with BF.7 infection showed a longer duration of viral shedding. The duration of viral shedding was associated with the variants age, alcohol use, the severity of COVID-19 and CT3minN. Moreover, the nomogram had excellent accuracy in predicting viral shedding. Conclusions: Our results indicated that patients with Omicron BF.7 had a longer period of contagiousness than those with BA.4/5. The duration of viral shedding was affected by a variety of factors and the nomogram may become an applicable clinical instrument to predict viral shedding. Furthermore, we developed a new COVID-19 viral shedding predicting model that can accurately predict the duration of viral shedding for COVID-19, and created a user-friendly website to apply this prediction model (https://puh3.shinyapps.io/CVSP_Model/).

The Clinical Characteristics, Treatment and Prognosis of Tuberculosis-Associated Chronic Obstructive Pulmonary Disease: A Protocol for a Multicenter Prospective Cohort Study in China.

Background: Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation. Methods: This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred. Discussion: The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.

Elevated CD4+ T Cell Senescence Associates with Impaired Immune Responsiveness in Severe COVID-19.

Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may impact vaccine efficacy. However, whether the senescence of T cells is associated with severe COVID-19 outcome in elderly individuals is unclear. Using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in peripheral blood from 100 hospitalized elderly COVID-19 patients and compared differences between those with mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit, and ELISPOT assay respectively, the cytokine production profile of COVID-19 reactive T cells, and plasma soluble factors by cytometric bead array (CBA). Our study found a significantly elevated level of CD4+ Tsens in patients with severe/critical disease compared to those with mild/moderate illness. Patients with a higher level of CD4+ Tsens (>19.78%) showed a decreased survival rate compared to those with a lower level (≤19.78%). This is more pronounced among patients with breakthrough infections. The percentage of CD4+ Tsens was negatively correlated with spike-specific antibody titers, neutralization ability, and COVID-19 reactive IL-2+CD4+ T cells. In addition, spike-specific antibody levels were positively correlated with IL-2 producing T cells and plasma IL-2 amount. Mechanistically, with defective CD40L, T cells from patients with CD4+ Tsens >19.78% were unable to support B cell proliferation and differentiation. Our data demonstrate that the percentage of CD4+ Tsens in peripheral blood may serve as a reliable biomarker for the prognosis of severe COVID-19 patients, especially in breakthrough infections. Therefore, restoring the immune response of CD4+ Tsens may be key to preventing severe illness and improving vaccine efficacy in older adults.

Impact of Lianhua Qingwen on viral shedding in omicron mild/asymtomatic patients: a real-world study.

Background: Lianhuaqingwen (LHQW), a traditional Chinese medicine comprised of 13 herbal extracts renowned for their robust heat-clearing and detoxifying properties, has gained widespread utilization in China but has yet to garner similar recognition abroad. It is believed to exhibit efficacy in ameliorating symptoms in individuals afflicted with coronavirus disease 2019 (COVID-19). However, the precise impact of LHQW on viral shedding (VS), particularly in the context of mild or asymptomatic infections caused by the Omicron BF.4/5 or BF.7 variants of COVID-19, remained inadequately elucidated. Consequently, a real-world study was conducted, involving patients diagnosed with COVID-19, with the primary objective of ascertaining the effectiveness of LHQW in this specific clinical context. Methods: We conducted an investigation on Omicron-infected patients through a single-center, propensity score-matched real-world study conducted at Xiaotangshan Fangcang Hospital from May to November 2022. A total of 3,368 COVID-19 patients were enrolled in the study, all of whom presented mild or asymptomatic infections caused by either BF.4/5 or BF.7 strains of the virus. Demographic and clinical data were systematically collected from medical records. Patients were allocated to receive treatment with LHQW (designated as the treatment group) or received no LHQW treatment (designated as the not-treated/no-treatment group). Viral load was quantified utilizing quantitative real-time PCR (qPCR), and the duration of VS was defined as the time interval between the initial negative test result and the date of COVID-19 diagnosis or symptom onset. Results: The study encompassed a cohort of 3,368 patients, and following propensity score matching, a subset of 296 patients was meticulously chosen for subsequent analysis. Notably, baseline characteristics exhibited disparities between the treatment and not-treated/no-treatment groups. However, post-matching, these characteristics achieved a commendable level of comparability. Our findings unequivocally demonstrated that there existed no statistically significant disparity in VS. This holds true when comparing patients subjected to LHQW treatment against those not administered LHQW, as well as when contrasting individuals presenting asymptomatic and mild COVID-19 manifestations. Conclusion: No statistically significant difference in VS was observed between patients who underwent LHQW treatment and those who did not. Additional investigations are imperative to provide a comprehensive assessment of LHQW's efficacy, particularly in patients afflicted with severe COVID-19 or those infected with viral strains distinct from BF.4/5 or BF.7.

Post-tuberculosis lung disease and chronic obstructive pulmonary disease.

ABSTRACT: The burden of chronic airway diseases, including chronic obstructive pulmonary disease (COPD), continues to increase, especially in low- and middle-income countries. Post-tuberculosis lung disease (PTLD) is characterized by chronic lung changes after the "cure" of pulmonary tuberculosis (TB), which may be associated with the pathogenesis of COPD. However, data on its prevalence, clinical manifestations, computed tomography features, patterns of lung function impairment, and influencing factors are limited. The pathogenic mechanisms underlying PTLD remain to be elucidated. This review summarizes the recent advances in PTLD and TB-associated COPD. Research is urgently needed both for the prevention and management of PTLD.

Rare case of pulmonary fat embolism and acute respiratory distress syndrome after liposuction and fat grafting: a case report.

Background: Pulmonary fat embolism usually occurs after fracture, yet rarely observed after liposuction and fat grafting. Case presentation: We describe a 19-year-old female patient who presented with acute respiratory failure and diffuse pulmonary opacities on chest radiographic image shortly after liposuction and fat grafting. Bronchoalveolar lavage was performed and lipid content in alveolar cells contribute to the diagnosis of the fat embolism syndrome. The patient was successfully treated with noninvasive mechanical ventilation and a short course of glucocorticoids. Conclusions: Early recognition and appropriate treatment are very important to improve the outcome of pulmonary fat embolism. Considering that liposuction and fat grafting are increasingly common cosmetic surgeries, our aim is to raise awareness for this rare adverse event.

Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study.

INTRODUCTION: Post-tuberculosis lung damage (PTLD) refers to the residual pulmonary impairment following the completion of antituberculosis (TB) therapy, characterised by persistent respiratory symptoms and abnormal pulmonary function. The risk factors and biomarkers for PTLD have been scarcely investigated. More importantly, whether and to what extent cigarette smoking is involved in PTLD remain to be known. METHODS AND ANALYSIS: This prospective observational study will enrol 400 male smoking or non-smoking patients aged 25-65 years, with newly confirmed active TB between 2022 and 2024, from the Department of Respiratory and Critical Care Medicine at Peking University Third Hospital and the Tuberculosis Department at Beijing Geriatric Hospital. Because females rarely smoke in China, we will enrol only males in this study. Demographic data, smoking history and amount, clinical symptoms, lung function, and chest CT findings will be prospectively collected. Respiratory questionnaires, lung function measurements and chest CT examinations will be performed immediately after, and 1 year, 2 years and 3 years after the completion of TB treatment. Peripheral blood samples will be obtained at baseline and at the end of anti-TB therapy, and a Luminex xMAP-based multiplex immunoassay will be used to measure inflammatory mediators and cytokines in serum. The collected data will be analysed to determine the incidence and factors/biomarkers of PTLD according to smoking status. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Peking University Third Hospital (approval number: (2022)271-03; approval date: 8 June 2022). The research results will be disseminated through scientific and medical conferences and will be published in an academic journal. TRIAL REGISTRATION NUMBER: NCT04966052.

More severe lung lesions in smoker patients with active pulmonary tuberculosis were associated with peripheral NK cell subsets.

BACKGROUND: Both pulmonary tuberculosis (PTB) and cigarette smoke (CS) exposure may lead to lung damage. The potential impact of CS exposure on tuberculosis-associated lung damage and the disturbance of immune cells and mediators involved, need to be further elucidated. METHODS: We firstly evaluated the chest X-ray (CXR) scores of a retrospective cohort of male patients with active PTB, followed for 6 months, and compared the scores between smoker (≥10 pack-years) and non-smoker patients. In a cross-sectional study, we measured the peripheral blood NK cell subsets and plasma inflammatory cytokines in male smoker and non-smoker patients with active PTB before anti-tuberculosis therapy, and the proportions of NK cell subsets and the levels of cytokines were analyzed for correlation with the CXR scores. RESULTS: In the retrospective cohort, male smoker patients with active PTB showed a higher CXR score, characterized by more cavitary lesions, enlarged lymph nodes and emphysema, as compared to non-smokers. The cross-sectional study revealed that the CXR score in smoker patients was correlated inversely with the percentages of blood CD107a+, NKP46+, and TIGIT+ NK cells. CONCLUSION: In patients with active PTB, CS exposure was associated with more severe lung lesions, which were correlated with peripheral NK cell subsets.

Differences in the lipid metabolism profile and clinical characteristics between eosinophilic and non-eosinophilic acute exacerbation of chronic obstructive pulmonary disease.

Objective: In this study, we aimed to investigate the differences in serum lipid metabolite profiles and their relationship with clinical characteristics between patients with eosinophilic and non-eosinophilic AECOPD. Methods: A total of 71 AECOPD patients were enrolled. Eosinophilic AECOPD was defined as blood EOS% ≥ 2% (n = 23), while non-eosinophilic AECOPD, as blood EOS< 2% (n = 48). Clinical data were collected, and serum lipid metabolism profiles were detected by liquid chromatography-mass spectrometry (LC-MS). The XCMS software package was used to pre-process the raw data, and then, lipid metabolite identification was achieved through a spectral match using LipidBlast library. Differences in lipid profiles and clinical features between eosinophilic and non-eosinophilic groups were analyzed by generalized linear regression. The least absolute shrinkage and selection operator (LASSO) was applied to screen the most characteristic lipid markers for the eosinophilic phenotype. Results: Eosinophilic AECOPD patients had less hypercapnic respiratory failures, less ICU admissions, a shorter length of stay in the hospital, and a lower fibrinogen level. In the lipid metabolism profiles, 32 significantly different lipid metabolites were screened through a t-test adjusted by using FDR (FDR-adjusted p < 0.05 and VIP> 1). Nine differential lipid metabolites were found to be associated with the three clinical features, namely, hypercapnia respiratory failure, ICU admission, and fibrinogen in further integration analysis. The species of triacylglycerol (TAG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and diacylglyceryl trimethylhomoserine (DGTS) were high in these eosinophilic AECOPD. The LASSO was applied, and three lipid metabolites were retained, namely, LPC (16:0), TAG (17:0/17:2/17:2), and LPC (20:2). The logistic regression model was fitted using these three markers, and the area under the ROC curve of the model was 0.834 (95% CI: 0.740-0.929). Conclusion: Patients with eosinophilic AECOPD had a unique lipid metabolism status. Species of TAGs and LPCs were significantly increased in this phenotype and were associated with better clinical outcomes.

[Expression and significance of programmed cell death 5 in patients of branchial asthma].

OBJECTIVE: To explore the expression and significance of serum programmed cell death 5 (PDCD5) in patients with bronchial asthma. METHODS: From June to December 2011, a total of 40 adults with bronchial asthma treated in Peking University Third Hospital were enrolled. Among them, the categories were acute phase (n = 12), chronic phase (n = 14) and remission phase (n = 14). Fifteen healthy adults were selected into the control group. The percentages of peripheral blood neutrophils and eosinophils were collected and detected for each patient. Serum PDCD5 was detected with enzyme-linked immunosorbent assay (ELISA) and asthma control test (ACT) questionnaire filled in. The relevant pulmonary functional indicators were analyzed with a pulmonary spirometer. Two-independent sample t-test and Pearson's correlation analysis were used for statistical analysis. RESULTS: No significant difference was found between two groups with regards to the percentages of peripheral blood eosinophils and neutrophils (all P > 0.05). Serum PDCD5 was significantly higher in the patient group ((47.7 ± 29.6) vs (19.3 ± 9.8) µg/L, P < 0.05). Patients of chronic and acute phases showed a significant higher expression in PDCD5 than the remission phase ((55.2 ± 24.5) & (68.5 ± 22.1) vs (16.0 ± 7.9) µg/L, both P < 0.05). Serum PDCD5 of asthmatics showed a negative correlation with FEV(1)%, FEV(1)/FVC ratio and ACT scores (r = -0.539 to -0.798, all P < 0.05). CONCLUSIONS: PDCD5 participates in the inflammatory process of asthmatic airway. Its abnormal expression may be associated with the uncontrolled state of asthmatics. It may serve as an indicator of assessing the levels of asthma control or a target for the treatment of asthma.

Missense mutation of SERPINC1 (p.Ser426Leu) in a young patient presenting as refractory and recurrent venous thromboembolism: A case report.

Genetic and acquired risk factors are extremely important mechanisms in the development of venous thromboembolism (VTE). Inherited antithrombin (AT) deficiency due to mutations in the SERPINC1 gene is a well-known risk factor for genetic thrombophilia. In this case, we reported a 28-year young abroad student who presented with refractory and recurrent VTE in-hospital. This patient presented with a 2-month history of right lower limb pain and 1 week of fever. The ultrasound showed deep venous thrombosis in the right common and superficial femoral veins. The CTPA confirmed acute pulmonary embolism with multiple filling defects in both pulmonary arteries. He was diagnosed with "pulmonary embolism, pneumonia, lower extremity venous thrombosis". The level of serum antithrombin was normal, yet gene sequencing revealed a heterozygous missense mutation of SERPINC1, c.1277C>T (p.Ser426Leu). The patient underwent anticoagulant therapy of heparin and inferior vena cava filter implantation. The patient had undergone recurrent VTE despite adequate anticoagulation with heparin during the first 2 weeks. The swelling, pain, and thrombosis of lower extremity veins got resolved from warfarin and rivaroxaban. Inherited antithrombin deficiency due to mutations in the SERPINC1 gene is the genetic basis of this patient, and warfarin/rivaroxaban, other than heparin, is beneficial.