A score for predicting invasive pulmonary aspergillosis in immunocompetent critically ill patients.

BACKGROUND: Delayed treatment leads to increased mortality in critically ill patients with invasive pulmonary aspergillosis (IPA). We aimed to develop and validate a prediction score based on novel biomarkers and clinical risk factors to identify IPA in immunocompetent patients in the intensive care unit (ICU). METHODS: A retrospective study was conducted to collect medical information and novel biomarkers upon ICU admission. Risk factors adopted for the final prediction score were identified using multivariate logistic regression analysis. RESULTS: We retrospectively collected 1841 critical ill patients between January 2018 and August 2022. Patients with IPA had higher C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio, systemic immune-inflammation index and lower prognostic nutritional index (PNI). Chronic obstructive pulmonary disease (COPD), continuous renal replacement therapy (CRRT), high dose of corticosteroids, broad-spectrum antibiotics, blood galactomannan (GM) positivity and high CAR were independent risk factors for IPA and were entered into the final prediction score. The score had good discrimination, with the area under receiver operating characteristic curve of 0.816 and 0.780 for the training and validation cohorts, respectively, and good calibration. CONCLUSION: A score based on six clinical and novel immunological biomarkers showed promising predictive value for antifungal treatment in immunocompetent ICU patients.

A prediction model for acute respiratory distress syndrome in immunocompetent adults with adenovirus-associated Pneumonia: a multicenter retrospective analysis.

BACKGROUND: In recent years, the number of human adenovirus (HAdV)-related pneumonia cases has increased in immunocompetent adults. Acute respiratory distress syndrome (ARDS) in these patients is the predominant cause of HADV-associated fatality rates. This study aimed to identify early risk factors to predict early HAdV-related ARDS. METHODS: Data from immunocompetent adults with HAdV pneumonia between June 2018 and May 2022 in ten tertiary general hospitals in central China was analyzed retrospectively. Patients were categorized into the ARDS group based on the Berlin definition. The prediction model of HAdV-related ARDS was developed using multivariate stepwise logistic regression and visualized using a nomogram. RESULTS: Of 102 patients with adenovirus pneumonia, 41 (40.2%) developed ARDS. Overall, most patients were male (94.1%), the median age was 38.0 years. Multivariate logistic regression showed that dyspnea, SOFA (Sequential Organ Failure Assessment) score, lactate dehydrogenase (LDH) and mechanical ventilation status were independent risk factors for this development, which has a high mortality rate (41.5%). Incorporating these factors, we established a nomogram with good concordance statistics of 0.904 (95% CI 0.844-0.963) which may help to predict early HAdV-related ARDS. CONCLUSION: A nomogram with good accuracy in the early prediction of ARDS in patients with HAdV-associated pneumonia may could contribute to the early management and effective treatment of severe HAdV infection.

High-flow nasal cannula versus conventional oxygen therapy in acute COPD exacerbation with mild hypercapnia: a multicenter randomized controlled trial.

BACKGROUND: High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain. METHODS: This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90. RESULTS: Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0-13.0] vs. 8.0 [interquartile range, 7.0-11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613-$3782] vs. $2005 [interquartile range, $1439-$2968]). There were no significant differences in other secondary outcomes between groups. CONCLUSIONS: In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups. TRIAL REGISTRATION: NCT03003559 . Registered on December 28, 2016.

Clinical characteristics of severe coronavirus disease 2019 patients with chronic obstructive pulmonary disease. / é‡åž‹æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žåˆå¹¶æ ¢æ€§é˜»å¡žæ€§è‚ºç–¾ç— æ‚£è€ ä¸´åºŠç‰¹å¾.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) in elderly and patients with chronic respiratory diseases (COPD) had a poor prognosis. COPD is one of the most common chronic respiratory diseases. We explore the epidemiological characteristics of patients with severe COVID-19 with COPD patients in order to provide medical evidence for the prevention and treatment of severe COVID-19. METHODS: We retrospectively analyzed the clinical baseline characteristics, treatment strategies, disease progression and prognosis of 557 severe COVID-19 patients admitted to the West Court of Union Hospital of Huazhong University of Science and Technology from January 29, 2020 to April 8, 2020. RESULTS: A total of 465 patients with severe COVID-19 were enrolled in the study, including 248 (53.3%) males and 217 (46.7%) females. The median age of severe COVID-19 patients was 62.0 years, and 53 patients were complicated with COPD. Common symptoms at the onset included fever (78.5%), dry cough (67.1%), shortness of breath (47.3%) and fatigue (40.9%). Compared with non-COPD patients, patients with COPD had significantly lower levels of SpO2 in admission (90.0% vs 92.0%, P=0.014). In terms of laboratory examinations, patients with COPD had higher levels of C-reactive protein, interleukin-6, procalcitonin, total bilirubin, blood urea nitrogen, serum creatinine, lipoprotein (a), high-sensitivity troponin I, and D-dimer, while had lower levels of platelet counts, albumin and apolipoprotein AI. Severe COVID-19 patients with COPD had higher Sequential Organ Failure Assessment scores [3.0(2.0, 3.0) vs 2.0(2.0, 3.0), P=0.038] and CURB-65 score [1.0(1.0, 2.0) vs1.0(0.0, 1.0), P<0.001], and a higher proportion of progressing to critical illness (28.3% vs 10.0%, P<0.001) with more complications [e.g. septic shock (15.1% vs 6.1%, P=0.034)], had higher incidence rates of antibiotic therapies (90.6% vs 77.2%, P=0.025), non-invasive (11.3% vs 1.7%, P<0.001) and invasive mechanical ventilation (17.0% vs 8.3%, P=0.039), ICU admission (17.0% vs 7.5%, P=0.021) and death (15.1% vs 6.1%, P=0.016). Cox proportion hazard model was carried out, and the results showed that comorbid COPD was an independent risk factor for severe COVID-19 patients progressing to critical type, after adjusting for age and gender [adjusted hazard ratio (AHR)=2.38(1.30-4.37), P=0.005] and additionally adjusting for chronic kidney diseases, hypertension, coronary heart disease [AHR=2.63(1.45-4.77), P<0.001], or additionally adjusting for some statistically significant laboratory findings [AHR=2.10(1.13-3.89), P=0.018]. CONCLUSIONS: Severe COVID-19 patients with COPD have higher levels of disease severity, proportion of progression to critical illness and mortality rate. Individualized treatment strategies should be adopted to improve the prognosis of severe COVID-19 patients.

[Fractional exhaled nitric oxide in bronchial inflammatory lung diseases].

OBJECTIVE: To explore the change of fractional exhaled nitric oxide (FeNO) and its correlation with forced expiratory volume in the first second (FEV1), the first second forced expiratory volume percentage of forced vital capacity (FEV1/FVC) in bronchial asthma and chronic obstructive pulmonary disease (COPD). METHODS: FeNO, FEV1 and FEV1/FVC were measured in 57 suspected asthmatics (21 acute onsets, 12 non-acute and 24 non-asthma), 38 COPD patients (25 acute exacerbations and 13 stable stages) and 26 healthy subjects. RESULTS: In the 57 suspected asthmatic patients, when the optimal cut off value of FeNO was 20.15 PPb, which was used to diagnose asthma and differentiate asthma and non-asthma, the positive predictive value, the negative predictive value, the sensitivity and the specificity was 94.1%, 95.7%, 97.0%, and 91.7% respectively. There was significant difference in the FeNO level between the 33 asthmatics and 26 healthy subjects (P<0.05). There was also significant difference in the FeNO level between the acute onset and the non-acute (P<0.05), but not in the FEV1 and FEV1/FVC level (both P>0.05). There was no significant correlation between FeNO and FEV1, FEV1/FVC in patients with asthma (r=-0.186, -0.236, both P>0.05). There was significant difference in the levels of FeNO, FEV1 and FEV1/FVC between the 38 COPD patients and the 26 healthy subjects (all P<0.05), and also between the 25 acute exacerbations and 13 stable COPDs (all P<0.05), but not between the 13 stable COPDs and 26 healthy subjects (all P>0.05). FeNO was not correlated with FEV1 and FEV1/FVC level in COPD patients (r=-0.167, -0.285, both P>0.05). CONCLUSION: FeNO level is increased obviously in patients with asthma. The optimal cut off value of FeNO at 20.15 PPb can differentiate asthma and non-asthma with high sensitivity and specificity. FeNO is higher for the acute onset than non-acute, which may be useful to evaluate the control degree. FeNO level is increased in COPD patients in the acute exacerbations, but there is no change in stable COPD patients compared with the healthy subjects.

Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testing: a retrospective study.

BACKGROUND: The recommended delivery mode for bronchodilators in bronchodilator responsiveness (BDR) testing remains controversial. OBJECTIVE: To compare the efficacy of salbutamol administration using a nebulizer versus a metered-dose inhaler (MDI) with spacer in BDR testing. DESIGN: A retrospective study. METHODS: This study examined the data of patients with chronic obstructive pulmonary disease who completed BDR testing between 1 December 2021 and 30 June 2022, at Xiangya Hospital, Central South University. After administering 400 µg of salbutamol through an MDI with spacer or 2.5 mg using a nebulizer, the changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were analyzed in patients with moderate-to-very severe spirometric abnormalities [pre-bronchodilator FEV1 percentage predicted values (FEV1%pred) ⩽59%]. Significant responsiveness was assessed as >12% and >200 mL improvement in FEV1 and/or FVC or >10% increase in FEV1%pred or FVC percentage predicted values (FVC%pred) from pre- to post-bronchodilator administration. RESULTS: Of the enrolled 894 patients, 83.2% were male (median age, 63 years). After propensity score matching, 240 pairs of patients were selected. The increment in FEV1 and increased FEV1 relative to the predicted value (ΔFEV1%pred) were significantly higher in patients <65 years and those with severe spirometric abnormalities in the nebulization group than patients in the MDI group (all p < 0.05). Compared with MDI with spacer, patients who used nebulization had a 30 mL greater increase in ΔFEV1 (95% CI: 0.01-0.05, p = 0.004) and a 1.09% greater increase in ΔFEV1%pred (95% CI: 0.303-1.896, p = 0.007) from baseline. According to the > 12% and >200 mL increase criterion, the significant BDR rate with nebulization was 1.67 times higher than that with an MDI with spacer (OR = 1.67, 95% CI: 1.13-2.47, p = 0.009). CONCLUSION: Salbutamol delivered using a nebulizer may be preferable to an MDI with spacer in certain circumstances. Nebulization has the potential to increase responsiveness to salbutamol in BDR testing.

Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testingBronchodilator responsiveness testing is commonly undertaken as an important part of spirometry testing to determine the degree of volume and airflow improvement after bronchodilator administration. BDR testing results may affect patients' diagnosis and treatment. This study compared the effects of two delivery models (a metered dose inhaler (MDI) with spacer and nebulization) on responsiveness to bronchodilators and the results of bronchodilator responsiveness testing among patients with chronic obstructive pulmonary disease. We found that the increment in forced expiratory volume in one second were significantly higher in patients aged <65 years and in those with severe spirometric abnormalities in the nebulization group than in those in the MDI group. The study provides evidence that salbutamol delivered by a nebulizer is preferable to an MDI with spacer in patients <65 years and in those with severe spirometric abnormalities and could increase positive responsiveness to bronchodilators. The study will assist in clinical decision-making by selecting the appropriate dosing regimen for different patients.

Serum Krebs von den Lungen-6 is associated with in-Hospital mortality of patients with severe Community-Acquired Pneumonia: A retrospective cohort study.

BACKGROUND: Currently, no ideal biomarker can accurately stratify the risk of patients with severe community-acquired pneumonia (SCAP). This study aimed to evaluate the role of serum Krebs von den Lungen-6 (sKL-6) in predicting in-hospital mortality in adults with SCAP. METHODS: In this retrospective cohort study, 249 severe pneumonia adult patients were recruited between 6 May 2021 to 30 April 2023 in Xiangya Hospital of Central South University. The sKL-6 level within 48 h of admission was measured, and the primary outcome assessed was in-hospital mortality. Multivariable logistic regression analysis was performed to calculate adjusted odds ratios (OR) with 95% confidence intervals (CI). Survival curves were plotted and subgroup analyses were conducted, stratified by relevant covariates. RESULTS: A total of 249 patients were included in the study,with 124 patients having normal sKL-6 levels, and 125 patients having abnormal sKL-6 levels. The overall in-hospital mortality rate was 28.9% (72 out of 249 patients). Univariate and multivariate logistic regression analysis revealed that the patients with abnormal sKL-6 levels had a higher risk of in-hospital mortality compared to those with normal sKL-6 levels, both in the total SCAP patient population (OR: 5.38, 95%CI: 2.41-12.01, P < 0.001) and the non-COVID-19 SCAP patients subgroup (OR: 8.12, 95%CI: 3.16-20.84, P < 0.001). Subgroup and interaction analyses confirmed the stability of the relationship between sKL-6 levels and in-hospital mortality(P for interaction > 0.05). Kaplan-Meier survival curves showed that patients with abnormal sKL-6 levels had a higher in-hospital mortality rate than those with normal sKL-6 levels (P < 0.05). However, the results of restricted cubic spline plots(RCS) analysis demonstrated a nonlinear association between sKL-6 levels (as a continuous variable) and in-hospital mortality in patients with SCAP. Similar results were observed in non-COVID-19 SCAP patients. Furthermore, the receiver operating characteristic curve (ROC) analysis revealed that sKL-6 had superior predictive performance compared to existing biomarkers (e.g., APACHE-II, SOFA, BUN/Cr, PCT, and D-dimer) for in-hospital mortality in non-COVID-19 SCAP patients. CONCLUSION: sKL-6 is a practical and useful biomarker for predicting in-hospital mortality in patients with SCAP.

KL-6 levels in the connective tissue disease population: typical values and potential confounders-a retrospective, real-world study.

Background: Krebs von den Lungen 6 (KL-6) is a potential biomarker for determining the severity of interstitial lung disease (ILD) in patients with connective tissue disease (CTD). Whether KL-6 levels can be affected by potential confounders such as underlying CTD patterns, patient-associated demographics, and comorbidities needs further investigation. Methods: From the database created by Xiangya Hospital, 524 patients with CTD, with or without ILD, were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers, autoimmune antibodies, and the KL-6 level at admission. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. The percent of predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and computed tomography (CT) scans were used to determine the severity of ILD. Results: Univariate linear regression analysis showed that BMI, lung cancer, TB, lung infections, underlying CTD type, white blood cell (WBC) counts, neutrophil (Neu) counts, and hemoglobin (Hb) were related to KL-6 levels. Multiple linear regression confirmed that Hb and lung infections could affect KL-6 levels independently; the ß were 9.64 and 315.93, and the P values were 0.015 and 0.039, respectively. CTD-ILD patients had higher levels of KL-6 (864.9 vs 463.9, P < 0.001) than those without ILD. KL-6 levels were closely correlated to the severity of ILD assessed both by CT and DLCO%. Additionally, we found that KL-6 level was an independent predictive factor for the presence of ILD and further constructed a decision tree model to rapidly determine the risk of developing ILD among CTD patients. Conclusion: KL-6 is a potential biomarker for gauging the incidence and severity of ILD in CTD patients. To use this typical value of KL-6, however, doctors should take Hb and the presence of lung infections into account.

Comparison of clinical, laboratory and radiological characteristics between Chlamydia psittaci and adenovirus pneumonias: a multicenter retrospective study.

OBJECTIVES: Pneumonia caused by Chlamydia psittaci is a significant global public health issue. Symptom onset and laboratory characteristics may be confused with those of other respiratory viral infections, including adenovirus pneumonia. We aimed to determine differences in clinical presentations and establish a simple nomogram to differentiate C. psittaci and adenovirus pneumonias. METHODS: We conducted a multicenter retrospective study in 10 tertiary general hospitals to compare patients with either C. psittaci (n = 78) or adenovirus (n = 102) pneumonia. A multivariable logistic regression model was used to identify risk factors of C. psittaci pneumonia that were used to establish a nomogram. RESULTS: C. psittaci and adenovirus pneumonia showed certain similar clinical symptoms, including fever, dyspnea, and fatigue, but differed in other characteristics. The multivariate logistic regression showed that age, sex, nervous system symptoms, lymphocyte count, C-reactive protein level, and bilateral lung lesions were risk factors for C. psittaci pneumonia. After incorporating these six factors, the established nomogram achieved a good concordance value (0.949 [95% CI 0.917-0.982]) in differentiating the types of pneumonia, with well-fitting calibration curves. CONCLUSION: Despite having similar clinical features, the variables of age, sex, nervous system symptoms, lymphocytes, C-reactive protein levels, and bilateral lung lesions were combined into a clinically useful nomogram for the rapid and early differentiation of C. psittaci pneumonia from adenovirus pneumonia. This nomogram may help improve treatments and clinical outcomes.

A scoring system based on novel biomarkers and clinical risk factors to predict invasive candidiasis in immunocompetent critically ill patients.

Background: Delayed diagnosis further increases the mortality of invasive candidiasis (IC) in intensive care unit (ICU) patients. This study aimed to develop and validate a score based on novel serological biomarkers and clinical risk factors for predicting IC in immunocompetent ICU patients. Methods: We retrospectively collected clinical data and novel serological markers on admission to ICU. Multivariate logistic regression was used to identify the risk factors associated with IC, which were adopted to establish a scoring system. Results: Patients with IC had a higher C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR) and lower prognostic nutritional index than those without IC. The NLR, CAR, sepsis, total parenteral nutrition, 1,3-ß-D-glucan (BDG)-positivity, and Sequential Organ Failure Assessment score were identified as independent risk factors for IC by multivariate logistic regression analysis and entered into the final scoring system. The area under receiver operating characteristic curve of the score were 0.883 and 0.892, respectively, in the development and validation cohort, higher than Candida score (0.883 vs.0.730, p < 0.001). Conclusion: We established a parsimonious score based on NLR, CAR, BDG-positivity, and clinical risk factors, which can accurately identify IC in ICU patients to give treatment on time and reduce mortality.

[Large-capacity whole-lung lavage in 1 patient with pulmonary alveolar proteinosis and severe hypoxemia and literature review].

To improve the diagnosis and treatment of pulmonary alveolar proteinosis, clinical data for the first successfully treated case of pulmonary alveolar proteinosis with severe hypoxemia by large-capacity whole lung lavage in our hospital were analyzed, and relevant literatures were reviewed. A 35-year-old Han male initially presented two years ago with increasing cough and dyspnea was admitted to our hospital. Admission examination revealed severe hypoxemia, interstitial lung disease, and heavy protein deposition in the alveoli by lung biopsy. The patient received large-capacity whole-lung lavage in the operation room under general anesthesia and treatment of granulocyte-macrophage colony stimulating factor (GM-CSF). The patient's symptoms of dyspnea were alleviated markedly, and radiological findings improved and A-aDO2 decreased.

Successful treatment of acute respiratory distress syndrome caused by hypervirulent Klebsiella pneumoniae with extracorporeal membrane oxygenation and continuous renal replacement therapy: A case report and literature review.

Hypervirulent Klebsiella pneumoniae (hvKP) causes invasive infections and leads to high morbidity and mortality rates. Here, we report the case of a Chinese man with diabetes mellitus who developed acute respiratory distress syndrome and septic shock due to hvKP belonging to the K1 strain. The patient was treated with venovenous extracorporeal membrane oxygenation and continuous renal replacement therapy, in combination with antibiotics and recovered well. Clinicians should be aware of fatal infections caused by hvKP and investigate the best treatment options for patients at various stages of infection.

A prediction model for acute respiratory distress syndrome among patients with severe acute pancreatitis: a retrospective analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe complication among patients with severe acute pancreatitis (SAP), which may be associated with increased mortality in hospitalized patients. Thus, an effective model to predict ARDS in patients with SAP is urgently required. METHODS: We retrospectively analyzed the data from the patients with SAP who recruited in Xiangya Hospital between April 2017 and May 2021. Patients meeting the Berlin definition of ARDS were categorized into the ARDS group. Logistic regression models and a nomogram were utilized in the study. Descriptive statistics, logistic regression models, and a nomogram were used in the current study. RESULTS: Comorbidity of ARDS occurred in 109 (46.58%) of 234 patients with SAP. The SAP patients with ARDS group had a higher 60-day mortality rate, an increased demand for invasive mechanical ventilation, and a longer intensive care unit (ICU) stay than those without ARDS (p < .001 for all). Partial pressure of oxygen (PaO2): fraction of inspired oxygen (FiO2) < 200, platelets <125 × 109/L, lactate dehydrogenase >250 U/L, creatinine >111 mg/dL, and procalcitonin >0.5 ng/mL were independent risk variables for development of ARDS in SAP patients. The area under the curve for the model was 0.814, and the model fit was acceptable [p = .355 (Hosmer-Lemeshow)]. Incorporating these 5 factors, a nomogram was established with sufficient discriminatory power (C-index 0.814). Calibration curve indicated the proper discrimination and good calibration in the predicting nomogram model. CONCLUSION: The prediction nomogram for ARDS in patients with SAP can be applied using clinical common variables after the diagnosis of SAP. Future studies would be warranted to verify the potential clinical benefits of this model.

A Clinically Applicable Nomogram for Predicting the Risk of Invasive Mechanical Ventilation in Pneumocystis jirovecii Pneumonia.

Objective: Pneumocystis jirovecii pneumonia (PCP) is a life-threatening disease associated with a high mortality rate among immunocompromised patient populations. Invasive mechanical ventilation (IMV) is a crucial component of treatment for PCP patients with progressive hypoxemia. This study explored the risk factors for IMV and established a model for early predicting the risk of IMV among patients with PCP. Methods: A multicenter, observational cohort study was conducted in 10 hospitals in China. Patients diagnosed with PCP were included, and their baseline clinical characteristics were collected. A Boruta analysis was performed to identify potentially important clinical features associated with the use of IMV during hospitalization. Selected variables were further analyzed using univariate and multivariable logistic regression. A logistic regression model was established based on independent risk factors for IMV and visualized using a nomogram. Results: In total, 103 patients comprised the training cohort for model development, and 45 comprised the validation cohort to confirm the model's performance. No significant differences were observed in baseline clinical characteristics between the training and validation cohorts. Boruta analysis identified eight clinical features associated with IMV, three of which were further confirmed to be independent risk factors for IMV, including age (odds ratio [OR] 2.615 [95% confidence interval (CI) 1.110-6.159]; p = 0.028), oxygenation index (OR 0.217 [95% CI 0.078-0.604]; p = 0.003), and serum lactate dehydrogenase level (OR 1.864 [95% CI 1.040-3.341]; p = 0.037). Incorporating these three variables, the nomogram achieved good concordance indices of 0.829 (95% CI 0.752-0.906) and 0.818 (95% CI 0.686-0.950) in predicting IMV in the training and validation cohorts, respectively, and had well-fitted calibration curves. Conclusions: The nomogram demonstrated accurate prediction of IMV in patients with PCP. Clinical application of this model enables early identification of patients with PCP who require IMV, which, in turn, may lead to rational therapeutic choices and improved clinical outcomes.

MiR-29a-3p Improves Acute Lung Injury by Reducing Alveolar Epithelial Cell PANoptosis.

Alveolar epithelial cell damage is an important determinant of the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the molecular mechanisms of alveolar epithelial death during the development of ALI/ARDS remain unclear. In this study, we explore the role of miR-29a-3p in ALI/ARDS and its molecular mechanism. Plasma samples were collected from healthy controls and ARDS patients. Mice were intratracheally instilled with lipopolysaccharide (LPS) to establish acute lung injury. N6-adenosine (m6A) quantification, RNA-binding protein immunoprecipitation, cell viability assay, quantitative real-time polymerase chain reaction, and western blotting were performed. We found that miR-29a-3p was down-regulated in plasma of ARDS patients and lung tissue of ALI model mice, and miR-29a-3p agomir injection down-regulated the levels of the inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the lungs, reducing alveolar epithelial cell PANoptosis as evaluated by the downregulation of Z-DNA binding protein 1 (ZBP1), gasdermin D (GSDMD), caspase-3, caspase-8, and mixed lineage kinase domain-like protein (MLKL), ultimately improving lung injury in the ALI model mice. Mechanism studies demonstrated that the knockout of methyltransferase 3 (N6-adenosine-methyltransferase complex catalytic subunit) removed the m6A modification of miR-29a-3p and reduced miR-29a-3p expression. Our findings suggest that miR-29a-3p is a potential target that can be manipulated for ALI/ARDS.

[Evaluating the short-term effect of gefitinib in advanced lung adenocarcinoma with positive EGFR-mutant by dual source volume perfusion CT].

OBJECTIVE: To investigate tumor vascularity by dual source volume perfusion computed tomography (VPCT) in advanced lung adenocarcinoma with positive EGFR-mutant and determine whether any of the VPCT parameters would predict the tumor response to gefitinib. METHODS: Twelve patients (5 males and 7 females, Median age: 53 years, range: 36 - 69 years) with advanced lung adenocarcinoma received VPCT scan. All patients with positive EGFR-mutant were confirmed by pathological biopsy. After a 6-week therapy of gefitinib, VPCT was repeated and the short-term effect evaluated by the RECIST criteria. The VPCT parameters (blood volume, blood flow and permeability surface) of 12 patients were compared with their differentiation grade and short-term effect. RESULTS: Short-term effects were poor in those cases in whom BF increased after a 6-week of targeted therapy (P = 0.030). BF and PS at pre-therapy were negatively correlated with differentiation grade (r = -0.603, -0.694, P = 0.038, 0.012). There was a negative correlation between the rate of BF decline and differentiation grade (r = -0.686, P = 0.029); a negative correlation existed between the trend of BF and RECIST criteria (r = -0.707, P = 0.010). But there was no significant correlation with differentiation grade (P = 0.059). If the BF decline was considered effective, the dual source VPCT could predict the effect of RECIST criteria. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of VPCT was 100%, 66.7%, 83.3%, 75% and 100% respectively. CONCLUSION: Dual source VPCT of advanced lung adenocarcinoma can assess effectively tumor vascularity and perfusion changes after the therapy of gefitinib. It is important in evaluating the response of targeted therapy in lung cancer.

High-Flow Nasal Cannula for COVID-19 Patients: A Multicenter Retrospective Study in China.

Background: High-flow nasal cannula (HFNC) may help avoid intubation of hypoxemic patients suffering from COVID-19; however, it may also contribute to delaying intubation, which may increase mortality. Here, we aimed to identify the predictors of HFNC failure among patients with COVID-19. Methods: We performed a multicenter retrospective study in China from January 15 to March 31, 2020. Two centers in Wuhan (resource-limited centers) enrolled 32 patients, and four centers outside Wuhan enrolled 34 cases. HFNC failure was defined as the requirement of escalation therapy (NIV or intubation). The ROX index (the ratio of SpO2/FiO2 to the respiratory rate) was calculated. Results: Among the 66 patients, 29 (44%) cases experienced HFNC failure. The ROX index was much lower in failing patients than in successful ones after 1, 2, 4, 8, 12, and 24 h of HFNC. The ROX index was independently associated with HFNC failure (OR = 0.65; 95% CI: 0.45-0.94) among the variables collected before and 1 h after HFNC. To predict HFNC failure tested by ROX index, the AUC was between 0.73 and 0.79 for the time points of measurement 1-24 h after HFNC initiation. The HFNC failure rate was not different between patients in and outside Wuhan (41% vs. 47%, p = 0.63). However, the time from HFNC initiation to intubation was longer in Wuhan than that outside Wuhan (median 63 vs. 22 h, p = 0.02). Four patients in Wuhan underwent intubation due to cardiac arrest; in contrast, none of the patients outside Wuhan received intubation (13 vs. 0%, p = 0.05). The mortality was higher in Wuhan than that out of Wuhan, but the difference did not reach statistical significance (31 vs. 12%, p = 0.07). Conclusion: The ROX index can be used to predict HFNC failure among COVID-19 patients to avoid delayed intubation, which may occur in the resource-limited area.

ECMO Rescues Patients With Acute Respiratory Failure Related to GPA.

Granulomatosis with polyangiitis (GPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis with a wide range of clinical symptoms related to the systemic involvement of small blood vessels. The respiratory system is one of the most frequently involved, and life-threatening acute respiratory failure could occur due to diffusive alveolar hemorrhage and tracheal stenosis. When maximum mechanical ventilation is unable to maintain oxygenation, extracorporeal membrane oxygenation (ECMO) should be considered as the final respiratory supportive method, if available. Here we present a 32-year-old male patient with acute respiratory failure (ARF) related to GPA, who was rescued by winning time for accurate diagnosis and appropriate treatment. Additionally, we reviewed more than 60 GPA-related ARF cases on multiple online databases, summarized the clinical manifestations of these patients, and concluded that ECMO plays an important role in further respiratory support for ARF patients with GPA and assists in accurate and timely diagnosis and appropriate treatment, thus helping them recuperate.

Early Prediction of Disease Progression in Patients with Severe COVID-19 Using C-Reactive Protein to Albumin Ratio.

BACKGROUND: Early identification of patients with severe coronavirus disease (COVID-19) at an increased risk of progression may promote more individualized treatment schemes and optimize the use of medical resources. This study is aimed at investigating the utility of the C-reactive protein to albumin (CRP/Alb) ratio for early risk stratification of patients. METHODS: We retrospectively reviewed 557 patients with COVID-19 with confirmed outcomes (discharged or deceased) admitted to the West Court of Union Hospital, Wuhan, China, between January 29, 2020 and April 8, 2020. Patients with severe COVID-19 (n = 465) were divided into stable (n = 409) and progressive (n = 56) groups according to whether they progressed to critical illness or death during hospitalization. To predict disease progression, the CRP/Alb ratio was evaluated on admission. RESULTS: The levels of new biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP/Alb ratio, and systemic immune-inflammation index, were higher in patients with progressive disease than in those with stable disease. Correlation analysis showed that the CRP/Alb ratio had the strongest positive correlation with the sequential organ failure assessment score and length of hospital stay in survivors. Multivariate logistic regression analysis showed that percutaneous oxygen saturation (SpO2), D-dimer levels, and the CRP/Alb ratio were risk factors for disease progression. To predict clinical progression, the areas under the receiver operating characteristic curves of Alb, CRP, CRP/Alb ratio, SpO2, and D-dimer were 0.769, 0.838, 0.866, 0.107, and 0.748, respectively. Moreover, patients with a high CRP/Alb ratio (≥1.843) had a markedly higher rate of clinical deterioration (log - rank p < 0.001). A higher CRP/Alb ratio (≥1.843) was also closely associated with higher rates of hospital mortality, ICU admission, invasive mechanical ventilation, and a longer hospital stay. CONCLUSION: The CRP/Alb ratio can predict the risk of progression to critical disease or death early, providing a promising prognostic biomarker for risk stratification and clinical management of patients with severe COVID-19.

Lipid metabolism changes in patients with severe COVID-19.

BACKGROUND: We investigated the dynamic changes in lipid profiles and their correlations with disease severity and clinical outcome in patients with severe COVID-19. METHODS: We retrospectively reviewed 519 severe COVID-19 patients with confirmed outcomes (discharged or deceased), admitted to the West Court of Union Hospital in Wuhan, China, between 29 January and 8 April 2020. RESULTS: Altogether, 424 severe COVID-19 patients, including 34 non-survivors and 390 survivors, were included in the final analyses. During hospitalization, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) showed an increasing trend in survivors, but showed a downward trend in non-survivors. The serum concentrations of HDL-C and apoA-I were inversely correlated with C-reactive protein (CRP), length of hospital stay of survivors, and disease severity scores. For in-hospital deaths, the areas under the receiver operating characteristic curves (AUCs) of the ratios of CRP/HDL-C and CRP/apoA-I at admission were 0.84 and 0.83, respectively. Moreover, patients with high ratios of CRP/HDL-C (＞77.39) or CRP/apoA-I (＞72.37) had higher mortality rates during hospitalization (log-rank p < 0.001). Logistic regression analysis demonstrated that hypertension, lactate dehydrogenase, SOFA score, and High CRP/HDL-C ratio were independent predictors of in-hospital mortality. CONCLUSIONS: During severe COVID-19, HDL-C and apoA-I concentrations are dramatically decreased in non-survivors. Moreover, High CRP/HDL-C ratio is significantly associated with an increase in mortality and a poor prognosis.