Dopamine inhibits group 2 innate lymphoid cell-driven allergic lung inflammation by dampening mitochondrial activity.

Neuronal signals have emerged as pivotal regulators of group 2 innate lymphoid cells (ILC2s) that regulate tissue homeostasis and allergic inflammation. The molecular pathways underlying the neuronal regulation of ILC2 responses in lungs remain to be fully elucidated. Here, we found that the abundance of neurotransmitter dopamine was negatively correlated with circulating ILC2 numbers and positively associated with pulmonary function in humans. Dopamine potently suppressed lung ILC2 responses in a DRD1-receptor-dependent manner. Genetic deletion of Drd1 or local ablation of dopaminergic neurons augmented ILC2 responses and allergic lung inflammation. Transcriptome and metabolic analyses revealed that dopamine impaired the mitochondrial oxidative phosphorylation (OXPHOS) pathway in ILC2s. Augmentation of OXPHOS activity with oltipraz antagonized the inhibitory effect of dopamine. Local administration of dopamine alleviated allergen-induced ILC2 responses and airway inflammation. These findings demonstrate that dopamine represents an inhibitory regulator of ILC2 responses in allergic airway inflammation.

Advances in research on virulence factors of Acinetobacter baumannii and their potential as novel therapeutic targets.

Acinetobacter baumannii is a strictly aerobic, nonmotile, nonfermenting, gram-negative bacillus. It is a highly infectious and invasive pathogen with high mortality and morbidity rates among immunodeficient patients. Due to increasing levels of drug resistance and the inefficiency of existing antimicrobial treatments, it is crucial to develop novel agents to control this pathogen. Several recent studies have investigated virulence factors that are associated with the pathogenesis of A. baumannii, and could thus serve as novel therapeutic targets. The present review comprehensively summarizes the current understanding of these virulence factors and their mechanisms in A. baumannii. We also highlight factors that could be potential therapeutic targets, as well as list candidate virulence factors for future researchers and clinical practitioners.

Critical Role of Intestinal Microbiota in ATF3-Mediated Gut Immune Homeostasis.

Secretory Ig A (sIgA) plays an important role in the maintenance of intestinal homeostasis via cross-talk with gut microbiota. The defects in sIgA production could elicit dysbiosis of commensal microbiota and subsequently facilitate the development of inflammatory bowel disease. Our previous study revealed activating transcription factor 3 (ATF3) as an important regulator of follicular helper T (TFH) cells in gut. ATF3 deficiency in CD4+ T cells impaired the development of gut TFH cells, and therefore diminished sIgA production, which increased the susceptibility to murine colitis. However, the potential role of microbiota in ATF3-mediated gut homeostasis remains incompletely understood. In this study, we report that both Atf3-/- and CD4creAtf3fl/fl mice displayed profound dysbiosis of gut microbiota when compared with their littermate controls. The proinflammatory Prevotella taxa, especially Prevotella copri, were more abundant in ATF3-deficient mice when compared with littermate controls. This phenotype was obviously abrogated by adoptive transfer of either TFH cells or IgA+ B cells. Importantly, depletion of gut microbiota dramatically alleviated the severity of colitis in Atf3-/- mice, whereas transfer of microbiota from Atf3-/- mice to wild-type recipients increased their susceptibility to colitis. Collectively, these observations indicate the importance of IgA-microbiota interaction in ATF3-mediated gut homeostasis.

Microbial Contamination Characteristics on Touch Surfaces in Outpatient Self-Service Facilities.

BACKGROUND: With the development of science and technology, self-service facilities have been widely used in hospitals. This study aimed to assess the microbial contamination characteristics on touch surfaces in outpatient, self-service facilities from Monday to Friday. METHODS: Touch surfaces in outpatient facilities were swabbed and surveyed for total microbial growth before and after work every morning. Selected bacteria were identified to screen for pathogenic organisms. RESULTS: There were 360 samples collected, 87 samples (24.2%) were culture-positive. Staphylococcus species were the main microbial contamination. The three most common bacteria were S. hominis, S. epidermidis and S. hemolyticus. After work, more microbial contamination was found on Monday (p = 0.029). There was no difference in sample positive rates between self-service facilities and manual service area. Although, the antibiotic resistance patterns of different staphylococcus species were different, the overall drug resistance rate is low. Only one S. aureus was methicillin-Sensitive S. aureus. CONCLUSIONS: The self-service facilities' touch surfaces microbial contamination were similar to manual service area, but the more used, the more microbial contamination was found. Hospitals should enhance cleaning times of self-service facilities to keep them clean, especially on Mondays.

A Case of Lung Involvement in Peripheral T Cell Lymphoma.

BACKGROUND: Lung involvement is rare in peripheral T cell lymphoma, and there is a lack of sufficient clinical study. The authors describe a rare case of lung involvement in a 40-year-old male patient with peripheral T cell lymphoma. METHODS: Hematological investigation, bone marrow aspirate, and lung biopsy were performed. RESULTS: The patient received 4 courses of CHOP regimen chemotherapy. He achieved partial response (PR) at the 2nd course, but showed disease progressive (PD) at the 4th course. Then he received 2 courses of GDP regimen chemotherapy. Unfortunately, the patient died of tumor overload with hyper-lactacidemia 6 months after the onset of the disease. CONCLUSIONS: Lung biopsy is important to confirm a diagnosis of primary pulmonary lymphoma. Lung involvement in peripheral T cell lymphoma as a prognostic factor needs further studies.

Risk Factors for Mortality Due to Ventilator-Associated Pneumonia in a Chinese Hospital: A Retrospective Study.

BACKGROUND As a common nosocomial infection, ventilator-associated pneumonia (VAP) often has high mortality. This study aimed to assess the risk factor for mortality owing to VAP. MATERIAL AND METHODS This retrospective clinical audit study screened medical records between the period of January 2014 and December 2017. All patients under mechanical ventilation MV) for ≥72 hours were screened against previously reported diagnostic criteria for VAP. The medical records were obtained for cases of documented diagnosis of VAP. RESULTS In all, 145 patients (5.0%) diagnosed with VAP were included in the study; the morbidity of VAP was 19.5 episodes per 1000 days of MV. The 30-day mortality rate was 42.8%. Univariate logistic analysis showed that elevated neutrophil-to-lymphocyte ratio (NLR), high blood urea nitrogen/albumin (BUN/ALB) ratio, Multidrug-resistant organism infection, and a higher sequential organ failure assessment (SOFA) score were risk factors for mortality caused by VAP. In the second multivariate analysis, elevated NLR levels (P=0.038), high BUN/ALB ratio (P=0.016), multidrug-resistant organism infections (P=0.036), and a higher SOFA score (P<0.001) were still associated with the 30-day mortality rate. CONCLUSIONS The 30-day mortality rate of VAP was high. Blood NLR and BUN/ALB levels can be used as risk factors to assess the 30-day VAP-related mortality to help clinicians improve the prognosis of VAP.

Elevated Blood Urea Nitrogen-to-Serum Albumin Ratio as a Factor That Negatively Affects the Mortality of Patients with Hospital-Acquired Pneumonia.

This study aimed to evaluate the factors that affect 30-day mortality of patients with HAP. The data used in this study were collected from all HAP occurred in our hospital between January 2014 and December 2017. A total of 1158 cases were included. 150 (13.0%) of whom died within 30 days. This reported mortality identified by the univariate Cox regression analysis is found to have been affected by the following factors: age greater than 70 years, presence of diabetes mellitus and chronic obstructive pulmonary disease, gastric tube intubation, administration of proton-pump inhibitor, blood albumin level less than 30 g/l, elevated neutrophil-to-lymphocyte ratio, antibiotics therapy in the preceding 90 days, intensive care unit (ICU) admission, blood lymphocyte count less than 0.8 × 109/L, elevated blood urea nitrogen/albumin (BUN/ALB) level, and presence of multidrug-resistant (MDR) pathogens. In the second multivariate analysis, administration of proton-pump inhibitor, administration of antibiotics in the preceding 90 days, ICU admission, blood lymphocyte count less than 0.8 × 109/L, elevated BUN/ALB level, and presence of MDR pathogens were still associated with 30-day mortality. The area under the receiver operating characteristic curves in the BUN/ALB predicting 30-day mortality due to HAP was 0.685. A high BUN/ALB was significantly associated with a worse survival than a low BUN/ALB (P < 0.001). Therefore, an elevated BUN/ALB level is a risk factor for mortality on patients with HAP.

Protective effects of caffeoylxanthiazonoside isolated from fruits of Xanthium strumarium on sepsis mice.

CONTEXT: The fruit of Xanthium strumarium L. (Asteraceae) has been used for the treatment of various inflammatory diseases. OBJECTIVE: This study investigates the protective effect of caffeoylxanthiazonoside (CYXD) isolated from fruits of X. strumarium on sepsis mice in vitro and in vivo. MATERIALS AND METHODS: Cecal ligation and puncture (CLP) operation was used to establish the sepsis mice model, and sham mice were also performed. CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then the survival rate was measured in 96 h. Additionally, sepsis mice were induced by injection LPS (2 mg/kg); CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then mice were sacrificed, and serum levels of TNF-α and IL-6 were determined by ELISA assay. Furthermore, the ability of CYXD to neutralize LPS was measured by using the LAL test, and expressions of TNF-α, IL-6 were determined by using real-time fluorogenic PCR. RESULTS: Results indicated that CYXD significantly elevated survival rates of sepsis mice induced by CLP (p < 0.05) with survival rates of 35%, 45%, and 65%. Furthermore, the LPS level was decreased obviously by CYXD (1, 2, and 4 mg/L) (p < 0.05). Additionally, CYXD (10, 20, and 40 mg/kg) can not only significantly decrease TNF-α and IL-6 levels induced by LPS in mice's serum (p < 0.05), but also inhibit mRNA expressions of TNF-α and IL-6 induced by LPS in RAW 264.7 cells at doses of 20, 40, and 80 µg/mL (p < 0.05). CONCLUSION: Our study demonstrated that CYXD has significant protective effects on sepsis mice.

Metabolomics Method in Understanding and Sensitizing Carbapenem-Resistant Acinetobacter baumannii to Meropenem.

Carbapenem-resistant Acinetobacter baumannii (CRAB) strains are prevalent worldwide and represent a major threat to public health. However, treatment options for infections caused by CRAB are very limited as they are resistant to most of the commonly used antibiotics. Consequently, understanding the mechanisms underlying carbapenem resistance and restoring bacterial susceptibility to carbapenems hold immense importance. The present study used gas chromatography-mass spectrometry (GC-MS)-based metabolomics to investigate the metabolic mechanisms of antibiotic resistance in clinically isolated CRAB. Inactivation of the pyruvate cycle and purine metabolism is the most typical characteristic of CRAB. The CRAB exhibited a reduction in the activity of enzymes involved in the pyruvate cycle, proton motive force, and ATP levels. This decline in central carbon metabolism resulted in a decrease in the metabolic flux of the α-ketoglutarate-glutamate-glutamine pathway toward purine metabolism, ultimately leading to a decline in adenine nucleotide interconversion. Exogenous adenosine monophosphate (AMP) and adenosine triphosphate (ATP) enhance the killing efficacy of Meropenem against CRAB. The combination of ATP and Meropenem also has a synergistic effect on eliminating CRAB persisters and the biofilm, as well as protecting mice against peritonitis-sepsis. This study presents a novel therapeutic modality to treat infections caused by CRAB based on the metabolism reprogramming strategy.

L-Serine enables reducing the virulence of Acinetobacter baumannii and modulating the SIRT1 pathway to eliminate the pathogen.

The emergence of high-virulent Acinetobacter baumannii strains increases the mortality of patients and seriously affects their prognosis, which motivates us to explore novel ways to control such infections. In this study, gas chromatography-mass spectrometry was adopted to explore the metabolic difference between high- and low-virulent A. baumannii strains, and the decreased L-serine levels were identified as the most crucial biomarker in low-virulent A. baumannii strains. In vitro, L-serine reduced the virulence of A. baumannii to Beas 2B cells and inhibited the activation of NLRP3 inflammasome via decreasing the generation of ROS and mtROS and the release of inflammatory cytokines (IL-18 and IL-1ß) through upregulating SIRT1. In vivo, the Galleria mellonella model was adopted. L-serine downregulated the levels of virulence genes (ompA, carO, and omp33-36), reduced the mortality of A. baumannii to G. mellonella, and decreased the blacking speed as well as the degree of G. mellonella after infection. Taken together, we found that L-serine can reduce the virulence of A. baumannii and enhance the host's defense against the pathogen, providing a novel strategy for the treatment of infections caused by A. baumannii.IMPORTANCEAcinetobacter baumannii has become one of the most common and severe opportunistic pathogens in hospitals. The high-virulent A. baumannii strains pose a great threat to patients and increase the risk of nosocomial infection. However, the mechanism of virulence in A. baumannii is still not well understood. In the present study, we identified potential biomarkers in low-virulent A. baumannii strains. Our analysis revealed the effect of L-serine on reducing the virulence of A.baumannii. This discovery suggests that targeting L-serine could be a promising strategy for the treatment or adjunctive treatment of A. baumannii infections. The development of treatments targeting virulence may provide a substitute for the increasingly failed traditional antibacterial treatment.

Seasonal Dynamics of the Upper Respiratory Tract Microbiome in Chronic Obstructive Pulmonary Disease.

Introduction: Increasing evidence suggests that seasonal changes can trigger the alternation of airway microbiome. However, the dynamics of the upper airway bacterial ecology of chronic obstructive pulmonary disease (COPD) patients across different seasons remains unclear. Methods: In this study, we present a 16S ribosomal RNA survey of the airway microbiome on 72 swab samples collected in different months (March, May, July, September, and November) in 2019 from 18 COPD patients and from six resampled patients in November in 2020. Results: Our study uncovered a dynamic airway microbiota where changes appeared to be associated with seasonal alternation in COPD patients. Twelve clusters of temporal patterns were displayed by differential and clustering analysis along the time course, systematically revealing distinct microbial taxa that prefer to grow in cool and warm seasons, respectively. Moreover, the upper airway microbiome composition was relatively stable in the same season in different years. Discussion: Given the tight association between airway microbiome and COPD disease progression, this study can provide useful information for clinically understanding the seasonal trend of disease phenotypes in COPD patients.

Differentiation Between Acinetobacter Baumannii Colonization and Infection and the Clinical Outcome Prediction by Infection in Lower Respiratory Tract.

Purpose: Acinetobacter baumannii is the most common microorganism in sputum cultures from long-term hospitalized patients and is often the cause of hospital-acquired pneumonia (HAP), which is usually associated with poor prognosis and high mortality. It is sometimes difficult to distinguish between A. baumannii infection and colonization. This study aimed to evaluate factors that differentiate infection from colonization and predict mortality in patients with nosocomial pneumonia caused by A. baumannii. Patients and Methods: The data used in this study were collected in our hospital between January 2018 and December 2020 from patients whose sputum cultures were positive for A. baumannii. Results: A total of 714 patients were included, with 571 in the infection group and 143 in the colonization group. The in-hospital mortality rate in the infection group was 20.5%. Univariate and multivariate logistic regression analyses showed that age, total number of inpatient departments, absolute neutrophil count, and C-reactive protein (CRP) level helped distinguish between infection and colonization. The area under the receiver operating characteristic curve (ROC) of the identification model was 0.694. In the infection group, age, Charlson comorbidity score, neutrophil-to-lymphocyte ratio, blood urea nitrogen/albumin ratio, CRP level, presence of multidrug resistance, and clinical pulmonary infection score (≥6) ratio were associated with in-hospital mortality. The area under the ROC curve for the prediction model was 0.828. The top three drug resistance rates in the infection group were 100% (cefazolin), 98.77% (ceftriaxone), and 71.8% (cefuroxime). Conclusion: The combination of common parameters helps identify A. baumannii respiratory tract infection or colonization. Several novel predictors can be used to predict the risk of death from A. baumannii pneumonia to reduce mortality. The drug resistance of A. baumannii remains high.

Nitrite Promotes ROS Production to Potentiate Cefoperazone-Sulbactam-Mediated Elimination to Lab-Evolved and Clinical-Evolved Pseudomonas aeruginosa.

Cefoperazone-sulbactam (SCF)-resistant Pseudomonas aeruginosa poses a big challenge in the use of SCF to treat infection caused by the pathogen. We have recently shown exogenous nitrite-enabled killing of naturally and artificially evolved Pseudomonas aeruginosa strains (AP-RCLIN-EVO and AP-RLAB-EVO, respectively) by SCF. However, the underlying mechanism is unknown. Here, reprogramming metabolomics was adopted to investigate how nitrite enhanced the SCF-mediated killing efficacy. Nitrite-reprogrammed metabolome displayed an activated pyruvate cycle (P cycle), which was confirmed by elevated activity of pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. The activated P cycle provided NADH for the electron transport chain and thereby increased reactive oxygen species (ROS), which potentiated SCF to kill AP-RCLIN-EVO and AP-RLAB-EVO. The nitrite-enabled killing of AP-RCLIN-EVO and AP-RLAB-EVO by SCF was inhibited by PDH inhibitor furfural and ROS scavenger N-Acetyl-L-cysteine but promoted by ROS promoter Fe3+. SCF alone could not induce ROS, but SCF-mediated killing efficacy was enhanced by ROS. In addition, the present study demonstrated that nitrite repressed antioxidants, which were partly responsible for the elevated ROS. These results reveal a nitrite-reprogrammed metabolome mechanism by which AP-RCLIN-EVO and AP-RLAB-EVO sensitivity to SCF is elevated. IMPORTANCE Antibiotic-resistant Pseudomonas aeruginosa has become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients. Understanding antibiotic resistance mechanisms and developing novel control measures are highly appreciated. We have recently shown that a reduced nitrite-dependent NO biosynthesis contributes to cefoperazone-sulbactam (SCF) resistance, which is reverted by exogenous nitrite, in both naturally and artificially evolved P. aeruginosa strains (AP-RCLIN-EVO and AP-RLAB-EVO, respectively). However, the mechanism is unknown. The present study reports that the nitrite-enabled killing of AP-RCLIN-EVO and AP-RLAB-EVO by SCF is attributed to the promoted production of reactive oxygen species (ROS). Nitrite activates the pyruvate cycle to generate NADH for the electron transport chain, which in turn promotes ROS generation. Nitrite-potentiated SCF-mediated killing is decreased by pyruvate dehydrogenase inhibitor furfural and ROS scavenger N-Acetyl-L-cysteine but increased by ROS promoter Fe3+. Furthermore, SCF-mediated killing is promoted by H2O2 in a dose-dependent manner. In addition, the combination of nitrite and H2O2 greatly enhances SCF-mediated killing. These results not only disclose a nitrite-ROS-potentiated SCF-mediated killing, but also show SCF-mediated killing is dependent upon ROS.

Blood urea nitrogen to serum albumin ratio independently predicts 30-day mortality and severity in patients with Escherichia coli bacteraemia.

BACKGROUND: Elevated blood urea nitrogen to serum albumin (BUN/ALB) ratio had been identified as an independent risk factor related to mortality in community-acquired and hospital-acquired pneumonia. This study aimed to investigate whether this clinical index can predict the clinical outcomes of E. coli bacteraemia. MATERIAL AND METHODS: Clinical data were collected from patients with E. coli bacteraemia attended at our hospital between January 2012 and December 2018. The endpoints were mortality within 30 days after the diagnosis of E. coli bacteraemia and intensive care (IC) requirement. Cox regression analysis was performed to evaluate the risk factors. RESULTS: A total of 398 patients with E. coli bacteraemia were enrolled in this study and 56 patients died within 30 days after bacteraemia onset. Multivariate Cox regression analysis showed that age greater than 65 years, lymphocyte count<.8×10e9/L, elevated BUN/ALB ratio, increased SOFA score, carbapenem resistance, central venous catheterization before onset of bacteraemia, and infection originating from abdominal cavity were independent risk factors for 30-day mortality (P<.05). The risk factors associated with IC requirement were similar to those for 30-day mortality except central venous catheterization before onset of bacteraemia. The area under the receiver-operating characteristic curve for BUN/ALB ratio predicting 30-day mortality and IC requirement was similar to that for SOFA score, but higher than that for lymphocyte count. The cut-off points of BUN/ALB ratio to predict 30-day mortality and IC requirement were both .3. CONCLUSIONS: BUN/ALB ratio is a simple but independent predictor of 30-day mortality and severity in E. coli bacteraemia. A higher BUN/ALB ratio at the onset of bacteraemia predicts a higher mortality rate and IC requirement.

Inactivation of Nitrite-Dependent Nitric Oxide Biosynthesis Is Responsible for Overlapped Antibiotic Resistance between Naturally and Artificially Evolved Pseudomonas aeruginosa.

Metabolic flexibility of Pseudomonas aeruginosa could lead to new strategies to combat bacterial infection. The present study used gas chromatography-mass spectrometry (GC-MS)-based metabolomics to investigate global metabolism in naturally and artificially evolved strains with cefoperazone-sulbactam (SCF) resistance (AP-RCLIN-EVO and AP-RLAB-EVO, respectively) from the same parent strain (AP-RCLIN). Inactivation of the pyruvate cycle and nitric oxide (NO) biosynthesis was identified as characteristic features of SCF resistance in both evolved strains. Nitrite-dependent NO biosynthesis instead of an arginine-dependent NO pathway is responsible for the reduced NO, which is attributed to lower nitrite and electrons from the oxidation of NADH to NAD+ provided by the pyruvate cycle. Exogenous fumarate, NADH, nitrate, and nitrite promoted the NO level and thereby potentiated SCF-mediated killing. Unexpectedly, fumarate caused the elevation of nitrite, while nitrite/nitrate resulted in the increase of Cyt bc1 complex (providing electrons). These interesting findings indicate that the nitrite-dependent NO biosynthesis and the pyruvate cycle are mutual to promote NO metabolism. In addition, the NO-potentiated sensitivity to SCF was validated by NO donor sodium nitroprusside. These results reveal an endogenous NO-mediated SCF resistance and develop its reversion by metabolites in P. aeruginosa. IMPORTANCE Infections with Pseudomonas aeruginosa have become a real concern among hospital-acquired infections, especially in cystic fibrosis patients and immunocompromised individuals. Control of the pathogen is challenging due to antibiotic resistance. Since bacterial metabolic state impacts sensitivity and resistance to antibiotics, exploring and disclosing bacterial metabolic mechanisms can be used to develop a metabolome-reprogramming approach to elevate bacterial sensitivity to antibiotics. Therefore, GC-MS-based metabolomics is used to explore the similarities and differences of metabolomes between naturally and artificially evolved cefoperazone-sulbactam (SCF)-resistant P. aeruginosa (AP-RCLIN-EVO and AP-RLAB-EVO, respectively) from the same parent strain (AP-RCLIN). It identifies the depressed nitrite-dependent nitric oxide (NO) biosynthesis as the most overlapping characteristic feature between AP-RCLIN-EVO and AP-RLAB-EVO. This is because the pyruvate cycle fluctuates, thereby generating fewer NADH and providing fewer electrons for nitrite-dependent NO biosynthesis than the control. Interestingly, exogenous fumarate, NADH, nitrate, and nitrite as well as NO donor sodium nitroprusside promote NO generation to elevate sensitivity to SCF. These results highlight the way to understand metabolic mechanisms of antibiotic resistance and explore metabolic modulation to combat the bacterial pathogen.

Main pulmonary artery enlargement predicts 90-day readmissions in Chinese COPD patients.

BACKGROUND: Numerous studies have shown pulmonary artery enlargement when measured by chest computed tomography (CT) could predict a worse outcome in chronic obstructive pulmonary disease (COPD) patients. Herein, we studied the prognostic implication of main pulmonary artery diameter (MPAD) in Chinese COPD patients. METHODS: This is an observational case-control study. Patients with 90-day readmissions are case group and those without 90-day readmission are control group. The study comprised of 417 COPD patients who underwent chest CT in their initial admission due to acute exacerbation of COPD (AECOPD). We analyzed their clinical characteristics such as MPAD, arterial blood gas (ABG) results, other chest CT findings and comorbidities to identify the cause of readmission within 90 days. RESULTS: Median age of our study population is 75 years old, and 79.6% of them are male. The median MPAD is 2.8 cm and 80.6% were also diagnosed with community acquired pneumonia (CAP) in their first admission. The median MPAD in patients with 90-day readmission was 3.1 cm while patients without 90-day readmission had median MPAD of 2.8 cm. Through multivariate logistic regression analysis CAP (P=0.019, OR: 3.105, 95% CI: 1.203-8.019) and MPAD (P<0.001, OR: 2.898, 95% CI: 1.824-4.605) were statistically significant. In the second stage of analysis, subgroup of patients diagnosed with CAP and AECOPD (pAECOPD) were analyzed, MPAD remained statistically significant (P<0.001, OR: 3.490, 95% CI: 1.929-6.316) and receiver operative characteristic (ROC) curve for pAECOPD patients; area under the curve (AUC) was 0.704 (95% CI: 0.631-0.778) with a MPAD cut off value of 2.9 cm (sensitivity 72%, specificity 53%). CONCLUSIONS: Enlarged MPAD and pAECOPD in initial admission are independent risk factors for 90-day readmission. In our pAECOPD patient population, MPAD >2.9 cm are at increased risk of 90-day readmission.

Deep Learning-Based Available and Common Clinical-Related Feature Variables Robustly Predict Survival in Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Although there are many predictors of death for CAP, there are still some limitations. This study aimed to build a simple and accurate model based on available and common clinical-related feature variables for predicting CAP mortality by adopting machine learning techniques. METHODS: This was a single-center retrospective study. The data used in this study were collected from all patients (≥18 years) with CAP admitted to research hospitals between January 2012 and April 2020. Each patient had 62 clinical-related features, including clinical diagnostic and treatment features. Patients were divided into two endpoints, and by using Tensorflow2.4.1 as the modeling framework, a three-layer fully connected neural network (FCNN) was built as a base model for classification. For a comprehensive comparison, seven classical machine learning methods and their integrated stacking patterns were introduced to model and compare the same training and test data. RESULTS: A total of 3997 patients with CAP were included; 205 (5.12%) died in the hospital. After performing deep learning methods, this study established an ensemble FCNN model based on 12 FCNNs. By comparing with seven classical machine learning methods, the area under the curve of the ensemble FCNN was 0.975 when using deep learning algorithms to classify poor from good prognosis based on available and common clinical-related feature variables. The predicted outcome was poor prognosis if the ControlNet's poor prognosis score was greater than the cutoff value of 0.50. To confirm the scientificity of the ensemble FCNN model, this study analyzed the weight of random forest features and found that mainstream prognostic features still held weight, although the model is perfect after integrating other factors considered less important by previous studies. CONCLUSION: This study used deep learning algorithms to classify prognosis based on available and common clinical-related feature variables in patients with CAP with high accuracy and good generalizability. Every clinical-related feature is important to the model.