RESUMO
The application of flexible sensors in the biomedical field is deepening. It is of great significance to develop flexible wearable sensors which are more in line with the needs of the public. A flexible polylactic acid membrane fabric was prepared by electrospinning method. The membrane was used as SERS active substrate by screen printing capture probe which combine Au nanoplates with antibodies to the target substance. Thioglycolic acid-labeled silver nanoparticles coupled with antibodies as SERS nanotags. The target substance can be fixed between the capture probe and SERS nanotags. Due to the high specific surface area between the spinning, the adhesion rate of the capture probe is higher than that of the rigid substrate, and the enrichment and hypersensitivity detection of the object to be tested could be realized. The membranes prepared are flexible, wearable, portable, highly biocompatible, and can be mass-produced for high-throughput detection. We then applied the sensor to the detection of SARS-CoV-2 with detection limits as low as 10 TU/mL. This membrane as a SERS substrate can offer a fast and non-invasive reference for the early diagnosis of respiratory infectious diseases similar to COVID-19.
Assuntos
COVID-19 , Nanopartículas Metálicas , Pneumonia , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Prata , Anticorpos , Sistema RespiratórioRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Nursing home-associated pneumonia (NHAP) is a common type of infection among long-term care residents. Moreover, the mortality of NHAP is also higher than community-acquired pneumonia (CAP). In traditional Chinese medicine (TCM), the decoctions of Banxia Houpo Tang (BHT) and Ding Chuan Tang (DCT) are two formulas supporting the lungs' natural defense systems, helps to expel mucus and promote detoxification. AIM OF THE STUDY: We designed a concentrated Chinese herbal extract formula called BDT1, that combines the compounds of BHT and DCT. In this study, we evaluated the safety and efficacy of BDT1 for NHAP prevention in high-risk older residents in the nursing home. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, 160 participants aged over 65 years old living in the nursing home were randomly assigned 1:1 to the BDT1 and placebo group. Besides regular medicine, participants received either BDT1 or a placebo for 12 consecutive weeks. The primary outcome was the hospitalization rate for pneumonia in the intervention period and half-year follow-up. The microscopic examination of Gram-stained sputum was also evaluated before and after the trial. Data were analyzed by using the Chi-square test and Wilcoxon Signed Ranks Test with SPSS. RESULTS: A total of 160 participants were enrolled into two study groups in this study, which was completed with 143 participants analyzed, including 70 subjects in the BDT1 group and 73 subjects in the placebo group. After the 12-week medical treatment, the hospitalization rate for pneumonia was 10.0% and 34.2% in the BDT1 and placebo group respectively. The risk of pneumonia in half a year was lower in the BDT1 group (adjusted hazard ratio = 0.422, 95% CI = 0.226-0.791). Compared to the placebo group, the level of Gram-negative bacilli in the BDT1 group is significantly declined in sputum samples (p < 0.05). CONCLUSION: In conclusion, the cumulative incidence of pneumonia and related-hospitalization rates declined significantly after 12-weeks of BDT1 treatment. Besides, Chinese herbal medicine BDT1 is a safe therapy without hepatotoxicity or nephrotoxicity.
Assuntos
Medicamentos de Ervas Chinesas , Pneumonia , Humanos , Idoso , Medicamentos de Ervas Chinesas/efeitos adversos , Casas de Saúde , Pneumonia/tratamento farmacológico , Pneumonia/prevenção & controle , Método Duplo-Cego , Resultado do TratamentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: As the second-largest traditional medical system in China, Tibetan medicine has a long history and abundant resources. To promote the development of the Tibetan medicine industry, it is essential to study the pharmacological activities of Tibetan medicine based on its traditional usage methods. AIM OF THE STUDY: Pneumonia has been a worldwide health problem with high morbidity and mortality rates, especially in the context of the COVID-19 epidemic. Given the unique advantages of traditional Tibetan medicine in treating pulmonary diseases, further research is warranted to develop potential anti-pneumonia drugs. MATERIALS AND METHODS: In our study, the potential combined decoction from traditional Tibetan medicine was determined by the data mining method. The antioxidant activity in vitro, anti-inflammatory effects on the macrophage cell model, as well as the anti-pulmonary inflammation effects on the LPS-induced mice model, have been explored to investigate the potential anti-pneumonia role of the decoction. Additionally, we conducted network pharmacology analysis to identify the potential targets against pneumonia, which were further confirmed by western blot assays. RESULTS: Following the combination therapy of Pterocephalodes hookeri (C.B.Clarke) V.Mayer & Ehrend. and Onosma hookeri var. longiflora (Duthie) A.V.Duthie ex Stapf ('P-O'), the clearance of DPPH radical and the total reducing power were all improved, as well as alleviated the toxicity. On the in vitro level, 'P-O' pre-treatment reduced the secretion of NO, TNF-α, IL-6, and IL-1ß in LPS-stimulated RAW264.7 cells, while promoting the concentration of IL-10. Meanwhile, on the in vivo level, the 'P-O' pre-treating also could alleviate LPS-induced pulmonary inflammation by reducing the pulmonary edema and leakage of the lung microvascular, improving the pathological change of lung tissue and regulating the cytokines content in bronchoalveolar lavage fluid (BALF). Furthermore, network pharmacology analysis revealed that the mechanism of 'P-O' in treating pneumonia in a multi-component, multi-target, and multi-pathway network, with the TLR4/NF-κB signaling pathway playing a crucial role, as demonstrated by the western blot assay results. CONCLUSION: In summary, the combination therapy of 'P-O' exhibited good antioxidant activity and anti-inflammatory activity in vitro, as well as a therapeutic effect against pulmonary inflammation in vivo. These findings provide evidence for the clinical application of 'P-O' and offer new approaches for treating pneumonia.
Assuntos
COVID-19 , Pneumonia , Camundongos , Animais , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/toxicidade , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Transdução de Sinais , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/prevenção & controle , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pseudomonas aeruginosa is an opportunistic bacterial pathogen which is the second leading cause of hospital-acquired pneumonia. Jingfang granule (JFG) is an herbal formula of Traditional Chinese medicine (TCM) widely used in treatment of acute respiratory tract infections in China. However, the molecular mechanisms of JFG in treatment of P. aeruginosa-induced acute pneumonia are not clear. AIM OF STUDY: This study aimed to investigate the mechanisms underlying the effects of JFG on P. aeruginosa-induced acute inflammation using a mouse model of bacterial acute pneumonia. MATERIALS AND METHODS: The chemical components and targets of JFG were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the P. aeruginosa pneumonia-related targets were obtained from the disease databases, including Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNet. The protein-protein interaction (PPI) network was constructed using STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Molecular docking was performed using AutoDockTools 1.5.6. Further in vivo experiments employed a mouse model of P. aeruginosa acute pneumonia to verify the target proteins and signaling pathways affected by JFG, which were predicted by the network pharmacology analysis. RESULTS: A total of 218 active components and 257 targets of JFG were retrieved from TCMSP database. Moreover, 99 intersectant targets were obtained between the 257 JFG targets and 694 disease targets. Among the intersectant targets, STAT3, IL-6, AKT1, TNF, MAPK1, MAPK3 and EGFR were identified to be the key therapeutic targets through PPI network analysis, and STAT3 was in the center of the network, which is a key regulator of IL-17 expression. KEGG pathway enrichment analysis suggested that IL-17 signaling pathway was one of the crucial inflammatory pathways affected by JFG in treatment of P. aeruginosa pneumonia. Furthermore, the in vivo experiments demonstrated that the JFG-treated mice displayed reduced proinflammatory cytokine production (IL-17, IL-1ß, IL-6 and TNF), diminished neutrophil infiltration and decreased mortality, compared with the non-drug-treated mice during P. aeruginosa lung infection. Moreover, the expression or phosphorylation levels of the key regulators in STAT3/IL-17/NF-κB axis including STAT3, ERK1/2 (MAPK3/1), AKT, NF-κB p65 and RORγt were significantly reduced in the lung tissues of the JFG-treated mice. CONCLUSION: JFG was effective in treatment of P. aeruginosa acute lung infection, which reduced inflammatory responses through suppressing STAT3/IL-17/NF-κB pathway.
Assuntos
Medicamentos de Ervas Chinesas , Pneumonia , Humanos , NF-kappa B , Pseudomonas aeruginosa , Farmacologia em Rede , Interleucina-17 , Interleucina-6 , Simulação de Acoplamento Molecular , Pneumonia/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fator de Transcrição STAT3RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica decursiva Franchet & Savatier is a traditional medicinal plant used to treat asthma, cough, headache, pyrexia and thick phlegm in China, Japan and Korea. A. decursiva contains many types of coumarins, which can exert several pharmacological activities including anti-inflammatory and antioxidant properties for treating various diseases such as pneumonitis, atopic dermatitis, diabetes, and Alzheimer's disease. AIM OF THE STUDY: In this study, we analyzed the components of A. decursiva ethanol extract (ADE) by high performance liquid chromatography (HPLC) and investigated the therapeutic effects of ADE against allergic asthma using lipopolysaccharide (LPS) stimulated RAW264.7 cells and an ovalbumin (OVA)-exposed allergic asthma model. To elucidate the mechanism of action of ADE, we examined the protein expression through network pharmacological analysis. MATERIALS AND METHODS: To establish asthma model, the mice were sensitized on day 0 and 14 via intraperitoneal injection of OVA with aluminum hydroxide. The mice were inhaled with OVA using an ultrasonic nebulizer on day 21, 22 and 23. ADE (50 and 100 mg/kg) was administered to mice by oral gave form day 18-23. On day 24, airway hyperresponsiveness (AHR) was measured using flexivent. On day 25, the mice were sacrificed and collected bronchoalveolar lavage fluids (BALF), serum and lung tissue. In LPS-stimulated RAW264.7 cell, nitric oxide and cytokines were measured. Additionally, expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB were detected using double-immunofluorescence. RESULTS: We detected the five coumarin components which included nodakenin, umbelliferon, (-)-marmesin (=nodakenetin), bergapten, and decursin, in ADE by high performance liquid chromatography. Treatment with ADE decreased the production of nitric oxide, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in LPS-stimulated RAW264.7 cells accompanied by the enhanced expression of nuclear factor erythroid-2-related factor (Nrf2) and suppression of nuclear factor (NF)-κB. In the asthma model, the administration of ADE reduced inflammatory cell count and airway hyperresponsiveness in OVA-exposed animals with decreased levels of IL-4, IL-13, and OVA-specific immunoglobulin E. These results were accompanied by the reduction of pulmonary inflammation and mucus secretion. Furthermore, ADE administration inhibited the expression of NF-κB and matrix metalloproteinase (MMP)-9 in OVA-exposed animals, which was consistent with the results of network pharmacological analysis. CONCLUSION: This study demonstrated that ADE effectively attenuated allergic inflammation induced by OVA inhalation through the enhancement of Nrf2 expression and suppression of NF-κB expression. Therefore, ADE may be a potential therapeutic agent for controlling asthma.
Assuntos
Angelica , Asma , Hipersensibilidade , Pneumonia , Animais , Camundongos , Ovalbumina/toxicidade , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Óxido Nítrico/metabolismo , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/metabolismo , Hipersensibilidade/tratamento farmacológico , Pulmão , Pneumonia/metabolismo , Líquido da Lavagem Broncoalveolar , Interleucina-6/metabolismo , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
BACKGROUND: Admission hyperglycemia is a common phenomenon in the early stages of injury. This study aimed to determine the relationship between admission hyperglycemia and postoperative pneumonia in geriatric patients with hip fractures. METHODS: A total of 600 geriatric patients admitted to Dandong Central Hospital with hip fractures were included. Patients were divided into four groups based on quartiles of admission blood glucose levels: Q1- Q4. Multivariable logistic regression and propensity score-matched analyses were conducted to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for postoperative pneumonia. Receiver operating characteristic (ROC) curves were used to determine the cut-off value of admission hyperglycemia for predicting postoperative pneumonia. RESULTS: The incidence of postoperative pneumonia was significantly higher among hyperglycemic patients than those with normal glucose levels (OR = 2.090, 95% CI: 1.135-3.846, p = 0.016). Admission hyperglycemia showed moderate predictive power, with an area under the ROC curve of 0.803. Furthermore, propensity score-matched analyses demonstrated that patients in the Q3 (OR = 4.250, 95% CI: 1.361-13.272, p = 0.013) and Q4 (OR = 4.667, 95% CI: 1.251-17.405, p = 0.022) quartiles had a significantly higher risk of postoperative pneumonia compared to patients in the Q1 quartile. CONCLUSIONS: Admission hyperglycemia in elderly hip fracture patients increases the risk of postoperative pneumonia. This biomarker can aid clinical assessment and perioperative management.
Assuntos
Fraturas do Quadril , Hiperglicemia , Pneumonia , Idoso , Humanos , Fraturas do Quadril/complicações , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Hospitalização , Hospitais , Hiperglicemia/diagnóstico , Hiperglicemia/epidemiologia , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/etiologiaRESUMO
BACKGROUND: Many factors determine empirical antibiotic treatment of community-acquired pneumonia (CAP). We aimed to describe the empirical antibiotic treatment CAP patients with an acute hospital visit and to determine if the current treatment algorithm provided specific and sufficient coverage against Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae (LMC). METHODS: A descriptive cross-sectional, multicenter study of all adults with an acute hospital visit in the Region of Southern Denmark between January 2016 and March 2018 was performed. Using medical records, we retrospectively identified the empirical antibiotic treatment and the microbiological etiology for CAP patients. CAP patients who were prescribed antibiotics within 24 h of admission and with an identified bacterial pathogen were included. The prescribed empirical antibiotic treatment and its ability to provide specific and sufficient coverage against LMC pneumonia were determined. RESULTS: Of the 19,133 patients diagnosed with CAP, 1590 (8.3%) patients were included in this study. Piperacillin-tazobactam and Beta-lactamase sensitive penicillins were the most commonly prescribed empirical treatments, 515 (32%) and 388 (24%), respectively. Our analysis showed that 42 (37%, 95% CI: 28-47%) of 113 patients with LMC pneumonia were prescribed antibiotics with LMC coverage, and 42 (12%, 95% CI: 8-15%) of 364 patients prescribed antibiotics with LMC coverage had LMC pneumonia. CONCLUSION: Piperacillin-tazobactam, a broad-spectrum antibiotic recommended for uncertain infectious focus, was the most frequent CAP treatment and prescribed to every third patient. In addition, the current empirical antibiotic treatment accuracy was low for LMC pneumonia. Therefore, future research should focus on faster diagnostic tools for identifying the infection focus and precise microbiological testing.
Assuntos
Infecções Comunitárias Adquiridas , Legionella pneumophila , Pneumonia , Humanos , Adulto , Mycoplasma pneumoniae , Estudos Transversais , Estudos Retrospectivos , Antibacterianos , Combinação Piperacilina e Tazobactam , Serviço Hospitalar de EmergênciaRESUMO
Background: Metagenomic next-generation sequencing (mNGS) is a powerful method for pathogen detection in various infections. In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of pneumonia in pediatric intensive care units (PICU) using bronchoalveolar lavage fluid (BALF) samples. Methods: A total of 104 pediatric patients with pneumonia who were admitted into PICU between June 2018 and February 2020 were retrospectively enrolled. Among them, 101 subjects who had intact clinical information were subject to parallel comparison of mNGS and conventional microbiological tests (CMTs) for pathogen detection. The performance was also evaluated and compared between BALF-mNGS and BALF-culture methods. Moreover, the diversity and structure of all 104 patients' lung BALF microbiomes were explored using the mNGS data. Results: Combining the findings of mNGS and CMTs, 94.06% (95/101) pneumonia cases showed evidence of causative pathogenic infections, including 79.21% (80/101) mixed and 14.85% (15/101) single infections. Regarding the pathogenesis of pneumonia in the PICU, the fungal detection rates were significantly higher in patients with immunodeficiency (55.56% vs. 25.30%, P =0.025) and comorbidities (40.30% vs. 11.76%, P=0.007). There were no significant differences in the α-diversity either between patients with CAP and HAP or between patients with and without immunodeficiency. Regarding the diagnostic performance, the detection rate of DNA-based BALF-mNGS was slightly higher than that of the BALF-culture although statistically insignificant (81.82% vs.77.92%, P=0.677) and was comparable to CMTs (81.82% vs. 89.61%, P=0.211). The overall sensitivity of DNA-based mNGS was 85.14% (95% confidence interval [CI]: 74.96%-92.34%). The detection rate of RNA-based BALF-mNGS was the same with CMTs (80.00% vs 80.00%, P>0.999) and higher than BALF-culture (80.00% vs 52.00%, P=0.045), with a sensitivity of 90.91% (95%CI: 70.84%-98.88%). Conclusions: mNGS is valuable in the etiological diagnosis of pneumonia, especially in fungal infections, and can reveal pulmonary microecological characteristics. For pneumonia patients in PICU, the mNGS should be implemented early and complementary to CMTs.
Assuntos
Microbiota , Pneumonia , Humanos , Criança , Líquido da Lavagem Broncoalveolar , Estudos Retrospectivos , Pneumonia/diagnóstico , Microbiota/genética , Sequenciamento de Nucleotídeos em Larga Escala , Unidades de Terapia Intensiva Pediátrica , PulmãoRESUMO
Background: The transcriptomic studies targeting circular RNAs (circRNAs) in bronchoalveolar lavage fluid (BALF) exosomes of acute respiratory distress syndrome (ARDS) patients caused by severe pneumonia have rarely been reported. This study aimed to screen and validate abnormally expressed circRNAs in exosomes from BALF of patients with ARDS caused by severe pneumonia and then evaluate the diagnostic values of these circRNAs for ARDS. Method: BALF was collected from four patients with ARDS caused by severe pneumonia and four healthy subjects. CircRNA expression profile was obtained by microarray analysis in BALF exosomes of the discovery cohort. The differentially expressed circRNAs in BALF exosomes were verified by real-time quantitative PCR (RT-qPCR) and underwent competitive endogenous RNA (ceRNA) network construction and functional enrichment analysis. Results: A total of 629 circRNAs were differentially expressed in BALF exosomes between ARDS patients and healthy subjects. Nine differentially expressed circRNAs were validated by RT-qPCR, and seven were consistent with the results of microarray analysis. CeRNA network analysis was performed for hsa_circRNA_002809, hsa_circRNA_042882, and hsa_circRNA_104034. Functional enrichment analysis showed that the target genes were mainly associated with hypoxia-induced damage, inflammatory response, and the HIF-1 signaling pathway. Hsa_circRNA_042882 and hsa_circRNA_104034 can be regarded as promising diagnostic biomarkers for patients with ARDS caused by severe pneumonia, with remarkable sensitivity and specificity of the area under the curve of 0.8050 and 1 or 0.835 and 0.799, respectively. Conclusion: This study obtained circRNA expression profiles of ARDS patients, and hsa_circRNA_042882 and hsa_circRNA_104034 were regarded as promising diagnostic biomarkers for patients with ARDS caused by severe pneumonia.
Assuntos
Exossomos , Pneumonia , Síndrome do Desconforto Respiratório , Humanos , RNA Circular , Líquido da Lavagem Broncoalveolar , Pneumonia/diagnóstico , Síndrome do Desconforto Respiratório/diagnóstico , BiomarcadoresRESUMO
The activation of the NLRP3 inflammasome pathway during infectious pathogen-induced immunopathology can lead to chronic inflammation and various adverse health outcomes. Identification of functional foods with anti-inflammatory properties is crucial for preventing inflammation triggered by NLRP3 inflammasome activation. This study aimed to investigate the anti-inflammatory properties of a proanthocyanidin-rich fraction obtained from red rice germ and bran against lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced condition in A549 lung cells. The proanthocyanidin-rich fraction from Yamuechaebia 3 red rice extract (YM3-PRF) was obtained using column chromatography with Sephadex LH20, and its total proanthocyanidin content was determined to be 351.43 ± 1.18 mg/g extract using the vanillin assay. A549 lung cells were pretreated with YM3-PRF at concentrations of 5-20 µg/mL prior to exposure to LPS (1 µg/mL) and ATP (5 nM). The results showed that YM3-PRF significantly inhibited the expression of inflammatory mRNAs (NLRP3, IL-6, IL-1ß, and IL-18) and the secretion of cytokines (IL-6, IL-1ß, and IL-18) in a dose-dependent manner (p < 0.05). Mechanistically, YM3-PRF exerted its anti-inflammatory effects by inhibiting NF-κB translocation and downregulating proteins associated with the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). These findings suggest that the proanthocyanidin-rich fraction from red rice germ and bran has protective effects and may serve as a potential therapeutic option for chronic inflammatory diseases associated with NLRP3 inflammasome activation.
Assuntos
Oryza , Pneumonia , Proantocianidinas , NF-kappa B , Inflamassomos , Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Interleucina-6 , Lipopolissacarídeos , Proantocianidinas/farmacologia , Inflamação , Alimento Funcional , Trifosfato de Adenosina , Pulmão , Extratos Vegetais/farmacologiaRESUMO
PURPOSE: Investigate the association between the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) about the presence of postoperative pneumonia (POP) in geriatric patients with hip fractures. Compare the predictive value of these biomarkers for POP and assess their potential for early detection of POP. METHODS: We retrospectively included elderly patients with hip fractures who underwent surgical treatment at our institution. POP was diagnosed according to the guidelines provided by the American Thoracic Society. We collected neutrophil, lymphocyte, and platelet counts upon admission to calculate the NLR, PLR, and SII. Receiver operating characteristic curves were utilized to establish the optimal cutoff values for each index. Multivariate logistic regression analysis and propensity score matching analysis were utilized to assess the independent association between each index and POP after adjusting for demographic, comorbidity, and surgery-related variables. RESULTS: The study included a total of 1199 patients, among whom 111 cases (9.26%) developed POP. NLR exhibited the highest predictive value for POP in elderly patients with hip fractures compared to PLR and SII (AUC = 0.648, 95% CI 0.594-0.701). A high NLR, using the optimal cutoff value of 5.84, was significantly associated with an increased incidence of POP (OR = 2.24, 95% CI 1.43-3.51). This finding remained statistically significant even after propensity score matching (OR = 2.04, 95% CI 1.31-3.20). CONCLUSIONS: Among the three inflammatory/immune markers considered, the NLR demonstrates the highest reliability as a predictor for POP in elderly patients with hip fractures. Therefore, it serves as a valuable tool for early identification.
Assuntos
Fraturas do Quadril , Pneumonia , Idoso , Humanos , Neutrófilos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fraturas do Quadril/cirurgia , Inflamação/diagnóstico , Pneumonia/diagnóstico , Pneumonia/etiologia , LinfócitosRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonia remains a major public health concern. Vital sign indices-shock index (SI; heart rate [HR]/systolic blood pressure [SBP]), shock index age (SIA, SI × age), MinPulse (MP; maximum HR-HR), Pulse max index (PMI; HR/maximum HR), and blood pressure-age index (BPAI; SBP/age)-are better predictors of mortality in patients with trauma compared to traditional vital signs. We hypothesized that these vital sign indices may serve as predictors of mortality in patients with severe COVID-19 pneumonia. This study aimed to describe the association between vital sign indices at admission and COVID-19 pneumonia mortality and to modify the CURB-65 with the best performing vital sign index to establish a new mortality prediction tool. METHODS: This retrospective study was conducted at a tertiary care center in southern Thailand. Adult patients diagnosed with COVID-19 pneumonia were enrolled in this study between January 2020 and July 2022. Patient demographic and clinical data on admission were collected from an electronic database. The area under the receiver operating characteristic (AUC) curve analysis was used to assess the predictive power of the resultant multivariable logistic regression model after univariate and multivariate analyses of variables with identified associations with in-hospital mortality. RESULTS: In total, 251 patients with COVID-19 pneumonia were enrolled in this study. The in-hospital mortality rate was 27.9%. Non-survivors had significantly higher HR, respiratory rate, SIA, and PMI and lower MP and BPAI than survivors. A cutoff value of 51 for SIA (AUC, 0.663; specificity, 80%) was used to predict mortality. When SIA was introduced as a modifier for the CURB-65 score, the new score (the CURSIA score) showed a higher AUC than the Acute Physiology and Chronic Health Evaluation II and CURB-65 scores (AUCs: 0.785, 0.780, and 0.774, respectively) without statistical significance. CONCLUSIONS: SIA and CURSIA scores were significantly associated with COVID-19 pneumonia mortality. These scores may contribute to better patient triage than traditional vital signs.
Assuntos
COVID-19 , Pneumonia , Adulto , Humanos , Estudos Retrospectivos , Mortalidade Hospitalar , APACHERESUMO
BACKGROUND: Double lumen tube (DLT) and single lumen tube (SLT) are two common endotracheal tube (ETT) types in esophageal cancer surgery. Evidence of the relationship between two ETT types and postoperative pneumonia (PP) remains unclear. We aimed to determine the association between two types of ETT (DLT and SLT) and PP and assess the perioperative risk-related parameters that affect PP. METHODS: This study included 680 patients who underwent esophageal cancer surgery from January 01, 2010 through December 31, 2020. The primary outcome was PP, and the secondary outcome was perioperative risk-related parameters that affect PP. The independent variable was the type of ETT: DLT or SLT. The dependent variable was PP. To determine the relationship between variables and PP, univariate and multivariate analyses were performed. The covariables included baseline demographic characteristics, comorbidity disease, neoadjuvant chemotherapy, tumor location, laboratory parameters, intraoperative related variables. RESULTS: In all patients, the incidence of postoperative pneumonia in esophagectomy was 32.77% (36.90% in DLT group and 26.38% in SLT group). After adjusting for potential risk factors, we found that using an SLT in esophagectomy was associated with lower risk of postoperative pneumonia compared to using a DLT (Odd ratio = 0.41, 95% confidence interval (CI): 0.22, 0.77, p = 0.0057). Besides DLT, smoking history, combined intravenous and inhalation anesthesia (CIIA) and vasoactive drug use were all significant and independent risk factors for postoperative pneumonia in esophagectomy. These results remained stable and reliable after subgroup analysis. CONCLUSIONS: During esophagectomy, there is significant association between the type of ETT (DLT or SLT) and PP. Patients who were intubated with a single lumen tube may have a lower rate of postoperative pneumonia than those who were intubated with a double lumen tube. This finding requires verification in follow-up studies.
Assuntos
Neoplasias Esofágicas , Pneumonia , Humanos , Esofagectomia , Estudos Retrospectivos , ChinaRESUMO
Due to the increase in bacterial resistance, improving the anti-infectious immunity of the host is rapidly becoming a new strategy for the prevention and treatment of bacterial pneumonia. However, the specific lung immune responses and key immune cell subsets involved in bacterial infection are obscure. Actinobacillus pleuropneumoniae (APP) can cause porcine pleuropneumonia, a highly contagious respiratory disease that has caused severe economic losses in the swine industry. Here, using high-dimensional mass cytometry, the major immune cell repertoire in the lungs of mice with APP infection was profiled. Various phenotypically distinct neutrophil subsets and Ly-6C+ inflammatory monocytes/macrophages accumulated post-infection. Moreover, a linear differentiation trajectory from inactivated to activated to apoptotic neutrophils corresponded with the stages of uninfected, onset, and recovery of APP infection. CD14+ neutrophils, which mainly increased in number during the recovery stage of infection, were revealed to have a stronger ability to produce cytokines, especially IL-10 and IL-21, than their CD14- counterparts. Importantly, MHC-II+ neutrophils with antigen-presenting cell features were identified, and their numbers increased in the lung after APP infection. Similar results were further confirmed in the lungs of piglets infected with APP and Klebsiella pneumoniae infection by using a single-cell RNA-seq technique. Additionally, a correlation analysis between cluster composition and the infection process yielded a dynamic and temporally associated immune landscape where key immune clusters, including previously unrecognized ones, marked various stages of infection. Thus, these results reveal the characteristics of key neutrophil clusters and provide a detailed understanding of the immune response to bacterial pneumonia.
Assuntos
Infecções por Actinobacillus , Actinobacillus pleuropneumoniae , Ascomicetos , Infecções por Mycoplasma , Pleuropneumonia , Pneumonia , Doenças dos Roedores , Doenças dos Suínos , Animais , Camundongos , Suínos , Neutrófilos , Pneumonia/veterinária , Pleuropneumonia/veterinária , Infecções por Mycoplasma/veterinária , Infecções por Actinobacillus/veterinária , PulmãoRESUMO
In China, the emergence of a nationally widespread epidemic infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has appeared within a month since December 7, 2022. To evaluate the risk factors for suffering from coronavirus disease 2019 (COVID-19) pneumonia due to infection with SARS-CoV-2 in different kinds of interstitial lung disease (ILD) patients with diverse immunizations, we conducted this retrospective study on 525 patients with ILDs who underwent regular follow-up in our ILD clinic. Among them, 128 ILD patients (24.4%) suffered from COVID-19 pneumonia after SARS-CoV-2 infection. Patients were older with a male predominance in the pneumonia group than in the nonpneumonia group (65.0 ± 10.0 years vs. 56.4 ± 11.7 years, p < 0.001, 55.5% vs. 39.5%, p = 0.002, respectively). Connective tissue disease-associated ILD (CTD-ILD) (25%), idiopathic pulmonary fibrosis (23.4%), and interstitial pneumonia with autoimmune features (21.1%) were the main pre-existing ILDs in the pneumonia group. In Cox multivariable analysis, only male sex and corticosteroid use were risk factors for COVID-19 pneumonia after infection. Two or three doses of vaccination were a protective factor for pre-existing ILD patients suffering from COVID-19 pneumonia. More than two doses of vaccination were strongly recommended for pre-existing ILD patients, particularly for males who were administered corticosteroids.
Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Pneumonia , Feminino , Humanos , Masculino , COVID-19/complicações , COVID-19/epidemiologia , População do Leste Asiático , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/epidemiologia , Pandemias , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: In immunocompromised populations, such as patients with AIDS and recipients of solid organ and hematopoietic stem cell transplants, BK polyomavirus (BKPyV) can reactivate and cause several diseases, which can lead to death in their severe forms. Unlike hemorrhagic cystitis and BKPyV-associated nephropathy, BKPyV-associated pneumonia is rare, with only seven known cases worldwide. However, the disease can rapidly progress with extremely high mortality. CASE PRESENTATION: Herein, we report two cases of BKPyV-associated pneumonia following hematopoietic stem cell transplantation. Both patients had consistent infectious pneumonia and graft-versus-host disease after stem cell transplantation. The diagnosis of BKPyV-associated pneumonia was confirmed by metagenomic next-generation sequencing and polymerase chain reaction after the sudden worsening of the pulmonary infection signs and symptoms concomitant with renal dysfunction and systemic immune weakening. Both patients eventually died of systemic multi-organ failure caused by severe pneumonia. CONCLUSIONS: Currently, BKPyV reactivation cannot be effectively prevented. Immunocompromised patients must actively manage their primary lung infections, pay close attention to pulmonary signs and imaging changes. Especially during and after steroid pulse therapy or immunosuppressive therapy for graft versus host diseases, BKPyV load in blood/urine needs to be regularly measured, and the immunosuppressive intensity should be adjusted properly after the BKPyV reactivation diagnosis. Clinical trials of new antiviral drugs and therapies for BKPyV are urgently needed.
Assuntos
Vírus BK , Cistite , Pneumonia , Humanos , Vírus BK/genética , Antivirais , Frequência CardíacaRESUMO
BACKGROUND: Pneumonia is a respiratory infection with an increasing incidence with age. However, limited evidence has identified factors associated with its outcome among different age groups, especially in the elderly and in the emergency department (ED) setting. We aimed to identify clinical factors associated with in-hospital mortality in elderly versus non-elderly pneumonia patients in the ED. METHODS: A retrospective observational study was conducted at the ED of Siriraj Hospital, Thailand. Patients aged at least 18 years old diagnosed with non-COVID pneumonia between June 1, 2021, and May 31, 2022, were included. They were categorized into the elderly (age ≥ 65 years) and non-elderly (age < 65 years) groups. The primary outcome was in-hospital mortality. We employed multivariate logistic regression models to identify independent factors associated with the outcome in each age group. RESULTS: We enrolled 735 patients, 515 elderly and 222 non-elderly. There was no difference in in-hospital mortality rate between the two groups (39.0% in the elderly and 32.9% in the non-elderly; p = 0.116). In the elderly cohort, independent factors associated with in-hospital mortality were do-not-resuscitate (DNR) status (adjusted odds ratio (aOR) 12.89; 95% confidence interval (CI) 7.19-23.1; p < 0.001), Glasgow Coma Scale (GCS) score (aOR 0.91; 95%CI 0.85-0.96; p = 0.002), hemoglobin level (aOR 0.9; 95%CI 0.82-0.98; p = 0.012) and the type of initial oxygen support (p = 0.05). Among non-elderly patients, independent factors were DNR status (aOR 6.81; 95%CI 3.18-14.59; p < 0.001), GCS score (aOR 0.89; 95%CI 0.8-0.99; p = 0.025), platelet level (aOR 1; 95%CI 1-1; p = 0.038), Charlson Comorbidity Index (CCI) (aOR 1.12; 95%CI 0.99-1.28; p = 0.078), and the type of initial oxygen support p = 0.079). CONCLUSION: In pneumonia patients presenting to the ED, DNR status, lower GCS score, and more invasive initial oxygen supplementation were independently associated with in-hospital mortality in both elderly and non-elderly groups. However, lower hemoglobin level was only associated with in-hospital mortality in the elderly, while higher CCI and lower platelet count were independent factors only in the non-elderly. These findings emphasize the importance of age-specific considerations for the disease, and these factors are potential prognostic markers that may be used in clinical practice to improve patient outcomes.
Assuntos
Pneumonia , Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Mortalidade Hospitalar , Oxigênio , Serviço Hospitalar de Emergência , HemoglobinasRESUMO
BACKGROUND: Chlamydia psittaci (C. psittaci) causes parrot fever in humans. Development of metagenomic next-generation sequencing (mNGS) enables the identification of C. psittaci. METHODS: This study aimed to determine the epidemiological and clinical characteristics of parrot fever cases in China. A multi-center observational study was conducted in 44 tertiary and secondary hospitals across 14 provinces and municipalities between April 2019 and October 2021. RESULTS: A total of 4545 patients with complicated or atypical pulmonary infection were included in the study, among which the prevalence of C. psittaci was determined to be 2.1% using mNGS. The prevalence of C. psittaci was further determined across demographic groups and types of specimens. It was significantly higher in patients with senior age (2.6% in those > 50 years), winter-spring (3.6%; particularly in December, January, and February), and southwestern (3.4%) and central and southern China (2.7%) (each P < 0.001). Moreover, the prevalence was the highest in bronchoalveolar lavage fluid (BALF) (2.9%), compared with sputum (1.1%) and peripheral blood specimens (0.9%). Additionally, co-infection of principal microorganisms was compared. Certain microorganisms were more likely to co-infect in parrot fever cases, such as Candida albicans in BALF (26.7%) and peripheral blood (6.3%), compared with non-parrot fever cases (19.7% and 1.3%); however, they did not significantly differ (each P > 0.05). CONCLUSION: Parrot fever remains low in patients with complicated or atypical pulmonary infection. It is likely to occur in winter-spring and southwestern region in China. BALF may be the optimal specimen in the application of mNGS. Co-infection of multiple microorganisms should be further considered.
Assuntos
Coinfecção , Pneumonia , Psitacose , Humanos , Pessoa de Meia-Idade , Psitacose/diagnóstico , Psitacose/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala , Candida albicans , China/epidemiologia , Pneumonia/epidemiologiaRESUMO
Immune checkpoint inhibitors (ICIs) play a significant antitumor role in the management of nonsmall cell lung cancer. The most broadly used ICIs are antiprogrammed death 1 (PD1), antiprogrammed cell deathligand 1, and anticytotoxic T lymphocyteassociated antigen4 monoclonal antibody. Compared with traditional chemotherapy, ICIs have the advantages of greater efficiency and more specific targeting. However, the resulting immunerelated adverse events limit the clinical application of ICIs, especially checkpoint inhibitor pneumonitis (CIP). CIP chiefly occurs within 6 months of administration of ICIs. Excessive activation and amplification of cytotoxic T lymphocytes, helper T cells, downregulation of regulatory T cells, and oversecretion of proinflammatory cytokines are the dominant mechanisms underlying the pathophysiology of CIP. The dysregulation of innate immune cells, such as an increase in inflammatory monocytes, dendritic cells, neutrophils and M1 polarization of macrophages, an increase in IL10 and IL35, and a decrease in eosinophils, may underlie CIP. Although contested, several factors may accelerate CIP, such as a history of previous respiratory disease, radiotherapy, chemotherapy, administration of epidermal growth factor receptor tyrosine kinase inhibitors, PD1 blockers, firstline application of ICIs, and combined immunotherapy. Interestingly, firstline ICIs plus chemotherapy may reduce CIP. Steroid hormones remain the primary treatment strategy against grade ≥2 CIP, although cytokine blockers are promising therapeutic agents. Herein, the current research on CIP occurrence, clinical and radiological characteristics, pathogenesis, risk factors, and management is summarized to further expand our understanding, clarify the prognosis, and guide treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Antígeno B7-H1 , Neoplasias Pulmonares/tratamento farmacológico , Fatores de Risco , CitocinasRESUMO
Stroke patients may have dysphagia and frequent aspiration increasing exposure to antibiotics and the chance of multidrug-resistant (MDR) bacteria infection. This study investigated clinical risk factors and related antibiotic use of MDR bacteria infection in stroke patients in the rehabilitation ward, hoping that it can help prevent and reduce the condition of MDR bacteria. A retrospective cohort study was conducted using the database of stroke patients with pneumonia admitted to the rehabilitation ward from January 1, 2020, to June 30, 2022. The selected stroke patients were divided into the MDR and non-MDR groups. Analyze the infection bacteria of the 2 groups. Forward logistic regression was applied to identify possible independent MDR bacteria infection risk factors. A total of 323 patients were included. The top 3 common MDR pathogens were Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Almost all Pseudomonas aeruginosa and Acinetobacter baumannii are resistant to ertapenem. National Institute of Health stroke scale at admission was associated with MDR bacteria infection pneumonia (OR [odds ratio] = 1.078, 95%CI [1.017, 1.142]). Long-term tracheotomy (OR = 2.695, 95%CI [1.232, 5.897]), hypoalbuminemia (OR = 473, 95%CI [1.318, 4.642]), and bilateral cerebral hemisphere stroke (OR = 4.021, 95%CI [2.009, 8.048]) were significant clinical risk factors of MDR pneumonia after stroke. The detection rate of MDR bacteria has increased. Understanding the distribution and drug resistance of MDR bacteria in stroke patients with pneumonia in the neurological rehabilitation ward and the related susceptibility of MDR bacteria infection is necessary. This way, the treatment plan can be adjusted more timely, avoiding the abuse of antibiotics.
