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2.
Rev. esp. quimioter ; 37(2): 1-15, abr. 2024.
Artigo em Inglês | IBECS | ID: ibc-ADZ-256

RESUMO

Respiratory syncytial virus (RSV) is a major public health problem that has undergone significant changes in recent years. First of all, it has become easier to diagnose with highly reliable and rapidly available confirmatory tests. This has led to a better understanding of its epidemiology and RSV has gone from being a disease of the pediatric age group, severe only in infants and immunosuppressed children, to being a common disease in people of all ages, particularly important in patients of advanced age or with immunosuppressive diseases. Recent therapeutic and prophylactic advances, both with long-lasting monoclonal antibodies and vaccines, are another reason for satisfaction. For these reasons, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has considered it pertinent to review this subject in the light of new knowledge and new resources for dealing with this infection. We have formulated a series of questions that we believe will be of interest not only to members of the College but also to any non-expert in this subject, with a particular focus on the situation of RSV infection in Spain. (AU)


El Virus Respiratorio Sincitial (VRS), es un problema de salud pública de primera magnitud que en años recientes ha experimentado cambios muy importantes. En primer lugar, se ha producido una mayor facilidad diagnóstica con pruebas confirmatorias altamente fiables y rápidamente disponibles. Esto ha permitido conocer mejor su epidemiología y VRS ha pasado de ser una enfermedad de la edad pediátrica, grave sólo en lactantes y niños inmunodeprimidos, a ser una enfermedad común en personas de toda edad, particularmente importante en pacientes de edades avanzadas o con enfermedades que inmunodeprimen. Los avances terapéuticos y profilácticos, recientes, tanto con anticuerpos monoclonales de larga duración como con vacunas, constituyen otro motivo de satisfacción. Por estos motivos, el Comité de COVID y de patógenos emergentes del Ilustre Colegio Oficial de Médicos de Madrid (ICOMEM) ha considerado pertinente revisar este tema, a la luz de los nuevos conocimientos y de los nuevos recursos para afrontar esta infección. Hemos formulado una serie de preguntas que creemos de interés no sólo para los colegiados si no para cualquier persona no experta en este tema, con una vista particular en la situación de la infección por VRS en España. (AU)


Assuntos
Humanos , Vírus , Pneumonia , Vacinas , Anticorpos Monoclonais , Ribavirina , Anticorpos , Hospedeiro Imunocomprometido , Espanha
3.
Sci Rep ; 14(1): 5095, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429374

RESUMO

The clinical application of conventional doxorubicin (CDOX) was constrained by its side effects. Liposomal doxorubicin was developed to mitigate these limitations, showing improved toxicity profiles. However, the adverse events associated with liposomal doxorubicin and CDOX have not yet been comprehensively evaluated in clinical settings. The FAERS data from January 2004 to December 2022 were collected to analyze the adverse events of liposomal doxorubicin and CDOX. Disproportionate analysis and Bayesian analysis were employed to quantify this association. Our analysis incorporated 68,803 adverse event reports related to Doxil/Caelyx, Myocet and CDOX. The relative odds ratios (RORs, 95%CI) for febrile neutropenia associated with CDOX, Doxil/Caelyx, and Myocet were 42.45 (41.44; 43.48), 17.53 (16.02; 19.20), and 34.68 (26.63; 45.15) respectively. For cardiotoxicity, they were 38.87(36.41;41.49), 17.96 (14.10; 22.86), and 37.36 (19.34; 72.17). For Palmar-Plantar Erythrodysesthesia (PPE), the RORs were 6.16 (5.69; 6.68), 36.13 (32.60; 40.06), and 19.69 (11.59; 33.44). Regarding onset time, significant differences adverse events including neutropenia, PPE, pneumonia and malignant neoplasm progression. This study indicates that clinical monitoring for symptoms of cardiotoxicity of CDOX and Myocet, and PPE and interstitial lung disease of Doxil should be performed. Additionally, the onset time of febrile neutropenia, malignant neoplasm progression, and pneumonia associated with Doxil and Myocet merits particular attention. Continuous surveillance, risk evaluations, and additional comparative studies between liposomal doxorubicin and CDOX were recommended.


Assuntos
Doxorrubicina/análogos & derivados , Neoplasias , Neutropenia , Pneumonia , Humanos , Cardiotoxicidade/tratamento farmacológico , Teorema de Bayes , Doxorrubicina/efeitos adversos , Lipossomos , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Pneumonia/tratamento farmacológico , Polietilenoglicóis
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 1-10, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38433624

RESUMO

Objective To investigate the impact of Pseudomonas aeruginosa(PA) infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice. Methods Two hours after human lung microvascular endothelial cell(HULEC-5a) were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5) were determined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin) were detected by immunofluorescence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through histopathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells. Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P<0.05),down-regulated mRNA level of CDH5(P=0.023),disrupted continuity and down-regulated protein level of VE-cadherin(P<0.001),and elevated lactate level(P=0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5(P=0.043),lowered lactate level(P=0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3(P=0.013 and P=0.003),elevated lactate level(P=0.015),and down-regulated mRNA level of CDH5(P=0.020) and protein level of VE-cadherin(P=0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascular endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expression of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice. Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmonary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.


Assuntos
Pneumonia , Infecções por Pseudomonas , Humanos , Animais , Camundongos , Células Endoteliais , Pseudomonas aeruginosa , Cálcio , Fatores de Transcrição , Pulmão , Lactatos , RNA Mensageiro
5.
PeerJ ; 12: e16997, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435993

RESUMO

Background: Although head elevation is an early first-line treatment for elevated intracranial pressure (ICP), the use of the head-down or prone position in managing neurocritical patients is controversial because a change in a position directly affects the intracranial and cerebral perfusion pressure, which may cause secondary brain injury and affect patient outcomes. This study compared the effects of two postural drainage positions (30° head-up tilt and 0° head flat) on the prognosis of neurocritical care patients with complicated pneumonia and a clinical pulmonary infection score (CPIS) ≥5 points to provide a reference for selecting appropriate postural drainage positions for patients with pneumonia in neurocritical care units. Methods: A prospective randomized controlled study was conducted with 62 neurocritical care patients with complicated pneumonia. The patients were categorized into control (=31) and experimental (=31) groups in a 1:1 ratio using a simple randomized non-homologous pairing method. Emphasis was placed on matching the baseline characteristics of the two groups, including patient age, sex, height, weight, Glasgow Coma Scale score, heart rate, mean arterial pressure, cough reflex, and mechanical ventilation usage to ensure comparability. Both groups received bundled care for artificial airway management. The control group maintained a standard postural drainage position of 0° head-flat, whereas the experimental group maintained a 30° head-up tilt. The efficacy of the nursing intervention was evaluated by comparing the CPIS and other therapeutic indicators between the two groups after postural drainage. Results: After the intervention, the within-group comparison showed a significant decrease in the CPIS (P < 0.001); procalcitonin levels showed a significant decreasing trend (P < 0.05); the arterial oxygen pressure significantly increased (P < 0.05); the oxygenation index significantly increased (P < 0.001); and the aspiration risk score showed a significant decreasing trend (P < 0.001). A between-group comparison showed no significant differences in any of the indicators before and after the intervention (P < 0.05). Conclusion: Postural drainage positions of 30° head-up tilt and 0° head-flat can improve the CPIS and oxygenation in patients without adverse effects. Therefore, we recommend that patients under neurological intensive care and having pneumonia be drained in a 30° head-up tilt position with good centralized care of the lung infection. Trial registration: The study, "Study of Angles of Postural Drainage in Neurocritical Patients with Pneumonia," was registered in the Protocol Registration Data Element Definitions for Interventional Study database (# ChiCTR2100042155); date of registration: 2021-01-14.


Assuntos
Pneumonia , Humanos , Estudos Prospectivos , Pneumonia/complicações , Drenagem Postural , Oxigênio , Manuseio das Vias Aéreas
7.
PLoS One ; 19(3): e0297159, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38466696

RESUMO

INTRODUCTION: In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model. METHODS: PERCH enrolled a cohort of 2189 HIV-negative children aged 2-59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011-2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2. RESULTS: Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99-5·99), HIV negative but exposed status (4·59, 1·81-11·7), moderate or severe malnutrition (6·85, 3·22-14·6) and younger age (infants compared to children 12-59 months old, OR 2·03, 95%CI 1·05-3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76). CONCLUSIONS: Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community.


Assuntos
Infecções por HIV , Desnutrição , Pneumonia , Lactente , Criança , Humanos , Pré-Escolar , Pneumonia/epidemiologia , Hospitalização , Desnutrição/complicações , Infecções por HIV/complicações , Hipóxia/etiologia
8.
J Healthc Manag ; 69(2): 118-131, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467025

RESUMO

GOAL: Patients engaged in self-care through information technology can potentially improve the quality of healthcare they receive. This study aimed to examine how electronic health record (EHR) system functionalities help hospitals mediate the impact of patient engagement on quality outcomes-notably, readmission rates. METHODS: A pooled cross-sectional study design employed data containing 3,547 observations from general acute care hospitals (2014-2018). The breadth of patient engagement functionalities adopted by a hospital was used as the independent variable and the degree of EHR presence was used as the mediating variable. Mean time to readmission for acute myocardial infarction (AMI), pneumonia, and heart failure were the dependent variables. The Baron and Kenny method was used to test mediation. PRINCIPAL FINDINGS: Patient engagement was associated with reduced AMI readmission rates both directly and via EHR system presence. Mediation effects were present, in that a 1-unit increase in patient engagement through EHR system presence was associated with a 0.33% decrease in AMI readmission rates (p < .05). For other disease categories (heart failure and pneumonia), a significant effect was not found. PRACTICAL APPLICATIONS: For hospitals with a comprehensive EHR system, patient engagement through information technology can potentially reduce readmission rates for some diseases. More research is needed to determine which specific clinical conditions are amenable to quality improvement through patient engagement. Synergies between patient engagement functionalities and an EHR system positively affect quality outcomes. Therefore, practitioners and hospital managers should leverage hospital investments made in their EHR system infrastructure and use it to engage patients in self-care.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Pneumonia , Humanos , Estados Unidos , Participação do Paciente , Estudos Transversais , Hospitais , Infarto do Miocárdio/terapia , Insuficiência Cardíaca/terapia , Pneumonia/terapia , Readmissão do Paciente , Registros Eletrônicos de Saúde
10.
Artigo em Inglês | MEDLINE | ID: mdl-38468632

RESUMO

Purpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is closely related to respiratory tract infection. The aim of this study was to investigate the clinical features and prognostic factors of CRKP-induced pneumonia in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. Methods: A single-centre, retrospective case-control study on COPD patients hospitalized for acute exacerbation and CRKP-induced pneumonia was conducted from January 1, 2016, to December 31, 2022. The mortality rate of acute exacerbation due to CRKP-induced pneumonia was investigated. The patients were divided into the CRKP-induced pneumonic acute exacerbation (CRKPpAE) group and the non-CRKP-induced pneumonic acute exacerbation (non-CRKPpAE) group, and the clinical characteristics and prognostic factors were compared using univariate analysis and multivariate analysis. Results: A total of 65 AECOPD patients were included, composed of 26 patients with CRKPpAE and 39 patients with non-CRKPpAE. The mortality rate of CRKPpAE was 57.69%, while non-CRKPpAE was 7.69%. Compared with non-CRKPpAE, a history of acute exacerbation in the last year (OR=8.860, 95% CI: 1.360-57.722, p=0.023), ICU admission (OR=11.736, 95% CI: 2.112-65.207, p=0.005), higher NLR levels (OR=1.187, 95% CI: 1.037-1.359, p=0.013) and higher D-dimer levels (OR=1.385, 95% CI: 1.006-1.905, p=0.046) were independently related with CRKPpAE. CRKP isolates were all MDR strains (26/26, 100%), and MDR strains were also observed in non-CRKP isolates (5/39, 12.82%). Conclusion: Compared with non-CRKPpAE, CRKPpAE affects the COPD patient's condition more seriously and significantly increases the risk of death.


Assuntos
Infecções por Klebsiella , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Klebsiella pneumoniae , Estudos Retrospectivos , Estudos de Casos e Controles , Antibacterianos/uso terapêutico , Klebsiella , Prognóstico , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pneumonia/tratamento farmacológico , Fatores de Risco , Farmacorresistência Bacteriana
11.
Ann Ital Chir ; 95(1): 64-69, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469614

RESUMO

OBJECTIVE: To investigate the relationship between the duration of surgery for thoracoscopic lobectomy and postoperative complications in patients with stage I non-small cell lung cancer (NSCLC). METHODS: The clinical data of patients who underwent thoracoscopic lobectomy in the Department of Cardiothoracic Surgery, Shaoxing Central Hospital from September 2018 to September 2023 were retrospectively analyzed. RESULTS: A total of 263 patients with thoracoscopic lobectomy were enrolled in this study. The duration of surgery was longer for patients with postoperative hospital stay >7 days, atrial fibrillation, postoperative pulmonary air leakage (>5 days), pleural effusion, or pneumonia compared to patients without corresponding complications, and the differences were statistically significant. Further regression analysis showed that prolonged duration of surgery was a risk factor for pneumonia, pleural effusion, atrial fibrillation, and postoperative hospital stay >7 days, and the predictive value of prolonged duration of surgery for the above complications was moderate. The results of chi-square tests showed that pneumonia, atelectasis, urinary tract infection, liver dysfunction, postoperative pulmonary air leakage (>5 days), pleural effusion, and atrial fibrillation were associated with postoperative hospital stay >7 days. CONCLUSION: Prolonged duration of surgery is a risk factor for complications such as pneumonia, pleural effusion, atrial fibrillation, and postoperative hospital stay >7 days.


Assuntos
Fibrilação Atrial , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Derrame Pleural , Pneumonia , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/métodos , Pneumonectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Tempo de Internação , Pneumonia/etiologia , Pneumonia/complicações , Derrame Pleural/epidemiologia , Derrame Pleural/etiologia
12.
Cell Mol Life Sci ; 81(1): 124, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466420

RESUMO

Acute lung injury (ALI) is an inflammatory disease associated with alveolar injury, subsequent macrophage activation, inflammatory cell infiltration, and cytokine production. Mesenchymal stem cells (MSCs) are beneficial for application in the treatment of inflammatory diseases due to their immunomodulatory effects. However, the mechanisms of regulatory effects by MSCs on macrophages in ALI need more in-depth study. Lung tissues were collected from mice for mouse lung organoid construction. Alveolar macrophages (AMs) derived from bronchoalveolar lavage and interstitial macrophages (IMs) derived from lung tissue were co-cultured, with novel matrigel-spreading lung organoids to construct an in vitro model of lung organoids-immune cells. Mouse compact bone-derived MSCs were co-cultured with organoids-macrophages to confirm their therapeutic effect on acute lung injury. Changes in transcriptome expression profile were analyzed by RNA sequencing. Well-established lung organoids expressed various lung cell type-specific markers. Lung organoids grown on spreading matrigel had the property of functional cells growing outside the lumen. Lipopolysaccharide (LPS)-induced injury promoted macrophage chemotaxis toward lung organoids and enhanced the expression of inflammation-associated genes in inflammation-injured lung organoids-macrophages compared with controls. Treatment with MSCs inhibited the injury progress and reduced the levels of inflammatory components. Furthermore, through the nuclear factor-κB pathway, MSC treatment inhibited inflammatory and phenotypic transformation of AMs and modulated the antigen-presenting function of IMs, thereby affecting the inflammatory phenotype of lung organoids. Lung organoids grown by spreading matrigel facilitate the reception of external stimuli and the construction of in vitro models containing immune cells, which is a potential novel model for disease research. MSCs exert protective effects against lung injury by regulating different functions of AMs and IMs in the lung, indicating a potential mechanism for therapeutic intervention.


Assuntos
Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Pneumonia , Camundongos , Animais , Macrófagos Alveolares/metabolismo , Lipopolissacarídeos/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/terapia , Pulmão/metabolismo , Macrófagos/metabolismo , Modelos Animais de Doenças , Inflamação/terapia , Inflamação/metabolismo , Organoides/metabolismo
13.
Front Immunol ; 15: 1302489, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476229

RESUMO

Background: Pre-neutrophils, while developing in the bone marrow, transcribe the Inhba gene and synthesize Activin-A protein, which they store and release at the earliest stage of their activation in the periphery. However, the role of neutrophil-derived Activin-A is not completely understood. Methods: To address this issue, we developed a neutrophil-specific Activin-A-deficient animal model (S100a8-Cre/Inhba fl/fl mice) and analyzed the immune response to Influenza A virus (IAV) infection. More specifically, evaluation of body weight and lung mechanics, molecular and cellular analyses of bronchoalveolar lavage fluids, flow cytometry and cell sorting of lung cells, as well as histopathological analysis of lung tissues, were performed in PBS-treated and IAV-infected transgenic animals. Results: We found that neutrophil-specific Activin-A deficiency led to exacerbated pulmonary inflammation and widespread hemorrhagic histopathology in the lungs of IAV-infected animals that was associated with an exuberant production of neutrophil extracellular traps (NETs). Moreover, deletion of the Activin-A receptor ALK4/ACVR1B in neutrophils exacerbated IAV-induced pathology as well, suggesting that neutrophils themselves are potential targets of Activin-A-mediated signaling. The pro-NETotic tendency of Activin-A-deficient neutrophils was further verified in the context of thioglycollate-induced peritonitis, a model characterized by robust peritoneal neutrophilia. Of importance, transcriptome analysis of Activin-A-deficient neutrophils revealed alterations consistent with a predisposition for NET release. Conclusion: Collectively, our data demonstrate that Activin-A, secreted by neutrophils upon their activation in the periphery, acts as a feedback mechanism to moderate their pro-NETotic tendency and limit the collateral tissue damage caused by neutrophil excess activation during the inflammatory response.


Assuntos
Vírus da Influenza A , Influenza Humana , Pneumonia , Animais , Camundongos , Humanos , Neutrófilos , Pulmão/patologia , Pneumonia/metabolismo , Influenza Humana/patologia , Ativinas/metabolismo
15.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473724

RESUMO

Although the SARS-CoV-2 vaccination is the primary preventive intervention, there are still few antiviral therapies available, with current drugs decreasing viral replication once the virus is intracellular. Adding novel drugs to target additional points in the viral life cycle is paramount in preventing future pandemics. The purpose of this study was to create and test a novel protein to decrease SARS-CoV-2 replication. We created the recombinant rod domain of vimentin (rhRod) in E. coli and used biolayer interferometry to measure its affinity to the SARS-CoV-2 S1S2 spike protein and the ability to block the SARS-CoV-2-ACE2 interaction. We performed plaque assays to measure rhRod's effect on SARS-CoV-2 replication in Vero E6 cells. Finally, we measured lung inflammation in SARS-CoV-2-exposed K18-hACE transgenic mice given intranasal and intraperitoneal rhRod. We found that rhRod has a high affinity for the S1S2 protein with a strong ability to block S1S2-ACE2 interactions. The daily addition of rhRod decreased viral replication in Vero E6 cells starting at 48 h at concentrations >1 µM. Finally, SARS-CoV-2-infected mice receiving rhRod had decreased lung inflammation compared to mock-treated animals. Based on our data, rhRod decreases SARS-CoV-2 replication in vitro and lung inflammation in vivo. Future studies will need to evaluate the protective effects of rhRod against additional viral variants and identify the optimal dosing scheme that both prevents viral replication and host lung injury.


Assuntos
COVID-19 , Pneumonia , Humanos , Camundongos , Animais , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/farmacologia , Vimentina , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas contra COVID-19/farmacologia , Escherichia coli/metabolismo , Replicação Viral
16.
BMC Microbiol ; 24(1): 86, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481150

RESUMO

INTRODUCTION: Psittacosis is a zoonosis caused by Chlamydia psittaci, the clinical manifestations of Psittacosis range from mild illness to fulminant severe pneumonia with multiple organ failure. This study aimed to evaluate the clinical characteristics of Chlamydia psittaci infection diagnosed based on metagenomic next-generation sequencing(mNGS), as well as the risk factors affecting the progress of Chlamydia psittaci infection, in order to improve the effect of therapeutics. METHODS: We retrospectively analyzed the clinical data of patients infected with chlamydia psittaci in the First Affiliated Hospital of Nanchang University from January 2021 to December 2021. The patient's past medical history, clinical manifestations, laboratory examinations, chest CT results, treatment status, and prognosis data were collected. we also investigated both the pathogenic profile characteristics and the lower respiratory tract microbiota of patients with Chlamydia psittaci pneumonia using mNGS. RESULTS: All cases of Chlamydia psittaci in our research have been confirmed by mNGS. Among 46 cases of Chlamydia psittaci pneumonia, Poultry exposure was reported in 35 cases. In severe cases of Chlamydia psittaci pneumonia, Neutrophils, Procalcitonin (PCT), Lactate Dehydrogenase (LDH), Hydroxybutyrate Dehydrogenase (HBDH), Creatine Kinase Isoenzymes-B (CK-MB) and D-Dimer levels were remarkably higher than that of non-severe cases, except for lymphocytes (all P < 0.05). Chest CT scans showed Bilateral (77.8%), multiple lobar lungs (85.2%), pleural effusions (44.4%) involvement in those suffering from severe Chlamydia psittaci pneumonia, whereas its incidence was 0%, 21.1% and 10.5% in non-severe patients, respectively (P < 0.05). Multivariate analysis revealed that higher lymphocyte concentrations (OR 0.836, 95% CI 0.714-0.962, P = 0.041) were the only protective factor for survival. mNGS results indicated that 41.3% of patients (19/46) had suspected coinfections with a coinfection rate of 84.2% (16/19) in the severe group, much higher than that in the non severe group (p < 0.05). No significantly different profiles of lower respiratory tract microbiota diversity were found between non severe group and severe group. CONCLUSION: A history of poultry exposure in patients can serve as an important basis for diagnosing Chlamydia psittaci pneumonia, and patients with severe Chlamydia psittaci pneumonia are more likely to develop elevated inflammatory biomarkers as well as elevated cardiac markers. Higher lymphocyte concentrations are protective factors associated with severe C. psittaci pneumonia. The higher proportion of patients with coinfections in our study supports the use of mNGS for comprehensive early detection of respiratory infections in patients with C. psittaci pneumonia.


Assuntos
Chlamydophila psittaci , Coinfecção , Pneumonia , Psitacose , Humanos , Psitacose/diagnóstico , Chlamydophila psittaci/genética , Estudos Retrospectivos , Sequenciamento de Nucleotídeos em Larga Escala , Fatores de Risco
17.
BMC Infect Dis ; 24(1): 308, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481149

RESUMO

BACKGROUND: Scedosporium apiospermum (S. apiospermum) belongs to the asexual form of Pseudallescheria boydii and is widely distributed in various environments. S. apiospermum is the most common cause of pulmonary infection; however, invasive diseases are usually limited to patients with immunodeficiency. CASE PRESENTATION: A 54-year-old Chinese non-smoker female patient with normal lung structure and function was diagnosed with pulmonary S. apiospermum infection by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). The patient was admitted to the hospital after experiencing intermittent right chest pain for 8 months. Chest computed tomography revealed a thick-walled cavity in the upper lobe of the right lung with mild soft tissue enhancement. S. apiospermum was detected by the mNGS of BALF, and DNA sequencing reads were 426. Following treatment with voriconazole (300 mg q12h d1; 200 mg q12h d2-d20), there was no improvement in chest imaging, and a thoracoscopic right upper lobectomy was performed. Postoperative pathological results observed silver staining and PAS-positive oval spores in the alveolar septum, bronchiolar wall, and alveolar cavity, and fungal infection was considered. The patient's symptoms improved; the patient continued voriconazole for 2 months after surgery. No signs of radiological progression or recurrence were observed at the 10-month postoperative follow-up. CONCLUSION: This case report indicates that S. apiospermum infection can occur in immunocompetent individuals and that the mNGS of BALF can assist in its diagnosis and treatment. Additionally, the combined therapy of antifungal drugs and surgery exhibits a potent effect on the disease.


Assuntos
Pneumonia , Scedosporium , Humanos , Feminino , Pessoa de Meia-Idade , Scedosporium/genética , Voriconazol/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Antifúngicos/uso terapêutico , Pulmão/diagnóstico por imagem , Pneumonia/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala
18.
Mol Genet Genomics ; 299(1): 34, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478130

RESUMO

Staphylococcus aureus (S. aureus) is an opportunistic gram-positive, non-motile, and non-sporulating bacteria that induces pneumonia, a provocative lung infection affecting mainly the terminal bronchioles and the small air sacs known as alveoli. Recently, it has developed antibiotic resistance to the available consortium as per the WHO reports; thereby, novel remedial targets and resilient medications to forestall and cure this illness are desperately needed. Here, using pan-genomics, a total of 1,387 core proteins were identified. Subtractive proteome analyses further identified 12 proteins that are vital for bacteria. One membrane protein (secY) and two cytoplasmic proteins (asd and trpG) were chosen as possible therapeutic targets concerning minimum % host identity, essentiality, and other cutoff values, such as high resistance in the MDR S. aureus. The UniProt AA sequences of the selected targets were modelled and docked against 3 drug-like chemical libraries. The top-ranked compounds i.e., ZINC82049692, ZINC85492658 and 3a of Isosteviol derivative for Aspartate-semialdehyde dehydrogenase (asd); ZINC38222743, ZINC70455378, and 5 m Isosteviol derivative for Anthranilate synthase component II (trpG); and finally, ZINC72292296, ZINC85632684, and 7 m Isosteviol derivative for Protein translocase subunit secY (secY), were further subjected to molecular dynamics studies for thermodynamic stability and energy calculation. Our study proposes new therapeutic targets in S. aureus, some of which have previously been reported in other pathogenic microorganisms. Owing to further experimental validation, we anticipate that the adapted methodology and the predicted results in this work could make major contributions towards novel drug discovery and their targets in S. aureus caused pneumonia.


Assuntos
Diterpenos do Tipo Caurano , Pneumonia , Staphylococcus aureus , Animais , Staphylococcus aureus/genética , Aspartato-Semialdeído Desidrogenase , Genômica/métodos , Antibacterianos/farmacologia , Descoberta de Drogas
19.
Clin Nutr ESPEN ; 60: 356-361, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479935

RESUMO

BACKGROUND & AIMS: Most of the 11.5 million feeding tubes placed annually in Europe and the USA are placed 'blind'. This carries a 1.6% risk that these tubes will enter the lung and 0.5% cause pneumothorax or pneumonia regardless of whether misplacement is identified prior to feeding. Tube placement by direct vision may reduce the risk of respiratory or oesophageal misplacement. This study externally validated whether an 'operator guide' would enable novice operators to differentiate the respiratory and alimentary tracts. METHODS: One IRIS tube was placed in each of 40 patients. Novice operators interpreted anatomical position using the built-in tube camera. Interpretation was checked from recorded images by consultant gastroenterologists and end-of-procedure checks using pH or X-ray checked by Radiologists and a consultant intensivist. RESULTS: The 40 patients were a median of 68y (IQR: 56-75), 70% male, mostly medical (65%), conscious (67.5%) and 70% had no artificial airway. Three tubes were removed due to failed placement. In the remaining 37 placements, novice operators identified the airway in 17 (45.9%) and airway + respiratory tract in 19 (51.4%), but redirected all these tubes into the oesophagus. By using direct vision to reduce the proportion of tubes near the airway or in respiratory tract from 0.514 to 0, operator discrimination between the respiratory and alimentary tracts was highly significant (0.514 vs 0: p < 0.0001, power >99.9% when significance = 0.05). In addition, organ boundaries (respiratory tract vs oesophagus, oesophagus vs stomach, stomach vs intestine) were identified in 100%. CONCLUSIONS: Novice operators, trained using the guide, identified all respiratory misplacements and accurately interpreted IRIS tube position. Guide-based training could enable widespread use of direct vision as a means to prevent tube-related complications.


Assuntos
Pneumonia , Pneumotórax , Humanos , Masculino , Feminino , Nutrição Enteral/métodos , Intubação Gastrointestinal/métodos , Estômago , Pneumotórax/etiologia
20.
Clin Nutr ESPEN ; 60: 343-347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479933

RESUMO

OBJECTIVE: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) recently released the first international consensus on the diagnostic criteria for Sarcopenic obesity (SO). The present study aimed to explore the ability of SO to predict the risk of pneumonia in patients with stable schizophrenia. METHODS: This was a prospective study involving hospitalized patients with schizophrenia aged ≥50 years from two mental health centers in western China. Baseline patient data were collected from September 1 to September 30, 2020. Follow-up data on pneumonia were collected from October 2020 to October 2022. The diagnosis of SO was based on the ESPEN/EASO criteria. Patients were assessed for handgrip strength (HGS), skeletal muscle mass/weight (SMM/W), and fat mass percentage (FM%). Logistic regression analysis was used to explore the effect of SO on the risk of pneumonia in patients with stable schizophrenia. RESULTS: A total of 320 patients with stable schizophrenia were included. Of these, 74 (23.13%) were diagnosed with SO, while 117 (36.56%) developed pneumonia. Compared with patients in the non-low HGS, non-low HGS + non-low SMM/W (or non-low HGS + low SMM/W or low HGS + non-low SMM/W) and non-SO groups, the proportions of patients with pneumonia in the low HGS (42.3% vs. 25.9%, p = 0.004), low HGS + low SMM/W (45.3% vs. 33.3%, p = 0.048), and SO (47.3% vs. 33.3%, p = 0.029) groups, respectively, were higher. However, there was no difference in the proportion of patients with pneumonia in the low SMM/W group and the obese group compared with the non-low SMM/W and non-obese groups. Further logistic regression analysis after adjustment for potential influencing factors showed that compared with the non-low HGS group, patients in the low HGS group had a higher risk of pneumonia (OR = 1.892, 95%CI: 1.096-3.264). CONCLUSION: SO defined according to the ESPEN/EASO criteria was not found to be significantly associated with the development of pneumonia in patients with stable schizophrenia. Further verification of these results is needed with larger sample sizes and the establishment of a cutoff value for this population.


Assuntos
Pneumonia , Sarcopenia , Esquizofrenia , Humanos , Sarcopenia/complicações , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Estudos Prospectivos , Força da Mão/fisiologia , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Composição Corporal/fisiologia , Obesidade/complicações , Obesidade/epidemiologia , Pneumonia/complicações , Pneumonia/diagnóstico
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