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1.
Trials ; 25(1): 4, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167115

RESUMO

BACKGROUND: Disseminated intravascular coagulation (DIC) occurs in 30-50% of septic patients and contributes to high mortality in the intensive care unit (ICU). However, there are few proven interventions for coagulation disorder management in sepsis. Experimental and clinical data have demonstrated that sepsis could benefit from unfractionated heparin (UFH) treatment. To date, there are no large multicenter trials to determine the safety and efficacy of UFH in septic patients with suspected DIC. METHODS: A multicenter, double-blinded, placebo-controlled randomized trial is designed to recruit 600 patients who met sepsis 3.0 criteria and suspected DIC. Participants will be randomized (1:1) to receive UFH or saline via continuous intravenous administration for 7 days within 6 h of enrolment. The primary outcome is ICU mortality. The secondary outcome includes 28-day all-cause mortality, the improvement of Sequential Organ Failure Assessment scores, and the incidence of major hemorrhage. Investigators, participants, and statisticians will be blinded to the allocation. DISCUSSION: The HepSIC trial is to evaluate the efficacy and safety of UFH on sepsis-related DIC across different areas of China. The small dosage of UFH administration would offer a new potential approach for treating sepsis-related coagulation disorders. ETHICS AND DISSEMINATION: Ethical approval was granted by all the ethics committees of 20 participant centers. Results will be disseminated via peer-reviewed publications and presented at conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT02654561. Registered on 13 January 2016.


Assuntos
Transtornos da Coagulação Sanguínea , Coagulação Intravascular Disseminada , Sepse , Humanos , Heparina/efeitos adversos , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/etiologia , Sepse/complicações , Sepse/diagnóstico , Sepse/tratamento farmacológico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Hemorragia/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
2.
Nat Commun ; 14(1): 7694, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001086

RESUMO

The oral delivery of nano-drug delivery systems (Nano-DDS) remains a challenge. Taking inspirations from viruses, here we construct core-shell mesoporous silica nanoparticles (NPs, ~80 nm) with virus-like nanospikes (VSN) to simulate viral morphology, and further modified VSN with L-alanine (CVSN) to enable chiral recognition for functional bionics. By comparing with the solid silica NPs, mesoporous silica NPs and VSN, we demonstrate the delivery advantages of CVSN on overcoming intestinal sequential barriers in both animals and human via multiple biological processes. Subsequently, we encapsulate indomethacin (IMC) into the nanopores of NPs to mimic gene package, wherein the payloads are isolated from bio-environments and exist in an amorphous form to increase their stability and solubility, while the chiral nanospikes multi-sited anchor and chiral recognize on the intestinal mucosa to enhance the penetrability and ultimately improve the oral adsorption of IMC. Encouragingly, we also prove the versatility of CVSN as oral Nano-DDS.


Assuntos
Portadores de Fármacos , Nanopartículas , Animais , Humanos , Indometacina , Solubilidade , Dióxido de Silício , Porosidade , Sistemas de Liberação de Medicamentos
3.
Heart Lung ; 61: 72-83, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37167901

RESUMO

BACKGROUND: Anticoagulation is critical in patients supported on extracorporeal membrane oxygenation (ECMO). The appropriate monitoring strategies for heparin remain unclear. OBJECTIVES: This systematic review aimed to compare the accuracy and safety of various monitoring strategies for patients supported on ECMO. METHODS: The PubMed and Web of Science databases were searched for articles in March 2023 without restrictions on publication date. Anticoagulation monitoring strategies for adults supported on ECMO were compared across all included studies. The incidence of bleeding, thrombosis, mortality, blood transfusion, correlation between tests and heparin dose, and the discordance between different tests were discussed in the included studies. The risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane Collaboration's tool. RESULTS: Twenty-six studies, including a total of 1,684 patients, met the inclusion criteria. The monitoring of anticoagulation by activated partial thromboplastin time (aPTT) resulted in less blood product transfusion than that by activated clotting time (ACT). Moreover, the monitoring of anticoagulation by anti-factor Xa (Anti-Xa) resulted in a more stable anticoagulation than that by aPTT. Anti-Xa and aPTT correlated with heparin dose better than ACT, and the discordance between different monitoring tests was common. Finally, combined monitoring showed some advantages in reducing mortality and blood product transfusion. CONCLUSION: Anti-Xa and aPTT are more suitable for anticoagulation monitoring for patients supported on ECMO than ACT. Thromboelastography and combination strategies are less applied. Most of the studies were retrospective, and their sample sizes were relatively small; thus, more appropriate monitoring strategies and higher quality research are needed.


Assuntos
Anticoagulantes , Oxigenação por Membrana Extracorpórea , Humanos , Adulto , Anticoagulantes/uso terapêutico , Estudos Retrospectivos , Heparina/uso terapêutico , Tempo de Tromboplastina Parcial
4.
Surgery ; 173(5): 1303-1310, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36774318

RESUMO

BACKGROUND: A blunt host defense response in older patients may contribute to different coagulation responses during sepsis. We aimed to investigate the differences in coagulation parameters between elderly and non-elderly patients with sepsis. METHODS: Adult patients diagnosed with sepsis within 24 hours after admission to the intensive care unit between September 2018 and December 2020 were prospectively enrolled. Patients were categorized into the adult (18-64 years) and elderly (age ≥65 years) groups. Conventional coagulation parameters and inflammatory markers were measured on intensive care unit admission and on Days 3 and 7. Thromboelastography was performed on intensive care unit admission. The differences in the coagulation parameters between the 2 groups were evaluated. The adult and elderly patients were matched to adjust for baseline characteristics. Correlations between inflammatory markers and coagulation-related parameters were also analyzed. RESULTS: Of the 567 patients, 303 (53.4%) were elderly. Compared with adult patients, elderly patients had lower prothrombin time elevation, lower fibrinogen, D-dimer, and fibrin/Fib degradation product levels, and lower proportion of disseminated intravascular coagulation on intensive care unit admission; and, they had lower dynamic platelet, lower fibrinogen, and D-dimer levels during the first week in the intensive care unit. Thromboelastography parameters were generally within the normal range, although elderly patients had lower R and K values and a higher alpha angle. Comparisons of coagulation parameters between the 2 groups revealed similar results in the matched cohort. The inflammatory markers correlated with prothrombin time, activated partial thromboplastin time, and antithrombin III. CONCLUSION: Elderly patients had milder coagulation activation, accompanied by a decreased inflammatory response during sepsis, compared to non-elderly patients.


Assuntos
Coagulação Intravascular Disseminada , Sepse , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/etiologia , Fibrinogênio/análise
5.
Shock ; 59(3): 368-374, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36562264

RESUMO

ABSTRACT: Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. Patients: We included adult patients (age ≥18 years) who developed SALD within the first 48 hours of intensive care unit (ICU) admission. We excluded patients who died or were discharged from the ICU within the first 48 hours of admission. Patients with abnormal liver function before ICU admission were also excluded. Measurements and Main Results: Patients in the MIMIC-IV 1.0 database served as a derivation cohort. Patients in the eICU database were used as validation cohort. We identified four subphenotypes of SALD (subphenotype α, ß, γ, δ) using K-means cluster analysis in 5234 patients in derivation cohort. The baseline characteristics and clinical outcomes were compared between the phenotypes using one-way analysis of variance/Kruskal-Wallis test and the χ 2 test. Moreover, we used line charts to illustrate the trend of liver function parameters over 14 days after ICU admission. Subphenotype α (n = 1,055) was the most severe cluster, characterized by shock with multiple organ dysfunction (MODS) group. Subphenotype ß (n = 1,179) had the highest median bilirubin level and the highest proportion of patients with underlying liver disease and coexisting coagulopathy (increased bilirubin group). Subphenotype γ (n = 1,661) was the cluster with the highest mean age and had the highest proportion of patients with chronic kidney disease (aged group). Subphenotype δ (n = 1,683) had the lowest 28-day and in-hospital mortality (mild group). The characteristics of clusters in the validation cohort were similar to those in the derivation cohort. In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.


Assuntos
Hepatopatias , Sepse , Humanos , Estudos Retrospectivos , Fenótipo , Análise por Conglomerados , Unidades de Terapia Intensiva
6.
Front Med (Lausanne) ; 10: 1174429, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38264049

RESUMO

The development of intensive care medicine is inseparable from the diversified monitoring data. Intensive care medicine has been closely integrated with data since its birth. Critical care research requires an integrative approach that embraces the complexity of critical illness and the computational technology and algorithms that can make it possible. Considering the need of standardization of application of big data in intensive care, Intensive Care Medicine Branch of China Health Information and Health Care Big Data Society, Standard Committee has convened expert group, secretary group and the external audit expert group to formulate Chinese Experts' Consensus on the Application of Intensive Care Big Data (2022). This consensus makes 29 recommendations on the following five parts: Concept of intensive care big data, Important scientific issues, Standards and principles of database, Methodology in solving big data problems, Clinical application and safety consideration of intensive care big data. The consensus group believes this consensus is the starting step of application big data in the field of intensive care. More explorations and big data based retrospective research should be carried out in order to enhance safety and reliability of big data based models of critical care field.

7.
Front Pharmacol ; 13: 989903, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36278186

RESUMO

Introduction: Whether aspirin or other antiplatelet drugs can reduce mortality among patients with coronavirus disease (COVID-19) remains controversial. Methods: We identified randomized controlled trials, prospective cohort studies, and retrospective studies on associations between aspirin or other antiplatelet drug use and all-cause mortality among patients with COVID-19 in the PubMed database between March 2019 and September 2021. Newcastle-Ottawa Scale and Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias. The I2 statistic was used to assess inconsistency among trial results. The summary risk ratio (RR) and odds ratio (OR) were obtained through the meta-analysis. Results: The 34 included studies comprised three randomized controlled trials, 27 retrospective studies, and 4 prospective cohort studies. The retrospective and prospective cohort studies showed low-to-moderate risks of bias per the Newcastle-Ottawa Scale score, while the randomized controlled trials showed low-to-high risks of bias per the Cochrane Risk of Bias Assessment Tool. The randomized controlled trials showed no significant effect of aspirin use on all-cause mortality in patients with COVID-19 {risk ratio (RR), 0.96 [95% confidence interval (CI) 0.90-1.03]}. In retrospective studies, aspirin reduced all-cause mortality in patients with COVID-19 by 20% [odds ratio (OR), 0.80 (95% CI 0.70-0.93)], while other antiplatelet drugs had no significant effects. In prospective cohort studies, aspirin decreased all-cause mortality in patients with COVID-19 by 15% [OR, 0.85 (95% CI 0.80-0.90)]. Conclusion: The administration of aspirin may reduce all-cause mortality in patients with COVID-19.

11.
Front Immunol ; 12: 733537, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745104

RESUMO

Sepsis is a complex syndrome promoted by pathogenic and host factors; it is characterized by dysregulated host responses and multiple organ dysfunction, which can lead to death. However, its underlying molecular mechanisms remain unknown. Proteomics, as a biotechnology research area in the post-genomic era, paves the way for large-scale protein characterization. With the rapid development of proteomics technology, various approaches can be used to monitor proteome changes and identify differentially expressed proteins in sepsis, which may help to understand the pathophysiological process of sepsis. Although previous reports have summarized proteomics-related data on the diagnosis of sepsis and sepsis-related biomarkers, the present review aims to comprehensively summarize the available literature concerning "sepsis", "proteomics", "cecal ligation and puncture", "lipopolysaccharide", and "post-translational modifications" in relation to proteomics research to provide novel insights into the molecular mechanisms of sepsis.


Assuntos
Biomarcadores/metabolismo , Ceco/cirurgia , Sepse/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Lipopolissacarídeos/imunologia , Processamento de Proteína Pós-Traducional , Proteômica , Punções , Sepse/diagnóstico , Sepse/genética
12.
Int Immunopharmacol ; 101(Pt B): 108205, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34653731

RESUMO

Sepsis is a dysregulated host response to infection. T cell dysfunction results in the failure to eradicate pathogens and the increased susceptibility to nosocomial infections and mortality during sepsis. Although PD-1 has shown to be a promising target to interfere with T cells dysfunction, the role of other coinhibitory receptors in sepsis remains largely elusive. Here we demonstrated that the immune checkpoint molecule TIGIT on lymphocytes and the critical role of TIGIT in regulating T cell responses in sepsis. Fifty septic patients and seventeen healthy donors were prospectively enrolled. The expression patterns of TIGIT and other molecules on lymphocytes were quantitated by flow cytometry. Ex vivo functional assays were also conducted. Results show that TIGIT expression on T cells was significantly upregulated in sepsis and septic shock patients relative to healthy donors. Elevated frequencies of TIGIT+ T cells correlated with aggravated inflammatory response and organ injuries. Of note, TIGIT expression on CD8+ T cells showed a competitive capability to predict ICU mortality in sepsis. TIGIT+ T cells expressed higher levels of PD-1, lower levels of CD226, and released fewer cytokines. Strikingly, ex vivo blockade of TIGIT using anti-TIGIT antibody restored the frequencies of cytokine-producing T cells from septic patients. These data illustrate that TIGIT on T cells is being used not only as a clinical predictor of poor prognosis but also as a potential target of novel immunotherapeutic intervention during sepsis.


Assuntos
Antígenos de Diferenciação de Linfócitos T/metabolismo , Proteínas de Checkpoint Imunológico , Receptor de Morte Celular Programada 1/metabolismo , Receptores Imunológicos/metabolismo , Sepse/metabolismo , Linfócitos T/fisiologia , Idoso , Antígenos de Diferenciação de Linfócitos T/genética , Citocinas/genética , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/genética , Receptores Imunológicos/genética , Sepse/imunologia , Regulação para Cima
13.
Front Med (Lausanne) ; 8: 659793, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712673

RESUMO

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

14.
Ann Transl Med ; 9(15): 1219, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532356

RESUMO

BACKGROUND: Shock is a critical illness that seriously threatens the lives of patients. This study explains the epidemiology of shock, mortality of shock, and identify factors that related to hospital death. METHODS: This is a multi-centre cross-sectional survey, which included 1,064 tertiary hospitals in 31 provinces, municipalities, and autonomous regions across China mainland. Totally 289,428 patients who diagnosed with shock based on the ICD-10 abstracted from the Hospital Quality Monitoring System (HQMS) in 2018, a national database administrated by National Health Commission of the PRC. RESULTS: Patients diagnosed with shock were screened and classified according to the type of shock. Regression analysis was used to identify factors that related to death. A total of 79,668,156 medical records were included in HQMS in 2018, from which a total of 289,428 records with shock were identified. Hypovolemic shock occurred in 128,436 cases (44.38%), septic shock occurred in 121,543 cases (41.99%), cardiogenic shock occurred in 44,597 cases (15.41), and obstructive shock occurred in 3,168 cases (1.09%). Of these, 8,147 cases (2.81%) had mixed shock, which means had two or more types of shock. For all the shock cases, the top three frequent concomitant diseases recorded were circulatory system diseases (55.22%), digestive system diseases (53.64%), and respiratory system diseases (53.31%). Of the four types of shock, cases with cardiogenic shock had the highest in-hospital mortality (31.6%), followed by those with obstructive shock (25.2%), septic shock (22.9%), and hypovolemic shock (15.5%). Interestingly, the combination of shock and malignant tumors is one of the major factors that related to hospital deaths. CONCLUSIONS: Shock is a serious disease with a high fatality rate and huge clinical costs. According to this epidemiological survey of shock in China 2018, we should clarify the factors related to the hospital death in shock cases.

15.
Asia Pac J Clin Nutr ; 30(1): 15-21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787036

RESUMO

BACKGROUND AND OBJECTIVES: The novel coronavirus disease (COVID-19) epidemic is spreading all over the world. With the number of cases increasing rapidly, the epidemiological data on the nutritional practice is scarce. In this study, we aim to describe the clinical characteristics and nutritional practice in a cohort of critically ill COVID-19 patients. METHODS AND STUDY DESIGN: This is a multicenter, ambidirectional cohort study conducted at 11 hospitals in Hubei Province, China. All eligible critical COVID-19 patients in the study hospital intensive care units at 00:00, March 6th, 2020, were included. Data collection was performed via written case report forms. RESULTS: A total of 44 patients were identified and enrolled, of whom eight died during the 28-day outcome follow- up period. The median interval between hospital admission and the study day was 24 (interquartile range, 13- 26) days and 52.2% (23 of 44) of patients were on invasive mechanical ventilation. The median nutrition risk in critically ill (mNUTRIC) score was 3 (interquartile range, 2-5) on the study day. During the enrolment day, 68.2% (30 of 44) of patients received enteral nutrition (EN), while 6.8% (3 of 44) received parenteral nutrition (PN) alone. Nausea and aspiration were uncommon, with a prevalence of 11.4% (5 of 44) and 6.8% (3 of 44), respectively. As for energy delivery, 69.7% (23 of 33) of patients receiving EN and/or PN were achieving their prescribed targets. CONCLUSIONS: The study showed that EN was frequently applied in critical COVID-19 patients. Energy delivery may be suboptimal in this study requiring more attention.


Assuntos
COVID-19/epidemiologia , COVID-19/terapia , Estado Terminal/epidemiologia , Estado Nutricional , Apoio Nutricional , Idoso , China/epidemiologia , Estudos de Coortes , Nutrição Enteral/estatística & dados numéricos , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral/estatística & dados numéricos , SARS-CoV-2
16.
J Intensive Med ; 1(1): 35-41, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36943814

RESUMO

Coagulopathy, characterized by a high D-dimer level, is a common pathological occurrence in coronavirus disease 2019 (COVID-19) and is associated with poor prognosis. Severe cases with COVID-19 is associated with a significantly higher risk of deep vein thrombosis and acute pulmonary embolism. Pulmonary intravascular coagulopathy is the characteristic coagulopathy in COVID-19. Unlike sepsis-induced coagulopathy and disseminated intravascular coagulation, which are manifestations of systemic coagulopathy, pulmonary intravascular coagulopathy is a manifestation of a local coagulation disorder in the lung. The progression from pulmonary intravascular coagulopathy to sepsis-induced coagulopathy or disseminated intravascular coagulation in the context of COVID-19 may indicate that the patient's coagulation dysfunction has progressed from local to systemic. Exploring the associated coagulation disease will aid in the understanding of the pathophysiological mechanisms underlying severe COVID-19.

17.
Front Immunol ; 11: 1829, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903604

RESUMO

Sepsis is the leading cause of death in intensive care units. MicroRNA-34a (miR-34a) is involved in sepsis progression, while its underlying mechanisms on sepsis-induced lung injury remain obscure. Oxidative stress, pyroptosis, and inhibition of autophagy can result in organ injury. MiR-34a has been reported to regulate oxidative stress and autophagy via inhibiting silent information regulator T1 (SIRT1) and autophagy gene 4B (ATG4B) signaling. This study aimed at identifying the function of miR-34a in oxidative stress, inflammation, pyroptosis, and autophagy in sepsis-induced lung injury. Male 8-week-old C57BL/6 mice were subjected to cecal ligation and puncture and treated with miR-34a antagomir/agomir. Survival (n = 10), histopathological changes (n = 6), and lung wet-to-dry ratio (n = 6) were recorded and assayed. Other detection (n = 6) was performed to investigate the level of oxidative stress, inflammation, pyroptosis, and autophagy in lung tissues. Results showed that miR-34a down-regulation ameliorated lung injury in septic mice as reflected by decreased lung injury scores (decrease from 3.00 ± 0.32 to 2.00 ± 0.32) and wet-to-dry ratio (0.36-fold decrease). MiR-34a down-regulation also decreased reactive oxygen species accumulation (0.36-fold decrease), and promoted superoxide dismutase activity and the expression of SIRT1 (1.24-fold increase), heme oxygenase-1 and nuclear factor erythroid 2 like 2 to inhibit oxidative stress in septic mice. Moreover, miR-34a down-regulation suppressed inflammatory response and pyroptosis in septic mice, as evidenced by decreased level of pro-inflammatory factors including tumor necrosis factor α, interleukin-6 (IL-6), IL-1ß, and IL-18, activity of caspase-1 (0.51-fold decrease) and expression of nucleotide-binding domain and leucine-rich repeat protein-3 (0.48-fold decrease), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D (0.36-fold decrease), and increased level of anti-inflammatory factors IL-10. MiR-34a down-regulation also enhanced autophagy in septic mice as evidenced by more autolysosomes and elevated expressions of ATG4B (0.90-fold increase), beclin1, ATG9, and LC3 II/I. Among these experiments, miR-34a up-regulation showed opposite effects on oxidative stress, inflammatory response, pyroptosis, and autophagy in septic mice. Additionally, miR-34a could bind to the 3'-untranslated region of SIRT1 and ATG4B. In conclusion, our findings demonstrated that miR-34a was implicated in oxidative stress, inflammation, pyroptosis, and autophagy in the development of sepsis. MiR-34a inhibition had a potential to alleviate sepsis-induced lung injury.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , MicroRNAs/antagonistas & inibidores , Lesão Pulmonar Aguda/imunologia , Animais , Autofagia/imunologia , Ceco/lesões , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/metabolismo , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/fisiologia , Punções , Piroptose/imunologia , Sepse/complicações , Sepse/imunologia , Sepse/metabolismo
19.
BMC Pulm Med ; 20(1): 37, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046709

RESUMO

BACKGROUND: Prolonged and difficult weaning is associated with higher rates of complications and mortality. Therefore, it is important to identify the associated factors. CASE PRESENTATION: We describe our experience with a 37-year-old man diagnosed with severe viral pneumonia (influenza A). He presented with acute respiratory failure type I on admission. During intubation, his blood pressure and heart rate decreased, and epinephrine and norepinephrine were administered. Although his clinical condition improved 8 days after intensive care unit (ICU) admission, he experienced difficulty weaning. He remained conscious but had a poor spontaneous cough with sputum production and weak limb muscle strength. His cough reflex was absent during bronchoscopic sputum suction, and he used abdominal breathing during the T-tube test. Magnetic resonance imaging revealed an Arnold-Chiari malformation type I, posterior dislocation of the odontoid process, and syringomyelia, with compression and deformation of the medulla and high cervical cord. The patient was successfully weaned from the ventilator at 20 days after ICU admission. CONCLUSIONS: Arnold-Chiari malformation type I and posterior dislocation of the odontoid process, which aggravate medullary compression and increase the risk of cervical nerve injury, might be a rare factor affecting prolonged weaning in critical illness.


Assuntos
Malformação de Arnold-Chiari/fisiopatologia , Processo Odontoide/patologia , Pneumonia Viral/complicações , Desmame do Respirador , Adulto , Malformação de Arnold-Chiari/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Processo Odontoide/diagnóstico por imagem
20.
Urol J ; 16(3): 312-317, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-30178453

RESUMO

PURPOSE: Catheter-associated urinary tract infection (CAUTI) occurs frequently in critical illness with signifi-cant morbidity, mortality, and additional hospital costs. The epidemiology of symptomatic ward-acquired CAUTI (within 48 hours of intensive care unit [ICU] admission) has not been carefully examined. The objective of our study was to identify the patient characteristics and microbiology of symptomatic CAUTI in critical illness. MATERIALS AND METHODS: A 4-year retrospective observational study (2013-2016) was conducted at a single adult ICU with 30 beds in a tertiary hospital in Northeast China. The enrolled patients were over 18 years of age and had been diagnosed as having symptomatic CAUTIs in the ICU from January 2013 to December 2016. The infor-mation of clinicopathological characteristics (such as age, sex, underlying diseases, hospital admission diagnosis, ICU admission source, severity of illness, duration of urinary catheterization, use of antibiotics, duration of ICU stay, and ICU mortality) was recorded in an electronic database by senior clinicians who were blinded to the study purpose and design. Microbiological data were retrieved from the computerized hospital database. RESULTS: Between January 2013 and December 2016, 4115 patients were admitted to the ICU. Ninety-eight symp-tomatic CAUTI cases were enrolled in this study, including 29 patients who had ward-acquired CAUTI and 69 pa-tients who had ICU-acquired CAUTI. Patients with ward-acquired symptomatic CAUTI had significantly shorter overall ICU length of stay and shorter urinary catheterization time, and the overall ICU mortality was significantly higher in patients who had ICU-acquired symptomatic CAUTI. More third-generation cephalosporins and carbap-enems were used prior to CAUTI in the patients with ICU-acquired symptomatic CAUTI. Escherichia coli and Acinetobacter baumannii were the most common bacteria causing ward-acquired and ICU-acquired CAUTI, re-spectively. There were a higher number of cases of non-Candida albicans infections in patients with ICU-acquired symptomatic CAUTI than in patients with ward-acquired symptomatic CAUTI. CONCLUSION: Clinical characteristics, microbiological characteristics, and prognosis were different between ward-acquired and ICU-acquired symptomatic CAUTI. Patients with ICU-acquired symptomatic CAUTI had higher overall ICU mortality.


Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Infecções Urinárias/epidemiologia , Idoso , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/microbiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologia
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