RESUMO
BACKGROUND AND AIMS: Coexisting atrial fibrillation (AF) and cancer challenge the management of both. The aim of the study is to comprehensively provide the epidemiology of coexisting AF and cancer. METHODS: Using Dutch nationwide statistics, individuals with incident AF (n = 320 139) or cancer (n = 472 745) were identified during the period 2015-19. Dutch inhabitants without a history of AF (n = 320 135) or cancer (n = 472 741) were matched as control cohorts by demographic characteristics. Prevalence of cancer/AF at baseline, 1-year risk of cancer/AF diagnosis, and their time trends were determined. The association of cancer/AF diagnosis with all-cause mortality among those with AF/cancer was estimated by using time-dependent Cox regression. RESULTS: The rate of prevalence of cancer in the AF cohort was 12.6% (increasing from 11.9% to 13.2%) compared with 5.6% in the controls; 1-year cancer risk was 2.5% (stable over years) compared with 1.8% in the controls [adjusted hazard ratio (aHR) 1.52, 95% confidence interval (CI) 1.46-1.58], which was similar by cancer type. The rate of prevalence of AF in the cancer cohort was 7.5% (increasing from 6.9% to 8.2%) compared with 4.3% in the controls; 1-year AF risk was 2.8% (stable over years) compared with 1.2% in the controls (aHR 2.78, 95% CI 2.69-2.87), but cancers of the oesophagus, lung, stomach, myeloma, and lymphoma were associated with higher hazards of AF than other cancer types. Both cancer diagnosed after incident AF (aHR 7.77, 95% CI 7.45-8.11) and AF diagnosed after incident cancer (aHR 2.55, 95% CI 2.47-2.63) were associated with all-cause mortality, but the strength of the association varied by cancer type. CONCLUSIONS: Atrial fibrillation and cancer were associated bidirectionally and were increasingly coexisting, but AF risk varied by cancer type. Coexisting AF and cancer were negatively associated with survival.
Assuntos
Fibrilação Atrial , Neoplasias , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/mortalidade , Fibrilação Atrial/complicações , Países Baixos/epidemiologia , Masculino , Neoplasias/mortalidade , Neoplasias/complicações , Neoplasias/epidemiologia , Feminino , Idoso , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Idoso de 80 Anos ou mais , AdultoRESUMO
Pulmonary endothelial barrier dysfunction is a major pathophysiology observed in acute respiratory distress syndrome (ARDS). Ghrelin, a key regulator of metabolism, has been shown to play protective roles in the respiratory system. However, its effects on lipopolysaccharide (LPS)-induced pulmonary endothelial barrier injury are unknown. In this study, the effects of ghrelin on LPS-induced ARDS and endothelial cell injury were evaluated in vivo and in vitro. In vivo, mice treated with LPS (3 mg/kg intranasal application) were used to establish the ARDS model. Annexin V/propidium iodide apoptosis assay, scratch-wound assay, tube formation assay, transwell permeability assay, and Western blotting experiment were performed to reveal in vitro effects and underlying mechanisms of ghrelin on endothelial barrier function. Our results showed that ghrelin had protective effects on LPS-induced ARDS and endothelial barrier disruption by inhibiting apoptosis, promoting cell migration and tube formation, and activating the PI3K/AKT signaling pathway. Furthermore, ghrelin stabilized LPS-induced endothelial barrier function by decreasing endothelial permeability and increasing the expression of the intercellular junction protein vascular endothelial cadherin. LY294002, a specific inhibitor of the PI3K pathway, reversed the protective effects of ghrelin on the endothelial cell barrier. In conclusion, our findings indicated that ghrelin protected against LPS-induced ARDS by impairing the pulmonary endothelial barrier partly through activating the PI3K/AKT pathway. Thus, ghrelin may be a valuable therapeutic strategy for the prevention or treatment of ARDS.
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Grelina/metabolismo , Síndrome do Desconforto Respiratório/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Feminino , Grelina/genética , Grelina/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/metabolismo , Junções Intercelulares/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
AIMS: Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We investigated the persistence with oral anticoagulants (OACs) and its association with prognosis among a nationwide cohort of NVAF patients. METHODS AND RESULTS: DOAC-naive NVAF patients who started to use DOACs for ischaemic stroke prevention between 2013 and 2018 were included using Dutch national statistics. Persistence with OACs was determined based on the presence of a 100-day gap between the last prescription and the end of study period. In 93 048 patients, 75.7% had a baseline CHA2DS2-VASc score of ≥2. The cumulative incidence of persistence with OACs was 88.1% [95% confidence interval (CI) 87.9-88.3%], 82.6% (95% CI 82.3-82.9%), 77.7% (95% CI 77.3-78.1%), and 72.0% (95% CI 71.5-72.5%) at 1, 2, 3, and 4 years after receiving DOACs, respectively. Baseline characteristics associated with better persistence with OACs included female sex, age range 65-74 years, permanent atrial fibrillation, previous exposure to vitamin K antagonists, stroke history (including transient ischaemic attack), and a CHA2DS2-VASc score ≥2. Non-persistence with OACs was associated with an increased risk of the composite outcome of ischaemic stroke and ischaemic stroke-related death [adjusted hazard ratio (aHR) 1.79, 95% CI 1.49-2.15] and ischaemic stroke (aHR 1.58, 95% CI 1.29-1.93) compared with being persistent with OACs. CONCLUSION: At least a quarter of NVAF patients were non-persistent with OACs within 4 years, which was associated with poor efficacy of ischaemic stroke prevention. The identified baseline characteristics may help identify patients at risk of non-persistence.
Assuntos
Fibrilação Atrial , Isquemia Encefálica , Acidente Vascular Cerebral , Administração Oral , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Feminino , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: Acute respiratory distress syndrome (ARDS) becomes a serious challenge in critical care medicine due to the lack of effective therapy. As the damage of alveolar epithelium is a characteristic feature of ARDS, inducing mesenchymal stem cells (MSCs) to differentiate into alveolar epithelial cells turns out to be a promising therapy for ARDS, but the differentiation efficiency is yet to be improved. The study aimed to investigate the effect of overexpressing FoxM1 on MSCs' differentiation into alveolar epithelial cells. METHODS: MSCs were isolated from mouse bone marrow, followed by transfected with lentivirus carrying the FoxM1 plasmid. Small airway epithelial cell growth medium was used as a culture system for inducing MSCs' differentiation into alveolar epithelial cells. Differentiation efficiency was assessed by detecting the expression levels of specific markers of alveolar epithelial cells mainly using quantitative reverse-transcription polymerase chain reaction and Western blot. To examine whether Wnt/ß-catenin signalling was involved in the regulation mechanism, a specific inhibitor of the pathway XAV-939 was used and nuclear and cytoplasmic proteins were also analysed respectively. Co-immunoprecipitation was performed to examine the potential interaction between FoxM1 and ß-catenin. RESULTS: Overexpressing FoxM1 statistically significantly increased the expression levels of specific markers of type II alveolar epithelial cells prosurfactant protein C and surfactant protein B, which was partially reversed by XAV-939 treatment, while the expression levels of specific marker of type I alveolar epithelial cells aquaporin 5 did not change significantly. Overexpressing FoxM1 also increased the nuclear translocation of ß-catenin and its transcriptional activity. A direct interaction between FoxM1 and ß-catenin was found in co-immunoprecipitation assay. CONCLUSION: Overexpression of FoxM1 could improve the efficiency of MSCs' differentiation into type II alveolar epithelial cells partly by activating Wnt/ß-catenin signalling.
Assuntos
Células Epiteliais Alveolares/citologia , Células Epiteliais Alveolares/metabolismo , Diferenciação Celular , Proteína Forkhead Box M1/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Via de Sinalização Wnt , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Masculino , Células-Tronco Mesenquimais/ultraestrutura , Camundongos Endogâmicos C57BL , beta Catenina/metabolismoRESUMO
BACKGROUND: To evaluate the association between crowding and transmission of viral respiratory infectious diseases, we investigated the change in transmission patterns of influenza and COVID-19 before and after a mass gathering event (i.e., carnival) in the Netherlands. METHODS: Information on individual hospitalizations related to the 2017/2018 influenza epidemic were accessed from Statistics Netherlands. The influenza cases were stratified between non-carnival and carnival regions. Distributions of influenza cases were plotted with time and compared between regions. A similar investigation in the early outbreak of COVID-19 was also conducted using open data from the Dutch National Institute for Public Health and the Environment. RESULTS: Baseline characteristics between non-carnival and carnival regions were broadly similar. There were 13,836 influenza-related hospitalizations in the 2017/2018 influenza epidemic, and carnival fell about 1 week before the peak of these hospitalizations. The distributions of new influenza-related hospitalizations per 100,000 inhabitants with time between regions followed the same pattern with a surge of new cases in the carnival region about 1 week after carnival, which did not occur in the non-carnival region. The increase of new cases for COVID-19 in the carnival region exceeded that in the non-carnival region about 1 week after the first case was reported, but these results warrant caution as for COVID-19 there were no cases reported before the carnival and social measures were introduced shortly after carnival. CONCLUSION: In this study, a mass gathering event (carnival) was associated with aggravating the spread of viral respiratory infectious diseases.
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Infecções por Coronavirus/epidemiologia , Aglomeração , Epidemias , Influenza Humana/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , COVID-19 , Humanos , Países Baixos/epidemiologiaRESUMO
Ghrelin has proven to be protective against sepsis-induced acute lung injury (ALI) via anti-inflammatory effects. However, its mechanisms remain poorly understood. Alveolar macrophages (AMs) play a key role in mediating inflammatory responses during sepsis-induced ALI by secretion of cytokines and chemokines. This study was undertaken to investigate whether ghrelin suppresses inflammatory effects of AMs and therefore may help to attenuate sepsis-induced ALI. A sepsis model in rats was achieved using cecal ligation and puncture. Ghrelin treatment markedly improved histopathological changes in the lungs and reduced pulmonary inflammation in septic rats. NF-κB translocation and p-Akt and inducible nitric oxide synthase (iNOS) activities in AMs from septic rats were suppressed by ghrelin. In vitro data indicated that ghrelin decreased the levels of LPS-induced IL-1ß, TNF-α, and IL-6, NF-κB translocation, and iNOS and Akt activities of AMs. Furthermore, the NF-κB/iNOS pathway or Akt signaling was positively correlated with LPS-induced inflammatory production of AMs in vitro. In conclusion, ghrelin exerts a protective role against sepsis-induced ALI probably by reducing the production of inflammatory cytokines from AMs via inhibition of the NF-κB/iNOS pathway or Akt signaling.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Grelina/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Sepse/complicações , Lesão Pulmonar Aguda/patologia , Animais , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Masculino , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Sepse/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacosRESUMO
Neural stem cells (NSCs) transplantation represents a promising strategy for the repair of injured neurons, since NSCs not only produce multiple neurotrophic growth factors but also differentiate into mature cells to replace damaged cells. Previous studies have shown that Notch signaling pathway had negative effects on neuronal differentiation; however, the precise mechanism remained inadequately understood. This research aimed to investigate whether inhibition of Notch1 signaling promotes neuronal differentiation and improves functional recovery in rat spinal cord injury through suppressing the activation of Ras homolog family member A (RhoA). QPCR, western blot, and immunofluorescence experiments were used to analyze Notch1 signaling pathways, RhoA, Ras homologous -associated coiled-coil containing protein kinase 1 (ROCK1), cleaved caspased-3, and neuronal/astrocytic differentiation markers. The expression of RhoA and ROCK1 was inhibited by lentivirus or specific biochemical inhibitors. In spinal cord injury (SCI), motor function was assessed by hind limbs movements and electrophysiology. Tissue repairing was measured by immunofluorescence, Nissl staining, Fluorogold, HE staining, QPCR, western blot, and magnetic resonance imaging (MRI) experiments. Our results demonstrate that inhibition of Notch1 in NSCs can promote the differentiation of NSCs to neurons. Knockdown of RhoA and inhibition of ROCK1 both can promote neuronal differentiation through inhibiting the activation of Notch1 signaling pathway in NSCs. In SCI, silencing RhoA enhanced neuronal differentiation and improved tissue repairing/functional recovery by inhibiting the activation of Notch1 signaling pathway. Since Notch1 inhibits neuronal differentiation through activating the RhoA/ROCK1 signaling pathway in NSCs, our data suggest that the Notch1/RhoA/ROCK1/Hes1/Hes5 signaling pathway may serve as a novel target for the treatment of SCI.
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Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/transplante , Receptor Notch1/metabolismo , Traumatismos da Medula Espinal/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Diferenciação Celular/fisiologia , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Transdução de Sinais/fisiologia , Transplante de Células-TroncoRESUMO
BACKGROUND: Peripheral artery disease (PAD) is often asymptomatic but increases the risk of developing cardiovascular events. Due to the uncertainties regarding the quality of related guidelines and a lack of clear-cut evidence, we performed a systematic review and critical appraisal of these guidelines to evaluate their consistency of the recommendations in asymptomatic PAD population. METHODS: Guidelines in English between January 1st, 2000 to December 31th, 2017 were screened in databases including Medline via PubMed, EMBASE, the G-I-N International Guideline Library, the National Guidelines Clearinghouse, the Canadian Medication Association Infobase and the National Library for Health. Those guidelines containing recommendations on screening and treatment for asymptomatic PAD were included, and three reviewers evaluated the quality of the guidelines using Appraisal of Guidelines Research and Evaluation (AGREE) II instrument. Related recommendations were then fully extracted and compared by two reviewers. RESULTS: Fourteen guidelines were included finally and the AGREE scores ranged from 39 to 73%. Most of included guidelines scored low in Rigor of development and Editorial independence, and only two guidelines (ACCF/AHA, AHA/ACC) reached the standard on Conflict of Interest from Institute of Medicine (IOM). Eight guidelines recommended screening at different strength while the others found insufficient evidence or were against screening. Conflicting recommendations on treatment were found in the target value of the lipid lowering and antiplatelet therapy. The treatment policies in three guidelines (BWG, CEVF, ESC) appeared more aggressive, but they had low transparency between guideline developer and industry or did not reach the standard of IOM. CONCLUSIONS: Current guidelines on asymptomatic PAD varied in the methodological quality and fell short of the standard in the rigor of development and editorial independence. Conflicting recommendations were found both on the screening and treatment. More effort is needed to provide clear-cut evidences with high quality and transparency among guideline developer and industry.
Assuntos
Técnicas de Diagnóstico Cardiovascular/normas , Medicina Baseada em Evidências/normas , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Guias de Prática Clínica como Assunto/normas , Doenças Assintomáticas , Consenso , Humanos , Valor Preditivo dos Testes , PrognósticoRESUMO
BACKGROUND/AIMS: In the process of abnormal apoptosis of pulmonary alveolar type II epithelial A549 cells in acute respiratory distress syndrome (ARDS), inducible nitric oxide synthase (iNOS) activity in the lung, nitric oxide (NO) production, and the level of protein S-nitrosylation were increased. However, the role of excessive NO production in sepsis-induced ARDS is controversial. Additionally, ghrelin is a growth hormone that exerts an inhibitory role in cell apoptosis. We examined the effect of NO and S-nitrosylation on apoptosis of A549 cells induced by Lipopolysaccharide (LPS) and molecular mechanism underlying the anti-apoptotic effect of ghrelin in this process. METHODS: Flow cytometry and qPCR were used to detect lentiviral infection efficiency and iNOS gene level, respectively. Extracellular and intracellular NO levels were observed by Griess assay kit and DAF-FM DA. Mitochondrial transmembrane potential, apoptosis rate and SNO levels were determined by flow cytometry, Biotin-Switch method and immunofluoresence staining. The expression of iNOS, apoptotic proteins and JNK were assessed by immunoblot analysis. RESULTS: The results showed about two times increase in iNOS expression and intracellular NO levels response to LPS exposure at 24 hours (P< 0.05), while not in extracellular NO levels. NO donors, S-nitroso-N-acetylpenicillamine (SNAP) significantly raised (36.7%, P< 0.05; 38.4%, P< 0.05; 41.8%, P< 0.05) extracellular NO levels without influencing the intracellular NO levels. LPS increased the apoptosis rate (42.4%±2.6% vs 2.8%±1%, P< 0.05) of A549 accompanied by increased Bax levels and decreased Bcl-2 levels through activating JNK signaling, which was reversed when we diminished the iNOS expression in A549 cells using lentiviral vectors encoding iNOS shRNA in the presence of LPS (24.8%±3.8% vs 42.4%±2.6%, P< 0.05). However, the apoptosis rate was increased when SNAP was added (38.8%±1.3% vs 24.8%±3.8%, P< 0.05). Furthermore, we investigated whether ghrelin exert a protective role against LPS-induced apoptosis and the potential mechanism involved in. Ghrelin alone appeared to decrease iNOS expression (32.3%, P< 0.05; 42.3%, P< 0.05), which showed no signifiant difference between LPS+ghrelin group and LPS group. However, this study showed that ghrelin decreased the intracellular NO production (38.9%, P< 0.05), protein S-nitrosylation levels (33.5%, P< 0.05), Bax protein expression (70.2%, P< 0.05), whereas increasing Bcl-2 protein expression (14.1%, P< 0.05) and mitochondrial transmembrane potential (∆ΨM) (20.7%, P< 0.05) in the presence of LPS. CONCLUSION: The data suggested that NO derived from iNOS induced by LPS stimulation exerts an important role in promoting apoptosis of A549 cells, and ghrelin abolished intracellular NO production and protein S-nitrosylation levels, abrogating the apoptosis of A549 cells partly through inhibiting mitochondrial-dependent pathways.
Assuntos
Apoptose/efeitos dos fármacos , Grelina/farmacologia , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Células A549 , Células Epiteliais Alveolares/citologia , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , S-Nitroso-N-Acetilpenicilamina/farmacologia , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Injury of alveolar epithelial cells and capillary endothelial cells is crucial in the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) are a promising cell source for ALI/ARDS treatment. Overexpression of Fork head box protein M1 (FoxM1) facilitates MSC differentiation into alveolar type II (AT II) cells in vitro. Moreover, FoxM1 has been shown to repair the endothelial barrier. Therefore, this study explored whether overexpression of FoxM1 promotes the therapeutic effect of bone marrow-derived MSCs (BMSCs) on ARDS by differentiation of BMSCs into AT II cells or a paracrine mechanism. METHODS: A septic ALI model was established in mice by intraperitoneal administration of lipopolysaccharide. The protective effect of BMSCs-FoxM1 on ALI was explored by detecting pathological variations in the lung, total protein concentration in bronchoalveolar lavage fluid (BALF), wet/dry (W/D) lung weight ratio, oxidative stress levels, cytokine levels, and retention of BMSCs in the lung. In addition, we assessed whether FoxM1 overexpression promoted the therapeutic effect of BMSCs on ALI/ARDS by differentiating into AT II cells using SPC-/- mice. Furthermore, the protective effect of BMSCs-FoxM1 on lipopolysaccharide-induced endothelial cell (EC) injury was explored by detecting EC proliferation, apoptosis, scratch wounds, tube formation, permeability, and oxidative stress, and analyzing whether the Wnt/ß-catenin pathway contributes to the regulatory mechanism in vitro using a pathway inhibitor. RESULTS: Compared with BMSCs-Vector, treatment with BMSCs-FoxM1 significantly decreased the W/D lung weight ratio, total BALF protein level, lung injury score, oxidative stress, and cytokine levels. With the detected track of BMSCs-FoxM1, we observed a low residency rate and short duration of residency in the lung. Notably, SPC was not expressed in SPC-/- mice injected with BMSCs-FoxM1. Furthermore, BMSCs-FoxM1 enhanced EC proliferation, migration, and tube formation; inhibited EC apoptosis and inflammation; and maintained vascular integrity through activation of the Wnt/ß-catenin pathway, which was partially reversed by XAV-939. CONCLUSION: Overexpression of FoxM1 enhanced the therapeutic effect of BMSCs on ARDS, possibly through a paracrine mechanism rather than by promoting BMSC differentiation into AT II cells in vivo, and prevented LPS-induced EC barrier disruption partially through activating the Wnt/ß-catenin signaling pathway in vitro.
Assuntos
Proteína Forkhead Box M1 , Lesão Pulmonar , Células-Tronco Mesenquimais , Síndrome do Desconforto Respiratório , Animais , Camundongos , beta Catenina/metabolismo , Células da Medula Óssea , Citocinas/metabolismo , Células Endoteliais/metabolismo , Lipopolissacarídeos/toxicidade , Células-Tronco Mesenquimais/metabolismo , Síndrome do Desconforto Respiratório/terapia , Proteína Forkhead Box M1/genéticaRESUMO
Importance: The temporal trend in adverse events regarding stroke prevention for nonvalvular atrial fibrillation (NVAF) in the direct oral anticoagulant (DOAC) era was rarely investigated comprehensively, especially taking into account potential changes in patient characteristics and anticoagulation treatment. Objective: To investigate time trends in patient characteristics, anticoagulation treatment, and prognosis of patients with incident NVAF in the Netherlands. Design, Setting, and Participants: This retrospective cohort study assessed patients with incident NVAF initially recognized within a hospitalization between 2014 and 2018, using data from Statistics Netherlands. Participants were followed-up for 1 year from the hospital admission at which the incident NVAF diagnosis was made or until death, whichever occurred first. Data were analyzed from January 15, 2021, to March 8, 2023. Exposure: Calendar year of the incident NVAF diagnosis, according to which the participants were categorized into 5 cohorts. Main Outcomes and Measures: Outcomes of interest were baseline patient characteristics, anticoagulation treatment, and occurrence of ischemic stroke or major bleeding within the 1-year follow-up after incident NVAF. Results: Between 2014 and 2018, 301â¯301 patients (mean [SD] age, 74.2 [11.9] years; 169â¯748 [56.3%] male patients) experienced incident NVAF in the Netherlands, each of whom was categorized into 1 of 5 cohorts by calendar year. Baseline patient characteristics were broadly the same between cohorts with a mean (SD) CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65 to 74 years, and sex category [female]) score of 2.9 (1.7). The median (IQR) proportion of days covered by OACs (ie, vitamin K antagonists or DOACs) within the 1-year follow-up increased from 56.99% (0%-86.30%) to 75.62% (0%-94.52%), and DOACs increased from 5102 patients (13.5%) to 32â¯314 patients (72.0%) among those who received OACs, gradually replacing VKAs as the first choice of OACs. Over the course of the study, there were statistically significant decreases in the 1-year cumulative incidence of ischemic stroke (from 1.63% [95% CI, 1.52%-1.73%] to 1.39% [95% CI, 1.30%-1.48%) and major bleeding (from 2.50% [95% CI, 2.37%-2.63%] to 2.07% [95% CI, 1.96%-2.19%]), and the association was consistent after adjusting for baseline patient characteristics and excluding those with preexisting chronic anticoagulation. Conclusions and Relevance: This cohort study of patients with incident NVAF diagnosed between 2014 and 2018 in the Netherlands found similar baseline characteristics, increased OAC use with DOACs being favored over time, and improved 1-year prognosis. Comorbidity burden, potential underuse of anticoagulation medications, and specific subgroups of patients with NVAF remain directions for future investigations and further improvement.
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Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos Retrospectivos , Estudos de Coortes , Países Baixos/epidemiologia , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Prognóstico , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , AVC Isquêmico/tratamento farmacológicoRESUMO
This population-based cohort study aimed to describe changes in incidence of cardiovascular disease (CVD) hospital diagnoses during the COVID-19 pandemic in The Netherlands compared with the pre-pandemic period. We used Dutch nationwide statistics about hospitalizations to estimate incidence rate ratios (IRR) of hospital diagnoses of CVD during the first and second COVID-19 waves in The Netherlands in 2020 versus the same periods in 2019. Compared with 2019, the incidence rate of a hospital diagnosis of ischemic stroke (IRR 0.87; 95% CI 0.79-0.95), major bleeding (IRR 0.74; 95% CI 0.68-0.82), atrial fibrillation (IRR 0.73; 95% CI 0.65-0.82), myocardial infarction (IRR 0.78; 95% CI 0.72-0.84), and heart failure (IRR 0.74; 95% CI 0.65-0.85) declined during the first wave, but returned to pre-pandemic levels throughout 2020. However, the incidence rate of a hospital diagnosis of pulmonary embolism (PE) increased during both the first and second wave in 2020 compared with 2019 (IRR 1.30; 95% CI 1.15-1.48 and IRR 1.31; 95% CI 1.19-1.44, respectively). In conclusion, we observed substantial declines in incidences of CVD during the COVID-19 pandemic in The Netherlands in 2020, especially during the first wave, with an exception for an increase in incidence of PE. This study contributes to quantifying the collateral damage of the COVID-19 pandemic.
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COVID-19 , Doenças Cardiovasculares , Embolia Pulmonar , Humanos , Doenças Cardiovasculares/epidemiologia , Incidência , Pandemias , Estudos de Coortes , Países Baixos/epidemiologia , COVID-19/epidemiologia , Hospitalização , Embolia Pulmonar/epidemiologiaRESUMO
[This corrects the article DOI: 10.3389/fcvm.2022.919716.].
RESUMO
Introduction: Evidence suspects proton pump inhibitor (PPI) use is a risk factor of poor prognosis of acute myocardial infarction (AMI). We aimed to investigate the association between pre-existing PPI use before emergency department (ED) visit and short-term prognosis of AMI patients. Materials and Methods: AMI patients admitted to ED were included and categorized as cohorts with or without pre-existing PPI use. Hospital mortality, length of hospital stay, being admitted to intensive care unit (ICU), and length of (total) ICU stay were studied as prognostic outcomes. Multivariable logistic regression or linear regression were used to estimate the associations between pre-existing PPI use and the outcomes after adjusting for potential confounders. Results: A total of 2001 AMI patients were included. No significant difference was found in hospital mortality and length of ICU stay between cohorts; patients with pre-existing PPI use showed a significantly longer length of hospital stay (median 3.81 vs. 3.20 days, P = 0.002) but lower proportion of being admitted to ICU (25.59% vs. 40.83%, P < 0.001) compared to those without pre-existing PPI use. Pre-existing PPI use was not associated with hospital mortality [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.58-1.99], length of hospital stay (ß = 0.23, 95% CI -0.35 to 0.82), and length of ICU stay (ß = -0.18, 95% CI -1.06 to 0.69), but was statistically significantly associated with lower risk of being admitted to ICU (OR 0.69, 95% CI 0.52-0.92). Conclusion: The current study does not support newly diagnosed AMI patients with pre-existing PPI use before ED visit would experience worse short-term prognosis than those without.
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BACKGROUND: Abnormal vitamin D is prevalent in critical care settings, but its association with prognosis remains unclear. The study aimed to investigate the prevalence and predictors of abnormal blood 25-hydroxyvitamin D (25(OH)D), as well as its association with prognosis in critically ill patients. METHODS: Patients aged ≥ 18 years who were once admitted to the intensive care units (ICUs) of the Beth Israel Deaconess Medical Center between 2008 and 2019 with at least one measurement record of blood 25(OH)D were included as study population. Baseline characteristics associated with deficient or elevated blood 25(OH)D were investigated by univariable logistic regression analysis. The association between abnormal blood 25(OH)D and hospital mortality was examined by multivariable logistic regression analysis. RESULTS: A total of 1091 patients were included. Deficient 25(OH)D (< 30 ng/mL) was found in 790 (72.41%) patients and 17 (1.56%) were with an elevated level (> 60 ng/mL). A younger age, male, comorbid liver disease, and dialysis were risk factors of deficient blood 25(OH)D, while comorbid myocardial infarction, dementia, and rheumatic disease were protective factors evaluated by univariable logistic regression. Being admitted to cardiac vascular ICU or coronary care unit were associated with increased risk of elevated blood 25(OH)D. Patients with elevated blood 25(OH)D showed non-significantly higher hospital mortality compared to those with normal or deficient blood 25(OH)D (35.29% versus 14.44% and 14.56%, P = 0.058). After adjusted for potential confounding factors, elevated blood 25(OH)D was associated with increased risk of hospital mortality [odds ratio (OR) 3.80, 95% confidence interval (CI) 1.22-11.82, P = 0.021] when compared to those with normal blood 25(OH)D, but there was no significant association between deficient blood 25(OH)D and hospital mortality (OR 1.12, 95% CI 0.74-1.72, P = 0.589). CONCLUSIONS: These findings suggest deficient blood 25(OH)D was rather common in critically ill patients, but was not an independent risk factor of hospital mortality, while elevated blood 25(OH)D was associated with worse prognosis.
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Estado Terminal , Deficiência de Vitamina D , Mortalidade Hospitalar , Humanos , Masculino , Prevalência , Vitamina D/análogos & derivados , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologiaRESUMO
BACKGROUND: Lung endothelial barrier injury plays a crucial role in the pathophysiology of acute respiratory distress syndrome. It has been demonstrated that bone marrow-derived mesenchymal stem cells-conditioned medium (BMSCs-CM) and ghrelin have a protective effect. This study investigated if ghrelin pretreatment enhanced the protective effect of BMSCs-CM on lipopolysaccharide (LPS)-induced endothelial cell injury. METHODS: BMSCs were isolated from rat bone marrow, expanded, then phenotypically tested for mesenchymal stem cell-identifying criteria by flow cytometry. The effects of the conditioned medium derived from ghrelin-pretreated BMSCs (BMSCs-ghrelin-pretreated-CM) on LPS-injured endothelial cells were evaluated by migration, apoptosis, permeability, and pro-inflammatory factor (e.g., tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6) assays in endothelial cells. Further, AKT/GSK3ß pathway activation in endothelial cells was examined by Western blot, and the gene expression profiles of ghrelin-pretreated BMSCs were examined by RNA sequencing. RESULTS: BMSCs-ghrelin-pretreated-CM had a greater protective effect on LPS-induced endothelial cell injury than BMSCs-CM by improving cell migration, alleviating apoptosis, and reducing endothelial permeability and the release of pro-inflammatory factors in endothelial cells. The mechanism is partly related to AKT/GSK3ß pathway activation after BMSCs-ghrelin-pretreated-CM treatment. There were five upregulated candidate genes (Wnt5a [i.e., Wnt Family Member 5A], S100b [i.e., S100 Calcium-Binding Protein B], Bmp2 [i.e., Bone Morphogenetic Protein 2], Id4 [i.e., Inhibitor Of DNA Binding 4], and PTHLH [i.e., Parathyroid Hormone Like Hormone]) in BMSCs after ghrelin treatment, and all were associated with AKT pathway activation and endothelial function. CONCLUSIONS: Ghrelin pretreatment enhanced the protective effect of BMSCs-CM on LPS-induced endothelial cell injury, partly by activating the AKT/GSK3ß pathway.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Medula Óssea , Células da Medula Óssea , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/metabolismo , Grelina/metabolismo , Grelina/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Lipopolissacarídeos/farmacologia , Células-Tronco Mesenquimais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de SinaisRESUMO
INTRODUCTION: Bloodstream infection (BSI) may occur after cardiac procedures, but this has rarely been investigated specifically in pediatric patients after percutaneous or surgical treatment for ventricular septal defect (VSD) or atrial septal defect (ASD) with recent data. The current study aimed to investigate the incidence, clinical features, and association with prognosis of BSI in this patient population. METHODS: Pediatric patients who received percutaneous or surgical procedure for VSD or ASD between 2010 and 2018 in a large children's hospital in China were retrospectively enrolled via the Pediatric Intensive Care database, but only those who had blood culture records within 24 h after the procedure and who had no prior positive blood culture records were included. BSI after the procedure was identified by reviewing blood culture records, and baseline characteristics associated with BSI were explored by univariable logistic regression. In-hospital mortality and length of hospitalization were studied as prognostic outcomes and compared between patients with and without BSI. RESULTS: A total of 1340 pediatric patients were included. Among them, 46 (3.43%) patients had BSI within 24 h after the procedure, of which the majority (78.26%, 36/46) were caused by Gram-positive bacteria and 65.22% (30/46) had antibiotic-resistant organisms. Age [odds ratio (OR) 0.98 per 1-month increase, 95% confidence interval (CI) 0.97-1.00, P = 0.021] and antibiotic use within 72 h before the procedure (OR 1.81, 95% CI 1.00-3.26, P = 0.049) were statistically significantly associated with developing BSI. Compared with patients without BSI, there was no statistically significant difference in in-hospital mortality (0.00% versus 0.54%, P = 1.000), but patients with BSI had statistically significantly longer length of hospitalization (median 14.51 versus 12.94 days, P = 0.006), while the association was not statistically significant after adjustment for baseline characteristics by multivariable linear regression (ß = 1.73, 95% CI -0.59 to 4.04, P = 0.144). CONCLUSION: BSI is relatively uncommon in pediatric patients after procedures for VSD or ASD, but a younger age seems a risk factor. Developing BSI appears to be associated with increased length of hospitalization but not in-hospital mortality.
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BACKGROUND: Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low. OBJECTIVE: To examine if pre-switch TTR determines persistence patterns in NVAF patients who are switched from a VKA to DOAC. PATIENTS/METHODS: Adult NVAF patients from three Dutch anticoagulation clinics who were newly switched from a VKA to DOAC between July 1, 2013 and September 30, 2018 were stratified by pre-switch TTR levels. DOAC prescription records were examined to determine persistence patterns according to a 100-day prescription gap. Cumulative incidences of non-persistence to DOAC were estimated using the cumulative incidence competing risk method. The association of pre-switch TTR levels with DOAC non-persistence was evaluated by Cox regression models. RESULTS: A total of 3696 NVAF patients were included, of whom 690 (18.7%) had a pre-switch TTR ≤ 45%. After switching from VKA to DOAC, 14.0% (95% confidence interval [CI] 11.3-17.0%) of the patients with a pre-switch TTR ≤ 45% became non-persistent to DOAC within 1 year, while 9.8% (95% CI 8.7-11.0%) did in those with a pre-switch TTR > 45%. In a multivariable model, a pre-switch TTR ≤ 45% was associated with a higher risk of non-persistence to DOAC (adjusted hazard ratio 1.55, 95% CI 1.22-1.97). Results were similar when using other cut-off points (60% or 70%) to define a low TTR. CONCLUSION: NVAF patients switching from VKA to DOAC due to a low pre-switch TTR saw a worse persistence pattern to DOAC after the switch compared to patients with a high pre-switch TTR.
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Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Adulto , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Vitamina KRESUMO
PURPOSE: To investigate the association of cardiac Troponin T (cTnT) with prognosis in critically ill patients without myocardial infarction. METHODS: Adult patients admitted to the intensive care units (ICUs) of the Beth Israel Deaconess Medical Center between 2008 and 2019 who were free of myocardial infarction with a length of ICU stay ≥24 hours and available cTnT records within 24 hours before and after ICU admission were included. The association between cTnT on ICU admission and hospital mortality was evaluated by multivariable logistic regression analysis. The discrimination capacity of cTnT on ICU admission for predicting hospital mortality was examined by receiver operating characteristic (ROC) analysis. RESULTS: A total of 2960 patients were included. Elevated cTnT (>0.01 ng/mL) was observed in 2730 (92.23%) patients with a higher hospital mortality compared to normal cTnT (11.21% versus 7.39%, P=0.075). There was no statistically significant association between elevated cTnT on ICU admission and hospital mortality (adjusted odds ratio 1.50, 95% confidence interval (CI) 0.88-2.57). Poor discrimination capacity was found for cTnT on ICU admission to predict hospital mortality (area under the ROC curve 0.48, 95% CI 0.44-0.53). CONCLUSION: cTnT on ICU admission has limited prognostic value in critically ill patients without myocardial infarction.
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OBJECTIVE: To investigate the characteristics and prognosis of abdominal or thoracic aortic aneurysm (AAA or TAA) patients admitted to intensive care unit (ICU) postoperatively. METHODS: Patients admitted to ICU postoperatively with a primary diagnosis of AAA or TAA were screened in the eICU Collaborative Research Database, which contained data from multiple ICUs throughout the continental United States in 2014 and 2015. Baseline characteristics and comorbidities and were investigated and factors associated with ICU mortality were explored using univariable logistic regression. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the prognosis predictive performance of the widely used severity scoring system APACHE IVa. RESULTS: A total of 974 patients including 677 AAA and 297 TAA patients admitted to ICU postoperatively were included. Compared with TAA, AAA patients had a significantly higher median age (72 versus 64 years, P<0.001). 89.07% AAA and 84.51% TAA patients underwent elective surgery (P=0.046), 8.71% AAA and 31.99% TAA patients were with aortic dissection (P<0.001), and 10.19% AAA and 2.36% TAA patients suffered from rupture of aortic aneurysm (P<0.001). Hypertension requiring treatment was the most common comorbidity (57.31% for AAA and 61.95% for TAA). TAA patients had significantly higher ICU mortality (9.43% versus 2.36%, P<0.001) than AAA. Several factors were found to be significantly associated with ICU mortality, including urgent surgery, with aortic dissection, rupture of aortic aneurysm, TAA, and a higher APACHE IVa score on ICU admission. APACHE IVa showed a good predictive performance for ICU mortality with an area under the ROC curve of 0.9176 (95% CI 0.8789-0.9390). CONCLUSION: The prognosis of aortic aneurysm patients admitted to ICU postoperatively is yet to improve, and factors associated with prognosis are mainly related to the condition itself. APACHE IVa can be used for prognosis prediction.