Coexisting atrial fibrillation and cancer: time trends and associations with mortality in a nationwide Dutch study.

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.

Changes in incidence of hospitalization for cardiovascular diseases during the COVID-19 pandemic in The Netherlands in 2020.

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.

Time Trends in Patient Characteristics, Anticoagulation Treatment, and Prognosis of Incident Nonvalvular Atrial Fibrillation in the Netherlands.

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, 301 301 patients (mean [SD] age, 74.2 [11.9] years; 169 748 [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 32 314 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.

Overexpression of FoxM1 optimizes the therapeutic effect of bone marrow mesenchymal stem cells on acute respiratory distress syndrome.

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.

Incidence, Clinical Features, and Association with Prognosis of Bloodstream Infection in Pediatric Patients After Percutaneous or Surgical Treatment for Ventricular Septal Defect or Atrial Septal Defect: A Retrospective Cohort Study.

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.

Corrigendum: Pre-existing proton pump inhibitor treatment and short-term prognosis of acute myocardial infarction patients.

[This corrects the article DOI: 10.3389/fcvm.2022.919716.].

Abnormal blood 25-hydroxyvitamin D in critically ill patients: prevalence, predictors, and its association with in-hospital mortality.

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.

Pre-existing Proton Pump Inhibitor Treatment and Short-Term Prognosis of Acute Myocardial Infarction Patients.

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.

Ghrelin pretreatment enhanced the protective effect of bone marrow-derived mesenchymal stem cell-conditioned medium on lipopolysaccharide-induced endothelial cell injury.

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.

Switching from vitamin K antagonists to direct oral anticoagulants in non-valvular atrial fibrillation patients: Does low time in therapeutic range affect persistence?

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.

Ghrelin protects against lipopolysaccharide-induced acute respiratory distress syndrome through the PI3K/AKT pathway.

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.

Overexpression of HOXB4 Promotes Protection of Bone Marrow Mesenchymal Stem Cells Against Lipopolysaccharide-Induced Acute Lung Injury Partially Through the Activation of Wnt/ß-Catenin Signaling.

PURPOSE: Pulmonary vascular endothelial cell (EC) injury is recognized as one of the pathological factors of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Bone marrow mesenchymal stem cell (BMSC)-based cytotherapy has attracted substantial attention over recent years as a promising therapeutic approach for ALI/ARDS; however, its use remains limited due to inconsistent efficacy. Currently, gene modification techniques are widely applied to MSCs. In the present study, we aimed to investigate the effect of BMSCs overexpressing Homeobox B4 (HOXB4) on lipopolysaccharide (LPS)-induced EC injury. METHODS: We used LPS to induce EC injury and established EC-BMSC coculture system using transwell chambers. The effect of BMSCs on ECs was explored by detecting EC proliferation, apoptosis, migration, tube formation, and permeability, and determining whether the Wnt/ß-catenin pathway is involved in the regulatory mechanism using XAV-939, inhibitor of Wnt/ ß-catenin. RESULTS: As compared to BMSCWT, BMSCHOXB4 coculture promoted EC proliferation, migration, and tube formation after LPS stimulation and attenuated LPS-induced EC apoptosis and vascular permeability. Mechanistically, BMSCHOXB4 coculture prevented LPS-induced EC injury by activating the Wnt/ß-catenin pathway, which is partially reversible by XAV-939. When cocultured with BMSCHOXB4, pro-inflammatory factors were dramatically decreased and anti-inflammatory factors were greatly increased in the EC medium compared to those in the LPS group (P<0.05). Additionally, when compared to BMSCWT coculture, the BMSCHOXB4 coculture showed an enhanced modulation of IL-6, TNF-α, and IL-10, but there was no statistically significant effect on IL-1ß and IL-4. CONCLUSION: Coculturing of BMSCHOXB4 prevented LPS-induced EC injury by reversing the inactivation of the Wnt/ß-catenin signaling pathway. An in vivo study remains warranted to ascertain whether engraftment of BMSCHOXB4 can be an attractive strategy for the treatment of ALI/ARDS.

Predictors, time course, and outcomes of persistence patterns in oral anticoagulation for non-valvular atrial fibrillation: a Dutch Nationwide Cohort Study.

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.

Association of Cardiac Troponin T Concentration on Admission with Prognosis in Critically Ill Patients without Myocardial Infarction: A Cohort Study.

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.

Risk of thrombotic complications in influenza versus COVID-19 hospitalized patients.

Background: Whereas accumulating studies on patients with coronavirus disease 2019 (COVID-19) report high incidences of thrombotic complications, large studies on clinically relevant thrombosis in patients with other respiratory tract infections are lacking. How this high risk in COVID-19 patients compares to those observed in hospitalized patients with other viral pneumonias such as influenza is unknown. Objectives: To assess the incidence of venous and arterial thrombotic complications in hospitalized patients with influenza as opposed to that observed in hospitalized patients with COVID-19. Methods: This was a retrospective cohort study; we used data from Statistics Netherlands (study period: 2018) on thrombotic complications in hospitalized patients with influenza. In parallel, we assessed the cumulative incidence of thrombotic complications-adjusted for competing risk of death-in patients with COVID-19 in three Dutch hospitals (February 24 to April 26, 2020). Results: Of the 13 217 hospitalized patients with influenza, 437 (3.3%) were diagnosed with thrombotic complications, versus 66 (11%) of the 579 hospitalized patients with COVID-19. The 30-day cumulative incidence of any thrombotic complication in influenza was 11% (95% confidence interval [CI], 9.4-12) versus 25% (95% CI, 18-32) in COVID-19. For venous thrombotic (VTC) complications and arterial thrombotic complications alone, these numbers were, respectively, 3.6% (95% CI, 2.7-4.6) and 7.5% (95% CI, 6.3-8.8) in influenza versus 23% (95% CI, 16-29) and 4.4% (95% CI, 1.9-8.8) in COVID-19. Conclusions: The incidence of thrombotic complications in hospitalized patients with influenza was lower than in hospitalized patients with COVID-19. This difference was mainly driven by a high risk of VTC complications in the patients with COVID-19 admitted to the Intensive Care Unit. Remarkably, patients with influenza were more often diagnosed with arterial thrombotic complications.

Characteristics and Prognosis of Abdominal or Thoracic Aortic Aneurysm Patients Admitted to Intensive Care Units After Surgical Treatment: A Multicenter Retrospective Observational Study.

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.

Why crowding matters in the time of COVID-19 pandemic? - a lesson from the carnival effect on the 2017/2018 influenza epidemic in the Netherlands.

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.

Overexpression of FoxM1 promotes differentiation of bone marrow mesenchymal stem cells into alveolar type II cells through activating Wnt/ß-catenin signalling.

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.

Association Between Blood Glucose Within 24 Hours After Intensive Care Unit Admission and Prognosis: A Retrospective Cohort Study.

PURPOSE: The aim of this study was to evaluate the association between blood glucose within 24 hours after intensive care unit (ICU) admission and prognosis. PATIENTS AND METHODS: A retrospective cohort study was conducted using data from a large critical care database. Patients who had a length of ICU stay ≥24 hours and at least two blood glucose records within 24 hours after ICU admission were included and hospital mortality was chosen as the primary outcome. The average, minimum, and maximum blood glucose within 24 hours after ICU admission were a priori selected as exposures and associations between each exposure and outcomes were assessed after adjusted for potential confounders. RESULTS: A total of 14,237 patients were included finally with an average age of 62.9±17.7 years and a mean SAPS II on admission of 34 (26-44). Among the study population, 20.2% (2872/14,237) had uncomplicated diabetes, and 6.7% (953/14,237) had complicated diabetes. Lowest hospital mortality rate was observed in the stratum with an average blood glucose ranged 110-140 mg/dL, a minimum blood glucose ranged 80-110 mg/dL, and a maximum blood glucose ranged 110-140 mg/dL. After adjusted for confounders including age, sex, disease severity scores and comorbidities, an average blood glucose ranged 110-140 mg/dL, a minimum blood glucose ranged 80-110 mg/dL, and a maximum blood glucose ranged 110-140 mg/dL were associated with the lowest risk of hospital mortality. Consistent results were found among patients without diabetes in the subgroup analyses stratified by diabetes. CONCLUSION: A range of 110-140 mg/dL for average and maximum blood glucose and a range of 80-110 mg/dL for minimum blood glucose within 24 hours after ICU admission predicted better prognosis especially among patients without diabetes.

Association Between Comorbid Chronic Obstructive Pulmonary Disease and Prognosis of Patients Admitted to the Intensive Care Unit for Non-COPD Reasons: A Retrospective Cohort Study.

Background and Aim: Chronic obstructive pulmonary disease (COPD) is a rather common comorbid condition among patients admitted to the intensive care unit (ICU), while evidence of how this comorbidity affects prognosis is limited. This study aimed to investigate the associations between COPD comorbidity and prognoses of patients who were admitted to the ICU for non-COPD reasons, and to examine whether the associations varied between different types of ICU. Methods: A retrospective cohort study was performed using data extracted from a freely accessible critical care database (MIMIC-III). Adult (≥18 years) patients of first ICU admission in the database were enrolled as study participants but those with a primary diagnosis of COPD were excluded. The primary endpoint was 28-day mortality after ICU admission and multivariable Cox regression analyses were employed to assess the associations between COPD comorbidity and the study endpoints. Different adjusting models including a propensity score were used to adjust potential confounders. Results: A total of 29,499 patients were enrolled finally, among which 3,332 patients (11.30%) were comorbid with COPD. A higher 28-day mortality was observed among patients with COPD than those without COPD (13.90% versus 8.07%, P<0.001), but there was no statistically significant difference in the proportion of patients who needed mechanical ventilation on the first day after ICU admission between the two groups. Multivariable Cox regression analyses found a significant association between COPD comorbidity and 28-day mortality (adjusted hazard ratio=1.32, 95% confidence interval=1.19-1.47, P<0.0001). The associations were broadly consistent among patients admitted to different types of ICU, but a much higher estimate was observed in patients admitted to cardiac surgery recovery unit (adjusted hazard ratio=2.03, 95% confidence interval=1.44-2.86, P<0.0001). Conclusion: Comorbid COPD increased the risk of 28-day mortality among patients admitted to the ICU for non-COPD reasons, especially for those admitted to the cardiac surgery recovery unit.