IntroductionAtrial fibrillation (AF) is a major cause of mortality and morbidity globally. This study aims to identify predictors of AF-related rehospitalization following an acute AF/flutter ...admission.MethodsPatients admitted to Westmead Hospital with a primary diagnosis of AF/flutter from 1 May 2014 to 31 May 2018 were included and followed up until 31 May 2019. We defined AF-related rehospitalization as an admission due to recurrent AF/flutter, congestive heart failure, stroke and/or myocardial infarction. Multivariable logistic regression was used to identify independent predictors of 30-day outcomes. Cox regression was used to identify independent predictors of long-term outcomesfirst AF-related rehospitalization or all-cause mortality.ResultsOf 1664 consecutive patients admitted with AF/flutter, 55.8% were male and the median age was 68.0. At 30 days, 123 (7.4%) had an AF-related readmission (110 for AF/flutter and 13 for other cardiovascular outcomes). During a mean follow-up period of 2.1 ± 1.5 years, 683 (41.0%) of patients had at least one AF-related rehospitalization (38.1%, n=634) or died (2.9%, n=49). Chronic kidney disease (CKD) (OR 1.94, 95% CI 1.07 - 3.50) was an independent predictor of 30-day AF-related rehospitalization. Age (HR 1.01, 95% CI 1.01 - 1.02 for each additional year), initial admission via emergency (HR 1.29, 95% CI 1.08 - 1.54), CKD (HR 1.64, 95% CI 1.24 - 2.18), chronic obstructive pulmonary disease (HR 1.42, 95% CI 1.09 - 1.83) and the presence of additional comorbidities (HR 1.38, 95% CI 1.04 - 1.83) were independent predictors of first AF-related rehospitalization or death (all p <0.05).ConclusionAF-related rehospitalization is common following an acute AF/flutter admission. AF/flutter patients with comorbidities, particularly renal and pulmonary diseases, are at high risk of readmission. Such patients could be targeted for increased surveillance and additional post-discharge support to prevent readmission.
Abstract only Introduction: New-onset atrial fibrillation (AF) following acute myocardial infarction (AMI) is associated with adverse outcomes, though studies exploring the interaction between AF and ...the full spectrum of acute coronary syndromes (ACS) are scarce. We aim to identify predictors of new-onset AF in the setting of ACS by analyzing data from the prospective CONCORDANCE multi-center registry. Methods: Patients admitted to 41 Australian hospitals from 2009-2018 with ACS and had an angiogram were included. New-onset AF was defined as AF detected on index ECG and/or in-hospital AF. Independent predictors of new-onset AF were identified using multivariable logistic regression models. Results: Of 9070 consecutive patients admitted with ACS, 648 (7.1%) patients developed new-onset AF. These patients had higher rates of major adverse in-hospital events and all-cause mortality compared to patients without new-onset AF. Age (adjusted odds ratio aOR 1.04, 95% confidence interval CI 1.03-1.05), male sex (aOR 1.62, 95%CI 1.29-2.04), higher admission heart rate (aOR 1.02, 95%CI 1.01-1.02), cardiac arrest on admission (aOR 1.98, 95%CI 1.23-3.20), Killip classes 2 (aOR 1.38, 95%CI 1.10-1.73) and 3/4 (aOR 1.72, 95%CI 1.24-2.40) versus 1 were independent predictors of new-onset AF, whereas hypertension (aOR 0.81, 95%CI 0.67-0.99), higher minimum hemoglobin (aOR 0.98, 95%CI 0.97-0.98), pre-admission statins (aOR 0.71, 95%CI 0.56-0.89) and undergoing PCI (aOR 0.64, 95%CI 0.53-0.77) were associated with decreased risk of new-onset AF. When angiographic disease burden was included, double and triple-vessel disease were independent predictors of new-onset AF. However, sequential addition of CABG to the model nullified this association; (CABG (aOR 3.94, 95%CI 2.83-5.49), disease burden non-significant). In the CABG subgroup, peripheral arterial disease (aOR 1.98, 95%CI 1.20-3.27) was an independent predictor of new-onset AF (all p<0.05). Conclusions: This present study identified patients at risk of new-onset AF in the setting of ACS. Such patients could be targeted for increased surveillance for AF and related adverse outcomes during the post-infarct period. In addition, future studies should explore strategies to prevent new-onset AF after ACS.
Congestive heart failure (CHF) is a risk factor for pulmonary embolism (PE). PE is also an independent predictor of death or re-hospitalization among CHF patients. We assessed the incidence of CHF ...admission following acute PE using population-linkage analysis.
Patients were identified from a comprehensive single-center PE database and CHF admissions or death after their PE were tracked from the statewide Admitted Patient Data Collection and Death registries respectively. Patients were divided into two groups: Group-1 were patients without a history of CHF and left ventricular ejection fraction (LVEF) ≥50%; Group-2 were patients with a history of CHF and/or LVEF <50%. Cox regression was used to identify independent predictors for post-PE CHF admission or death.
The study cohort comprised 515 patients (Group-1: n = 338 65.6%; Group-2: n = 177 34.4%). The incidence of first CHF hospitalization after discharge for acute PE over a mean (±SD) follow-up period of 4.7 ± 3.7 years for the total cohort was 71 (13.8%), with the rate significantly higher in Group-2 than Group-1 (Group-2: n = 58 9.11 per-100-patient-years vs Group-1: n = 13 0.73 per-100-patient-years). Independent predictors for CHF admission or death after acute PE were older age, male gender, history of CHF or malignancy, low day-1 serum hemoglobin, on diuretics during index PE admission, LVEF <50%, and elevated right ventricular-atrial pressure gradient on echocardiography.
We report a high incidence of CHF requiring hospital admission after acute PE. Surveillance for new-onset heart failure and close monitoring for heart failure decompensation following acute PE particularly in at-risk groups may be warranted.
•There is a bidirectional relationship between PE and CHF.•The incidence of CHF hospitalization after acute PE is high.•Older age, male, prior CHF, malignancy, anemia, on diuretics, and pulmonary hypertension predicted CHF admission.•Closer surveillance for new-onset CHF is needed in at-risk groups after acute PE.
Chronic hepatitis B virus (CHB) is currently treated with either interferon-based or nucleot(s)ide-based antiviral therapies. However, treatment with pegylated interferon alpha results in a durable ...antiviral response in only about 30% patients and is associated with side effects. Most patients receiving nucleot(s)ide analogue treatment do not establish long-term, durable control of infection and have rebounding viremia after cessation of therapy. Thus, novel therapy strategies are necessary to achieve the induction of potent and durable antiviral immune responses of the patients which can maintain long-term control of viral replication. Therapeutic vaccination of HBV carriers is a promising strategy for the control of hepatitis B. Here the authors review new therapeutic vaccination strategies to treat chronic hepatitis B which may be introduced for patient treatment in the future.
Differentiation of inflammatory macrophages from monocytes is characterized by an orderly integration of epi- genetic and transcriptional regulatory mechanisms guided by lineage-determining ...transcription factors such as PU.1. Further activation of macrophages leads to a stimulus- or microenvironment-specific signal integration with subse- quent transcriptional control established by the action of tissue- or signal-associated transcription factors. Here, we assess four histone modifications during human macrophage activation and integrate this information with the gene expression data from 28 different macrophage activation conditions in combination with GM-CSF. Bioinformatically, for inflammatory macrophages we define a unique network of transcriptional and epigenetic regulators （TRs）, which was characterized by accessible promoters independent of the activation signal. In contrast to the general accessibil- ity of promoters of TRs, mRNA expression of central TRs belonging to the TR network displayed stimulus-specific expression patterns, indicating a second level of transcriptional regulation beyond epigenetic chromatin changes. In contrast, stringent integration of epigenetic and transcriptional regulation was observed in networks of TRs estab- lished from somatic tissues and tissue macrophages. In these networks, clusters of TRs with permissive bistone marks were associated with high gene expression whereas clusters with repressive chromatin marks were associated with absent gene expression. Collectively, these results support that macrophage activation during inflammation in con- trast to lineage determination is mainly regulated transcriptionally by a pre-defined TR network.
Temporal trends of perfluoroalkyl substances (PFASs) have been determined in the blood samples from several countries globally including a female population in Sweden recently, yet little is known ...about the time trends in the blood levels of these compounds in Swedish male populations over recent years. In this study, the fourteen target PFASs consisted of four perfluorosulfonates (PFSAs) and ten perfluorocarboxylates (PFCAs) in the whole blood samples, collected from 153 Swedish elderly men during the period between 2008 and 2010, were analyzed via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). As the dominant PFASs contaminants in the blood samples, perfluorooctane sulfonate (PFOS) showed the highest geometric mean (GM) at 8.5 ng/mL, ranging from 1.7 to 29 ng/mL, while blood perfluorooctanoic acid (PFOA) contained the GM of 1.8 ng/mL, ranging from 0.35 to 6.4 ng/mL. Both the levels of these two compounds were lower than those determined in the blood samples of Swedish elderly populations derived from the late 1990s. According to the temporal trend analysis, over the three years, the blood levels of PFOS in Swedish male populations declined 16 % per annum, while those of perfluoroundecanoic acid (PFUnDA) increased 6.1 % per annum, which were consistent with those reported previously for the populations from other countries.
DNA methylation is a heritable epigenetic mark, enabling stable but reversible gene repression. In mammalian cells, DNA methyltransferases (DNMTs) are responsible for modifying cytosine to ...5-methylcytosine (5mC), which can be further oxidized by the TET dioxygenases to ultimately cause DNA demethylation. However, the genome-wide cooperation and functions of these two families of proteins, especially at large under-methylated regions, called canyons, remain largely unknown.
Here we demonstrate that DNMT3A and TET1 function in a complementary and competitive manner in mouse embryonic stem cells to mediate proper epigenetic landscapes and gene expression. The longer isoform of DNMT3A, DNMT3A1, exhibits significant enrichment at distal promoters and canyon edges, but is excluded from proximal promoters and canyons where TET1 shows prominent binding. Deletion of Tet1 increases DNMT3A1 binding capacity at and around genes with wild-type TET1 binding. However, deletion of Dnmt3a has a minor effect on TET1 binding on chromatin, indicating that TET1 may limit DNA methylation partially by protecting its targets from DNMT3A and establishing boundaries for DNA methylation. Local CpG density may determine their complementary binding patterns and therefore that the methylation landscape is encoded in the DNA sequence. Furthermore, DNMT3A and TET1 impact histone modifications which in turn regulate gene expression. In particular, they regulate Polycomb Repressive Complex 2 (PRC2)-mediated H3K27me3 enrichment to constrain gene expression from bivalent promoters.
We conclude that DNMT3A and TET1 regulate the epigenome and gene expression at specific targets via their functional interplay.
Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as melanoma, ...smoking-induced lung cancers and bladder cancer-with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary
. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers
. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins-SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.
The global burden of viral hepatitis is substantial; in terms of mortality, hepatitis B virus and hepatitis C virus infections are on a par with HIV, malaria and tuberculosis, among the top four ...global infectious diseases. In 2016, the 194 Member States of the World Health Organization committed to eliminating viral hepatitis as a public health threat by 2030, with a particular focus on hepatitis B virus and hepatitis C virus infection. With only 10 years to go until the 2030 deadline is reached, and although much progress has been made towards elimination, there are still some important gaps in terms of policy and progress. In this Viewpoint, we asked a selection of scientists and clinicians working in the viral hepatitis field for their opinions on whether elimination of viral hepatitis by 2030 is feasible, what the key areas of progress are and what the focus for the next 10 years and beyond should be for viral hepatitis elimination.
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