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Heart (British Cardiac Society) Jan 2020Prevention of stroke and systemic thromboembolism remains the cornerstone for management of atrial fibrillation (AF) and flutter. Multiple risk assessment models for... (Review)
Review
Prevention of stroke and systemic thromboembolism remains the cornerstone for management of atrial fibrillation (AF) and flutter. Multiple risk assessment models for stroke and systemic thromboembolism are currently available. The score, with its known limitations, remains as the recommended risk stratification tool in most major guidelines. Once at-risk patients are identified, vitamin K antagonists (VKAs) and, more recently, direct oral anticoagulants (DOACs) are the primary medical therapy for stroke prevention. In those with contraindication for long-term anticoagulation, left atrial appendage occluding devices are developing as a possible alternative therapy. Some controversy exists regarding anticoagulation management for cardioversion of acute AF (<48 hours); however, systemic anticoagulation precardioversion and postcardioversion is recommended for those with longer duration of AF. Anticoagulation management peri-AF ablation is also evolving. Uninterrupted VKA and DOAC therapy has been shown to reduce perioperative thromboembolic risk with no significant escalation in major bleeding. Currently, under investigation is a minimally interrupted approach to anticoagulation with DOACs periablation. Questions remain, especially regarding the delivery of anticoagulation care and integration of wearable rhythm monitors in AF management.
Topics: Ablation Techniques; Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Preventive Health Services; Recurrence; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Treatment Outcome
PubMed: 31533990
DOI: 10.1136/heartjnl-2019-314898 -
Digestive Diseases and Sciences Mar 2021Bile acids are a group of chemically different steroids generated at the host/microbial interface. Indeed, while primary bile acids are the end-product of cholesterol... (Review)
Review
Bile acids are a group of chemically different steroids generated at the host/microbial interface. Indeed, while primary bile acids are the end-product of cholesterol breakdown in the host liver, secondary bile acids are the products of microbial metabolism. Primary and secondary bile acids along with their oxo derivatives have been identified as signaling molecules acting on a family of cell membrane and nuclear receptors collectively known as "bile acid-activated receptors." Members of this group of receptors are highly expressed throughout the gastrointestinal tract and mediate the bilateral communications of the intestinal microbiota with the host immune system. The expression and function of bile acid-activated receptors FXR, GPBAR1, PXR, VDR, and RORγt are highly dependent on the structure of the intestinal microbiota and negatively regulated by intestinal inflammation. Studies from gene ablated mice have demonstrated that FXR and GPBAR1 are essential to maintain a tolerogenic phenotype in the intestine, and their ablation promotes the polarization of intestinal T cells and macrophages toward a pro-inflammatory phenotype. RORγt inhibition by oxo-bile acids is essential to constrain Th17 polarization of intestinal lymphocytes. Gene-wide association studies and functional characterizations suggest a potential role for impaired bile acid signaling in development inflammatory bowel diseases (IBD). In this review, we will focus on how bile acids and their receptors mediate communications of intestinal microbiota with the intestinal immune system, describing dynamic changes of bile acid metabolism in IBD and the potential therapeutic application of targeting bile acid signaling in these disorders.
Topics: Bile Acids and Salts; Gastrointestinal Microbiome; Humans; Immune System Phenomena; Inflammatory Bowel Diseases; Intestinal Mucosa; Receptors, Cytoplasmic and Nuclear; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 33289902
DOI: 10.1007/s10620-020-06715-3 -
Cell Host & Microbe Jun 2021Microbiota play critical roles in regulating colitis and colorectal cancer (CRC). However, it is unclear how the microbiota generate protective immunity against these...
Microbiota play critical roles in regulating colitis and colorectal cancer (CRC). However, it is unclear how the microbiota generate protective immunity against these disease states. Here, we find that loss of the innate and adaptive immune signaling molecule, TAK1, in myeloid cells (Tak1) yields complete resistance to chemical-induced colitis and CRC through microbiome alterations that drive protective immunity. Tak1 mice exhibit altered microbiota that are critical for resistance, with antibiotic-mediated disruption ablating protection and Tak1 microbiota transfer conferring protection against colitis or CRC. The altered microbiota of Tak1 mice promote IL-1β and IL-6 signaling pathways, which are required for induction of protective intestinal Th17 cells and resistance. Specifically, Odoribacter splanchnicus is abundant in Tak1 mice and sufficient to induce intestinal Th17 cell development and confer resistance against colitis and CRC in wild-type mice. These findings identify specific microbiota strains and immune mechanisms that protect against colitis and CRC.
Topics: Animals; Bacteroidetes; Colitis; Colorectal Neoplasms; Cytokines; Disease Models, Animal; Feces; Female; Gastrointestinal Microbiome; Host Microbial Interactions; Immunity, Innate; Interleukin-1beta; Interleukin-6; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid Cells; Signal Transduction; Th17 Cells
PubMed: 33894128
DOI: 10.1016/j.chom.2021.03.016 -
The New England Journal of Medicine Apr 2017Catheter ablation of atrial fibrillation is typically performed with uninterrupted anticoagulation with warfarin or interrupted non-vitamin K antagonist oral... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Catheter ablation of atrial fibrillation is typically performed with uninterrupted anticoagulation with warfarin or interrupted non-vitamin K antagonist oral anticoagulant therapy. Uninterrupted anticoagulation with a non-vitamin K antagonist oral anticoagulant, such as dabigatran, may be safer; however, controlled data are lacking. We investigated the safety of uninterrupted dabigatran versus warfarin in patients undergoing ablation of atrial fibrillation.
METHODS
In this randomized, open-label, multicenter, controlled trial with blinded adjudicated end-point assessments, we randomly assigned patients scheduled for catheter ablation of paroxysmal or persistent atrial fibrillation to receive either dabigatran (150 mg twice daily) or warfarin (target international normalized ratio, 2.0 to 3.0). Ablation was performed after 4 to 8 weeks of uninterrupted anticoagulation, which was continued during and for 8 weeks after ablation. The primary end point was the incidence of major bleeding events during and up to 8 weeks after ablation; secondary end points included thromboembolic and other bleeding events.
RESULTS
The trial enrolled 704 patients across 104 sites; 635 patients underwent ablation. Baseline characteristics were balanced between treatment groups. The incidence of major bleeding events during and up to 8 weeks after ablation was lower with dabigatran than with warfarin (5 patients [1.6%] vs. 22 patients [6.9%]; absolute risk difference, -5.3 percentage points; 95% confidence interval, -8.4 to -2.2; P<0.001). Dabigatran was associated with fewer periprocedural pericardial tamponades and groin hematomas than warfarin. The two treatment groups had a similar incidence of minor bleeding events. One thromboembolic event occurred in the warfarin group.
CONCLUSIONS
In patients undergoing ablation for atrial fibrillation, anticoagulation with uninterrupted dabigatran was associated with fewer bleeding complications than uninterrupted warfarin. (Funded by Boehringer Ingelheim; RE-CIRCUIT ClinicalTrials.gov number, NCT02348723 .).
Topics: Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Dabigatran; Female; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Postoperative Complications; Stroke; Warfarin
PubMed: 28317415
DOI: 10.1056/NEJMoa1701005 -
Frontiers in Bioscience (Landmark... Jan 2017Tumor ablation by thermal, chemical and radiological sources has received substantial attention for the treatment of many localized malignancies. The primary goal of... (Review)
Review
Tumor ablation by thermal, chemical and radiological sources has received substantial attention for the treatment of many localized malignancies. The primary goal of most ablation procedures is to eradicate all viable malignant cells within a designated target volume through the application of energy or chemicals. Methods such as radiotherapy, chemical and biological ablation, photodynamic therapy, cryoablation, high-temperature ablation (radiofrequency, microwave, laser, and ultrasound), and electric-based ablation have been developed for focal malignancies. In recent years a large volume of data emerged on the effect of tumor destruction (ablation) on inflammatory and immune components resulting in systemic anti-tumor reactions. It is evident that tumor ablation can involve tumor antigen release, cross presentation and the release of DAMPS and make the tumor its own cellular vaccine. Tumor tissue destruction by ablation may stimulate antigen-specific cellular immunity engendered by an inflammatory milieu. Dendritic cells (DCs) attracted to this microenvironment, will undergo maturation after internalizing cellular debris containing tumor antigens and will be exposed to damage associated molecular pattern (DAMP). Mature DCs can mediate antigen-specific cellular immunity via presentation of processed antigens to T cells. The immunomodulatory properties, exhibited by ablation could portend a future collaboration with immunotherapeutic measures. In this review are summarized and discuss the preclinical and clinical studies pertinent to the phenomena of stimulation of specific anti-tumor immunity by various ablation modalities and the immunology related measures used to boost this response.
Topics: Animals; Cancer Vaccines; Combined Modality Therapy; Humans; Hyperthermia, Induced; Immunization; Immunotherapy; Molecular Targeted Therapy; Neoplasms; Photochemotherapy
PubMed: 27814617
DOI: 10.2741/4487