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Purpose@#Advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no oral anticoagulant (OAC) in AF patients with advanced CKD or ESRD on dialysis. @*Materials and Methods@#Using data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate <30 mL/min per 1.73/m2 ) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC groups; and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed. @*Results@#During a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group [hazard ratio (HR) 0.11, 95% confidence interval (CI) 0.01 to 0.93, p=0.043]. In addition, the risk of composite adverse clinical outcomes (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.16, 95% CI 0.03 to 0.91, p=0.039). @*Conclusion@#Among AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcomes compared to no OAC.ClinicalTrials.gov (NCT02786095)
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Background@#The prognostic significance of resting heart rate and its therapeutic target in atrial fibrillation (AF) is uncertain. We sought to investigate the relationship between resting heart rate and cardiovascular outcomes in patients with non-paroxysmal AF (non-PAF). @*Methods@#In this propensity score-weighted, multi-center prospective cohort study, 3217 patients with non-PAF were analyzed. Patients were categorized according to the baseline resting heart rate and cardiovascular outcomes were accessed for a median follow-up of 30 months. The primary outcome was a composite of cardiovascular death, heart failure hospitalization, and myocardial infarction/critical limb ischemia. @*Results@#Freedom from primary outcome was longest among patients with resting heart rate 80–99 beats per minute (bpm) whereas shortest among those with ≤ 59 bpm (weighted log rank, p = 0.008). Compared with heart rate ≥ 100 bpm, resting heart rate 80–99 and 60–79 bpm was associated with reduced risk of primary outcome (weighted hazard ratio [WHR] 0.52, 95% confidence interval [CI] 0.32–0.84, p = 0.008 and WHR 0.58, 95% CI 0.37–0.92, p = 0.021 for heart rate 80–99 and 60–79 bpm, respectively). Using weighted restricted cubic spline curves, there was a U-shaped association between the resting heart rate and primary outcome with reduced risk of primary outcome in heart rate range of 68–99 bpm. This association was maintained regardless of atrioventricular node (AVN) blocker use or persistent/permanent AF (p for interaction 0.767 for AVN blocker use and 0.720 for AF type). @*Conclusion@#Resting heart rate was associated with cardiovascular outcomes in patients with non-PAF and those with resting heart rate between 68 and 99 bpm had lower risk of adverse cardiovascular events regardless of AVN blocker use or persistent/permanent AF.
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Background and Objectives@#In patients with atrial fibrillation (AF), females taking vitamin K antagonist are at higher risk of stroke or systemic embolism (SSE), bleeding and all-cause death than males. This study investigated the relationship between sex and adverse clinical events in a contemporary AF patient cohort taking anticoagulation. @*Methods@#This prospective multicenter AF registry study comprised 6,067 patients with AF (mean age, 70±9 years; men, 59%) with intermediate to high risk of stroke (CHA 2 DS 2-VAscore ≥1) and receiving oral anticoagulation therapy. Adverse clinical outcomes, including SSE, bleeding, death were evaluated in patients stratified by sex and anticoagulation patterns. @*Results@#Women were older and used more direct oral anticoagulants (85% vs. 78%, p<0.001) than men. During a median (25 the and 75 the percentiles) follow-up of 30 (24, 38) months, the incidence rate and risk of SSE (0.7 in women vs. 0.7 in men per 100 person-years) and major bleeding (0.1 in women vs. 0.1 in men per 100 person-years) were not different between the sexes. However, women had a lower all-cause death rate (0.4 in women vs. 0.6 in men per 100 person-years, hazard ratio: 0.48, 95% confidence interval: 0.25–0.91, p=0.025) than men. @*Conclusions@#In contemporary anticoagulation for AF, SSE and major bleeding risks did not differ between sexes. However, women showed a lower risk of all-cause death rate than men, indicating that the use of oral anticoagulants for treating AF in females does not appear to be a risk factor for adverse clinical events.
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Purpose@#The incidence of stroke and/or systemic thromboembolism (SSE) has not been properly evaluated in well-anticoagulated atrial fibrillation (AF) patients. This study investigated the incidence of SSE according to CHA2DS2-VASc score in contemporary well-anticoagulated Korean AF patients. @*Materials and Methods@#From the prospective multicenter COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry, we identified 9503 patients with non-valvular AF (mean age, 68±8 years; female 35.5%) enrolled between June 2016 and May 2020 with eligible follow-up visits. Stroke incidence in the CODE-AF registry was compared with that in an oral anticoagulant (OAC)-naïve AF cohort from the Korean National Health Insurance database. @*Results@#The usage rates of OACs and antiplatelet agents were 73.5% (non-vitamin K OACs, 56.4%; warfarin, 17.1%) and 23.8%, respectively. During a mean follow-up period of 26.3±9.6 months, 163 (0.78 per 100 person-years) patients had SSE. The incidence rate (per 100 person-years) of SSE was 0.77 in the total population, 0.26 in low-risk patients [CHA2DS2-VASc score 0 (male) or 1 (female)], and 0.88 in high-risk patients (CHA2DS2-VASc score ≥2). Contemporary AF patients had a stroke rate that was about one-fifth the stroke rate reported in a Korean OAC-naïve AF cohort. In this cohort, most risk factors for CHA2DS2-VASc score showed significant associations with SSE. Female sex was not associated with an increased risk of stroke/SSE in well-anticoagulated AF patients. @*Conclusion@#Contemporary AF patients have a stroke rate about one-fifth that in OAC-naïve AF patients and exhibit different stroke risk factors.
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A 12-year-old, castrated male, mixed dog presented with a history of gradual abdominal distention for a year and anorexia recently, with abdominal radiographs showing a gastric pylorus distention. A solitary, pedunculated, heterogeneous mass arising from the mucosal layer in the pylorus with intact wall layers was identified during ultrasound and computed tomography. The gastric muscular layer was evenly thick. After surgical excision of the mass, histological examination confirmed hypertrophic pyloric gastropathy with polypoid growth and Helicobacter spp. infiltrating the gastric mucosal epithelium. This is the first reported diagnostic imaging case of hypertrophic pyloric gastropathy with Helicobacter spp. in a dog.
ABSTRACT
Atrial fibrillation (AF) is a strong risk factor for embolic stroke. In patients with AF, optimal anticoagulation therapy, administered according to the stroke risk scoring system, can effectively reduce the stroke risk. However, AF episodes are frequently asymptomatic, with a significant number of them detected after a stroke event. Therefore, the early detection of subclinical AF and the subsequent administration of optimal oral anticoagulation therapy is expected to reduce the risk of stroke. However, this strategy requires more effective screening for the detection of AF in the asymptomatic stage, which accounts for the recent research interest in silent/subclinical AF. Today, the widespread use of cardiac implantable electronic devices and wearable rhythm monitors has enabled the detection of atrial high-rate episodes/subclinical AF in a substantial number of patients. The risk of stroke appears to be related to the duration of this phenomenon. Subclinical AF increases the risk of stroke, but generally not as much as clinical AF, but whether long-term anticoagulation therapy is required in patients with subclinical AF is unclear. Here we review existing data on the epidemiology, clinical significance, and suggest guidelines on management of subclinical AF and the optimal screening strategies aimed at its detection.
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The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.
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The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.
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Background/Aims@#Comparative occurrence of ischemic stroke for rhythm versus rate control strategy in patients with non-valvular atrial fibrillation (NVAF) is still inconclusive. The purpose of this study was to investigate whether the rhythm control strategy is associated with a lower risk of ischemic stroke compared to the rate control strategy in NVAF patients. @*Methods@#The CODE-AF registry prospectively enrolled 6,280 consecutive patients who were treated for NVAF at 10 tertiary referral centers in South Korea. Of these, 2,513 NVAF patients (age, 67 ± 10 years; male, 61.8%) were clinically followed up for over 1-year and divided into rate and rhythm control groups. @*Results@#Those treated with the rhythm control strategy were younger and had less proportions of underlying disease compared to those treated with the rate control strategy. After the propensity matching analysis, those treated with the rhythm control strategy had similar baseline characteristics including the CHA 2 DS 2 -VASC score compared to those treated with the rate control strategy.The rate of oral anticoagulation, all bleeding, and hospitalization were also similarly between the two groups. The incidence rate of ischemic stroke in the rhythm control group was significantly lower than in the rate control group (0.7 vs. 6.9 per 1,000 person-years, p = 0.011). @*Conclusions@#The rhythm control strategy demonstrated a beneficial effect to lower the risk of ischemic stroke during a 1-year follow-up compared to the rate control strategy.
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A 12-year-old, castrated male, mixed dog presented with a history of gradual abdominal distention for a year and anorexia recently, with abdominal radiographs showing a gastric pylorus distention. A solitary, pedunculated, heterogeneous mass arising from the mucosal layer in the pylorus with intact wall layers was identified during ultrasound and computed tomography. The gastric muscular layer was evenly thick. After surgical excision of the mass, histological examination confirmed hypertrophic pyloric gastropathy with polypoid growth and Helicobacter spp. infiltrating the gastric mucosal epithelium. This is the first reported diagnostic imaging case of hypertrophic pyloric gastropathy with Helicobacter spp. in a dog.
ABSTRACT
Atrial fibrillation (AF) is a strong risk factor for embolic stroke. In patients with AF, optimal anticoagulation therapy, administered according to the stroke risk scoring system, can effectively reduce the stroke risk. However, AF episodes are frequently asymptomatic, with a significant number of them detected after a stroke event. Therefore, the early detection of subclinical AF and the subsequent administration of optimal oral anticoagulation therapy is expected to reduce the risk of stroke. However, this strategy requires more effective screening for the detection of AF in the asymptomatic stage, which accounts for the recent research interest in silent/subclinical AF. Today, the widespread use of cardiac implantable electronic devices and wearable rhythm monitors has enabled the detection of atrial high-rate episodes/subclinical AF in a substantial number of patients. The risk of stroke appears to be related to the duration of this phenomenon. Subclinical AF increases the risk of stroke, but generally not as much as clinical AF, but whether long-term anticoagulation therapy is required in patients with subclinical AF is unclear. Here we review existing data on the epidemiology, clinical significance, and suggest guidelines on management of subclinical AF and the optimal screening strategies aimed at its detection.
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Subject(s)
Animals , Humans , Male , Adenocarcinoma , Adenoma , Communicable Diseases , Fibroma , Incidence , Lung , Mammals , Penis , Rodentia , Sebaceous Glands , UterusABSTRACT
Subject(s)
Female , Humans , Male , Anticoagulants , Atrial Fibrillation , Heart Valve Diseases , Hemorrhage , Kidney Failure, Chronic , Multivariate Analysis , Myocardial Infarction , Platelet Aggregation Inhibitors , Prospective Studies , Smoke , Smoking , Stroke , WarfarinABSTRACT
Background@#Symptom burden is an important factor in determining the treatment of atrial fibrillation (AF). AF is frequently accompanied by heart failure (HF). This study investigated the characteristics of AF symptoms with concomitant HF. @*Methods@#A total of 4885 patients with AF were consecutively enrolled through a prospective observational registry (the Comparison Study of Drugs for Symptom Control and Complication Prevention of Atrial Fibrillation [CODE-AF] registry). Clinically diagnosed HF was divided into three categories (preserved, mid-range, and reduced ejection fraction [EF]). Symptom severity was assessed using the European Heart Rhythm Association (EHRA) classification. @*Results@#The presence of AF-related symptoms was comparable irrespective of concomitant HF. Patients with HF with reduced EF demonstrated severe (EHRA classes 3 and 4) and atypical symptoms. HF with preserved EF was also associated with atypical symptoms. Female sex and AF type were associated with the presence of symptoms in AF without HF, and non-maintenance of sinus rhythm and increased left atrial pressure (E/e′ ≥ 15) were factors related to the presence of symptoms in AF with HF. @*Conclusion@#AF with concomitant HF presented with more severe and atypical symptoms than AF without HF. Maintaining the sinus rhythm and reducing the E/e’ ratio are important factors for reducing symptoms in AF with concomitant HF.
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Purpose@#Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. This study investigated anticoagulation patterns and outcomes in patients with chronic kidney disease (CKD). @*Materials and methods@#In a prospective observational registry (CODE-AF), 3445 patients with non-valvular AF including 1129 with CKD (estimated glomerular filtration rate ≤ 60 mL min−1 1.73 m−2) were identified between June 1, 2016, and July 3, 2017. @*Results@#Compared with patients with no-CKD, patients with CKD more frequently had a high stroke risk (94.9% vs. 67.0%, p < 0.001) and higher NOAC usage rate (61.1% vs. 47.8%, p < 0.001). Among 718 patients with renal indication for dose reduction (RIDR), 7.5% were potentially overdosed. Among 2587 patients with no-RIDR, 79% were potentially underdosed. Compared with patients with no-RIDR, the underdose rates of dabigatran (0% vs. 88.6%, p = 0.001) and rivaroxaban (0% vs. 79.5%, p = 0.001) were lower in patients with RIDR. However, the underdose rate of apixaban was not different (62.5% vs. 53.9%, p = 0.089). The overdose rate of dabigatran (7.5% vs. 0%) and rivaroxaban (13.7% vs. 0%) was higher in RIDR than in no-RIDR patients. Stroke/transient ischemic attack was significantly higher in CKD patients (1.4 vs. 0.6 per 100 person-years, p = 0.045). Aspirin significantly increased minor bleeding in CKD patients compared with controls (p = 0.037). @*Conclusion@#CKD patients might have a high stroke risk and NOAC usage rate. The underdose rate of NOACs decreased in CKD patients, except for apixaban. Aspirin significantly increased minor bleeding in CKD patients.
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Background/Aims@#Efforts to reduce stroke in patients with atrial fibrillation (AF) have focused on increasing physician adherence to oral anticoagulant (OAC) guidelines; however, the high early discontinuation rate of vitamin K antagonists (VKAs) is a limitation. Although non-VKA OACs (NOACs) are more convenient to administer than warfarin, their lack of monitoring may predispose patients to nonpersistence. We compared the persistence of NOAC and VKA treatment for AF in real-world practice. @*Methods@#In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 7,013 patients with nonvalvular AF (mean age 67.2 ± 10.9 years, women 36.4%) were consecutively enrolled between June 2016 and June 2017 from 10 tertiary hospitals in Korea. This study included 3,381 patients who started OAC 30 days before enrollment (maintenance group) and 572 patients who newly started OAC (new-starter group). The persistence rate of OAC was evaluated. @*Results@#In the maintenance group, persistence to OAC declined during 6 months, to 88.3% for VKA and 95.5% for NOAC (p < 0.0001). However, the persistence rate was not different among NOACs. In the new-starter group, persistence to OAC declined during 6 months, to 78.9% for VKA and 92.1% for NOAC (p < 0.0001). The persistence rate was lower for rivaroxaban (83.7%) than apixaban (94.6%) and edoxaban (94.1%, p < 0.001). In the new-starter group, diabetes, valve disease, and cancer were related to nonpersistence of OAC. @*Conclusions@#Nonpersistence was significantly lower with NOAC than VKA in both the maintenance and new-starter groups. In only the new-starter group, apixaban or edoxaban showed higher persistence rates than rivaroxaban.
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Tumor incidence in wild mammals is reportedly very low. Wild nutria, a large rodent, is known to carry many infectious diseases, but rarely exhibits neoplastic diseases. We necropsied a male wild nutria and found a large nodular mass in the left inguinal region, adjacent to the penis. Histopathologically, the mass was diagnosed as preputial gland adenoma. Spontaneous preputial gland adenomas are extremely rare in all animals. Moreover, reports of tumors in nutrias have been limited to adenocarcinomas of the lungs and uterus, as well as subcutaneous fibromas. Here, we describe preputial gland adenoma in a wild nutria.
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Tumor incidence in wild mammals is reportedly very low. Wild nutria, a large rodent, is known to carry many infectious diseases, but rarely exhibits neoplastic diseases. We necropsied a male wild nutria and found a large nodular mass in the left inguinal region, adjacent to the penis. Histopathologically, the mass was diagnosed as preputial gland adenoma. Spontaneous preputial gland adenomas are extremely rare in all animals. Moreover, reports of tumors in nutrias have been limited to adenocarcinomas of the lungs and uterus, as well as subcutaneous fibromas. Here, we describe preputial gland adenoma in a wild nutria.
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The choice of an adequate antithrombotic regimen for atrial fibrillation patients undergoing emergent or elective percutaneous coronary intervention (PCI) should be based on the ischemic event and on the risk of bleeding. Recent randomized controlled trials have consistently demonstrated that dual antithrombotic therapeutic regimens, using non-vitamin K anticoagulants and clopidogrel, are superior to triple or dual therapy with warfarin and aspirin. This report incorporates findings of recent notable studies to provide concrete, clinically useful details and recommendations for bleeding risk assessment and optimal antithrombotic therapeutic strategies after PCI. In addition, we introduce guidelines for antithrombotic management after structural heart disease intervention.
Subject(s)
Humans , Anticoagulants , Aspirin , Atrial Fibrillation , Heart Diseases , Heart , Hemorrhage , Percutaneous Coronary Intervention , Risk Assessment , WarfarinABSTRACT
Non-vitamin K antagonist oral anticoagulants (NOACs) are alternatives to vitamin K antagonists to prevent stroke in patients with non-valvular atrial fibrillation (AF) and have emerged as the preferred choice. The use of NOACs is rapidly increasing in Korea after coverage by insurance since 2015. However, the rate of prescribing anticoagulants in Korean patients with AF remains low compared to other countries. Most of the NOAC anticoagulant prescriptions are issued at hospitals. As the prevalence rate of AF in Korea is expected to increase rapidly with the increase in the elderly population, the need to prescribe NOACs in primary care clinics will also increase. Therefore, The Korean Heart Rhythm Society organized the Korean Atrial Fibrillation Management Guideline Committee and analyzed all available studies based on the 2018 European Heart Rhythm Association Practical Guide on the use of NOACs for managing AF, as well as studies on Korean patients. The authors would like to introduce practical guidelines for NOAC prescriptions in Korean patients with AF.