Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Duration and Time Trends in Hospital Stay for Very Preterm Infants Differ Across European Regions

Contains fulltext : 199466.pdf (publisher's version ) (Open Access

Histopathological evidence of invasive gastric mucormycosis after transarterial chemoembolization and liver transplantation

We describe a case of a 62-year-old diabetic woman with hepatocellular carcinoma due to chronic hepatitis B virus infection. Two weeks after orthotopic liver transplantation, endoscopy for massive upper gastrointestinal bleeding revealed a large necrotic area in the gastric fundus. The patient underwent emergency resection. Histopathologically, angioinvasive mold infection compatible with mucormycosis was diagnosed in a large area of necrosis, mimicking an atypically localized gastric ulcer. Foreign bodies originating from transarterial chemoembolization (TACE) performed 7 and 8months earlier and 40days before transplantation were identified in the submucosal tissue. The patient was treated with liposomal amphotericin B (LAB) for 5weeks, followed by 7weeks of posaconazole. Follow-up biopsies after 1 and 5months confirmed successful treatment. Review of the radiological images of the TACE procedure showed that some of the TACE material had been diverted to the stomach via an accessory gastric branch originating from the left hepatic artery. TACE agents may be associated with chronic, refractory gastroduodenal ulcers. We hypothesize that the ischemic lesion was first colonized with presumed Mucorales mold and invasive growth was promoted by the posttransplantation immunosuppression. Careful exploration of extrahepatic collaterals during TACE may prevent this complication

Histopathological evidence of invasive gastric mucormycosis after transarterial chemoembolization and liver transplantation

We describe a case of a 62-year-old diabetic woman with hepatocellular carcinoma due to chronic hepatitis B virus infection. Two weeks after orthotopic liver transplantation, endoscopy for massive upper gastrointestinal bleeding revealed a large necrotic area in the gastric fundus. The patient underwent emergency resection. Histopathologically, angioinvasive mold infection compatible with mucormycosis was diagnosed in a large area of necrosis, mimicking an atypically localized gastric ulcer. Foreign bodies originating from transarterial chemoembolization (TACE) performed 7 and 8months earlier and 40days before transplantation were identified in the submucosal tissue. The patient was treated with liposomal amphotericin B (LAB) for 5weeks, followed by 7weeks of posaconazole. Follow-up biopsies after 1 and 5months confirmed successful treatment. Review of the radiological images of the TACE procedure showed that some of the TACE material had been diverted to the stomach via an accessory gastric branch originating from the left hepatic artery. TACE agents may be associated with chronic, refractory gastroduodenal ulcers. We hypothesize that the ischemic lesion was first colonized with presumed Mucorales mold and invasive growth was promoted by the posttransplantation immunosuppression. Careful exploration of extrahepatic collaterals during TACE may prevent this complication

Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty.

This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty.In this randomized, double-blind study, we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily, beginning after surgery, or 40 mg of enoxaparin subcutaneously once daily, beginning the evening before surgery, plus a placebo tablet or injection. The primary efficacy outcome was the composite of deep-vein thrombosis (either symptomatic or detected by bilateral venography if the patient was asymptomatic), nonfatal pulmonary embolism, or death from any cause at 36 days (range, 30 to 42). The main secondary efficacy outcome was major venous thromboembolism (proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death from venous thromboembolism). The primary safety outcome was major bleeding.A total of 3153 patients were included in the superiority analysis (after 1388 exclusions), and 4433 were included in the safety analysis (after 108 exclusions). The primary efficacy outcome occurred in 18 of 1595 patients (1.1\%) in the rivaroxaban group and in 58 of 1558 patients (3.7\%) in the enoxaparin group (absolute risk reduction, 2.6\%; 95\% confidence interval [CI], 1.5 to 3.7; P<0.001). Major venous thromboembolism occurred in 4 of 1686 patients (0.2\%) in the rivaroxaban group and in 33 of 1678 patients (2.0\%) in the enoxaparin group (absolute risk reduction, 1.7\%; 95\% CI, 1.0 to 2.5; P<0.001). Major bleeding occurred in 6 of 2209 patients (0.3\%) in the rivaroxaban group and in 2 of 2224 patients (0.1\%) in the enoxaparin group (P=0.18).A once-daily, 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily, 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty. The two drugs had similar safety profiles. (ClinicalTrials.gov number, NCT00329628.

The association between patterns of atrial fibrillation, anticoagulation, and cardiovascular events.

AIMS: Guidelines do not recommend to take pattern of atrial fibrillation (AF) into account for the indication of anticoagulation (AC). We assessed AF pattern and the risk of cardiovascular events during 2-years of follow-up. METHODS AND RESULTS: We categorized AF as paroxysmal, persistent, or permanent in 29 181 patients enrolled (2010-15) in the Global Anticoagulant Registry In the FIELD of AF (GARFIELD-AF). We used multivariable Cox regression to assess the risks of stroke/systemic embolism (SE) and death across patterns of AF, and whether this changed with AC on outcomes. Atrial fibrillation pattern was paroxysmal in 14 344 (49.2%), persistent in 8064 (27.6%), and permanent 6773 (23.2%) patients. Median CHA2DS2-VASc, GARFIELD-AF, and HAS-BLED scores assessing the risk of stroke/SE and/or bleeding were similar across AF patterns, but the risk of death, as assessed by the GARFIELD-AF risk calculator, was higher in non-paroxysmal than in paroxysmal AF patterns. During 2-year follow-up, after adjustment, non-paroxysmal AF patterns were associated with significantly higher rates of all-cause death, stroke/SE, and new/worsening congestive heart failure (CHF) than paroxysmal AF in non-anticoagulated patients only. In anticoagulated patients, a significantly higher risk of death but not of stroke/SE and new/worsening CHF persisted in non-paroxysmal compared with paroxysmal AF patterns. CONCLUSION: In non-anticoagulated patients, non-paroxysmal AF patterns were associated with higher risks of stroke/SE, new/worsening HF and death than paroxysmal AF. In anticoagulated patients, the risk of stroke/SE and new/worsening HF was similar across all AF patterns. Thus AF pattern is no longer prognostic for stroke/SE when patients are treated with anticoagulants. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

New AI Prediction Model Using Serial PT-INR Measurements in AF Patients on VKAs: GARFIELD-AF

Aims: Most clinical risk stratification models are based on measurement at a single time-point rather than serial measurements. Artificial intelligence (AI) is able to predict one-dimensional outcomes from multi-dimensional datasets. Using data from Global Anticoagulant Registry in the Field (GARFIELD)-AF registry, a new AI model was developed for predicting clinical outcomes in atrial fibrillation (AF) patients up to 1 year based on sequential measures of prothrombin time international normalized ratio (PT-INR) within 30 days of enrolment. Methods and results: Patients with newly diagnosed AF who were treated with vitamin K antagonists (VKAs) and had at least three measurements of PT-INR taken over the first 30 days after prescription were analysed. The AI model was constructed with multilayer neural network including long short-term memory and one-dimensional convolution layers. The neural network was trained using PT-INR measurements within days 0–30 after starting treatment and clinical outcomes over days 31–365 in a derivation cohort (cohorts 1–3; n = 3185). Accuracy of the AI model at predicting major bleed, stroke/systemic embolism (SE), and death was assessed in a validation cohort (cohorts 4–5; n = 1523). The model’s c-statistic for predicting major bleed, stroke/SE, and all-cause death was 0.75, 0.70, and 0.61, respectively. Conclusions: Using serial PT-INR values collected within 1 month after starting VKA, the new AI model performed better than time in therapeutic range at predicting clinical outcomes occurring up to 12 months thereafter. Serial PT-INR values contain important information that can be analysed by computer to help predict adverse clinical outcomes

Histopathological evidence of invasive gastric mucormycosis after transarterial chemoembolization and liver transplantation

We describe a case of a 62-year-old diabetic woman with hepatocellular carcinoma due to chronic hepatitis B virus infection. Two weeks after orthotopic liver transplantation, endoscopy for massive upper gastrointestinal bleeding revealed a large necrotic area in the gastric fundus. The patient underwent emergency resection. Histopathologically, angioinvasive mold infection compatible with mucormycosis was diagnosed in a large area of necrosis, mimicking an atypically localized gastric ulcer. Foreign bodies originating from transarterial chemoembolization (TACE) performed 7 and 8 months earlier and 40 days before transplantation were identified in the submucosal tissue. The patient was treated with liposomal amphotericin B (LAB) for 5 weeks, followed by 7 weeks of posaconazole. Follow-up biopsies after 1 and 5 months confirmed successful treatment. Review of the radiological images of the TACE procedure showed that some of the TACE material had been diverted to the stomach via an accessory gastric branch originating from the left hepatic artery. TACE agents may be associated with chronic, refractory gastroduodenal ulcers. We hypothesize that the ischemic lesion was first colonized with presumed Mucorales mold and invasive growth was promoted by the posttransplantation immunosuppression. Careful exploration of extrahepatic collaterals during TACE may prevent this complication

The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis

Intestinal fibrosis and stenosis are common complications of Crohn's disease [CD], frequently requiring surgery. Anti-inflammatory strategies can only partially prevent fibrosis; hence, anti-fibrotic therapies remain an unmet clinical need. Oxysterols are oxidised cholesterol derivatives with important roles in various biological processes. The enzyme cholesterol 25-hydroxylase [CH25H] converts cholesterol to 25-hydroxycholesterol [25-HC], which modulates immune responses and oxidative stress. In human intestinal samples from CD patients, we found a strong correlation of CH25H mRNA expression with the expression of fibrosis markers. We demonstrate reduced intestinal fibrosis in mice deficient for the CH25H enzyme, using the sodium dextran sulphate [DSS]-induced chronic colitis model. Additionally, using a heterotopic transplantation model of intestinal fibrosis, we demonstrate reduced collagen deposition and lower concentrations of hydroxyproline in CH25H knockouts. In the heterotopic transplant model, CH25H was expressed in fibroblasts. Taken together, our findings indicate an involvement of oxysterol synthesis in the pathogenesis of intestinal fibrosis

Determination of rivaroxaban by different factor Xa specific chromogenic substrate assays: reduction of interassay variability

Rivaroxaban and other oral direct factor Xa inhibitors (ODiXa) are currently developed for prophylaxis and treatment of thromboembolic diseases using fixed doses. Although routine monitoring is not required, assessing the intensity of anticoagulation may be useful under certain clinical conditions. ODiXa prolong coagulation times of several clotting assays and, thus, their concentration may be determined in factor Xa specific chromogenic substrate assays. So far, no standardized and validated assay is commercially available. Here, five methods (A through E) are studied and optimized to reduce interassay variability. Human pooled plasma was spiked by a serial dilution of rivaroxaban (25–900 ng/ml). The release of para-nitroaniline from the chromogenic substrates was measured by the optical density (OD) at 405 nm. Method B was identified to yield the lowest sum of deviations from the mean value of the OD concentration curve calculated from all assays. Spline functions were developed for OD versus concentration curves for all methods. The calculated OD versus concentration curves overlapped for all methods. The coefficient of variation for all assays and concentrations of rivaroxaban decreased from 25.3 ± 11.4% using the original data to 3.8 ± 2.2% using the calculated data (P < 0.0001). The robustness of the chromogenic assay (method B) remains to be corroborated in interlaboratory comparisons