Citations

Background Available outcomes data for anticoagulation therapy in adults with congenital heart disease ( CHD ) provide assessment of global risk of this therapy for CHD patients (a heterogeneous population), but the risk of complications for the different CHD diagnoses is unknown. The purpose of the study was to describe the indications for anticoagulation, and the incidence and risk factors for major bleeding complication in adults with tetralogy of Fallot. Methods and Results We queried Mayo Adult Congenital Heart Disease (MACHD) database for tetralogy of Fallot patients (aged ≥18 years) that received anticoagulation, 1990–2017. Of 130 patients (42±14 years, 75 men [58%]), warfarin and direct oral anticoagulants were used in 125 (96%) and 5 (4%), respectively because atrial arrhythmias (n=109), mechanical prosthetic valve (n=29), intracardiac thrombus (n=4), pulmonary embolism (n=6), stroke (n=3), and perioperative anticoagulation (n=44). The median hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score for the entire cohort was 1 (0–2) and 27 (21%) had hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2. There were 14 minor bleeding events (1.6% per year) and 11 major bleeding events (1.3% per year) in 8 patients during median follow‐up of 74 months (856 patient‐years). Mechanical prosthesis (hazard ratio 1.78, CI 1.29–3.77, P =0.021) and hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2 (hazard ratio 1.41, CI 1.03–3.88, P =0.046) were risk factors for major bleeding events. All‐cause mortality was higher in patients with major bleeding events (n=6, 75%) compared with patients without major bleeding events (n=25, 21%), P =0.001. Conclusions Considering the heterogeneity of the CHD population, data from the current study may be better suited for clinical decision‐making in tetralogy of Fallot patients.

Study Design: This is a retrospective study. Objective: To report the safety profile of S2-alar-iliac (S2AI) in patients over 60, comparing S2AI screws with iliac screws (ISs). Summary of Background Data: The surgical management involving the lumbosacropelvic spine remains a challenge due to high mechanical demand and risk of pseudarthrosis. Previous articles showed lower rates of complications in patients receiving S2AI screws than ISs; however, none of them have focused on patients aged over 60 who may harbor significant comorbidities and thus require more meticulous perioperative management, given these invasive and lengthy procedures. Materials and Methods: Retrospective review of clinical records from 2010 to 2015 identified 60 patients undergoing lumbosacropelvic fixation (17 patients with ISs and 43 patients with S2AI screws) who satisfied the following criteria: (1) patients aged over 60 years old and (2) patients with >1-year follow-up periods. Rates of complications such as unplanned reoperation and cardiorespiratory complications were collected and statistically analyzed. Results: Baseline characteristics such as age, sex, and comorbidities were similar in both groups. The S2AI group had lower rates of reoperation (18.6% vs. 47.4%; P=0.02), surgical site infection (2.3% vs. 29.4%; P=0.006), wound dehiscence (2.3% vs. 29.4%; P=0.006), and postoperative anemia (7.0% vs. 29.4%; P=0.03) and had lower total volume of estimated blood loss (EBL) (mL) (1846.4 vs. 2721.2; P=0.02) and transfused red blood cell units (7.2 vs. 4.7; P=0.04) than the IS group, while rates of L5–S1 pseudarthrosis and other cardiorespiratory complications were similar in both groups. In multivariate analysis, operative time, body mass index, and use of S2AI screws over ISs were independent predictors of EBL. Conclusions: Use of S2AI screws over ISs in patients aged over 60 was associated with lower rates of reoperation, surgical site infection, wound dehiscence, and lower volume of EBL and red blood cell transfusion and is a viable surgical option.

Objectives Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF). Methods The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment. Results In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months. Conclusions Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk. Trial registration number NCT00412984.

How dipeptide repeats cause pathology A repeat expansion in the chromosome 9 open reading frame 72 ( C9orf72 ) gene is the most common known cause of two neurodegenerative diseases: frontotemporal dementia and amyotrophic lateral sclerosis. This expansion leads to the abnormal production of proteins of repeating dipeptides, but their contribution to disease pathogenesis remains unclear. Zhang et al. engineered a mouse model to study the consequences of one of these dipeptides—prolinearginine dipeptide repeat protein, poly(PR)—in the brain. They found that poly(PR) caused neuron loss as well as motor and memory impairments. These detrimental effects resulted from poly(PR)-induced perturbation of heterochromatin function, a tightly packed form of DNA that represses gene expression. Science , this issue p. eaav2606

AbstractObjectiveTo review our experience with balloon testing prior to atrial septal defect (ASD) closure in adults with left ventricular (LV) diastolic dysfunction.BackgroundASD closure in patients with LV diastolic dysfunction may precipitate LV failure. Temporary ASD occlusion has been used in this scenario but data are limited.MethodsRetrospective review of 27 patients age ≥ 50 years undergoing temporary ASD balloon occlusion between 2000 and 2018 for suspected LV diastolic dysfunction or elevated LV end‐diastolic pressure (LVEDP).ResultsMedian age was 72 years (IQR 66.7; 75.2). Atrial fibrillation was seen in 58% of patients, hypertension in 58%, and coronary artery disease in 26%; 52% were females. Median ASD size was 13 mm (10; 18) and Qp/Qs 1.8 (1.6; 2.2). Median LVEDP was 14 mmHg (12; 22); pulmonary artery wedge pressure (PAWP) 12 mmHg (9; 16.5) and left atrial pressure (LAP) 13.5 mmHg (8; 16.3). After a median of 5 min (3; 10) of balloon occlusion, patients with baseline LVEDP ≥15 mmHg had more significant increases in LVEDP (9 [6; 12] vs. 2 mmHg [0.5; 5]; p = 0.03) and LAP/PAWP (10.5 [8.3; 16.3] vs. 1.5 mmHg [−1.5; 3]; p = 0.0003) than those with baseline LVEDP <15 mmHg. None of those with a baseline LVEDP <15 mmHg had a LAP/PAWP >15 mmHg during balloon testing compared to 92% of patients with a baseline LVEDP ≥15 mmHg.ConclusionLVEDP might be used to predict LAP post‐ASD closure. Comorbidities typically associated with LV diastolic dysfunction are common in these patients and should be considered in their management.

Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. The biofabrication method in the present study examined 3D printing and collagen injection molding for rapid prototyping of customized living biliary stents with clinical applications in the setting of malignant and benign bile duct obstructions. XL-PVA stents showed hydrophilic swelling and addition of radiocontrast to the stent matrix improved radiographic opacity. Collagen loaded with PMSCs contracted tightly around hydrophilic stents and dense choloangiocyte coatings were verified through histology and fluorescence microscopy. It is anticipated that design elements used in these stents may enable appropriate stent placement, provide protection of the stent-stem cell matrix against bile constituents, and potentially limit biofilm development. Overall, this approach may allow physicians to create personalized bio-integrating stents for use in biliary procedures and lays a foundation for new patient-specific stent fabrication techniques.