Prediction of permanent pacemaker implantation after transcatheter aortic valve replacement: The role of machine learning

BACKGROUND Atrioventricular block requiring permanent pacemaker(PPM) implantation is an important complication of transcatheter aortic valve replacement(TAVR).Application of machine learning could potentially be used to predict preprocedural risk for PPM.AIM To apply machine learning to be used to predict pre-procedural risk for PPM.METHODS A retrospective study of 1200 patients who underwent TAVR(January 2014-December 2017) was performed. 964 patients without prior PPM were included for a 30-d ...     

Long-Term Clinical Outcomes of Underdosed Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Atrial Flutter

BackgroundAlthough direct oral anticoagulants (DOACs) have been shown to be effective at reducing the risk of stroke in patients with atrial fibrillation/flutter (AF), they are sometimes underdosed off-label to mitigate their associated higher bleeding risk. We sought to evaluate frequency and clinical outcomes of inappropriate underdosing of DOACS in patients with AF.MethodsWe conducted a study of subjects with AF who had a clinical indication for stroke prophylaxis (with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 47 years, sex category [CHA₂DS₂-VASc] of 2 or greater) and were prescribed 1 of the 4 clinically approved DOACs (apixaban, rivaroxaban, dabigatran, or edoxaban). We compared all-cause mortality, composite of stroke and systemic embolism, composite of myocardial infarction (MI), acute coronary syndromes (ACS), and coronary revascularization, and major bleeding between patients appropriately dosed and inappropriately underdosed.ResultsA total of 8125 patients met inclusion criteria, with a mean follow up of 2.2 ± 2 years. Of those, 1724 patients (21.2%) were inappropriately dosed. After adjusting for baseline variables, there was no difference in all-cause mortality, risk of stroke or systemic embolism, International Society on Thrombosis and Haemostasis (ISTH) major bleeding, or composite of myocardial infarction, acute coronary syndromes, or coronary revascularization between patients appropriately dosed and inappropriately underdosed. In subgroup analysis, only apixaban demonstrated an increased incidence all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.03-1.49) with inappropriate underdosing. There was no difference in the remaining clinical outcomes noted on subgroup analysis.ConclusionUnderdosing of DOACs did not minimize risk of bleeding, systemic embolization or all-cause mortality in patients with AF. Inappropriate underdosing with apixaban in particular was associated with increased all-cause mortality.     

Animal models for SARS-CoV-2 and SARS-CoV-1 pathogenesis,transmission and therapeutic evaluation

There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral infections. The coronavirus family, which includes severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2, crossed the species barrier and infected humans, causing a global outbreak in the 21^st century. Because humans do not have pre-existing immunity against these viral infections and with ethics governing clinical trials, animal models are therefore being used in clinical studies to facilitate drug discovery and testing efficacy of vaccines. The ideal animal models should reflect the viral replication, clinical signs, and pathological responses observed in humans. Different animal species should be tested to establish an appropriate animal model to study the disease pathology, transmission and evaluation of novel vaccine and drug candidates to treat coronavirus disease 2019. In this context, the present review summarizes the recent progress in developing animal models for these two pathogenic viruses and highlights the utility of these models in studying SARS-associated coronavirus diseases.     

Vasculitis of the nervous system

Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PNS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS. Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PMS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS. “Primary angiitis of the CNS” is the term used to describe isolated CNS involvement by vasculitis, in which neither the clinical presentation and behaviour of the disease, nor the histopathology is uniform. This heterogeneity indicates a spectrum, depending on the type and extent of the vascular involvement seen within the CNS, covering a group of disorders, rather than a single disease. This may explain the different prognosis and response to treatments.. In clinical practice vasculitis of the nervous system, secondary to a known cause or underlying disease is more commonly seen than as a primary disorder. Primary systemic vasculitides and connective-tissue disorders, Behçet's Disease, lymphoproliferative diseases and other malignancies, some infections and related conditions, drugs and substance abuse are some of the conditions known to cause vasculitis in the nervous system. There is a broad variety of pathogenetic mechanisms. Both the CNS and the PNS may be involved, either separately or together.     

Mixed-Micellar Proliposomal Systems for Enhanced Oral Delivery of Progesterone

The objective of our study was to develop a mixed-micellar proliposomal formulation of poorly water-soluble drug progesterone and evaluate the dissolution profile and membrane transport. Several formulations of proliposomes were prepared by mixing different concentrations of lipid, progesterone, polysorbate 80, and microcrystalline cellulose. The mixed-micellar formulation of drug:dimyristoyl-phosphatidycholine:polysorbate 80 (1:20:3.3) exhibited the maximum dissolution (75.27%), while pure progesterone resulted in low dissolution. The above formulation showed a 4-fold increase in transport in Caco-2 cells and a 6-fold increase in transport across the everted rat intestinal sac experiments compared with control. Proliposomal formulations enhance the extent of dissolution and membrane transport of progesterone and serve as ideal carriers for oral delivery of drugs with low water solubility.     

Hypertension and stroke in Asia: A comprehensive review from HOPE Asia

Stroke is the primary cause of disability and vascular death worldwide, including Asia. Asian characteristics that differ from the West lead to higher stroke incidence. Stroke epidemiology studies in Asia have shown varying levels of mortality, incidence, prevalence, and burden of disease. Hypertension is the most prevalent risk factor found in Asia. Besides ethnicity that is associated with stroke incidence, both systolic blood pressure, diastolic blood pressure, and blood pressure variability are positively correlated with stroke incidence. Post‐stroke cognitive impairment is one of the sequelae that affect one‐third of stroke survivors and has become a significant public health concern that is often neglected despite its increasing prevalence. Therefore, it is very important to prevent recurrence by treating stroke optimally and effectively. Increasing awareness and treatment adherence to hypertension, the leading risk factor for stroke, became the main goal in several countries in Asia.     

Use of ACIST™ contrast injection device in carotid artery stenting in high-surgical-risk patients

ObjectiveThe objective is to see if use of the ACIST? device during carotid stenting would be feasible without an increase in primary end points when compared to historic controls.BackgroundCarotid stenting has been studied as an effective alternative to endarterectomy in high-surgical-risk patients. Traditional angiography involves manual contrast injection. It leads to excess contrast volume and greater fluoroscopy times. The Acist contrast injection device helps with the regulation and lowering of contrast volume.MethodsThis is a consecutive, non-randomized, open-label, multiple-operator-based study. Inclusion criteria were as follows: (a) subject is considered at high risk for carotid endarterectomy, (b) subject requires percutaneous carotid angioplasty and stenting for carotid disease, and (c) subject must be asymptomatic with ≥ 80% stenosis of the internal and/or common carotid artery. The primary end points measured were, death from any cause, myocardial infarction, transient ischemic attack or stroke within 30 days of intervention. Secondary end points were contrast volume and fluoroscopy time.ResultsFour operators in one institution performed interventions from June 2007 to May 2012 on 133 consecutive patients. They were predominantly men (59.4%). The mean age (SD) was 73.64 (7.952) years. Stroke occurred in 3% (N = 4), transient ischemic attack in 0.8% (N = 1) and myocardial infarction in 0.8% (N = 1). Three study subjects died (2.3%). The mean (SD) contrast volume was 121.24 (67.79) mL. The mean (SD) fluoroscopy time was 18.34 (11.31) minutes.ConclusionsThe use of the ACIST? device was feasible in carotid stenting in a high-risk population without an increase in end points when compared to historic controls.     

Lung Scedosporiosis in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

A 31-year-old African American woman with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS) (recent CD4 count of 66/mm³) presented to the emergency room with a tension pneumothorax that required an emergent chest tube placement. Computed tomography scan showed fungus balls in multiple lung cavities and surrounding infiltrates. The patient showed remarkable improvement with voriconazole suggesting aspergillosis. However, the patient was serologically negative for Aspergillus and other common fungal infections. Because of a persistent air leak, surgical intervention was needed. The histological finding was consistent with invasive mycosis, and cultures were positive for Scedosporium apiospermum. Literature review showed that, among patients with HIV/AIDS, Scedosporium can present from focal localized to systemic disease, is resistant to traditional antifungal agents, and may respond to prompt management with voriconazole.     

Pharmacologic Therapy of Chronic Heart Failure

Over the past 2 decades, investigators have learned more about the pathophysiologic changes that occur in systolic and diastolic dysfunction. Ironically, in some cases, the biologic pathways that have protected the heart during acute dysfunction are the same pathways that cause progressive deleterious effects with chronic activation. In particular, it is the activation of the neurohormonal system that has a significant impact on disease progression. As a result, the neurohormonal system has provided a key target for pharmacologic therapy in patients with heart failure secondary to systolic dysfunction. These targets include the renin-angiotensin-aldosterone system as well as the sympathetic nervous system. Neurohormonal manipulation, however, is often ineffective in the pharmacologic therapy of patients with endstage heart failure, therefore other treatment strategies - including the use of inotropic agents to improve pump function and diuretics to control fluid balance are needed.