Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT-V Study.

Background: The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH.

Aims: In the US multicentre SHUNT-V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy.

Methods: Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices.

Duration of anticoagulation for venous thromboembolism in pediatric patients: Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) trial outcomes at 2 years.

Background: The Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children multinational, randomized clinical trial revealed noninferiority of a 6-week vs 3-month duration of anticoagulation for the treatment of provoked venous thromboembolism (VTE) in patients <21 years old in regard to net clinical benefit at 1 year.

Objectives: To evaluate noninferiority at 2 years.

Methods: Patients whose repeat imaging 6 weeks after VTE diagnosis did not show complete veno-occlusion were randomized to discontinue anticoagulation vs receive a total 3-month course and followed for 2 years for the occurrence of symptomatic recurrent VTE (efficacy outcome) and clinically relevant bleeding (safety outcome).

The Oral Cholate Challenge Test Quantifies Risk for Liver-Related Clinical Outcomes in Primary Sclerosing Cholangitis.

Background And Aims: We quantified hepatic functional impairment using quantitative function tests and linked severity of functional impairment to liver-related complications and outcome in primary sclerosing cholangitis.

Methods: Forty-seven patients had baseline testing, and 40 were retested after 1 year. For each test, cholates labeled with cold, nonradioactive isotopes were administered orally (DuO, SHUNT tests) and intravenously (SHUNT test), and blood was analyzed at 20 and 60 minutes (DuO), or 0, 5, 20, 45, 60, and 90 minutes (SHUNT).

Liver function and portal-systemic shunting quantified by the oral cholate challenge test and risk for large oesophageal varices.

Background: The quantitative HepQuant SHUNT test of liver function and physiology generates a disease severity index (DSI) that correlates with risk for clinical complications, such as large oesophageal varices (LEVs). A derivative test, HepQuant DuO, generates an equivalent DSI and simplifies testing by requiring only oral administration of the test solution and two blood samples at 20 and 60 min.

Aims: Since the DSIs measured from DuO and SHUNT are equivalent, we compared the diagnostic performance for large oesophageal varices (LEVs) between the DSIs measured from DuO and SHUNT tests.

Within-individual reproducibility of a dual sample oral cholate challenge test (DuO) and simplified versions of the HepQuant SHUNT test.

Current noninvasive liver tests measure fibrosis, inflammation, or steatosis and do not measure function. The HepQuant platform of noninvasive tests uniquely assesses both liver function and physiology through the hepatic uptake of stable isotopes of cholate. However, the prototypical HepQuant SHUNT test (SHUNT V1.

Advances in noninvasive measurement of liver function and physiology: The HepQuant DuO test.

Current noninvasive liver tests are surrogates for fibrosis and lack ability to directly measure liver function. HepQuant tests measure liver function and physiology through hepatic uptake of stable cholate isotopes. HepQuant SHUNT (V1.

Repeat Ivermectin Mass Drug Administrations for Malaria Control II: Protocol for a Double-blind, Cluster-Randomized, Placebo-Controlled Trial for the Integrated Control of Malaria.

Background: The gains made against malaria have stagnated since 2015, threatened further by increasing resistance to insecticides and antimalarials. Improvement in malaria control necessitates a multipronged strategy, which includes the development of novel tools. One such tool is mass drug administration (MDA) with endectocides, primarily ivermectin, which has shown promise in reducing malaria transmission through lethal and sublethal impacts on the mosquito vector.

Effect of Anticoagulant Therapy for 6 Weeks vs 3 Months on Recurrence and Bleeding Events in Patients Younger Than 21 Years of Age With Provoked Venous Thromboembolism: The Kids-DOTT Randomized Clinical Trial.

Importance: Among patients younger than 21 years of age, the optimal duration of anticoagulant therapy for venous thromboembolism is unknown.

Objective: To test the hypothesis that a 6-week duration of anticoagulant therapy for provoked venous thromboembolism is noninferior to a conventional 3-month therapy duration in patients younger than 21 years of age.

Design, Setting, And Participants: Randomized clinical trial involving 417 patients younger than 21 years of age with acute, provoked venous thromboembolism enrolled at 42 centers in 5 countries from 2008-2021.

Ultrasonic Bone Scalpel (USBS) Does Not Reduce Blood Loss During Posterior Spinal Fusion (PSF) in Patients with Adolescent Idiopathic Scoliosis (AIS): Randomized Clinical Trial.

Study Design: Randomized Clinical Trial.

Objective: The aim of this study was to compare the efficacy of USBS with standard-of-care surgical instruments during posterior spinal fusion (PSF) in patients with adolescent idiopathic scoliosis (AIS) by evaluating the difference in estimated blood loss per level fused (EBL/level).

Summary Of Background Data: PSF surgery for AIS is often associated with high blood loss.

Treatment-Dose LMWH versus Prophylactic/Intermediate Dose Heparins in High-Risk COVID-19 Inpatients: Rationale and Design of the HEP-COVID Trial.

Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment.

The within-individual reproducibility of the disease severity index from the HepQuant SHUNT test of liver function and physiology.

The HepQuant SHUNT test quantifies liver function and blood flow using systemic and portal clearances of cholate. The test can identify the risk of well-compensated patients to develop complications of cirrhosis. To confirm the reliability of a single HepQuant SHUNT test we defined its within-individual reproducibility.

Group sequential designs for clinical trials with bivariate endpoints.

Although all clinical trials are designed and monitored using more than one endpoint, methods are needed to assure that decision criteria are chosen to reflect the clinically relevant tradeoffs that assure the trial's scientific integrity. This article presents a framework for the design and monitoring clinical trials in a bivariate outcome space. The framework uses a rectangular hyperbola to define a bivariate null curve that divides outcome space into regions of benefit and lack of benefit.

Does disability level impact the relationship of muscle strength to walking performance in people with multiple sclerosis? a cross-sectional analysis.

Background And Purpose: Strength training can improve muscle weakness in people with multiple sclerosis (MS), but does not consistently improve walking. Disability level may impact the relationship of muscle weakness and walking performance in people with MS, but few studies have investigated the impact of disability on the relationship of strength and walking. The purpose of this study was to compare the relationships of strength in lower body and trunk muscles to walking performance between mild and moderate disability groups in people with MS.

Rivaroxaban in Peripheral Artery Disease after Revascularization.

Background: Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain.

Methods: In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.

Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease.

Objective: Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome.

Association of high-density lipoprotein particle concentration with cardiovascular risk following acute coronary syndrome: A case-cohort analysis of the dal-Outcomes trial.

Background: High-density lipoprotein cholesterol (HDL-C) concentration is inversely related to risk of major adverse cardiovascular events (MACE) in epidemiologic studies but is a poorer predictor of MACE in patients with established coronary heart disease. HDL particle concentration (HDLP) has been proposed as a better predictor of risk. We investigated whether HDLP is associated with risk of MACE after acute coronary syndrome (ACS).

Effective B cell activation in vitro during viremic HIV-1 infection with surrogate T cell stimulation.

Identifying HIV-1-associated B cell defects and responses to activation may direct interventions to circumvent their impaired antibody responses to infection and vaccines. Among 34 viremic HIV-1-infected and 20 seronegative control adults, we measured baseline frequencies and activation of B and T cell subsets, expression of activation-induced cytidine deaminase (AID), potential determinants of B cell activation in vivo and B and T cell responses in vitro. At baseline, HIV-1 infection was associated with increased IgM memory and decreased anergic cell frequencies, as well as increased activation in all 10 B cell subsets compared with controls.

Feasibility of a targeted strengthening program to improve gait in people with multiple sclerosis: a brief report.

This study aims to determine feasibility of strengthening muscles that are important contributors to gait for people with multiple sclerosis, yet are not routinely targeted in the literature. An 8-week strengthening intervention targeted ankle plantarflexion, hip abduction, and trunk muscles using a repeated-measures design. Outcomes included satisfaction, adherence, muscle strength, gait speed (timed 25-foot walk), gait endurance (6-min walk test), and self-reported gait-related participation (Multiple Sclerosis Walking Scale-12).

Rationale and design for the Vascular Outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD).

Background: Patients with peripheral artery disease (PAD) undergoing a lower-extremity revascularization are at heightened risk for ischemic cardiac and limb events. Although intensification of antithrombotic therapy after revascularization has demonstrated benefit in coronary disease populations, this approach has not been well studied or shown consistent benefit in PAD. Recent trial evidence demonstrated that a treatment strategy of rivaroxaban added to background antiplatelet therapy reduced ischemic risk in patients following recent acute coronary syndromes, as well as in patients with stable atherosclerotic vascular disease.

Contributions of Ankle, Knee, Hip, and Trunk Muscle Function to Gait Performance in People With Multiple Sclerosis: A Cross-Sectional Analysis.

Background: The relative importance of lower extremity and trunk muscle function to gait in people with multiple sclerosis (MS) is unknown.

Objective: This study aimed to investigate the association of lower extremity and trunk muscle function with gait performance in people who have MS and mild-to-moderate disability.

Design: This was a cross-sectional, observational study.

Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following Acute Coronary Syndrome: Analysis of the dal-Outcomes Randomized Clinical Trial.

Importance: It is uncertain whether lipoprotein(a) [Lp(a)], which is associated with incident cardiovascular disease, is an independent risk factor for recurrent cardiovascular events after acute coronary syndrome (ACS).

Objective: To determine the association of Lp(a) concentration measured after ACS with the subsequent risk of ischemic cardiovascular events.

Design, Setting, And Participants: This nested case-cohort analysis was performed as an ad hoc analysis of the dal-Outcomes randomized clinical trial.