Metavert synergises with standard cytotoxics in human PDAC organoids and is associated with transcriptomic signatures of therapeutic response.

Background: Despite some recent advances, pancreatic ductal adenocarcinoma (PDAC) remains a growing oncological challenge. New drugs capable of targeting more than one oncogenic pathway may be one way to improve patient outcomes. This study characterizes the effectiveness of Metavert a first-in-class dual inhibitor of GSK3-β and histone deacetylase in treating PDAC as a single agent or in combination with standard cytotoxics.

Racial variation in healthcare resource utilization and expenditures in knee/hip osteoarthritis patients: a retrospective analysis of a Medicaid population.

Background: Osteoarthritis (OA) is a leading cause of chronic pain and disability. Prior studies have documented racial disparities in the clinical management of OA. The objective of this study was to assess the racial variations in the economic burden of osteoarthritis within the Medicaid population.

Baricitinib decreases anti-dsDNA in patients with systemic lupus erythematosus: results from a phase II double-blind, randomized, placebo-controlled trial.

Background: Patients with systemic lupus erythematosus (SLE) have substantial unmet medical need. Baricitinib is a Janus kinase (JAK)1 and 2 inhibitor that was shown to have therapeutic benefit in patients with SLE in a phase II clinical trial. The purpose of this study was to evaluate the median change from baseline in conventional serologic biomarkers in subgroups and the overall population of baricitinib-treated patients with SLE, and the SLE Responder Index-4 (SRI-4) response by normalization of anti-dsDNA.

Using Patient-Reported Health Data From Social Media to Identify Diverse Lupus Patients and Assess Their Symptom and Medication Expressions: A Feasibility Study.

Objective: Patient communities use social media for peer support and information seeking. This study assessed the feasibility of using public patient-generated health data from the social network Twitter to identify diverse lupus patients and gather their perspectives about disease symptoms and medications.

Methods: We extracted public lupus-related Twitter messages (n = 47,715 tweets) in English posted by users (n = 8,446) in the US between September 1, 2017 and October 31, 2018.

The global approach to rehabilitation following an osteoporotic fragility fracture: A review of the rehabilitation working group of the International Osteoporosis Foundation (IOF) committee of scientific advisors.

Purpose: To conduct a review of the current state of the evidence for rehabilitation strategies post-fragility fracture.

Methods: Narrative review conducted by the Rehabilitation Working Group of the International Osteoporosis Foundation Committee of Scientific Advisors characterizing the range of rehabilitation modalities instrumental for the management of fragility fractures.

Results: Multi-modal exercise post-fragility fracture to the spine and hip is strongly recommended to reduce pain, improve physical function, and improve quality of life.

Neuropsychiatric Events in Systemic Lupus Erythematosus: Predictors of Occurrence and Resolution in a Longitudinal Analysis of an International Inception Cohort.

Objective: To determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE).

Methods: Upon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician-determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time-to-event analysis using a multistate modeling structure.

Economic Evaluation of Damage Accrual in an International Systemic Lupus Erythematosus Inception Cohort Using a Multistate Model Approach.

Objective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling.

Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis.

Cerebrovascular Events in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

Objective: To determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic/racial inception cohort of patients with systemic lupus erythematosus (SLE).

Methods: A total of 1,826 patients were assessed annually for 19 neuropsychiatric (NP) events, including 5 types of CerVEs: 1) stroke, 2) transient ischemia, 3) chronic multifocal ischemia, 4) subarachnoid/intracranial hemorrhage, and 5) sinus thrombosis. Global disease activity (Systemic Lupus Erythematosus Disease [SLE] Activity Index 2000), damage scores (SLE International Collaborating Clinics/American College of Rheumatology Damage Index), and Short Form 36 (SF-36) scores were collected.

CD8+ T Cells Contribute to the Development of Coronary Arteritis in the Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease.

Objective: Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries. Coronary lesions in KD in humans are characterized by an increased presence of infiltrating CD3+ T cells; however, the specific contributions of the different T cell subpopulations in coronary arteritis development remain unknown. Therefore, we sought to investigate the function of CD4+ and CD8+ T cells, Treg cells, and natural killer (NK) T cells in the pathogenesis of KD.

Cumulative Corticosteroid Dose Over Fifty-Two Weeks in Patients With Systemic Lupus Erythematosus: Pooled Analyses From the Phase III Belimumab Trials.

Objective: To examine the effects of treatment with belimumab on corticosteroid dose in patients with systemic lupus erythematosus (SLE) over 52 weeks in 2 randomized, controlled trials.

Methods: Data on patients who were taking corticosteroids at baseline in the Study of Belimumab in Subjects with SLE trials were pooled post hoc to compare patients who received belimumab 10 mg/kg plus standard therapy with those who received placebo plus standard therapy. The primary end point was cumulative change from baseline in corticosteroid dose (prednisone equivalent) through week 52.

A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach.

Objective: To study bidirectional change and predictors of change in estimated glomerular filtration rate (GFR) and proteinuria in lupus nephritis (LN) using a multistate modeling approach.

Methods: Patients in the Systemic Lupus International Collaborating Clinics inception cohort were classified annually into estimated GFR state 1 (>60 ml/minute), state 2 (30-60 ml/minute), or state 3 (<30 ml/minute) and estimated proteinuria state 1 (<0.25 gm/day), state 2 (0.

Mood Disorders in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

Objective: To examine the frequency, characteristics, and outcome of mood disorders, as well as clinical and autoantibody associations, in a multiethnic/racial, prospective inception cohort of patients with systemic lupus erythematosus (SLE).

Methods: Patients were assessed annually for mood disorders (4 types, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 18 other neuropsychiatric events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 subscales, mental and physical component summary scores were collected.

Role of modern 3D echocardiography in valvular heart disease.

Three-dimensional (3D) echocardiography has been conceived as one of the most promising methods for the diagnosis of valvular heart disease, and recently has become an integral clinical tool thanks to the development of high quality real-time transesophageal echocardiography (TEE). In particular, for mitral valve diseases, this new approach has proven to be the most unique, powerful, and convincing method for understanding the complicated anatomy of the mitral valve and its dynamism. The method has been useful for surgical management, including robotic mitral valve repair.

Use of FRAX®-based fracture risk assessments to identify patients who will benefit from osteoporosis therapy.

Several pharmacological interventions, including selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab, and strontium ranelate have demonstrated efficacy in reducing the incidence of osteoporotic fractures, the most severe consequence of postmenopausal osteoporosis. Until recently, bone mineral density (BMD) was the primary factor used to determine which postmenopausal women may require osteoporosis treatment. However, clinical guidelines now recommend the use of the Fracture Risk Assessment Tool (FRAX(®)), a computer-based algorithm introduced by the World Health Organization, to help primary care physicians identify postmenopausal women who may be candidates for pharmacological osteoporosis therapy based on the level of fracture risk.

Ernest Henry Starling (1866-1927) on the glomerular and tubular functions of the kidney.

Around the turn of the 20th century, Ernest Henry Starling (1866-1927) made many fundamental contributions to the understanding of human physiology. With a deep interest in how fluid balance is regulated, he naturally turned to explore the intricacies of kidney function. Early in his career he focused upon the process of glomerular filtration and was able to substantiate the view of Carl Ludwig that this process can be explained entirely upon the basis of hydrostatic and oncotic pressure gradients across the glomerular capillary wall and that the process can be regulated by alterations in the tone of the afferent and efferent arterioles.

Restoring the function of a diseased kidney via its microvasculature.

Background: Based upon observations which indicate that chronic intrarenal hypoxia and microvascular obliteration play an important role in the pathogenesis of renal scarring and loss of function, the idea is presented that restoration of kidney structure and function by arresting microvascular drop-out and restoring the interstitial capillary network could be a feasible approach to regeneration of a diseased kidney. This paper addresses the reasoning behind this possibility.

Summary: A 'unifying vasculogenic hypothesis' is discussed which proposes that, in hypoxic nephrons which retain poorly functioning vascular and epithelial elements, the disease process can be slowed or arrested, and nephrons regenerated, by adoptive transfer of endothelial progenitor cells to restore interstitial and glomerular vascular integrity.

Ernest Henry Starling (1866-1927) on the formation and reabsorption of lymph.

Ernest Henry Starling laid the groundwork for our modern understanding of how the interstitial fluid, which he referred to as 'lymph', is regulated. Together with his colleague, William Bayliss, he provided the crucial insight into how fluid is driven out of the capillary to form interstitial fluid. That was to measure (estimate) the capillary pressure in different parts of the circulation and to relate changes in these pressures to altered lymph formation.

On reporting of effect size in randomized clinical trials.

Published reports of randomized clinical trials tend to emphasize the statistical significance of the treatment effect (p values) rather than its magnitude (effect size), although the clinical importance of the evidence depends more on the latter than on the former. We, therefore, compared the standard measures of effect size (relative and absolute risk reduction) and nonstandard composites of these measures (the product of the relative and absolute risk reductions and information content) with conventional assessments of statistical significance for 100 trials published in The New England Journal of Medicine. The p values were reported for 100% of the trials, relative risk reductions for 89%, and absolute risk reductions for 39%.

Individualizing osteoporosis therapy.

Guidelines for osteoporosis treatment are available; however, these guidelines suggest when to treat patients, without specific recommendations on what drugs to prescribe in various situations. Choice of osteoporosis therapy should be individualized based on consideration of the efficacy, safety, cost, convenience (i.e.

Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study.

Unlabelled: In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated.

Introduction: This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years.