National survey of financial burden and experience among patients with cancer and autoimmune disease receiving charitable copay assistance.

Background: Little is known about the role that charitable copay assistance (CPA) plays in addressing access to care and financial distress. The study sought to evaluate financial distress and experience with CPA among patients with cancer and autoimmune disease.

Methods: This is a national cross-sectional self-administered anonymous electronic survey conducted among recipients of CPA to cover the costs of a drug for cancer or autoimmune disease.

National survey of patient perspectives on cost discussions among recipients of copay assistance.

Background: Individuals with cancer and other medical conditions often experience financial concerns from high costs-of-care and may utilize copay assistance programs (CAP). We sought to describe CAP recipients' experiences/preferences for cost discussions with clinicians.

Methods: We conducted a national, cross-sectional electronic-survey from 10/2022 to 11/2022 of CAP recipients with cancer or autoimmune conditions to assess patient perspectives on cost discussions.

Autoantibodies Targeting Nephrin in Podocytopathies.

Background: Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear.

Methods: We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls.

Introduction of a novel chimeric active immunization mouse model of PLA2R1-associated membranous nephropathy.

The phospholipase A2 receptor 1 (PLA2R1) is the major target antigen in patients with membranous nephropathy (MN), an antibody-mediated autoimmune glomerular disease. Investigation of MN pathogenesis has been hampered by the lack of reliable animal models. Here, we overcome this issue by generating a transgenic mouse line expressing a chimeric PLA2R1 (chPLA2R1) consisting of three human PLA2R1 domains (cysteine-rich, fibronectin type-II and CTLD1) and seven murine PLA2R1 domains (CTLD2-8) specifically in podocytes.

Non-functional ubiquitin C-terminal hydrolase L1 drives podocyte injury through impairing proteasomes in autoimmune glomerulonephritis.

Little is known about the mechanistic significance of the ubiquitin proteasome system (UPS) in a kidney autoimmune environment. In membranous nephropathy (MN), autoantibodies target podocytes of the glomerular filter resulting in proteinuria. Converging biochemical, structural, mouse pathomechanistic, and clinical information we report that the deubiquitinase Ubiquitin C-terminal hydrolase L1 (UCH-L1) is induced by oxidative stress in podocytes and is directly involved in proteasome substrate accumulation.

The classical pathway triggers pathogenic complement activation in membranous nephropathy.

Membranous nephropathy (MN) is an antibody-mediated autoimmune disease characterized by glomerular immune complexes containing complement components. However, both the initiation pathways and the pathogenic significance of complement activation in MN are poorly understood. Here, we show that components from all three complement pathways (alternative, classical and lectin) are found in renal biopsies from patients with MN.

Podocyte expression of human phospholipase A2 receptor 1 causes immune-mediated membranous nephropathy in mice.

Antibody-mediated autoimmune pathologies like membranous nephropathy are difficult to model, particularly in the absence of local target antigen expression in model organisms such as mice and rats; as is the case for phospholipase A2 receptor 1 (PLA2R1), the major autoantigen in membranous nephropathy. Here, we generated a transgenic mouse line expressing the full-length human PLA2R1 in podocytes, which has no kidney impairment after birth. Beginning from the age of three weeks, these mice spontaneously developed anti-human PLA2R1 antibodies, a nephrotic syndrome with progressive albuminuria and hyperlipidemia, and the typical morphological signs of membranous nephropathy with granular glomerular deposition of murine IgG in immunofluorescence and subepithelial electron-dense deposits by electron microscopy.

Strategies Towards Antigen-Specific Treatments for Membranous Nephropathy.

Membranous nephropathy (MN) is a rare but potentially severe autoimmune disease and a major cause of nephrotic syndrome in adults. Traditional treatments for patients with MN include steroids with alkylating agents such as cyclophosphamide or calcineurin inhibitors such as cyclosporine, which have an undesirable side effect profile. Newer therapies like rituximab, although superior to cyclosporine in maintaining disease remission, do not only affect pathogenic B or plasma cells, but also inhibit the production of protective antibodies and therefore the ability to fend off foreign organisms and to respond to vaccination.

Financial toxicity in cancer care: origins, impact, and solutions.

Financial toxicity describes the financial burden and distress that can arise for patients, and their family members, as a result of cancer treatment. It includes direct out-of-pocket costs for treatment and indirect costs such as travel, time, and changes to employment that can increase the burden of cancer. While high costs of cancer care have threatened the sustainability of access to care for decades, it is only in the past 10 years that the term "financial toxicity" has been popularized to recognize that the financial burdens of care can be just as important as the physical toxicities traditionally associated with cancer therapy.

Glomerular Endothelial Cell-Derived microRNA-192 Regulates Nephronectin Expression in Idiopathic Membranous Glomerulonephritis.

Background: Autoantibodies binding to podocyte antigens cause idiopathic membranous glomerulonephritis (iMGN). However, it remains elusive how autoantibodies reach the subepithelial space because the glomerular filtration barrier (GFB) is size selective and almost impermeable for antibodies.

Methods: Kidney biopsies from patients with iMGN, cell culture, zebrafish, and mouse models were used to investigate the role of nephronectin (NPNT) regulating microRNAs (miRs) for the GFB.

A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients.

The phospholipase A2 receptor 1 (PLA2R1) is the major autoantigen in patients suffering from membranous nephropathy. To date, the lack of endogenous glomerular expression of PLA2R1 in mice and rats has impeded the establishment of PLA2R1-dependent animal models of this disease. Here, we generated a transgenic mouse line expressing murine full-length PLA2R1 in podocytes.

Clinical Relevance of Domain-Specific Phospholipase A Receptor 1 Antibody Levels in Patients with Membranous Nephropathy.

Background: Antibodies against phospholipase A receptor 1 (PLAR1) are found in 80% of patients with membranous nephropathy, and previous studies described three autoantibody-targeted PLAR1 epitope regions. Although anti-PLAR1 antibody levels are closely associated with treatment response and disease prognosis, the clinical role of epitope regions targeted by autoantibodies is unclear.

Methods: In a prospective cohort of 150 patients with newly diagnosed PLAR1-associated membranous nephropathy, we investigated the clinical role of epitope-recognition patterns and domain-specific PLAR1 antibody levels by western blot and ELISA.

Association of comorbid depression with inpatient outcomes in critical limb ischemia.

There is a growing body of evidence that peripheral artery disease (PAD) may be impacted by depression. The objective of this study is to determine whether outcomes, primarily major amputation, differ between patients with depression and those without who presented to hospitals with critical limb ischemia (CLI), the end-stage of PAD. A retrospective cohort of patients hospitalized for CLI during 2012 and 2013 was identified from the National Inpatient Sample (NIS) using ICD-9 codes.

Peripheral Artery Disease Is Associated with a Deficiency of Erythrocyte Membrane n-3 Polyunsaturated Fatty Acids.

Population-based data suggest that individuals who consume large dietary amounts of n-3 polyunsaturated fatty acids (PUFA) have lower odds of peripheral artery disease (PAD); however, clinical studies examining n-3 PUFA levels in patients with PAD are sparse. The objective of this study is to compare erythrocyte membrane fatty acid (FA) content between patients with PAD and controls. We conducted a cross-sectional study of 179 vascular surgery outpatients (controls, 34; PAD, 145).

Fish Oil Increases Specialized Pro-resolving Lipid Mediators in PAD (The OMEGA-PAD II Trial).

Background: N-3 polyunsaturated fatty acid (PUFA) supplementation has been associated with reduced mortality and inflammation in patients with cardiovascular disease. There are limited data on the effects of n-3 PUFA supplementation in patients with peripheral artery disease (PAD).

Materials And Methods: The OMEGA-PAD II trial was a double-blinded, randomized, placebo-controlled trial to assess the effect of 3 mo of high-dose oral n-3 PUFA supplementation on inflammation, endothelial function, and walking ability in patients with PAD.

Leptinemia is Associated With Peripheral Artery Disease.

Background: Leptin, adiponectin, and resistin are in a class of hormones called adipokines that are produced by adipocytes and have been implicated in the causal pathway of atherosclerosis. We examined the association between adipokine levels and peripheral artery disease (PAD), hypothesizing that after adjusting for fat mass, leptin and resistin would be higher, whereas adiponectin would be lower, in patients with PAD.

Methods: A cross-sectional sample of 179 predominately male (97%) vascular surgery outpatients was recruited from the San Francisco Veterans Affairs Medical Center (SFVAMC).

Radial Artery Tonometry is Associated With Major Adverse Cardiac Events in Patients With Peripheral Artery Disease.

Background: Peripheral artery disease (PAD) is associated with increased arterial stiffness, as measured by an increasing radial artery augmentation index (AIX). However, it has not yet been clearly demonstrated whether AIX is associated with adverse cardiovascular outcomes in a PAD population.

Materials And Methods: Seventy-two patients with PAD were recruited between 2011 and 2016.

Serum resistin is associated with impaired endothelial function and a higher rate of adverse cardiac events in patients with peripheral artery disease.

Objective: Resistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD.