Infectious diseases, cardio-cerebrovascular health and vaccines: pathways to prevention.

Cardiovascular and infectious diseases both feature among the leading causes of death among men and women in the world. The pathophysiological pathways of infection and cardiovascular disease intersect, and there is a bidirectional relationship between the two. Vaccines are available for the most common infectious diseases affecting older adults, such as influenza, pertussis, pneumococcal disease, herpes zoster, COVID and respiratory syncytial virus (RSV).

The Rapidly Changing Treatment Landscape of IgA Nephropathy.

The past few years have heralded a sea change in the treatment landscape of IgA nephropathy (IgAN). An increasing understanding of its pathogenesis coupled with favorable changes in the regulatory approval pathway has led to an explosion of clinical drug development in this disease. This has directly resulted in the approval of three novel therapies specifically for the treatment of IgAN (nefecon, sparsentan, and iptacopan), and several others are in the late stages of clinical development.

Factor B as a therapeutic target for the treatment of complement-mediated diseases.

The complement system, consisting of three initiating pathways-classical, lectin and alternative, is an important part of innate immunity. Dysregulation of the complement system is implicated in the pathogenesis of several autoimmune and inflammatory diseases. Therapeutic inhibition of the complement system has been recognized as a viable approach to drug development and has been successful with the approval of a small number of complement inhibitors for diseases such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, neuromyelitis optica, myasthenia gravis and geographic atrophy.

Musculoskeletal diseases, infections and vaccines: state of the art, research perspectives and educational needs.

Musculoskeletal disorders are a significant public health burden concern, projected to increase in the coming decades, and will substantially contribute to the rising prevalence of functional impairment, frailty and disability in a growing global population. Since persons with musculoskeletal disorders tend to have immune dysfunction, inflammation or be taking immunosuppressive medication, prevention of vaccine-preventable diseases (VPDs) in this group is particularly important. The European Interdisciplinary Council for Aging (EICA) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) jointly convened a 2-day in-person and virtual meeting on 26-27 September 2023, to review the state of the evidence on the link between musculoskeletal diseases, infections and vaccines.

Cyclospora Genotypic Variations and Associated Epidemiologic Characteristics, United States, 2018-2021.

Seasonal cyclosporiasis outbreaks occur in the United States every year. To better understand the disease, the Centers for Disease Control and Prevention developed a novel genotyping system that successfully clusters nonclonal eukaryotes. We examined temporal-geographic distributions of Cyclospora cluster consensus genotypes (CCGs) and applied regression analyses to identify correlations between Cyclospora spp.

Is Parasitic Contamination of Soil in the Southern United States Related to Poverty and Does It Represent a Human Health Threat? A Perspective.

In recent years, multiple reports have emerged describing real-time quantitative polymerase chain reaction (qPCR) detection of DNA derived from human parasite species in environmental soil samples. In one such report, sampling was focused in impoverished areas of the southeastern United States, and a link between poverty and the presence of parasite DNA in soil was proposed. Whether transmission of certain parasitic diseases persists in the United States in association with poverty remains an important question.

Treatment of patients with IgA nephropathy: a call for a new paradigm.

IgA nephropathy (IgAN), the world's most common primary glomerular disease, carries a significant lifetime risk for kidney failure as well as an enormous socioeconomic burden. In the past, studies in patients with IgAN largely focused on optimizing so-called supportive care, that is, blockade of the renin-angiotensin system, blood pressure control, and lifestyle modifications. The effectiveness of immunosuppressive measures, particularly high-dose corticosteroid therapy, has been reported variably, but there is considerable evidence for an increase in serious adverse effects with such therapies.

Study Design and Baseline Characteristics of ALIGN, a Randomized Controlled Study of Atrasentan in Patients With IgA Nephropathy.

Introduction: Endothelin A (ETA) receptor activation is a driver of proteinuria, kidney inflammation, and fibrosis in IgA nephropathy (IgAN). Atrasentan, a selective ETA receptor antagonist, has potential to reduce proteinuria and preserve kidney function in IgAN. ALIGN (NCT04573478) is a phase 3, randomized, double-blind, placebo-controlled clinical trial of atrasentan in patients with IgAN at high risk of kidney function loss.

Efficacy and Safety of Nefecon in Patients with IgA Nephropathy from Mainland China: 2-Year NefIgArd Trial Results.

Background: IgA nephropathy (IgAN), an immune-mediated kidney disease, is particularly prevalent among individuals of East Asian ancestry. Nefecon is a novel, oral, targeted-release budesonide formulation designed to inhibit galactose-deficient IgA1 formation underlying IgAN pathophysiology. We present findings in patients with IgAN from mainland China participating in the 2-year, multicenter, randomized, double-blind, phase 3 NefIgArd trial of nefecon.

Scoping Review of Economic Analyses of Rare Kidney Diseases.

Introduction: Rare kidney diseases (RKDs) place a substantial economic burden on patients and health systems, the extent of which is unknown and may be systematically underestimated by health economic techniques. We aimed to investigate the economic burden and cost-effectiveness evidence base for RKDs.

Methods: We conducted a systematic scoping review to identify economic evaluations, health technology assessments, and cost-of-illness studies relating to RKDs, published since 2012.

Global Insights from Patients, Providers, and Staff on Challenges and Solutions in Managing Neovascular Age-Related Macular Degeneration.

Introduction: Neovascular age-related macular degeneration is a global public-health concern, associated with a considerable burden to individuals, healthcare systems, and society. The objective of this study was to understand different perspectives on the challenges associated with the clinical management of neovascular age-related macular degeneration, which could elucidate measures to comprehensively improve clinical care and outcomes.

Methods: A survey was carried out of patients with neovascular age-related macular degeneration, their providers, and clinic staff in 77 clinics across 24 countries on six continents, from a diverse range of healthcare systems, settings, and reimbursement models.

Improving Clinical Management of Diabetic Macular Edema: Insights from a Global Survey of Patients, Healthcare Providers, and Clinic Staff.

Introduction: In contrast with patients receiving therapy for retinal disease during clinical trials, those treated in routine clinical practice experience various challenges (including administrative, clinic, social, and patient-related factors) that can often result in high patient and clinic burden, and contribute to suboptimal visual outcomes. The objective of this study was to understand the challenges associated with clinical management of diabetic macular edema from the perspectives of patients, healthcare providers, and clinic staff, and identify opportunities to improve eye care for people with diabetes.

Methods: We conducted a survey of patients with diabetic macular edema, providers, and clinic staff in 78 clinics across 24 countries on six continents, representing a diverse range of individuals, healthcare systems, settings, and reimbursement models.

Post-transplant IgA nephropathy: a rapidly evolving field of kidney transplant medicine.

IgA nephropathy is the commonest pattern of primary glomerular disease in the world, with high rates of progression to kidney failure. As IgA nephropathy commonly causes kidney failure at a young age, kidney transplantation is commonly used to treat kidney failure. However, high rates of recurrent disease in the allograft remain a common management challenge.

Geo-classification of drug-resistant travel-associated using and gene sequences (USA, 2018-2021).

Travel-related malaria is regularly encountered in the United States, and the U.S. Centers for Disease Control and Prevention (CDC) characterizes drug-resistance genotypes routinely for travel-related cases.

The association between intra-arrest arterial blood pressure and return of spontaneous circulation in out-of-hospital cardiac arrest.

Background: The optimal haemodynamic parameter for goal-directed resuscitation in out-of-hospital cardiac arrest (OHCA) remains uncertain. This study aimed to characterise the association between invasive blood pressure (IBP) measurements and return of spontaneous circulation (ROSC) in adult OHCA patients, to identify this parameter.

Methods: A retrospective observational study was conducted at East Anglian Air Ambulance (EAAA).

Long-Term Results from an Open-Label Extension Study of Atacicept for the Treatment of IgA Nephropathy.

Background: B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) play key roles in the pathogenesis of IgA nephropathy. Atacicept is a novel fully humanized fusion protein, self-administered at home by subcutaneous injection, that binds and inhibits BAFF and APRIL. By inhibiting BAFF and APRIL, atacicept targets the underlying B-cell–mediated pathogenesis driving disease progression.

Atrasentan in Patients with IgA Nephropathy.

Background: Patients with IgA nephropathy and severe proteinuria have a high lifetime risk of kidney failure. The efficacy and safety of the selective endothelin type A receptor antagonist atrasentan in reducing proteinuria in patients with IgA nephropathy are incompletely understood.

Methods: We are conducting a phase 3, multinational, double-blind, randomized, controlled trial involving adults with biopsy-proven IgA nephropathy, a total urinary protein excretion of at least 1 g per day, and an estimated glomerular filtration rate of at least 30 ml per minute per 1.

Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy.

Background: The alternative complement pathway plays a key role in the pathogenesis of IgA nephropathy. Iptacopan specifically binds to factor B and inhibits the alternative pathway.

Methods: In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled adults with biopsy-confirmed IgA nephropathy and proteinuria with a 24-hour urinary protein-to-creatinine ratio of 1 or higher (with protein and creatinine both measured in grams) despite optimized supportive therapy.

Mucosal targeting in IgA nephropathy targeting the gut associated lymphoid tissue.

IgA nephropathy is a mucosally driven disease and new therapeutic approaches are specifically targeting the mucosal production of IgA in the hope that this will lead to a reduction in circulating IgA immune complexes and mesangial IgA deposition. In this lecture, I discuss the rationale for targeting the mucosal immune system of the gut and the existing data from clinical trials supporting such an approach as a disease modifying treatment for IgA nephropathy.