Allergen immunotherapy (AIT) has been acknowledged as the only disease-modifying treatment for respiratory diseases since its introduction in 1911. Although the efficacy and safety have convincingly been established in numerous randomized clinical trials (RCTs), the AIT study results may vary substantially. Several factors that may influence the outcome of RCTs will be addressed. First, the choice of the primary endpoint is essential. Lack of validated endpoints with proven clinical relevance may contribute to the variation in study results. Secondly, heterogeneity of the patient population affects the study outcome, thereby raising the question of whether current selection criteria should be further optimized to capture those patients who will benefit from immunotherapy. Thirdly, variability and particularly low allergen exposure may lead to unsuccessful AIT trials. Fourthly, unsuccessful trials may stem from large placebo effects. Furthermore, discrepancies between Phase II and III studies are asking for cautious interpretation of Phase II studies when planning Phase III studies. Flaws in trial design, inadequate reporting of the clinical trial protocol and data may hamper the interpretation of study results. In addition, this review addresses specific aspects of AIT trial design in children and asthmatic patients. To improve future AIT trials, innovative solutions are urgently needed, including the establishment of an internationally accepted minimal clinically important difference (MCID), the validation of primary endpoints, the integration of field studies and allergen exposure chamber studies, and the publication of negative study results.

The International Diabetes Federation estimated that in 2024, 215 million adults-more than one-third of the global diabetes population-were living with diabetes within the Western Pacific Region (WPR), which includes nations with some of the highest prevalence worldwide. Rapid urbanization and economic development have profoundly reshaped lifestyles, which interact with biological predispositions resulting in an earlier onset of type 2 diabetes. These predispositions are not uniform across the heterogeneous populations within the WPR. Asian individuals tend to have a β-cell secretory failure phenotype with type 2 diabetes arising at lower adiposity, distinct from the high-adiposity phenotype with pronounced insulin resistance common among Pacific peoples. Improvements in diabetes care in high-income countries have reduced vascular complications and improved survival, shifting the clinical profile of individuals with type 2 diabetes toward an older population characterized by multimorbidity. In contrast, low-income settings continue to face a high prevalence of type 2 diabetes, compounded by limited access to medications and diagnostic tools, shortage of trained health care professionals, and other logistical barriers to care. In this diverse region where countries are at different stages of health care development, there are considerable opportunities for sharing of best practices through collaborative and translational research. These may include social and public health policies, health care delivery, use of registers to track disease patterns and care standards, and use of technologies to support self-management. For implementation of these actions, a major shift is required, toward prevention, capacity building, and demonstrating the impact of value-based prevention and data-driven care.

Pulmonary hypertension associated with left heart disease, or group 2 pulmonary hypertension, is common in patients with advanced heart failure. In at least a third of these patients, the pulmonary pressures are disproportionately elevated relative to left heart filling pressures and are classified as combined post- and precapillary pulmonary hypertension (CpcPH). CpcPH is thought to result not only from chronically elevated left heart filling pressures but also from neurohormonal activation, a genetic predisposition, and other risk factors. Traditional pulmonary vasodilator therapies are not efficacious and may be harmful in CpcPH. For patients with advanced heart failure, higher-risk CpcPH hemodynamics, particularly significantly elevated or nonreversible pulmonary vascular resistance and transpulmonary gradient, may preclude isolated heart transplantation, while acute vasodilator testing may identify patients who can proceed with acceptable risk. Strategies to minimize posttransplant risk in recipients with CpcPH based on donor selection, for example, oversizing of the donor by relative predicted heart mass or selecting donors with preexisting PH, remain unproven. This review serves to (1) highlight new insights into the pathophysiology and epidemiology of CpcPH; (2) summarize the existing literature surrounding indications for, and interpretation of response to, acute pulmonary vasodilator testing; (3) provide recommendations for management of patients with heart failure and CpcPH, with a particular focus on advanced therapies; and (4) identify knowledge gaps and future research priorities.

Congenital complete atrioventricular block (CCAVB) is a well-recognized manifestation of neonatal lupus erythematosus (NLE), caused by transplacental transfer of maternal anti-Ro/Sjögren's Syndrome Type A (SSA) and anti-La/Sjögren's Syndrome Type B (SSB) antibodies. Although non-cardiac manifestations of NLE typically resolve within the first year of life, the long-term autoimmune risk in affected offspring remains unclear. We report a 24-year-old woman with CCAVB secondary to maternal Sjögren's disease who presented with acute heart failure, nephrotic-range proteinuria, bicytopenia, pericardial effusion, and findings concerning for Libman-Sacks endocarditis. Despite negative conventional lupus serologies, renal biopsy demonstrated Class IV/V lupus-like immune-complex glomerulonephritis with full-house immune complex deposition, leading the multidisciplinary team to favor seronegative lupus nephritis. This case demonstrates the diagnostic limitations of serology-based approaches in atypical lupus presentations and underscores the critical role of tissue biopsy. The case also raises questions regarding long-term autoimmune risk after autoimmune congenital heart block, an area for which prospective data and evidence-based surveillance strategies remain limited.