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As a hallmark of autoimmune rheumatic diseases, autoantibodies have been used in diagnosis for decades. However, the immunological mechanism underlying their generation has only become clear following the identification of T follicular helper (TFH) cells and T follicular regulatory (TFR) cells. TFH cells are instrumental in supporting antibody affinity maturation in germinal centre reactions and humoral memory formation, whereas TFR cells suppress TFH cell-mediated antibody responses. Evidence indicates that patients with autoimmune rheumatic diseases have increased numbers of TFH cells that can be hyperactive, and also potentially have altered numbers of TFR cells with reduced function, suggesting a conceivable dysregulation in the balance between TFH cells and TFR cells in these diseases. Therefore, by identifying the molecular mechanisms underlying the development and function of these cell populations, new opportunities have emerged to develop novel therapeutic targets. An increased knowledge of TFH cells and TFR cells has inspired, and hopefully will inspire more, approaches to reinstate the balance of these cells in the prevention and treatment of rheumatic diseases.

The germinal center (GC) is a specialized microstructure that forms in secondary lymphoid tissues, producing long-lived antibody secreting plasma cells and memory B cells, which can provide protection against reinfection. Within the GC, B cells undergo somatic mutation of the genes encoding their B cell receptors which, following successful selection, can lead to the emergence of B cell clones that bind antigen with high affinity. However, this mutation process can also be dangerous, as it can create autoreactive clones that can cause autoimmunity. Because of this, regulation of GC reactions is critical to ensure high affinity antibody production and to enforce self-tolerance by avoiding emergence of autoreactive B cell clones. A productive GC response requires the collaboration of multiple cell types. The stromal cell network orchestrates GC cell dynamics by controlling antigen delivery and cell trafficking. T follicular helper (Tfh) cells provide specialized help to GC B cells through cognate T-B cell interactions while Foxp3 T follicular regulatory (Tfr) cells are key mediators of GC regulation. However, regulation of GC responses is not a simple outcome of Tfh/Tfr balance, but also involves the contribution of other cell types to modulate the GC microenvironment and to avoid autoimmunity. Thus, the regulation of the GC is complex, and occurs at multiple levels. In this review we outline recent developments in the biology of cell subsets involved in the regulation of GC reactions, in both secondary lymphoid tissues, and Peyer's patches (PPs). We discuss the mechanisms which enable the generation of potent protective humoral immunity whilst GC-derived autoimmunity is avoided.

Conventional wisdom is that previous infection with omicron subvariant BA.1 or BA.2 does not protect against BA.5, but data from Portugal show considerable protection against BA.5 infection from previous BA.1 or BA.2 infection.

Abstract Public health indicators serve as vital monitoring tools of population’s health while assisting policy makers in their leadership role while guiding policy decisions. Standardized indicator development continues to face substantial obstacles regarding their conceptual definition, methodological precision, and national compatibility. The aim of this review was to combine academic and institutional literature to assess the application of quality indicators in public health settings. A scoping review of the existing literature on public health quality indicators was conducted. The search was performed in PubMed, EMBASE, and CINAHL databases. Eleven publications were included, and the extracted data were organized in a structured table. Research findings showed that indicators must retain a balance between usefulness, national context adaptability and standardized frameworks. The ECHI, EUHPID, and PAHO’s frameworks established systematic methods to organize indicators and create measurement systems. Subnational programs highlighted that data quality and coverage remained insufficient. Public health indicators serve as essential tools for tracking population health status while assisting in policy decisions. The practical application of indicators depends on their methodological soundness, ethical approach and their practical implementation possibilities. Research demonstrates that public health indicators require continuous investment regarding their technical infrastructure and conceptual frameworks. Future research should include indicator policy impact assessment, framework improvement and real-time public health system assessment.

Autoantibodies are produced within germinal centers (GC), in a process regulated by interactions between B, T follicular helper (Tfh), and T follicular regulatory (Tfr) cells. The GC dysregulation in human autoimmunity has been inferred from circulating cells, albeit with conflicting results due to diverse experimental approaches. We applied a consistent approach to compare circulating Tfr and Tfh subsets in patients with different autoimmune diseases. We recruited 97 participants, including 72 patients with Hashimoto’s thyroiditis (HT, n = 18), rheumatoid arthritis (RA, n = 16), or systemic lupus erythematosus (SLE, n = 32), and 31 matched healthy donors (HD). We found that the frequency of circulating T follicular subsets differed across diseases. Patients with HT had an increased frequency of blood Tfh cells ( p  = 0.0215) and a reduced Tfr/Tfh ratio ( p  = 0.0338) when compared with HD. This was not observed in patients with systemic autoimmune rheumatic diseases (RA, SLE), who had a reduction in both Tfh ( p  = 0.0494 and p  = 0.0392, respectively) and Tfr ( p  = 0.0003 and p  = 0.0001, respectively) cells, resulting in an unchanged Tfr/Tfh ratio. Activated PD-1 + ICOS + Tfh and CD4 + PD-1 + CXCR5 – Tph cells were raised only in patients with SLE ( p  = 0.0022 and p  = 0.0054), without association with disease activity. Our data suggest that GC dysregulation, assessed by T follicular subsets, is not uniform in human autoimmunity. Specific patterns of dysregulation may become potential biomarkers for disease and patient stratification.

Background Healthcare systems aim to enhance the health status and well-being of the individuals and populations they serve. To achieve this, measuring and evaluating the quality and safety of services provided and the outcomes achieved is essential. Like other countries, Romania faces challenges regarding the quality of care provided in its public hospitals. To address this, the Romanian Ministry of Health initiated reforms in 2022, including implementing a pay-for-performance model based on quality indicators. This paper presents a descriptive analysis of processes, methods, results and lessons learned from developing and piloting a set of Quality of Care indicators for Romanian public hospitals. Methods World Health Organization’s Athens Office on Quality of Care and Patient Safety assisted Romania in developing and piloting a set of quality-of-care indicators for public hospitals. The development phase included defining indicator domains, identifying potential indicators across these domains, and defining the final indicator set. The piloting phase involved selecting and recruiting piloting hospitals, developing data collection and validation methods and tools, training hospital staff, and collecting and analysing indicator data. Piloting ended with an evaluation workshop. Mixed, quantitative and qualitative methods were used, including literature reviews, stakeholder consultation workshops, survey instruments developed for this study, modified Delphi panels and consensus-building meetings. National stakeholders were actively involved throughout the process. Results Four priority domains were defined for quality-of-care indicators for Romanian public hospitals: patient safety, patient experience, healthcare workforce training and safety, and clinical effectiveness. 25 core indicators were selected across these domains. During the pilot, hospitals achieved an average completion rate of 90% for data submission, with all domains rated equally relevant during post-pilot evaluations. Lessons included the need for supportive legislation, improved internal auditing practices and enhanced staff training, refinement of indicator data collection methods and alignment of indicators with hospital-specific contexts. Conclusions This work presents a significant stride in improving Romanian public hospitals’ quality of care and patient safety. It underscores the importance of high-level commitment, stakeholder engagement, and robust data practices in driving successful quality improvement efforts. Emphasising the role of data-driven and patient-centric approaches in achieving optimal healthcare outcomes, lessons learned offer insights for the continuation of quality improvement work in Romania but also for healthcare systems elsewhere.

Abstract Health systems today face overlapping pressures—from demographic shifts, workforce shortages, climate change, and geopolitical and economic instability. This strains their ability to deliver effective and equitable care and erodes public trust. Traditional approaches to quality of care, often focused on service volumes or process compliance, are proving insufficient to address these system-wide challenges. In response, this paper proposes a transformational vision for quality of care that moves beyond traditional models. This vision is rooted in two interconnected pillars. First, a focus on outcomes that truly matter to people and populations, prioritizing health and well-being over service volume. The second pillar is a whole-systems perspective that embeds quality across all levels of governance, policy, and financing. This transformation is made possible through three key enablers. First, an empowered workforce and accountable leadership are needed to drive change. Second, data must be used transparently to build trust and guide results-focused work. Finally, innovative solutions and tools must enhance quality and be aligned with equity. Drawing on practical implementation examples, this paper outlines a roadmap for system-wide alignment of health systems—to rebuild trust, improve resource use, and advance health equity. This makes quality a lasting foundation for resilient, sustainable, and equitable healthcare.

Introduction: Multiple symmetric lipomatosis (MSL) is a rare disease of unknown etiology characterized by multiple subcutaneous lipomas with a symmetrical distribution. One interesting aspect about MSL is a high incidence of sudden cardiac death despite a low incidence of metabolic syndrome and coronary arterial disease. Autonomic nervous system dysfunction may probably explain this feature of MSL. Case Report: A 74-year-old man was admitted with acute heart failure and atrial fibrillation. He had a morphotype suggestive of MLS. A 123 I-metaiodobenzylguanidine myocardial scintigraphy was conducted for evaluation of cardiac autonomic nervous integrity, since atrial fibrillation precluded the classical approach. The heart-to-mediastinum ratio was 1.68 (normal >2.2). Ischemia was not detected in myocardial perfusion scintigraphy. Conclusion: We present the first reported case of MSL autonomic neuropathy detected by 123 I- metaiodobenzylguanidine scintigraphy and suggest that this approach could play a role in MSL stratification by risk of sudden cardiac death and in exploring MSL disease mechanisms.