Simone Baldovino

Cardiologists consider degenerative or infectious causes when evaluating valvular heart disease. However, the role of autoimmune disorders, though less frequent, remains clinically significant. This report describes a young male patient presenting with persistent coronary disease and a suspected valvular cusp perforation initially attributed to infective endocarditis, which ultimately proved to be a manifestation of IgG4-related disease. IgG4-related disease is a rare condition, more prevalent in Asian populations, that typically affects the pancreas, salivary glands, lacrimal glands, and the retroperitoneum. Cardiac involvement, although uncommon, can present in various ways, including pericarditis, pulmonary arterial hypertension, valve dysfunction, cardiac pseudotumor, and coronary disease. Diagnosing and managing IgG4-related cardiac involvement requires heightened clinical suspicion, serological and histopathological assessment, and prompt interdisciplinary collaboration. Notably, involving rheumatologists in the management of these rare yet impactful autoimmune cardiac diseases is essential.

Background: Climate change represents a major global health challenge, with rising temperatures and altered precipitation patterns influencing the spread of infectious diseases. This study investigated the association between climatic factors (average temperature and precipitation) and the monthly proportion of laboratory-confirmed Legionella pneumophila serogroup 1 and West Nile Virus infections among clinically suspected patients in a large teaching hospital in Northern Italy. Methods: We retrospectively analyzed data from 2021 to 2024. The primary outcome was the monthly proportion of positive tests (standardized per 1000 clinically suspected patients) for Legionella pneumophila serogroup 1 (urinary antigen) and West Nile Virus (serology). Associations with climatic variables were assessed using linear and multivariate regression models, as well as Generalized Additive Models (GAMs). Seasonal effects were evaluated through ANOVA. Results: For Legionella pneumophila, precipitation was not significantly associated with the proportion of positive tests (p = 0.1438; R² = 0.049). In contrast, average temperature was a significant predictor: each 1 °C increase was associated with +0.52 positive cases per 1000 tested patients (p = 0.000283; R² = 0.267). Multivariate models confirmed temperature as the dominant factor. For West Nile Virus, precipitation showed no meaningful effect (p = 0.914). However, average temperature demonstrated a significant positive association with the proportion of positive cases (p = 0.00293; coefficient = 9.33), with seasonal analysis highlighting a marked summer peak (mean = 399.68 positive cases per 1000 tested; p = 0.00653). Conclusions: Our findings underline the predominant role of temperature over precipitation in driving the burden of both Legionella pneumophila and West Nile Virus infections among hospitalized patients. These results strengthen the evidence that the life cycles of these pathogens are tightly climate-dependent. Developing effective adaptation strategies is essential to mitigate climate-related health risks.

Background: Antiphospholipid syndrome (APS) is diagnosed by characteristic clinical manifestations supported by positivity for lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies. However, a proportion of patients, especially those with systemic lupus erythematosus, remain seronegative despite high clinical suspicion. Anti-phosphatidylserine/prothrombin antibodies (aPS/PT) have emerged as potential biomarkers in this setting. We conducted an expert perception-based Health Technology Assessment (HTA) to evaluate the clinical, ethical, and organizational impact of implementing aPS/PT testing. Methods: A structured HTA was performed across five domains: safety, perceived efficacy, equity, ethics, and organizational implications. A survey was distributed to 110 APS specialists; 50 experts contributed responses (45.5% response rate; 66% clinicians, 18% laboratory personnel, 8% nurses, 8% administrative/other). For each domain, Z-scores were calculated to compare current diagnostic practice (AS IS) with a scenario integrating aPS/PT testing (TO BE). Correlation analyses explored relationships across domains. Results: Across all five domains, the TO BE scenario scored substantially higher than standard practice. The largest improvements were observed in perceived diagnostic efficacy (ΔZ = +2.65) and safety (ΔZ = +2.03), followed by equity (ΔZ = +2.25), ethical/social impact (ΔZ = +1.96), and organizational feasibility (ΔZ = +1.61). Perceived diagnostic effectiveness showed a strong positive correlation with both equity (r = 0.70, p < 0.001) and ethics (r = 0.67, p < 0.001). Participants consistently rated the assay as safe, clinically useful, equitable, and organizationally easy to introduce in routine laboratory workflows. Conclusions: Experts perceived the addition of aPS/PT testing as a meaningful enhancement to APS diagnostics, particularly for SLE patients who are seronegative on conventional assays. Its favorable profile across all HTA domains supports further evaluation in prospective cohorts and consideration for integration into future diagnostic algorithms.

Background: Undiagnosed rare diseases (URDs) are a complex and multifaceted challenge, especially in low-and medium-income countries. They affect individuals with unique clinical features and lack a clear diagnostic label. Although the Undiagnosed Diseases Network International (UDNI) definition of URDs is not universally accepted, it is widely recognized.Methods: We surveyed UDNI members and participants from other countries to explore the challenges posed by URDs and identify possible solutions. Participation in the survey was completely voluntary.Results: The survey revealed a need for more consensus on a universally accepted definition for URDs. Still, the UDNI definition gained widespread recognition and serves as a valuable framework for understanding and addressing the challenges of URDs. In addition to national or international networks, fostering a more substantial engagement and resource-sharing ethos among member countries is critical. Despite advances in genomics and diagnostic tools, the diagnostic journey for people living with URDs (PLURDs) remains arduous and often inconclusive. The availability of specialized centers and the utilization of whole exome sequencing (WES) and whole genome sequencing (WGS) vary across countries, with disparities due to healthcare systems, economic status, and government policies. Advocacy groups play a crucial role in supporting PLURDs.Conclusion: A unified commitment to prioritizing URDs on the global health agenda, paired with targeted funding, stipulated national strategies, and aligned international cooperation, is imperative to leveling the playing field for the diagnosis and management of URDs and capitalizing on the potential of Advocacy Groups as allies in this endeavor.

Background/Objectives: Inflammation and immunological dysregulation are central to systemic lupus erythematosus (SLE), a complex autoimmune disease. Recently, there has been increasing interest in the potential role of dietary factors in SLE. This study aimed to explore the relationship between diet and SLE by addressing patient needs, conducting a systematic review, and providing guidance to the patient community. Methods: This four-step study started with a survey of patients with SLE that was conducted to gather frequently asked questions (FAQs) related to diet. Using the PICO framework, two comprehensive systematic literature searches were performed in PubMed to address these FAQs. Subsequently, the evidence retrieved was used to answer FAQs and provide guidance to people with SLE. A second survey was conducted to gather patient feedback on the topics and guidance provided. Results: A literature review of 28 systematic reviews was performed, evaluating the impact of diet on inflammation, immune response, and health outcomes in SLE patients. The review focused on key nutritional elements, including vitamin D, omega-3 fatty acids, curcumin supplements, and low-calorie or low-glycemic index diets. Seven guidance statements were developed based on these findings. All the answers provided were positively assessed by participants. Conclusions: This patient-centered study improves our understanding of the diet–SLE relationship through systematic reviews and patient feedback. While specific dietary recommendations for SLE are not yet established, patient input underscores the need for ongoing research to optimize treatment strategies and quality of life for those with SLE.

The lymphatic kidney system plays a crucial role in managing interstitial fluid removal, regulating fluid balance, and tuning immune response. It also assists in the reabsorption of proteins, electrolytes, cytokines, growth factors, and immune cells. Pathological conditions, including tissue damage, excessive interstitial fluid, high blood glucose levels, and inflammation, can initiate lymphangiogenesis—the formation of new lymphatic vessels. This process is associated with various kidney diseases, including polycystic kidney disease, hypertension, ultrafiltration challenges, and complications post-organ transplantation. Although lymphangiogenesis has beneficial effects in removing excess fluid and immune cells, it may also contribute to inflammation and fibrosis within the kidneys. In this review, we aim to discuss the biology of the lymphatic system, from its development and function to its response to disease stimuli, with an emphasis on renal pathophysiology. Furthermore, we explore how innovative treatments targeting the lymphatic system could potentially enhance the management of kidney diseases.

Background: The gold standard for diagnosis of lupus nephritis (LN) is still represented by renal biopsy, and serological prognostic biomarkers are still lacking. Dickkopf homolog-3 (DKK3) has been suggested as a marker of tissue fibrosis in different conditions; however, its role in autoimmune diseases needs to be elucidated. Here, we investigated the prognostic role of DKK3 in systemic lupus erythematosus (SLE) patients with and without LN, assessing its changes in relation to kidney function, flares, and interstitial fibrosis. Methods: Overall, 132 SLE patients (57 with LN) were included and prospectively followed up for at least 36 months. DKK3 was measured in serum at baseline. Biopsies were evaluated for glomerular involvement, interstitial fibrosis, and tubular atrophy. Results: Patients with biopsy-proven LN had significantly higher levels of DKK3 than those without (median [min–max]: 215 ng/mL [81–341] vs. 21.1 ng/mL [1–69], p < 0.01). DKK3 levels were associated with prevalent chronic kidney diseases (OR: 4.31 [C.I. 2.01–6.61] per DKK3 doubling, p < 0.01), higher chronicity index at biopsy (1.75 [1.51–2.77] per DKK3 doubling, p < 0.01), and flares rate (OR: 1.45 [C.I. 1.1–5.71] per DKK3 doubling, p < 0.044). Conclusions: While kidney biopsy still represents the gold standard for diagnostic and prognostic assessment in LN, DKK3 could represent an additional prognostic tool to monitor SLE patients and guide therapeutic choices.

To support the management of rheumatoid arthritis (RA) patients treated with tofacitinib, we designed the TuTOR (tailoring tofacitinib oral therapy in rheumatoid arthritis) mobile app. The impact of the app on medical adherence was evaluated using a crossover design alternating a paper-diary and the TuTOR App. Twenty patients with RA (mean age at inclusion, 59 ± 13 years) were included in the study. A statistically significant decrease in DAS28 was observed since the first month of therapy (mean DAS28 at baseline, 3.9 ± 1 vs. 1° month 3.1 ± 1, p = 0.0016). Similarly, the numerical rating scale (NRS) of perceived activity of disease and subjective fatigue progressively decreased. No differences were reported in DAS28 or NRS between the TuTOR app and the paper-diary groups. A significant decrease was observed in HAQ during the follow-up (baseline 1.38 ± 1.11 vs. six months 0.83 ± 0.9; p = 0.01). When filling out the self-reporting questionnaires, most of the patients (82%) preferred the TuTOR App helping them to remember to take the pills. Furthermore, 82% of patients used the app regularly (vs. 53% for the paper diary). Three patients suspended tofacitinib due to gastrointestinal intolerance. Both digital and paper devices can help maximize adherence to therapy; however, the TuTOR app was preferred by the patients for its simplicity and immediacy.