Hereditary hemorrhagic telangiectasia is an inherited disease related to an alteration in angiogenesis, manifesting as cutaneous telangiectasias and epistaxis. As complications, it presents vascular malformations in organs such as the lung, liver, digestive tract, and brain. Currently, diagnosis can be made using the Curaçao criteria or by identifying the affected gene. In recent years, there has been an advance in the understanding of the pathophysiology of the disease, which has allowed the use of new therapeutic strategies to improve the quality of life of patients. This article reviews some of the main and most current evidence on the pathophysiology, clinical manifestations, diagnostic approach, screening for complications, and therapeutic options, both pharmacological and surgical.

Most rare diseases (RDs) encompass a diverse group of inherited disorders that affect millions of people worldwide. A significant proportion of these diseases are driven by functional haploinsufficiency, which is caused by pathogenic genetic variants. Currently, most treatments for RDs are limited to symptom management, emphasizing the need for therapies that directly address genetic deficiencies. Recent advancements in gene therapy, particularly with adeno-associated viruses (AAVs) and lipid nanoparticle-encapsulated messenger RNA (mRNA), have introduced promising therapeutic approaches. AAV vectors offer durable gene expression, extensive tissue tropism, and a safety profile that makes them a leading choice for gene delivery; however, limitations remain, including packaging size and immune response. In contrast, mRNA therapeutics, formulated in LNPs, facilitate transient protein expression without the risk of genomic integration, supporting repeated dosing and pharmacokinetic control, though with less long-term expression than AAVs. This review analyzes the latest developments in AAV and mRNA technologies for rare monogenic disorders, focusing on preclinical and clinical outcomes, vector design, and delivery challenges. We also address key regulatory and immunological considerations impacting therapeutic success. Together, these advancements in AAV and mRNA technology underscore a new era in RD treatment, providing innovative tools to target the genetic root of these diseases and expanding therapeutic approaches for patients who currently face limited medical options.

Endothelial dysfunction (ED) is associated with progressive changes contributing to clinical complications related to macro- and microvascular diseases. Garlic (Allium sativum L.) and its organosulfur components have been related to beneficial cardiovascular effects and could improve endothelial function. The ENDOTALLIUM Study aimed to evaluate the effect of the regular consumption of encapsulated purple garlic oil on microvascular function, endothelial-related biomarkers, and the components of metabolic syndrome (MetS) in untreated subjects with cardiometabolic alterations. Fifty-two individuals with at least one MetS component were randomized (1:1) in a single-center, single-blind, placebo-controlled, parallel-group study. The participants received encapsulated purple garlic oil (n = 27) or placebo (n = 25) for five weeks. Skin microvascular peak flow during post-occlusive reactive hyperemia significantly increased in the purple garlic oil group compared to the placebo group (between-group difference [95%CI]: 15.4 [1.5 to 29.4] PU; p = 0.031). Likewise, hs-CRP levels decreased in the purple garlic group compared to the control group (−1.3 [−2.5 to −0.0] mg/L; p = 0.049). Furthermore, we observed a significant reduction in the mean number of MetS components in the purple garlic group after five weeks (1.7 ± 0.9 vs. 1.3 ± 1.1, p = 0.021). In summary, regular consumption of encapsulated purple garlic oil significantly improved microvascular function, subclinical inflammatory status, and the overall MetS profile in a population with cardiometabolic alterations.

Objective: We aimed to test the non-inferiority of oral versus intravenous hydration in the incidence of contrast-associated acute kidney injury (CA-AKI) in elderly outpatients undergoing a contrast-enhanced computed tomography (CE-CT) scan. Methods: PNIC-Na (NCT03476460) is a phase-2, single-center, randomized, open-label, non-inferiority trial. We included outpatients undergoing a CE-CT scan, >65 years having at least one risk factor for CA-AKI, such as diabetes, heart failure, or an estimated glomerular filtration rate (eGFR) of 30–59 mL/min/1.73 m². Participants were randomized (1:1) to oral sodium-chloride capsules or intravenous hydration. The primary outcome was an increase in serum creatinine >0.3 mg/dL or a reduction in eGFR >25% within 48 h. The non-inferiority margin was set at 5%. Results: A total of 271 subjects (mean age 74 years, 66% male) were randomized, and 252 were considered for the main analysis (per-protocol). A total of 123 received oral hydration and 129 intravenous. CA-AKI occurred in 9 (3.6%) of 252 patients and 5/123 (4.1%) in the oral-hydration group vs. 4/129 (3.1%) in the intravenous-hydration group. The absolute difference between the groups was 1.0% (95% CI −4.8% to 7.0%), and the upper limit of the 95% CI exceeded the pre-established non-inferiority margin. No major safety concerns were observed. Conclusion: The incidence of CA-AKI was lower than expected. Although both regimens showed similar incidences of CA-AKI, the non-inferiority was not shown.

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by α-galactosidase A deficiency, leading to glycosphingolipid accumulation and progressive organ damage. Beyond substrate storage, low-grade inflammation and complement activation have been increasingly implicated in FD pathogenesis, yet a comprehensive characterization of this immuno-inflammatory profile is lacking. In this exploratory cross-sectional study, fifteen patients with FD and fifteen age- and sex-matched healthy controls (HCs) were assessed using a broad panel of systemic inflammatory, humoral immunity/complement, hematological, and endothelial biomarkers, integrated through univariate analysis (Cliff’s delta, δ), penalized least absolute shrinkage and selection operator (LASSO) regression, and unsupervised hierarchical clustering. Fibrinogen (δ = 0.60, 95% confidence interval (CI) 0.24–0.88), sTNFR2 (δ = 0.48, 95% CI 0.08–0.80), complement C4 (δ = 0.53, 95% CI 0.13–0.84), and lymphocyte count (δ = 0.52, 95% CI 0.15–0.85) showed the largest between-group effect sizes among the immuno-inflammatory biomarkers assessed, with higher levels in FD. Fibrinogen and sTNFR2 were the most stable predictors in LASSO bootstrap resampling (selected in 75.0% and 69.5% of iterations, respectively), and unsupervised clustering segregated FD from HCs with high accuracy (90% FD enrichment in the high-biomarker cluster; p < 0.001). These convergent findings indicate that FD is characterized by a distinct low-grade immuno-inflammatory profile dominated by innate immune and complement activation.