European Journal of Internal Medicine最新文献

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease with variable manifestations across Mediterranean regions. This study compares FMF cohorts from Italy (Apulia) and Lebanon. We analyzed a cohort of 443 FMF patients, 165 Italians (females: males = 90:75) and 278 Lebanese (females: males = 173:105). Clinical records/interviews provided data on demographics, MEFV genetic testing, and treatments. A 55-item questionnaire in 54 Italians and 42 Lebanese patients assessed disease knowledge, management, misdiagnoses, attack frequency (yearly), duration (days), body temperature, symptoms prevalence and frequency, and severity score before/after treatment. Italians were significantly older at disease onset, diagnosis, and had longer diagnostic delay than Lebanese patients (p < 0.00001). The most common MEFV variants were E148Q and R202Q in Italians, and M694V and E148Q in Lebanese, with fewer pathogenic and homozygous cases in Italians. Italian patients had lower prevalence of FMF symptoms (10-92% vs. 30-99%; p < 0.00001) and fewer attacks. All Italians received treatment compared to 88.5% of Lebanese. Colchicine was first-line treatment, while biological drug use was higher in Italians. In the subgroups study, Italians reported lower disease knowledge and were followed up mainly by internists, while Lebanese were followed up by gastroenterologists or pediatricians. Italians were misdiagnosed with appendicitis, whereas Lebanese were misdiagnosed with gastrointestinal diseases. Italians exhibited lower symptom frequency, lower severity scores, and a better response compared to Lebanese patients. In conclusion, FMF presentation differed by country, with Italians showing milder symptoms and better treatment response, while Lebanese showed severe symptoms linked to pathogenic MEFV variants. Gene-environment interactions require further studies.

Background: The risk-benefit profile of direct oral anticoagulants (DOACs) in kidney transplant recipients (KTRs) with atrial fibrillation (AF) remains under-investigated.

Purpose: To evaluate the safety and efficacy of DOACs compared with vitamin K antagonists (VKAs) in KTRs with AF.

Methods: Retrospective analysis from TriNetX network. Adult KTRs with AF were included. Patients with mechanical valves, antiphospholipid syndrome, or an estimated eGFR <15 mL/min/1.73 m² were excluded. Anticoagulated patients were stratified into two cohorts (DOACs versus VKAs) . The first 3 months post-transplant were excluded, and follow-up for outcomes started at 9 months post-transplant and continued for 12 months thereafter. Propensity score matching (1:1) balanced baseline characteristics. The primary outcome was a composite of all-cause death, thromboembolic events, major bleeding. Secondary outcomes included each component of the composite outcome and kidney transplant rejection.

Results: Of the 1367 KTRs with AF, 695 received DOACs (65.0 ± 10.0 years, 30.5% female), while 672 received VKAs (64.0 ± 10.1 years, 29.9% female). After matching, each cohort included 553 patients. At one-year follow-up, compared with VKAs, DOACs were associated with a lower risk of the composite outcome (HR 0.66, 95%CI 0.50-0.87), and kidney transplant rejection (HR 0.46, 95%CI 0.30-0.71). A non-significant trend was observed toward a lower risk of all-cause death (HR 0.64, 95%CI 0.41-1.01), major bleeding (HR 0.66, 95%CI 0.43-1.01), thromboembolic events (HR 0.68, 95%CI 0.43-1.07).

Conclusion: In this real-world cohort of KTRs with AF, DOACs use was associated with lower risk of the composite outcome and kidney transplant rejection.

Chronic obstructive pulmonary disease (COPD) is often associated with cardiovascular disease and the both conditions share common risk factors (smoke), associated pathophysiological mechanisms (pulmonary hyperinflation and vasoconstriction, systemic inflammation and sympathetic activation) and drug use (beta agonists and/or antagonists, steroids, amiodarone). Moreover, COPD is known to be linked to peripheral arterial disease (PAD), mainly represented by aneurysmal dilations. Overall, this chronic immune-inflammatory context might be related to the growth and expansion of malignant clones with specific and well-known biologic traits. Recent improvement in the knowledge of molecular basis of COPD, heart diseases and PAD have pointed out a strong, complex and fascinating relationship linking these conditions, not simply definable as comorbidities. From these premises, we here aim at discussing on the novel and emerging integrated therapeutic perspectives, in some instances exploited from immune-oncology, which strongly deserve a multidisciplinary clinical management.

Objective: IgA vasculitis (IgAV) is a small-vessel vasculitis. The diversity of clinical presentations and outcomes requires the identification of groups with a distinct phenotype for management and follow-up.

Methods: The French retrospective IGAVAS database (n = 260) includes adult-onset IgAV. Agglomerative hierarchical clustering was performed, using k-means and Ward's method, based on 7 parameters (sex, age, constitutional symptoms, skin necrosis, joint and digestive involvement, abnormal kidney function). These results were validated on an independent cohort of Slovenian patients (n = 208).

Results: Of 260 IgAv patients, 3 identified clusters were identified. Cluster 1 (n = 114, 44%) included a majority of men (68%), of young age (median 42 years), with gastrointestinal (100%) and joint (77%) involvement, with low rate of renal insufficiency (7%). Cluster 2 (n = 96, 37%) included 56% males, with a mean age of 49 years, without gastro-intestinal involvement, and 4% renal insufficiency. Cluster 3 (n = 50, 19%, 66% men) included older patients (mean age 70 years), with skin necrosis (52%), and abnormal kidney function (90%). Very similar clusters were found in the Slovenian cohort. Of the 144 renal biopsies available, cluster 3 had more tubulointerstitial damage, there was no significative difference of extracapillary proliferation. Regarding outcome, cluster 1 an 2 tended to have more relapses (20 and 25%), cluster 3 had more residual chronic renal failure (79%).

Discussion: Through this clustering study, validated in an independent cohort, three very distinct groups in adult-onset IgAV emerged with clear-cut presentations and outcomes. This approach enables a personalized evaluation to be proposed at baseline and during the follow-up.

Transthyretin (ATTR) amyloidosis is a multisystem disease caused by misfolding and aggregation of the plasma protein transthyretin (TTR) into insoluble amyloid fibrils in various organs. In clinical practice, ATTRwt amyloidosis manifests as a predominant cardiomyopathy (ATTR-CM), while ATTRv amyloidosis is typically associated with polyneuropathy (ATTR-PN) as well as cardiomyopathy. Over the past decade, major advances in the understanding of ATTR pathophysiology have enabled the development of disease-modifying therapies, marking a paradigm shift toward precision medicine in this condition. Among these, RNA-targeted therapies have emerged as a cornerstone of treatment by directly suppressing hepatic production of TTR. This review provides an overview of the biological rationale, molecular mechanisms, and clinical translation of RNA-based therapeutics in ATTR amyloidosis, with a particular focus on RNA interference (RNAi) and antisense oligonucleotide (ASO) strategies. Key mechanistic differences between small interfering RNAs and ASOs are discussed, including intracellular pathways, pharmacokinetic properties, and delivery platforms such as lipid nanoparticles and GalNAc conjugation for hepatocyte-specific targeting. Major clinical trials evaluating first- and second-generation RNA-targeted agents-including patisiran, vutrisiran, inotersen, and eplontersen-are summarized, highlighting efficacy, safety profiles, dosing regimens, and relevance across different ATTR phenotypes. As RNA-based therapies continue to evolve, integration of molecular insights with clinical phenotyping and real-world evidence will be essential to fully realize the potential of precision medicine for patients with ATTR amyloidosis.