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Povezava med alelnim bremenom JAK2 V617F in koronarno kalcifikacijo pri bolnikih z esencialno tormbocitemijo
Get PDFJAK2 V617F (JAK2) mutation is associated with clonal hemopoiesis in myeloproliferative neoplasms as well as with faster progression of cardiovascular diseases. Little is known about the relationship between allele burden and the degree of atherosclerotic alteration of coronary vasculature. We previously reported that carotid artery stiffness progressed faster in patients with JAK2 positive essential thromocythemia (ET) patients. After a four-year follow-up we investigated whether mutation burden of a JAK2 allele correlates with a higher coronary calcium score. Patients and methods. Thirty-six patients with JAK2 positive ET and 38 healthy matched control subjects were examined twice within four years. At each visit clinical baseline characteristics and laboratory testing were performed, JAK2 mutation burden was determined, and coronary calcium was measured. Results. JAK2 allele burden decreased in 19 patients, did not change in 5 patients, and increased in 4 patients. The coronary calcium Agatston score increased slightly in both groups. Overall, there was no correlation between JAK2 allele burden and calcium burden of coronary arteries. However, in patients with the JAK2 mutation burden increase, the coronary calcium score increased as well. Conclusions. The average JAK2 allele burden decreased in our patients with high-risk ET during the four-year period. However, in the small subgroup whose JAK2 mutation burden increased the Agatston coronary calcium score increased as well. This finding, which should be interpreted with caution and validated in a larger group, is in line with emerging evidence that JAK2 mutation accelerates atherosclerosis and can be regarded as a non-classical risk factor for cardiovascular disease
Systemic auto-inflammatory manifestations in patients with spondyloarthritis
Get PDFObjectives. – (1) characterizing a group of spondyloarthritis (SpA) patients with systemic autoinflammatory symptoms (S-SpA)(2) comparing SpA features with and without auto-inflammatory symptoms(3) comparing the auto-inflammatory features of S-SpA and Still’s disease (SD). Methods. – Retrospective observational study. Clinical data of adult and pediatric patients with S-SpA, SD or SpA were collected retrospectively and analyzed. Results. – Forty-one subjects with S-SpA, 39 with SD and 42 with SpA were enrolled. The median latency between systemic and articular manifestations in S-SpA was 4.4 (IQR: 7.2) years. S-SpA and SpA had similar frequency of peripheral arthritis and enthesitis (N.S.), while tenosynovitis was more frequent(P = 0.01) and uveitis less frequent (P < 0.01) in S-SpA. MRI showed signs of sacroiliac inflammation and damage in both S-SpA and SpA equally (N.S.). S-SpA patients had less corner inflammatory lesions (P < 0.05) and inflammation at the facet joints (P < 0.01), more interspinous enthesitis (P = 0.01) and inter-apophyseal capsulitis (P < 0.01). Compared to SD, S-SpA patients had lower-grade fever (P < 0.01), less rash (P < 0.01) and weight loss (P < 0.05), but more pharyngitis (P < 0.01), gastrointestinal symptoms (P < 0.01) and chest pain (P < 0.05). ESR, CRP, WBC, ANC, LDH tested higher in SD (P < 0.01). Resolution of systemic symptoms was less frequent in S-SpA than SD on corticosteroid (P < 0.01) and methotrexate (P < 0.05) treatment. When considering all SD patients, a complete response to corticosteroids in the systemic phase significantly reduced the likelihood of developing SpA (OR = 0.06, coefficient −2.87 [CI: −5.0 to −0.8]). Conclusions. – SpA should be actively investigated in patients with auto-inflammatory manifestations, including undifferentiated auto-inflammatory disease and S
The incidence of pulmonary hypertension and the association with bronchopulmonary dysplasia in preterm infants of extremely low gestational age
Get PDFBackground: Pulmonary hypertension (PH) occurs in ~25% of infants with moderate-tosevere bronchopulmonary dysplasia (BPD) and is associated with substantial morbidity and mortality. The American Heart Association and American Thoracic Society recommend routine echocardiographic screening for PH in preterm infants with BPD at 36 weeks’ postmenstrual age (PMA), yet the true incidence remains unclear owing to non-uniform diagnostic criteria. Emerging evidence suggests a potential role for earlier screening. Objectives: (i) to determine the incidence of pulmonary hypertension (PH) and bronchopulmonary dysplasia (BPD) in preterm infants of extremely low gestational age(ii) to determine the incidence of PH among infants diagnosed with BPD (BPD-PH)and (iii) to evaluate the utility of early screening at 7 days of life and late screening at discharge in relation to subsequent BPD. Methods: We conducted a prospective cohort study of all infants born at 22 + 0 to 28 + 6 weeks’ gestation and admitted to our tertiary NICU between 1 September 2022 and 31 December 2024. Clinical and echocardiographic assessments for PH and BPD were performed by neonatologists trained in neonatal echocardiography. Results: Seventy-eight infants born at 22 + 0–28 + 6 weeks’ gestation were enrolled 71 underwent early screening and 57 underwent late screening. Early echocardiography at day 7 and late screening at discharge identified no cases of PH. PH was diagnosed clinically and/or echocardiographically in 10 infants before day 7 and in one infant at 38 weeks’ PMA. BPD developed in 42 of 57 infants (73.7%). Conclusions: In this cohort of extremely lowgestational-age infants, echocardiographic screening performed by neonatologists detected no PH at day 7 and only one case at late screening (at 38 weeks’ PMA/before discharge). Most PH was identified prior to day 7 on clinical and/or echocardiographic ground
Epidemiological and Clinical Data from the European lipodystrophy (ECLip) registry
Get PDFObjective: Lipodystrophy syndromes comprise a group of rare diseases characterized by loss of adipose tissue without nutritional or catabolic causes. As the rarity of these conditions necessitates collaboration, the European Consortium of Lipodystrophies (ECLip) established an international, longitudinal registry for patients with all forms of lipodystrophy (excluding HIV-associated cases). Methods: From December 2017 to November 2023, 19 centres from 13 countries recruited 631 patients into the ECLip registry. Cross-sectional data were analysed using descriptive statistics. Results: Prospective data was available for 467 patients (82.7%, female86.5% adultsmedian age 44.0 years). Familial partial lipodystrophy (FPLD) was the most common subtype (57.4%), especially FPLD2 (37.9%). However, in men congenital generalized lipodystrophy was nearly as common as FPLD (33.3% vs. 35.8%). Symptoms at onset varied by subtype, with loss of adipose tissue being the most frequent. More than 70% of the patients suffered from metabolic complications, particularly dyslipidaemia (59.0%) and diabetes (48.4%) but prevalence and severity varied between subtypes (prevalence of diabetes for example 76.9% in patients with acquired partial lipodystrophy vs 8.7% in acquired localized lipodystrophy). Metreleptin, the only disease-specific treatment, was used by 11.6% of all patients. 34 deaths were documented, primarily due to cardiovascular events and cancer. Patients with generalized forms of lipodystrophy died earlier compared to patients with partial forms (median age at death 27.0 vs. 72.0 years). Conclusion: This study describes the largest cohort of patients with lipodystrophy reported to date. The dataset offers a comprehensive view of the epidemiology, clinical presentation, and associated comorbidities of lipodystrophy
Addressing cardiovascular toxicities of Bruton tyrosine kinase inhibitors in chronic lymphocytic leukaemia
Get PDFAdvances in understanding the biology of chronic lymphocytic leukaemia (CLL) translated into revolutionary treatments with improved survival outcomes. Consequently, the traditional chemoimmunotherapy courses shifted to targeted therapies, including inhibitors of the Bruton tyrosine kinase (BTKis). BTKis correlate with an increased risk over time of toxicities of the cardiovascular (CV) system, which require proper management. An expert meeting involving 14 haematology and cardiology opinion leaders from 5 Central Eastern European countries was held, aiming to find pragmatic approaches for haematologists to identify the CLL patients at CV risk before starting the BTKis therapy, and further recognize, manage and monitor de novo cardiotoxicities occurring under treatment. Geographical variations have been described, including availability of reimbursed BTKis, national registries, and presence of cardio-oncology units. The experts discussed controversies, unmet needs and potential solutions by exemplifying local challenges and best practices. Each patient requires a personalized strategy based on multiple factors, hence practical pathways to follow during the continuity of care in CLL patients requiring BTKis have been proposed. Rigorous evaluation of the CV risk, periodic assessments of cardiotoxicity during BTKis treatment and work in multidisciplinary teams are vital for managing CV complications without unnecessary interruptions of the CLL treatment
Circular RNAs and their emerging roles in muscular immune-related diseases
Get PDFCircular RNAs (circRNAs) have recently emerged as a highly stable and versatile class of non-coding RNAs that play critical roles in gene regulation, yet their involvement in immune-mediated muscle disorders remains largely underexplored. This review synthesizes how circRNAs influence key processes in both skeletal muscle and immune cells, from myogenesis, regeneration, and muscle stem cell function to inflammatory signaling and muscle wasting. Our aim was to identify circRNA insights across muscle immune-mediated diseases. However, we found no idiopathic inflammatory myopathy-focused circRNA studies, only a limited body of work in Duchenne muscular dystrophy, and predominantly peripheral blood mononuclear cell-based evidence in myasthenia gravis. These gaps highlight clear priorities: subtype-resolved circRNA atlases for idiopathic inflammatory myopathypaired muscle–biofluid and cell-type–resolved profiling (including infiltrating immune populations)rigorous in vivo functional validation beyond correlative expressionfuller mechanistic delineation beyond miRNA competition (e.g., RNA binding protein interactions, translation, epigenetic regulation)and longitudinal cohorts linking circRNA dynamics to disease activity and treatment response. We particularly noted lack of in-depth studies addressing the interplay between muscle and immune cells in these conditions. Furthermore, we examine pioneering efforts to engineer circRNAs as therapeutic agents, capable of either neutralizing pathogenic pathways that drive muscle atrophy or restoring dystrophin expression in genetic disease models. Finally, we outline future directions for circRNA profiling in patient tissues and biofluids, rigorous functional validation in vivo, and the development of circRNA-based diagnostics. This positions circRNAs at the forefront of next-generation strategies for understanding and combating immune-related muscular disorders
Venous thromboembolism in pregnancy
Get PDFVenous thromboembolism (VTE) is notably more common in pregnancy, with at least a 5‑fold higher risk than in nonpregnant women, and an even greater surge postpartum. Pregnancy induces a hypercoagulable state with venous stasis and vascular changes, making VTE a leading cause of maternal morbidity and mortality, particularly in the postpartum period. Clinical presentation is often subtle or nonspecific, highlighting the need for objective diagnostic strategies adapted to pregnancy. Emerging diagnostic algorithms, including D‑dimer– guided approaches and pregnancy‑specific rules, such as the pregnancy‑adapted YEARS criteria, are improving diagnostic accuracy while limiting unnecessary imaging. Prevention and treatment regimens are tailored to pregnant patients, with low‑molecular‑weight heparin remaining the cornerstone of therapy. Ongoing research is exploring individualized prophylaxis based on personal risk profiles, biomarker‑driven risk stratification, and optimized postpartum management protocols. Under‑recognized issues, such as superficial vein thrombosis and rare but high‑risk thrombophilias (eg, antithrombin deficiency) are also garnering attention for their contribution to pregnancy‑associated VTE risk. This review provides a comprehensive update on pregnancy‑related VTE, highlighting evolving concepts in epidemiology, diagnosis, prevention, and management of deep and superficial venous thromboses and pulmonary embolism from pregnancy through the postpartum period