Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children and adolescents, increasing the risk of its progression toward nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. There is an urgent need for noninvasive early diagnostic and prognostic tools such as epigenetic marks (epimarks), which would replace liver biopsy in the future. We used plasma samples from 67 children with biopsy‐proven NAFLD, and as controls we used samples from 20 children negative for steatosis by ultrasound. All patients were genotyped for patatin‐like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane bound O‐acyltransferase domain containing 7 (MBOAT7), and klotho‐β (KLB) gene variants, and data on anthropometric and biochemical parameters were collected. Furthermore, plasma cell‐free DNA (cfDNA) methylation was quantified using a commercially available kit, and ImageStream(X) was used for the detection of free circulating histone complexes and variants. We found a significant enrichment of the levels of histone macroH2A1.2 in the plasma of children with NAFLD compared to controls, and a strong correlation between cfDNA methylation levels and NASH. Receiver operating characteristic curve analysis demonstrated that combination of cfDNA methylation, PNPLA3 rs738409 variant, coupled with either high‐density lipoprotein cholesterol or alanine aminotransferase levels can strongly predict the progression of pediatric NAFLD to NASH with area under the curve >0.87. Conclusion: Our pilot study combined epimarks and genetic and metabolic markers for a robust risk assessment of NAFLD development and progression in children, offering a promising noninvasive tool for the consistent diagnosis and prognosis of pediatric NAFLD. Further studies are necessary to identify their pathogenic origin and function.

Atrial fibrillation (AF) is a progressive disease, associated with increased risk of mortality, stroke, heart failure, and worsens quality of life. There is a high incidence of AF recurrence despite the treatment. The aim of the study was to assess the time to recurrence of AF after sinus rhythm restoration with electrical or pharmacological cardioversion and to identify the risk factors. This study included 101 patients with AF (56% females) at a mean age of 68.02±7 years, after sinus rhythm restoration in a clinical observation of 1-year placebo-controlled treatment with spironolactone (1: 1). The patients were analyzed on the basis of AF recurrence, hospitalization, demographic parameters, comorbidities, embolic risk, and value of biomarker galectin-3 (Gal-3). The average number of AF recurrences was1.62 per patient per year. The median time of occurrence of at least one new episode was 48 days, 95% confidence interval (CI) 14.24-81.76. Female patients experienced significantly more recurrences than male-53.3% vs. 28.6% hazard ration (HR) =1.76, 95% CI 1.02-3.03, p=0.036. The recurrences were more common with increased age, although not significantly. Patients with arterial hypertension had a threefold risk of recurrences than those without hypertension (p=0.025), independently of the treatment. CHA2DS2-VASc score was significantly associated with AF recurrent episodes. Patients with gout had a twofold increased risk, without statistical significance (p=0.15). There was no difference in the AF episodes according to treatment with spironolactone. The levels of Gal-3 did not affect the number of AF recurrences (p=0.9). AF is associated with frequent recurrences after restoration of sinus rhythm in the majority of the patients. Most of them occurred within the first 3 months. Female sex, arterial hypertension, and CHA2DS2-VASc score were significant predictors of AF recurrence. Spironolactone did not reduce AF recurrences.

Introduction: Cardiac fibrosis is the hallmark of atrial remodeling in atrial fibrillation. Galectin-3 (Gal-3) is a biomarker of fibrosis. It is well studied in heart failure, but the data about its role in atrial fibrillation are sparse.Aim: The aim of the study was to evaluate the levels of Gal-3 in patients with atrial fibrillation after sinus rhythm restoration, to examine the association between this biomarker and other factors for developing atrial fibrillation and to assess its prognostic role.Materials and methods: We included 67 patients (35 male) at the mean age of 67.36±7.25 years, with Gal-3 test after sinus rhythm restoration, a subgroup of participants in placebo-controlled randomized clinical trial of treatment with spironolactone. They were followed up for atrial fibrillation recurrence and hospitalizations. The effect of demographic parameters and other factors on Gal-3 levels were evaluated before and one year after treatment.Results: Mean Gal-3 at baseline was 16.9±6.8 ng/ml. Higher levels of Gal-3 were associated with female gender (р=0.008), increasing age (р=0.005), renal dysfunction (p<0.0001) and gout (р=0.002). Higher thromboembolic risk as assessed by CHA2DS2-VASc score was significantly related to Gal-3. The levels of biomarker did not affect the number of atrial fibrillation recurrences (p=0.9) and hospitalizations. No correlation was found with treatment with spironolactone, antiarrhythmic and antihypertensive drugs.Conclusions: Higher Gal-3 in atrial fibrillation was associated with female sex, renal dysfunction, and history of gout. The levels of Gal-3 were not related to rhythm control. Treatment with spironolactone did not affect the biomarker of fibrosis Gal-3 in AF patients. Higher Gal-3 was related to high embolic risk.

Objective: Atrial fibrillation is progressive disease with important health consequences, in which fibrosis is a key player. The aim of our study is to assess the effect of mineralcorticoid blockade on top of standard treatment in patients with atrial fibrillation after sinus rhythm restoration on the recurrence of the arrhythmia, hospitalizations and on the changes in levels of Galectin-3 as a marker of fibrosis. Methods: We prospectively studied 101 consecutive patients (56 females) at mean age 68.2 ± 7 with atrial fibrillation and sinus rhythm restoration, who were randomized on treatment with spironolactone on top of standard treatment or “usual care”. They were followed up for recurrences, hospitalization and death. The effect of spironolactone on safety was evaluated. Results: Recurrences of AF were detected in 64% of non-spironolactone group vs 57% in spironolactone group (p = 0.44). Spironolactone reduced the hospitalizations for AF, but it was not significant (p = 0.14). A Cox regression model showed only protective effect of spironolactone on AF hospitalizations, HR = 0.48, 95%CI = 0.2–1.15, р = 0.098. The same survival model for all-cause hospitalizations reached significance, with reduction of the events in the spironolactone group, HR- 0.44, 95% CI 0.2–0.94, р = 0.035. There was no difference regarding the composite endpoint (recurrences, all cause hospitalizations and death). Treatment with spironolactone did not influence the Gal-3 levels. Treatment with spironolactone has not influenced significantly the levels of serum potassium and creatinine. Conclusion: Treatment with spironolactone has protective effect regarding hospitalization for atrial fibrillation and significantly reduces all cause hospitalizations. It does not influence the biomarker of fibrosis Gal-3 after one-year treatment. The use of spironolactone in patients with AF is safe, but regular follow up is needed and recommended. Further studies are necessary, to clarify the potential of spironolactone to improve the AF prognosis.

Methods for assessment of cardiac fibrosis. Part I

От 2019 г. човечеството води неуморна борба с пандемията, предизвикана от SARS-CoV-2 вирус. Респираторният дистрес синдром е основното клинично проявление на COVID-19, при който най-често се постига пълно излекуване, но нерядко приключва летално. Интерес за съвременната медицина представлява малка група от пациенти, при които заболяването персистира до месеци, т.нар. „Long COVID”. Това състояние предразполага за развитието на макар и рядък, но животозастрашаващ синдром, който се манифестира и определя като едно от най-сериозните усложнения на SARS-CoV-2 инфекция, а имено мултисистемен възпалителен синдром при възрастни (MIS-A). За първи път този синдром беше описан при деца и наречен мултисистемен възпалителен синдром при деца (MIS-C). Засегнатата популация са пациенти ≥ 21 години, независимо от половата принадлежност. Въпреки множеството проучвания, клинико-лабораторни и демографски анализи все още съществуват разногласия по отношение на честота на разпространение, патогенезата и диагностично-терапевтичния алгоритъм на поведение при тези болни. Целта на настоящата статия е да систематизира натрупания опит и познания, както и да демонстрира тяхното приложение в клиничната практика. Since 2019, humanity has been relentlessly fi ghting the pandemic caused by the SARS-CoV-2 virus. Respiratory distress syndrome is the main clinical manifestation of COVID-19, which often results in full recovery but can also end fatally. Of interest to modern medicine is a small group of patients in whom the disease persists for months, known as “Long COVID.” This condition predisposes to the development of a rare but life-threatening syndrome, manifested and defi ned as one of the most serious complications of SARS-CoV-2 infection – multisystem Infl ammatory Syndrome in Adults (MIS-A). This syndrome was fi rst described in children and called MIS-C (Multisystem Infl ammatory Syndrome in Children). The affected population consists of patients ≥ 21 years old, regardless of gender. Despite numerous studies, clinical-laboratory and demographic analyses, there are still disagreements regarding the frequency of occurrence, pathogenesis, and diagnostic-therapeutic algorithm for these patients. The purpose of this article is to systematize the congested experience and knowledge, as well as to demonstrate their application in clinical practice.