Citations

Abstract Background and Aims Stroke and systemic embolism are recognized but poorly characterized complications of atrial fibrillation (AF) and left atrial flutter (AFL) catheter ablation. Their incidence, outcomes, and procedural associations remain insufficiently defined. Methods Retrospective global registry was initiated by the European Heart Rhythm Association Scientific Committee. A secure database captured data from ablation centres worldwide on general AF and left AFL ablation activity, as well as detailed information on patients with symptomatic embolic events between 2017 and 2024. Results Overall, 204 centres reported 335 743 ablation procedures and 550 embolic events (incidence 0.16%). Centre-level rate ranged from 0% to 3.1%. Most events were cerebral (94%), followed by peripheral (5%), and combined (1%). Coronary air embolism accounted for 62% of all peripheral events. Intraprocedural events occurred in 93 patients (17%), within 72 h in 357 (78%) and beyond 72 h in 100 (22%); 128 cases (23%) were diagnosed after hospital discharge. Nonparoxysmal AF (0.23% vs 0.15%; P < .001), centre experience, and ablation energy source (radiofrequency, 0.16%; cryoballoon, 0.16%; pulsed field ablation, 0.25%; laserballoon, 0.88%; P < .001) were associated with embolic risk. Median NIHSS score after stroke was 4 (interquartile range, 2–9). Three-month follow-up was available for 518 patients with embolism (95%): 181 (35%) had sequelae and 16 (3%) died. Conclusions Symptomatic embolic events are infrequent but associated with significant morbidity and mortality. Most events occur early, though a substantial proportion arise later. Higher event rates were observed with laser and possibly with pulsed field ablation. A greater centre experience was associated with a lower embolism incidence.

Abstract The human X chromosome accounts for ∼5% of the genome. Despite its size, the role of X-chromosomal variants in human diseases is not well understood, mainly due to its distinct inheritance pattern and the frequent omission of sex chromosomes from genome-wide association studies. This study used whole-genome sequencing data from 888 multiple system atrophy (MSA) cases and 7128 controls to perform an X-chromosome-wide common variant association study. Our analyses revealed two sex-differential risk loci: one located at Xq28, associated with increased risk for MSA in females [index variant: rs4898389, odds ratio (OR) = 1.69, 95% confidence interval (CI) = 1.40–2.03, P-value = 2.43 × 10⁻⁸], and another at Xp22.2 within the TBL1X gene, identified in males (index variant: rs6638956, OR = 1.48, 95%CI = 1.26–1.73, P-value = 9.92 × 10⁻⁷). In the Xq28 locus, colocalization analyses pointed to FAM3A and PLXNA3 as genes of interest. These findings emphasize the vital role of sex-differential genetic factors in the pathogenesis of MSA.

AbstractINTRODUCTIONSelf‐reported sex influences brain resilience, but its role in genetic frontotemporal dementia (FTD) remains unclear.METHODSWe analyzed 394 genetic‐FTD patients and 279 controls from the ALLFTD consortium, assessing annual neuropsychological performance and MRI‐based cortical thickness. Clinical characteristics and cortical thickness were compared between sexes. We used the residuals of linear regression models, which predict each participant's cognitive and behavioral performance levels relative to cortical thickness, as a proxy for reserve. We then modeled sex differences in longitudinal trajectories with linear mixed‐effects models.RESULTSSymptomatic females with genetic FTD had lower frontal cortical thickness than males, and the C9orf72 subgroup showed lower‐than‐expected frontal cortical thickness for a given level of executive functioning. Differences in cognitive reserve between sexes peaked near symptom onset but diminished thereafter.DISCUSSIONFemales with genetic FTD showed higher cognitive reserve than males, suggesting that self‐reported sex modulates resilience to frontotemporal neurodegeneration.Highlights Females with genetic FTD showed higher cognitive reserve than males. Those differences were particularly pronounced in the C9orf72 and GRN subgroups. The higher cognitive reserve in females declined as the disease progressed.

Importance Since 2005, a total of 50 face transplants have been reported from 18 centers in 11 countries. The overall survival of the grafts has not yet been established. Objective To assess the survival of the face transplant grafts and evaluate factors potentially influencing it. Design, Setting, and Participants Data on all the transplants included in this multicenter cohort study were collected at participating transplant centers for updated nonpublished data, supplemented with literature review for nonparticipating centers. Data from 2005 until September 2023, were included. Data were analyzed from November 11, 2005, through September 18, 2023. Patients included the first 50 patients in the world to have received a face transplant. Exposure Face transplant graft. Main Outcomes and Measures The primary outcome was the overall survival of the face transplant graft, defined as either transplant loss or patient death. The secondary outcome was the number of acute rejection episodes per year. Results The 50 transplants were performed on 39 men (81%) and 9 women (19%) with a median age of 35 (range, 19-68) years at the time of the transplant. The median follow-up time was 8.9 (range, 0.2-16.7) years. During the follow-up, 6 transplants were lost with 2 patients retransplanted. There were 10 patients who died, 2 of whom had lost a transplant. The 5- and 10-year survival of the transplants was 85% (SD, 5%) and 74% (SD, 7%), respectively. The sequential number of the transplant in the world was a significant predictor of survival (hazard ratio, 95; 95% CI, 90-100; P < 05). The median number of acute rejection episodes per year was 1.2 (range, 0-5.3) for the transplants that were lost and 0.7 (range, 0-4.6) for the transplants that survived. No correlation with patient and transplant variables was detected for either the transplant survival or the number of rejection episodes. Conclusions and Relevance In this study, the overall survival of the face transplants is encouraging. These data suggest that the acceptable long-term survival of face transplants makes them a reconstructive option for extensive facial defects.

Abstract Generating an immune response to T-dependent antigens requires the cooperative interaction of APC, T helper cells, and B cells. T helper cells recognize antigen, not as soluble, native antigen, but as processed antigen in association with Ia molecules on the surface of an APC. Investigators from our laboratory demonstrated previously that some B lymphoma cell lines will present antigen to antigen-reactive T cells in an MHC-restricted fashion. These tumor lines are used in this study as a model system to examine the biochemical basis of antigen processing. Five different H-2d tumor cell lines, which differ in their ability to express Ia molecules and function as APC, are all shown to biochemically degrade sperm whale Mb in a similar manner. Intact Mb and four Mb fragments (4.3 to 12.5 Kd) were reproducibly recovered from each of these Mb-pulsed cell lines. This processed Mb is shown to be nonrandomly distributed in external and internal compartments, with the two smallest Mb fragments being enriched in the intracellular compartment. The Mb and Mb fragments can be completely removed from the surface of the APC by enzymatic proteolysis without quantitatively changing the ability of these cells to present Mb to Mb-reactive T cell lines. These results suggest that the processed Mb that is located intracellularly is the primary immunoreactive antigen for antigen presentation to T helper cells.

Abstract Background Subjects with lower socioeconomic status (SES) are exposed to higher levels of environmental stressors. The cumulative effects of chronic stressors on cardiometabolic health can be evaluated using the allostatic load (AL) score. Despite the accepted social gradient, clear relationships between social determinants and cardiometabolic health in populations with different socio-cultural contexts have been rarely explored. This study aimed to compare the relationships of social determinants with AL in different socioeconomic contexts: unstable Venezuela (VE) and stable Czechia (CZ). Methods 25-64 years old subjects from two cross-sectional population-based samples from CZ (2013-2014, n = 1579, 56% females) and VE (2014-2017, n = 1652, 70% females). The AL score (scaled 0-8) was calculated using 8 cardiometabolic biomarkers (BMI, waist circumference, systolic and diastolic blood pressure, total and HDL-cholesterol, triglycerides). Social characteristics included education in both countries, household income in CZ, and composite measure of SES based on source of income, household head's profession, motheŕs education, and housing conditions in VE. Ordinal regression was performed separately in men and women. Results In CZ, men and women with low education and women with low income were more likely to have higher score of AL compared to those with high education and income (OR 1.45, 2.29 and 1.69). In VE, women with low education and low SES were more likely to have higher AL (OR 1.47 and 1.51), while men with low education and low SES were less likely to have higher AL (OR 0.64 and 0.61), compared to those with high education and high SES. Independently of age, sex, and socioeconomic characteristics, Venezuelans were more likely to have higher AL than Czechs. Conclusions Associations of social position indices and cardiometabolic health (proxied by AL) differed between CZ and VE, most likely reflecting differences in social environment between the countries. Key messages

AbstractPrimary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%–2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus‐based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow‐up during and after therapy.

AbstractBackground and purposeClinical trials in spinocerebellar ataxia type 3 (SCA3) will require biomarkers for use as outcome measures.MethodsTo evaluate total tau (t‐tau), glial fibrillary acidic protein (GFAP), ubiquitin carboxy‐terminal hydrolase L1 (UCHL1) and neurofilament light‐chain (NfL) as fluid biomarkers in SCA3, ATXN3 mutation carriers (n = 143) and controls (n = 172) were clinically assessed, and the plasma concentrations of the four proteins were analysed on the Simoa HD‐1 platform. Eleven ATXN3 mutation carrier cerebrospinal fluid samples were analysed for t‐tau and phosphorylated tau (p‐tau181). A transgenic SCA3 mouse model (MJDTg) was used to measure cerebellar t‐tau levels.ResultsPlasma t‐tau levels were higher in mutation carriers below the age of 50 compared to controls, and the Inventory of Non‐Ataxia Signs was associated with t‐tau in ataxic patients (p = 0.004). Pre‐ataxic carriers showed higher cerebrospinal fluid t‐tau and p‐tau181 concentrations compared to ataxic patients (p = 0.025 and p = 0.014, respectively). Cerebellar t‐tau was elevated in MJDTg mice compared to wild‐type (p = 0.033) only in the early stages of the disease. GFAP and UCHL1 did not show higher levels in mutation carriers compared to controls. Plasma NfL concentrations were higher in mutation carriers compared to controls, and differences were greater for younger carriers. The Scale for the Assessment and Rating of Ataxia was the strongest predictor of NfL in ataxic patients (p < 0.001).ConclusionOur results suggest that tau might be a marker of early disease stages in SCA3. NfL can discriminate mutation carriers from controls and is associated with different clinical variables. Longitudinal studies are required to confirm their potential role as biomarkers in clinical trials.

The aim of the present study was to evaluate the association between television viewing/physical activity (TVV/PA) interactions and cardiometabolic risk in an adult European population. A total of 2155 subjects (25–64 years) (45.2% males), a random population-based sample were evaluated in Brno, Czechia. TVV was classified as low (<2 h/day), moderate (2–4), and high (≥4). PA was classified as insufficient, moderate, and high. To assess the independent association of TVV/PA categories with cardiometabolic variables, multiple linear regression was used. After adjustments, significant associations were: High TVV/insufficient PA with body mass index (BMI) (β = 2.61, SE = 0.63), waist circumference (WC) (β = 7.52, SE = 1.58), body fat percent (%BF) (β = 6.24, SE = 1.02), glucose (β = 0.25, SE = 0.12), triglycerides (β = 0.18, SE = 0.05), and high density lipoprotein (HDL-c) (β = −0.10, SE = 0.04); high TVV/moderate PA with BMI (β = 1.98, SE = 0.45), WC (β = 5.43, SE = 1.12), %BF (β = 5.15, SE = 0.72), triglycerides (β = 0.08, SE = 0.04), total cholesterol (β = 0.21, SE = 0.10), low density protein (LDL-c) (β = 0.19, SE = 0.08), and HDL-c (β = −0.07, SE = 0.03); and moderate TVV/insufficient PA with WC (β = 2.68, SE = 1.25), %BF (β = 3.80, SE = 0.81), LDL-c (β = 0.18, SE = 0.09), and HDL-c (β = −0.07, SE = 0.03). Independent of PA levels, a higher TVV was associated with higher amounts of adipose tissue. Higher blood glucose and triglycerides were present in subjects with high TVV and insufficient PA, but not in those with high PA alone. These results affirm the independent cardiometabolic risk of sedentary routines even in subjects with high-levels of PA.

In contrast to the decreasing burden related to cardiovascular disease (CVD), the burden related to dysglycemia and adiposity complications is increasing in Czechia, and local drivers must be identified. A comprehensive literature review was performed to evaluate biological, behavioral, and environmental drivers of dysglycemia and abnormal adiposity in Czechia. Additionally, the structure of the Czech healthcare system was described. The prevalence of obesity in men and diabetes in both sexes has been increasing over the past 30 years. Possible reasons include the Eastern European eating pattern, high prevalence of physical inactivity and health illiteracy, education, and income-related health inequalities. Despite the advanced healthcare system based on the compulsory insurance model with free-for-service healthcare and a wide range of health-promoting initiatives, more effective strategies to tackle the adiposity/dysglycemia are needed. In conclusion, the disease burden related to dysglycemia and adiposity in Czechia remains high but is not translated into greater CVD. This discordant relationship likely depends more on other factors, such as improvements in dyslipidemia and hypertension control. A reconceptualization of abnormal adiposity and dysglycemia into a more actionable cardiometabolic-based chronic disease model is needed to improve the approach to these conditions. This review can serve as a platform to investigate causal mechanisms and secure effective management of cardiometabolic-based chronic disease.