AIMS: Stand-alone minimal invasive epicardial and hybrid atrial fibrillation ablation (EHAFA) has evolved to a recognized treatment option in challenging patients. The EHAFA registry was initiated to describe the applied diagnostic and therapeutic approaches used in routine practice for these procedures, as well as the outcomes in terms of rhythm, symptoms, and complications. METHODS AND RESULTS: Between January 2016 and March 2018, patients who underwent an EHAFA procedure for all types of atrial fibrillation (AF) were consecutively enrolled in the international, prospective, observational EHAFA registry. Follow-up occurred after 1 year. A total of 468 patients were enrolled from 17 centres in 10 countries. Stand-alone ablation (n = 464) was performed epicardially in 47% (n = 220) or as epi-/endocardial hybrid in 53% (n = 244). The predominate type of AF was non-paroxysmal in 74% (n = 342), and 36% (n = 166) of patients had failed previous catheter ablation. The main lesion sets applied consisted of pulmonary vein isolation (99%, n = 460) and isolation of the left atrial (LA) posterior wall (82%, n = 383). In 82% (n = 382), the LA appendage was managed. The overall in-hospital major complication rate was 8.2% (n = 38/464). Freedom from atrial arrhythmias > 30 s with and without antiarrhythmic drug usage was 79% and 64% (n = 279/353, n = 223/351, respectively). The EHRA score at follow-up was clearly reduced compared to preoperatively (EHRA I: 72%, n = 233/325, vs. 3%, n = 14/464). CONCLUSION: This international registry revealed good rhythm control efficacy for epicardial and hybrid AF ablation in patients with advanced AF, leading to improvement in AF-related symptoms. However, a certain associated complication rate needs to be considered.

• Klíčová slova
• Atrial fibrillation, Epicardial ablation, Hybrid ablation, Registry, Surgical ablation,
• MeSH
• časové faktory MeSH
• fibrilace síní * chirurgie   patofyziologie   diagnóza   MeSH
• katetrizační ablace * metody   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• perikard * chirurgie   MeSH
• prospektivní studie MeSH
• recidiva MeSH
• registrace MeSH
• senioři MeSH
• venae pulmonales * chirurgie   patofyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Primary chronic rhinosinusitis (CRS) can be classified based on the sinuses involved and the dominant endotype of the mucosal inflammation. Since the introduction of type 2 targeted biologics as treatment option for CRS, assessment of the inflammatory status has gained importance in CRS patients. We here aimed to characterize CRS patients with and without elevated markers of type 2 inflammation. METHODS: CRS patients who visited the outpatient ENT clinic in one of the 10 tertiary centers in 7 European countries were invited to use the Galenus Health mobile application for the monitoring of their disease. RESULTS: CRS patients (n = 281) were stratified according to blood eosinophil counts or BEC (< 150 cells/μL: 21.6% of patients, ≥ 150 cells/μL: 78.4%; < 250 cells/μL: 36.3%, ≥ 250 cells/μL: 63.7%) and serum total IgE (< 100 IU/mL: 59.9%, ≥ 100 IU/mL: 40.1%). BEC and serum total IgE did not correlate well (Spearman r = 0.06; p = 0.39). CRS patients with BEC ≥ 150 cell/μL or ≥ 250 cells/μL, respectively, showed increased NPS, SNOT-22, VAS for total CRS symptoms, loss of smell, nasal blockage, runny nose compared to patients with BEC below 150 or 250 cells/μL. CRS patients with increased serum total IgE (≥ 100 IU/mL) did not show differences in the outcome parameters compared to patients with levels below 100 IU/mL. CRS patients with asthma (58.9%) showed increased SNOT-22 and VAS loss of smell compared to patients without asthma. CONCLUSIONS: A significant proportion of CRS patients exhibit a type 2 endotype, characterized by blood eosinophilia (78%), increased serum total IgE (40%) and/or concomitant asthma (59%). Our results underline the usefulness of eosinophils as a marker of type 2 inflammation and severity but challenge the utility of serum total IgE since it does not correlate with any of the markers of severity.

• Klíčová slova
• asthma, eosinophils, mobile application, real world data, total IgE,
• Publikační typ
• časopisecké články MeSH

AIMS: To assess the efficacy and safety of switching from premixed insulin to a once-daily, fixed-ratio combination of insulin glargine 100 U/mL + lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D). METHODS: In this phase 4, 24-week, single-arm study, participants switched from once-daily or twice-daily premixed insulin to iGlarLixi (EudraCT number 2021-003711-25). Key inclusion criteria: ≥18 years; premixed insulin therapy for ≥3 months and < 10 years; ± 1-2 oral antidiabetic drugs (OADs); HbA1c ≥7.5% to ≤10.0%. The primary endpoint was the change in HbA1c from baseline to Week 24. Secondary endpoints included: participants achieving HbA1c <7% and change in body weight at Week 24, and safety. RESULTS: Overall, 162 participants switched to iGlarLixi (89.5% from twice-daily premixed insulin); mean duration of diabetes was 15.7 (standard deviation [SD]: 8.3) years. Mean baseline HbA1c (8.5%) reduced by least squares (LS) mean of 1.2% (95% confidence interval [CI]: -1.4, -1.1) at Week 24, and 37.6% of participants had achieved an HbA1c target of <7% (95% CI: 30.0, 45.7). LS mean body weight change from baseline to Week 24 was -1.0 kg (95% CI: -1.6, -0.5). Fasting and post-prandial plasma glucose decreased from baseline to Week 24 by 45.6 mg/dL (SD ± 52.4) and 67.6 mg/dL (SD ± 65.1), respectively. Confirmed symptomatic hypoglycaemia occurred in 38.3% of participants (ADA level 1: 35.8%; level 2: 15.4%; level 3: 0.0%). CONCLUSIONS: iGlarLixi initiation was associated with improved glycaemic control, without body weight gain or increased hypoglycaemia over 24 weeks.

• Klíčová slova
• clinical trial, iGlarLixi, insulin glargine, lixisenatide, phase IV study, type 2 diabetes,
• MeSH
• diabetes mellitus 2. typu * farmakoterapie   krev   MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• glykovaný hemoglobin analýza   MeSH
• hypoglykemie chemicky indukované   MeSH
• hypoglykemika * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• inzulin glargin * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• krevní glukóza účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada léků * MeSH
• peptidy * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• receptor pro glukagonu podobný peptid 2 MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• multicentrická studie MeSH
• Názvy látek
• fixní kombinace léků MeSH
• glykovaný hemoglobin MeSH
• hemoglobin A1c protein, human MeSH Prohlížeč
• hypoglykemika * MeSH
• inzulin glargin * MeSH
• krevní glukóza MeSH
• lixisenatide MeSH Prohlížeč
• peptidy * MeSH
• receptor pro glukagonu podobný peptid 2 MeSH

Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 109/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 109/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 109/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 109/L or ≥ 30 × 109/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 109/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19.

• Klíčová slova
• adults, immune thrombocytopenia, platelets, quality of life, response,
• MeSH
• aplikace orální MeSH
• dospělí MeSH
• idiopatická trombocytopenická purpura * farmakoterapie   krev   MeSH
• inhibitory proteinkinas * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• inhibitory tyrosinkinasy MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet trombocytů MeSH
• proteinkinasa BTK * antagonisté a inhibitory   MeSH
• pyrimidiny * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• Názvy látek
• inhibitory proteinkinas * MeSH
• inhibitory tyrosinkinasy MeSH
• proteinkinasa BTK * MeSH
• pyrimidiny * MeSH

Fabry disease is an X-linked lysosomal storage disorder that causes accumulation of glycosphingolipids in body tissues and fluids, leading to progressive organ damage and life-threatening complications. It can affect both males and females and can be classified into classic or later-onset phenotypes. The disease severity in females ranges from asymptomatic to the more severe, classic phenotype. Most females are hemizygous and the X-linked inheritance is associated with variable X-activation pattern and residual enzymatic activity. The heterogeneity of clinical presentation in females requires different approaches to diagnosis and management than males. A European group of 7 physicians, experienced in the management of Fabry disease, convened to discuss patient perspectives and published guidelines. The experts discussed the need to focus on psychological treatment in relation to individual coping styles when monitoring targets, and the lack of data supporting the use of plasma globotriaosylsphingosine over enzyme activity in the diagnosis of these patients. It was suggested that the high phenotypic variability in female patients may be related to the dynamic nature of the X-chromosome inactivation process and further understanding of this process could help predict the progression of Fabry disease in females and facilitate timely intervention. Due to the range of disease severity they exhibit, female patients with Fabry disease may require a more individualized treatment approach than males. Despite current recommendations, the experts agreed that early disease-specific treatment initiation in high-risk females could improve clinical outcome.

• Klíčová slova
• Early diagnosis, Enzyme replacement therapy, Fabry disease, Female, Patient-reported outcome measures,
• MeSH
• Fabryho nemoc * terapie   genetika   diagnóza   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIM: To evaluate the efficacy of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) using derived time-in-range (dTIR). METHODS: Participant-level data from LixiLan-L, LixiLan-O and LixiLan-G were pooled and dTIR (70-180 mg/dL), derived time-above-range (> 180 mg/dL) and derived time-below-range (dTBR; < 70 mg/dL) were calculated from participant seven-point self-monitored blood glucose profiles. RESULTS: This pooled analysis included data from 2420 participants receiving iGlarLixi (n = 1093), iGlar (n = 836), Lixi (n = 234) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA) (n = 257). Numerically greater improvements in least square (LS) means dTIR were seen from baseline to end of treatment (EOT) with iGlarLixi (25.7%) versus iGlar (15.8%), Lixi (11.7%) or GLP-1 RA (16.2%). At EOT, the mean (standard deviation) dTBR was 0.71% ± 3.4%, 0.61% ± 3.2%, 0.08% ± 1.0% and 0.0% ± 0.0% for iGlarLixi, iGlar, Lixi and GLP-1 RA, respectively. In a subgroup analysis, participants aged younger than 65 years (n = 1690) and 65 years or older (n = 713) showed numerically greater improvements in LS means dTIR from baseline to EOT with iGlarLixi versus iGlar, Lixi or GLP-1 RA. CONCLUSIONS: iGlarLixi achieved improvements in dTIR, with low dTBR values, providing further evidence to inform clinical outcomes with the use of iGlarLixi.

• Klíčová slova
• derived time‐in‐range, fixed‐ratio combination, iGlarLixi, real‐world data, type 2 diabetes,
• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• diabetes mellitus 2. typu * farmakoterapie   krev   MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• glykovaný hemoglobin analýza   metabolismus   účinky léků   MeSH
• hypoglykemika * terapeutické užití   MeSH
• inzulin glargin * terapeutické užití   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• krevní glukóza * účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidy * terapeutické užití   aplikace a dávkování   MeSH
• randomizované kontrolované studie jako téma MeSH
• receptor pro glukagonu podobný peptid 2 MeSH
• selfmonitoring glykemie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• fixní kombinace léků MeSH
• glykovaný hemoglobin MeSH
• hypoglykemika * MeSH
• inzulin glargin * MeSH
• krevní glukóza * MeSH
• lixisenatide MeSH Prohlížeč
• peptidy * MeSH
• receptor pro glukagonu podobný peptid 2 MeSH

Fabry Registry data were analyzed among 83 agalsidase beta-treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein-creatinine ratio [UPCR], plasma globotriaosylceramide [GL-3], plasma globotriaosylsphingosine [lyso-GL-3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre- and postswitch periods. eGFR decreased throughout both periods (preswitch: -0.85 mL/min/1.73 m2/year; postswitch: -1.96 mL/min/1.73 m2/year; both p < 0.0001), with steeper decline postswitch (ppre/post = 0.01) in both classic and late-onset patients. UPCR increased significantly postswitch (ppre/post = 0.003) among classic patients and was stable in both periods among late-onset patients. GL-3 trajectories worsened postswitch across phenotypes (ppre/post = 0.0005 classic, 0.02 late-onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (-0.51 mm/year, p = 0.0005; ppre/post = 0.0009), primarily among late-onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (ppre/post = 0.02 IVST, 0.01 LVMI). Among late-onset patients, IVST significantly decreased postswitch (ppre/post = 0.0003); LVMI was stable over time (ppre/post = 0.89). Ultimately, eGFR and GL-3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late-onset patients. These findings indicate variability in long-term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring.

• Klíčová slova
• Fabry disease, agalsidase beta, chaperone, enzyme replacement therapy (ERT), migalastat,
• MeSH
• 1-deoxynojirimycin * analogy a deriváty   terapeutické užití   aplikace a dávkování   MeSH
• alfa-galaktosidasa * terapeutické užití   MeSH
• dospělí MeSH
• enzymová substituční terapie metody   MeSH
• Fabryho nemoc * farmakoterapie   MeSH
• glykolipidy MeSH
• hodnoty glomerulární filtrace * MeSH
• izoenzymy * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• registrace * MeSH
• sfingolipidy krev   MeSH
• trihexosylceramidy metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-deoxynojirimycin * MeSH
• agalsidase beta MeSH Prohlížeč
• alfa-galaktosidasa * MeSH
• globotriaosyl lysosphingolipid MeSH Prohlížeč
• globotriaosylceramide MeSH Prohlížeč
• glykolipidy MeSH
• izoenzymy * MeSH
• migalastat MeSH Prohlížeč
• sfingolipidy MeSH
• trihexosylceramidy MeSH

MOTIVATION: Lipid nanoparticles (LNPs) are the most widely used vehicles for mRNA vaccine delivery. The structure of the lipids composing the LNPs can have a major impact on the effectiveness of the mRNA payload. Several properties should be optimized to improve delivery and expression including biodegradability, synthetic accessibility, and transfection efficiency. RESULTS: To optimize LNPs, we developed and tested models that enable the virtual screening of LNPs with high transfection efficiency. Our best method uses the lipid Simplified Molecular-Input Line-Entry System (SMILES) as inputs to a large language model. Large language model-generated embeddings are then used by a downstream gradient-boosting classifier. As we show, our method can more accurately predict lipid properties, which could lead to higher efficiency and reduced experimental time and costs. AVAILABILITY AND IMPLEMENTATION: Code and data links available at: https://github.com/Sanofi-Public/LipoBART.

• MeSH
• lipidy * chemie   MeSH
• liposomy MeSH
• messenger RNA metabolismus   MeSH
• nanočástice * chemie   MeSH
• transfekce * metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Lipid Nanoparticles MeSH Prohlížeč
• lipidy * MeSH
• liposomy MeSH
• messenger RNA MeSH

• Klíčová slova
• fixed‐ratio combination, iGlarLixi, insulin glargine and lixisenatide, pooled analysis, prior insulin use, type 2 diabetes,
• MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• fixní kombinace léků MeSH
• glykovaný hemoglobin analýza   účinky léků   metabolismus   MeSH
• hypoglykemika * terapeutické užití   MeSH
• inzulin glargin * terapeutické užití   aplikace a dávkování   MeSH
• krevní glukóza účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidy * terapeutické užití   aplikace a dávkování   MeSH
• receptor pro glukagonu podobný peptid 2 MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• fixní kombinace léků MeSH
• glykovaný hemoglobin MeSH
• hemoglobin A1c protein, human MeSH Prohlížeč
• hypoglykemika * MeSH
• inzulin glargin * MeSH
• krevní glukóza MeSH
• lixisenatide MeSH Prohlížeč
• peptidy * MeSH
• receptor pro glukagonu podobný peptid 2 MeSH

INTRODUCTION: Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently a substantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100 U/ml and a GLP-1 RA lixisenatide. METHODS: Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor. PLANNED OUTCOMES: The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04945070.

• Klíčová slova
• Complex insulin therapy simplification, Fixed-ratio combination of GLP-1 receptor agonist and basal insulin (FRC), Insulin glargine/lixisenatide (iGlarLixi), Insulin therapy de-intensification, Intensified insulin therapy (IIT), Multiple daily injections insulin regimen (MDI), Type 2 diabetes (T2D),
• Publikační typ
• časopisecké články MeSH