Vitkovice - Research and Development (Czechia)

Abstract Background JAK inhibitors (JAKi) are small molecules that cross the placenta from early pregnancy.1 Evidence on the safety of in utero JAKi exposure remains limited, particularly regarding pregnancy outcomes, infant infections, vaccine responses, and early development.2, 3 Methods We conducted a multicenter retrospective study within the ECCO CONFER network, including pregnant women with inflammatory bowel disease (IBD) exposed to tofacitinib (TOFA), upadacitinib (UPA), or filgotinib (FILGO). Data were collected from 22 centers across 16 countries and included maternal characteristics, disease activity, medication patterns, and pregnancy and infant outcomes. Results Among 55 JAKi exposed pregnancies, 21 (38.2%) were unplanned and 30 (54.6%) had active disease. Nine women (16.4%) initiated JAKi during pregnancy. Overall, 38 (69.1%) received TOFA, 15 (27.3%) UPA, and 2 (3.6%) FILGO; 39 (70.9%) continued treatment throughout pregnancy. JAKi discontinuation in 1st-2nd trimester led to disease activity in 9/16 cases (56.3%). Maternal complication risk was low: no DVT or (pre) eclampsia occurred; three cases of premature rupture of membranes (GA 34–37) and four required hospitalizations due to infection or other complications. A total of 10 abortions occurred - five spontaneous (9.1%) and five induced (9.1%), including three due to concern about JAKi exposure. Among 45 live births, two infants (3.6%) were preterm, four (7.3%) small for gestational age, and two (3.6%) had Apgar <7 at 5 minutes. No congenital abnormalities were reported. Infant follow-up findings are summarized in Table 1. One-third of breastfeeding women continued JAKi postpartum. A high adherence rate to the national immunization schedule was seen. Eight (19.5%) received the live BCG-vaccine within the first 30 days of life. No adverse events followed live or inactivated vaccines, and no malignancies were observed. Conclusion In this global cohort of JAKi-exposed pregnancies in women with IBD, maternal complication rates were low, and no increased risk of adverse outcomes among live births was identified. While disease activity was common, particularly following discontinuation of JAKi, infant outcomes - including development, infection risk, and vaccine response - were reassuring. These findings provide important preliminary safety data to inform decision-making regarding JAKi use in pregnancy, though prospective studies are needed to confirm long-term safety.

Abstract Background Comparative data on risankizumab (RISA) and upadacitinib (UPA) in Crohn’s disease (CD) are limited. In this preliminary analysis, we assessed treatment persistence with these agents and explored whether the choice should be modified according to disease location. Methods Data from the Czech National Prospective Registry of Biological and Innovative Therapies for Inflammatory Bowel Disease (CREdIT) were analysed to evaluate treatment persistence in adult and paediatric patients with CD who began treatment with RISA or UPA, with a minimum follow-up period of three months. Patients with missing outcomes or dual advanced therapy were excluded. Inverse-probability-of-treatment weighting (IPTW) based on a propensity score including demographic, disease activity and treatment history variables was applied to reduce confounding factors. Treatment persistence was analysed using Kaplan–Meier curves and Cox proportional hazards models, clustered by patient. We evaluated whether disease location (ileal vs non-ileal) altered treatment persistence by using group-specific survival analyses. Results A total of 474 treatment observations were identified in patients receiving RISA or UPA. Following the application of exclusion criteria, the analysis included 370 observations from 323 patients, of which 157 (42%) were on RISA and 213 (58%) were on UPA. Of these, 11 (7%) were paediatric patients in the RISA group and 22 (10%) in the UPA group. The median number of actual lines of advanced therapy was four in both groups, with 38% of RISA observations and 39% of UPA observations representing ≥ 5th treatment line. Groups differed only in age at treatment start (median 38 vs 37 years). Ileal disease only was present in 23 (15%) RISA patients and 28 (13%) UPA patients. Unadjusted data (Figure 1) demonstrated higher persistence of RISA vs. UPA treatment. After balancing the cohort using IPTW, all standardised mean differences between groups were below 0.1. Compared with RISA, UPA was associated with a higher risk of treatment discontinuation (hazard ratio: 2.83; 95% confidence interval: 1.50–6.34). Interaction analysis by disease location was not feasible because no RISA failures occurred in the ileal subgroup. Therefore, only descriptive stratified curves are shown in Figure 2. Conclusion In this preliminary analysis of refractory CD, treatment persistence was greater with RISA than with UPA. These real-world data suggest that RISA may be a more durable treatment option, particularly for patients with ileal CD. However, confirmation in larger patient groups is required. Conflict of interest: Dr. Hradsky, Ondrej: Lectures/congress fees/consultancy from MSD, AbbVie, Takeda, Sandoz, Nutricia, Ferring, Pfizer, and Lilly. Duricova, Dana: Lectures/congress fees/consultancy (outside the scope of the submitted work) from Johnson & Johnson, Takeda, AbbVie, Pfizer, Ferring, Eli Lilly, and Celltrion. Lukás, Milan: Research Support / Clinical trials: Biogen, Takeda, Janssen Consultant / Speaker : Abbvie, Ferring, Takeda, Janssen Speakers Bureau / Advisory Board Member: Pfizer, Roche, Egis, Celltrion, Takeda, Janssen, Eli Lilly Employee: ISCARE a.s./1stMedical Faculty, Charles University, Prague Nedbalova, Lenka: No conflict of interest Bouchner, Luděk: No conflict of interest Pipek, Barbora: Lectures/congress fees/consultancy (outside the scope of the submitted work) from Johnson & Johnson, Takeda, AbbVie, Pfizer, and Eli Lilly. Svoboda, Pavel: Lectures/congress fees/consultancy (outside the scope of the submitted work) from AbbVie, Takeda, Janssen-Cilag, Celltrion, Tillotts, Alfasigma, Sandoz, Pfizer, and Eli Lilly. Siroky, Milan: No conflict of interest Bronsky, Jiri: Lectures/congress fees/consultancy (outside the scope of the submitted work) from AbbVie, Sandoz, Danone-Nutricia, Nestlé, Sanofi, Pfizer, and Vitabalans. Bortlik, Martin: Lectures/congress fees/consultancy (outside the scope of the submitted work) from AbbVie, Takeda, Janssen-Cilag, Celltrion, Roche, AstraZeneca, Biogen, Tillotts, Ferring, Alfasigma, PRO.MED.CS, Sandoz, Bristol-Myers Squibb, Pfizer, and Swedish Orphan Biovitrum.

Abstract Complicated tibia fractures are still connected with significant problems of healing. Hence, the external Ilizarov fixators are applied, and then they are sometimes converted to internal fixators. The aim of this work is to investigate the effects of different levels and timing of mechanical stimulation in the treatment of tibia with measuring strain gauges. Different levels of mechanical stimulus would lead to different degrees and rates of healing. The evaluated timing of stimulus application is a critical factor for the success of the treatment response.

SummaryVariation in response to clopidogrel represents a significant clinical challenge in patients with ischemic stroke. Genetic polymorphisms cytochrome P450 2C19 (CYP2C19) are a known cause of resistance to clopidogrel. Platelet microRNAs (miRNAs) can modulate the efficacy of antiplatelet therapy. This study focuses solely on clopidogrel because it is the most widely used alternative to aspirin in patients with aspirin intolerance or contraindications. Our aim was to investigate its pharmacogenomic and epigenetic modulation in a targeted and homogeneous cohort. CYP2C19 genotypes are commonly reported as *1/*1 (wild type), *1/*2 (intermediate metabolizer), *2/*2 (poor metabolizer) and *2/*3 (poor metabolizer). These denote the number and type of loss-of-function alleles that affect clopidogrel metabolism. Clopidogrel treatment is typically a component of broader secondary prevention strategies, including lifestyle modifications, statins, and control of blood pressure. Relevant bibliographic references have been added to support the background statements provided in the introduction and methodology. To evaluate the expression of selected platelet miRNAs (miR-126-3p, miR-19a-3p, miR-19b-3p, miR-22-3p, miR-185-5p) in patients with ischemic stroke in relation to the CYP2C19 genotype (*1/*1,*1/*2, *2/*2) during clopidogrel treatment. Seventy patients treated with clopidogrel (75 mg daily) were enrolled. Patients were genotyped for the CYP2C19 *2 and *3 alleles by real-time polymerase chain reaction (polymerase chain reaction (PCR)) and miRNA expression was measured in plasma. All abbreviations used throughout the manuscript have been defined at their first appearance for the sake of clarity. No significant differences in miRNA expression were found between the genotypic groups (p > 0.05). Patients with genotype *2/*2 (poor metabolizer) showed a trend towards higher levels of miR-126-3p and miR-185-5p (approximately 1.5 to 1.7 times) compared to *1/*1 (wild type). The clinical parameters did not differ significantly between the groups. Poor clopidogrel metabolizers can exhibit upregulation of some platelet miRNAs as a potential compensatory mechanism. This pilot study suggests a possible epigenetic modulation of the response to antiplatelet therapy through platelet miRNAs.

Entomological investigations are usually carried out in natural habitats, with the aim of capturing the local species composition and revealing occurrence of remarkable (rare, endangered, bioindicative) species. In intensively used agricultural landscapes or residential environments, similar surveys are usually considered "unattractive" and, therefore, relatively uncommon (Hluchý & Dobšík 1984; Wolda et al. 1994; Šafář 2010 ). However, their numbers are increasing due to insect declines and efforts to change landscape structure to support biodiversity (Kadlec et al. 2009; Ekroos et al. 2010; Botham et al. 2015) . Alternatively, research in these habitats is focused on a very limited spectrum of harmful species (the Central Institute for Supervising and Testing in Agriculture light trap network) or is targeted at opportunities to control methods of individual harmful species. This research aimed to investigate the moth fauna of the agricultural landscape, with a primary focus on what harmful species occur there (which important crops may damaged) and what share they have in the overall moth assemblage, i.e. also to determine the overall moth diversity expressed in numbers of species, individuals and basic synecological indices, and whether species

Abstract Thirteen species of the Agromyzidae are recorded from Cambodia for the first time. Of these one is here described as new and illustrated: Agromyza cambodiae sp. nov., the remaining twelve species are newly recorded from the country. With these additions a total of 16 species in 6 genera of Agromyzidae are currently known from the country.

Pancreatic steatosis (PS) has both metabolic consequences and local effects on the pancreas itself. Magnetic resonance imaging (MRI) is the most reliable non-invasive method for diagnosing PS. We investigated the impact of metabolic syndrome (MS) on the presence of PS, differences in individuals with and without PS, and the metabolic effects of bariatric procedures. Changes in anthropometric and basic biochemistry values and MS occurrence were evaluated in 34 patients with obesity who underwent a bariatric procedure. After the procedure, patients underwent MRI with manual 3D segmentation mask creation to determine the pancreatic fat content (PFC). We compared the differences in the PFC and the presence of PS in individuals with and without MS and compared patients with and without PS. We found no significant difference in the PFC between the groups with and without MS or in the occurrence of PS. There were significant differences in patients with and without PS, especially in body mass index (BMI), fat mass, visceral adipose tissue (VAT), select adipocytokines, and lipid spectrum with no difference in glycemia levels. Significant metabolic effects of bariatric procedures were observed. Bariatric procedures can be considered effective in the treatment of obesity, MS, and some of its components. Measuring PFC using MRI did not show any difference in relation to MS, but patients who lost weight to BMI < 30 did not suffer from PS and had lower overall fat mass and VAT. Glycemia levels did not have an impact on the presence of PS.