Krajská Nemocnice Liberec

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.

The prognostic role of dendritic cells (DCs) in colorectal cancer (CRC) and paired liver metastases (LM) remains unclear, particularly regarding the dynamics of immature CD1a+ and mature CD208+ subsets across anatomical compartments and synchronous versus metachronous disease. Patients and methods. This retrospective cohort included patients undergoing resection of primary CRC (pCRC) and synchronous LM (N = 55) or metachronous LM (N = 44). Immunohistochemical staining for CD1a and CD208 was performed on non-tumor adjacent mucosa (NAM), as well as tumor center (TC), inner margin (IM), outer margin (OM), and peritumoral zone (PT) of both pCRC and LM. Cell densities were quantified on whole-slide images using QuPath software and correlated with overall survival (OS). Results. CD1a+ DCs were nearly absent in NAM but enriched in pCRC TC, whereas CD208+ DCs predominated in lymphoid aggregates associated with NAM and peripheral compartments of pCRC and LM. CD1a+ cells followed a TC/IM > OM/PT gradient, while CD208+ cells showed the opposite, consistent with a recruitment–maturation axis. In synchronous cases, CD1a+ densities were higher in pCRC than LM, supporting the role of the primary tumor as a “monocyte reservoir.” Survival analysis revealed that high CD208+ density in TC of synchronous LM (hazard ratio (HR) = 0.47; p = 0.033) and high CD1a+ density in TC of metachronous LM (HR = 0.44; p = 0.050) were both associated with reduced mortality risk. Conclusion. This study provides the first detailed mapping of CD1a+ and CD208+ DCs across NAM, pCRC and paired LM, indicating that their prognostic impact is determined not only by absolute numbers but, more importantly, by compartmental distribution and the temporal pattern of metastasis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00262-025-04238-2.

Abstract BACKGROUND Astrocytoma, IDH-mutant, is the most common primary brain tumor in young adults, with peak incidence between 30 and 40 years of age. It is defined by mutations in the IDH1 or IDH2 genes and the absence of 1p/19q codeletion, and it frequently harbors alterations in ATRX and TP53. Rarely, astrocytoma, IDH-mutant, amay exhibit primitive neuronal differentiation, morphologically resembling “small round blue cell” tumors or large anaplastic embryonal-like cells. METHODS We analyzed 18 cases of astrocytoma, IDH-mutant, with primitive neuronal differentiation. In 11 cases where both the primitive neuronal and glial components were available, macrodissection was performed by a pathologist. Each component was subjected to separate genetic (next-generation sequencing) and epigenetic (DNA methylation profiling) analyses. Morphological and immunophenotypic features were also evaluated. RESULTS The primitive neuronal component was characterized by absent or markedly reduced GFAP expression, positivity for neuronal markers, a high Ki-67 proliferation index, and frequent TTF1 expression. This component also exhibited distinct epigenetic signatures and copy number alterations compared to the glial component. All tumors were high-grade, with extensive copy number variations, frequent MYCN amplification, and RB1 loss. DISCUSSION Astrocytoma, IDH-mutant, with a primitive neuronal component expands the morphological spectrum of IDH-mutant astrocytomas and presents a significant diagnostic challenge. Recognition of this rare subtype is critical due to its aggressive biological behavior. This work was supported by Masaryk University in Brno, Czech Republic, under Grant MUNI/A/1621/2024, the Ministry of Health, Czech Republic, grant project no. NU23-03-00100 and by the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU.

IntroductionCongenital immune system defects represent an ever-growing group of diseases characterized by increased susceptibility to infections and association with autoimmune, autoinflammatory, allergic and malignant complications. Here, we provide the first comprehensive report on inborn errors of immunity (IEIs) in Czechia based on the analysis of patient data from the Czech national registry (CzNR) of IEIs.Material and methodsThe online platform of CzNR of IEIs was established in 2012, compiling data about epidemiology, type of diagnosis, clinical and laboratory parameters, as well as the treatment of patients diagnosed with IEIs since 1981.ResultsThe total of 1,443 registered patients includes 697 males (48.3%) and 746 females (51.7%). The median age at diagnosis was 21.0 (0–86) years. The most represented group of patients was those with antibody deficiencies (788 patients; 54.6%). This was followed by complement deficiencies (242; 16.8%), combined immunodeficiencies with syndromic features (250; 17.3%), combined immunodeficiencies (55; 3.8%), congenital defects of phagocyte number, function, or both (31; 2.1%), autoinflammatory disorders (28; 1.9%), immune dysregulation diseases (24; 1.7%), intrinsic and innate immunity defects (21; 1.5%), primary immunodeficiency phenocopies (3; 0.2%), and bone marrow failure disorders (1; 0.1%). Common variable immunodeficiency (504; 34.9%), hereditary angioedema (222; 15.4%), and DiGeorge syndrome (182; 12.6%) were the most frequent diagnoses.ConclusionIn this article, we report the epidemiology of IEIs in the Czech Republic for the first time based on the CzNR of IEIs data. The prevalence of IEIs is approximately 13.2 patients per 100000 inhabitants of the Czech Republic.

Leishmania is a genus of the family Trypanosomatidae that unites obligatory parasitic flagellates causing a variety of vector-borne diseases collectively called leishmaniasis. The symptoms range from relatively innocuous skin lesions to complete failures of visceral organs. The disease is exacerbated if a parasite harbors Leishmania RNA viruses (LRVs) of the family Pseudototiviridae. Screening a novel isolate of L. braziliensis, we revealed that it possesses not a toti-, but a bunyavirus of the family Leishbuviridae. To the best of our knowledge, this is a very first discovery of a bunyavirus infecting a representative of the Leishmania subgenus Viannia. We suggest that these viruses may serve as potential factors of virulence in American leishmaniasis and encourage researchers to test leishmanial strains for the presence of not only LRVs, but also other RNA viruses.

In the anatomically complex terrain of the head and neck, the use of 3D intraoperative models serves as an effective verification tool, determining the size, shape, and number of foreign bodies. This allows the main operator to maximize their capacities for careful wound revision and receive real-time information about the remaining content of the sought-after bodies. Penetrating foreign bodies of various origins in the head and neck are uncommon, but potentially hazardous injuries. Complete removal of foreign bodies from soft tissues is essential for optimal healing, minimizing complications, and significantly reducing the risk of the need for reoperation. Despite various technological systems and safeguards available, unintentionally retained surgically placed foreign bodies remain difficult to eliminate completely. A 34-year-old female patient with a cut on the right side of her face who was initially treated with sutures at a general surgical clinic presented for a follow-up examination. A foreign body was verified subcutaneously on the anterior-posterior x-ray image on the right side. Computed tomography confirmed a total of 7 foreign bodies with a density corresponding to dental enamel, distributed subcutaneously, subfascially, and intramuscularly in the right temporal region. As part of the preoperative preparation and analysis, the bone segment of the right temporal fossa with the zygomatic bone and the glass fragments were segmented from the CT data and printed on an SLA printer. The physical 3D models were autoclave sterilized and present during surgery. The position, shape, and number of each individual glass fragment was compared with 3D-printed one. The benefits of producing 3D models of foreign bodies are undeniable, particularly in their perioperative comparison with the removed foreign bodies from wounds.

The paper describes the research and development of system for recondition of laying patient. The device uses four electronical cams. The cams emulate gait of patients in laying position. This simulation of natural gait in all phases is limited by the patient's position. An overview of verticalization techniques and equipment is presented. This is followed by an analysis of gait in the context of electronic CAM design. The benefit is validation and redesign according to the specific needs of the patient and staff in the Intensive Care Unit. The graphical user interface design is part of this system.

Composite nanofibrous yarns (CNY), featuring a submicron electrospun sheath coated on a micro-scale core yarn have gained attention within the academic and industrial communities due to their unique structure. When braided, these CNYs hold great promise as next-generation surgical yarns. However, large-scale production of CNYs using conventional electrospinning techniques remains technologically challenging, and maintaining the integrity of the fibrous sheath during braiding presents further difficulties. Here, we propose a novel approach for continuously fabricating functional braided CNYs using collectorless alternating current (AC) electrospinning and braiding technology. Our approach utilized polycaprolactone-polylactic acid (PCL-PLA) blends and PCL-PLA with chlorhexidine (CHX) or triclosan (TRC) electrospun fibers for the sheath layer, while PLA micro-yarns acted as the core layer. Morphological analyses confirmed the successful fabrication of braided CNYs. Additionally, infrared spectroscopy validated the presence of CHX or TRC in the resulting yarns. The resulting braided CNYs exhibited excellent breaking force (29 N) and thermal stability (270 °C). Cytotoxicity and antibacterial assessments demonstrated that CHX-loaded braided CNYs could serve as biocompatible antibacterial surgical sutures. The proposed method offers a versatile approach for producing various functional braided CNYs applicable in tissue engineering scaffolds, filters, wearable electronics, and sensors.

The objective of this study was to investigate the association and combined prognostic significance of the PD-L1, Smoothened protein and β-catenin expressions in patients with clear cell renal cell carcinoma (ccRCC). The PD-L1, Smoothened protein and β-catenin expression were evaluated in 104 ccRCC patients. All studied tumor samples were acquired from nephrectomy specimens of primary tumors and not from biopsies or metastases. An indirect immunohistochemistry using polyclonal rabbit anti-Smoothened antibody, monoclonal mouse anti-human β-catenin-1 antibody, immunohistochemical assay PD-L1 28-8 pharmDx using monoclonal rabbit anti-PD-L1 antibody and anti-VHL (C- terminal) rabbit antibody was used. Immunohistochemistry was scored semiquantitavely. Median overall survival (OS) was significantly better in patients with lower PD-L1 expression (≤5%), Smoothened protein (SMO) expression (<5%) or cytoplasmic β-catenin expression (≤75%) than in patients with higher expressions of these biomarkers (P<0.001, P=0.047, and P<0.001, respectively). Membranous β-catenin showed an opposite effect with its lower expression (≤75%) being associated with longer OS (P=0.020). There was significant association between PD-1 and PD-L1 expression (P=0.007) and significant association of tumor grade (WHO 2016) with membranous β-catenin (P<0.001), cytoplasmic β-catenin (P=0.005), pVHL (P=0.042), PD-L1 (P=0.049) and PD-1 (P=0.028) expression. The present study provides the first data on the potential association and combined prognostic significance of frequency of primary cilia, PD-L1, Smoothened protein and β-catenin expression with the outcome in clear cell renal cell carcinoma.