10 results on '"Angyal D"'
Search Results
2. Reply to: Cystic fibrosis transmembrane conductance regulator (CFTR) variants and CFTR function in patients with pancreatitis.
- Author
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Melotti P, Angyal D, Bijvelds MJC, and Frulloni L
- Subjects
- Humans, Cystic Fibrosis genetics, Cystic Fibrosis metabolism, Mutation, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Pancreatitis genetics, Pancreatitis metabolism
- Published
- 2024
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3. Efficacy, drug sustainability, and safety of ustekinumab treatment in Crohn's disease patients over three years.
- Author
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Barkai LJ, Gonczi L, Balogh F, Angyal D, Farkas K, Farkas B, Molnar T, Szamosi T, Schafer E, Golovics PA, Juhasz M, Patai A, Vincze A, Sarlos P, Farkas A, Dubravcsik Z, Toth TG, Szekely H, Miheller P, Lakatos PL, and Ilias A
- Subjects
- Humans, Male, Female, Adult, Treatment Outcome, Middle Aged, Prospective Studies, Follow-Up Studies, Remission Induction, Hungary, Crohn Disease drug therapy, Ustekinumab therapeutic use, Ustekinumab adverse effects
- Abstract
Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications., (© 2024. The Author(s).)
- Published
- 2024
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- View/download PDF
4. CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants.
- Author
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Angyal D, Kleinfelder K, Ciciriello F, Groeneweg TA, De Marchi G, de Pretis N, Bernardoni L, Rodella L, Tomba F, De Angelis P, Surace C, Pintani E, Alghisi F, de Jonge HR, Melotti P, Sorio C, Lucidi V, Bijvelds MJC, and Frulloni L
- Subjects
- Humans, Bicarbonates metabolism, Chlorides, Mutation, Quinolones, Cystic Fibrosis genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Pancreatitis genetics, Pancreatitis metabolism
- Abstract
Background: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants., Methods: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI)., Results: Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function., Conclusions: CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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5. Burden of Mental Health among Patients with Inflammatory Bowel Disease-A Cross-Sectional Study from a Tertiary IBD Center in Hungary.
- Author
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Lontai L, Elek LP, Balogh F, Angyal D, Pajkossy P, Gonczi L, Lakatos PL, and Iliás Á
- Abstract
Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively affect the patient's quality of life. With the spread of the biopsychosocial model, the role of mental health in the activity and course of inflammatory bowel disease is becoming more and more recognized. Our study aimed to assess the prevalence of anxiety and depression in IBD patients in our tertiary referral center and determine the predictive factors of these mental conditions. Methods: A total of 117 patients were included consecutively between 1 December 2021 and 28 February 2022. We used a questionnaire to gather demographic information, disease course, and IBD-specific symptoms. We assessed anxiety symptoms using the GAD-7 and depressive complaints using the PHQ-9 questionnaire. We evaluated disease activity using CDAI and pMayo scores. Results: Of the 117 patients (male/female: 63/54), 88 suffered from Crohn's disease, and 29 were diagnosed with ulcerative colitis. Only 6 patients were taking medication for mood disorders, and 38 individuals sought mental support during their lifetime. A total of 15% of the population suffered from moderate-severe anxiety disorder, and 22% were affected by moderate-severe depression. The GAD-7 and PHQ9 values showed a significant correlation between the number of stools, bloody stools, abdominal pain, number of flare-ups, and CDAI scores. Conclusions: Our study confirmed that there is a high incidence of anxiety and depressive symptoms among IBD patients. Our results highlighted the symptoms that could be associated with mental disorders. It is important to assess the mental status of IBD patients to improve their quality of life.
- Published
- 2024
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- View/download PDF
6. Burden of perianal disease in Crohn's disease: Accelerating medical therapy and high rates of perianal surgery over the last four decades - Results from a population-based study over four decades.
- Author
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Gonczi L, Lakatos L, Golovics PA, Angyal D, Balogh F, Ilias A, Pandur T, David G, Erdelyi Z, Szita I, and Lakatos PL
- Subjects
- Humans, Follow-Up Studies, Immunosuppressive Agents therapeutic use, Disease Progression, Drainage, Treatment Outcome, Crohn Disease drug therapy, Crohn Disease epidemiology, Crohn Disease surgery, Rectal Fistula surgery
- Abstract
Background: Few population-based studies have investigated the prevalence and disease course of perianal manifestation in Crohn's disease., Aims: To analyse the prevalence and outcomes of perianal Crohn's disease including medical therapies and need for perianal surgery, over different therapeutic eras based on the time of diagnosis; cohort A (1977-1995), cohort B (1996-2008), and cohort C (2009-2018) METHODS: Patient inclusion lasted between 1977 and 2018. We followed patients prospectively, and regularly reviewed both in-hospital and outpatient records. We defined a perianal surgical procedure as any perianal incision and excision, fistulotomy, or abscess drainage., Results: We included 946 incident patients. Perianal disease at diagnosis was present in 17.4% (n = 165) of the total cohort, with a declining prevalence in cohorts A/B/C, respectively (24.7%/18.5%/13.2%; p = 0.001). By the end of follow-up, an additional 9.3% (n = 88) of the total cohort developed perianal disease. Cumulative immunosuppressive and biologic exposure increased over time; biologic use was higher in patients with perianal disease [pLog Rank < 0.001]. The overall rate of perianal surgery was 44.7% (113/253), with a probability of 28.3% (95% CI: 25.4-31.2) after 10 years, 41.0% (95% CI: 37.5-44.5) after 20 years, and 64.1% (95% CI: 59-69.2) after 30 years. There was no statistically significant difference in the probability of first perianal surgery among cohorts A/B/C [Log Rank = 0.594]., Conclusions: The burden of perianal disease and perianal surgery rates were high in this cohort. Therapeutic strategy was accelerated in patients with perianal Crohn's over time with higher exposure to immunosuppressives and biologics. Surgical management of perianal disease remained unchanged amongst the cohorts., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
- Published
- 2024
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7. Pro-inflammatory cytokines stimulate CFTR-dependent anion secretion in pancreatic ductal epithelium.
- Author
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Angyal D, Groeneweg TA, Leung A, Desain M, Dulla K, de Jonge HR, and Bijvelds MJC
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- Swine, Animals, Tumor Necrosis Factor-alpha, Cystic Fibrosis Transmembrane Conductance Regulator, Interleukin-6, Epithelium, Cytokines, Bicarbonates
- Abstract
Background: Loss of CFTR-dependent anion and fluid secretion in the ducts of the exocrine pancreas is thought to contribute to the development of pancreatitis, but little is known about the impact of inflammation on ductal CFTR function. Here we used adult stem cell-derived cell cultures (organoids) obtained from porcine pancreas to evaluate the effects of pro-inflammatory cytokines on CFTR function., Methods: Organoids were cultured from porcine pancreas and used to prepare ductal epithelial monolayers. Monolayers were characterized by immunocytochemistry. Epithelial bicarbonate and chloride secretion, and the effect of IL-1β, IL-6, IFN-γ, and TNF-α on CFTR function was assessed by electrophysiology., Results: Immunolocalization of ductal markers, including CFTR, keratin 7, and zonula occludens 1, demonstrated that organoid-derived cells formed a highly polarized epithelium. Stimulation by secretin or VIP triggered CFTR-dependent anion secretion across epithelial monolayers, whereas purinergic receptor stimulation by UTP, elicited CFTR-independent anion secretion. Most of the anion secretory response was attributable to bicarbonate transport. The combination of IL-1β, IL-6, IFN-γ, and TNF-α markedly enhanced CFTR expression and anion secretion across ductal epithelial monolayers, whereas these cytokines had little effect when tested separately. Although TNF-α triggered apoptotic signaling, epithelial barrier function was not significantly affected by cytokine exposure., Conclusions: Pro-inflammatory cytokines enhance CFTR-dependent anion secretion across pancreatic ductal epithelium. We propose that up-regulation of CFTR in the early stages of the inflammatory response, may serve to promote the removal of pathogenic stimuli from the ductal tree, and limit tissue injury., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
8. Kinetic Role of Reactive Intermediates in Controlling the Formation of Chlorine Dioxide in the Hypochlorous Acid-Chlorite Ion Reaction.
- Author
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Angyal D, Fábián I, and Szabó M
- Abstract
An advanced experimental protocol is reported for studying the kinetics and mechanism of the complex redox reaction between chlorite ion and hypochlorous acid under acidic condition. The formation of ClO
2 is followed directly by the classical two-component stopped-flow method. In sequential stopped-flow experiments, the target reaction is chemically quenched using NaI solution and the concentration of each reactant and product is monitored as a function of time by utilizing the principles of kinetic discrimination. Thus, in contrast to earlier studies, not only the formation of one of the products but the decay of the reactants was also directly followed. This approach provides a firm basis for postulating a detailed mechanism for the interpretation of the experimental results under a variety of conditions. The intimate details of the reaction are explored by simultaneously fitting 78 kinetic traces, i.e., the concentration vs. time profiles of ClO2 - , HOCl, and ClO2 , to an 11-step kinetic model. The most important reaction steps were identified, and it was shown that two reactive intermediates have a pivotal role in the mechanism. While chlorate ion predominantly forms via the reaction of Cl2 O, chlorine dioxide is exclusively produced in reaction steps involving Cl2 O2 . This study leads to clear conclusions on how to control the stoichiometry of the reaction and achieve optimum conditions to produce chlorine dioxide and to reduce the formation of the toxic chlorate ion in practical applications.- Published
- 2023
- Full Text
- View/download PDF
9. Malignant solid tumor associated with hypereosinophilic syndrome
- Author
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Lontai L, Angyal D, Folhoffer A, Istenes I, Szirtes I, and Iliás Á
- Subjects
- Male, Humans, Middle Aged, Leukocytosis pathology, Bone Marrow pathology, Eosinophils, Hypereosinophilic Syndrome diagnosis, Hypereosinophilic Syndrome pathology, Myeloproliferative Disorders
- Abstract
Hypereosinophilic syndrome is characterized by chronic eosinophil overproduction, resulting in multiple organ damages due to eosinophil infiltration and mediator release. According to the etiology, we distinguish between myeloproliferative disorders, parasitic infections, solid tumors, T-cell lymphomas and idiopathic forms. In our case report, the 49-year-old man was hospitalized with weight loss, leg edema and tachycardia. In his laboratory tests increased biliary obstructive parameters as well as extreme leukocytosis and eosinophilia had been highlighted. We started our evaluation with a strong suspicion of hematologic malignancy. The CT scan of the thorax, abdomen and pelvis described hepatosplenomegaly, multiple intrahepatic lesions and an uncertain solitary cystic lesion in the tail of the pancreas with abnormal lymph nodes and pleural fluid. The described CT image and the other clinical parameters were primarily consistent with the manifestation of chronic myeloid leukemia. However, the diagnosis was not confirmed by peripheral blood smear, flow cytometry, bone marrow biopsy or genetic tests. After these results, we continued the assessment towards solid tumor associated leukemoid reaction, core biopsy was performed to verify the liver lesions. The biopsy confirmed the infiltration of a poorly differentiated epithelial tumor as a metastasis of pancreatobiliary carcinoma. To the best of our knowledge, this is the first case report on hypereosinophilic syndrome associated with gastrointestinal solid tumors in the Hungarian medical literature. It draws attention to the differential diagnosis of extreme leukocytosis and eosinophil ratios and by the absence of confirmed hematological disease the importance of early biopsy sampling of solid lesions.
- Published
- 2022
- Full Text
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10. Bicarbonate Transport in Cystic Fibrosis and Pancreatitis.
- Author
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Angyal D, Bijvelds MJC, Bruno MJ, Peppelenbosch MP, and de Jonge HR
- Subjects
- Animals, Biological Transport, Cystic Fibrosis genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Humans, Mutation genetics, Pancreatitis genetics, Bicarbonates metabolism, Cystic Fibrosis metabolism, Pancreatitis metabolism
- Abstract
CFTR, the cystic fibrosis (CF) gene-encoded epithelial anion channel, has a prominent role in driving chloride, bicarbonate and fluid secretion in the ductal cells of the exocrine pancreas. Whereas severe mutations in CFTR cause fibrosis of the pancreas in utero, CFTR mutants with residual function, or CFTR variants with a normal chloride but defective bicarbonate permeability (CFTR
BD ), are associated with an enhanced risk of pancreatitis. Recent studies indicate that CFTR function is not only compromised in genetic but also in selected patients with an acquired form of pancreatitis induced by alcohol, bile salts or smoking. In this review, we summarize recent insights into the mechanism and regulation of CFTR-mediated and modulated bicarbonate secretion in the pancreatic duct, including the role of the osmotic stress/chloride sensor WNK1 and the scaffolding protein IRBIT, and current knowledge about the role of CFTR in genetic and acquired forms of pancreatitis. Furthermore, we discuss the perspectives for CFTR modulator therapy in the treatment of exocrine pancreatic insufficiency and pancreatitis and introduce pancreatic organoids as a promising model system to study CFTR function in the human pancreas, its role in the pathology of pancreatitis and its sensitivity to CFTR modulators on a personalized basis.- Published
- 2021
- Full Text
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