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BACKGROUND: Gelsectan® is a formulation of xyloglucan (XG), pea protein, grape seed extract (PPGS) and xylo-oligosaccharides (XOS). Our aim was to examine the effect of Gelsectan® on rectal sensitivity in an animal model, abdominal pain in irritable bowel syndrome with diarrhoea (IBS-D) subjects and intestinal permeability in both conditions. METHODS: Animals: Wistar rats received gavage with XOS, XG + PPGS or XG + PPGS + XOS, as a single dose or for 7 days before a partial restraint stress (PRS). Visceromotor response to rectal distension and total gut paracellular permeability to 51Cr-EDTA were assessed. Humans: IBS-D and control patients were involved. After initial colonoscopy with biopsy sampling Gelsectan® was administered to IBS-D patients for 12 weeks. Stool count and pain scores were documented. After treatment, colonoscopy was repeated. The permeability of biopsy samples was measured in Ussing-chambers. Adherent mucus layer, Muc-2 expression as well as TNFα, Interferon IFNγ were evaluated by histology/immunohistochemistry and ELISA assays, respectively. RESULTS: Animal studies: In control rats, PRS significantly increased visceromotor response as well as gut paracellular permeability. Single dose administration of XG + PPGS + XOS failed to reverse PRS, but 7 days of oral treatment reversed PRS-induced rectal hypersensitivity and gut hyperpermeability. Human studies: Gelsectan® treatment significantly reduced and abdominal pain. Intestinal permeability in IBS-D patients was elevated compared with controls, Gelsectan® restored permeability in the ascendent colon. Periodic acid-Schiff-stained mucus layer was significantly thinner in IBS-D patients compared with controls, In both segments, mucus thickness and the proportion of Muc-2 positive cells were not affected by Gelsectan® treatment. IFNγ tissue level in the sigmoid colon shows modest mucosal inflammation in IBS-D. CONCLUSIONS: Gelsectan® prevented rectal hypersensitivity in rats, abdominal pain in human and intestinal hyperpermeability in rat and human studies respectively. These effects involve restoration of gut permeability. Based on this translational study, Gelsectan® can be considered as an effective therapy for IBS-D symptoms.
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In this case of a young female, ulcerations around the ileostoma appeared after colectomy and were thought to be due to surgical site infection. Given inadequate treatment, an extensive defect of the abdominal wall developed. Peristomal pyoderma gangrenosum was diagnosed, for which ustekinumab was given successfully.
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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.
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Doença de Crohn , Ustekinumab , Humanos , Doença de Crohn/tratamento farmacológico , Ustekinumab/uso terapêutico , Ustekinumab/efeitos adversos , Masculino , Feminino , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Estudos Prospectivos , Seguimentos , Indução de Remissão , HungriaRESUMO
BACKGROUND Computer-aided design (CAD) has been used in the Nuss procedure to determine the bar length and shape. Despite computer aid, the shape and design remain quite intuitive. We tested a new algorithm to determine the optimal bar shape. MATERIAL AND METHODS The normal sterno-vertebral distance was defined on computed tomography (CT) scans of patients without pectus excavatum (PEx) at the same level where the deepest depression was found on CT scans of 97 patients with PEx. Four points were marked on the CT scan of 60 patients with PEx at the deepest deformity: P1: edge of the vertebra; P2: edge of the deformity; P3: the expected contact point of the bar and the rib; and P4: the expected end of the bar. The algorithm generated 3 circles upon these points, and the fusion of the arcs drew the line of the ideal bar. Corrected and normal sterno-vertebral distance values were compared with the Mann-Whitney U test. Ten bars were bent manually guided by a 1: 1 printout of the designed bar and were implanted in 10 adolescents. RESULTS The shortest sterno-vertebral distance was 3 cm below the intermammillary line in PEx patients. The normal mean sterno-vertebral distance at this level was 10.16±1.35 cm in non-PEx patients. The mean virtually corrected sterno-vertebral distance was 10.28±1.27 cm. No significant difference was found (P=0.44). The bars were seamless and were successfully implanted. No bar needed adjustment, the operation time was shorter, and the patient satisfaction score was 9.4/10. CONCLUSIONS With our new algorithm, an optimal Nuss bar can be designed.
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Algoritmos , Desenho Assistido por Computador , Tórax em Funil , Tomografia Computadorizada por Raios X , Humanos , Tórax em Funil/cirurgia , Tórax em Funil/diagnóstico por imagem , Adolescente , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Criança , Esterno/diagnóstico por imagemRESUMO
Complex perianal fistula is a common complication of Crohn's disease (CD) which leads to negative impact on patient's quality of life. Successful management of the disease requires a multidisciplinary approach, including a gastroenterologist and a colorectal surgeon, applying combined surgical and medical therapy. One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.Darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Following approval of darvadstrocel, the INSPIRE registry is being conducted in order to evaluate long-term safety and effectiveness of the drug on a large, heterogenous population.An online expert meeting was held from March 20 to March 30, 2023, which provided relevant insights into the decision-making process regarding seton use and obtained feedback on the first experiences with darvadstrocel. The aim of this article is to present the perspectives from gastroenterologists and colorectal surgeons practicing in Czechia, Hungary, Israel, Lithuania, Serbia, and Slovenia in topics such as diagnosis and treatment options for patients with complex Crohn's perianal fistulas (CPF), specifically focusing on the use of setons and darvadstrocel.During this virtual session, unavailability of comprehensive data on safety and efficacy of available treatment procedures was emphasized as an important obstacle towards development of standardized recommendations and improvement of outcomes in treatment of (CPF). Furthermore, achieving consensus in seton use, duration of its placement, and frequency of change is recognized as one of CPF treatments major challenges. Despite these issues, it is important to promote better understanding and treatment of complex perianal fistulas in order to improve the quality of life of those affected by this condition.
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BACKGROUND: Choosing an optimal post-polypectomy management strategy of malignant colorectal polyps is challenging, and evidence regarding a surveillance-only strategy is limited. AIM: To evaluate long-term outcomes after endoscopic removal of malignant colorectal polyps. METHODS: A single-center retrospective cohort study was conducted to evaluate outcomes after endoscopic removal of malignant colorectal polyps between 2010 and 2020. Residual disease rate and nodal metastases after secondary surgery and local and distant recurrence rate for those with at least 1 year of follow-up were investigated. Event rates for categorical variables and means for continuous variables with 95% confidence intervals were calculated, and Fisher's exact test and Mann-Whitney test were performed. Potential risk factors of adverse outcomes were determined with univariate and multivariate logistic regression models. RESULTS: In total, 135 lesions (mean size: 22.1 mm; location: 42% rectal) from 129 patients (mean age: 67.7 years; 56% male) were enrolled. The proportion of pedunculated and non-pedunculated lesions was similar, with en bloc resection in 82% and 47% of lesions, respectively. Tumor differentiation, distance from resection margins, depth of submucosal invasion, lymphovascular invasion, and budding were reported at 89.6%, 45.2%, 58.5%, 31.9%, and 25.2%, respectively. Residual tumor was found in 10 patients, and nodal metastasis was found in 4 of 41 patients who underwent secondary surgical resection. Univariate analysis identified piecemeal resection as a risk factor for residual malignancy (odds ratio: 1.74; P = 0.042). At least 1 year of follow-up was available for 117 lesions from 111 patients (mean follow-up period: 5.59 years). Overall, 54%, 30%, 30%, 11%, and 16% of patients presented at the 1-year, 3-year, 5-year, 7-year, and 9-10-year surveillance examinations. Adverse outcomes occurred in 9.0% (local recurrence and dissemination in 4 patients and 9 patients, respectively), with no difference between patients undergoing secondary surgery and surveillance only. CONCLUSION: Reporting of histological features and adherence to surveillance colonoscopy needs improvement. Long-term adverse outcome rates might be higher than previously reported, irrespective of whether secondary surgery was performed.
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Diagnostic imaging techniques provide a new aspect of the ante-mortem and post-mortem diagnostics in fish medicine. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) can provide more information about the internal organs and pathognomic lesions. The authors used diagnostic imaging techniques to evaluate and describe the neoplastic malformation in a 3-year-old female rainbow trout (Oncorhynchus mykiss). The fish was examined with Siemens Somatom Definition AS + CT scanner and Siemens Biograph mMR scanner. The animal was lethargic and showed anorectic signs and muscular dystrophy. During the post-mortem investigation, histopathology and immunohistochemistry were also performed allowing us to identify the neoplasms. The results showed a large soft tissue mass in the first mid-intestine segment, which proved to be an adenocarcinoma. This subsequently led to digestion problems and absorption disorders. Immunohistochemically, neoplastic cells of carcinoma revealed E-cadherin and pancytokeratin positivity. This is the first study to report the use of MRI and CT for studying gastrointestinal adenocarcinoma in rainbow trout.
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Adenocarcinoma , Doenças dos Peixes , Imageamento por Ressonância Magnética , Oncorhynchus mykiss , Animais , Adenocarcinoma/veterinária , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Feminino , Doenças dos Peixes/diagnóstico por imagem , Doenças dos Peixes/patologia , Imageamento por Ressonância Magnética/veterinária , Tomografia Computadorizada por Raios X/veterinária , Ultrassonografia/veterináriaRESUMO
A preliminary clinical report of implant placements with 2 immersive reality technologies is described: augmented reality with head mounted display and mixed reality with a tablet PC. Both immersive realities are promising and could facilitate innovative dental applications. However, mixed reality requires further development for clinical optimization.
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Background: Different endoscopic scoring systems for assessing ulcerative colitis (UC) severity are available. However, most of them are not correlated with disease extent. Objectives: Our study aimed to compare the predictive value of the PanMay score versus the endoscopic Mayo (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Dublin score in predicting long-term outcomes of UC. Design: This retrospective study enrolled consecutive UC patients who underwent colonoscopy before at least a 3-year follow-up. Methods: The PanMayo, MES, UCEIS, and Dublin scores and the baseline clinical and demographic characteristics of the participants were assessed. Endpoints were disease flare that required novel biological therapy, colectomy, and hospitalization. Patients were stratified using baseline clinical activity. Results: Approximately 62.8% of the 250 enrolled patients were in clinical remission. In these patients, the PanMayo, MES, and Dublin scores were positively associated with the risk of clinical flare. The MES score increased with clinical flare. The PanMayo score (>12 points), but not the MES score, was associated with the need for novel biological initiation and biological escalation. Furthermore, the Dublin and UCEIS scores of patients in remission who need novel biological treatment had a similar trend. Colectomy risk was associated with PanMayo and Dublin scores. Conclusion: The combined endoscopic assessment of disease extent and severity can be more accurate in predicting outcomes among patients with UC. PanMayo score can be utilized in addition to the existing scoring systems, thereby leading to a more accurate examination. Summary: UC endoscopic scores do not assess extension. Our study aimed to analyze the predictive value of the PanMayo score. Based on 250 patients, results showed that the long-term disease outcomes of UC could be predicted with the PanMayo score more accurately.
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INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.
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Produtos Biológicos , Colectomia , Colite Ulcerativa , Piperidinas , Complicações Pós-Operatórias , Pirimidinas , Humanos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/tratamento farmacológico , Masculino , Feminino , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Readmissão do Paciente/estatística & dados numéricos , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Tromboembolia Venosa/epidemiologia , Reoperação/estatística & dados numéricos , Infecção da Ferida Cirúrgica/epidemiologia , IdosoRESUMO
Forest damage has become more frequent in Hungary in the last decades, and remote sensing offers a powerful tool for monitoring them rapidly and cost-effectively. A combined approach was developed to utilise high-resolution ESA Sentinel-2 satellite imagery and Google Earth Engine cloud computing and field-based forest inventory data. Maps and charts were derived from vegetation indices (NDVI and ZâNDVI) of satellite images to detect forest disturbances in the Hungarian study site for the period of 2017-2020. The NDVI maps were classified to reveal forest disturbances, and the cloud-based method successfully showed drought and frost damage in the oak-dominated Nagyerdo forest of Debrecen. Differences in the reactions to damage between tree species were visible on the index maps; therefore, a random forest machine learning classifier was applied to show the spatial distribution of dominant species. An accuracy assessment was accomplished with confusion matrices that compared classified index maps to field-surveyed data, demonstrating 99.1% producer, 71% user, and 71% total accuracies for forest damage and 81.9% for tree species. Based on the results of this study and the resilience of Google Earth Engine, the presented method has the potential to be extended to monitor all of Hungary in a faster, more accurate way using systematically collected field-data, the latest satellite imagery, and artificial intelligence.
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Concomitant medications may alter the effect of biological therapy in inflammatory bowel disease. The aim was to investigate the effect of proton pump inhibitors on remission rates in patients with inflammatory bowel disease treated with the gut-selective vedolizumab. Patients from the Hungarian nationwide, multicenter vedolizumab cohort were selected for post hoc analysis. Primary outcomes were the assessment of clinical response and endoscopic and clinical remission at weeks 14 and 54. Secondary outcomes were the evaluation of the combined effect of concomitant steroid therapy and other factors, such as smoking, on remission. A total of 108 patients were identified with proton pump inhibitor data from 240 patients in the original cohort. Patients on steroids without proton pump inhibitors were more likely to have a clinical response at week 14 than patients on concomitant PPI (95% vs. 67%, p = 0.005). Non-smokers with IBD treated with VDZ were more likely to develop a clinical response at week 14 than smokers, particularly those not receiving PPI compared with patients on co-administered PPI therapy (81% vs. 53%, p = 0.041, and 92% vs. 74%, p = 0.029, respectively). We found that the use of PPIs in patients treated with VDZ may impair the achievement of response in certain subgroups. Unnecessary PPI prescriptions should be avoided.
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BACKGROUND AND AIMS: Crohn's disease [CD] and ulcerative colitis [UC] require lifelong treatment and patient monitoring. Current biomarkers have several limitations; therefore, there is an unmet need to identify novel biomarkers in inflammatory bowel disease [IBD]. Previously, the role of plasminogen activator inhibitor 1 [PAI-1] was established in the pathogenesis of IBD and suggested as a potential biomarker. Therefore, we aimed to comprehensively analyse the selectivity of PAI-1 in IBD, its correlation with disease activity, and its potential to predict therapeutic response. METHODS: Blood, colon biopsy, organoid cultures [OC], and faecal samples were used from active and inactive IBD patients and control subjects. Serpin E1 gene expressions and PAI-1 protein levels and localisation in serum, biopsy, and faecal samples were evaluated by qRT-PCR, ELISA, and immunostaining, respectively. RESULTS: The study population comprised 132 IBD patients [56 CD and 76 UC] and 40 non-IBD patients. We demonstrated that the serum, mucosal, and faecal PAI-1 concentrations are elevated in IBD patients, showing clinical and endoscopic activity. In responders [decrease of eMayoâ ≥3 in UC; or SES-CDâ â 50% in CD], the initial PAI-1 level decreased significantly upon successful therapy. OCs derived from active IBD patients produced higher concentrations of PAI-1 than the controls, suggesting that epithelial cells could be a source of PAI-1. Moreover, faecal PAI-1 selectively increases in active IBD but not in other organic gastrointestinal diseases. CONCLUSIONS: The serum, mucosal, and faecal PAI-1 concentration correlates with disease activity and therapeutic response in IBD, suggesting that PAI-1 could be used as a novel, non-invasive, disease-specific, faecal biomarker in patient follow-up.
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Colite Ulcerativa , Doença de Crohn , Doenças do Esôfago , Inibidor 1 de Ativador de Plasminogênio , Humanos , Biomarcadores , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Inibidor 1 de Ativador de Plasminogênio/análise , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Fezes/químicaRESUMO
BACKGROUND: The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk. METHODS: A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis. RESULTS: In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%. CONCLUSIONS: This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.