BACKGROUND: Interleukin 40 (IL-40) is a cytokine implicated in malignancies and rheumatic disorders. Its association with fibrotic mediators has been previously described. Since inflammation and fibrosis are hallmarks of systemic sclerosis (SSc), we aimed to analyze the role of IL-40 in SSc. METHODS: IL-40 levels were analyzed in the serum of 90 SSc patients and 75 healthy controls (HCs). IL-40 expression in dermal biopsies from 5 SSc patients and 5 HCs was assessed via immunohistochemistry. IL-40 was analyzed in 39 SSc patients with interstitial lung disease treated with cyclophosphamide (CPA) and in 24 SSc patients with active progressive disease treated with rituximab (RTX). SSc activity was assessed by the European Scleroderma Study Group (ESSG) index. The effect of recombinant IL-40 on peripheral blood mononuclear cells (PBMCs) from 10 SSc patients was determined in vitro. IL-40 was analyzed in 24 individuals at risk of developing SSc (VEDOSS), who were categorized as progressors (n = 11) and nonprogressors (n = 13). RESULTS: IL-40 expression was elevated in the skin of SSc patients compared to HCs, particularly in fibroblasts and immune infiltrates. Serum IL-40 was increased in SSc compared to HCs (p < 0.0001) and was associated with ESSG (r = 0.372, p = 0.0005) and gastrointestinal involvement (p < 0.05). IL-40 correlated with serum IL-8 (r = 0.270, p = 0.019) and TGF-β1 (r = 0.301, p = 0.024) levels. In the CPA and RTX cohort, no significant changes in the serum IL-40 were observed upon treatment. Baseline and changes in IL-40 levels were associated with changes in several clinical parameters. IL-40 was elevated in patients at risk of SSc compared to HCs (p = 0.0003). No significant changes were observed in progressors vs. nonprogressors; however, IL-40 was associated with capillaroscopy findings (p < 0.05). IL-40 induced the upregulation of IL-6 (p = 0.002), MCP-1 (p = 0.002) and IL-10 (p = 0.002) in PBMCs from SSc patients in vitro. CONCLUSIONS: IL-40 was upregulated in the skin and serum of SSc patients and was associated with disease activity, gastrointestinal involvement and fibrotic mediators. Our in vitro findings indicate that IL-40 might be involved in the immune response and fibrotic processes in SSc.

• Klíčová slova
• Biomarkers, Interleukin 40, Systemic sclerosis,
• MeSH
• dospělí MeSH
• fibróza MeSH
• gastrointestinální nemoci * krev   imunologie   MeSH
• imunohistochemie MeSH
• kůže patologie   metabolismus   MeSH
• leukocyty mononukleární metabolismus   účinky léků   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• systémová sklerodermie * krev   imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Neurogastroenterology, a rapidly evolving field, investigates the intricate interactions between the nervous system and the organs of the gastrointestinal tract. This review offers a comprehensive summary of innervation of the gastrointestinal tract, focusing on both extrinsic and intrinsic components. Extrinsic innervation involves the autonomic nervous system, with sympathetic and parasympathetic fibers controlling various digestive functions, while intrinsic innervation, represented by the enteric nervous system, operates largely independently, orchestrating complex processes such as motility, secretion, and immune responses. Recent advances highlight the crucial role of the enteric nervous system, often referred to as the second brain, in maintaining gastrointestinal health and its involvement in various pathologies. The text also provides a basic overview of the pathophysiology of achalasia, Chagas disease, gastroesophageal reflux disease, gastroparesis, diabetic gastroenteropathy, irritable bowel syndrome, chronic intestinal pseudo-obstruction, and Hirschsprung's disease, which are conditions in which innervation of the gastrointestinal tract is more or less affected. The insights provided could pave the way for new interventions, offering hope for patients suffering from related conditions.

• Klíčová slova
• Enteric nervous system, Gastrointestinal disorders, Gastrointestinal innervation, Neurogastroenterology,
• MeSH
• gastrointestinální nemoci * patofyziologie   MeSH
• gastrointestinální trakt * inervace   patofyziologie   fyziologie   MeSH
• lidé MeSH
• střevní nervový systém * fyziologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Upper gastrointestinal bleeding is a relatively common but potentially fatal medical emergency. Many medical disciplines are involved in the diagnosis and treat-ment of this condition. The patients are usually admitted primarily to surgical wards and the attending surgeon is responsible for management of the patients. Surgery may also be an ultimatum refugium when less invasive treatments fail. OBJECTIVE: The aim of this study is to review the current practice in the management of patients with upper gastrointestinal bleeding based on a literature review and our own experience in the management of these patients. CONCLUSIONS: Upper gastrointestinal bleeding is a relatively common emergency. It is a hemorrhage whose the source is proximal to the ligament of Treitz. The diagnosis and treatment require a multidisciplinary approach. Today, endoscopy plays a key role in the diagnosis and treatment. The correct timing of each step is essential for patient survival. This article provides a clear summary of the current recommended procedures from initial resuscitation, fluid therapy, administration of blood substitutes, ad-justment of coagulation parameters in patients on anticoagulant and antithrombotic therapy, endoscopic diagnostic and therapeutic options, and procedures for recurrent bleeding, including angiointervention and surgical treatment, with a main focus on nonvariceal bleeding.

• Klíčová slova
• endoscopy, peptic ulcer, proton pump inhibitors, upper gastrointestinal bleeding,
• MeSH
• gastrointestinální krvácení * terapie   diagnóza   etiologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Mutations in the Sterile alpha motif domain containing 9 (SAMD9) gene have been described in patients with severe multisystem disorder, MIRAGE syndrome, but also in patients with bone marrow (BM) failure in the absence of other systemic symptoms. The role of hematopoietic stem cell transplantation (HSCT) in the management of the disease is still unclear. Here, we present a patient with a novel mutation in SAMD9 (c.2471 G>A, p.R824Q), manifesting with prominent gastrointestinal tract involvement and immunodeficiency, but without any sign of adrenal insufficiency typical for MIRAGE syndrome. He suffered from severe CMV (cytomegalovirus) infection at 3 months of age, with a delayed development of T lymphocyte functional response against CMV, profound T cell activation, significantly reduced B lymphocyte counts and impaired lymphocyte proliferative response. Cultured T cells displayed slightly lower calcium flux and decreased survival. At the age of 6 months, he developed severe neutropenia requiring G-CSF administration, and despite only mild morphological and immunophenotypical disturbances in the BM, 78% of the BM cells showed monosomy 7 at the age of 18 months. Surprisingly, T cell proliferation after CD3 stimulation and apoptosis of the cells normalized during the follow-up, possibly reflecting the gradual development of monosomy 7. Among other prominent symptoms, he had difficulty swallowing, requiring percutaneous endoscopic gastrostomy (PEG), frequent gastrointestinal infections, and perianal erosions. He suffered from repeated infections and periodic recurring fevers with the elevation of inflammatory markers. At 26 months of age, he underwent HSCT that significantly improved hematological and immunological laboratory parameters. Nevertheless, he continued to suffer from other conditions, and subsequently, he died at day 440 post-transplant due to sepsis. Pathogenicity of this novel SAMD9 mutation was confirmed experimentally. Expression of mutant SAMD9 caused a significant decrease in proliferation and increase in cell death of the transfected cells. Conclusion: We describe a novel SAMD9 mutation in a patient with prominent gastrointestinal and immunological symptoms but without adrenal hypoplasia. Thus, SAMD9 mutations should be considered as cause of enteropathy in pediatric patients. The insufficient therapeutic outcome of transplantation further questions the role of HSCT in the management of patients with SAMD9 mutations and multisystem involvement.

• Klíčová slova
• MIRAGE, SAMD9, cytomegalovirus infection, dysphagia, gastrointestinal disorder, hematopoietic stem cell transplantation, immunodeficiency, neutropenia,
• MeSH
• cytomegalovirové infekce genetika   imunologie   MeSH
• kojenec MeSH
• lidé MeSH
• mutace MeSH
• neutropenie genetika   MeSH
• předškolní dítě MeSH
• protein Smad8 genetika   MeSH
• syndromy imunologické nedostatečnosti genetika   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protein Smad8 MeSH
• SMAD9 protein, human MeSH Prohlížeč

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare tumors of the digestive tract that have seen significant advances in diagnosis and treatment in recent years. A key breakthrough was the identification of c-KIT and PDGFRA gene mutations, which enabled the introduction of targeted therapies. The cornerstone of the treatment for localized disease is radical (R0) surgical resection, with adjuvant imatinib recommended for patients at high risk of recurrence. In advanced or metastatic disease, standard care involves sequential treatment with tyrosine kinase inhibitors, including imatinib, sunitinib, and regorafenib. A major advance is represented by ripretinib, which effectively inhibits a broad spectrum of KIT and PDGFRA mutations and has been shown to prolong survival in patients with advanced GIST refractory to current options of systemic therapy. The expanding range of targeted therapies, such as avapritinib for the PDGFRA D842V mutation, underscores the importance of molecular profiling in guiding optimal treatment strategies. AIM: This review aims to summarize current knowledge on the diagnosis and treatment of GIST, with a focus on the role of molecular-genetic profiling, the therapeutic value of individual tyrosine kinase inhibitors, and emerging options for advanced disease, with particular emphasis on ripretinib.

• Klíčová slova
• GIST, avapritinib, chronic myeloid leukemia, imatinib, regorafenib, ripretinib, sunitinib, systemic treatment,
• MeSH
• cílená molekulární terapie MeSH
• gastrointestinální nádory * terapie   diagnóza   genetika   MeSH
• gastrointestinální stromální tumory * diagnóza   terapie   genetika   farmakoterapie   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• protinádorové látky terapeutické užití   MeSH
• protoonkogenní proteiny c-kit genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• inhibitory proteinkinas MeSH
• protinádorové látky MeSH
• protoonkogenní proteiny c-kit MeSH

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology present a list of key performance measures for endoscopy services. We recommend that these performance measures be adopted by all endoscopy services across Europe. The measures include those related to the leadership, organization, and delivery of the service, as well as those associated with the patient journey. Each measure includes a recommendation for a minimum and target standard for endoscopy services to achieve. We recommend that all stakeholders in endoscopy take note of these ESGE endoscopy services performance measures to accelerate their adoption and implementation. Stakeholders include patients and their advocacy groups; service leaders; staff, including endoscopists; professional societies; payers; and regulators.

• MeSH
• bezpečnost normy   MeSH
• gastrointestinální endoskopie škodlivé účinky   normy   MeSH
• informovaný souhlas pacienta normy   MeSH
• komfort pacienta normy   MeSH
• konziliární vyšetření a konzultace normy   MeSH
• lidé MeSH
• pracovní síly normy   MeSH
• soukromí MeSH
• ukazatele kvality zdravotní péče * MeSH
• vůdcovství MeSH
• výběr pacientů MeSH
• vzdělávání pacientů jako téma normy   MeSH
• zapojení pacienta MeSH
• zdravotnická zařízení normy   MeSH
• zdravotnické prostředky normy   MeSH
• zlepšení kvality * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH

• MeSH
• Burkittův lymfom mortalita   chirurgie   MeSH
• dítě MeSH
• gastrointestinální nádory mortalita   chirurgie   MeSH
• lidé MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Ghana MeSH

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal (GI) tract. They are believed to originate from the interstitial cells of Cajal (ICCs) or from the precursors of ICCs. Most GISTs show an activating mutation in either the c-kit or platelet-derived growth factor receptor alpha (PDGFRA) gene. Tumor size, mitotic rate, and anatomic location correlate with potential malignancy and recurrence rate. PATIENTS AND METHODS: A total of 12 patients were diagnosed to have GIST based on histology or immunohistochemistry of a biopsy or resection specimen obtained from the GI tract in the 2004-2009 period. The material was obtained using retrospective data collection. RESULTS: The male to female ratio was 1:1; mean age 68.2 +/- 7.0 years. The stomach was involved in seven cases (58.3%), the small intestine in four (33.3%), and from a lymph node without the finding of a primary tumor was material obtained in one case (8.3%). The course was asymptomatic in four patients (incidental findings). All 12 patients had surgery; a curative procedure was undertaken in 11 patients. A spindle-cell pattern was present in 8/12 of the specimens examined, epithelioid in 2/12 and a mixed pattern in two cases. Ten specimens were CD117 positive (83.3%), two were negative; all 10 examined specimens exhibited CD34 positivity while two were not examined. The findings were classified as GISTs with a high risk of progressive disease in three patients, with a moderate risk in one patient, and a low or very low degree of malignancy in five patients. GISTs smaller than 2 cm in three patients were regarded as essentially benign. All patients with low and very low risk of progressive disease survive for 1 to 5 years free of signs. Of the three patients with high degree of malignancy, one died within one year for dissemination, the two remaining patients survive for over two years and six month postoperatively on therapy with tyrosine kinase inhibitors. CONCLUSION: Tumors classified as GISTs with low and very low risk of progression are associated with a very good prognosis, with virtually all patients surviving 5 years. In patients with high risk or progressive diseases, the prognosis of 5-year survival is much poorer. The main therapeutic option is surgical removal of the tumor (resection or broad excision). Agents showing promise for patients with malignant forms of GISTs are tyrosine kinase receptor inhibitors. Although imatinib is currently used as a first line treatment for all patients with metastatic or unresectable GISTs, it is likely that this treatment will change in the future based on the underlying mutational status.

• MeSH
• adjuvantní chemoterapie MeSH
• benzamidy MeSH
• délka pobytu MeSH
• gastrointestinální nádory farmakoterapie   metabolismus   mortalita   patologie   chirurgie   MeSH
• gastrointestinální stromální tumory farmakoterapie   metabolismus   mortalita   patologie   chirurgie   MeSH
• imatinib mesylát MeSH
• imunohistochemie MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• piperaziny terapeutické užití   MeSH
• progrese nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• pyrimidiny terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzamidy MeSH
• imatinib mesylát MeSH
• inhibitory proteinkinas MeSH
• piperaziny MeSH
• protinádorové látky MeSH
• pyrimidiny MeSH

Food proteins and their peptides play a significant role in the important biological processes and physiological functions of the body. The peptides show diverse biological benefits ranging from anticancer to antihypertensive, anti-obesity, and immunomodulatory, among others. In this review, an overview of food protein digestion in the gastrointestinal tract and the mechanisms involved was presented. As some proteins remain resistant and undigested, the multifarious factors (e.g. protein type and structure, microbial composition, pH levels and redox potential, host factors, etc.) affecting their colonic fermentation, the derived peptides, and amino acids that evade intestinal digestion are thus considered. The section that follows focuses on the mechanisms of the peptides with anticancer, antihypertensive, anti-obesity, and immunomodulatory effects. As further considerations were made, it is concluded that clinical studies targeting a clear understanding of the gastrointestinal stability, bioavailability, and safety of food-based peptides are still warranted.

• Klíčová slova
• Bioactive peptides, Food proteins, Food-based peptides, Gastrointestinal digestion, Mechanisms,
• MeSH
• antihypertenziva * farmakologie   MeSH
• biologická dostupnost MeSH
• dietní proteiny * metabolismus   MeSH
• gastrointestinální trakt metabolismus   MeSH
• imunologické faktory farmakologie   MeSH
• imunomodulační látky farmakologie   MeSH
• látky proti obezitě * farmakologie   MeSH
• lidé MeSH
• peptidy * farmakologie   MeSH
• protinádorové látky * farmakologie   MeSH
• střevní mikroflóra účinky léků   MeSH
• trávení * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antihypertenziva * MeSH
• dietní proteiny * MeSH
• imunologické faktory MeSH
• imunomodulační látky MeSH
• látky proti obezitě * MeSH
• peptidy * MeSH
• protinádorové látky * MeSH

Gastrointestinal (GI) cancers are common in all parts of the world. Effective prevention and early detection of GI cancers are not universally implemented. Therefore, it must be anticipated that the incidence and the mortality of GI cancers will remain high within the next decades. The European Society for Medical Oncology (ESMO) Gastrointestinal Cancer Faculty aims to increase the skills of medical oncologists and other disciplines involved in treating GI malignancies. We aimed to increase the survival chances for patients with GI cancers, augment their quality of life and enable successful return to normal social and professional life during the period of survivorship. ESMO also aims to decrease the economic burden of GI cancer in our societies and national healthcare systems. Therefore, the ESMO Gastrointestinal Cancer Faculty initiated a consensus process based on the Delphi method to identify the most important educational needs of physicians who are concerned with GI malignancies. This paper summarises the process and its results and outlines the mission of ESMO in education.

• Klíčová slova
• clinical training, decision making, education, gastrointestinal cancer, multidisciplinarity,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH