• Publikační typ
• časopisecké články MeSH
• tisková chyba MeSH

Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.

• Klíčová slova
• MYO5B, PFIC, congenital diarrheal diseases, enteropathy, genotype–phenotype correlation, lack of protein, microvillus inclusion disease, myosin Vb, progressive familial intrahepatic cholestasis, tail domain,
• Publikační typ
• časopisecké články MeSH

BACKGROUND & AIMS: A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management. METHODS: A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence. RESULTS: Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density. CONCLUSIONS: These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk.

• Klíčová slova
• ASCA, Complications, Growth Impairment, NOD2/CARD15, Polymorphism, Prognostic Factors, Serology, Structuring or Penetrating Disease,
• MeSH
• Crohnova nemoc diagnóza   terapie   MeSH
• dítě MeSH
• hodnocení výsledků zdravotní péče MeSH
• kojenec MeSH
• konsensus MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• prediktivní hodnota testů MeSH
• předškolní dítě MeSH
• prognóza MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH

BACKGROUND & AIMS: A better understanding of prognostic factors in ulcerative colitis (UC) could improve patient management and reduce complications. We aimed to identify evidence-based predictors for outcomes in pediatric UC, which may be used to optimize treatment algorithms. METHODS: Potential outcomes worthy of prediction in UC were determined by surveying 202 experts in pediatric UC. A systematic review of the literature, with selected meta-analysis, was performed to identify studies that investigated predictors for these outcomes. Multiple national and international meetings were held to reach consensus on evidence-based statements. RESULTS: Consensus was reached on 31 statements regarding predictors of colectomy, acute severe colitis (ASC), chronically active pediatric UC, cancer and mortality. At diagnosis, disease extent (6 studies, N = 627; P = .035), Pediatric Ulcerative Colitis Activity Index score (4 studies, n = 318; P < .001), hemoglobin, hematocrit, and albumin may predict colectomy. In addition, family history of UC (2 studies, n = 557; P = .0004), extraintestinal manifestations (4 studies, n = 526; P = .048), and disease extension over time may predict colectomy, whereas primary sclerosing cholangitis (PSC) may be protective. Acute severe colitis may be predicted by disease severity at onset and hypoalbuminemia. Higher Pediatric Ulcerative Colitis Activity Index score and C-reactive protein on days 3 and 5 of hospital admission predict failure of intravenous steroids. Risk factors for malignancy included concomitant diagnosis of primary sclerosing cholangitis, longstanding colitis (>10 years), male sex, and younger age at diagnosis. CONCLUSIONS: These evidence-based consensus statements offer predictions to be considered for a personalized medicine approach in treating pediatric UC.

• Klíčová slova
• Acute Severe Colitis, Cancer, Colectomy, Mortality, Pediatric Ulcerative Colitis, Prediction, Prognostic Factors,
• MeSH
• dítě MeSH
• hodnocení výsledků zdravotní péče MeSH
• kojenec MeSH
• kolektomie MeSH
• konsensus MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• prediktivní hodnota testů MeSH
• předškolní dítě MeSH
• prognóza MeSH
• ulcerózní kolitida diagnóza   terapie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH

OBJECTIVE: We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn's disease [CD]. METHODS: We formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained. RESULTS: We established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone. CONCLUSIONS: We present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.

• Klíčová slova
• Crohn’s disease/therapy, Practice guideline, algorithms, child,
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Despite existence of international guidelines for diagnosis and management of inflammatory bowel diseases (IBD) in children, there might be differences in the clinical approach. METHODS: A survey on clinical practice in paediatric IBD was performed among members of the ESPGHAN Porto IBD working group and interest group, PIBD-NET, and IBD networks in Canada and German-speaking countries (CIDsCANN, GPGE), using a web-based questionnaire. Responses to 63 questions from 106 paediatric IBD centres were collected. RESULTS: Eighty-four percentage of centres reported to fulfil the revised Porto criteria in the majority of patients. In luminal Crohn disease (CD), exclusive enteral nutrition is used as a first-line induction therapy and immunomodulators (IMM) are used since diagnosis in the majority of patients. Infliximab (IFX) is mostly considered as first-line biological. Sixty percentage of centres have experience with vedolizumab and/or ustekinumab and 40% use biosimilars. In the majority of ulcerative colitis (UC) patients 5-aminosalicylates are continued as concomitant therapy to IMM (usually azathioprine [AZA]/6-MP). After ileocaecal resection (ICR) in CD patients without postoperative residual disease, AZA monotherapy is the preferred treatment. CONCLUSIONS: A majority of centres follows both the Porto diagnostic criteria as well as paediatric (ESPGHAN/ECCO) guidelines on medical and surgical IBD management. This reflects the value of international societal guidelines. However, potentially desirable answers might have been given instead of what is true daily practice, and the most highly motivated people might have answered, leading to some bias.

• MeSH
• biosimilární léčivé přípravky terapeutické užití   MeSH
• chirurgie trávicího traktu metody   normy   statistika a číselné údaje   MeSH
• Crohnova nemoc diagnóza   terapie   MeSH
• dítě MeSH
• dodržování směrnic statistika a číselné údaje   MeSH
• gastroenterologie metody   normy   statistika a číselné údaje   MeSH
• gastrointestinální látky terapeutické užití   MeSH
• idiopatické střevní záněty diagnóza   terapie   MeSH
• imunologické faktory terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• lékařská praxe - způsoby provádění statistika a číselné údaje   MeSH
• lidé MeSH
• mladiství MeSH
• pediatrie metody   normy   statistika a číselné údaje   MeSH
• průzkumy zdravotní péče MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• ulcerózní kolitida diagnóza   terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Kanada MeSH
• Německo MeSH
• Názvy látek
• biosimilární léčivé přípravky MeSH
• gastrointestinální látky MeSH
• imunologické faktory MeSH
• infliximab MeSH

BACKGROUND AND AIMS: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. METHODS: A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. RESULTS: Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. CONCLUSIONS: Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.

• Klíčová slova
• Genetics and molecular epidemiology, TNGS, VEO-IBD, monogenic disorders, paediatrics,
• MeSH
• dítě MeSH
• idiopatické střevní záněty diagnóza   etiologie   terapie   MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• prediktivní hodnota testů MeSH
• předškolní dítě MeSH
• věk při počátku nemoci MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. RESULTS: These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. CONCLUSIONS: These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.

• MeSH
• ambulantní péče normy   MeSH
• dítě MeSH
• fyziologie výživy dětí MeSH
• lidé MeSH
• společnosti lékařské MeSH
• ulcerózní kolitida diagnóza   terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND AND AIM: Acute severe colitis (ASC) is one of the few emergencies in pediatric gastroenterology. Tight monitoring and timely medical and surgical interventions may improve outcomes and minimize morbidity and mortality. We aimed to standardize daily treatment of ASC in children through detailed recommendations and practice points which are based on a systematic review of the literature and consensus of experts. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Fifteen predefined questions were addressed by working subgroups. An iterative consensus process, including 2 face-to-face meetings, was followed by voting of the national representatives of ECCO and all members of the Paediatric Inflammatory Bowel Disease (IBD) Porto group of ESPGHAN (43 voting experts). RESULTS: A total of 24 recommendations and 43 practice points were endorsed with a consensus rate of at least 91% regarding diagnosis, monitoring, and management of ASC in children. A summary flowchart is presented based on daily scoring of the Paediatric Ulcerative Colitis Activity Index. Several topics have been altered since the previous 2011 guidelines and from those published in adults. DISCUSSION: These guidelines standardize the management of ASC in children in an attempt to optimize outcomes of this intensive clinical scenario.

• MeSH
• dítě MeSH
• fyziologie výživy dětí MeSH
• lidé MeSH
• společnosti lékařské MeSH
• stupeň závažnosti nemoci MeSH
• ulcerózní kolitida diagnóza   terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Evropa MeSH

The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.

• MeSH
• adjuvantní chemoterapie MeSH
• anastomóza chirurgická MeSH
• antiflogistika terapeutické užití   MeSH
• biologická terapie MeSH
• Crohnova nemoc farmakoterapie   chirurgie   MeSH
• dítě MeSH
• elektivní chirurgické výkony MeSH
• imunosupresiva terapeutické užití   MeSH
• kolektomie * metody   MeSH
• lidé MeSH
• perioperační péče metody   MeSH
• pooperační komplikace etiologie   terapie   MeSH
• recidiva MeSH
• sekundární prevence metody   MeSH
• tenké střevo chirurgie   MeSH
• výběr pacientů MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH
• Názvy látek
• antiflogistika MeSH
• imunosupresiva MeSH