BACKGROUND: Pediatric acute pancreatitis (AP) is rare but increasing. Severe AP is associated with higher morbidity and mortality. However, there are no universally accepted prognostic criteria for AP. METHODS: This retrospective study included children with AP admitted to an intensive care unit (ICU) of our tertiary pediatric center between January 2009 and December 2018. The severity of organ dysfunction in AP was assessed according to the modified Atlanta criteria using the Pediatric Sequential Organ Failure Assessment (pSOFA) and Computed Tomography Severity Index (CTSI). RESULTS: Seventy acute episodes of AP were evaluated in 55 children with primary pancreatitis. In addition, secondary AP was diagnosed in 15 patients originally admitted to ICU for different indications. Mild AP [no organ dysfunction, normal computed tomography (CT) finding] was the most prevalent (64/85 episodes in 49 children), followed by moderate AP (15 children; pSOFA 2-9 points, CTSI 3-4 points on admission). Severe AP (pSOFA 4-17 points, CTSI 6-10 points) was diagnosed in 6 children with traumatic or secondary AP. The most frequent etiologies of primary AP episodes were idiopathic (39%) and biliary (31%). Children with idiopathic AP had frequent relapses and comorbidities. Hereditary AP was typically mild, but presented with high pancreatic enzyme levels and recurrence rates. Admission at ICU and an interval without enteral nutrition (EN) were relatively short in drug-induced AP and relatively long in secondary and traumatic AP. Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 13 patients with biliary AP and in 4 patients with traumatic AP. No AP-related death was observed. CONCLUSION: pSOFA score accurately reflects the severity and prognosis of AP in children.

• Klíčová slova
• Acute pancreatitis, Children, Organ dysfunction, Prognosis, pSOFA score,
• MeSH
• akutní nemoc MeSH
• dítě MeSH
• jednotky intenzivní péče MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• pankreatitida * diagnostické zobrazování   etiologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• vyhodnocení orgánové dysfunkce MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Diamond-Blackfan anemia (DBA) is predominantly underlined by mutations in genes encoding ribosomal proteins (RP); however, its etiology remains unexplained in approximately 25 % of patients. We previously reported a novel heterozygous RPS7 mutation hg38 chr2:g.3,580,153G > T p.V134F in one female patient and two asymptomatic family members, in whom mild anemia and increased erythrocyte adenosine deaminase (eADA) activity were detected. We observed that altered erythrocyte metabolism and oxidative stress which may negatively affect the lifespan of erythrocytes distinguishes the patient from her asymptomatic family members. Pathogenicity of the RPS7 p.V134F mutation was extensively validated including molecular defects in protein translational activity and ribosomal stress activation in the cellular model of this variant.

• Klíčová slova
• BCCIP, CRISPR/Cas9, Diamond-Blackfan anemia (DBA), RPS7, Ribosomal stress, Wnt pathway, c-Myc,
• MeSH
• Diamondova-Blackfanova anemie * genetika   MeSH
• erytrocyty metabolismus   MeSH
• lidé MeSH
• missense mutace MeSH
• proteosyntéza MeSH
• ribozomální proteiny * genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• ribozomální proteiny * MeSH

Anemia is the most common extraintestinal systemic complication of inflammatory bowel disease. Iron deficiency anemia and anemia of chronic disease are among the most frequent types. Intestinal iron absorption is controlled by the activity of ferroportin. Cells with high expression of ferroportin include enterocytes, and also macrophages and hepatocytes. Iron homeostasis is controlled by the hepcidin-ferroportin axis. Hepcidin is a central regulator of iron metabolism and can also serve as a marker of systemic inflammation. During systemic inflammatory response, the synthesis of hepcidin increases, and hepcidin binds to ferroportin and inhibits its activity. Thus, iron is not absorbed from the bowel into the circulation and also remains sequestered in macrophages. Conversely, hepcidin synthesis is suppressed during conditions requiring increased iron intake for enhanced erythropoiesis, such as iron deficiency anemia or hypoxia. Here, ferroportin is not blocked, and iron is actively absorbed into the bloodstream and also released from the stores. Production of hepcidin is influenced by the status of total body iron stores, systemic inflammatory activity and erythropoietic activity. Oral iron therapy is limited in inflammatory bowel diseases due to ongoing gastrointestinal inflammation. It is less effective and may worsen the underlying disease. Therefore, the choice between oral and parenteral iron therapy must be made with caution. Oral iron would be ineffective at high hepcidin levels due to concurrent ferroportin blockage. Contrarily, low levels of hepcidin indicate that oral iron therapy should be successful. An understanding of hepcidin can help in understanding the body's reaction to iron depletion during the inflammatory process.

• Klíčová slova
• Anemia, Childhood, Hepcidin, Inflammatory bowel disease,
• MeSH
• anemie etiologie   terapie   MeSH
• ferroportin MeSH
• hepcidiny metabolismus   MeSH
• idiopatické střevní záněty komplikace   MeSH
• lidé MeSH
• proteiny přenášející kationty metabolismus   MeSH
• regulace genové exprese MeSH
• železo aplikace a dávkování   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• ferroportin MeSH
• hepcidiny MeSH
• proteiny přenášející kationty MeSH
• železo MeSH

Diamond Blackfan anemia (DBA) is predominantly an autosomal dominant inherited red cell aplasia primarily caused by pathogenic germline variants in ribosomal protein genes. DBA due to pathogenic RPL35A variants has been associated with large 3q29 deletions and phenotypes not common in DBA. We conducted a multi-institutional genotype-phenotype study of 45 patients with DBA associated with pathogenic RPL35A germline variants and curated the variant data on 21 additional cases from the literature. Genotype-phenotype analyses were conducted comparing patients with large deletions versus all other pathogenic variants in RPL35A. Twenty-two of the 45 cases had large deletions in RPL35A. After adjusting for multiple tests, a statistically significant association was observed between patients with a large deletion and steroid-resistant anemia, neutropenia, craniofacial abnormalities, chronic gastrointestinal problems, and intellectual disabilities (p<0.01) compared with all other pathogenic variants. Non-large deletion pathogenic variants were spread across RPL35A with no apparent hot spot and 56% of the individual family variants were observed more than once. In this, the largest known study of DBA patients with pathogenic RPL35A variants, we determined that patients with large deletions have a more severe phenotype that is clinically different from those with non-large deletion variants. Genes of interest also deleted in the 3q29 region that could be associated with some of these phenotypic features include LMLN and IQCG. Management of DBA due to large RPL35A deletions may be challenging due to complex problems and require comprehensive assessments by multiple specialists including immunologic, gastrointestinal, and developmental evaluations to provide optimal multidisciplinary care.

• MeSH
• Diamondova-Blackfanova anemie * genetika   MeSH
• fenotyp MeSH
• genetické asociační studie MeSH
• lidé MeSH
• mutace MeSH
• ribozomální proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• ribozomální proteiny MeSH
• RPL35A protein, human MeSH Prohlížeč

Linezolid is an antibiotic increasingly used for treatment of resistant Gram-positive infections, which blocks bacterial proteosythesis through direct inhibition of mitochondrial ribosomes. The most common adverse effects of linezolid include gastrointestinal symtoms, peripheral neuropathy, bone marrow depression and lactic acidosis. Here we present a rare case of a 9-year-old female, a survivor of acute lymphoblastic leukemia (ALL) and a hematopoietic stem cell transplant (HSCT), who developed life-threatening lactic acidosis with vomiting, impaired consciousness and Kussmaul breathing after 51 days of intravenous linezolid administration due to mycobacterial infection. She fully recovered after drug discontinuation and normalization of the plasma levels. We conclude that plasma lactate concentrations should be monitored closely during any linezolid treatment, particularly in patients with hepatic or renal dysfunction.

• Klíčová slova
• Adverse event, Child, Lactic acidosis, Linezolid, Plasma concentration,
• MeSH
• acidóza laktátová * chemicky indukované   MeSH
• akutní lymfatická leukemie * farmakoterapie   MeSH
• antibakteriální látky škodlivé účinky   MeSH
• Bacteria MeSH
• dítě MeSH
• lidé MeSH
• linezolid škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antibakteriální látky MeSH
• linezolid MeSH

Diamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia, underlied by haploinsufficient mutations in genes coding for ribosomal proteins (RP) in approximately 70% of cases. DBA is frequently associated with somatic malformations, endocrine dysfunction and with an increased predisposition to cancer. Here we present clinical and genetic characteristics of 62 patients from 52 families enrolled in the Czech and Slovak DBA Registry. Whole exome sequencing (WES) and array comparative genomic hybridization (aCGH) were employed to identify causative mutations in newly diagnosed patients and in cases with previously unrecognized molecular pathology. RP mutation detection rate was 81% (50/62 patients). This included 8 novel point mutations and 4 large deletions encompassing some of the RP genes. Malignant or predisposing condition developed in 8/62 patients (13%): myelodysplastic syndrome in 3 patients; breast cancer in 2 patients; colorectal cancer plus ocular tumor, diffuse large B-cell lymphoma and multiple myeloma each in one case. These patients exclusively harbored RPL5, RPL11 or RPS19 mutations. Array CGH is beneficial for detection of novel mutations in DBA due to its capacity to detect larger chromosomal aberrations. Despite the importance of genotype-phenotype correlation in DBA, phenotypic differences among family members harboring an identical mutation were observed.

• Klíčová slova
• Cancer, Diamond-Blackfan anemia (DBA), Mutations, Registry, Ribosomal proteins (RP),
• MeSH
• Diamondova-Blackfanova anemie komplikace   epidemiologie   genetika   MeSH
• genetické asociační studie MeSH
• lidé MeSH
• mutace * MeSH
• nádory etiologie   MeSH
• registrace MeSH
• ribozomální proteiny genetika   MeSH
• rodina MeSH
• sekvenování exomu MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH
• Názvy látek
• ribosomal protein L11 MeSH Prohlížeč
• ribosomal protein L5, human MeSH Prohlížeč
• ribosomal protein S19 MeSH Prohlížeč
• ribozomální proteiny MeSH

BACKGROUND: Autoimmune hepatitis (AIH) is a rare progressive liver disease, which manifests as acute hepatitis in 40%-50% of pediatric cases. This refers predominantly to spontaneous exacerbations of previously unrecognized subclinical AIH with laboratory and histological signs of chronic hepatitis, or to acute exacerbations of known chronic disease. Only a few of these patients fulfill criteria for acute liver failure (ALF). METHODS: Forty children diagnosed with AIH in our center between 2000 and 2018 were included in this study. All of them fulfilled revised diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) for probable or confirmed AIH, and other etiologies of liver diseases were excluded. Patients were divided into two groups: acute AIH (A-AIH) or chronic AIH (C-AIH). RESULTS: Acute onset of AIH occurred in 19/40 children (48%). Six of them fulfilled the criteria of ALF with coagulopathy and encephalopathy. Five of 6 children with ALF suffered from exacerbation of previously undiagnosed chronic AIH, among which 4 children were histologically confirmed as micronodular cirrhosis. The remaining one patient had fulminant AIH with centrilobular necrosis, but no histological signs of previous chronic liver damage. We observed significantly lower levels of albumin, higher levels of aminotransferases, bilirubin, INR, IgG, higher IAIHG score and more severe histological findings in A-AIH than in C-AIH. No differences in patient age and presence of autoantibodies were observed between A-AIH and C-AIH. All children, including those with ALF and cirrhosis, were treated with corticosteroids, and are alive and achieved AIH remission. Liver transplant was not indicated in any patient. CONCLUSION: Rapid and accurate diagnosis of A-AIH may be difficult. However, timely start of immunosuppressive therapy improves prognosis and decreases number of indicated liver transplantations in children with AIH.

• Klíčová slova
• Acute liver failure, Autoimmune hepatitis, Children, Onset,
• MeSH
• akutní nemoc MeSH
• akutní selhání jater etiologie   MeSH
• autoimunitní hepatitida komplikace   diagnóza   farmakoterapie   MeSH
• dítě MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunosupresiva MeSH

AIM: The aim of this study was to compare changes in serum hepcidin levels in paediatric patients with inflammatory bowel disease during therapy and correlate them with markers of iron metabolism, inflammation and type of treatment. METHODS: Children with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) were included in this longitudinal study. Blood and stool samples were collected to assess levels of serum hepcidin and markers of iron metabolism parameters and inflammation. The parameters were examined before treatment (baseline levels) and compared with levels in the follow-up period during maintenance therapy (mean follow-up of 39 months after diagnosis). RESULTS: Patients with CD (n = 30) had higher serum hepcidin levels (expressed as a median and interquartile range) at diagnosis than subjects with UC (n = 13). These levels significantly decreased during the follow-up (from 36.5 (11.5-79.6) to 2.1 (0.9-6.7) ng/mL). In contrast, no significant serum hepcidin level changes were observed in the UC patients (5.4 (3.4-16.6) vs. 4.8 (0.9-8.1) ng/mL). While hepcidin level changes correlated with disease activity and inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein), in CD patients, they correlated only with serum iron levels in patients with UC. Biological therapy was accompanied by a significant decrease in C-reactive protein and interleukin-6 compared to conventional anti-inflammatory therapy in CD patients. CONCLUSIONS: Children with CD had higher serum hepcidin levels on diagnosis compared to subjects with UC. During an anti-inflammatory therapy, serum hepcidin decreased in the CD group but remained consistently low in children with UC.

• Klíčová slova
• Crohn's disease, anaemia, children, hepcidin, ulcerative colitis,
• MeSH
• antiflogistika terapeutické užití   MeSH
• biologické markery MeSH
• dítě MeSH
• hepcidiny MeSH
• idiopatické střevní záněty * farmakoterapie   MeSH
• lidé MeSH
• longitudinální studie MeSH
• studie případů a kontrol MeSH
• ulcerózní kolitida * farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• biologické markery MeSH
• hepcidiny MeSH

AIM: Hepcidin is a central regulator of iron homeostasis. Its production is also influenced by systemic inflammation. The aims of this study were to compare hepcidin levels in paediatric patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) and to determine the association of hepcidin levels with laboratory and clinical parameters of inflammatory bowel disease (IBD) activity. METHODS: Children with newly diagnosed IBD between January 2012 and September 2016 were enrolled in this comparative cross-sectional study. We analysed levels of serum hepcidin, C-reactive protein, iron, ferritin, soluble transferrin receptors, blood count and faecal calprotectin in all subjects. Serum hepcidin levels were measured by reverse-phase liquid chromatography. The Paediatric Crohn's Disease Activity Index was used to evaluate CD in children, and Paediatric Ulcerative Colitis Activity Index was used for the assessment of UC disease activity. RESULTS: Subjects with CD (n = 53) had significantly higher serum hepcidin levels compared with subjects with UC (n = 23) - 22.6 ng/mL (range 8.5-65.0) versus 6.5 ng/mL (range 2.4-25.8) (P < 0.05). Hepcidin was independently associated with ferritin levels in all IBD patients (P < 0.05). Moreover, there was a significant positive correlation between hepcidin and platelet count (P < 0.05) in children with CD and a negative correlation between hepcidin and faecal calprotectin (P < 0.05) in children with UC. CONCLUSION: Different hepcidin levels between children with newly diagnosed CD and UC suggest the distinct contribution of iron deficiency and/or systemic inflammation to anaemia and may help clinicians choose the best anti-anaemic treatment.

• Klíčová slova
• Crohn's disease, anaemia, children, hepcidin, inflammatory bowel disease, ulcerative colitis,
• MeSH
• antiinfekční látky krev   MeSH
• C-reaktivní protein analýza   MeSH
• dítě MeSH
• feces chemie   MeSH
• ferritiny krev   MeSH
• hepcidiny krev   MeSH
• idiopatické střevní záněty diagnóza   MeSH
• leukocytární L1-antigenní komplex krev   MeSH
• lidé MeSH
• mladiství MeSH
• průřezové studie MeSH
• železo krev   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiinfekční látky MeSH
• C-reaktivní protein MeSH
• ferritiny MeSH
• hepcidiny MeSH
• leukocytární L1-antigenní komplex MeSH
• železo MeSH

BACKGROUND: Numerous articles related to S100 proteins have been recently published. This review aims to introduce this large protein family and its importance in the diagnostics of many pathological conditions in children and adults. DATA SOURCES: Based on original publications found in database systems, we summarize the current knowledge about the S100 protein group and highlight the most important proteins with focus on pediatric use. RESULTS: The S100 family is composed of Ca2+ and Zn2+ binding proteins, which are present only in vertebrates. Some of these proteins can be used as diagnostic markers in cardiology (S100A1, S100A12), oncology (S100A2, S100A5, S100A6, S100A14, S100A16, S100P, S100B), neurology (S100B), rheumatology (S100A8/A9, S100A4, S100A6, and S100A12), nephrology and infections (S100A8, S100A9, S100A8/A9, S100A12). The most useful S100 proteins in pediatrics are S100A8, S100A9, heterodimers S100A8/A9, S100B and S100A12. CONCLUSIONS: The S100 family members are promising biomarkers and provide numerous possibilities for implementation into clinical practice to optimize the differential diagnostic process.

• Klíčová slova
• Diagnostics, Marker, Pediatrics, S100,
• MeSH
• biologické markery krev   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• neonatologie * MeSH
• novorozenec MeSH
• pediatrie * MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• proteiny S100 krev   MeSH
• senzitivita a specificita MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• proteiny S100 MeSH