Kolestaza je poremećaj stvaranja i/ili protoka žuči koji dovodi do zadržavanja žuči u jetri. Javlja se kod 1 : 2500 terminske dojenčadi, najčešće u prva tri mjeseca života. Konjugirana ...hiperbilirubinemija je biokemijska manifestacija kolestaze o kojoj govorimo kada je konjugirani bilirubin veći od 17 umol/L i/ili na njega otpada više od 20% ukupnog bilirubina. Kolestaza je uvijek patološka i zahtijeva opsežnu obradu. Najčešći pojedinačni uzroci su atrezija žučnih vodova, infekcija, kolestaza uzrokovana parenteralnom prehranom i manjak alfa-1 antitripsina, dok u četvrtine bolesnika etiologija ostaje nerazjašnjena pa govorimo o idiopatskom neonatalnom hepatitisu. Kliničke su manifestacije kolestaze žutica, pruritus i pojava svijetlih (hipokoličnih ili akoličnih) stolica i tamnijeg urina. Otežana apsorpcija masti i vitamina topivih u masti, pothranjenost i pruritus izazovni su klinički problemi koje susrećemo u ovih bolesnika. Zaključak: Kolestaza u dojenačkoj dobi rijetko je stanje koje je često uzrokovano teškim bolestima, te je stoga temeljna zadaća svakog pedijatra pravovremeno prepoznati ove bolesnike i uputiti ih na daljnju obradu.
Crigler-Najjar syndrome (CNS) is an exceedingly rare autosomal recessive disease with an estimated incidence of 1 in a million live births. CNS type 1 (CNS1) is the most severe form, characterized by ...severe unconjugated hyperbilirubinemia since birth due to the absence of hepatic uridine 5'-diphosphate glucuronyltransferase (UGT1A1) activity. Daily phototherapy (PT) and liver transplant (LT) are the mainstays of therapy. Here, we present a higher-than-expected incidence of CNS1 in Croatia (6,1 in a million). In the last 31 years, we treated eight CNS1 patients from five families with no reported consanguinity. Four patients are descendants of an isolated enclave in Kosovo with a small gene pool and a high potential for inbreeding. Severe unconjugated hyperbilirubinemia was verified in a neonatal period and PT was initiated. Four patients underwent LT from living-related donors. One of them had unsuccessful hepatocyte transplantation earlier. LT was successful in three patients, and one patient died due to primary graft dysfunction. Four patients are currently treated with 9–12 h daily PT with inconsistent disease control, and gradually increasing bilirubin. One patient developed kernicterus before LT, while others have normal psychomotor development and no neurologic impairment. Genetic testing of the UGT1A1 gene in six patients from three families revealed three different homozygous mutations (c.722_723 delAG, c.717_718 delAG, and c.1021 C >T), all previously described in other populations. There is a possibility of the founder effect as an explanation for the higher incidence of CNS1 in at least a subgroup of Croatians.
To present patients with Crigler-Najjar syndrome type 1 (CN1). It is a rare autosomal recessive disorder with an incidence of 1: 1 000 000 live births, characterised by severe unconjugated ...hyperbilirubinemia which arises as a consequence of the absence of hepatic bilirubin uridine diphosphate glucuronosyl transferase(UGT1A1) activity.In the last 30 years we treated seven children with this syndrome at the Department of Pediatrics, University Hospital Center Zagreb.They were from five families- two pairs of siblings (brother and sister) and three unrelated patients (two boys and a girl). Genetic testing of UGT1A1 gene was performed in six patients (two pairs of siblings and two unrelated boys). Unfortunately, one patient’s result was lost.Three patients had frameshift mutations in exon 1: Patient 1 (c.722_723delAG p.Glu241Glyfs*16), Patients 2 and 3 were siblings and had identical mutation (c.717_718delAG p.Q239fsX256). Two patients (4 and 5, also siblings) had identical nonsense mutation in exon 3 (c.1021C>T p.Arg341*).Genetic testing, as it was not widely available at the time, was not performed in one girl whose diagnosis was made by the chromatographic analysis of bilirubin glucuronides in the bile.Four patients underwent a liver transplant from living related donors. In two auxillary procedure was performed (siblings at the age of 7 and 9 years) and in two segmental liver transplant (at the age of 6 and 10 years). Prior to surgery, there was also an unsuccessful attempt of hepatocyte transplantation in one patient.Three liver transplant procedures were successful, and one patient died in the early post-operative course due to primary graft dysfunction.Three patients who have not yet undergone liver transplant (a 3-year-old boy and two siblings 1.5-year-old girl and her 6-month-old brother) are currently treated with phototherapy. At least 10-14 hours long treatment is necessary to keep their bilirubin at an acceptable level (around 250 umol/L). Their psychomotor development is appropriate and they have no neurologic impairment.Considering the number of births per year in Croatia we noticed a remarkably high incidence of CN1, more than five times as expected (5,4: 1 000 000). We don’t have explanation for this finding, at least not by mutations observed. Nevertheless, three of our patients are offspring of two families originating in small Croatian enclave in Kosovo where they were isolated for several centuries. Perhaps there are epigenetic factors we are unaware of that may play a role and contribute to this unexpectedly high incidence.
Celiac disease (CD) is an immune-mediated systemic inflammatory disease triggered by gluten ingestion in genetically predisposed individuals with a wide spectrum of sings and symptoms. Genetic ...predisposition is strongly associated with HLA-DQ2 and DQ8 heterodimers (HD), also related to a higher risk of occurrence in other autoimmune conditions.ObjectiveTo investigate clinical and immunogenetic characteristics of patients with celiac disease diagnosed in a tertiary center.The data collected retrospectively from medical records from 2008.-2018.included age at the time of diagnosis, clinical presentation, results of specific antibody testing, small bowel biopsy and HLA typing A total of 55 patients were enrolled, 29 females and 26 males (1.12:1), mean age 11.7 ± 4.62 years. A classical form of CD (diarrhea, abdominal distension, failure to thrive) was found in 22 patients, (mean age at diagnosis 3.41±3, 23 yrs, median 1, 88). 18 patients had an atypical, extraintestinal presentation (mean age 9.31±3, 86 yrs, and median 9 yrs).The asymptomatic disease was found in 15 patients, mainly with diabetes type I (T1D), (mean age 9,27±2,67yrs, median 9). Out of 39 patients who underwent HLA typing, 36 patients were positive for either single or double dose of DQ2.5 or DQ8 HD. Among three HD negative patients, one was geneDQB1*02 double dose positive (HD DQ2.2 homozygous), one was positive for DQA gene of DQ2.5 HD, while the third one was negative for all DQA or DQB genes from CD predisposing DQ HDs. A total of 17 patients positive at very high CD risk according to the presence of either DQ2.5 in double dose or heterozygous DQ2.5/DQ8 genotype or double DQB1*02 gene dose (DQ2.5/DQ2.2 genotype) were mainly asymptomatic. Furthermore, among 11 patients positive for DQ2.5/DQ2 or DQ2.5/DQ8 genotype (double HD dose), 7 were also T1D patients, while in the remaining 28 DQ2.5 or DQ8 heterozygous and HD negative patients, only 4 were diagnosed with T1D; the observed difference was statistically significant (p=0,004).In our group of CD patients, clinical presentation related to age was similar to the literature data, with typical gastrointestinal manifestation in the youngest patients. Considering HLA-DQ heterodimer frequency, our patients had a similar distribution to other European and non-European patients with CD. However, since the majority of children with either DQ2.5 homozygous genotype or DQ2.5/DQ8 heterozygous genotype were CD asymptomatic patients primarily diagnosed with T1D, we would like to emphasize the importance of screening for celiac disease in this group of patients.
Acute esophageal necrosis (black esophagus, Gurvits syndrome) is a rare clinical entity which leads to upper gastrointestinal bleeding. First description dates to 1990, with around115 cases described ...in the literature. The condition has pathognomonic endoscopic appearance characterized by circumferential black mucosa in the distal esophagus, and discontinuing abruptly at the gastroesophageal junction. The pathogenesis is unclear, apparently multifactorial mucosal ischemia due to low flow vascular state or microvascular thrombosis is predisposing to topical damage by gastric content reflux. It’s commonly seen in elderly men, with risk factors like diabetes, malignancy, alcohol consumption, shock, major surgery.Diagnosis is made endoscopically.Management requires hemodynamic stabilization, acid suppressive medication with avoidance of nasogastric tube placement. The condition has very poor prognosis, with mortality rate up to 35%, and various complications including strictures and stenosis, perforation with mediastinitis and abscess formation.Our patient, a 15 year old boy underwent surgery for scoliosis. During the immediate post surgical period he had hematemesis with consequent hemorrhagic shock. He was stabilized (IV fluids, packed red blood cells), nasogastric tube was inserted with evacuation of around 160 mL of blood and he was referred to our ICU. He required mechanical respiratory support and inotropic medications. Continuous parenteral PPI therapy was commenced.Black, charcoal-like content was draining from the nasogastric tube, with further deterioration in hemoglobin levels.Esophagogastroduodenoscopy showed black mucosa of lower esophagus, partly circumferential, partly linear, with cutoff at gastroesophageal junction.There were no radiological signs of esophageal perforation, bilateral lung consolidates were surrounded by ground-glass interstitial changes.Patient was kept NPO, on parenteral nutrition, with PPI and antibiotic treatment. He was weaned mechanical ventilation after three days, followed by brief stint of non-invasive respiratory support.Unfortunately, significant stenosis with stricture formed in the area overlying initial necrosis. After several attempts of endoscopic ballon dilatation, refractory strictures reemerged. Surgical gastrostomy was performed to enable sufficient enteral caloric intake, and bring the patient to ideal physical condition for further treatment.Planned colonic interposition surgery was not performed because of inadequate length of colon, hence thoracic surgeons performed retrosternal esophagogastroplasty Our patient had no further postoperative complications and was able to establish adequate oral feeding.Acute esophageal necrosis should be considered as one of the causes of upper gastrointestinal bleeding, especially because its high mortality and complications rate requires immediate and aggressive early management.
This is a one-year follow-up study looking into the nutritional status and the rate of re-hospitalizations in children at the UHC Zagreb, Dept. of Paediatrics who were first evaluated during the ...nutritionDay (nDay) in November 2018. The aim is to evaluate the accuracy of STRONGkids questionnaires, subjective assessment within nDay survey and anthropometry in detecting malnutrition and possible relation to number of hospital admissions and disease outcomes (for oncology patients) within a year.The study included 50 patients (mean age 13.48 years ±3.79, 22 males) whose nutritional status was estimated in November 2018. Additional data were collected after the period of 12 months. Mann-Whitney U, Kruskal Wallis and Wilcoxon signed-ranks tests were applied.A significantly different BMI was found among subgroups categorized through the nDay survey (without risk, at risk, malnourished patients) and among subgroups assessed by STRONGkids (low, medium and high risk for malnutrition) (p1=0.002, p2=0.003, resp.). Post hoc tests showed that statistical significance could be contributed to differences between groups malnourished patients vs. those not at risk within nDay (p3=0.009) and between groups low vs. high and medium vs. high risk defined through STRONGkids questionnaires (p4=0.020, p5=0.004, resp.). In the one-year follow-up period, 28/50 children were re-hospitalized once or several times.The number of re-hospitalizations was significantly higher for children classified by STRONGkids to have high risk for malnutrition (p6=0.002), as well as for those categorized as malnourished through the nDay survey (p7=0.024). No significant difference in z-score BMI values was found between years 2018 and 2019 (Wilcoxon signed-rank test: p8=0.086).Re-hospitalized oncology patients (11) were additionally analysed in respect of their disease status: favourable outcome (disease regression; 8/11) vs.unfavourable outcome (progression or unchanged state; 3/11). No difference was observed in the initial BMI between these groups (Mann-Whitney U test: p9=0.921), and no significant change in their BMI during this period was observed in either group (Wilcoxon signed-rank test: p10=0.161, p11=0.593).Patients categorized as malnourished both with STRONGkids and nDay survey had significantly lower BMI than the rest of subjects. Our data support the hypothesis that malnourished patients have a higher rate of re-hospitalizations. Within the observational period, re-hospitalized patients neither improved nor worsened their nutritional status according to the BMI z-scores. We were not able to connect the nutritional status of oncology patients with their disease outcome after one year, perhaps due to a rather small sample or short time of follow-up.
ObjectiveReevaluation of our experiences in adherence to the established local guidelines in our population of pediatric patients diagnosed with foreign body ingestion.MethodsA retrospective study of ...patients aged 0-18 years who were admitted to pediatric emergency department of the University Hospital Centre Zagreb between 1.1.2015. and 31.12.2019. due to suspected foreign body ingestion. We grouped them according to their age and localization of the foreign body along the digestive tract. We analyzed how many patients and with what success underwent endoscopy in relation to the applicable guidelines in our Institution.ResultsOf the 410 patients with suspected foreign body ingestion, a foreign body was found in 175 patients (x = 4 years ± 9 months), more common in male children (100/175). Most of them (78/175, 45%) were in the age group 3-7 years, followed by 1-3 year group (51/175, 29%). Foreign body was localized radiologically in 165 (94%), by endoscopy in 8 (5%) patients, while in the two patients localization hasn’t been determined, and there was also one spontaneous foreign body expulsion. Most common foreign bodies were coins in 61 children (35%), followed by another metal object in 51 (29%), button battery in 35 (20%) and plastic object in 7 (4%) patients. In 11 children (6%) it was food bolus impaction, and 10 of them swallowed other objects. Most foreign bodies were localized in the stomach (95 patients, 54%), followed by the small intestine (38 patients, 22%), the esophagus (27 patients, 15%) and the colon (9 patients, 5%). Two toothpicks were found in piriform sinus and tonsils. Endoscopy was performed in a third of patients (59/175; 34%), and it was successful (resulting in foreign body extraction) in 48 of them (81%). In 25/27 of patients with foreign body localized in the esophagus endoscopy was performed, while the two asymptomatic patients were observed. 7/8 patients with food bolus impaction were previously diagnosed with esophageal stenosis. According to guidelines, 41 endoscopies (70%) were warranted and 18 (30%) were not. We compared our results from this period (III) with the two previous ones: before the adoption of guidelines (I) and the early period following the introduction of guidelines (II). The following was shown: endoscopy in 67% of patients with foreign body ingestion with 77% success rate (I), endoscopy in 20% of patients with 90% success rate, and in 34% of patients with 81% success rate (III).ConclusionGlobal experiences suggest that endoscopic extraction is indicated in 10-20% of cases of all foreign body ingestions in children. In the study period, in one third of 34% of patients in which the endoscopy was performed, it was not indicated according to current guidelines. Despite the existence of guidelines, tenacity and the vigilance of adherence to them decreases over time. Their existence by itself is not sufficient in reducing children’s exposure to unnecessary and potentially harmful interventions.
ObjectiveComparing the referral diagnosis as an indication for EGD with final histological diagnosis, and to assess whether it was justified to perform these endoscopies in our ...patients.MethodsRetrospective analysis of patients who underwent gastroscopy with biopsy in the period from 1.1.2016. to 29.02.2020 at the Clinical Hospital Center Zagreb. The study did not include foreign body removal procedures, follow up endoscopies and endoscopies for the purpose of placing medical orthopedic aids. We have described the symptoms leading to referral for endoscopy, as well as their average duration prior to endoscopy. We analyzed the correlation between referral and final histological diagnosis.ResultsIn a cohort of a total of 100 patients, the most common indication for gastroscopy in 24/100 (24%) was abdominal pain, and in approximately half of them (13/24, 54.2%) the histological cause of the discomfort was found (gastritis in 12 and celiac disease in 1). Of the 20 gastroscopies performed on suspicion of gastritis, in 12/20 (60%) pathological substrate was found (9 gastritis, 2 eosinophilic esophagitis, 1 celiac disease). Due to celiac disease suspicion, we endoscopied 18 patients, of whom in 10 (55.6%) celiac disease was histologically confirmed. In 6/11 (54.5%) patients with dyspeptic symptoms diagnosis of gastritis was made after the endoscopy. In almost half of the patients, the pathohistological finding was normal. From 52 pathological findings; 31/52 (59.6%) corresponds to gastritis, 12/52 (23.1%) to celiac disease, 5/52 (9.6%) to eosinophilic esophagitis, and in 2 patients (3.8%) esophageal varices and stomach polyps were found.The average duration of discomfort was 10 months and 26 days, while the largest number of patients; 17 of them had symptoms for a year, 16 had problems for 6 months, 9 had symptoms for 2 years, and 8 had symptoms for 1 and 3 months, respectively before the endoscopy. It should be noted that 10 were asymptomatic and were referred for endoscopy on the basis of pathological laboratory findings (complete blood count, iron, antibodies to tissue transglutaminase) or specific anamnesis (body weight loss, failure to thrive). Endoscopy completion rate by entering into the distal end of duodenum was 100%. We did not record any complications.ConclusionConsidering the nonspecific symptoms of the disease that greatly correlate with functional difficulties the number of negative findings is not surprising. But since gastroscopy is the most sensitive method of confirmation/exclusion of the disease itself it is clear that a high number of negative findings point to the necessity of developing clearer guidelines to avoid unnecessary endoscopies. Furthermore, comparing our results with the results of similar foreign studies we can say that we are within the world average and that this indeed is a global problem that requires team effort especially at a time when the number of endoscopic procedures grows rapidly every day due to increased endoscopic possibilities.
ObjectiveTo describe the characteristics of patients with cystic fibrosis-associated liver disease (CFLD), a complication of cystic fibrosis (CF) that is often asymptomatic until an advanced ...stage.MethodsRetrospective analysis included patients aged 0-20 years followed in 2018. at the Cystic Fibrosis Centre of the University Hospital Centre Zagreb. CFLD1 was diagnosed if ≥2 of the following were present: hepatomegaly and/or splenomegaly, elevated transaminases or gamma-glutamyl transferase (GGT) 3 times during 12 months, ultrasound signs of liver involvement or portal hypertension (PTH), suggestive pathohistological findings. Severe CFLD was defined as a disease with signs of PTH.Results61 patients with a mean age of 10.9 years (9 months-19 years, male: female = 34:27) were included. 9/61 (14.8%) of them had CFLD, 6 girls and 3 boys, aged 2-19 years (average age 10.7 years). They all had at least one F508del mutation, and 7/9 were homozygous. Regarding the severity of the disease, 4 patients (3 boys and 1 girl, 6-19 years) had a severe form of CFLD with PTH and presumed cirrhosis, which was confirmed by liver biopsy in one patient. Two patients also had impaired synthetic liver function, two had hypersplenism with platelet count <80x109/L, and one had esophageal varices without bleeding. The remaining 5/9 patients had mild CFLD with ultrasound changes (hyperechoic or nodular liver parenchyma, periportal fibrosis) and/or elevated liver enzymes.We observed a trend of poor nutritional status in patients with severe CFLD (mean BMI z-value -0.66, range -0.26 to 0.62) compared to those with mild form of CFLD (mean BMI z-value -0.41, range – 2.76 to 1.49), but the difference wasn’t significant, and the most severely malnourished patient had mild CFLD.We also assessed some noninvasive biomarkers of fibrosis: the APRI index was elevated (≥0.5) in all patients with severe CFLD and in one with mild CFLD, and Fibrosis-4 score was pathological in only one patient with PTH. Elastography was performed in 5 patients: it was normal in one patient with mild CFLD, whereas in four increased liver stiffness was found (significantly increased in two patients with severe CFLD, and mildly in two patients with mild CFLD).4/9 patients with CFLD had meconium ileus, which is approximately twice the frequency compared to all included CF patients.ConclusionThe diversity of clinical expression and findings in our patients is consistent with the literature data on the spectrum of CFLD manifestations. We confirmed a higher incidence of meconium ileus and severe mutations, and male dominance in CFLD with PTH. In all CF patients, liver disease should be actively sought from an early age (clinical examination once a year + abdominal ultrasound + AST, ALT, GGT).
ObjectivesFunctional constipation in children should be diagnosed in primary care, based on Rome criteria. Management in tertiary care is rarely needed. The aim of this study was to assess the ...frequency and structure of paediatric patients diagnosed with functional constipation in a tertiary hospital setting.MethodsThis study enrolled children referred to the paediatric gastroenterologist (PG) at the UHC Zagreb from January 1st 2017 to December 31st 2017 (N=1729). Data on patients was extracted retrospectively from clinical records. The subjects were classified in three age groups: infants and toddlers (0–3 years), children (4–10 years) and adolescents (11–18 years). Descriptive statistics and chi-square test were used, statistical significance was determined as p<0.05ResultsAfter appropriate evaluation, about 8% of all outpatients seen by the PG at the UHC Zagreb during year 2017 had functional constipation with or without encopresis (7.63% or 132 patients, boys: 56,1% vs girls: 43,9%). Half of the patients were in the age group of 4 to 10 years (66/132 or 50%), about 1/3 was 0 to 3 years old (41/132), and about 1/5 were adolescents (25/132). It was the most common functional gastrointestinal disorder (FGID) (132/328 or 40.24%), both in girls and boys. Also, it was the leading FGID in the infant/toddler (41/57) and the children group (66/124). Retentive encopresis was present in about 1/5 of children (29/132 or 21.9%) Accompanied encopresis was mainly observed in the age group of 4–10 years (22/66 or 33.3%, χ²=9.9431, p<0.05). Also, encopresis tends to be more frequent among male patients with functional constipation (male, 27% vs female, 15.5%). In patients who visited PG for the first time, substantial discordance in the referral and the final diagnosis was observed. About 1/3 of patients with diagnosed constipation was referred with another diagnosis (29/92 or 31.5%). However, most of patients with constipation as referral diagnosis had the same disorder as final diagnosis (49/53 or 92.5%).DiscussionFrequency of functional constipation in paediatric patients in tertiary hospital setting, as well as sex and age distribution, is comparable to reported incidences in the population. The discordance of referral and final diagnosis shows that constipation is not adequately recognized in primary care, but when recognized, it is mostly diagnosed correctly.ConclusionFunctional constipation is not recognized enough in primary care and more efforts are needed to assure a positive diagnosis of this disorder prior to the referral to tertiary care.
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