Jernej Brecelj

Treatment of oesophageal bile reflux in children : The results of a prospective study with omeprazole

Objectives: Reflux of duodenal juice into the oesophagus has a role in the pathogenesis of both oesophageal and laryngopharyngeal inflammatory and neoplastic lesions. As little is known about effective therapy, we studied the effect of proton pump inhibitor therapy on oesophageal bile reflux in children. Methods: Twenty-nine children with moderate to severe erosive oesophagitis and abnormal oesophageal bile reflux were studied before and after treatment with omeprazole 1 mg/kg per day. Outcomes included a clinical symptom score, oesophageal acid and bile reflux (simultaneous 24-hour pH and Bilitec 2000 monitoring), and mucosal healing. Results: After 8 weeks of therapy, 17 (59%) of the patients were symptom-free, and 5 (17%) had minimal symptoms. Mucosal healing or reduction to low-grade oesophagitis was achieved in 25 children (86%; P < 0.0005). Mean percentages of total, upright, and supine time with oesophageal pH less than 4 were reduced from 17.0%, 16.8%, and 19.2% before treatment, to 2.83%, 3.17%, and 2.07%, respectively, after treatment (all P < 0.00001). Similarly, mean percentages of total, upright, and supine time with bile reflux were reduced from 16.96%, 12.67%, and 22.0%, to 2.27%, 1.91%, and 2.23%, respectively (P < 0.000001, P < 0.0001, and P < 0.000001, respectively). Conclusions: Omeprazole 1 mg/kg per day is an effective therapy for the majority of children with severe erosive oesophagitis due to abnormal isolated bile reflux or combined acid and bile reflux. It remains unclear how patients with treatment-resistant bile reflux should be managed.

Effect of proton pump inhibition on acid, weakly acid and weakly alkaline gastro-esophageal reflux in children

BackgroundThe effect of proton pump inhibitors on the characteristics of gastroesophageal reflux (GER) in children and adolescents was evaluated.MethodsTwenty-one children and adolescents with symptoms suggesting GER disease (GERD) underwent upper endoscopy and a 24-hour multichannel intraluminal impedance/pH (MII-pH) monitoring before and at the end of 2 months of therapy with proton pump inhibitors (PPIs).ResultsFourteen (67%) patients reported clinically relevant symptom improvement after 2 months of PPIs intake. At the first endoscopy, 8 (38%) patients had macroscopic signs of reflux esophagitis; after two months of therapy, 6/8 (75%) patients had a complete mucosal recovery. There was a significant reduction in the total percentage of mean acid reflux time (from 13.1% to 3.8%), and the De Meester score dropped to normal (from 46.4 to 13.1). The mean number of acid refluxes decreased significantly from 48 to 15 per 24 hours, while inversely, the mean number of weakly acid refluxes increased significantly from 26 to 64 per 24 hours. PPI therapy did not affect the total number of reflux episodes, the number of liquid and mixed refluxes, the duration of esophageal bolus exposure and proximal extent of the reflux.ConclusionsIn children and adolescents with GERD, PPIs do not affect the total number of reflux episodes. PPIs only decrease the acidity of refluxate. Nevertheless, the majority of patients with typical reflux symptoms may report symptom improvement. Esophagitis can be healed after PPI treatment. The treatment of weakly acid and weakly alkaline reflux remains a challenge for physicians in the future.

Ketamine with and without midazolam for gastrointestinal endoscopies in children.

Objectives: Numerous publications on sedation of and anaesthesia for diagnostic procedures in children prove that no ideal scheme is available. Therefore, we decided to study the protocol with midazolam and ketamine used by nonanaesthetists at our institution. The study aimed to establish the lowest effective starting dose of ketamine and to estimate a difference in the frequency of adverse reactions with or without the use of midazolam as premedication, with special stress on emergence reactions. Methods: During 1 year we prospectively randomised children scheduled for gastrointestinal endoscopies to a first group with and to a second group without midazolam premedication. The starting ketamine dose was increased until the appropriate dissociative state was reached. Physiological functions were closely monitored and adverse reactions noted. Results: The median age of 201 analysed patients (111 girls, 90 boys) was 8.2 years. The median starting dose of ketamine was 0.97 mg/kg (the group with midazolam premedication) and 0.99 mg/kg TT (without midazolam premedication). Laryngospasm was observed in 6 patients without statistical difference between the 2 groups. All of the adverse reactions were short lasting; they resolved by symptomatic treatment without complications. Emergence reactions during the observation period at the hospital occurred more often in the group sedated with ketamine without midazolam premedication (P = 0.02). Conclusions: The sedation protocol with ketamine is safe and efficient. The starting dose of ketamine should be at least 1 mg/kg. There is an advantage to the use of midazolam as premedication before ketamine in paediatric patients because the frequency of emergence reactions in hospital was reduced compared with sole ketamine use.

Effects of formula supplementation in breast-fed infants with failure to thrive

Background:  The aim of the present study was to assess whether formula supplementation of infants with failure to thrive can improve underweight without jeopardizing breast‐feeding.

Autoimmune hepatitis as a presenting manifestation of mixed connective tissue disease in a child Case report and review of the literature

BackgroundLiver disease is rare in the course of mixed connective tissue disease. Most commonly liver steatosis or elevated liver function tests are reported and only a few cases of mixed connective tissue disease associated with autoimmune hepatitis were described.Case presentationWe report a case of an 11-year old boy with hepatitis on admission to the hospital and symptoms and signs of mixed connective tissue disease. Autoimmune hepatitis has been confirmed by liver biopsy.ConclusionTo the best of our knowledge this is the youngest patient with autoimmune hepatitis as a presenting manifestation of mixed connective tissue disease.

JAK2V617F mutation in a 9-year-old girl with polycythemia vera and Budd-Chiari syndrome: a case report.

To the Editor: Splanchnic vein thrombosis is frequently an early or presenting feature of an undiagnosed myeloproliferative disorder, being identified as the underlying disorder in 28% to 49% of cases of hepatic vein thrombosis [Budd-Chiari syndrome (BCS)] and 14% to 35% of patients with portal vein thrombosis. JAK 2V617F mutation is detectable in 90% to 95% of cases of polycythemia vera (PV). This is the case history of a 12year-old girl with BCS and PV. The girl was admitted to the gastroenterology unit in March 2007 when she was 9 years old because of acute liver failure. She presented with abdominal pain, vomiting, and jaundice. Examinations showed hepatomegaly, ascites, palmar erythema, hemoglobin of 157g/L (normal, 115 to 150), white blood cell count of 17.5 10/L (normal, 4.5 to 13.5), red blood cell count of 7.1 10/L (normal, 3.8 to 5.5), hematocrit of 0.49 (normal, 35 to 45), mean cell volume of 70 fL (normal, 77 to 95), and platelet count of 437 10/L (normal, 150 to 350). Other laboratory findings were albumin of 33 g/L, total bilirubin of 82 mmol/L (normal, <17.0), direct bilirubin of 9.8 mmol/L (normal, <5.0), aspartate aminotransferase of 6.7mkat/L (normal, <0.52), alanine aminotransferase of 11.1mkat/L (normal, <0.56), g-glutamyl transpeptidase of 0.72mkat/L (normal, <0.63), alkaline phosphatase of 2.4mkat/L (normal, <5.5), prothrombin time of 42% (normal 70 100), and partial thromboplastin time of 56 s (normal, 26 to 36). The peripheral blood smear was normal. Her parents were healthy, although it should be noted that they are distant relatives of one another. In her past, she was treated in the neonatal period for presumed sepsis, neonatal hemolytic anemia (she once received a transfusion of red blood cell concentrate), and had bleeding in the left suprarenal gland without latter consequences. An extensive personal history showed that headache with nausea and emesis began 2 years and 6 months ago, and that a hemogram was recorded at the neurology clinic 1 year ago, which was a follows: hemoglobin of 164 g/L (normal, 115 to 150); hematocrit of 49% (normal , 35 to 45); and platelets of 728 10/l (normal, 150 to 350). Extensive blood work-up for infectious, metabolic, toxic, and autoimmune causes of liver failure did not show the cause. Upper abdominal computed tomography with contrast showed hepatosplenomegaly and diffuse hepatic parenchymal changes with hypoperfusion of the majority of right and left liver lobes. A. hepatica, v. portae, and v. cava had a normal blood flow. The hepatic veins were not visible. A liver biopsy showed partially confluent centrilobular necroses and fibrointimal hyperplasia of the central veins with complete obliteration and partial recanalization. Treatment with Defibrotide for possible veno-occlusive disease was unsuccessful. A complete thrombophilia screening showed only a heterozygous carrier of C677 T polymorphism in the gene for methyltetrahydrofolate reductase. No acquired thrombophilic risk factors were found. A heterozygous JAK2 V617F mutation was detected. PV with BCS was the most probable diagnosis. Owing to the worsening of ascites, liver synthetic function, and the development of hepato-renal syndrome, she was transferred to Bergamo (Italy) for liver transplantation, as split-liver transplantation is not performed in Slovenia. The diagnosis of BCS was confirmed with computed tomography angiography. As the main problem was portal hypertension and as the liver function had stabilized, transjugular intrahepatic portosystemic shunt (TIPS) was performed. After the TIPS procedure, low molecular weight heparin and, later, warfarin were introduced. The liver and renal function normalized. She now lives a normal life and phlebotomy is performed approximately every 2 to 3 months. Owing to the TIPS occlusion in October 2008, it was recanalized and a new coated stent was placed inside.

Morphological and Functional Assessment of Oesophageal Mucosa Integrity in Children With Cystic Fibrosis.

Objectives: The aim of the study was to investigate morphological and functional characteristics of oesophageal epithelial barrier in children with cystic fibrosis (CF) with or without gastro-oesophageal reflux disease (GORD) in comparison to healthy controls. Methods: Oesophagogastroduodenoscopy with oesophageal biopsies and combined oesophageal multichannel intraluminal impedance-pH monitoring was performed in 17 children with CF (CFtot) with (CFgord) or without GORD (CFnorm). Histological combined severity score was calculated and widths of spaces between epithelial cells were measured. Basal impedance value was used to assess functional integrity of epithelial barrier. Results of each investigation were compared with a group of children without oesophageal disease. Results: CFtot, but also CFnorm, had more severe pathohistological changes included in the compound severity score than controls (0.75 ± 0.32 and 0.75 ± 0.20 vs 0.27 ± 0.25; P < 0.001 and P = 0.001, respectively). They also had more dilated intercellular spaces (2.6 &mgr;m ± 0.6 and 2.7 &mgr;m ± 0.5 vs 1.9 &mgr;m ± 0.2; P = 0.001 and P < 0.001, respectively). Baseline impedance values between proximal and distal pairs of electrodes were significantly lower in CFtot (2876 &OHgr; ± 484, 2590 &OHgr; ± 1013) and also in CFnorm (2922 &OHgr; ± 363, 2844 &OHgr; ± 457) than in controls (3703 &OHgr; ± 859, 3753 &OHgr; ± 1070) (P = 0.012 and P = 0.002; and P = 0.027 and P = 0.005, respectively). The treatment of CFgord with proton pump inhibitor increased, but did not normalise the baseline impedance values (2860 &OHgr; ± 560 to 3355 &OHgr; ± 750 and 2178 &OHgr; ± 1564 to 3057 &OHgr; ± 594). Conclusions: Children with CF had morphological and functional changes of oesophageal mucosal integrity even in the absence of GORD.

Success and safety of high infliximab trough levels in inflammatory bowel disease

Abstract Objective: A prospective trial suggests target infliximab trough levels of 3–7 μg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce. Aim: To explore whether high infliximab trough levels (≥7 μg/mL) are more effective and still safe. Material and methods: In this cohort study of 183 patients (109 Crohn’s disease and 74 ulcerative colitis) on infliximab maintenance treatment at a tertiary referral center we correlated fecal calprotectin and C-reactive protein to trough levels (426 samples) at different time points during treatment. Rates of infections were compared in quadrimesters (four-month periods) with high trough levels to quadrimesters with trough levels <7 μg/mL during 420 patient-years. Results: Fecal calprotectin and C-reactive protein (median [interquartile range]) were lower in patients with high trough levels (fecal calprotectin 66 mg/kg [30–257]; C-reactive protein 3 mg/L [3–3]) compared to trough levels below 7 μg/mL (fecal calprotectin 155 mg/kg [72–474]; C-reactive protein 3 mg/L [3–14.5]) (p < .001). High trough levels were superior also after excluding samples with trough levels <3 μg/mL from analysis. No differences in rates of infections were observed in quadrimesters with high trough levels (16/129 [12.4%]) compared to quadrimesters with trough levels <7 μg/mL (32/344 [9.3%]) (p = .32). Maintaining high trough levels resulted in 32% (interquartile range: 2–54%) increase of infliximab consumption. Conclusion: High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.

Gastroesophageal Reflux and Cystic Fibrosis

Cystic fibrosis is an autosomal recessive genetic disease characterized by chronic suppurative lung disease, exocrine pancreatic dysfunction, hepatobiliary disease, gastrointestinal disease, and many other clinical manifestations. Gastroesophageal reflux is a primary phenomenon in cystic fibrosis patients and is more prevalent than in general population. Lung aspirations of duodenogastric fluid are an underestimated risk factor for the lung disease progression. Advanced lung disease additionally increases gastroesophageal reflux risk. Many symptoms and signs of cystic fibrosis are overlapping with those of gastroesophageal reflux disease and are not a prognostic factor for its presence or severity level. Despite a lot of evidence, controversies regarding gastroesophageal reflux disease diagnosis and treatment in cystic fibrosis patients still exist. One of diagnostic challenges is lung aspiration detection. Proton pump inhibitors are the mainstay of the treatment employed in half of all patients. Antireflux operation in selected patients probably slows the decline of lung function. In addition, other topics of interest in cystic fibrosis patients interrelated with gastroesophageal reflux are addressed: respiratory physiotherapy, gastrostomy, and lung transplantation. With the prolongation of life expectancy, late complications of gastroesophageal reflux disease will become more prevalent. Gastroesophageal reflux in cystic fibrosis patients is a challenging field for clinical practice and research.

GUIDELINES FOR MANAGEMENT OF CHILDREN WITH CYSTIC FIBROSIS

BACKGROUND Cystic fibrosis is the most common autosomal recessive hereditary disease. The clinicalconsequences include multisystem disease characterised by progressive pulmonary disease leading to respiratory failure, pancreatic disfunction, liver disease that may progressto chirrhosis and men infertility due to atresia of the vas deferens. Early intervention andprevention of lung disease is of paramount importance, since the prognosis of the diseaseis substantially dependent on chronic respiratory infection and inflammation. Cysticfibrosis is a complex disease requiring a multidisciplinary approach to treatment. Centercare by a team of experienced health professionals is essential for optimal patient management and outcome. CONCLUSIONS The article presents diagnostic and therapeutic recommendations for the management of children with cystic fibrosi