Alantolactone ameliorates graft versus host disease in mice.

The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2-18 (n = 4) and non-GVHD patients between ages 2-50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naïve phenotype (CD62L+ CD44-). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in pro-inflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.

Chemical compounds isolated from aerial parts of Bolanthus aziz-sancarii, a new species from Türkiye.

Bolanthus aziz-sancarii identified in 2019 for the first time is an endemic species of Bolanthus genus belonging to Caryophyllaceae family. Ten compounds were isolated from aerial parts of the plant. The potential antioxidant and anti-inflammatory effects of all four phases (hexane, chloroform, ethyl acetate, and water) from the methanol extract of the plant were investigated. After considering the findings regarding both antioxidant and anti-inflammatory capacities, it was decided to investigate the phytochemical profile of the EtOAc layer of B. aziz-sancarii. An abscisic acid-type sesquiterpene glucoside and nine flavonoid derivatives were isolated from the ethyl acetate fraction of the B. aziz-sancarii methanol extract through the use of column chromatography with silica gel.

The frequency of Duchenne muscular dystrophy/Becker muscular dystrophy and Pompe disease in children with isolated transaminase elevation: results from the observational VICTORIA study.

Introduction: Elevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia. Methods: This multi-center, prospective study enrolled patients aged 3-216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels >2× the upper limit of normal (ULN) for ≥3 months. Patients with a known history of liver or muscle disease or physical examination findings suggestive of liver disease were excluded. Patients were screened for creatinine phosphokinase (CPK) levels, and molecular genetic tests for DMD/BMD in male patients and enzyme analysis for PD in male and female patients with elevated CPK levels were performed. Genetic analyses confirmed PD. Demographic, clinical, and laboratory characteristics of the patients were analyzed. Results: Overall, 589 patients [66.8% male, mean age of 63.4 months (standard deviation: 60.5)] were included. In total, 251 patients (188 male and 63 female) had CPK levels above the ULN. Of the patients assessed, 47% (85/182) of male patients were diagnosed with DMD/BMD and 1% (3/228) of male and female patients were diagnosed with PD. The median ALT, AST, and CPK levels were statistically significantly higher, and the questioned neurological symptoms and previously unnoticed examination findings were more common in DMD/BMD patients than those without DMD/BMD or PD (p < 0.001). Discussion: Questioning neurological symptoms, conducting a complete physical examination, and testing for CPK levels in patients with isolated hypertransaminasemia will prevent costly and time-consuming investigations for liver diseases and will lead to the diagnosis of occult neuromuscular diseases. Trial Registration: Clinicaltrials.gov NCT04120168.

Gastrointestinal endoscopic findings of autoimmune and autoinflammatory diseases in pediatric rheumatology patients.

OBJECTIVE: Rheumatic diseases in children are chronic and multisystemic diseases. In this study, it was aimed to evaluate gastrointestinal endoscopic findings in children diagnosed as autoimmune or autoinflammatory rheumatic diseases consulted with pediatric gastroenterology for gastrointestinal complaints. METHODS: The patients followed up by the Pediatric Rheumatology Department and consulted to the Pediatric Gastroenterology Department due to gastrointestinal complaints were included in the study. File records of the patients were analyzed retrospectively. RESULTS: A total of 28 patients were included in the study. Twelve of the patients had autoimmune disease (Juvenile idiopathic arthritis [JIA], systemic lupus erythematosus, Sjögren's syndrome, and scleroderma) and the other 16 had autoinflammatory disease (familial Mediterrnean fever, hyper Immunoglobulin D syndrome, undifferantiated systemic autoinflammatory disease, and systemic JIA). Four of the patients with familial Mediterrnean fever also diagnosed as JIA. The mean age of the patients was 11.7±3.5 years. The main gastrointestinal complaints of patients with both autoimmune and autoinflammatory diseases were abdominal pain and diarrhea. Inflammatory bowel disease was found in 33% of those with autoimmune disease and 56% of those with autoinflammatory disease in patients underwent endoscopic evaluation. M694V mutation was present in 62% of the patients with autoinflammatory disease presented with gastrointestinal complaints. CONCLUSION: Both autoimmune and autoinflammatory rheumatic diseases can cause gastrointestinal complaints and should be referred to a pediatric gastroenterologist for early diagnosis.

Multichannel Intraluminal Impedance and pH Monitoring are Complementary Methods in the Diagnosis of Gastroesophageal Reflux Disease in Children.

OBJECTIVE: Gastroesophageal reflux is considered to be a disease when reflux of gastric contents causes troublesome symptoms in infants and children. The aim of this study was to compare the diagnostic value of the multichannel intraluminal impedance monitoring and only pH monitoring in the diagnosis of gastroesophageal reflux disease in infants and children. MATERIALS AND METHODS: This prospective cross-sectional study consisted of pediatric patients aged between 1 month and 18 years old with symptoms suggestive of gastroesophageal reflux disease. Patients were divided into 2 groups as younger than 24 months (group 1) and older than 24 months (group 2). Twentyfour hours multichannel intraluminal impedance-pH monitoring was performed on the patients. RESULTS: This study included 50 pediatric patients. The mean age of the patients was 5.35 ± 4.92 years. In group 1, total reflux events were fewer than group 2 (P = .03) by pH monitoring. In group 1, the number of non-acid reflux events was higher than in group 2 and in group 2, the number of acidic reflux events was higher than group 1 (P = .04). Reflux was detected by multichannel intraluminal impedance-pH monitoring in 13 (40%) of 32 patients who were assessed as negative by pH monitoring. CONCLUSION: It was concluded that more reliable results were obtained when the 2 methods were used together in this study.

The effect of passive smoking on the laryngospasm rate in children sedated during the esophagogastroduodenoscopy.

OBJECTIVES: To investigate the rate of laryngospasm with sedation during the esophagogastroduodenoscopy (EGD) procedure in children exposed to passive smoking and to examine the frequency of complications due to laryngospasm. METHODS: A single-blind, prospective, observational study with a total of 518 patients evaluated according to the American Society of Anesthesiologists (ASA) physical status as classification I-II, aged between 1-18 years, and planned to undergo an EGD procedure, were included. Age, gender, weight, ASA assessment, exposure to smoking (the mother, the father, both parents were smokers, or not exposed to smoking), drug doses used in sedation, and anesthesia-related complications, such as cough, decrease in oxygen saturation, and laryngospasm were recorded. RESULTS: Of the 518 patients included in the study, 213 had no smoking exposure history. Oxygen saturation did not decrease below 90% in patients who did not have any smoking exposure. In addition, no laryngospasm was observed in this group. However, 4 (11.4%) of 31 patients whose mother only smoked, 10 (5.1%) of 187 child patients whose father only smoked, and 12 (16.4%) of 61 patients whose mother and father both smoked experienced laryngospasm during the procedure. CONCLUSION: The rate of cough, laryngospasm, and hypoxia development increased during the sedation carried out in the EGD procedure in children who were exposed to passive smoke.Clinicaltrial.gov ID: NCT03920046.

Fluoroscopy-guided balloon dilatation of benign esophageal strictures in children: 11-year experience.

BACKGROUND: The esophageal stricture is an important clinical problem in children, and the treatment is difficult. OBJECTIVE: To evaluate the results of fluoroscopy-guided balloon dilatation of benign pediatric esophageal strictures and to suggest a safety range for balloon diameters. MATERIALS AND METHODS: We retrospectively reviewed the medical records of children who underwent fluoroscopy-guided esophageal balloon dilatation for treatment of benign esophageal stricture from February 2008 to July 2019. We recorded the demographic data of the children, technical details of each procedure, balloon diameter, number of repeated procedures, clinical and technical success rates, complications and follow-up period. Technical success was defined as the disappearance of the waist formation on the balloon catheter, and clinical success was defined as no need for re-dilation or other treatment methods during the 1-year follow-up after the procedure. These children were divided into groups and evaluated according to esophageal stricture etiology. RESULTS: Technically successful procedures included 375 balloon dilatations in 116 patients (67 boys; age range: 1 month to 18 years; mean age: 4.3 ± 4.8 standard deviation [SD] years at the initial dilatation). The follow-up period was 1-138 months (median: 41 months; mean: 44 months) since the last dilatation. In this study, the clinical success rate was 34% per procedure (120 of 353 procedures) and 85% per patients (91 of 107 patients). The total complication rate per procedure was 0.5%, and the perforation rate was 0.25% per session. CONCLUSION: Fluoroscopy-guided esophageal balloon dilatation is an effective and reliable method for treating benign esophageal strictures in children.

Coexistence of Three Different Mutations in a Male Infant: neurofibromatosis Type 1, Progressive Familial Intrahepatic Cholestasis Type 2 and LPIN3.

IntroductionThe coexistence of progressive familial intrahepatic cholestasis type 2, failure to thrive due to an LPIN3 mutation, and stigmata of neonatal neurofibromatosis represents a complex diagnostic challenge. Case report: We present a child with cholestasis requiring hepatic transplantation, explained by the progressive familial intrahepatic cholestasis type 2, failure to thrive could be contributed to by the LPIN3 mutation, and skin findings along with the family history of the patient was due to neurofibromatosis type 1. Conclusion: Our case illustrates the complexities of multiple genetic mutations in a child.

Liver Involvement in Children during the Diagnosis of Celiac Disease: A Single-Center Experience from Turkey.

BACKGROUND: Liver abnormalities in Celiac disease (CD) are common. The aim of this study was to investigate the children with CD who were followed up in our clinic presenting with elevated aminotransferase levels. METHODS: In this study, the data of 419 pediatric patients with CD were retrospectively analyzed, and those with elevated aminotransferase levels during the diagnosis of CD were assessed. RESULTS: Elevation of aminotransferase levels was found in 66 (15.7%) patients among the 419 patients during the diagnosis of CD. The mean age of these patients was 7.33±3.96 years. Liver enzymes were mildly elevated in 63 (95.4%) patients. However, half of the patients with elevated liver enzymes had a 1.25-fold increase in aminotransferase levels. Patients with hypertransaminasemia had higher weight loss and lower folic acid values compared with patients with normal liver enzymes. Patients' liver tests were reverted to normal, except for two patients with chronic liver disease, after 9.27±3.16 months of administering a gluten-free diet. CONCLUSION: Patients with liver involvement should be investigated for CD. Especially, mildly elevation of aminotransferase levels should be taken into account by pediatricians for Celiac hepatitis.

The Assessment of the Quality of Life in Children with Chronic Liver Disease.

BACKGROUND: Improvement in the quality of life (QoL) of patients with chronic diseases is as important as medical care. This study aimed to evaluate the QoL of children with chronic liver diseases and to determine related factors. METHODS: For this study, 101 children with chronic liver disease, 100 healthy controls, and their parents were included. The Pediatric Quality of Life Scale (PedsQL) was used to evaluate health-related QoL; higher scores indicate better QoL. Patients were evaluated before and after initiation of treatment and being educated about their illness. RESULTS: The mean patient age was 12.9 ± 3.9 years. Total PedsQL scores of the patients and the healthy control group were 38.6 ± 18.9 and 55.4 ± 14.3, respectively (P = .01). The scores of the parents of the patient and control groups were 35.4 ± 14.2 and 54.0 ± 16.9, respectively (P = .02). Patient and parent scores were positively correlated. Significantly higher scores were found in the 5-10 age group compared to the 10-15 and 15-18 age groups in the psychosocial score category. An increase in the QoL scores of patients who were started on medication other than steroid treatment was observed in the sixth month of treatment (35.8 ± 13.4 vs. 33.6 ± 8.9, P = .01, respectively). CONCLUSION: Both children with chronic liver diseases and their parents have a perceived lower QoL than healthy peers. The effect of chronic liver disease on psychosocial health is more pronounced in children older than 10 years. The quality of life is inversely proportional to the severity of the disease. It was observed that primary or symptomatic treatments have a positive impact on the perception of QoL, with the exception of steroid treatment.

Aspirin-induced hepatotoxicity and anemia in children with acute rheumatic fever.

BACKGROUND: The aim of this study was to investigate the frequency of anemia and hepatotoxicity associated with aspirin use in patients with acute rheumatic fever. METHODS: Patients with acute rheumatic fever followed at Erciyes University, Faculty of Medicine, Department of Pediatric Cardiology between 2015-2018 were reviewed retrospectively. RESULTS: A total of 286 patients with acute rheumatic fever were analysed. Aspirin treatment was started in 53 of the 286 patients (18.5%) due to arthritis. The mean age of the patients who used aspirin was 10.7 ± 2.5 years. Aspirin-induced hepatotoxicity developed in 9 (17%) of the 53 patients. Naproxen or ibuprofen was given to these patients as an alternative to aspirin. No side effects occurred in patients receiving naproxen or ibuprofen. In addition, 30% of 53 patients were initially anemic. The mean duration of aspirin use in the hepatotoxic patients who had anemia was longer than patients without anemia (p=0.02). CONCLUSIONS: Patients with acute rheumatic fever should be closely monitored for aspirin hepatotoxicity. When aspirin hepatotoxicity develops, naproxen or ibuprofen treatment can be used safely.

Hepatitis-associated aplastic anemia in pediatric patients: single center experience.

INTRODUCTION: Hepatitis-associated aplastic anemia is a rare type of acquired aplastic anemia that occurs after hepatitis. This study investigated cases with hepatitis-associated aplastic anemia. METHODS: The files of patients with hepatitis-associated aplastic anemia who were followed up in our hospital between 2011-2019 were reviewed retrospectively. RESULTS: A total of 15 patients with hepatitis-associated aplastic anemia (10 males, 5 girls; mean age 10.26 ± 3.61 years) were analyzed. The mean duration between hepatitis and aplastic anemia was 5.06 ± 4.19 months. The majority of patients had mild hepatitis. The causes of hepatitis were detected only in six patients: three had hepatitis B, one had hepatitis A, one had autoimmune hepatitis and, one had a hydatid cyst. The cause of hepatitis was not found in nine patients. Only one patient with hepatitis-associated aplastic anemia developed spontaneous remission, and the others required immunosuppressive therapy and/or hematopoietic stem cell transplantation. Only one patient died because of sepsis. The other patients are still under follow-up and treatment. CONCLUSION: Patients with hepatitis-associated aplastic anemia, mostly of unknown cause, can be successfully treated with immunosuppressive therapy and/or hematopoietic stem cell transplantation.

Liver Involvement in Congenital Hypopituitarism.

OBJECTIVE: Cholestatic jaundice in early infancy is a complex diagnostic challenge. Cholestasis caused by endocrine disease is rare and poorly recognized. The aim of this paper is to report patients with liver dysfunctions resulting from hypopituitarism. METHODS: Six patients with liver dysfunction diagnosed as hypopituitarism were studied and followed up at Uludag University Faculty of Medicine. RESULTS: The median age of the patients at first presentation was 2.5 mo. Three patients were diagnosed with congenital hypopituitarism at the first visit, and the other three were diagnosed during follow-up. Serum aminotransferase levels were very high in two patients and only moderately elevated in the others. Combined adrenal, thyroid, and growth hormone deficiencies were diagnosed in two patients, while remaining 4 patients had various combinations of adrenal, thyroid, and growth hormone deficiencies. Liver function abnormalities resolved between 10 d and 2 mo follow-up after hormone replacement therapy. CONCLUSIONS: Abnormal liver biochemical test results due to hormonal deficiencies in infants should be considered in the differential diagnosis by pediatricians. Hormone replacement therapy is the basis of treatment.

A rare cause of vomiting in an adolescent: gastric Burkitt`s lymphoma.

Altay D, Özcan A, Ünal E, Deniz K, Özkan KU, Patiroglu T, Arslan D. A rare cause of vomiting in an adolescent: gastric Burkitt`s lymphoma. Turk J Pediatr 2019; 61: 431-435. Burkitt`s lymphoma, which is the most commonly diagnosed pediatric gastrointestinal tumor, usually affects the intestinal tract. However, the diagnosis of gastric Burkitt`s lymphoma in childhood is extremely rare. Here, we have reported the case of an adolescent male patient with vomiting and weight loss symptoms who was diagnosed with Burkitt`s lymphoma of the pyloric antrum. The patient responded very well to chemotherapy and he did not develop tumor lysis syndrome. Based on this case report, gastric Burkitt`s lymphoma might be included in the differential diagnoses of pediatric patients who experience vomiting that results in significant weight loss.

Helicobacter pylori Infection in Children: Nutritional Status and Associations with Serum Leptin, Ghrelin, and IGF-1 Levels.

BACKGROUND: Helicobacter pylori is associated with gastrointestinal diseases such as gastritis, peptic ulcers, malignancy and lymphoma, and extra-gastrointestinal conditions. H. pylori infection is negatively associated with children's growth. Chronic inflammation of the stomach that results in the loss of appetite and, dysregulation of neuroendocrine hormones such as leptin, and ghrelin are the probable reasons of this negative association. The objective of this study is to determine the serum levels of leptin, ghrelin, and IGF-1 in H. pylori-infected children and their relations with growth. MATERIALS AND METHODS: A hundred and sixty-one school children aged between 6 and 14 years were selected randomly from five primary schools representing a cross section of population. Demographic and sociocultural characteristics, and anthropometric measurements were recorded. Serum H. pylori IgG, insulin-like growth factor-1, leptin, and ghrelin levels were measured in all children. The children were grouped according to the nutritional status and Helicobacter pylori seropositivity. Nutritional indices were compared among groups in association with serum leptin, ghrelin, and insulin-like growth factor-1 levels. RESULTS: H. pylori IgG positivity was found in 34.2%, and 14.9% of children were malnourished. H. pylori seropositivity was significantly higher in older ages (10.32 ± 2.26 vs 9.53 ± 2.36 years, p = .036), and body weight and height Z scores were significantly lower in H. pylori-seropositive children (-0.33 ± 1.08 vs 0.04 ± 1.26, p = .044 and 0.13 ± 0.92 vs 0.23 ± 0.91, p = .018 respectively). H. pylori seropositivity was found to be an independent risk factor for shorter body height (p = .01). Serum leptin, ghrelin, and IGF-1 levels were not associated with H. pylori IgG seropositivity (0.35 vs 0.55 ng/mL, p = .3; 3267.4 ± 753.0 vs 2808.3 ± 911.4 pg/mL, p = .06; 470 ± 176 vs 521 ± 179 ng/mL, p = .32, respectively). CONCLUSIONS: Children infected with H. pylori are prone to short stature. This effect seems to be independent of neuroendocrine hormones.