Fecal Calprotectin and Phenotype Severity in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis / 대한소아소화기영양학회지

Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator protein dysfunction, pancreatic insufficiency, or prolonged pulmonary infection. Fecal calprotectin (FC) has been used as a noninvasive method to detect inflammation. Therefore, the aim of the current metaanalysis was to investigate the relationship between FC and phenotype severity in patients with CF. In this study, searches were conducted in PubMed, Science Direct, Scopus, and Embase databases up to August 2021 using terms such as “cystic fibrosis,” “intestine,” “calprotectin,” and “inflammation.” Only articles published in English and human studies were selected. The primary outcome was the level of FC in patients with CF. The secondary outcome was the relationship between FC and clinical severity. Statistical analysis was performed using Comprehensive Meta-Analysis software. Of the initial 303 references, only six articles met the inclusion criteria. The mean (95% confidence interval [CI]) level of FC was 256.5 mg/ dL (114.1-398.9). FC levels were significantly associated with pancreatic insufficiency (mean, 243.02; 95% CI, 74.3 to 411.6; p=0.005; I2 =0), pulmonary function (r=–0.39; 95% CI, –0.58 to –0.15; p=0.002; I2 =60%), body mass index (r=–0.514; 95% CI, 0.26 to 0.69; p2 =71%). While FC is a reliable noninvasive marker for detecting gastrointestinal inflammation, it is also correlated with the severity of the disease in patients with CF.

Growth factors in cystic fibrosis

Introduction: Cystic fibrosis is one of the most common autosomal recessive diseases that affects sweat glands and mucosa. CF is a hereditary disease with annual incidence of about 2500 new cases in United Kingdom. Insulin-like growth factor-1 [IGF-1] and insulin-like growth factor binding protein-3 levels decrease in CF. The aim of this study was to assess the role of growth peptides in patients with CF

Method: We searched PubMed, Google scholar, IranMedex, and Scientific Information Database [SID] in September 2012 to April 2014. We included clinical studies with available abstracts and full texts that were in English or Persian languages. Manual searching was conducted within the reference lists of articles. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data

Result: The earliest study was published in 1997 and the most recent one was in 2014. Study participants were adults in 3 studies [20%] and 12 studies [80%] were conducted in children. Patients with CF have lower levels of IGF-1 and there is a significant correlation between IGF-1 levels and growth index in patients with CF

Conclusions: IGF-1 decreases in children with CF and might be the cause of poor growth and low body mass index in these children

Medical treatment for hepatopulmonary syndrome:a systematic review

Introduction: Hepatopulmonary syndrome [HPS] is known as a chronicliver disease associated with severe pulmonary deoxygenation due tointrapulmonary vascular vasodilation. Although liver transplantationis accepted as a main treatment of HPS, identifying effective drugs forrecovery of HPS can be effective in postponing the transplantation anddecreasing the mortality rate of patients before the transplantation. In thisstudy we briefly reviewed the pathogenesis of HPS and also systematicallyreviewed the current pharmacological treatment of HPS

Method: Pubmed, Scopus, and Google scholar were searched for therelevant English language clinical and experimental articles about themedications used in the treatment of HPS

Results: A total of 38 articles were included in this study which mostlyresulted in decreasing NOS expression, NO production, endothelin-1activation, intrapulmonary angiogenesis and increasing oxygenation

Conclusion: Various drugs have been proposed in treatment of HPS butmore large controlled trial studies, is necessary to determine the exactefficacy of each drugs for HPS recovery

Synbiotic for prevention of antibiotic-associated diarrhea in children: a randomized clinical trial

Antibiotic- associated diarrhea is a common problem in pediatric population. There is growing interest in probiotics, probiotics and synbiotics for prevention of this complication because of their worldwide availability as dietary supplements. The aim of this study was to assess the efficacy of a synbiotic mixture in prevention of antibiotic- associated diarrhea. In this randomized controlled trial, 218 patients [111 in the synbiotic and 107 in the placebo group] aged 6 months to 14 years with respiratory tract infection and/ or otitis media who needed antibiotic treatment in outpatient setting, were enrolled. They received 1 billion Colony Forming Unit of seven probiotics species plus Fructooligosaccharide in form of powder or placebo [matched for size, shape, and volume] for 7 days. Amoxicillin, Amoxicillin-clavalanic acid, cefixim and Azithromicin were the most common drugs used by physcicians Mothers recorded stool frequency and consistency daily for 7 days. We found no significant difference [P>0.05] in occurrence of diarrhea between synbiotic and placebo groups. This synbiotic mixture did not appear to reduce antibiotic- associated diarrhea in children. Further studies are needed to investigate the potential benefits of Synbiotics in prevention of this disease

Synbiotics in children with cow's milk allergy: a randomized controlled trial

Cow's milk protein allergy usually occurs in infants within the first months of life. It can affect several organs, but gastrointestinal symptoms are the most clinical symptoms observed. The most effective treatment is restricting the cow 's milk protein in mother and infant's diet. Lactobacillus GG supplementation in infant could be effective through modulation of the immune system and the gut microflora. Thirty two breastfed infants with Cow's milk protein allergy were enrolled in a double-blinded randomized controlled trial in which they received Synbiotic [n=16] or placebo [n=16] once a day for one month, simultaneously with Cow's milk protein restriction in mother and infant's diet. Clinical gastrointestinal symptoms [vomiting, colic, rectal bleeding and diarrhea], head circumference, body length and weight were recorded at the beginning, the end of the first and third month of study. Percentage of increment in head circumference and weight were statistically more in synbiotic group compared with placebo group at the end of the first and third month of study. There was no significant difference in resolution of clinical gastrointestinal symptoms [vomiting, colic, rectal bleeding or diarrhea] and percentage of increment in body length. Synbiotic supplementation in infants may improve increment of head circumference and weight gain, but has no effect on resolution of clinical symptoms

Characteristics and outcome of three forms of autoimmune hepatitis in Iranian children

To define the clinical features, biochemical and histological findings and outcome of three forms of autoimmune hepatitis. In a cross sectional study between November 2001 to January 2008 in Tehran and Mashhad university of medical sciences, 61 children who diagnosed as AIH [40 girls and 21 boys] have been analyzed for their clinical, serological, and histological data. Variables analyzed included age, sex, clinical presentation, hepatic function, immunoglobulins, autoimmunity markers, histology and clinical evolution. According to the auto-antibodies profile, AIH patients were classified as type I AIH [ANA or smooth-muscle antibodies or both positive], type II [anti-LKM-1 positive] and type III [antibody negative]. We analyzed data of 61 children with AIH. 51 patients [median age: 10 [0.7-14] years had anti-nuclear and/or smooth muscle antibody [ANA/ASMA or both], 5 [median age: 7 [2-8] years] had liver/kidney microsomal antibody [LKM-1]. 5 patients had no detectable autoantibody. At presentation: 60% had jaundice or symptoms of acute hepatitis; LKM-1 positive were younger. Interface hepatitis was seen in 100% and fibrosis +/- cirrhosis were found in 70%. Frequency of AIH was 2:1 in girls. Type 1 was the most frequent diagnosis [83%] and was more frequent in older children. Relapse and treatment failure were common in type II. AIH may have different clinical presentation in children. Althout most of cases may have high inflammatory activity or cirrhosis, good response to treatment and remission may accur

Determine efficacy of a short course of montelukast in children with intermittent asthma and viral infection

Mild intermittent asthma is common in children and viral infections are responsible for the majority of exacerbations. As leukotrienes are potent inflammatory mediators, some studies have shown that Montelukast, a leukotriene receptor antagonist, may be effective on reduction of asthma symptom. To determine whether a short course of Montelukast in asthmatic children with common cold would modify the severity of an asthma episode. Children, aged 6-12 years with intermittent asthma participated in this randomized, double-blind, placebo-controlled clinical trial. Treatment with Montelukast or placebo was initiated at the onset of viral upper respiratory tract infection and continued for 7 days. Primary outcomes included the clinical manifestation: duration of episodes, daily symptom, nights symptoms and activity limitation. Secondary outcomes included the need for beta agonist usage, oral prednisolone, physician visit, hospital admission and school absence. A total of 187 children with intermittent asthma were randomized, 93 to Montelukast group and 94 to placebo group. Montelukast significantly decreased the cough by 17.3% [P<0.001], nighttime awakenings by 5.4% [P=0.01], interference with normal activity by 6% [P<0.01], time off from school by 6% [P<0.01], beta-agonist usage by 17.2% [P<0.001] and doctor visits by12.2% [P<0.01] compared to placebo. Whereas there was a non significant reduction in wheezing, tachypnea, respiratory distress, asthma exacerbation, oral prednisolone and hospitalization [P=0.8]. A short course of Montelukast, introduced at the first sign of a viral infection, results in a reduction in cough, beta-agonist use and nights awakened, time off from school and limitation of activity. More studies are needed to evaluate the optimal dose and duration of treatment

Kawasaki disease presenting as acute clinical hepatitis

Kawasaki disease is a systemic vasculitis of children. Among gastrointestinal symptoms of this disease jaundice occurs uncommonly. We present a 23 month boy with icter and clinical hepatitis and final diagnosis of kawasaki disease

Quality of life in cystic fibrosis children

Cystic fibrosis [CF] is a chronic, multisystem genetic disease with a wide variability in clinical severity. The measurement of quality of life in CF provides additional information about the impact of this disease. This article tries to assess quality of life [QoL] in children and adolescents with CF and to compare it with control group. Patients 2-18 years old with admission diagnosis of cystic fibrosis entered the study. QoL was observed in CF patients and compared with control group. Based on children's reports, significant differences between the CF patients and control group were noted for emotional, physical, social, school performance, and total scores [P<0.05]. Based on parents' reports, quality of life score in CF patients from the physical point of view as well as social and total scores were decreased [P<0.05]. QoL in CF patients seems to be low, and therapy programs should take into account the suggestive perceived quality of life

Ultrasonographic triangular cord sign and gallbladder abnormality in diagnosis of biliary atresia

Early diagnosis of biliary atresia is very important for better outcome of treatment. Ultrasonography is one of the diagnostic tools for early differentiation of biliary atresia from other causes of neonatal cholestasis. It has been reported that triangular cord sign [TACS] in sonography is a reliable sign for diagnosis of biliary atresia. The aim of this study was to re-assess the accuracy of TACS alone and coupled with an abnormal gallbladder in the diagnosis of biliary atresia. Infants with prolonged cholestatic jaundice underwent ultrasonography and liver biopsy. Results of ultrasound scans [TASC and gallbladder abnormality] were compared with histopathological findings. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Ultrasonographic findings for diagnosis of biliary atresia based on liver histopathology were studied. The sensitivity, specificity and accuracy of TACS for diagnosis of biliary atresia were 36%, 95% and 77% respectively. Positive predictive value and negative predictive value was 77%. The sensitivity and specificity of gallbladder abnormality for diagnosis of biliary atresia were 36% and 88% respectively. Positive predictive value of TACS coupled with gallbladder abnormality for diagnosis of biliary atresia was 100%. The Ultrasonographic TACS is very specific for diagnosis of biliary atresia. Positive predictive value and accuracy of this sign is much higher than of gallbladder abnormality. The sensitivity of TACS for diagnosis of biliary atresia is very low

Role of pulse oximetry in detecting mild to moderate hepatopulmonary syndrome in children

Hepatopulmonary syndrome [HPS] refers to arterial hypoxemia caused by pulmonary vasodilation, which is a consequence of portal hypertension. HPS is associated with increased morbidity and mortality; thus, it is important to diagnose this entity as soon as possible for treatment to be administered. In a cross-sectional study, 40 children [6 months to 14 years old] with chronic liver disease were enrolled. In all patients, measurements of Oxygen saturation [SaO[2]] were performed with a pulse oximeter in the supine position [SPO[2]] and then in the upright position [delta SPO[2]]. Children were divided into three groups: i] those with both SPO[2]>96% and deltaSPO[2]>4%; ii] children with either SPO[2]>96% or delta SPO[2] > 4%; and iii] those with neither of these signs. Then, contrast-enhanced echocardiography [CEE] and arterial blood gas [ABG] were performed. Finally, the prevalence of mild to moderate HPS was calculated in the three groups. There were 30 patients who had neither of the two signs, of which 9 had HPS. Ten patients had one of the two signs, in whom 4 had HPS. None of the patients had both signs. The sensitivity of the pulse oximetry was 30%, specificity was 77%, positive predictive value was 38% and negative predictive value was 70%.There is a significant prevalence of HPS in cirrhotic patients which effects prognosis. Based on our study results, we have determined that pulse oximetry could not be a reliable screening procedure in mild to moderate HPS. It is recommended to use gold standard tests [echocardiography and arterial blood gasometry] for the screening and diagnosis of HPS in children.

Predisposing factors for nephrolithiasis and nephrocalcinosis in cystic fibrosis

Cystic fibrosis [CF] is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentration. There is controversy about predisposing factors of nephrolithiasis and nephrocalcinosis in patients with cystic fibrosis. We assessed the results of metabolic evaluation in patients with cystic fibrosis and its correlation with nephrocalcinosis. Forty five CF patients, mean age 47.1 months, were enrolled in the study. No one had past history of nephrolithiasis and/or nephrocalcinosis. The records were reviewed for clinical characteristics and all patients underwent metabolic evaluation including serum electrolyte measurements and spot urine analysis. Ultrasonography was performed in all patients to detect nephrocalcinosis and urolithiasis. Nephrocalcinosis was found in 5 [11%] patients. No patient had clinical symptoms of nephrolithiasis and/or micro/macroscopic hematuria. Metabolic evaluation of the CF patients versus normal reference values showed decreased serum uric acid in 48.8%, elevated serum phosphate in 24.4%, and urine oxalate excretion in 51%. Metabolic evaluation of the nephrocalcinosis positive patients versus nephrocalcinosis negative group showed no statistical difference in serum electrolytes. The mean value of urine calcium excretion was lower in patients with nephrocalcinosis [P=0.001]. Despite lack of any significant correlation, higher numerical hyperoxaluria was observed in patients with severe steatorrhea. There was no statistical correlation between steatorrhea and urine calcium as well as oxalate excretion. Hypocalciuria in the nephrocalcinotic CF patients may be seen. It can be hypothesized that hypocalciuria may be due to a primary defect in renal calcium metabolism in CF patients

Evidence based medicine in pediatric practice: brief review

Practicing medicine according to the best evidence is gaining popularity in the medical societies. Although this concept, which is usually called Evidence Based Medicine [EBM] has been explained in many resources, it has not been addressed enough in pediatrics. In this review, we briefly explained Evidence Based Medicine approach and its applications in pediatrics in order to help the pediatricians to efficiently integrate EBM into their daily practice

Autoimmune hepatitis in children, clinical features and biochemical of Iranian children

There are only a very small number of reports which discuss subtype, sex distribution, clinical features and laboratory characteristics of autoimmune hepatitis in children. The aim of this study was both to define the clinical features, biochemical and histological findings and also to determine the age and sex related distribution of autoimmune hepatitis [AIH]. Data of 30 children presenting with AIH [20 girls and 10 boys] have been analyzed for their clinical, serological, and histological profile. The most common presenting signs or symptoms were jaundice [60%], abdominal mass [23.4%] and constitutional symptoms [weakness, anorexia and paleness] [6.7%]. About 10% of patients had an acute hepatitis like clinical presentation. Twenty two children [73.3%] [15 girls, 7 boys, 2.1:1] had AIH type 1 and 4 patients [13.3%] type 2 due to specific autoantibodies. Four children could not be classified. In liver biopsy, 100% of patients had interface hepatitis and fibrosis with or without cirrhosis were found in 60%. In our cohort the prevalence of AIH was 2:1 in girls. Type 1 was the most frequent diagnosis [73.3%] and was more prevalent in older children. Patients with type 2 were younger. The clinical presentation of AIH in children was unspecific and each type could only be differentiated by the determination of the specific autoantibodies

Autoimmune hepatitis in children, clinical features and biochemical of Iranian children

There are only a very small number of reports which discuss subtype, sex distribution, clinical features and laboratory characteristics of autoimmune hepatitis in children. The aim of this study was both to define the clinical features, biochemical and histological findings and also to determine the age and sex related distribution of autoimmune hepatitis [AIH]. Data of 30 children presenting with AIH [20 girls and 10 boys] have been analyzed for their clinical, serological, and histological profile. The most common presenting signs or symptoms were jaundice [60%], abdominal mass [23.4%] and constitutional symptoms [weakness, anorexia and paleness] [6.7%]. About 10% of patients had an acute hepatitis like clinical presentation. Twenty two children [73.3%] [15 girls, 7 boys, 2.1:1] had AIH type 1 and 4 patients [13.3%] type 2 due to specific autoantibodies. Four children could not be classified. In liver biopsy, 100% of patients had interface hepatitis and fibrosis with or without cirrhosis were found in 60%. In our cohort the prevalence of AIH was 2:1 in girls. Type 1 was the most frequent diagnosis [73.3%] and was more prevalent in older children. Patients with type 2 were younger. The clinical presentation of AIH in children was unspecific and each type could only be differentiated by the determination of the specific autoantibodies