Acquired factor VII deficiency in pediatric inflammatory bowel disease: Report of three cases.

Bleeding disorders can exacerbate gastrointestinal bleeding in inflammatory bowel disease (IBD) at the time of diagnosis or flares. Factor VII (FVII) deficiency is a life-threatening rare congenital bleeding disorder in childhood. This study describes three adolescent patients with IBD accompanied by acquired FVII deficiency. This is the first case series of patients with IBD accompanied by FVII deficiency. We hypothesized that inflammation, accelerated consumption, disease severity, and weight loss can cause decreased FVII activity in patients diagnosed with IBD. To control intestinal bleeding, we must keep in mind factor deficiencies in IBD.

Evaluation of children diagnosed with a lower respiratory tract infection due to Human metapneumovirus.

BACKGROUND: Human metapneumovirus (hMPV) is one of the leading causes of acute respiratory infections and bronchiolitis in infants. A history of prematurity and chronic diseases such as congenital heart disease or asthma/reactive airway disease (RAD) increases the risk of severe lower respiratory tract infection (LRTI) due to hMPV. In this cross-sectional study, we aimed to analyze the clinical outcome and risk factors for severe disease in children with LRTI due to hMPV. METHODS: The current cross-sectional study included children between 28 days and 18 years of age with the diagnosis of hMPV-associated LRTI hospitalizations, over two years from January 2016 to September 2018 in Health Science University Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital. hMPV virus was detected by the multiplex polymerase chain test (PCR) (Commercial Multiplex Real-Time PCR: FTD Respiratory 21 plus, Fast Track Diagnostics, Luxembourg) from a nasopharyngeal swab. Patients who had positive results in multiplex PCR tests with other viral agents simultaneously were not included in the study. Data were retrospectively collected from the computerized hospital system. RESULTS: In this cross-sectional study, 62 patients who were hospitalized with the diagnosis of LRTI due to hMPV infection were included. Thirty-five (55.7%) of the patients were male. The median age was one year (2 months-15 years). Fifty-one (82.2%) patients were younger than two years. The median hospital length of stay was found to be 10 days (2-33 days) in patients with an underlying disease and 7,5 days (ranging from 2 to 20 days) in the patients without an underlying disease, this difference was significant (p=0.031). CONCLUSIONS: Clinicians should consider hMPV as an important pathogen of LRTI even in healthy children, although we expect a poor course of disease in children with an underlying disease.

COmparisoN of TastES of Available NutriTional integrated or non-integrated formulas for infants older than 1 year of age with cow's milk allergy: A multicenter, prospective, single blind, cross-sectional observational clinical study (CONTEST Study).

Palatability of the infant formulas lacking cow milk protein formulas is reported by parents to be an important drawback. The purpose of this study is to examine decisions made by mothers of infants having cow milk protein allergy, and physicians concerning the palatability of unflavored extensively hydrolyzed formulas and amino acid-based formulas. We conducted a multi-center, randomized, single-blinded, observational taste study involving 149 pediatricians from gastroenterology and allergy subspecialties at 14 tertiary healthcare units from different regions of Turkey and involving 94 mothers of infants with cow milk protein allergy. Blinding was performed for seven formulas available in the market, which were the most commonly prescribed for feeding: four AAFs (Neocate-Numil®, Aptamil Pregomin AS-Numil®, Alfamino-Nestle®, Comidagen-Mamma®), one AAF specifically designed to address the growing nutritional and lifestyle needs of children >1 year (Neocate Junior-Numil®), 2 eHFs (Bebelac Pepti Junior-Numil®, Similac Alimentum-Abott®). Considering all three formula characteristics, Neocate junior-Numil® ranked as the number 1 product among seven products by mothers (63.8%) and physicians (69.8%). The ratings of mothers were significantly higher than the physicians (8.1 points and 6.1 points, respectively; p < 0.001). No difference was found in terms of taste, smell, and appearance for Neocate junior-Numil® between the mothers' and physicians' ratings. Since caregivers have responsibility for careful selection of replacement products for infants with cow milk protein allergy, it is noteworthy that increased awareness and confidence in the palatability characteristics of these products should motivate mothers and physicians to comply with replacement treatment in the long term.

[Role of Hematological Parameters in the Diagnosis of Juvenile Idiopathic Arthritis in Children with Arthritis]. / Papel de los parámetros hematológicos en el diagnóstico de Artritis Idiopatica Juvenil en niños con artritis.

INTRODUCTION: Early diagnosis and treatment of arthritis are essential for the prognosis of the disease. Especially during the active phase of juvenile idiopathic arthritis (JIA), a prompt diagnosis is necessary to ma nage the disease properly. New inflammation markers such as neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), mean platelet volume (MPV), and platelet distribution width (PDW) have been investigated in various inflammatory disorders. This study aimed at the diagnostic value of NLR, MLR, MPV, and PDW in differentiating JIA in children with arthritis. PATIENTS AND METHOD: Case-control study with 324 children with arthritis (case group) and 324 healthy children (control group). Additionally, children with arthritis were grouped into JIA and non-JIA. Medical records of children aged 0-18 were retrospectively reviewed. Hematological parameters at the time of diagnosis were recorded. NLR, MLR, MPV, and PDW were analyzed in the study groups. RESULTS: In the case group, 52.8% were boys, and 47.2% were girls; the mean age was 7.7 ± 4.0 years. The NLR in the case group was significantly higher than the control one (p = 0.001). The mean MPV was lower in the case group than the control group (p = 0.001). There were no differences in NLR and MPV between JIA and non-JIA groups (p = 0.062, p = 0.689). The JIA group's mean PDW was lower than the non-JIA group (p = 0.001). CONCLUSION: The increase in NLR may indicate inflammation but has no superiority in distinguishing JIA from other arthritis causes. Platelet distribution width was lower in JIA patients, but its clinical utility is limited.

Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Influenza-related hospitalizations due to acute lower respiratory tract infections in a tertiary care children's hospital in Turkey.

BACKGROUND: The influenza virus is a significant cause of acute lower respiratory tract infections (LRTI) requiring hospitalization in childhood and leads to severe morbidity and mortality, especially in certain risk groups. OBJECTIVES: The study aims to evaluate acute LRTI due to influenza in a tertiary care hospital and the risk factors for hospitalization among Turkish children. STUDY DESIGN: Children between 1 month and 18 years of age who were hospitalized at Dr. Behçet Uz Children's Hospital between January 2016 and March 2018 with lower respiratory tract infection that tested positive for influenza by PCR were included. Children with viral coinfections were excluded. Patient files were retrospectively scanned from the hospital computerized system in terms of age, underlying diseases, whether antiviral therapy was used, and length of hospital stay. Statistical analysis was performed using SPSS statistical software. RESULTS: The study included 131 patients with a median age of 2 years (1 month-15 years). Sixty-seven (51,1%) patients were younger than two years. Influenza A was isolated in 129 patients and B in 2 patients. Fifty-two patients (39,7%) had underlying medical conditions, and the most common one was malignancies (12/52, 23%). This was followed by neurodevelopmental diseases (9/52, 17,3%), prematurity (9/52 patients, 17,3%), primary immunodeficiency (8/52, 15,4%), asthma (7/52, 13,4%), Down syndrome (4/52, 7,7%), chronic renal disease (2/52, 3,8%) and congenital heart diseases (1/52, 1,9%). The mean length of stay (LOS) was 12,3 ± 9,5 days (2-60 days). The LOS was found to be statistically longer (15,2 ± 12,1 days, 3-60 days) in patients with an underlying disease compared to previously healthy patients (10,4 ± 6,7 days, 2-35 days) (p = 0.01). CONCLUSIONS: Hospitalization due to influenza-related acute LRTI is not an issue only for patients with an underlying medical condition. Vaccination should be considered not only for those with underlying medical conditions but also for healthy children.

MicroRNA-17, MicroRNA-19b, MicroRNA-146a, MicroRNA-302d Expressions in Hepatoblastoma and Clinical Importance.

Hepatoblastoma (HB) is the most common liver malignancy in children. The prognosis changes according to the histologic subtypes of HB. In the present study, we aimed to characterize the expression level of selected microRNAs (miRNAs) in HB as well as in histologic subtypes, and to consider the association with the prognosis. A total of 22 HB tumor samples, subtyped as fetal (n=16) and embryonal (n=6), and 10 nontumorous surrounding liver samples were evaluated in this study. Expressions of miR-17, miR-146a, miR-302d, and miR-19b were analyzed in 22 HB tumor samples and 10 nontumorous surrounding liver samples by quantitative real-time polymerase chain reaction. Lower miRNA-17 expression levels were obtained in tumor samples in comparison with nontumorous surrounding liver samples (P=0.028). Lower miRNA-17 expression was significant for predicting prognosis in HB patients (area under receiver-operator characteristic curve=0.875, P=0.044). A higher-level of miR-19b was found in embryonal samples (P=0.008). Overall and event-free survival was not found to correlate with miRNA expression levels (P>0.05). This research finds miRNA-17 and miRNA-19b expression levels can provide important data on diagnosis and prognosis in HB showing different clinical behaviors.

Efficacy and safety of long-term thiopurine maintenance treatment for ulcerative colitis in Turkey: A single-center experience.

BACKGROUND/AIMS: Thiopurines are widely used in the treatment of inflammatory bowel disease, but data are limited. Or aim was to determine the outcome of thiopurine application in children diagnosed with ulcerative colitis (UC). MATERIALS AND METHODS: Forty-eight patients with UC, diagnosed at our center between 2005 and 2016 and applied azathiopurine (AZA), were included in the study. Data were collected retrospectively. The diagnosis of UC was based on the conventional clinical, radiological, histological, and endoscopic assessment. All patients with UC at this intercept were analyzed at the 4- and 6-week and 3-month intervals after remission to determine patient characteristics, thiopurine properties, and its efficacy and toxicity. Determination of remission, relapse, and steroid refractoriness/dependency were guided according to the European Crohn's and Colitis Organisation consensus. RESULTS: Azathiopurine was started at the median 1 month (0-12 months), and it was applied thereafter for maintenance (n=43). Response to remission induction was obtained in 40 (93.7%) patients. The median duration of the AZA treatment was 24 months (5-63). In 34 (85%) of the 40 children, it was well tolerated until the last visit. During the follow-up, adverse events occurred in 6 patients. These are leucopenia, neutropenia, vomiting, diarrhea, and skin rush. CONCLUSION: Thiopurine is an appropriate treatment option for remission in patients with UC. For a long-term follow-up, it is very important to identify patients with UC who have clinical remission with side effects and with thiopurine application.

Infant colic or early symptom of autism spectrum disorder?

BACKGROUND: Gastrointestinal (GI) disorders are common in autism spectrum disorder (ASD). Infant colic (IC), the functional GI disorder of infancy, has not been evaluated in this patient group. The aim of this study was therefore to determine the rate of IC in ASD and investigate a possible association between ASD and IC. METHODS: The subjects consisted of 100 ASD patients (mean age, 6.6 ± 3.5 years) and 100 healthy controls (mean age, 5.3 ± 2.8 years). The parents were questioned using the diagnostic criteria for infant colic for clinical research purposes defined in Rome IV to diagnose IC, retrospectively. The sample size was estimated using a maximum type I error probability of 5% (alpha) and a type II error of 20%. RESULTS: The rate of IC was 16% and 17% in the ASD group and control group, respectively (P ˃ 0.05). Excessive crying with late onset and long duration in infants was defined as persistent crying. The rate of persistent crying was significantly higher in the ASD group than in the control group (32% vs 9%, P < 0.001). The relative risk of persistent crying was 4.40 in ASD. The likelihood of being misdiagnosed with IC in this group was 78%. CONCLUSION: The rate of IC is not increased in patients with ASD, but infants with excessive crying should be very thoroughly evaluated before being diagnosed with IC. In particular, persistent crying in infants (i.e. excessive crying with late onset and long duration) may be an early symptom of ASD.

Post-transplant malignancies in pediatric liver transplant recipients: Experience of two centers in Turkey.

BACKGROUND/AIMS: A liver transplant is the preferred treatment for patients with end-stage liver disease, as it usually results in longterm survival. However, due to the use of chronic immunosuppressive therapy, which is necessary to prevent rejection, de novo cancer is a major risk after transplantation. The aim of this study was to assess the incidence of post-transplant malignancies in children after liver transplantations. MATERIALS AND METHODS: The study group consisted of 206 liver transplant recipients, with no history of cancer, including hepatocellular carcinoma, in two liver transplantation centers in Turkey between 1997 and 2015. Data were obtained from patient's data chart. RESULTS: In the study group, de novo cancer was diagnosed in 13 of the 206 patients. Post-transplant lymphoproliferative disease (PTLD) occurred in seven (53.8%) patients and other malignancies in six of the 13 patients. The types of PTLD were as follows: B-cell origin (n=2), Epstein-Barr virus (EBV)-related (n=2), T-cell origin (n=1), and Hodgkin's lymphoma (n=2). EBV DNA was isolated from seven patients, three of whom developed PTLD. The others developed Kaposi's sarcomas, Burkitt's lymphomas, cutaneous large-cell lymphomas, Hodgkin's lymphomas, and liver sarcomas. CONCLUSION: After transplantation, immunosuppressive treatment is unavoidable, increasing the risk of malignancies. However, a close follow-up and periodic screening can reduce cancer-related mortality and morbidity.

Higher-Than-Conventional Subcutaneous Regular Insulin Doses Following Diabetic Ketoacidosis in Children and Adolescents

OBJECTIVE: To evaluate the effect of initial insulin dosage on glycemic control in the first 48 hours of subcutaneous regular insulin therapy after resolution of diabetic ketoacidosis (DKA). METHODS: Records of patients with DKA hospitalized in the past 3 years [n=76, median age=10.0 (6.0-12.0) years, Male/Female: 44/32] were reviewed. The patients were designated into two groups according to distribution of starting doses of subcutaneous insulin. Group 1 (n=28) received a median dose of 1.45 U/kg/day (1.41-1.5) and group 2 (n=48) a median dose of 0.96 U/kg/day (0.89-1). Clinical and laboratory data were analyzed. RESULTS: Median, minimum, and maximum blood glucose levels of Group 1 in the first 48 hours of treatment were significantly lower than that of Group 2 [213 (171-242) vs. 255 (222-316), p=<0.001; 102 (85-151) vs. 129 (105-199), p=0.004; and 335 (290-365) vs. 375 (341-438), p=0.001, respectively]. The number of patients who experienced hypoglycemia (<70 mg/dL) were similar [Group 1, 5 (17.9%) vs. Group 2, 4 (8.3%), p=0.276] and none had severe hypoglycemia. In Group 1, the ratio of blood glucose levels within the target range (100-200 mg/dL) were higher (37.5% vs. 12.5%) and the number of results >200 mg/dL were lower (50% vs. 81.3%) compared to Group 2 (p=0.001 and p<0.001, respectively). CONCLUSION: After resolution of DKA, a higher initial dose of 1.4-1.5 U/kg/day regular insulin is associated with better glycemic control in children and adolescents without an increase in risk of hypoglycemia.

Trichobezoar in Vagina: Assessment for Child Sexual Abuse and Diagnostic Result of Forensic Science.

Vaginal discharge and bleeding in children require a through and thoughtful evaluation to diagnose the underlying problem including infections, sexual abuse, and vaginal foreign bodies. We report a 6-year-old girl presenting with bloody vaginal discharge, carefully evaluated for sexual abuse, and finally diagnosed as a vaginal foreign body after vaginoscopy. A rolling hair ball was extracted from the vagina and was diagnosed as trichobezoar pathologically without any endo-ecto-mesodermal residual tissue. The hair ball was genetically detected and diagnosed to belong herself by containing no foreign structure. Child sexual abuse was ruled out by forensic interview at CAC and report of forensic science that reported genetic structure belonging to the child. Medicolegal assessment helped in final diagnosis to exclude child sexual abuse.

Autoimmune hepatitis and long-term disease course in children in Turkey, a single-center experience.

INTRODUCTION: The aim of this study is to determine clinic and laboratory features, treatment protocols, treatment responses, and long term follow-up of children with autoimmune hepatitis (AIH) in a region of Turkey followed at Ege University. MATERIALS AND METHODS: The records of 47 children with AIH between 1998 and 2012 were retrospectively analyzed for clinical profiles, treatment response, relapse rate, and long-term side effects. RESULTS: The median age of the children was 10±4.1 years (55.3% females). A total of 29 patients presented with chronic hepatitis (61.7%). According to the autoantibody profiles, 40 (85.1%) and seven (14.9%) cases were classified as type 1 and type 2, respectively. Presentation with acute hepatitis and chronic hepatitis was significantly higher in type 1 disease. Laboratory findings at presentation was found similar among races as well as AIH types (P>0.05). The prednisolone was used for remission induction in 37 patients; 86.4% (n: 32) achieved a complete response, 2.7% (n: 1) achieved a partial response, and four patients (10.8%) showed no response. Maintenance was attained by low-dose steroid plus thiopurine and relapse in steroid responders (n: 32) was 9.4% (n: 3) at 8, 12, and 48 months. A total of 36% (n: 24) had neither acute nor chronic treatment side effects. Bone marrow suppression was observed in five patients and hyperglycemia was observed in one patient (10.6 and 2.1%), respectively. CONCLUSION: AIH type 1 prevails in children in a region of Turkey during the second decade of life. Low-dose corticosteroids combined with azathioprine are found.

Validity and reliability study of the pediatric Rome III questionnaire for Turkish children and adolescents.

BACKGROUND/AIMS: Questionnaire on Pediatric Gastrointestinal Symptoms: Rome III version (QPGS-RIII), originally developed in English, was adapted to different languages in order to widen its use. The aim of this study was to evaluate the validity and reliability of a questionnaire on the Pediatric QPGS-RIII parent-report form for children and self-report form for children and adolescents, which has been adapted into Turkish. MATERIALS AND METHODS: The study group comprised 7-18-year-old children/adolescents (n=690) who presented to Ege University School of Medicine, Department of Child Health and Diseases outpatient clinic. In the study, the validity and reliability of the QPGS-RIII Turkish version of the questionnaire was established. RESULTS: Confirmatory factor analysis (CFA) resulted in a 10-factor model satisfactory construct for the validity and in acceptable indices of goodness of fit. Standardized coefficients determined with CFA in the Turkish version of the instrument ranged between 0.15 and 0.87 in the 7-9-year-old children and between 0.13 and 0.98 in the 10-18-year-old children/adolescents. t-values of all the factor loadings were significant. In addition, the test-retest analyses were above 0.70, except for the abdominal migraine factor. CONCLUSION: Findings relating to the validity and reliability of the study indicated that the Turkish version of the instrument could be adequately used to assess functional gastrointestinal disorders (FGIDs) in Turkish children and adolescents. The Turkish version of the instrument is therefore recommended to be used in epidemiologic studies and in clinical trials to be conducted in a Turkish-speaking population.

Can neonatal hepatitis be more fatal than biliary atresia?

BACKGROUND/AIMS: The basic problem in diagnosis of neonatal cholestasis (NC) is to differentiate biliary atresia (BA) from other non-obstructive disorders. Because if bile flow cannot be provided by surgery, BA leads to cirrhosis and death within the first year of life. The aim of the present study is to determine histopathological features that may help to differentiate BA from neonatal hepatitis (NH). MATERIAL AND METHODS: This retrospective study was carried out on 105 liver biopsy specimens of 74 infants with NC who were diagnosed between 2003 and 2012. RESULTS: The mean age was 76.5 ± 40.64 days. The most valuable biopsy findings for the discrimination between NH and BA, in decreasing order of importance, were ductular proliferation (p < 0.001), cholestasis in neoductuli (p < 0.001), fibrosis (p = 0.002), and extramedullar hematopoiesis (p = 0.02). While Kasai operations were performed in 19 cases, liver transplantation was performed in 10 cases. Survival rate among the death cases with BA was longer than the survival time of the death cases with NH (p = 0.023). Currently more children live with a close to normal quality of life with portoenterostomy and/or liver transplantation. On the contrary, NH can be more fatal with associated disorders such as growth retardation, specific infections, respiratory distress, and metabolic or endocrine diseases.

Prevelance of hepatitis D co-enfection in children with hepatitis B infection: cross-sectional analyses from Western Turkey.

BACKGROUND/AIMS: Effective hepatitis B virus control has warranted a decline in hepatitis B virus prevalence over the world with a relevant reduction in hepatitis B virus-associated delta hepatitis. However, despite the dramatic decline in hepatitis D virus infection rate, no further decrease was recorded after 2000. This cross-sectional study aims to investigate: I- The prevalence of hepatitis D virus co-infection in children with hepatitis B virus infection in Western Turkey; II- The influence of neonatal hepatitis B virus vaccination on hepatitis D virus co-infection rate; and III- The impact of co-infection on prognosis of liver disease. MATERIALS AND METHODS: Serological markers of hepatitis B virus and hepatitis D virus infections were determined by ELISA in patients with chronic hepatitis during immune tolerance, immunoactive, HBeAg-negative chronic, and inactive carrier state. Delta co-infection rate was evaluated in two groups, children born before and after the national neonatal mass vaccination has started (before and after 2000). Viral load, serum alanine aminotransferase, and histological grade were evaluated in co-infected cases. RESULTS: Overall hepatitis delta virus infection rate was 1,76% (3/170); two patients with eAg-negative chronic hepatitis B and one patient in the immunoactive phase were infected with hepatitis D virus. Mean fibrosis score of hepatitis D virus -infected cases and hepatitis B virus -infected counterparts were 4±1,7 and 1,3±1, respectively (p: 0,006). Hepatitis D virus infection was detected in 2 out of 158 children born before and in 1 of 12 born after the neonatal vaccination program. Hepatitis B e-antibody was detected in two patients with delta co-infection (11 and 6 years old), and all mothers of delta hepatitis cases were chronically hepatitis B virus-infected. CONCLUSIONS: Delta hepatitis is rare among hepatitis B virus-infected children in the Western region of Turkey. Despite the success of the national vaccination program, delta hepatitis is not a vanishing disease and it has a grave prognosis due to development of early cirrhosis.

An autoimmune disease refractory to immunosuppressive regimens: celiac disease diagnosed long after liver transplantation.

CD is defined as T-lymphocyte-mediated gluten sensitivity. Although CD is known to affect the small intestine, it is nonetheless a multisystem disorder. Liver involvement in CD may vary from isolated hypertransaminasemia to cirrhosis. Because CD is an inappropriate immune response to gluten proteins, strict gluten-free diet is the principal therapy, along with management of liver dysfunction. In patients who fail to respond to a gluten-free diet, immunosuppressive drugs may improve intestinal inflammatory activity in untreated CD. The present case report is of a 25-yr-old woman with diarrhea lasting several weeks. The patient had received a liver transplant 13 yr earlier, and presented with cryptogenic cirrhosis diagnosed as CD. This appears to be the first case of its kind in which a pediatric long-term liver transplant patient presents with diarrhea eventually diagnosed as CD whose diet included gluten, and who was treated by an immunosuppressive drug regimen. Because of the normalization of CD-related antibodies in the post-transplantation period without gluten restriction, CD should be part of a list of diagnostic possibilities in liver transplant patients presenting with diarrhea of unknown etiology.