Manuscript Review at the Journal of Pediatric Gastroenterology and Nutrition: The Impact of Reviewers on Editor Decisions.

OBJECTIVE: Given the importance of scholarly work in academic medicine, better understanding of the manuscript review process (MRP) is useful for authors, reviewers, and editorial boards. We aim to describe the MRP at the Journal of Pediatric Gastroenterology and Nutrition (JPGN), assess the correlation between editor decisions and reviewer recommendations, and provide transparency to this process. METHODS: All manuscripts submitted in 2018 to JPGN were included in this analysis. Data included reviewers' manuscript scores and recommendations, time spent on each review by reviewers, the editor's rating of the reviewers' reviews, the editor's first decision, and final outcome. Data were collated using the JPGN manuscript submission website, Editorial Manager. RESULTS: 1023 manuscripts were submitted to JPGN in 2018 and included in this analysis. Of these, 486 manuscripts had at least two peer reviewers. The recommendations of the two reviewers were in agreement 43% of the time. Intra-class correlation (ICC) between the two reviewers suggests moderate agreement (ICC = 0.40). When both reviewers agreed to Not Reject (289/486), the editor agreed in 93% of cases (269/289). When both reviewers agreed to Reject (55/486), the editor agreed 100% of the time (55/55). The reviewers disagreed in about one-third of submissions (142/486), and the editor recommended to Reject in two-thirds of these cases (95/142). Overall, inter-reviewer agreement strongly correlated with the editor's initial decision (P < 0.001). CONCLUSIONS: The editor most often agreed with reviewers' assessments when there was concordance between the two reviewers' recommendations. About a third of peer reviews result in discordant recommendations between the two reviewers.

Complications of indwelling central venous catheters in pediatric liver transplant recipients.

In pLT recipients, the advantages of ICVCs need to be weighed against the risk of complications. This single-center retrospective study aimed to review ICVC complications in our cohort of pLT recipients. We performed chart reviews of pLT patients having undergone transplant between 01/2000 and 03/2014 and who underwent ICVC placement either before or after LT. We identified 100 ICVC in 85 patients. Overall observation time was 90 470 catheter-days. There was no difference in catheter lifespan between those inserted pre- or post-transplant; 46% of ICVC presented a complication. Most frequent complications were MD and infection. The infection rate was 0.09 per 1000 catheter-days, and MD rate was 0.36 per 1000 catheter-days. Patients having received technical variant grafts were more at risk of complications. To the best of our knowledge, this is the first study examining ICVC complications in pLT recipients. We conclude that ICVC have a high rate of MD. Children receiving technical variants may be more at risk of complications. By removing ICVC in a select number of patients at six months post-insertion, we might avoid as much as 60% of complications.

Risk factors for early and late biliary complications in pediatric liver transplantation.

BC are a common source of morbidity after pediatric LT. Knowledge about risk factors may help to reduce their incidence. Retrospective analysis of BC in 116 pediatric patients (123 LT) (single institution, 05/1990-12/2011, medium follow-up 7.9 yr). One-, five-, and 10-yr survival was 91.1%, no patient died of BC. Prevalence and risk factors for anastomotic and intrahepatic BC were examined. There were 29 BC in 123 LT (23.6%), with three main categories: 10 (8.1%) primary anastomotic strictures, eight (6.5%) anastomotic leaks, and three (2.4%) intrahepatic strictures. Significant risk factors for anastomotic leaks were total operation time (increase 1.26-fold) and early HAT (<30 days post-LT; increase 5.87-fold). Risk factor for primary anastomotic stricture was duct-to-duct choledochal anastomosis (increase 5.96-fold when compared to biliary-enteric anastomosis). Risk factors for intrahepatic strictures were donor age >48 yr (increase 1.09-fold) and MELD score >30 (increase 1.2-fold). To avoid morbidity from anastomotic BC in pediatric LT, the preferred biliary anastomosis appears to be biliary-enteric. Operation time should be kept to a minimum, and HAT must by all means be prevented. Children with a high MELD score or receiving livers from older donors are at increased risk for intrahepatic strictures.

High bone density in adolescents with obesity is related to fat mass and serum leptin concentrations.

OBJECTIVES: Obesity has been associated with increased bone mass, but the mechanisms involved are still poorly understood. We aimed to explore the relation between bone mineral density and factors known to influence bone formation in obese and lean adolescents. METHODS: We recruited 24 obese and 25 lean adolescents in a case-control study. Total body bone mineral density (TB-BMD) z scores and body composition were determined using dual-energy x-ray absorptiometry. We measured 25-hydroxyvitamin D (25-OH-D), glucose, insulin, and leptin concentrations. Physical activity (PA) level was quantified using accelerometer. RESULTS: TB-BMD z score was higher, whereas 25-OH-D and PA levels were lower in obese compared with lean subjects (TB-BMD z score 1.06 ±â€Š0.96 vs 0.26 ±â€Š0.91, P = 0.004; 25-OH-D 9.9 ±â€Š6.4 vs 18.5 ±â€Š7.4 ng mL, P < 0.001; PA level 308.3 ±â€Š22.1 vs 406.8 ±â€Š29.2 count min, P = 0.01). TB-BMD z score was not related to 25-OH-D or PA levels, but was positively correlated with leptin concentration and fat mass (P < 0.05). Vitamin D concentration was negatively correlated with fat mass (P < 0.001). CONCLUSIONS: Despite lower serum vitamin D and PA levels, BMD was higher in adolescents with obesity and associated with higher serum leptin concentrations. Furthermore, adolescents with obesity have lower vitamin D serum concentrations than lean controls, probably owing to its distribution in adipose tissue.

Parental functioning improves the developmental quotient of pediatric liver transplant recipients.

Psychomotor development in pediatric liver transplant (LT) recipients depends on several factors. Our aim was to evaluate the importance of parental involvement and family dynamics on psychomotor development by assessing (i) children and parents individually, (ii) the parent-child relationship, and (iii) the correlation between parental functioning and patient outcome, all before and after LT. Age-appropriate scales were used before and after LT. Twenty-one patients, 19 mothers, and 16 fathers were evaluated. Developmental quotient (DQ): No subjects scored in the "very good" range. The proportion of children with deficits increased from LT to two yr: 17.6% vs. 28.6%. Subjects 0-2 yr were more likely to have normal DQ at transplant (66.7% vs. 50% for older children). Abnormal DQ was more prevalent two yr post-LT in children older at LT (p = 0.02). The mother-child relationship was normal in 59% of families pre-LT and in 67% at two yr. The relationship was more favorable when the child received a transplant as an infant (p = 0.014 at 12 months post-LT). Normal DQ was associated with higher maternal global functioning score pre-LT (p = 0.03). Paternal performance scores were higher than maternal scores. Children transplanted after two yr of age suffer greater long-term deficits than those transplanted as infants.

Increased pancreatic fat fraction is present in obese adolescents with metabolic syndrome.

OBJECTIVES: Little is known about pancreatic fat accumulation and its possible associations with metabolic syndrome (MetS) and glucose metabolism. The aim of the present study was to quantify pancreatic fat fraction (PFF) in lean and obese adolescents and explore its relation to metabolic parameters. METHODS: We recruited 25 lean and 24 obese adolescents. PFF and visceral adipose tissue (VAT) were determined using magnetic resonance imaging. We measured blood pressure, fasting glucose, insulin, liver enzymes, leptin, and lipid levels. Obese subjects underwent an oral glucose tolerance test. RESULTS: PFF was significantly higher in obese than in lean subjects (4.8±1.2 vs 3.6±0.9; P<0.001) and was associated with VAT, γ-glutamyltransferase, triglycerides, high-density lipoprotein cholesterol, leptin concentrations, and MetS (P<0.05 for all). None of the obese subjects had glucose intolerance, but when adjusted for VAT, the following 3 parameters correlated negatively with PFF: fasting and 30- minute and 120-minute insulin levels. We divided subjects into 3 groups: group I, lean without MetS; group II, obese without MetS; and group III, obese with MetS, and observed that PFF increased gradually among groups (I: 3.56%±0.88%; II: 4.70%±1.06%; III: 5.34%±1.49%; P<0.001). CONCLUSIONS: Obese adolescents accumulate fat in the pancreas. PFF correlates with the presence of MetS. Even in the absence of glucose intolerance, pancreatic fat deposition is associated with impaired insulin response to glucose overload. This suggests that ß-cell dysfunction may already be present in nondiabetic obese adolescents, mirroring what has been shown in adults, and that pancreatic fat accumulation may participate in obesity-associated pancreatic endocrine dysfunction.

Electrogastrography abnormalities appear early in children with diabetes type 1.

OBJECTIVE: The objective of the study was to evaluate gastric myoelectrical activity in young patients with diabetes and to correlate it with their metabolic control [fasting blood glucose, glycosylated haemoglobin, and fructosamine] and BMI during a 3 years follow-up. METHODS: Surface electrogastrography (EGG) was performed on 49 children with diabetes aged 10.3±4.4 (mean±SD) years and 17 age-matched healthy controls after fasting glucose, glycosylated haemoglobin, and fructosamine were measured. EGG parameters [percentage of bradygastria, 3 cycles per minute, tachygastria, dominant frequency instability coefficient, and power ratio] were analysed and compared with blood analysis. RESULTS: Patients with diabetes exhibited an increase in preprandial bradygastria 7.9±8.8 cpm (mean±SD) compared with controls 2.1±1.0 (P=0.011), with an associated decrease in preprandial normogastria (72.2±14.5 vs. 82.7±14.7; P=0.013). Normogastric power ratio (postprandial/ preprandial power) was significantly increased in the children with diabetes compared with controls (mean: 6.67 vs. 3.14, P=0.034). A longer duration of diabetes was associated with an increased risk of EGG abnormalities (P=0.036). Marked hyperglycaemia at the time of study was associated with postprandial bradygastria (P=0.01) and power ratio bradygastria (P=0.042). Changes in glycosylated haemoglobin, fructosamine and BMI did not affect EGG parameters. CONCLUSIONS: EGG abnormalities, presented early in a high proportion of diabetic children, are related to the acute hyperglycaemia. These abnormalities are not consistently present in the follow-up studies and not related to the glycosylated haemoglobin and fructosamine. Diabetic autonomic neuropathy is therefore an unlikely pathogenic factor for EGG abnormalities in children with diabetes.

Molecular and biochemical characterisation of a novel mutation in POLG associated with Alpers syndrome.

BACKGROUND: DNA polymerase γ (POLG) is the only known mitochondrial DNA (mtDNA) polymerase. It mediates mtDNA replication and base excision repair. Mutations in the POLG gene lead to reduction of functional mtDNA (mtDNA depletion and/or deletions) and are therefore predicted to result in defective oxidative phosphorylation (OXPHOS). Many mutations map to the polymerase and exonuclease domains of the enzyme and produce a broad clinical spectrum. The most frequent mutation p.A467T is localised in the linker region between these domains. In compound heterozygote patients the p.A467T mutation has been described to be associated amongst others with fatal childhood encephalopathy. These patients have a poorer survival rate compared to homozygotes. METHODS: mtDNA content in various tissues (fibroblasts, muscle and liver) was quantified using quantitative PCR (qPCR). OXPHOS activities in the same tissues were assessed using spectrophotometric methods and catalytic stain of BN-PAGE. RESULTS: We characterise a novel splice site mutation in POLG found in trans with the p.A467T mutation in a 3.5 years old boy with valproic acid induced acute liver failure (Alpers-Huttenlocher syndrome). These mutations result in a tissue specific depletion of the mtDNA which correlates with the OXPHOS-activities. CONCLUSIONS: mtDNA depletion can be expressed in a high tissue-specific manner and confirms the need to analyse primary tissue. Furthermore, POLG analysis optimises clinical management in the early stages of disease and reinforces the need for its evaluation before starting valproic acid treatment.

Immune reconstitution inflammatory syndrome and solid organ transplant recipients: are children protected?

The IRIS was initially described in HIV-positive patients as a sudden clinical deterioration after the introduction of highly active retroviral therapy. It is believed that IRIS is caused by a restored and exaggerated inflammatory immune response to different infectious or non-infectious triggers. This abnormal response is the consequence of an imbalance between pro-inflammatory and anti-inflammatory states. Recently, IRIS has also been reported in adult SOT recipients, causing local and systemic manifestations, and compromising long-term graft function and patient survival. However, IRIS has to date not been reported in pediatric SOT recipients. Here we review what is known and speculated about the pathogenesis of IRIS and propose that children may be relatively protected from IRIS.

An overview of cow's milk allergy in children.

Food allergies have increased over the past decade and are an important problem in daily clinical practice. They affect 6% of children and 3 to 4% of adults. Furthermore, around 20% of the population falsely believe that they are allergic to some foods and follow unnecessarily restrictive diets. For infants, the problem is even more acute as they need appropriate feeding in order to achieve normal growth and avoid bone and metabolic problems. Although any food can cause a reaction, few foods are responsible for the large majority of the symptoms: i.e., milk, eggs, wheat, peanuts, nuts, fish, shellfish. Of these, cow's milk allergy is frequently suspected in small children. It can be responsible of a variety of symptoms and can be caused by IgE-mediated or non-IgE-mediated reactions. The diagnosis relies on a detailed history, skin tests, laboratory tests, an elimination diet and food challenges. The overall natural evolution of the disease is favourable with most patients achieving tolerance to milk by the age of five years, but some patients will remain allergic for life.

Food poisoning as a cause of acute liver failure.

We report a 9-year-old girl with cereulide-producing Bacillus cereus food poisoning, who developed fulminant hepatitis, renal and pancreatic insufficiency, shock, and prolonged seizures. She was transferred to our institution for hepatic transplantation before her diagnosis was established. As a result of rapid identification of the microorganism and supportive care, liver transplantation was avoided, and she recovered fully.

Hyperinflammation in chronic granulomatous disease and anti-inflammatory role of the phagocyte NADPH oxidase.

Chronic granulomatous disease (CGD) is an immunodeficiency caused by the lack of the superoxide-producing phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. However, CGD patients not only suffer from recurrent infections, but also present with inflammatory, non-infectious conditions. Among the latter, granulomas figure prominently, which gave the name to the disease, and colitis, which is frequent and leads to a substantial morbidity. In this paper, we systematically review the inflammatory lesions in different organs of CGD patients and compare them to observations in CGD mouse models. In addition to the more classical inflammatory lesions, CGD patients and their relatives have increased frequency of autoimmune diseases, and CGD mice are arthritis-prone. Possible mechanisms involved in CGD hyperinflammation include decreased degradation of phagocytosed material, redox-dependent termination of proinflammatory mediators and/or signaling, as well as redox-dependent cross-talk between phagocytes and lymphocytes (e.g. defective tryptophan catabolism). As a conclusion from this review, we propose the existence of ROS high and ROS low inflammatory responses, which are triggered as a function of the level of reactive oxygen species and have specific characteristics in terms of physiology and pathophysiology.