Pediatric inflammatory bowel disease: What's new and what has changed?

The incidence and prevalence of inflammatory bowel disease (IBD) is on the rise in North America and worldwide, with young children being the fastest growing patient population. It is therefore essential for pediatricians and pediatric sub-specialists to be able to recognize signs and symptoms suspicious for a new diagnosis of IBD, as well as potential complications associated with IBD or its treatment. This article reviews the most recent literature regarding clinical presentation, helpful diagnostic clues, newer monitoring tools being used by pediatric gastroenterologists, and emerging new biologic and small molecule treatments.

Intestinal Failure-Associated Liver Disease and Growth Pre- and Post-Transition to a Composite Lipid Emulsion.

OBJECTIVES: Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups. METHODS: At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons. RESULTS: Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 µmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 µmol/L; P = 0.54) and by PN cessation (4 vs 4 µmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores ( P > 0.05). CONCLUSIONS: In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.

Pediatric Patient and Caregiver Satisfaction With the Use of Transabdominal Bowel Ultrasound in the Assessment of Inflammatory Bowel Diseases.

OBJECTIVES: Transabdominal bowel ultrasound (TABUS) is emerging as an attractive, noninvasive tool in inflammatory bowel disease (IBD). Patient and caregiver experience with TABUS is not well described. We aimed to determine pediatric patient and caregiver satisfaction with TABUS and the impact of IBD severity, gender, age, and a history of anxiety on satisfaction. METHODS: Pediatric patients (0-18 years old) with suspected IBD prospectively underwent baseline TABUS, magnetic resonance enterography (MRE), blood work, stool studies, and endoscopy. Patients and their caregiver each completed a cross-sectional satisfaction questionnaire (5-point Likert scale) after the baseline investigations. RESULTS: There were 54 patients included (67% male). The majority were completely satisfied and strongly agree TABUS was better tolerated than other investigations, regardless of disease severity ( P > 0.05). Patients with higher Simple Endoscopic Score for Crohn Disease (SES-CD) scores felt that TABUS increased their understanding of their IBD ( P < 0.05) and disease location ( P < 0.05). Patients with Crohn disease had similar responses to those with ulcerative colitis, but more strongly agreed that TABUS was better than MRE and endoscopy ( P < 0.05). Those with anxiety did not have an increased level of worry about potential ultrasound findings ( P > 0.05). CONCLUSIONS: Pediatric patients and their caregivers were highly satisfied with TABUS, preferring it to other modalities. It did not lead to increased worry, and was particularly important in those with severe IBD. These findings support wider implementation of this well tolerated and preferred monitoring tool in pediatrics.

New Feeding Assessment Scale for individuals with genetic syndromes: Validity and reliability in the CHARGE syndrome population.

AIM: To develop a feeding scale for parents/care givers of individuals of all ages with genetic syndromes experiencing extensive feeding and swallowing problems. Second, to assess its validity and reliability in CHARGE syndrome. METHODS: The new Feeding Assessment Scale (FAS) was adapted from a scale for children who need prolonged tube feeding (Paediatric Assessment Scale for Severe Feeding Problems, PASSFP). Ten parents piloted the new scale before it was sent out with the PASSFP and feeding history questions. A subset completed the new scale again 4-8 weeks later. RESULTS: One hundred parents of individuals with CHARGE syndrome participated from around the world. The new scale had good construct validity, with a significant effect for an increased number of feeding risk factors having higher scale scores (P < 0.001). Face validity was high, as scores significantly differed between individuals whose parents identified their feeding difficulties as very mild, mild, moderate, severe and very severe (P < 0.001). Test-retest reliability (r = 0.94, P < 0.001) and internal consistency (Cronbach's alpha 0.91) were both high. There was significant convergent validity between the new scale and the PASSFP (r = -0.79, P < 0.001). CONCLUSIONS: This new tool is reliable and valid for parents/care givers of individuals with CHARGE syndrome. It can be used to assess the current severity of feeding difficulties and to track progress before and after treatment. It expands upon previous existing tools in that it can be used in both individuals who are not tube fed, as well as in those who are, as well as across the life-span.

#Cleftlip/Palate: What Is the World Talking About?

OBJECTIVE: Studies have begun analyzing how the world converses on social media platforms about medical/surgical topics. This study's objective was to examine how cleft lip and palate, two of the most common birth defects in the world, are discussed on the social media platform Twitter. No study to date has analyzed this topic. METHODS: Tweets were identified using any of the following: cleft, cleft lip, cleft palate, #cleft, #cleftlip, #cleftpalate. Eight months between 2017 and 2018 were analyzed. MAIN OUTCOME MEASURES: The primary outcome was the tweet subject matter. Secondary outcomes were author characteristics, tweet engagement, multimedia, and tweet accuracy. RESULTS: A total of 1222 tweets were included. #Cleft was the most common hashtag (71%), and it was significantly associated with more retweets (P = .03). Twenty-seven countries tweeted, with the United States (34%) and India (27%) producing the most. Charities (36%), hospitals (14%), and physicians (13%) were the most common authors. Over three-quarters of tweets were self-promotional. The top content included charity information (22%) and patients' cleft stories (14%). Tweets about patient safety/care and surgical service trips generated the most engagement. The accuracy of educational tweets was 38% low accuracy and 1% inaccurate. One hundred forty-nine tweets (12%) discussed a published research article, but 41 tweets did not share a link. CONCLUSIONS: Charities dominate the cleft lip/palate "Twitterverse." Most tweets were self-promotional, and over a third of educational tweets were low accuracy. As the cleft social media community continues to grow, we recommend using the hashtag #cleft to reach a wider audience.

Gastrointestinal and feeding difficulties in CHARGE syndrome: A review from head-to-toe.

CHARGE syndrome is an autosomal dominant genetic condition that is primarily diagnosed based on clinical features, with genetic testing available for confirmation. The CHARGE mnemonic stands for some of the common characteristics: coloboma, heart defects, atresia/stenosis of the choanae, retardation of growth/development, genitourinary anomalies, and ear abnormalities (CHARGE). However, many of the common clinical features are not captured by this mnemonic, including cranial nerve dysfunction, considered by some to be one of the major diagnostic criteria. Over 90% of individuals experience feeding and gastrointestinal dysfunction, which carries great morbidity and mortality. The aim of this review is to examine the nature of gastrointestinal (GI) symptoms and feeding difficulties in CHARGE syndrome, focusing on their underlying pathology, associated investigations, and available treatment options. We also provide information on available tools (for parents, clinicians, and researchers) that are important additions to the lifelong healthcare management of every individual with CHARGE syndrome. We review how cranial nerve dysfunction is one of the most important characteristics underlying the pervasive GI and feeding dysfunction, and discuss the need for future research on gut innervation and motility in this genetic disorder.

Imaging and endoscopic tools in pediatric inflammatory bowel disease: What's new?

Pediatric inflammatory bowel disease (IBD) is a chronic inflammatory disorder, with increasing incidence and prevalence worldwide. There have been recent advances in imaging and endoscopic technology for disease diagnosis, treatment, and monitoring. Intestinal ultrasound, including transabdominal, transperineal, and endoscopic, has been emerging for the assessment of transmural bowel inflammation and disease complications (e.g., fistula, abscess). Aside from surgery, IBD-related intestinal strictures now have endoscopic treatment options including through-the-scope balloon dilatation, injection, and needle knife stricturotomy and new evaluation tools such as endoscopic functional lumen imaging probe. Unsedated transnasal endoscopy may have a role in patients with upper gastrointestinal Crohn's disease or those with IBD with new upper gastrointestinal symptoms. Improvements to dysplasia screening in pediatric patients with longstanding colonic disease or primary sclerosing cholangitis hold promise with the addition of virtual chromoendoscopy and ongoing research in the field of artificial intelligence-assisted endoscopic detection. Artificial intelligence and machine learning is a rapidly evolving field, with goals of further personalizing IBD diagnosis and treatment selection as well as prognostication. This review summarized these advancements, focusing on pediatric patients with IBD.

Characterizing the human intestinal chondroitin sulfate glycosaminoglycan sulfation signature in inflammatory bowel disease.

The intestinal extracellular matrix (ECM) helps maintain appropriate tissue barrier function and regulate host-microbial interactions. Chondroitin sulfate- and dermatan sulfate-glycosaminoglycans (CS/DS-GAGs) are integral components of the intestinal ECM, and alterations in CS/DS-GAGs have been shown to significantly influence biological functions. Although pathologic ECM remodeling is implicated in inflammatory bowel disease (IBD), it is unknown whether changes in the intestinal CS/DS-GAG composition are also linked to IBD in humans. Our aim was to characterize changes in the intestinal ECM CS/DS-GAG composition in intestinal biopsy samples from patients with IBD using mass spectrometry. We characterized intestinal CS/DS-GAGs in 69 pediatric and young adult patients (n = 13 control, n = 32 active IBD, n = 24 IBD in remission) and 6 adult patients. Here, we report that patients with active IBD exhibit a significant decrease in the relative abundance of CS/DS isomers associated with matrix stability (CS-A and DS) compared to controls, while isomers implicated in matrix instability and inflammation (CS-C and CS-E) were significantly increased. This imbalance of intestinal CS/DS isomers was restored among patients in clinical remission. Moreover, the abundance of pro-stabilizing CS/DS isomers negatively correlated with clinical disease activity scores, whereas both pro-inflammatory CS-C and CS-E content positively correlated with disease activity scores. Thus, pediatric patients with active IBD exhibited increased pro-inflammatory and decreased pro-stabilizing CS/DS isomer composition, and future studies are needed to determine whether changes in the CS/DS-GAG composition play a pathogenic role in IBD.

Dual Biologic Therapy in a Patient With Niemann-Pick Type C and Crohn Disease: A Case Report and Literature Review.

Dual biologic therapy has become a new area of interest in inflammatory bowel disease (IBD). Monogenic/polygenic IBD and the role of genetics in IBD is an evolving field, with many of these patients having difficult treatment courses. We present a case of a teenage patient with Niemann-Pick disease type C and Crohn colitis, who sustained clinical remission only after escalating to dual biologic therapy (anti-tumor necrosis factor alpha [infliximab] and anti-interleukin-12/anti-interleukin-23 [ustekinumab]). A literature review of dual biologic therapy in pediatric IBD revealed 8 case series and 1 cohort study. In pediatric patients with genetic disorders and IBD who are not responding adequately to biologic therapy, adding a second biologic medication with a different mechanism of action may be efficacious. Targeting both anti-tumor necrosis factor alpha (which induces pro-inflammatory cytokines) and the pro-inflammatory cytokines themselves (interleukin-12/interleukin-23) may be important in impaired macrophage function and increased cytokine response. Our case adds to the sparse literature on the utility of combining ustekinumab and infliximab in pediatric IBD and is the first to describe its use for treating ongoing active luminal disease.

Safety and Benefits of Intraoperative Enteral Nutrition in Critically Ill Pediatric Burn Patients: A Systematic Review and Pooled Analysis.

Burn injuries significantly increase a patient's metabolic demand. Adequate nutrition is essential as an adjunct to recovery and reducing morbidity and mortality. In contrast to adults, this is especially important for pediatric patients who have limited reserves and are in a period of growth. Burn patients often require multiple anesthetic procedures that are accompanied by standard perioperative fasting periods that result in substantial nutritional interruptions. Continuous intraoperative feeding has been proposed as a solution, but there is no current consensus on its role and safety, particularly in the pediatric population. Thus, the goal of this study was to examine the safety and benefits of intraoperative nutrition in critically ill pediatric burn injured patients. A systematic review of MEDLINE, PubMed, Scopus, and Web of Science was conducted using the following terms: feeding or enteral or nutrition or fasting and adolescent or youth or pediatric or child or teen and burn or thermal injury or fire. The primary outcome was incidence of aspiration. Secondary outcomes included patient nutritional status (caloric deficit and weight), wound healing, days spent in the intensive care unit, ventilator days, pneumonia, number of surgeries, length of hospital stay, and mortality. Pooled analyses of binary outcomes were computed. Four studies consisting of 496 patients, met inclusion criteria. All studies were level IV evidence, but had high methodological quality. The median burn TBSA was 43.8% (interquartile range 33.4%-58.8%), with a median of 30% of patients having an inhalational injury. Patients underwent a median of 4.2 surgeries (interquartile range 1.8-7.4). Intraoperative feeding was conducted through nasoduodenal tubes. There were no aspiration events. Pooled analysis demonstrated that there were no differences in rates of aspiration, pneumonia, or wound infection (P > .05) between patients who were intraoperatively fed and those who were not. Those fed intraoperatively had significantly more surgeries, ventilator days, longer hospital stays, but lower mortality (P < .05). There was large heterogeneity in nutritional assessment methods. Intraoperatively fed patients had an average gain of 144.4 kcal/kg, 1.7 days of exclusive enteral nutrition (vs loss of -119.1 kcal/kg and -1.4 days), and a cumulative positive caloric balance of +2673 kcal ± 2147 (vs loss of -7899 kcal ± 3123) compared to those with interrupted feeding. Continuous intraoperative duodenal feeding during burn surgery appears to be safe in the pediatric burn population, with no reported episodes of aspiration. Uninterrupted feeding was also associated with weight maintenance and reduced caloric deficit. It may also have a survival benefit, as continuously fed patients needed more surgeries and intensive/hospital care, but had decreased mortality.

Reduction Mammaplasty for Macromastia in Adolescents: A Systematic Review and Pooled Analysis.

BACKGROUND: Reduction mammaplasty for macromastia is one of the most common operations performed by plastic surgeons. There remains hesitancy in operating on adolescents, as there is ongoing debate about breast regrowth and potential impact on breastfeeding. The goal of this study was to analyze these concerns by reviewing the current literature. METHODS: A systematic review of MEDLINE, Scopus, and Google Scholar was conducted using the following terms: "breast reduction" or "mammaplasty" or "breast reconstruction" and "adolescent" or "youth" or "pediatric" or "child" or "teen." Primary outcomes were success of breastfeeding after the procedure and procedure-related complications. RESULTS: Twenty-three studies (87 percent retrospective), consisting of 2926 patients with preoperative cup sizes of C to KK (mean, DDD), met inclusion criteria. Mean age at the time of surgery ranged from 16 to 21 years, with the youngest patient being 12 years old. The overall complication rate was 27.3 percent (95 percent CI, 14.4 to 42.5 percent). Minor complications (22.8 percent; 95 percent CI, 10.2 to 38.5 percent) were more common than major (4.2 percent; 95 percent CI, 1.6 to 7.9 percent). Eighteen percent of patients (95 percent CI, 2.2 to 43.8 percent) reported regrowth of their breast tissue postoperatively, with 2.7 percent (95 percent CI, 0.9 to 5.5 percent) undergoing a second revision mammaplasty. Fifty-three percent of patients (95 percent CI, 36.0 to 69.3 percent) did not attempt breastfeeding. Of those who attempted, 55.1 percent (95 percent CI, 34.4 to 74.9 percent) were successful. CONCLUSIONS: Prospective data are lacking. Patient counseling should focus on encouraging a trial of breastfeeding, despite surgical history. One-fifth of adolescent patients may notice breast regrowth postoperatively; however, the amount of regrowth is likely small and unlikely to reexacerbate symptoms, as the rate of revision surgery is small.

Discrepancies between Registered and Published Primary and Secondary Outcomes in Randomized Controlled Trials within the Plastic Surgery Literature: A Systematic Review.

BACKGROUND: Recent studies have identified a high incidence of discrepancy between registered and published outcomes in registered medical and surgical randomized controlled trials. This has not yet been studied in the plastic surgery literature. METHODS: The authors systematically assessed plastic surgery randomized controlled trials published between 2012 and 2016 in seven high-impact plastic surgery journals. Data were collected from the registration website and published articles using a standardized data extraction form. RESULTS: A total of 145 randomized controlled trials were identified, with a 39 percent trial registration rate (n = 57). Forty-nine trials were included in the final analysis. Forty-three (88 percent) had a discrepancy between registered and published outcomes: 26 (53 percent) for primary outcome(s), and 39 (80 percent) for secondary outcome(s). The number of discrepancies in an individual trial ranged from one to seven for primary outcomes and one to 12 for secondary outcomes. Aesthetic surgery had the largest number of trials with outcome discrepancies (n = 15). The prevalence of unreported registered outcomes was 13 percent for primary outcomes and 38 percent for secondary outcomes. Registered nonsignificant primary outcomes were published as nonsignificant secondary outcomes in 30 percent of trials. Publishing new nonregistered secondary outcomes (65 percent) and changing the assessment timing of published primary outcomes (61 percent) were the most common types of discrepancies. Discrepancies favored a statistically significant positive outcome in 19 (44 percent) of the 43 trials with an outcome discrepancy. Discrepancies that resulted in published outcomes with improved patient relevance were found in eight trials (16 percent) for primary outcome discrepancies and 14 trials (29 percent) for secondary outcome discrepancies. CONCLUSIONS: The plastic surgery literature has high rates of discrepancies between registered and published trial outcomes. Outcome reporting discrepancy is even more problematic for secondary outcomes, an area of analysis that has previously been poorly studied. The high rate of discrepancy change favoring a statistically significant outcome and more patient-relevant outcomes may indicate the pressure to demonstrate significant results to be accepted for publication in high-impact journals.

Reporting Adverse Events in Plastic Surgery: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Accurate knowledge of adverse events is critical for evaluation of the safety of interventions. Historically, adverse events in surgical trials have been poorly reported. The objective of this study was to systematically evaluate the reporting of adverse events in randomized controlled trials in the plastic surgery literature. METHODS: Two independent reviewers conducted a systematic search using MEDLINE, Embase, and Scopus of the top seven plastic surgery journals with the highest impact factors. Randomized controlled trials describing a potentially invasive treatment, published between January of 2012 and December of 2016, were included. RESULTS: One hundred forty-five randomized controlled trials involving 10,266 patients were included, of which 30 percent were registered. Anticipated adverse events were clearly defined in 15 percent of trials, and in 70 percent it was not clear who would be documenting adverse events. Furthermore, 72 percent of randomized controlled trials reported the occurrence of adverse events, of which 61 percent failed to report events occurring in the intrainterventional period. Binary logistic regression revealed that funded randomized controlled trials were 4.04 times more likely to report adverse events compared with nonfunded randomized controlled trials (95 percent CI, 1.41 to 10.83; p = 0.009). CONCLUSIONS: The authors' findings suggest the need for reporting standards for adverse events in the plastic surgery literature, as such reporting remains heterogeneous and is lacking rigor. Improved quality and transparency are needed to strengthen evidence-based practice and permit a balanced intervention assessment. This study provides a set of recommendations aimed at improving adverse event reporting.