Efficacy of Infliximab Biosimilar for Maintenance Therapy in Pediatric Inflammatory Bowel Disease Following Infliximab Originator.

The safety, efficacy, and cost-effectiveness of Infliximab biosimilar agents in the management of inflammatory bowel disease in adults have been shown. These agents have been recommended for pediatric inflammatory bowel disease, and although institutions are initiating therapy with the biosimilar agents (IFX-B), few are switching maintenance therapy from the originator (IFX-O). The aim was to compare biochemical markers of disease activity of children with inflammatory bowel disease on maintenance therapy with IFX-B to their previous markers on IFX-O. Methods: Single-center, retrospective chart review of 25 children with inflammatory bowel disease who transitioned from Remicade (IFX-O) to the biosimilar agent Inflectra (IFX-B) for maintenance therapy. Analysis included demographics and various biochemical markers of disease control. The nonparametric-related samples Wilcoxon signed-rank test was used to compare mean ranks of these markers (C-reactive protein, erythrocyte sedimentation rate, hemoglobin, platelet count, albumin, body mass index z score) between the last 12 months on IFX-O and the first 12 months on IFX-B. Results: Between March 2018 and June 2018, the majority of patients with pediatric inflammatory bowel disease on maintenance therapy with IFX-O at our institution were transitioned to maintenance therapy with IFX-B. Of the 25 children included, 17 were diagnosed with Crohn disease and 8 with ulcerative colitis. The results of all, except albumin value, supported retention of the null hypothesis that there would not be a statistically significant difference in the biochemical markers of disease activity between the 2 medications. Conclusions: IFX-B is as effective as IFX-O for maintenance therapy in pediatric inflammatory bowel disease when comparing biochemical markers of disease activity.

The Effectiveness of Methylprednisolone as a Premedication Among the Pediatric Population for Preventing Infusion-Related Reactions to Infliximab.

Administering medications prior to infliximab infusions to prevent infusion-related infliximab reactions is a common practice in the United States. However, the premedication protocol varies among different institutions. The purpose of this study was to demonstrate whether the use of methylprednisolone was effective as a premedication to prevent infusion reactions while infliximab was administered to children with inflammatory bowel disease. The effect of concurrent use of other immunomodulators on the rate of reaction incidents was also studied. This was a retrospective chart review, assessing children younger than 21 years diagnosed with inflammatory bowel disease from January 2008 to April 2018. The incident rate of infusion reactions was also compared between two cohorts: those who received the premedication of methylprednisolone and those who did not. Subgroup analysis of concomitant immunomodulators, infliximab dose and frequency, and anti-infliximab assay were also performed. A total of 34 subjects received methylprednisolone as a premedication and 151 subjects did not. No statistically significant difference of allergic reactions was found between the two groups (p = .727). Concomitant immunomodulator therapy lowered the likelihood of developing reactions (p = .048). This study was conducted to help pediatric gastroenterology and infusion nurses better understand and implement evidence-based approaches in the premedication protocol for infusions of anti-tumor necrosis factor-α (anti-TNF-α) antibody products.

His bundle pacing: Tips and tricks.

His bundle (HB) pacing is an established modality for achieving physiological pacing with a low risk of long-term lead-related complications. The development of specially designed lead and delivery tools has improved the feasibility and safety of HB pacing (HBP). Knowledge of the anatomy of HB region and the variations is essential for successful implantation. Newer delivery systems have further improved procedural outcomes. Challenging implant cases can be successfully performed by reshaping the current sheaths, using "sheath in sheath" technique or "two-lead implantation technique." Special attention to the lead parameters at implant, programming, and follow-up is necessary for successful long-term outcomes with HBP. Widespread use of HBP by electrophysiologists and further advances in dedicated delivery systems and leads are essential to further improve the effectiveness of the implantation.

Radiofrequency Catheter Ablation: How to Manage and Prevent Collateral Damage?

Radiofrequency catheter ablation has become the standard of care for the management of various arrhythmias and, in fact, the first-line therapy for many tachyarrhythmias. It entails creating scar tissue in the heart in regions where abnormal impulses form or propagate to restore normal cardiac conduction. As the heart is a complex organ and is surrounded by and related to many other anatomical structures, it is important to avoid the collateral damage that can happen from radiofrequency (RF) ablation on the endocardium as well as on the epicardium. This review explores methods for mitigating or limiting collateral damage during catheter ablation.

Rectal Prolapse in Children: An Update to Causes, Clinical Presentation, and Management.

BACKGROUND: Rectal prolapse is a protrusion of rectal mucosa through the anal sphincter. Although uncommon, it is seen more often in children, younger than 4 years of age. The last data analysis of rectal prolapse and its clinical characteristics in children was performed over 30 years ago. Since that time, many medical advances have occurred that may alter our workup and management of this disease in children. We performed a chart review to reassess the clinical characteristics of rectal prolapse and its management. METHODS: This was a retrospective descriptive analysis study, assessing children less than 18 years of age that were diagnosed with rectal prolapse from 1999 to 2014 at a single tertiary care center. The onset of presentation, demographics, etiology, clinical characteristics, and management were analyzed. RESULTS: A total of 158 patients were diagnosed with rectal prolapse, with mean age of onset being 3 years. Constipation was the leading cause, with straining being the most common complaint. Stool consistencies with constipation varied. Many patients diagnosed with idiopathic recurrent rectal prolapse had either a social stressor or were described as having unusual behaviors associated with prolapse. Cystic fibrosis was only diagnosed in 4 patients. Thirty-four patients (22%) required surgical correction. CONCLUSIONS: Constipation remains the main cause of rectal prolapse. Cystic fibrosis is no longer a common etiology for rectal prolapse, because of the implementation of newborn screening. Patients with social stressors or atypical behavior may be at risk for recurrent rectal prolapse.

The Effect of Biologics on Postoperative Complications in Children With Inflammatory Bowel Disease and Bowel Resection.

OBJECTIVES: There has been limited investigation of pediatric patients with inflammatory bowel disease (IBD) who have been treated with biologic agents and undergo operative management. Postoperative complications in the adult setting have been mixed and in the pediatric population the data have been limited. This study compares children with IBD treated with biologic agents to patients treated with nonbiologic therapy before bowel resection. METHODS: This is a single-center, retrospective chart review study of 62 children with IBD who underwent bowel resection between 2001 and 2017. Analysis included patient demographics, medications used before surgery, incidence of postoperative complications, indication for surgery, type of operation, and additional surgeries required. Postoperative complications were defined as superficial skin infection, leak at anastomotic site, intra-abdominal abscess, wound dehiscence, and so on. Complications were compared based on medical therapy. RESULTS: Of the 62 children reviewed, 21 carried the diagnosis of ulcerative colitis, 40 had Crohn disease, and 1 had IBD-unspecified. Thirty-seven of the patients were treated with infliximab, adalimumab, or vedolizumab before their bowel resection. There were 4 complications documented within 30 days of the operation, with an overall complication rate of 6.45%. There were 2 complications in each of the cohorts, including intra-abdominal abscess (2), abdominal wall abscess (1), and pouchitis (1). CONCLUSION: The number of complications was the same between those who did and did not receive a preoperative biologic agent. This study suggests that biologics may be safe to use in patients undergoing bowel resection.

Short article: Risk of small intestinal bacterial overgrowth with chronic use of proton pump inhibitors in children.

BACKGROUND: Some theorize that prolonged use of proton pump inhibitors (PPIs) may increase the risk of small intestinal bacterial overgrowth (SIBO). Chronic acid suppression and resultant hypochlorhydria may lead to an altered intraluminal environment, which, in turn, may promote the growth of bacteria in the small intestine. A handful of studies measured the risk of SIBO in adults taking PPIs and obtained mixed results; however, this risk has not been exclusively measured in children. AIM: This study aimed to measure the risk of SIBO in children taking PPI versus those not taking PPI. PATIENTS AND METHODS: This was a prospective cohort study. Evaluation of SIBO was performed using the glucose hydrogen breath test. Patients younger than 18 years of age taking a PPI longer than 6 months were compared with healthy control participants. After ingestion of glucose substrate, breath samples were obtained every 15 min for 2 h. An increase in breath hydrogen or methane above 12 ppm was considered diagnostic of SIBO. RESULTS: Overall, 83 participants were tested, of whom 56 were taking PPIs. SIBO was detected in five (8.9%) of the 56 participants taking PPI versus one (3.7%) of the 27 participants in the control group (P=0.359), with a relative risk of 2.4 (95% confidence interval: 0.29-19.6). CONCLUSION: To our knowledge, this is the first study in the English literature measuring the risk of SIBO in children taking PPIs. Our results indicate a potential risk of SIBO in chronic PPI users; however, this is not statistically significant. This is an important finding as PPIs are readily prescribed for children and are often taken longer than 6 months' duration.

Rectal Prolapse in Children: Significance and Management.

Rectal prolapse is a herniation of the rectum through the anus. It is rare in children. When it does occur, it is usually prior to 4 years of age and due to anatomical variants. A few conditions predispose children to rectal prolapse, the most common being constipation. Cystic fibrosis used to be commonly associated with rectal prolapse, but with the advent of cystic fibrosis newborn screening, this association is no longer as frequently seen. Many recent case reports, detailed in this chapter, describe conditions previously unknown to be associated with rectal prolapse. Management is usually supportive; however, rectal prolapse requires surgical management in certain situations. This review details the presentation of rectal prolapse, newly described clinical manifestations, and associated conditions, and up-to-date medical and surgical management.

Anatomic distribution of culprit lesions in patients with non-ST-segment elevation myocardial infarction and normal ECG.

BACKGROUND: In patients presenting with non-ST-elevation myocardial infarction (NSTEMI), left anterior descending (LAD) coronary artery and three-vessel disease are the most commonly encountered culprit lesions in the presence of ST depression, while one third of patients with left circumflex (LCX) artery related infarction have normal ECG. We sought to determine the predictors of presence of culprit lesion in NSTEMI patients based on ECG, echocardiographic, and clinical characteristics. METHODS: Patients admitted to the coronary care unit with the diagnosis of NSTEMI between June 2012 and December 2013 were retrospectively identified. Admission ECG was interpreted by an electrophysiologist that was blinded to the result of the coronary angiogram. Patients were dichotomized into either normal or abnormal ECG group. The primary endpoint was presence of culprit lesion. Secondary endpoints included length of stay, re-hospitalization within 60 days, and in-hospital mortality. RESULTS: A total of 118 patients that were identified; 47 with normal and 71 with abnormal ECG. At least one culprit lesion was identified in 101 patients (86%), and significantly more among those with abnormal ECG (91.5% vs. 76.6%, P=0.041).The LAD was the most frequently detected culprit lesion in both groups. There was a higher incidence of two and three-vessel disease in the abnormal ECG group (P=0.041).On the other hand, there was a trend of higher LCX involvement (25% vs. 13.8%, P=0.18) and more normal coronary arteries in the normal ECG group (23.4% vs. 8.5%, P=0.041). On multivariate analysis, prior history of coronary artery disease (CAD) [odds ratio (OR) 6.4 (0.8-52)], male gender [OR 5.0 (1.5-17)], and abnormal admission ECG [OR 3.6 (1.12-12)], were independent predictors of a culprit lesion. There was no difference in secondary endpoints between those with normal and abnormal ECG. CONCLUSIONS: Among patients presenting with NSTEMI, prior history of CAD, male gender and abnormal admission ECG were independent predictors of a culprit lesion. An abnormal ECG was significantly associated with two and three-vessel disease, while normal ECG was more associated with LCX involvement or normal angiogram. Admission ECG did not impact secondary outcomes.

Bladder and bowel dysfunction: evidence for multidisciplinary care.

PURPOSE: We examined the symptoms of bladder-bowel dysfunction (ie severity of voiding dysfunction and stool consistency) and psychosocial difficulties in children presenting to the pediatric urology clinic for voiding dysfunction and to the pediatric gastroenterology clinic for functional constipation. MATERIALS AND METHODS: Parents of children seen at the gastroenterology clinic were recruited during the outpatient clinic appointment, and parents of children seen at the urology clinic were randomly selected from the research database and matched to the gastroenterology sample based on age and gender of the child. All parents completed the Dysfunctional Voiding Scoring System, Bristol Stool Form Scale, Pediatric Symptom Checklist and Parenting Stress Index™-Short Form, which assessed severity of voiding dysfunction, stool consistency, level of psychosocial difficulties and level of parenting stress, respectively. RESULTS: Children seen at the urology and gastroenterology clinics did not differ significantly on any of the measures, indicating that the severity of their bladder-bowel dysfunction is similar. However, they had significantly more severe voiding dysfunction, more constipated stool and more psychosocial difficulties than historical healthy controls. Additionally, level of parenting stress was significantly correlated with patient level of psychosocial difficulties and severity of voiding dysfunction. CONCLUSIONS: Patients with bladder and bowel dysfunction represent a homogeneous group that would potentially benefit from a multidisciplinary treatment approach involving urology, gastroenterology and psychology professionals.

Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.

Mutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T>C) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin.

Hepatic failure, neonatal hemochromatosis and porto-pulmonary hypertension in a newborn with trisomy 21--a case report.

Liver failure in neonates is a rare but often fatal disease. Trisomy 21 is not usually associated with significant infantile liver disease. If present, hepatic dysfunction in an infant with Trisomy 21 is likely to be attributed to transient myeloproliferative disorder with hepatic infiltration by hematopoietic elements and may be associated with secondary hemosiderosis. A less commonly recognized cause of liver failure in neonates with Trisomy 21 is neonatal hemochromatosis (NH); this association has been reported in nine cases of Trisomy 21 in literature. NH is a rare, severe liver disease of intra-uterine onset that is characterized by neonatal liver failure and hepatic and extrahepatic iron accumulation that spares the reticuloendothelial system. NH is the most frequently recognized cause of liver failure in neonates and the commonest indication for neonatal liver transplantation. Although porto-pulmonary hypertension (PPH) has been reported as a complication of liver failure in adults and older children, this has not been reported in neonates with liver failure of any etiology. This is probably due to the rarity of liver failure in newborns, delayed diagnosis and high mortality. The importance of recognizing PPH is that it is reversible with liver transplantation but at the same time increases the risk of post-operative mortality. Therefore, early diagnosis of PPH is critical so that early intervention can improve the chances of successful liver transplantation. We report for the first time the association of liver failure with porto-pulmonary hypertension secondary to NH in an infant with Trisomy 21.