Utility of colonic manometry in children with Hirschsprung disease.

OBJECTIVES: Abnormal motility of the residual colon has been reported in post-pull-through Hirschsprung disease (PT-HSCR) patients with persistent defecation problems. We reviewed the role of colonic manometry (CM) in the management of defecation disorders in these patients. METHODS: We retrospectively reviewed the medical record of PT-HSCR children who underwent CM for persistent symptoms of abnormal defecation. We reviewed their clinical course and its relation to CM findings. RESULTS: Thirty PT-HSCR patients underwent CM, of which five were diagnosed with transition zone pull-through and were excluded. Of the remaining 25 patients, 16 had colonic dysmotility, 8 had normal CM, and one had colonic hypermotility. In patients with dysmotility, five responded to ongoing medical management, three required surgical intervention (ileostomy), three remained symptomatic with medical management but not yet received surgical intervention, and five were lost to follow-up. In patients with normal CM, four responded to ongoing medical therapy, two required additional surgery (antegrade enema procedure), and two were lost to follow-up. The patient with hypermotility improved with adding loperamide. CONCLUSIONS: Colonic dysmotility can occur in PT-HSCR patients with persistent defecation problems. CM was helpful in delineating the degree of colonic neuromuscular dysfunction. CM results were used in conjunction with other clinical data to determine optimal management. Our findings support that medical management should first be optimized before consideration of colonic manometry and surgical interventions.

Characteristics of Pediatric Patients With Celiac Disease Identified Due to an Affected First-Degree Family Member.

The incidence of celiac disease in first-degree relatives of affected individuals is higher than in the general population, yet the clinical characteristics of this unique subset of patients has not been well described. Through a retrospective review of patients seen in a tertiary care pediatric celiac disease clinic, we identified 49 patients diagnosed with celiac disease following screening due to an affected first-degree relative. Although 51% of patients screened due to an affected first-degree relative were asymptomatic, their disease histology was as severe as those screened for symptoms suggestive of celiac disease. These findings support current recommendations to screen all first-degree relatives of patients with celiac disease regardless of clinical symptoms.

Accuracy of Screening Tests for Celiac Disease in Asymptomatic Patients With Type 1 Diabetes.

INTRODUCTION: To evaluate the diagnostic performance of celiac serologic tests in asymptomatic patients with type 1 diabetes (T1D). METHODS: Patients with T1D asymptomatic for celiac disease were prospectively screened with immunoglobulin A anti-tissue transglutaminase. Test characteristics were calculated and optimal cutoffs for a positive screen determined. RESULTS: Two thousand three hundred fifty-three patients were screened and 101 proceeded to biopsy. The positive predictive value of immunoglobulin A anti-tissue transglutaminase at the assay referenced upper limit of normal (30CU) was 85.9%, and the sensitivity and specificity were 100% and 38%, respectively. DISCUSSION: Thresholds extrapolated from the general population for the diagnostic evaluation of celiac disease are not suitable for use in asymptomatic T1D patients. Population-specific screening cutoffs are required.

In Screening for Celiac Disease, Deamidated Gliadin Rarely Predicts Disease When Tissue Transglutaminase Is Normal.

OBJECTIVE: While tissue transglutaminase (tTG) antibodies are the most established serological test for celiac disease, newer deamidated gliadin peptide (DGP) screening tests are increasingly being completed. No pediatric study has systematically assessed the incidence of celiac disease in patients with an isolated positive DGP result. We sought to determine the positive predictive value of DGP serology for biopsy-confirmed celiac disease in pediatric patients with elevated DGP and normal tTG, to help guide clinicians' decision making when screening for this common condition and avoid unnecessary invasive follow-up diagnostic testing. METHODS: A multicenter retrospective review of children, from birth to age 18, with isolated DGP immunoglobulin G (IgG) positive serology referred to 3 Canadian centers was completed. The positive predictive value of an isolated elevated DGP result was calculated. RESULTS: Forty patients with DGP positive, tTG negative serology underwent endoscopy with duodenal biopsy. Of these, only 1 patient had biopsy-confirmed celiac disease. This patient was IgA deficient. This yields a positive predictive value of 2.5% (95% confidence interval 0.1%-14.7%) for isolated DGP IgG positive serology. CONCLUSIONS: In isolation, DGP positive serology has a poor positive predictive value for celiac disease in children, especially in IgA sufficient individuals. Our findings suggest that DGP IgG testing should not be completed as part of the initial screening for celiac disease in the pediatric population as it does not effectively differentiate between individuals with and without the disease. Further research is needed to clarify to role of DGP IgG in children under the age of 2 and those with IgA deficiency.

Iron Status in Pediatric Celiac Disease: A Retrospective Chart Review.

The present study assessed the role of serum ferritin as a noninvasive biomarker in the diagnosis and monitoring of pediatric celiac disease. A retrospective chart review was performed on patients younger than 18 years old at time of diagnosis (n = 193) between 1998 and 2015. A total of 653 paired values demonstrated a weak negative correlation between serum ferritin and tissue transglutaminase-immunoglobulin A (r = -0.114; P = 0.004), necessitating further evaluation. A significant relationship was found between reduction of tissue transglutaminase-immunoglobulin A and increase in serum ferritin after institution of a gluten-free diet (P < 0.0001), suggesting that resolution of villous damage is necessary for promoting adequate iron absorption.

Age-related shift in neural complexity related to task performance and physical activity.

The human brain undergoes marked structural changes with age including cortical thinning and reduced connectivity because of the degradation of myelin. Although these changes can compromise cognitive function, the brain is able to functionally reorganize to compensate for some of this structural loss. However, there are interesting individual differences in outcome: When comparing individuals of similar age, those who engage in regular physical activity are less affected by the typical age-related decline in cognitive function. This study used multiscale entropy to reveal a shift in the way the brain processes information in older adults that is related to physical activity. Specifically, older adults who were more physically active engaged in more local neural information processing. Interestingly, this shift toward local information processing was also associated with improved executive function performance in older adults, suggesting that physical activity may help to improve aspects of cognitive function in older adults by biasing the neural system toward local information processing. In the face of age-related structural decline, the neural plasticity that is enhanced through physical activity may help older adults maintain cognitive health longer into their lifespan.

Impact of antegrade enema initiation on healthcare utilization in pediatric patients: A population-based cohort study.

BACKGROUND: When constipation is refractory to first-line interventions, antegrade enema use may be considered. We aimed to assess the impact of this intervention on healthcare utilization. METHODS: We conducted a population-based, quasi-experimental study with pre-post comparison of the intervention group and a non-equivalent control group using linked clinical and health administrative data from Ontario, Canada. Subjects included children (0-18 years) who underwent antegrade enema initiation from 2007 to 2020 and matched controls (4:1) from the general population. To assess the change in healthcare utilization following antegrade enema initiation, we used negative binomial generalized estimating equations with covariates selected a priori. KEY RESULTS: One hundred thirty-eight subjects met eligibility criteria (appendicostomy = 55 (39.9%); cecostomy tube = 83 (60.1%)) and were matched to 550 controls. There was no significant difference in the change in the rate of hospitalizations (rate ratio (RR) 1.05, 95% confidence interval (CI) 0.35-1.75), outpatient visits (RR 1.05, 95% CI 0.91-1.18), or same-day surgical procedures (RR 1.51, 95% CI 0.60-2.43) across cases in 2 years following antegrade enema initiation compared with controls. Cases had an increased rate of emergency department (ED) visits, which was not observed in controls (RR 1.52, 95% CI 1.11-1.79), driven in part by device-related complications. CONCLUSIONS AND INFERENCES: Understanding healthcare utilization patterns following antegrade enema initiation allows for effective health system planning and aids medical decision-making. The observed increase in ED visits for device-related complications speaks to the need to improve preventive management to help mitigate emergency care after initiation of antegrade enemas.

CFTR modulators increase risk of acute pancreatitis in pancreatic insufficient patients with cystic fibrosis.

Patients with pancreatic insufficient cystic fibrosis rarely develop acute pancreatitis due to insufficient acinar reserve. We describe a series of five patients under the age of 18 (range 8-16 years) with pancreatic insufficient cystic fibrosis who developed a phenotype in keeping with acute pancreatitis following initiation of CFTR modulator therapy. This occurred at a median of 30 months following CFTR modulator initiation. 3/5 of these patients also developed pancreatic sufficiency or at least an intermediary pancreas status, indicated by fecal elastases above 100 µg/g. This series highlights a mostly unrecognized potential side effect of this therapy as well as the potential of CFTR modulator therapies to improve exocrine pancreatic function, even in adolescent patients.

Sulfite preservatives effects on the mouth microbiome: Changes in viability, diversity and composition of microbiota.

OVERVIEW: Processed foods make up about 70 percent of the North American diet. Sulfites and other food preservatives are added to these foods largely to limit bacterial contamination. The mouth microbiota and its associated enzymes are the first to encounter food and therefore likely to be the most affected. METHODS: Eight saliva samples from ten individuals were exposed to two sulfite preservatives, sodium sulfite and sodium bisulfite. One sample set was evaluated for bacteria composition utilizing 16s rRNA sequencing, and the number of viable cells in all sample sets was determined utilizing ATP assays at 10 and 40-minute exposure times. All untreated samples were analyzed for baseline lysozyme activity, and possible correlations between the number of viable cells and lysozyme activity. RESULTS: Sequencing indicated significant increases in alpha diversity with sodium bisulfite exposure and changes in relative abundance of 3 amplicon sequence variants (ASV). Sodium sulfite treated samples showed a significant decrease in the Firmicutes/Bacteroidetes ratio, a marginally significant change in alpha diversity, and a significant change in the relative abundance for Proteobacteria, Firmicutes, Bacteroidetes, and for 6 ASVs. Beta diversity didn't show separation between groups, however, all but one sample set was observed to be moving in the same direction under sodium sulfite treatment. ATP assays indicated a significant and consistent average decrease in activity ranging from 24-46% at both exposure times with both sulfites. Average initial rates of lysozyme activity between all individuals ranged from +/- 76% compared to individual variations of +/- 10-34%. No consistent, significant correlation was found between ATP and lysozyme activity in any sample sets. CONCLUSIONS: Sulfite preservatives, at concentrations regarded as safe by the FDA, alter the relative abundance and richness of the microbiota found in saliva, and decrease the number of viable cells, within 10 minutes of exposure.

Nephrocalcinosis in a young male with anorexia nervosa.

Nephrocalcinosis (NC) has been described as a long-term complication of anorexia nervosa (AN). This is the first report of this complication in an adolescent male patient. We describe the case of a 12-year-old male with AN who presented with acute food restriction and excessive exercising leading to three inpatient admissions. The patient experienced an isolated episode of dysuria and hematuria while on calcium and vitamin D supplementation. Investigations revealed hypophosphatemia, hypercalciuria and mild NC. Follow-up confirmed the presence of NC and possible nephrolithiasis (NL). We discuss the pathophysiology and risk factors of NC and NL in the context of an early presentation of AN. We suggest fluid intake should be liberalized under observation and calcium and vitamin D supplementation should be initiated with caution in patients presenting with AN and risk factors for NC and NL.

Subdivisions of inferior temporal cortex in squirrel monkeys make dissociable contributions to visual learning and memory.

Inferior temporal cortex of squirrel monkeys consists of caudal (ITC), intermediate (ITI), and rostral (ITR) subdivisions, possibly homologous to TEO, posterior TE, and anterior TE of macaque monkeys. The present study compared visual learning in squirrel monkeys with ablations of ITC; ITI and ITR (group ITRd); or ITI, ITR, and more ventral cortex, including perirhinal cortex (group ITR+), with visual learning in unoperated controls. The ITC monkeys had significant impairments on pattern discriminations and milder deficits on delayed non-matching to sample (DNMS) of objects. The ITRd monkeys had deficits on some pattern discriminations but not on DNMS. The ITRd monkeys were significantly impaired on DNMS and some pattern discriminations. These results are similar to those found in macaques and support the proposed homologies.