Paediatric obesity and Crohn's disease: a descriptive review of disease phenotype and clinical course.

Objectives: In an era of increasing paediatric obesity and inflammatory bowel disease (IBD), this study evaluates the disease phenotype and clinical course of Crohn's disease (CD) in paediatric patients who are obese or overweight. Methods: This is a retrospective, single-center, descriptive observational study from January 2010 to May 2020. Participants were included if they were: aged 2 to 18 years at the time of diagnosis, had a confirmed diagnosis of CD, and met WHO criteria for overweight or obesity at the time of diagnosis or within one year before diagnosis. Results: A total of 345 patient charts with CD were screened during the study period, with 16 patients meeting inclusion criteria. Median age of patients was 15.5 years (IQR = 13.6, 16.1). Of the 15 patients over 10 years of age, median anthropometrics at diagnosis included body mass index (BMI) of 27.2 (IQR = 24.9, 29.4) and BMI for age z-score of 1.82 (IQR = 1.58, 2.19). Presenting symptoms included abdominal pain (80.0%), diarrhea (66.7%), hematochezia (66.7%), and weight loss (26.7%). Five patients (33.3%) had obesity-related complications. Median time from symptom onset to diagnosis was 146 days (IQR = 31, 367), and median time from diagnosis to remission was 229 days (IQR = 101.8, 496.3). Conclusions: Patients with elevated BMI and CD present with typical symptoms of IBD, although weight loss was a less common presenting symptom. Time to disease remission is delayed, and obesity-related complications are common. Primary care providers must have a high degree of clinical suspicion in patients to prevent delays to gastroenterology referral and to improve time to disease remission.

Home-based fecal calprotectin utilization in a general pediatric gastroenterology clinic.

OBJECTIVE: Remote investigation and monitoring have gained importance in ambulatory practice. A home-based fecal calprotectin (FC) test has been developed where the sample is processed and analyzed at home through a smartphone application. We aimed to assess the use of standard ELISA (sFC) versus home-based (hFC) FC testing in a general pediatric gastroenterology clinic. METHODS: Ambulatory pediatric patients with hFC or sFC performed between August 2019 and November 2020 were included. Data regarding demographics, clinical characteristics, medication use, investigations, and final diagnosis, categorized as inflammatory bowel disease (IBD), functional gastrointestinal (GI) disorders, organic non-IBD (ONI) GI disorders, non-GI disorders, and undetermined after 6 months of investigation, were recorded. RESULTS: A total of 453 FC tests from 453 unique patients were included. Of those, 249 (55%) were hFC. FC levels (median) were higher in children with IBD compared to non-IBD diagnosis (sFC 795 vs. 57 µg/g, hFC 595 vs. 47 µg/g, p < 0.001), and in ONI compared to functional GI disorders (sFC 85 vs. 54 µg/g, p = 0.003, hFC 57 vs. 40 µg/g, p < 0.001). No significant difference was observed between different ONI GI disorders or subtypes of functional disorders. Age did not significantly influence levels. CONCLUSIONS: Overall, hFC and sFC provide similar results in the general pediatric GI ambulatory setting. FC is a sensitive but not disease-specific marker to identify patients with IBD. Values appear to be higher in ONI GI disorders over functional disorders, although cut-off values have yet to be determined.

Experience of Pediatricians and Pediatric Surgeons With Virtual Care During the COVID-19 Pandemic: Descriptive Study.

BACKGROUND: Prior to the COVID-19 pandemic, in-clinic visits were the standard of care for pediatric physicians and surgeons at our center. At the pandemic onset, web-based care was adopted at an unprecedented scale and pace. OBJECTIVE: This descriptive study explores the web-based care experience of pediatric physicians and surgeons during the pandemic by determining factors that supported and challenged web-based care adoption. METHODS: This study took place at the Children's Hospital at London Health Sciences Centre, a children's hospital in London, Ontario, Canada, which provides pediatric care for patients from the London metropolitan area and the rest of Southwestern Ontario. The Donabedian model was used to structure a web-based survey evaluating web-based care experience, which was distributed to 121 department-affiliated pediatric physicians (including generalists and subspecialists in surgery and medicine). Recruitment occurred via department listserv email. Qualitative data were collected through discrete and free-text survey responses. RESULTS: Survey response rate was 52.1% (63/121). Before the pandemic, few physicians within the Department of Paediatrics used web-based care, and physicians saw <10% of patients digitally. During March-May 2020, the majority transitioned to web-based care, seeing >50% of patients digitally. Web-based care use in our sample fell from June to September 2020, with the majority seeing <50% of patients digitally. Telephone and Ontario Telemedicine Network were the platforms most used from March to September 2020. Web-based care was rated to be convenient for most providers and their patients, despite the presence of technical difficulties. Challenges included lack of physical exam, lower patient volumes, and poor patient digital care etiquette. Regardless of demographics, 96.4% (116/121) would continue web-based care, ideally for patients who live far away and for follow-ups or established diagnoses. CONCLUSIONS: Transition to web-based care during COVID-19 was associated with challenges but also positive experiences. Willingness among pediatricians and pediatric surgeons to continue web-based care was high. Web-based care experiences at our center could be improved with patient education and targeting select populations. Future research is needed to improve practice efficiency and to inform regulatory guidelines for web-based care.

CFTR:F508d/A613T Mutation Is Associated With Recurrent Episodes of Pancreatitis.

Pancreatic insufficiency (PI) is found in 85% of individuals with cystic fibrosis (CF). Of the remaining who are pancreatic sufficient (PS), there is potential for developing pancreatitis, and is described in ~20% of PS individuals. We report a case of a 17.5-year-old female presenting with acute recurrent pancreatitis (ARP) and PS, later diagnosed with CF. This is the first reported case of ARP in an individual with a F508d/A613T genotype. To date, there are only 6 other individuals with this genotype, and the mechanisms of it causing ARP and no overt respiratory symptoms of CF are unclear. Her diagnosis occurred 10 years after her initial presentation of pancreatitis, highlighting the importance of screening for CFTR mutations in the workup for ARP with no clear etiology.

Sarcopenia in Children With End-Stage Liver Disease on the Transplant Waiting List.

Sarcopenia predicts morbidity and mortality in adults with end-stage liver disease (ESLD) and is determined by total psoas muscle area (tPMA) measurement from computed tomography (CT) imaging. Recently developed pediatric age- and sex-specific tPMA growth curves provide the opportunity to ascertain prevalence and impact of sarcopenia in children awaiting liver transplantation (LT). This retrospective single-center study evaluated sarcopenia in children between 1 and 16 years with ESLD and a clinically indicated abdominal CT less than 3 months before first isolated LT. Sarcopenia was defined as tPMA z score less than -2 measured at the intervertebral L4-5 level. Patient demographic, biochemical, and outcome data were recorded. tPMA was compared with other measures of nutritional status using univariate and multivariate logistic analyses. Outcome measures included 1-year morbidity events and mortality after LT. CT images from 25 (64% female) children with median age of 5.50 (interquartile range [IQR], 3.75-11.33) years were reviewed. Ten children (40%) had a tPMA z score less than -2. Sarcopenia was associated with lower z scores for weight (odds ratio [OR], 0.38; P = 0.02), height (OR, 0.32; P = 0.03), and nutritional support before LT (OR, 12.93; P = 0.01). Sarcopenic children had a longer duration of pediatric intensive care unit (PICU) stay (3.50 [IQR, 3.00-6.00] versus 2.00 [IQR, 2.00-3.50] days; P = 0.03). Sarcopenia was prevalent in 40% of children with ESLD awaiting LT, and lower tPMA z score was associated with deficient anthropometrics and need for nutritional support before LT. Post-LT PICU duration was increased in children with sarcopenia, reflecting adverse outcomes associated with muscle loss. Further studies are needed to elucidate the underlying mechanisms of sarcopenia in children with ESLD.

Role of transient elastography and APRI in the assessment of pediatric cystic fibrosis liver disease.

Background: Diagnosis and monitoring of cystic fibrosis liver disease (CFLD) is challenging. Transient elastography (TE) is a rapid, non-invasive method for assessing liver fibrosis. Its role in detecting fibrosis in CFLD has only begun to be explored. The aspartate aminotransferase to platelet ratio index (APRI) has been validated as a predictor of hepatic fibrosis in other chronic liver diseases. The purpose of this study was to assess the utility of APRI and TE in identifying liver fibrosis in pediatric CF patients. Methods: Patients aged 2-18 years were recruited from the British Columbia Children's Hospital CF clinic. Patients were determined to have CFLD using standard criteria. Charts were reviewed, and each patient underwent TE. Results: Of the 55 patients included in the study (50.9% male, mean age 11.6 y), 22 (40%) had CFLD. All mean liver enzymes were higher in the CFLD group, notably alanine transaminase (p = 0.031). Mean liver stiffness (LS) and APRI were also higher in the CFLD group (LS: 5.9 versus 4.5 kPa, p = 0.015; APRI: 0.40 versus 0.32, p = 0.119). Linear regression showed a mild positive association between the two (r 2 = 0.386). Conclusions: TE values were higher among CFLD patients and correlated with APRI values, suggesting that these tools may have clinical applications for identifying and following this population. Further research is needed on a larger scale to determine the relative value and clinical utility of TE and APRI among patients with CFLD.

Paediatric reference values for total psoas muscle area.

BACKGROUND: Sarcopenia, the unintentional loss of skeletal muscle mass, is associated with poor outcomes in adult patient populations. In adults, sarcopenia is often ascertained by cross-sectional imaging of the psoas muscle area (PMA). Although children with chronic medical illnesses may be at increased risk for muscle loss because of nutritional deficiencies, physical deconditioning, endocrine anomalies, and systemic inflammation, consistent quantitative definitions for sarcopenia in children are lacking. We aimed to generate paediatric reference values for PMA at two intervertebral lumbar levels, L3-4 and L4-5. METHODS: In this cross-sectional study, we analysed abdominal computed tomography scans of consecutive children presenting to the emergency department. Participants were children 1-16 years who required abdominal cross-sectional imaging after paediatric trauma between January 1, 2005 and December 31, 2015 in a large Canadian quaternary care centre. Children with a documented chronic medical illness or an acute spinal trauma at presentation were excluded. Total PMA (tPMA) at levels L3-4 and L4-5 were measured in square millimetres (mm2 ) as the sum of left and right PMA. Age-specific and sex-specific tPMA percentile curves were modelled using quantile regression. RESULTS: Computed tomography images from 779 children were included. Values of tPMA at L4-5 were significantly larger than at L3-4 at all ages, but their correlation was high for both girls (r = 0.95) and boys (r = 0.98). Amongst girls, tPMA 50th percentile values ranged from 365 to 2336 mm2 at L3-4 and from 447 to 2704 mm2 for L4-5. Amongst boys, 50th percentile values for tPMA ranged between 394 and 3050 mm2 at L3-4 and from 498 to 3513 mm2 at L4-5. Intraclass correlation coefficients were excellent at L3-4 (0.97, 95% CI 0.94 to 0.981) and L4-5 (0.99, 95% CI 0.986 to 0.995). Weight and tPMA were correlated, stratified by sex for boys (L3-4 r = 0.90; L4-5 r = 0.90) and for girls (L3-4 r = 0.87; L4-5 r = 0.87). An online application was subsequently developed to easily calculate age-specific and sex-specific z-scores and percentiles. CONCLUSIONS: We provide novel paediatric age-specific and sex-specific growth curves for tPMA at intervertebral L3-4 and L4-5 levels for children between the ages of 1-16 years. Together with an online tool (https://ahrc-apps.shinyapps.io/sarcopenia/), these tPMA curves should serve as a reference enabling earlier identification and targeted intervention of sarcopenia in children with chronic medical conditions.

Passenger Lymphocyte Syndrome After Pediatric Liver Transplantation.

BACKGROUND: Passenger lymphocyte syndrome (PLS) is a less known etiology of acute onset anemia following ABO-compatible (ABO-c) liver transplantation (LT). Available literature on PLS after pediatric LT is limited. Therefore, we evaluated the prevalence, clinical course, and risk factors of PLS in children following ABO-c LT. METHODS: A single-center retrospective review of all children who underwent LT between 2000 and 2017 was performed. PLS was defined as a drop-in hemoglobin >20 g/L within 30 days of LT, with positive direct antiglobulin test and 1 laboratory test confirming hemolysis. Chi square and student t tests compared variables between subjects with and without PLS. RESULTS: Amongst 333 pediatric LT performed, 51 children received an ABO-c graft. PLS was diagnosed in 7 (14%) subjects at a median of 10 days after LT. There were no significant differences in patient demographics, graft type, or immunosuppression between those who did and did not develop PLS. Recipient blood group A+ receiving a donor O+ graft was a risk factor for PLS (P = 0.015). All PLS subjects recovered with blood transfusions (median 2), and no additional interventions. Three subjects initially received recipient (instead of donor) blood group red cells. CONCLUSIONS: We report a 14% prevalence of PLS following pediatric ABO-c LT. Recipient blood group A+ receiving a donor O+ graft is a risk factor for PLS. Recognition of PLS as a cause of early acute anemia in pediatric ABO-c LT enables timely transfusion with donor (rather than recipient) blood group red cells.

Province-wide Biliary Atresia Home Screening Program in British Columbia: Evaluation of First 2 Years.

BACKGROUND AND OBJECTIVES: Biliary atresia (BA), a rare newborn liver disease, is the leading cause of liver-related death in children. Early disease recognition and timely surgical Kasai hepatoportoenterostomy (KP) offers long-term survival without liver transplant. Universal BA screening in Taiwan using infant stool color cards (ISCCs) has proven effectiveness. We report our experience with infant stool color card (ISCC) BA screening in a province-wide program in British Columbia (BC). The objective of this study is to assess program performance and cost from launch April 1, 2014 to March 31, 2016. METHODS: ISCCs distributed to families upon maternity ward discharge. Parents were instructed to monitor their infant's stool color for 1 month and contacted the screening center with concerns. The number of live births, ISCC distribution, BA cases, and costs were recorded. Cases with Program screen success had both acholic stool recognition (ISCC screen success) and timely referral for BA. RESULTS: All 126 maternity units received ISCCs. Of 87,583 live births there were 6 BA cases. Of the 5 cases with ISCC Screen Success 3 had Program Screen Success. The median KP age in the program screen success and failure groups was 49 (42-52) and 116 (49-184) days, respectively. Program sensitivity was 50%, specificity 99%, positive predictive value 4%, and negative predictive value 99%. A random sample of 1054 charts at BC Children's Hospital found an ISCC distribution rate of 94%. After a phase-in period, the annual program cost was $30,033.82, and the ISCC cost per birth was $0.68. CONCLUSIONS: The screening program has high specificity and distribution with low cost. Successful program case identification had earlier age at KP. Program modifications aim to improve sensitivity. Longer-term studies will determine program impact on health outcomes.

Examination of cadmium-induced expression of the small heat shock protein gene, hsp30, in Xenopus laevis A6 kidney epithelial cells.

Cadmium is a highly toxic environmental pollutant that has been classified as a human carcinogen. Toxicological responses to cadmium exposure include respiratory diseases, neurological disorders and kidney damage. In the present study, we have characterized the effect of cadmium on the accumulation of the small heat shock protein (HSP), HSP30, in Xenopus laevis A6 kidney epithelial cells. Incubation of A6 cells with cadmium chloride induced the accumulation of HSP30 protein and hsp30 mRNA. While HSP70 protein and hsp70 mRNA accumulation were also induced, the relative levels of actin remained relatively unaffected. Elevated levels of HSP30 were detected in cells undergoing prolonged exposure of cells to cadmium chloride or in cells recovering from cadmium chloride treatment. Immunocytochemical analysis of cadmium chloride-treated A6 cells revealed HSP30 accumulation primarily in the cytoplasm in a punctate pattern supplemented with larger HSP30 staining structures. Also, HSP30 co-localized with the F-actin cytoskeleton at higher cadmium chloride concentrations. The combination of mild heat shock temperatures plus cadmium chloride concentrations employed in this study resulted in a synergistic accumulation of HSP30 protein and hsp30 mRNA. Finally, in contrast to heat shock, prior exposure of Xenopus A6 cells to cadmium chloride treatment, sufficient to induce the accumulation of HSPs, did not protect the cells against a subsequent thermal challenge.

Shortcomings in interventional radiology in Canada and what is needed for change.

PURPOSE: To describe the current and future financial needs of interventional radiology (IR) in Canada. MATERIALS AND METHODS: The Millennium Research Group, an independent market research firm, was commissioned by the Canadian Interventional Radiology Association to create a report examining the current status and outlook of interventional radiology in Canada. This article presents some of the key findings. RESULTS: The incidence of some of the major diseases relevant to interventional radiologists, as well as smoking and obesity, is predicted to increase over the next few years, leading to an expected increased demand for IR procedures. This will in turn further exacerbate a current shortage. To become a G7 leader in terms of number of IR procedures performed per population, Canada would need to increase its number of interventional radiologists by an additional 241% from 2005 levels. Canada must spend an additional Can$221.3 million annually to support IR in Canada, which would lead to estimated savings of at least Can$180.3 million in direct health care costs and Can$92.3 million in societal costs annually, as well as at least 402 lives and 98,010 hospital-bed days saved. CONCLUSIONS: Canada, and more specifically hospital administrators, politicians, and medical policy-makers, must substantially increase funding, awareness, and support of interventional radiology in Canada to ensure first-world medical care to the Canadian population. By not doing so, dollars, lives, complications, and waiting times are being and will continue to be forfeited.