33 results on '"Attard T"'
Search Results
2. 359 Access to endoscopic retrograde cholangiopancreatography in children and adolescents with cystic fibrosis
- Author
-
Pathak, S., primary, Attard, T., additional, Arain, M., additional, Ly, N., additional, Heyman, M., additional, and Perito, E., additional
- Published
- 2022
- Full Text
- View/download PDF
3. INVESTIGATING NEED AND APPROPRIATENESS FOR PHARMACIST-LED VACCINATION SERVICES WITHIN A HEALTHCARE SYSTEM.
- Author
-
Attard, T., Wirth, F., and Azzopardi, L. M.
- Published
- 2024
- Full Text
- View/download PDF
4. Management of Familial Adenomatous Polyposis in Children and Adolescents: Position Paper From the ESPGHAN Polyposis Working Group
- Author
-
Hyer W, Cohen S, Attard T, Vila-Miravet V, Pienar C, Auth M, Septer S, Hawkins J, Durno C, and Latchford A
- Subjects
digestive system diseases - Abstract
Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, characterized by the development of hundreds to thousands of adenomas in the colorectum, with implications in children and adolescents. Almost all adult patients will develop colorectal cancer if they are not identified and treated early enough. Identifying and screening for FAP commences in adolescence. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the adenomatous polyposis (APC) gene. This European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) position paper provides a guide for diagnosis, assessment, and management of FAP in children and adolescents.This is the first position paper regarding FAP published by ESPGHAN. Literature from PubMed, Medline, and Embase was reviewed and in the absence of evidence, recommendations reflect the opinion of paediatric and adult experts involved in the care of polyposis syndromes. Because many of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, these of the recommendations are supported on expert opinion. This position paper will instruct on the appropriate management and timing of procedures in children and adolescents with FAP.
- Published
- 2019
5. Diagnosis of celiac disease and applicability of ESPGHAN guidelines in Mediterranean countries: A real life prospective study
- Author
-
Smarrazzo, A. Misak, Z. Costa, S. Mičetić-Turk, D. Abu-Zekry, M. Kansu, A. Abkari, A. Bouziane-Nedjadi, K. Ben Hariz, M. Roma, E. Velmishi, V. Legarda Tamara, M. Attard, T. Djurisic, V. Greco, L. Magazzù, G.
- Abstract
Background: We assessed how the diagnosis of Celiac Disease (CD) is made and how the new ESPGHAN guidelines can be applied in children from countries with different resources. Methods: A real life prospective study was performed in 14 centres of 13 different Mediterranean countries. Participants were asked to apply the usual diagnostic work-up for CD according to their diagnostic facilities. Results: There were 1974 patients enrolled in the study, mean age 4 years, 10 months; 865 male, 1109 female. CD was confirmed in 511 (25.9%) and was unconfirmed in 1391 (70.5%) patients; 14 patients were diagnosed as having CD according to the new ESPGHAN guidelines, 43 patients were classified as having potential CD. In all participating countries the diagnosis of CD relied on histology of duodenal biopsy; in 5 countries, HLA, and in one country endomysial antibodies (EMA) were not available. Symptoms did not add a significant increase to the pre-test probability of serological tests. The positive predictive value of tissue transglutaminase type 2 (tTG) antibodies performed with different kits but all corresponding to those recommended by ESPGHAN was 96.1% (95% CI 94-97.9%) in presence of tTG > 10xULN. In 135 patients with tTG >10xULN, HLA genotyping was performed and in all it was compatible with CD. Conclusions: The results of our study show that CD diagnosis still relies on intestinal biopsy in the Mediterranean area. New ESPGHAN criteria are not applicable in 5 countries due to lack of resources needed to perform HLA genotyping and, in one country, EMA assay. Further simplification of the new ESPGHAN guidelines might be made according to what preliminarily the present results suggest if confirmed by new prospective studies. © 2017 The Author(s).
- Published
- 2017
6. Endoscopist Experience with pediatric intentional recurrent foreign body ingestion: a path forward.
- Author
-
Low Kapalu, C., Lerner, D., Uraizee, O., Thomson, M., and Attard, T.
- Published
- 2022
- Full Text
- View/download PDF
7. Juvenile polyposis syndrome in children: The impact of SMAD4 and BMPR1A mutations on clinical phenotype and polyp burden.
- Author
-
Cohen S, Yerushalmy-Feler A, Rojas I, Phen C, Rudnick DA, Flahive CB, Erdman SH, Magen-Rimon R, Copova I, Attard T, Latchford A, and Hyer W
- Subjects
- Humans, Child, Male, Female, Adolescent, Child, Preschool, Follow-Up Studies, Smad4 Protein genetics, Bone Morphogenetic Protein Receptors, Type I genetics, Intestinal Polyposis genetics, Intestinal Polyposis congenital, Phenotype, Mutation, Neoplastic Syndromes, Hereditary genetics
- Abstract
Objective: A constitutional disease-causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%-60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV-positive JPS compared to DCV-negative JPS., Methods: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group., Results: A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow-up of 4 (2.8-6.4) years. DCV-positive children were diagnosed at an older age compared to DCV-negative children [12 (8-15.7) years vs. 5 (4-7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93-9.63, p < 0.001) in the DCV-positive group compared to the DCV-negative group, with an average of 12.2 versus 2 new polyps for every year of follow-up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations., Conclusions: This largest international cohort of pediatric JPS revealed that DCV-positive and DCV-negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
- Published
- 2024
- Full Text
- View/download PDF
8. Availability and utilization of endoscopic retrograde cholangiopancreatography at children's hospitals.
- Author
-
Pathak SJ, Attard T, Hall M, Arain M, Heyman MB, and Perito ER
- Subjects
- Humans, Child, Male, Female, United States, Child, Preschool, Adolescent, Infant, Pancreatic Diseases therapy, Pancreatic Diseases surgery, Healthcare Disparities statistics & numerical data, Biliary Tract Diseases therapy, Retrospective Studies, Cholangiopancreatography, Endoscopic Retrograde statistics & numerical data, Hospitals, Pediatric statistics & numerical data, Health Services Accessibility statistics & numerical data
- Abstract
Objectives: No study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors., Methods: Healthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service., Results: From 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses leading to ERCP were chronic (47.2%) and acute pancreatitis (43.2%); biliary diagnoses were calculus (68.3%) and obstruction (14.8%). No ERCP was available for 25.0% of pancreatic encounters and 8.1% of biliary encounters. In multivariable analysis, children with public insurance, rural residence, or of Black race were less likely to have pancreatic ERCP availability; those with rural residence or Asian race were less likely to have biliary ERCP availability. Black children or those with public insurance were less likely to undergo pancreatic ERCP where available. Among encounters for calculus or obstruction, those of Black race or admitted to hospitals in the West were less likely to undergo ERCP when available., Conclusions: One-in-four children with pancreatic disorders and one-in-12 with biliary disorders may have limited access to ERCP. We identified racial and geographic disparities in availability and utilization of ERCP. Further studies are needed to understand these differences to ensure equitable care., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
- Published
- 2024
- Full Text
- View/download PDF
9. Ciliopathy patient variants reveal organelle-specific functions for TUBB4B in axonemal microtubules.
- Author
-
Dodd DO, Mechaussier S, Yeyati PL, McPhie F, Anderson JR, Khoo CJ, Shoemark A, Gupta DK, Attard T, Zariwala MA, Legendre M, Bracht D, Wallmeier J, Gui M, Fassad MR, Parry DA, Tennant PA, Meynert A, Wheway G, Fares-Taie L, Black HA, Mitri-Frangieh R, Faucon C, Kaplan J, Patel M, McKie L, Megaw R, Gatsogiannis C, Mohamed MA, Aitken S, Gautier P, Reinholt FR, Hirst RA, O'Callaghan C, Heimdal K, Bottier M, Escudier E, Crowley S, Descartes M, Jabs EW, Kenia P, Amiel J, Bacci GM, Calogero C, Palazzo V, Tiberi L, Blümlein U, Rogers A, Wambach JA, Wegner DJ, Fulton AB, Kenna M, Rosenfeld M, Holm IA, Quigley A, Hall EA, Murphy LC, Cassidy DM, von Kriegsheim A, Papon JF, Pasquier L, Murris MS, Chalmers JD, Hogg C, Macleod KA, Urquhart DS, Unger S, Aitman TJ, Amselem S, Leigh MW, Knowles MR, Omran H, Mitchison HM, Brown A, Marsh JA, Welburn JPI, Ti SC, Horani A, Rozet JM, Perrault I, and Mill P
- Subjects
- Animals, Humans, Mice, Mutation, Protein Isoforms genetics, Protein Isoforms metabolism, Male, Female, Mice, Knockout, Axoneme metabolism, Centrioles metabolism, Cilia metabolism, Ciliary Motility Disorders genetics, Ciliary Motility Disorders metabolism, Tubulin genetics, Tubulin metabolism
- Abstract
Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type- and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the TUBB4B isotype that specifically perturbed centriole and cilium biogenesis. Distinct TUBB4B variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.
- Published
- 2024
- Full Text
- View/download PDF
10. Endoscopist experience with pediatric recurrent and intentional foreign body ingestion (RIFBI): Management considerations and future directions.
- Author
-
Low Kapalu CM, Uraizee O, Lerner DG, Thomson M, and Attard T
- Subjects
- Adult, Humans, Child, Digestive System, Endoscopy, Gastrointestinal, Eating, Autism Spectrum Disorder complications, Foreign Bodies surgery, Foreign Bodies complications
- Abstract
Objectives and Study: Accidental foreign body ingestion (FBI) is a common pediatric referral concern. In contrast, recurrent and intentional FBI (RIFBI) is infrequent and associated with greater endoscopic and surgical intervention in adults. Although pediatric guidelines exist for FBI, the risk and therapeutic implications of RIFBI are not addressed. An anonymous international survey on pediatric gastroenterologist experience with RIFBI was distributed., Methods: A 33-item REDCap© survey was distributed via email to pediatric gastroenterologists identified through mailing and email lists obtained from pediatric gastroenterology professional organizations., Results: During 9-12/2021 we accrued 202 completed surveys. Respondents were from 27 countries and across the career span. Eighty percent reported experience with RIFBI; 74% reported seeing ≤ 3 patients with RIFBI within the past 24 months and 4% reported seeing ≥ 6. Of those who treated RIFBI, 38% reported an average number of annual ingestions per patient was ≥5. Frequent morbidity but not mortality was reported. Half reported adherence to FBI guidelines. Later-career endoscopists treated RIFBI more aggressively than accidental ingestion. Ninety-six percent noted that patients with RIFBI had psychiatric comorbidities. Providers at academic medical centers reported referring to behavioral health more than those in other settings., Conclusion: Most gastroenterologists surveyed reported encountering RFBI several times a year and in patients with psychiatric comorbidities. Greater likelihood of adverse outcomes associated with endoscopy was reported. Most reported referral to behavioral health and few had RIFBI management protocols. A broader spectrum of psychologic comorbidities in the pediatric population with RIFBI, notably depression and autism spectrum disorder, were reported., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
- Published
- 2024
- Full Text
- View/download PDF
11. Endoscopy in pediatric polyposis syndromes: why, when and how.
- Author
-
Cohen S, Hyer W, and Attard T
- Subjects
- Adolescent, Humans, Child, Colonoscopy adverse effects, Colonoscopy methods, Colorectal Neoplasms epidemiology, Polyps
- Abstract
Single or multiple polyps are frequently encountered during colonoscopy among children and adolescents and may be indicative of hereditary polyposis syndrome (HPS). The management of children with single or multiple polyps is guided by the number of polyps, their distribution and the histological findings. Children with HPS carry a high risk of complications, including intestinal and extra-intestinal malignancies. The goals of surveillance in pediatric HPS are to treat symptoms, monitor the burden of polyps and prevent short- and long-term complications. Therefore, the management of children with HPS is based on therapeutic endoscopy. The strategy of therapeutic endoscopy is a careful assessment and characterization of the polyps and performing polypectomies using advanced endoscopic techniques. A multidisciplinary approach, comprising clinical, interventional endoscopy, cancer surveillance and support of familial and emotional aspects is essential in the management of children with HPS., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
12. Fundic Gland Polyps: Strategizing a Surveillance Framework for Children and Adolescents.
- Author
-
Sami AS, Sylvester FA, Attard T, and Mir S
- Subjects
- Humans, Adolescent, Child, Gastric Fundus pathology, Polyps pathology, Stomach Neoplasms pathology, Adenomatous Polyps pathology
- Abstract
Competing Interests: The authors report no conflicts of interest.
- Published
- 2023
- Full Text
- View/download PDF
13. Incidental Finding of an Inverted Appendix.
- Author
-
Alatorre-Jimenez M and Attard T
- Subjects
- Humans, Incidental Findings, Appendectomy, Appendix surgery
- Abstract
Competing Interests: The authors report no conflicts of interest.
- Published
- 2023
- Full Text
- View/download PDF
14. The membrane activity of the antimicrobial peptide caerin 1.1 is pH dependent.
- Author
-
Sani MA, Le Brun AP, Rajput S, Attard T, and Separovic F
- Subjects
- Histidine chemistry, Australia, Lipid Bilayers chemistry, Cell Membrane metabolism, Water, Hydrogen-Ion Concentration, Antimicrobial Peptides, Antimicrobial Cationic Peptides metabolism
- Abstract
Antimicrobial peptides are an important class of membrane-active peptides that can provide alternatives or complements to classic antibiotics. Among the many classes of AMPs, the histidine-rich family is of particular interest since they may induce pH-sensitive interactions with cell membranes. The AMP caerin 1.1 (Cae-1), from Australian tree frogs, has three histidine residues, and thus we studied the pH dependence of its interactions with model cell membranes. Using NMR spectroscopy and molecular dynamics simulations, we showed that Cae-1 induced greater perturbation of the lipid dynamics and water penetrations within the membrane interior in an acidic environment compared with physiological conditions. Using
31 P solid-state NMR, the packing, chemical environment, and dynamics of the lipid headgroup were monitored.2 H solid-state NMR showed that Cae-1 ordered the acyl chains of the hydrophobic core of the bilayer. These results supported the molecular dynamics data, which showed that Cae-1 was mainly inserted within the lipid bilayer for both neutral and negatively charged membranes, with the charged residues pulling the water and phosphate groups inward. This could be an early step in the mechanism of membrane disruption by histidine-rich antimicrobial peptides and indicated that Cae-1 acts via a transmembrane mechanism in bilayers of neutral and anionic phospholipid membranes, especially in acidic conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
15. A fresh look at proton pump inhibitor (PPI)-associated adverse events through a CYP2C19 pharmacogenetic lens.
- Author
-
Chevalier R, Attard T, Van Driest SL, and Shakhnovich V
- Subjects
- Humans, Cytochrome P-450 CYP2C19 genetics, Genotype, Proton Pump Inhibitors adverse effects, Pharmacogenetics
- Published
- 2023
- Full Text
- View/download PDF
16. Analysis of Neurogastrointestinal and Motility Disorders From the National Pediatric Database (Kid's Inpatient Database): Exploring Demographic Access and Outcomes.
- Author
-
Patel D, Al-Hammadi N, Xu E, Hinyard L, and Attard T
- Subjects
- Adolescent, Child, Databases, Factual, Hospitalization, Humans, Length of Stay, United States, Inpatients, Quality of Life
- Abstract
Objectives: Pediatric neurogastroenterology and motility (PNGM) disorders impose a significant impact on health-related quality of life and cost of health care in children and adolescents. The detailed understanding of its burden across demographic groups is unknown. The objective of our study is to characterize the demographic and hospitalization trends of patients undergoing PNGM tests., Methods: We used Healthcare Cost and Utilization Project (HCUP) Inpatient Database (KID) for years 2003-2016 to perform a trend analysis in US hospitalizations for International Classification of Diseases (ICD)-9 and -10 Clinical Modification (CM)-identified PNGM studies in patients (<18 years of age) with elective admission and a length of stay (LOS) <3 days. The hospitalization rates were analyzed by year, hospital region, facility type, and patient sociodemographic characteristics. Multivariable logistic regression was used to examine factors influencing the receipt of motility studies., Results: There was an overall increase trend in hospitalizations, rates of PNGM studies, and median hospital charges from 2003 to 2016. Patients with private insurance and living in the high-income zip codes were more likely to receive a PNGM study compared with those with governmental insurance and lower income area. Although the race was not found to influence the receipt of the study, a major difference in the LOS was noted across the regions., Conclusions: There are income- and insurance-based differences in the rates of inpatient PNGM studies. PNGM studies significantly add to health care burden. Standardization of PNGM practices across the country may decrease the LOS and associated expenses. Future analysis should include ambulatory PNGM services to understand combined inpatient and outpatient trends., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
- Published
- 2022
- Full Text
- View/download PDF
17. PTEN Hamartoma Syndrome in a Child Presenting With Malrotation, Panintestinal Polyps, Severe Anemia, and Protein-Losing Enteropathy.
- Author
-
Stoecklein N, Ahmed AA, Lawson CE, and Attard T
- Abstract
PTEN hamartoma syndrome (PTEN-HS) is a rare syndrome including neurologic, neurodevelopmental, integumentary, endocrine, and gastrointestinal manifestations. Eosinophilic disorders of the gastrointestinal system are diverse group of disorders reported to be more common in PTEN-HS. Our patient had malrotation and obstruction in infancy and subsequently developed macrocephaly and a lipoma. She presented at 4 years of age with both iron deficiency anemia and hypoalbuminemia from protein-losing enteropathy. She went on to endoscopy, colonoscopy, and video capsule endoscopy showing gastric, small intestinal, and colonic polyps but with histology including both a mixed histologic characterization of the polyps as expected with PTEN-HS, along with eosinophilic esophagitis, gastric, duodenal, colonic and polyp eosinophilia. She improved with enteral nutritional support and budesonide. Intestinal malrotation is a previously unrecognized feature of PTEN-HS, in our patient protein-losing enteropathy may have resulted from polyposis or eosinophilic gastrointestinal disorder. Albeit rare, PTEN-HS represents an elusive differential diagnosis with a broad spectrum including gastrointestinal symptomatology. Our case report illustrates the overlap of clinical, endoscopic, and histologic findings that can complicate PTEN-HS., Competing Interests: The authors report no conflicts of interest, (Copyright © 2021 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
- Published
- 2021
- Full Text
- View/download PDF
18. Correction: DCLK1 isoforms and aberrant Notch signaling in the regulation of human and murine colitis.
- Author
-
Roy BC, Ahmed I, Stubbs J, Zhang J, Attard T, Septer S, Welch D, Anant S, Sampath V, and Umar S
- Published
- 2021
- Full Text
- View/download PDF
19. DCLK1 isoforms and aberrant Notch signaling in the regulation of human and murine colitis.
- Author
-
Roy BC, Ahmed I, Stubbs J, Zhang J, Attard T, Septer S, Welch D, Anant S, Sampath V, and Umar S
- Abstract
Alternative promoter usage generates long and short isoforms (DCLK1-L and DCLK1-S) of doublecortin-like kinase-1 (DCLK1). Tight control of Notch signaling is important to prevent and restitute inflammation in the intestine. Our aim was to investigate whether Notch1-DCLK1 axis regulates the mucosal immune responses to infection and whether this is phenocopied in human models of colitis. In the FFPE (formalin-fixed paraffin-embedded) sections prepared from the colons of ulcerative colitis (UC) and immune-mediated colitis (IRAEC) patients, expression of DCLK1 isoforms correlated positively with Notch1 and negatively with a transcriptional repressor, FoxD3 (Forkhead Box D3). DCLK1 protein staining in these sections was predominantly sub-epithelial (stromal) wherein DCLK1 co-localized with NICD, CD68, CD11c, and neutrophil elastase (NE). NE also co-stained with Citrullinated-H3 indicating the presence of neutrophil extracellular traps. In human neutrophils, elevated levels of DCLK1-S, CXCL-10, Ly6G, MPO, NE, and Notch1/2 in LPS-treated cells were inhibited when LPS was added in conjunction with Notch blocker dibenzazepine (DBZ; LPS + DBZ group). In CR-infected Rag1
-/- mice, higher levels of DCLK1 in the colonic crypts were inhibited when mice received DBZ for 10 days coincident with significant dysbiosis, barrier disruption, and colitis. Concurrently, DCLK1 immunoreactivity shifted toward the stroma in CR + DBZ mice with predominance of DCLK1-S that coincided with higher Notch1 levels. Upon antibiotic treatment, partial restoration of crypt DCLK1, reduction in MPO activity, and increased survival followed. When intestinal epithelial cell-specific Dclk1-knockout (Dclk1ΔIEC ) or Dclk1ΔIEC ;Rag1-/- double knockout (DKO) mice were infected with CR and given a single dose of DBZ, they developed barrier defect and severe colitis with higher levels of stromal DCLK1-S, Ly6G, NE, and Notch1. We therefore propose that, by regulating the mucosal immune responses, the Notch-DCLK1 axis may be integral to the development of murine or human colitis.- Published
- 2021
- Full Text
- View/download PDF
20. Small Bowel Hemolymphangioma Treated by Polypectomy in a Pediatric Patient with Cystic Fibrosis.
- Author
-
Halma J and Attard T
- Abstract
Competing Interests: The authors report no conflicts of interest.
- Published
- 2021
- Full Text
- View/download PDF
21. Pediatric Recurrent Intentional Foreign Body Ingestion: Case Series and Review of the Literature.
- Author
-
Low Kapalu CM, Ibrahimi N, Mentrikoski JM, and Attard T
- Subjects
- Adolescent, Child, Preschool, Digestive System, Eating, Female, Humans, Male, Autism Spectrum Disorder, Foreign Bodies complications, Foreign Bodies diagnostic imaging, Foreign Bodies surgery, Pediatrics
- Abstract
Although foreign body ingestion (FBI) is a common pediatric referral concern, intentional or recurrent FBI (RFBI) in youth is poorly defined. In adults, several subgroups of patients with psychiatric comorbidities account for a large portion of FBIs. A similar classification system and corresponding management recommendations are yet to be outlined in pediatrics. We report 3 patients with RFBI: a 16-year-old, African American boy with 22 admissions and 27 endoscopic procedures for FBI removal; a 4-year-old, African American boy with autism spectrum disorder admitted twice after delayed presentation of ingestion of magnets; and a 15-year-old Caucasian girl with a complex mental health history who presented twice after intentional ingestion to self-harm. We also present a literature review of pediatric RFBI. Patients with RFBI require a nuanced, multidisciplinary management approach to address acute concerns and reduce subsequent ingestion. A behavioral taxonomy and treatment considerations are presented.
- Published
- 2020
- Full Text
- View/download PDF
22. The Clinical Characteristics of Fractures in Pediatric Patients Exposed to Proton Pump Inhibitors.
- Author
-
Fleishman N, Richardson T, and Attard T
- Subjects
- Adult, Child, Cohort Studies, Databases, Factual, Humans, Odds Ratio, Risk Factors, Fractures, Bone chemically induced, Fractures, Bone epidemiology, Proton Pump Inhibitors adverse effects
- Abstract
Objectives: There are increasing concerns regarding proton pump inhibitor (PPI) use and the risk of fractures in adults. Few studies have evaluated this risk among pediatric patients. This study examined fractures and fracture location among pediatric patients exposed to PPI compared with those without documented exposure., Study Design: Encounters for patients 6 months to 15.5 years were identified between July 1, 2011 to December 31, 2015 in the Pediatric Hospital Information System database. Exclusion criteria was applied for chronic illnesses, conditions or medications predisposing to fracture. Encounters were classified as PPI encounters if a charge for PPI was documented. PPI encounters were propensity matched to non-PPI encounters. Following initial encounter, patients were evaluated over a 2-year period for hospitalizations resulting from fracture., Results: There was a statistically significant higher rate of fractures among the PPI-exposed group (1.4% vs 1.2%, P = 0.019). Adjusting for remaining differences in sex, race, encounter type, payer, and resource intensity after matching, the difference remained statistically significant (P = 0.017) with an adjusted odds ratio (95% CI) of 1.2 (1.0--1.4). Upper extremity was the most common location for fracture; however, the PPI cohort was more likely to suffer from lower extremity, rib, and spinal fractures (P = 0.01)., Conclusions: This study suggests an increased risk of fracture among pediatric patients taking PPI. Among patients hospitalized with a fracture, those with PPI exposure had a higher rate of lower extremity, rib, and spine fractures compared with controls. This appeared to be a class effect not related to individual PPI agent.
- Published
- 2020
- Full Text
- View/download PDF
23. Preventing Self-Harm From Repeat Foreign-Body Ingestion.
- Author
-
Low Kapalu C, Lantos J, Booser A, Thomson M, and Attard T
- Subjects
- Adolescent, Bioethical Issues, Foreign Bodies complications, Foreign Bodies diagnostic imaging, Gastroenterology ethics, Humans, Male, Personal Autonomy, Recurrence, Secondary Prevention ethics, Secondary Prevention methods, Self-Injurious Behavior psychology, Foreign Bodies prevention & control, Orthodontic Wires ethics, Orthodontics ethics, Self-Injurious Behavior prevention & control
- Abstract
Mental health disorders in adolescents present some of the most challenging of all ethical dilemmas. This is particularly true when they lead to self-injurious behavior that can only be prevented by either limiting the freedom of the adolescent or forcing treatments on them that they do not want. Intentional and repeated foreign-body ingestion (FBI) in youth is a poorly understood self-injurious behavior that can be life-threatening. It poses unique clinical and ethical challenges. Ingestion of sharp or magnetic objects increases the need for endoscopic retrieval or surgical intervention with associated risks, including perforation and anesthesia-related adverse events. When behavior modification efforts fail to prevent recurrent FBI, the cumulative risk of medical intervention mounts. Sometimes, as a last resort, doctors consider surgical procedures that limit jaw movement and may physically prevent recurrent FBI. In this Ethics Rounds article, we present a case in which doctors consider whether it is in the best interest of a teenager with this behavior to undergo orthodontic jaw wiring as a next step in treatment of repeated FBI. Doctor commentary on the ethical decision-making process is provided., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)
- Published
- 2020
- Full Text
- View/download PDF
24. Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2 (PKM2).
- Author
-
James AD, Richardson DA, Oh IW, Sritangos P, Attard T, Barrett L, and Bruce JIE
- Subjects
- Adenosine Triphosphate metabolism, Calcium metabolism, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal pathology, Carrier Proteins antagonists & inhibitors, Cell Line, Tumor, Cell Movement drug effects, Cell Survival drug effects, Cytosol drug effects, Glycolysis drug effects, Humans, Membrane Proteins antagonists & inhibitors, Naphthoquinones pharmacology, Pancreas drug effects, Pancreas metabolism, Pancreas pathology, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Thyroid Hormone-Binding Proteins, Carcinoma, Pancreatic Ductal drug therapy, Carrier Proteins genetics, Cell Proliferation genetics, Membrane Proteins genetics, Pancreatic Neoplasms drug therapy, Thyroid Hormones genetics
- Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) has poor survival and treatment options. PDAC cells shift their metabolism towards glycolysis, which fuels the plasma membrane calcium pump (PMCA), thereby preventing Ca
2+ -dependent cell death. The ATP-generating pyruvate kinase-M2 (PKM2) is oncogenic and overexpressed in PDAC. This study investigated the PKM2-derived ATP supply to the PMCA as a potential therapeutic locus., Methods: PDAC cell growth, migration and death were assessed by using sulforhodamine-B/tetrazolium-based assays, gap closure assay and poly-ADP ribose polymerase (PARP1) cleavage, respectively. Cellular ATP and metabolism were assessed using luciferase/fluorescent-based assays and the Seahorse XFe96 analyzer, respectively. Cell surface biotinylation identified membrane-associated proteins. Fura-2 imaging was used to assess cytosolic Ca2+ overload and in situ Ca2+ clearance. PKM2 knockdown was achieved using siRNA., Results: The PKM2 inhibitor (shikonin) reduced PDAC cell proliferation, cell migration and induced cell death. This was due to inhibition of glycolysis, ATP depletion, inhibition of PMCA and cytotoxic Ca2+ overload. PKM2 associates with plasma membrane proteins providing a privileged ATP supply to the PMCA. PKM2 knockdown reduced PMCA activity and reduced the sensitivity of shikonin-induced cell death., Conclusions: Cutting off the PKM2-derived ATP supply to the PMCA represents a novel therapeutic strategy for the treatment of PDAC.- Published
- 2020
- Full Text
- View/download PDF
25. Upper GI in patients with FAP-the need for formal research.
- Author
-
Martin I, Hawkins J, Hyer W, Attard T, Cohen S, Spigelman A, Clark SK, and Latchford A
- Subjects
- Child, Gastrointestinal Transit, Humans, Adenomatous Polyposis Coli
- Published
- 2020
- Full Text
- View/download PDF
26. Targeting transcription factor TCF4 by γ-Mangostin, a natural xanthone.
- Author
-
Krishnamachary B, Subramaniam D, Dandawate P, Ponnurangam S, Srinivasan P, Ramamoorthy P, Umar S, Thomas SM, Dhar A, Septer S, Weir SJ, Attard T, and Anant S
- Abstract
Given that colon cancer is the third most common cancer in incidence and cause of death in the United States, and current treatment modalities are insufficient, there is a need to develop novel agents. Towards this, here we focus on γ-Mangostin, a bioactive compound present in the Mangosteen ( Garcinia mangostana ) fruit. γ-Mangostin suppressed proliferation and colony formation, and induced cell cycle arrest and apoptosis of colon cancer cell lines. Further, γ-Mangostin inhibited colonosphere formation. Molecular docking and CETSA (Cellular thermal shift assay) binding assays demonstrated that γ-Mangostin interacts with transcription factor TCF4 (T-Cell Factor 4) at the β-catenin binding domain with the binding energy of -5.5 Kcal/mol. Moreover, γ-Mangostin treatment decreased TCF4 expression and reduced TCF reporter activity. The compound also suppressed the expression of Wnt signaling target proteins cyclin D1 and c-Myc, and stem cell markers such as LGR5, DCLK1 and CD44. To determine the effect of γ-Mangostin on tumor growth in vivo , we administered nude mice harboring HCT116 tumor xenografts with 5 mg/Kg of γ-Mangostin intraperitoneally for 21 days. γ-Mangostin treatment significantly suppressed tumor growth, with notably lowered tumor volume and weight. In addition, western blot analysis revealed a significant decrease in the expression of TCF4 and its downstream targets such as cyclin D1 and c-Myc. Together, these data suggest that γ-Mangostin inhibits colon cancer growth through targeting TCF4. γ-Mangostin may be a potential therapeutic agent for colon cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest., (Copyright: © 2019 Krishnamachary et al.)
- Published
- 2019
- Full Text
- View/download PDF
27. Linking Nanoscale Chemical Changes to Bulk Material Properties in IEPM Polymer Composites Subject to Impact Dynamics.
- Author
-
Attard T and He L
- Abstract
A synthesizable interfacial epoxy-polyurea-hybridized matrix (IEPM), composed of chemical bonded nanostructures across an interface width ranging between 2 and 50 μm, is a candidate for dialing-in molecular vibrational properties and providing high-impact dynamics resistance to conventional fiber(x)-reinforced epoxy (F/E), engendering an x-hybrid polymeric matrix composite system (x-IEPM- t
c ). Atomic force microscopy and scanning electron microscopy elucidate the interfacial nanoscale morphology and chemical structure via reaction kinetics of curing epoxy (as a function of time, tc ) and fast-reacting (prepolymerized) polyurea. Nano-infrared spectroscopy (nano-IR) spectra, per non-negative matrix factorization analysis, reveal that simultaneous presence of characteristic epoxy and polyurea vibrational modes, within a nanoscale region, along with unique IEPM characteristics and properties following thermomechanical analysis and dynamic mechanical analysis (DMA), indicate chemical bonding, enabling IEPM reaction kinetics, as a function of tc , to control natural bond vibrations and type/distribution of interfacial chemical bonds and physical mixtures, likely due to the bond mechanism between -NCO in polyurea and epoxide and -NH2 in epoxy hardener (corresponding to characteristic absorption peaks in nano-IR results), leading to enhanced IEPM quality (fewer defects/voids). Test results of ballistic-resistant panels, integrated with thin intermediate layers of x-IEPM-b- tc , confirm that lower tc significantly enhances loss modulus (∝ material damping and per DMA) in impact dynamics environments.- Published
- 2019
- Full Text
- View/download PDF
28. Management of Peutz-Jeghers Syndrome in Children and Adolescents: A Position Paper From the ESPGHAN Polyposis Working Group.
- Author
-
Latchford A, Cohen S, Auth M, Scaillon M, Viala J, Daniels R, Talbotec C, Attard T, Durno C, and Hyer W
- Subjects
- Child, Child, Preschool, Colonoscopy standards, Consensus, Evidence-Based Medicine, Genetic Testing standards, Humans, Intestinal Polyps diagnosis, Intestinal Polyps etiology, Intestinal Polyps surgery, Intussusception etiology, Mass Screening methods, Neoplasms etiology, Neoplasms genetics, Neoplasms prevention & control, Peutz-Jeghers Syndrome complications, Peutz-Jeghers Syndrome genetics, Risk Assessment, Mass Screening standards, Peutz-Jeghers Syndrome diagnosis, Peutz-Jeghers Syndrome therapy
- Abstract
Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps, and characteristic mucocutaneous freckling. Development of small bowel intestinal polyps may lead to intussusception in children may require emergency laparotomy with potential loss of bowel. Gastrointestinal polyps may lead to bleeding and anemia. This European Society for Paediatric Gastroenterology Hepatology and Nutrition position paper provides a guide for diagnosis, assessment, and management of PJS in children and adolescents and guidance on avoiding complications from PJS or from the endoscopic procedures performed on these patients.This is the first position paper regarding PJS published by European Society for Paediatric Gastroenterology Hepatology and Nutrition. Literature from PubMed, Medline, and Embase was reviewed and in the absence of evidence, recommendations reflect the opinion of pediatric and adult experts involved in the care of polyposis syndromes. Because many of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, some of the recommendations are based on expert opinion. This position paper will be helpful in the appropriate management and timing of procedures in children and adolescents with PJS.
- Published
- 2019
- Full Text
- View/download PDF
29. Effectiveness of Double-balloon Enteroscopy-facilitated Polypectomy in Pediatric Patients With Peutz-Jeghers Syndrome.
- Author
-
Belsha D, Urs A, Attard T, and Thomson M
- Subjects
- Adolescent, Child, Feasibility Studies, Female, Follow-Up Studies, Humans, Laparoscopy, Male, Peutz-Jeghers Syndrome diagnostic imaging, Prospective Studies, Treatment Outcome, Double-Balloon Enteroscopy, Peutz-Jeghers Syndrome surgery
- Abstract
Sizable small-bowel (SB) polyps in Peutz-Jeghers syndrome (PJS) pose a high risk for intussusception, often necessitating laparotomy and intraoperative enteroscopy. This series examines the effectiveness of double-balloon enteroscopy (DBE) facilitated polypectomy for pediatric patients with PJS. Prospective analysis of collected data (6 years) on all patients with PJS referred for DBE-facilitated SB polypectomy at a pediatric tertiary-referral center. A total of 16 pediatric patients with PJS were referred for DBE-facilitated SB polypectomy. Twenty-two DBEs were performed. Large polyps (≥1 cm) were confirmed in 14 patients. Successful clearance of large SB polyps by DBE or laparoscopically assisted DBE (Lap-DBE) was achieved in all patients. One patient experienced post-Lap-DBE pelvic abscess. All other patients remained asymptomatic and intervention free throughout follow-up (median 26 months). This series demonstrates that DBE-facilitated polypectomy is an effective therapeutic option in pediatric patients with PJS. It should be considered at an early age where possible.
- Published
- 2017
- Full Text
- View/download PDF
30. Diagnosis of celiac disease and applicability of ESPGHAN guidelines in Mediterranean countries: a real life prospective study.
- Author
-
Smarrazzo A, Misak Z, Costa S, Mičetić-Turk D, Abu-Zekry M, Kansu A, Abkari A, Bouziane-Nedjadi K, Ben Hariz M, Roma E, Velmishi V, Legarda Tamara M, Attard T, Djurisic V, Greco L, and Magazzù G
- Subjects
- Autoantibodies blood, Biopsy, Child, Preschool, Connective Tissue immunology, Female, GTP-Binding Proteins immunology, Genotyping Techniques, HLA Antigens genetics, Health Resources, Humans, Intestines pathology, Male, Mediterranean Region, Prospective Studies, Protein Glutamine gamma Glutamyltransferase 2, Transglutaminases immunology, Celiac Disease diagnosis, Guideline Adherence, Practice Guidelines as Topic
- Abstract
Background: We assessed how the diagnosis of Celiac Disease (CD) is made and how the new ESPGHAN guidelines can be applied in children from countries with different resources., Methods: A real life prospective study was performed in 14 centres of 13 different Mediterranean countries. Participants were asked to apply the usual diagnostic work-up for CD according to their diagnostic facilities., Results: There were 1974 patients enrolled in the study, mean age 4 years, 10 months; 865 male, 1109 female. CD was confirmed in 511 (25.9%) and was unconfirmed in 1391 (70.5%) patients; 14 patients were diagnosed as having CD according to the new ESPGHAN guidelines, 43 patients were classified as having potential CD. In all participating countries the diagnosis of CD relied on histology of duodenal biopsy; in 5 countries, HLA, and in one country endomysial antibodies (EMA) were not available. Symptoms did not add a significant increase to the pre-test probability of serological tests. The positive predictive value of tissue transglutaminase type 2 (tTG) antibodies performed with different kits but all corresponding to those recommended by ESPGHAN was 96.1% (95% CI 94-97.9%) in presence of tTG > 10xULN. In 135 patients with tTG >10xULN, HLA genotyping was performed and in all it was compatible with CD., Conclusions: The results of our study show that CD diagnosis still relies on intestinal biopsy in the Mediterranean area. New ESPGHAN criteria are not applicable in 5 countries due to lack of resources needed to perform HLA genotyping and, in one country, EMA assay. Further simplification of the new ESPGHAN guidelines might be made according to what preliminarily the present results suggest if confirmed by new prospective studies.
- Published
- 2017
- Full Text
- View/download PDF
31. A Novel Compound-Heterozygous Epithelial Cell Adhesion Molecule Mutation in Tufting Enteropathy.
- Author
-
Shakhnovich V, Dinwiddie D, Hildreth A, Attard T, and Kingsmore S
- Subjects
- Diarrhea, Infantile diagnosis, Humans, Infant, Infant, Newborn, Intestinal Mucosa pathology, Male, Mutation, Diarrhea, Infantile genetics, Epithelial Cell Adhesion Molecule genetics, Intestinal Mucosa abnormalities
- Published
- 2017
- Full Text
- View/download PDF
32. Familial adenomatous polyposis in pediatrics: natural history, emerging surveillance and management protocols, chemopreventive strategies, and areas of ongoing debate.
- Author
-
Septer S, Lawson CE, Anant S, and Attard T
- Subjects
- Adenomatous Polyposis Coli diagnosis, Adolescent, Adult, Chemoprevention methods, Child, Child, Preschool, Colectomy, Colorectal Neoplasms prevention & control, Duodenal Neoplasms prevention & control, Endoscopy, Gastrointestinal, Fibromatosis, Aggressive prevention & control, Genetic Counseling economics, Genetic Testing economics, Humans, Infant, Mutation, Prophylactic Surgical Procedures methods, Thyroid Neoplasms prevention & control, Treatment Outcome, Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli therapy, Adenomatous Polyposis Coli Protein genetics, Early Detection of Cancer methods, Genetic Counseling psychology
- Abstract
Familial adenomatous polyposis (FAP) is a hereditary condition with a near 100 % lifetime risk of colorectal cancer without prophylactic colectomy. Most patients with FAP have a mutation in the adenomatous polyposis coli gene on chromosome 5q22. This condition frequently presents in children with polyps developing most frequently in the second decade of life and surveillance colonoscopy is required starting at age ten. Polyps are found not only in the colon, but in the stomach and duodenum. Knowledge of the natural history of FAP is important as there are several extra-colonic sequelae which also require surveillance. In infants and toddlers, there is an increased risk of hepatoblastoma, while in teenagers and adults duodenal carcinomas, desmoid tumors, thyroid cancer and medulloblastoma are more common in FAP than in the general population. Current chemopreventive strategies include several medications and natural products, although to this point there is no consensus on the most efficacious and safe agent. Genetic counseling is an important part of the diagnostic process for FAP. Appropriate use and interpretation of genetic testing is best accomplished with genetic counselor involvement as many families also have concerns regarding future insurability or discrimination when faced with genetic testing.
- Published
- 2016
- Full Text
- View/download PDF
33. Desmoid tumors complicating Familial Adenomatous Polyposis: a meta-analysis mutation spectrum of affected individuals.
- Author
-
Slowik V, Attard T, Dai H, Shah R, and Septer S
- Subjects
- Adenomatous Polyposis Coli complications, Fibromatosis, Aggressive complications, Humans, Adenomatous Polyposis Coli genetics, Biomarkers, Tumor genetics, Fibromatosis, Aggressive genetics, Genes, APC, Genetic Predisposition to Disease, Mutation
- Abstract
Background: Desmoid tumors are a group of benign, invasive, solid tumors that are relatively rare in the general population, but can occur in up to 21 % of patients with Familial Adenomatous Polyposis (FAP). They can be difficult to treat and have high rates of recurrence even after resection. Our goal with this study was to identify the genetic mutations that put certain patients with FAP at high risk for desmoid tumors and could be future targets for research., Methods: We performed a search in Pubmed, Ovid Medline and Embase to identify subjects with desmoid tumors and FAP. As a reference group for APC mutations in the unselected FAP population, we used the UMD-APC database referenced in the Orphanet portal which includes APC mutation data on 2040 individuals with FAP., Results: Mutations were able to be broken down into 7 regions based on previously published data. Mutations in the APC gene from codons 1310 to 2011 were the most common region encompassing 48 % of published desmoid cases and 40 % of the reference population. It had a slightly elevated odds ratio of 1.4 that was statistically significant along with codon region 543-713 that had an odds ratio of 2.0. Using a combination of p-value and CI, the remaining 5 regions did not meet statistical significance as either the p >0.05 or the CI included 1.0. The most common point mutation found was codon 1309 (13.1 %), but it was also the most commonly found mutation in our reference population (12.9 %) and had an odds ratio of 1.0., Conclusions: There is an increased risk for desmoid tumors in individuals with APC mutations between codons 543-713 and 1310-2011 when compared to a reference population. These patients may benefit from further study to develop surveillance protocols that could improve outcomes.
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.