title: Towards a proposal for a universal diagnostic definition of protein-losing enteropathy in Fontan patients: a systematic review.
abstract: A standardised diagnostic definition of protein-losing enteropathy (PLE) in Fontan patients serves both patient care and research. The present study determined whether a diagnostic definition of PLE was routinely used in published clinical Fontan studies, and to identify potentially relevant diagnostic criteria for composing a uniform PLE definition.
  
  
  
  A systematic review was conducted in adherence to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. Published clinical Fontan studies that were written in English and included at least four patients with PLE were selected. PLE definitions were quantitatively analysed using a lateral thinking tool in which definitions were fractionated into constituent pieces of information (building blocks or diagnostic criteria).
  
  
  
  We identified 364 papers. In the final analysis, data from 62 published articles were extracted. A diagnostic definition of PLE was used in only 27/62 (43.5%) of selected studies, and definitions were very heterogeneous. We identified eight major diagnostic criteria. Hypoalbuminaemia (n=23 studies, 85.2%), clinical presentation (n=18, 66.7%), documentation of enteric protein loss (n=16, 59.3%) and exclusion of other causes of hypoproteinaemia (n=17, 63.0%), were the most frequently used diagnostic criteria. Most studies used three diagnostic variables (n=13/27, 48.1%). Cut-off values for laboratory parameters (serum albumin, protein or faecal α-1-antitrypsin) were frequently incorporated in the PLE definition (n=16, 59.3%).
  
  
  
  Establishment of a universally accepted PLE definition for routine use in clinical research and daily practice is required. The diagnostic criteria may help constitute a diagnostic PLE definition.
authors.affiliation: Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany.
authors.forename: Floris Ea
authors.initials: FE
authors.lastname: Udink Ten Cate
authors.affiliation: Department of Paediatrics, Children's Hospital, University Hospital of Cologne, Cologne, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hannes
authors.affiliation: Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Germund
authors.affiliation: Paediatric Heart Centre, Justus-Liebig University, Giessen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Khalil
authors.affiliation: Department of Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Huntgeburth
authors.affiliation: Department of Paediatric Cardiology, University Children's Hospital Ulm, Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Apitz
authors.affiliation: Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Brockmeier
authors.affiliation: Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Cologne, Germany.
authors.forename: Narayanswami
authors.initials: N
authors.lastname: Sreeram
mesh_terms: D032921:Consensus; D018729:Fontan Procedure / Q000009:adverse effects*; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000601:surgery*; D006801:Humans; D011237:Predictive Value of Tests; D011504:Protein-Losing Enteropathies / Q000145:classification / Q000175:diagnosis* / Q000209:etiology; D009626:Terminology as Topic; D016896:Treatment Outcome