title: A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia.
abstract: BACKGROUND
  Endothelial barrier breakdown is a hallmark of septic shock, and proteins that physiologically regulate endothelial barrier integrity are emerging as promising biomarkers of septic shock development. Patients with cancer and febrile neutropenia (FN) present a higher risk of sepsis complications, such as septic shock. Nonetheless, these patients are normally excluded or under-represented in sepsis biomarker studies. The aim of our study was to validate the measurement of a panel of microvascular permeability modulators as biomarkers of septic shock development in cancer patients with chemotherapy-associated FN.
  
  
  METHODS
  This was a prospective study of diagnostic accuracy, performed in two distinct in-patient units of a university hospital. Levels of vascular endothelial growth factor A (VEGF-A), soluble fms-like tyrosine kinase-1 (sFlt-1) and angiopoietin (Ang) 1 and 2 were measured after the onset of neutropenic fever, in conditions designed to mimic the real-world use of a sepsis biomarker, based on our local practice. Patients were categorized based on the development of septic shock by 28 days as an outcome.
  
  
  RESULTS
  A total of 99 consecutive patients were evaluated in the study, of which 20 developed septic shock and 79 were classified as non-complicated FN. VEGF-A and sFlt-1 levels were similar between both outcome groups. In contrast, Ang-2 concentrations were increased in patients with septic shock, whereas an inverse finding was observed for Ang-1, resulting in a higher Ang-2/Ang-1 ratio in patients with septic shock (5.29, range 0.58 to 57.14) compared to non-complicated FN (1.99, range 0.06 to 64.62; P = 0.01). After multivariate analysis, the Ang-2/Ang-1 ratio remained an independent factor for septic shock development and 28-day mortality.
  
  
  CONCLUSIONS
  A high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia.
authors.forename: Maiara Marx
authors.initials: MM
authors.lastname: Luz Fiusa
authors.forename: Carolina
authors.initials: C
authors.lastname: Costa-Lima
authors.forename: Gleice Regina
authors.initials: GR
authors.lastname: de Souza
authors.forename: Afonso Celso
authors.initials: AC
authors.lastname: Vigorito
authors.forename: Francisco Jose
authors.initials: FJ
authors.lastname: Penteado Aranha
authors.forename: Irene
authors.initials: I
authors.lastname: Lorand-Metze
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
authors.forename: Carmino Antonio
authors.initials: CA
authors.lastname: de Souza
authors.forename: Erich V
authors.initials: EV
authors.lastname: De Paula
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D064147:Febrile Neutropenia / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D011446:Prospective Studies; D012307:Risk Factors; D012772:Shock, Septic / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D015996:Survival Rate / Q000639:trends; D055815:Young Adult
chemical_list: C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers
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