Sarah-May M L The1,2, Tim G J de Meij3,4,5, Andries E Budding6, Roel Bakx7,4, Johanna H van der Lee8,9, Linda Poort6, Huib A Cense10, Hugo A Heij7, L W Ernst van Heurn7,4,5, Ramon R Gorter7,4,5. 1. Department of Pediatric Surgery, Emma Children's Hospital, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands. s.the@amsterdamumc.nl. 2. Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands. s.the@amsterdamumc.nl. 3. Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands. 4. Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands. 5. Amsterdam Gastroenterology and Metabolism Research Insititute, Amsterdam, The Netherlands. 6. Inbiome, Amsterdam, 1098 XG, The Netherlands. 7. Department of Pediatric Surgery, Emma Children's Hospital, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands. 8. Pediatric Clinical Research Office, Emma Children's Hospital, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands. 9. Dutch Knowledge Institute, Federation of Medical Specialists, Utrecht, 3528 BL, The Netherlands. 10. Department of Surgery, Red Cross Hospital, Beverwijk, 1942 LE, The Netherlands.
Abstract
Currently, accurate biomarkers differentiating simple (phlegmonous) from complex (gangrenous and/or perforated) appendicitis in children are lacking. However, both types may potentially require different treatment strategies, and the search for diagnostic modalities remains warranted. Previously, we demonstrated a distinct microbiota (both an increased bacterial diversity and abundance) in the appendix of children with complex compared to simple appendicitis. From the same cohort of patients we have collected 35 rectal swabs under general anesthesia prior to appendectomy and microbiota analysis was performed by IS-pro, a 16S-23S rDNA-based clinical microbiota profiling technique. Using the obtained IS-profiles, we performed cluster analyses (UPGMA), comparison of diversity (Shannon Diversity Index) and intensity (abundance in relative fluorescence units) on phylum level, and comparison on species level of bacteria between simple and complex appendicitis. Regarding these analyses, we observed no clear differences between simple and complex appendicitis. However, increased similarity of the microbial composition of the appendix and rectal swab was found within children with complex compared to simple appendicitis. Furthermore, PLS-DA regression analysis provided clear visual differentiation between simple and complex appendicitis, but the diagnostic power was low (highest AUC 0.65). Conclusion: Microbiota analysis of rectal swabs may be viable to differentiate between simple and complex appendicitis prior to surgery as a supervised classification model allowed for discrimination of both types. However, the current diagnostic power was low and further validation studies are needed to assess the value of this method. What is Known: • Simple and complex appendicitis in children may require different treatment strategies, but accurate preoperative biomarkers are lacking. • Clear differentiation can be made between both types in children based upon the microbial composition in the appendix. What is New: • Increased similarity was found between the microbial composition of the appendix and rectal swab within children with complex compared to simple appendicitis. • Using a supervised classification model rectal swabs may be viable to discriminate between simple and complex appendicitis, but the diagnostic power was low.
Currently, accurate biomarkers differentiating simple (phlegmonous) from complex (gangrenous and/or perforated) appendicitis in children are lacking. However, both types may potentially require different treatment strategies, and the search for diagnostic modalities remains warranted. Previously, we demonstrated a distinct microbiota (both an increased bacterial diversity and abundance) in the appendix of children with complex compared to simple appendicitis. From the same cohort of patients we have collected 35 rectal swabs under general anesthesia prior to appendectomy and microbiota analysis was performed by IS-pro, a 16S-23S rDNA-based clinical microbiota profiling technique. Using the obtained IS-profiles, we performed cluster analyses (UPGMA), comparison of diversity (Shannon Diversity Index) and intensity (abundance in relative fluorescence units) on phylum level, and comparison on species level of bacteria between simple and complex appendicitis. Regarding these analyses, we observed no clear differences between simple and complex appendicitis. However, increased similarity of the microbial composition of the appendix and rectal swab was found within children with complex compared to simple appendicitis. Furthermore, PLS-DA regression analysis provided clear visual differentiation between simple and complex appendicitis, but the diagnostic power was low (highest AUC 0.65). Conclusion: Microbiota analysis of rectal swabs may be viable to differentiate between simple and complex appendicitis prior to surgery as a supervised classification model allowed for discrimination of both types. However, the current diagnostic power was low and further validation studies are needed to assess the value of this method. What is Known: • Simple and complex appendicitis in children may require different treatment strategies, but accurate preoperative biomarkers are lacking. • Clear differentiation can be made between both types in children based upon the microbial composition in the appendix. What is New: • Increased similarity was found between the microbial composition of the appendix and rectal swab within children with complex compared to simple appendicitis. • Using a supervised classification model rectal swabs may be viable to discriminate between simple and complex appendicitis, but the diagnostic power was low.
Authors: A E Budding; M E Grasman; F Lin; J A Bogaards; D J Soeltan-Kaersenhout; C M J E Vandenbroucke-Grauls; A A van Bodegraven; P H M Savelkoul Journal: FASEB J Date: 2010-07-19 Impact factor: 5.191
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Authors: Ramon R Gorter; Anne Loes van den Boom; Hugo A Heij; C M Frank Kneepkens; Caroline C Hulsker; Mark Tenhagen; Imro Dawson; Johanna H van der Lee Journal: J Surg Res Date: 2015-08-31 Impact factor: 2.192
Authors: L Daniels; A E Budding; N de Korte; A Eck; J A Bogaards; H B Stockmann; E C Consten; P H Savelkoul; M A Boermeester Journal: Eur J Clin Microbiol Infect Dis Date: 2014-06-04 Impact factor: 3.267
Authors: Hope T Jackson; Emmanuel F Mongodin; Katherine P Davenport; Claire M Fraser; Anthony D Sandler; Steven L Zeichner Journal: PLoS One Date: 2014-04-23 Impact factor: 3.240
Authors: Andries E Budding; Matthijs E Grasman; Anat Eck; Johannes A Bogaards; Christina M J E Vandenbroucke-Grauls; Adriaan A van Bodegraven; Paul H M Savelkoul Journal: PLoS One Date: 2014-07-14 Impact factor: 3.240