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MULTIMORBIDITY BURDEN AND DEVELOPMENTAL TRAJECTORY IN RELATION TO APPENDECTOMY: EVIDENCE FROM A LARGE-SCALE COHORT STUDY
Meng Kang
1, Tian Fu
2,1, Yuexin Zhu
3, Tianyi Che
4, Fangmin Jing
1, Xixian Ruan
1, Sidan Wang
1, Xiaocang Cao
5, Xiaoyan Wang
1, Jie Chen
*11Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, --- Select One ---, China; 2Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, School Of Medicine, Westlake University, Hangzhou, --- Select One ---, China; 3Beijing Anzhen Hospital, Capital Medical University, Beijing, China; 4Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 5Department of Hepato-Gastroenterology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
Background: The appendix is rich in lymphoid tissue and is thought to play an important role in multiple diseases especially immunity and gut microbiological maintenance, and multimorbidity burden might exist after appendectomy. In recent years, an increasing number of studies have explored the potential health effects of appendectomy, but with inconsistent conclusions. Therefore, we aimed to clarify the comorbidity pattern of appendectomy and potential time-dependent sequence.
Methods: We conducted a phenome-wide association study (PheWAS) and disease trajectory analyses based on UK Biobank participants, a large-scale cohort study. In the PheWAS analysis, Cox regression models were utilized to examine the hazard ratios and corresponding confidence intervals for risk of various health outcomes and all-cause mortality in relation to appendectomy. Further disease trajectory analyses were employed to explore and visualize the sequential patterns of the multimorbidity among individuals after appendectomy. Specifically, we included comorbidities occurring in at least 1% after appendectomy, and used a binomial test to assess the order of disease with both diagnoses, with a nested case-control design and conditional logistic regression models finally applied to evaluate the strength of the associations.
Results: The PheWAS analysis observed 277 comorbidities and all-cause mortality were at higher risk among participants with appendectomy. Three sequential patterns of comorbidity network including gastrointestinal dynamics-related diseases, immune-related diseases and intestinal flora-related diseases after appendectomy were observed and established in the subsequent disease trajectories analyses. Intermediary diseases such as irritable bowel syndrome, constipation, rheumatoid arthritis, polymyalgia rheumatica, depression and Parkinson's disease were mainly observed, which primarily resulted in psychogenic disorder, renal failure, heart failure, hypovolemia, and all-cause mortality.
Conclusion: This study observed associations between appendectomy and a broad range of systematic diseases, particularly involving intestinal flora, immune system, and gastrointestinal dynamics. Our findings underscore the need for long-term follow-up and comprehensive management of post-appendectomy patients, with targeted interventions to support gut health and immune function, to optimize overall health outcomes.
Figure1: Significant outcomes associated with Appendectomy in observational PheWAS in UK Biobank.The x axis represents distinct phenotypic groups by using different colors. The y axis shows the effect size of increased disease risk in patients with Appendectomy compared to matched individuals (HR>1). All risk increases are statistically significant (false discovery rate < 0.05). HR, hazard ratio; PheWAS, phenome-wide association study.
Figure2: Trajectories of disease clusters among Appendectomy individuals.
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