Paragraph: To differentiate different entities of appendicitis through studying cluster/outbreak, ascertain common setting of cluster/outbreak, and provide the epidemiological evidences of infectious etiology of appendicitis. Background: Differential diagnosis and management for perforated appendicitis and non-perforated appendicitis and the infectious etiology of appendicitis are current hot topics. Methods: Field investigation for Tibetan students were carried out and reports published in English and Chinese medical journals were reviewed. The literature review included 473 patients in 7 cluster/outbreaks of appendicitis in 6 provinces and autonomous regions. All the clusters/outbreaks occurred in group living units. We found two classic entities of appendicitis with natural history from nonperforated appendicitis to perforated appendicitis and two entities of non-perforated appendicitis. In classic entities, one may represent majority of sporadic patients and the other may represent partial sporadic patients with obvious gastrointestinal manifestation. In entities of non-perforated appendicitis, one was identical to features of sporadic nonperforated appendicitis and the other one is identical to the following Tibetan students and associated with Fusobacterium. The field investigation for 120 Tibetan students with appendicitis showed that the resected appendices exhibited diffuse or focal hemorrhages and infiltration by eosinophils and by lymphocytes. Most patients had normal body temperature, white blood cell count and neutrophil count. This is a new entity of appendicitis. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint 3 The clusters/outbreaks of appendicitis showed the features of infectious disease in epidemiology. The entity of perforated appendicitis was not found. Studying cluster/outbreak is a good method to differentiate different entities of appendicitis and infectious etiology. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint . Cluster/outbreak often results from common cause, therefore almost every patient in cluster/outbreak belongs to the same entity and appeared in certain stage of same entity. Connecting each stage, we can know full natural histories of different entities and accordingly demonstrate whether or not perforated appendicitis and non-perforated appendicitis are different entities. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint METHODS Field investigation of cluster/outbreak was carried out according to Reingold AL's methods 35 and literature review was carried out to find the other cluster/outbreak. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint of non-perforated and perforated appendicitis: Implications for pathophysiology and management. Ann Surg 2007; 245(6):886-892. 7. Andersson RE. The natural history and traditional management of appendicitis revisited:Spontaneous resolution and predominance of prehospital perforations imply that a correct diagnosis is more important than an early diagnosis. World J Surg 2007; 31(1):86-92. 8. Körner H1, Söndenaa K, Söreide JA. Incidence of acute non-perforated and perforated appendicitis: age-specific and sex-specific analysis. World J Surg. 1997; 21(3):313-317. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint 32. Lead from MMWR. Investigation of a cluster of appendicitis outbreaks-Texas. JAMA 1987; 258(3):310-311. 33. Guo Y, Xiao SY, Yan H, Sun ND, Jiang MS, Liu DY. Cluster of acute hemorrhagic appendicitis among high school students in Wuhan, China. Am J Surg 2004; 188(2):115-121. 34. Swidsinski A, Loening-Baucke V, Biche-Ool S, et al. Mucosal invasion by All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 
 Title: Demonstration of four entities of appendicitis in China through studying cluster/outbreak
Output: False