You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
A multiplex polymerase chain reaction assay for the detection of Mycobacterium paratuberculosis DNA in Crohn's disease tissue.
Abstract 1:
BACKGROUND Mycobacterium paratuberculosis is implicated as a possible cause of Crohn 's disease . However , due to lack of an appropriate diagnostic method , this has been a subject of significant controversy . Our aim was therefore to develop a multiplex polymerase chain reaction ( MPCR ) for the detection of M. paratuberculosis DNA in Crohn 's disease tissue . METHODS Biopsy sample s were collected by endoscopic forceps from terminal ileum , and genomic DNA was isolated . M. paratuberculosis-specific marker genes were amplified by using the present MPCR method . RESULTS Here we report a new MPCR for detection of M. paratuberculosis DNA in Crohn 's disease tissue . In this technique two genetic markers , IS900 and a newly described specific marker of MP2 , were amplified in a single tube simultaneously . The method was evaluated using biopsy specimens from 10 Crohn 's disease patients , 6 ulcerative colitis patients , and 21 irritable bowel syndrome patients . The patients were characterized by using st and ard clinical and histologic observations . The present MPCR method could not detect M. paratuberculosis DNA in the biopsy specimens . However , the marker genes were amplified from the sample s that were spiked with M. paratuberculosis before DNA extraction . The marker genes were also not detected in 10 closely related mycobacterial strains and human genomic DNA . CONCLUSIONS The present MPCR method is highly specific and can detect M. paratuberculosis DNA more reliably . These findings do not support an aetiologic role of M. paratuberculosis in Crohn 's disease


Title 2:
Mycobacterium paratuberculosis in intestinal tissue from patients with Crohn's disease demonstrated by a nested primer polymerase chain reaction.
Abstract 2:
BACKGROUND The etiology of Crohn 's disease remains unknown , but current research has concentrated on autoimmunity and /or mycobacterial infection . The polymerase chain reaction ( PCR ) enables the detection of genetic material even when very few microorganisms are present . METHODS A nested primer PCR for detection of a multi-copy insertional element ( IS900 ) specific for Mycobacterium paratuberculosis was applied to DNA extracted from fresh and from paraffin-embedded intestinal tissue obtained from patients undergoing surgery .  RESULTS In fresh intestinal tissue from 11 of 24 patients with Crohn 's disease , from 2 of 10 patients with ulcerative colitis , and from 3 of 28 patients with other colonic disorders , specific M. paratuberculosis DNA was found . In paraffin-embedded Crohn 's disease tissue the presence of specific M. paratuberculosis DNA was also increased . CONCLUSIONS Whether the presence of M. paratuberculosis is connected to the inflammatory bowel disease or is a mere coincidence can not be stated . We find this presence interesting and encouraging for further investigations


Title 3:
Role of Mycobacterium paratuberculosis in Crohn's disease: A prospective, controlled study using polymerase chain reaction
Abstract 3:
PURPOSE : Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohn 's disease . The purpose of this study was to determine whether M. paratuberculosis was present in tissue from patients with Crohn 's disease in a defined geographic area . METHODS : We prospect ively evaluated , using polymerase chain reaction and culture , whether M. paratuberculosis was present in 44 specimens ( 37 from intestinal mucosal biopsies and 7 from surgical resections ) from patients with Crohn 's disease , ulcerative colitis , or normal colonic mucosa . RESULTS : Of the 25 specimens tested from the 21 Crohn 's patients , only 1 positive specimen was noted , whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction . Cultures of all specimens revealed no growth of M. paratuberculosis . CONCLUSION : M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohn 's disease . These results do not support a common causative role of M. paratuberculosis in Crohn 's disease


Title 4:
Prevalence of enteropathogenic bacteria in surgically treated chronic inflammatory bowel disease.
Abstract 4:
BACKGROUND / AIMS In order to assess the potential impact of bacterial eradication on recurrence rates , the prevalence of various enteropathogenic bacteria and toxins in chronic inflammatory bowel diseases ( CIBD ) was prospect ively examined . METHODOLOGY Stool , sera and gut tissue sample s from a total of 59 patients ( 33 males , 26 females ; mean age : 42 years + /- 14 ; 21 Crohn 's disease , 14 ulcerative colitis , 24 controls ) were examined for the presence of enteropathogenic bacteria by culture , immunoblotting and PCR . RESULTS Conventional cultures failed to detect obligate pathogenic bacteria . By PCR , mycobacteria were found in 85 % of all groups , with mycobacterium paratuberculosis not detected . Yersinia species were observed in 63 % of patients with Crohn 's disease , in 46 % of patients with ulcerative colitis , and in 36 % of the control patients . Pathogenic E. coli were identified in stool sample s of three patients with ulcerative colitis ( 21 % ) by amplifying the EAE-gene , one of whom exhibited shiga-like-toxin as well . CONCLUSIONS We concluded that mycobacteria do not play a causative role in CIBD . Yersinia species seem to persist in intestinal tissue in CIBD patients without adequate immune response and might , thus , contribute to tissue destruction . E. coli infections contribute to the disease process in a small group of patients with ulcerative colitis and their eradication might eliminate the need for immediate surgical intervention
The data confirms the observation that MAP is detected more frequently among CD patients compared with controls .
However , the pathogenic role of this bacterium in the gut remains uncertain .
Our analysis demonstrates that there is an association between MAP and CD , across many sites , by many investigators , and controlling for a number of factors ; however , this association remains controversial and inconclusive .