In addition strains continue to evolve making current treatments ineffective

By contrast with the higher specificity, these tumor markers had low sensitivities that were not sufficiently low to exclude non-EC when the tumor marker concentrations are lower than the cut-off values. Although we tried to avoid bias in the process of identifying studies, screening, assessing, data extraction, and data analyses, the present study has several limitations. First, the exclusion of conference abstracts and letters to journal editors may have led to publication bias, an inflation of accuracy estimates due to preferential acceptance of papers reporting favorable results, and the potential for publication bias in studies included in the present meta-analysis. Second, we did not calculate the diagnostic accuracy for early stage cancers because sufficient raw data was not provided. Although we aimed to evaluate the diagnostic value of tumor markers for the early diagnosis of the cancer, cancer patients regardless of disease stage were used to evaluate the diagnostic power because of the limited amount of information. Primary data was unavailable for investigation of elevated or decreased tumor marker-positive values as a function of tumor type, histology, age, or degree. Also, because of lack of required data reported in the original publications, we did not calculate the diagnostic value of the combination of tumor markers. Thirdly, we excluded 20 studies because they did not provide data allowing construction of 2��2 tables. We did not contact authors to obtain further data, potentially resulting in biased results and less precise estimates of pooled diagnostic accuracy. EIPA Finally, we only included five biomarkers because the other 12 biomarkers could not be pooled as lacking of insufficient studies. As we all known, meta-analysis must pool two studies at least. The last but not the least, in all 44 studies, cancer patients diagnosed by histology was regarded as positive. However, the negative controls without cancer that were healthy or had benign disease were not diagnosed by histology. In addition, most of the studies did not report whether the investigators were blinded. Therefore, such non-strict designs could exaggerate the diagnostic accuracy and lead to bias due to unfavorable representation of the participants. The accuracy of tumor marker determinations for EC seems to be similar to that of conventional tests such as cytological examination, which has high specificity and low sensitivity. This similarity might make tumor markers less useful in practice because they do not have test properties that EDTA complement the properties of conventional tests. However, it should be pointed out that, to date, there are insufficient related studies to evaluate the diagnostic accuracy of the combination of two or more tumor markers in EC. Influenza A viruses are highly infectious pathogens responsible for seasonal epidemics and for pandemics.

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