The authors suggest that if surgical outcome was the primary outcome measure in the MIST2 trial, there would be no difference between the tPA and tPA plus DNase groups. However, there was a statistically significant improvement in surgical referral in the tPA plus DNase group (OR, 0.17; P = .03) and not in the tPA group (OR, 0.29; P = .1) compared with placebo. The differences were small (down to one patient); however, these were secondary outcomes, and any treatment effect should be treated with caution. If all data from the trial are taken together, it is clear that the tPA plus DNase group demonstrates consistent improvement in several outcomes (chest radiograph, surgical referral, hospital stay, and reduction of fever) compared with placebo, whereas tPA only shows a modest effect in surgical referral that is statistically nonsignificant. This, in parallel to the MIST1 trial result, suggests that fibrinolytics alone are not effective in the treatment of pleural infection. Our view remains that the published data suggest that combination tPA and DNase has been shown to be superior to placebo and the agents individually and that further large trials are required to provide precise data on the treatment effect on surgical, hospital stay, and mortality outcomes.