severe disease uncontrolled systemic infection active concurrent morbidity current septicemia visceral disease crisis threatening metastases metastasis life rapid liver severe infection uncontrolled eligible patients subjects active stratum untreated study participation infection controlled antibiotics active eligible uncontrolled patients judged antimicrobial treatment threatening life infection uncontrolled active disease untreated patients antimicrobial severe spread threatening visceral term life short symptomatic complications risk advanced threatening life potentially autoimmune active disease second activated patients history