Fifteen-year follow-up of association between telomere length and incident cancer and cancer mortality.

roid insufficiency does not conform to that of the ACCM, which states that a corticotropin test should not be used to identify patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids. In the HYPOLYTE study, patients with adapted corticosteroid function had a short median time of exposure to hydrocortisone (median, 34 hours; interquartile range, 20-49). We reported a decreased hospital-acquired pneumonia rate at day 28 in all patients, but the study was neither designed nor powered to evaluate the safety of treatment in patients with adapted corticosteroid function. Regarding the threshold of cortisolemia, the current definition of critical illness–related corticosteroid insufficiency was not available at the time the study was started. When using this definition, the risk of hospitalacquired pneumonia at day 28 remained lower in the hydrocortisone group (hazard ratio, 0.41; 95% CI, 0.20-0.88; P=.02). We thus believe that a corticotropin test should be performed to identify trauma patients who may benefit from prolonged low-dose hydrocortisone. In a systematic review of corticosteroid use in patients with severe sepsis, a long course of low-dose corticosteroids did not alter superinfection rate (relative risk, 1.01; 95% CI, 0.82-1.25; P=.92). Also, the rate of polyneuromyopathy, which is low in trauma patients, was not increased in septic patients treated with corticosteroids. Dr Johnson suggests that hydrocortisone may have biased the diagnosis of hospital-acquired pneumonia. In the setting of community-acquired pneumonia, patients treated with a high dose of glucocorticoid presented a slightly decreased body temperature (less than 0.5°C) as compared with patients treated with placebo. To our knowledge, the effects of stress-dose hydrocortisone on body temperature in patients with corticosteroid insufficiency are unknown. In our study, body temperature exceeded 38.0°C in 23 of 28 episodes (82.1%) of hospital-acquired pneumonia in the corticosteroid group and in 35 of 47 episodes (74.5%) in the placebo group, with no difference between the 2 groups (P=.60). It is unlikely that the antipyretic properties of hydrocortisone explain the decreased hospital-acquired pneumonia rate in the hydrocortisone group. Drs Salluh and Póvoa question the safety of corticosteroids. Pharmacological (ie, prednisolone) and physiological (ie, hydrocortisone) glucocorticoids display different properties. Stress doses of hydrocortisone reprogram rather than inhibit immune cells. Corticosteroid effects depend on the inflammatory status of the host; thus, the timing of corticosteroid initiation is critical, and no patients were treated late in our study. The suggestion by Salluh and Póvoa to consider combined lower respiratory tract infections is questionable. First, the morbidity of tracheobronchitis remains unknown in trauma patients whereas pneumonia clearly increases morbidity. Second, mechanical ventilation–free days, a surrogate marker of the efficacy of the treatment of pneumonia, increased with hydrocortisone in our study. We agree that evaluation of mortality is critical, and there is no randomized study using stress doses of hydrocortisone that have shown an increased mortality rate in sepsis, acute respiratory distress syndrome, or trauma. In a recent systematic review, analyses of the trials investigating a prolonged course ( 5 days) of stress-dose corticosteroid treatment in sepsis and septic shock demonstrated a significant reduction in 28-day all-cause mortality and hospital mortality with no increase in superinfections. In the setting of trauma, the most frequent causes of deaths are acute intracranial hypertension and hemorrhagic shock, which occur within the first few hours. We believe that mortality should remain a safety end point but not a primary end point for evaluation of stress-dose hydrocortisone in patients with multiple trauma. Our study was not powered to test the noninferiority of hydrocortisone vs placebo on mortality.