Impact of supplemental parenteral nutrition early during critical illness on invasive fungal infections: a secondary analysis of the EPaNIC randomized controlled trial.

OBJECTIVE: In the EPaNIC RCT (N=4640), postponing the administration of parenteral nutrition (PN) to beyond 1 week in the intensive care unit (ICU) (late-PN) reduced the number of ICU-acquired infections and the costs for antimicrobial drugs compared with initiation of PN within 24-48 hours of admission (early-PN). In a secondary analysis, we hypothesize that late-PN reduces the odds to acquire an invasive fungal infection (IFI) in the ICU. METHODS: The impact of late-PN (N=2328) versus early-PN (N=2312) on acquired IFI and on the likelihood to acquire an IFI over time was assessed in univariable and multivariable analyses. Subsequently, we performed multivariable analyses to assess the effect of the mean total daily administered calories from admission until day 3, day 5, and day 7 on the likelihood over time of acquiring an IFI. RESULTS: Fewer late-PN patients acquired an IFI compared with early-PN patients (77/2328 versus 112/2312) (p 0.008). After adjusting for risk factors, the odds to acquire an IFI and the likelihood of acquiring an IFI at any time were lower in late-PN (adjusted odds ratio 0.66, 95% CI 0.48-0.90, p 0.009; adjusted hazard ratio (HRadj) 0.70, 95% CI 0.52-0.93, p 0.02). Larger caloric amounts from admission until day 7 were associated with a higher likelihood to acquire an IFI over time (HRadj 1.09, 95% CI 1.02-1.16, p 0.009). CONCLUSION: Postponing PN to beyond 1 week and smaller caloric amounts until day 7 in the ICU reduced ICU-acquired IFIs and the likelihood to develop an IFI over time.

Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review.

Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.