Strategies for Antibiotic Administration for Bowel Preparation Among Patients Undergoing Elective Colorectal Surgery: A Network Meta-analysis.

Importance: There are discrepancies in guidelines on preparation for colorectal surgery. While intravenous (IV) antibiotics are usually administered, the use of mechanical bowel preparation (MBP), enemas, and/or oral antibiotics (OA) is controversial. Objective: To summarize all data from randomized clinical trials (RCTs) that met selection criteria using network meta-analysis (NMA) to determine the ranking of different bowel preparation treatment strategies for their associations with postoperative outcomes. Data Sources: Data sources included MEDLINE, Embase, Cochrane, and Scopus databases with no language constraints, including abstracts and articles published prior to 2021. Study Selection: Randomized studies of adults undergoing elective colorectal surgery with appropriate aerobic and anaerobic antibiotic cover that reported on incisional surgical site infection (SSI) or anastomotic leak were selected for inclusion in the analysis. These were selected by multiple reviewers and adjudicated by a separate lead investigator. A total of 167 of 6833 screened studies met initial selection criteria. Data Extraction and Synthesis: NMA was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by multiple independent observers and pooled in a random-effects model. Main Outcomes and Measures: Primary outcomes were incisional SSI and anastomotic leak. Secondary outcomes included other infections, mortality, ileus, and adverse effects of preparation. Results: A total of 35 RCTs that included 8377 patients were identified. Treatments compared IV antibiotics (2762 patients [33%]), IV antibiotics with enema (222 patients [3%]), IV antibiotics with OA with or without enema (628 patients [7%]), MBP with IV antibiotics (2712 patients [32%]), MBP with IV antibiotics with OA (with good IV antibiotic cover in 925 patients [11%] and with good overall antibiotic cover in 375 patients [4%]), MBP with OA (267 patients [3%]), and OA (486 patients [6%]). The likelihood of incisional SSI was significantly lower for those receiving IV antibiotics with OA with or without enema (rank 1) and MBP with adequate IV antibiotics with OA (rank 2) compared with all other treatment options. The addition of OA to IV antibiotics, both with and without MBP, was associated with a reduction in incisional SSI by greater than 50%. There were minimal differences between treatments in anastomotic leak and in any of the secondary outcomes. Conclusions and Relevance: This NMA demonstrated that the addition of OA to IV antibiotics were associated with a reduction in incisional SSI by greater than 50%. The results support the addition of OA to IV antibiotics to reduce incisional SSI among patients undergoing elective colorectal surgery.

Type I interferons are important co-stimulatory signals during T cell receptor mediated human MAIT cell activation.

Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells that can be stimulated either via their TCR or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also co-stimulatory signals, such as TLR agonists, that can modulate TCR-mediated activation. Recently, type I interferons (T1-IFNs) have been identified as contributing to cytokine-mediated MAIT cell activation. However, it is unknown whether T1-IFNs also have a role during TCR-mediated MAIT cell activation. In this study, we investigated the co-stimulatory role of T1-IFNs during TCR-mediated activation of MAIT cells by the MR1 ligand 5-amino-6-d-ribitylaminouracil/methylglyoxal. We found that T1-IFNs were able to boost interferon-γ and granzyme B production in 5-amino-6-d-ribitylaminouracil/methylglyoxal-stimulated MAIT cells. Similarly, influenza virus-induced T1-IFNs enhanced TCR-mediated MAIT cell activation. An essential role of T1-IFNs in regulating MAIT cell activation by riboflavin synthesising bacteria was also demonstrated. The co-stimulatory role of T1-IFNs was also evident in liver-derived MAIT cells. T1-IFNs acted directly on MAIT cells to enhance their response to TCR stimulation. Overall, our findings establish an important immunomodulatory role of T1-IFNs during TCR-mediated MAIT cell activation.

Perioperative immunonutrition in patients undergoing liver transplantation: a randomized double-blind trial.

UNLABELLED: Preliminary work suggested that perioperative immunonutrition (IMN) enriched in n-3 fatty acids, arginine, and nucleotides may improve preoperative nutritional status, enhance postoperative recovery, and reduce postoperative infectious complications in patients undergoing liver transplantation (LT). The current study examined these outcomes in a double-blind, randomized, controlled trial. Patients wait-listed for LT (n = 120) were randomized to either supplemental (0.6 L/d) oral IMN or an isocaloric control (CON). Enteral IMN or CON was resumed postoperatively and continued for at least 5 days. The change in total body protein (TBP) measured by neutron activation from study entry until immediately prior to LT was the primary endpoint and TBP measurements were repeated 10, 30, 90, 180, and 360 days after LT. Infectious complications were recorded for the first 30 postoperative days. Nineteen patients died or were delisted prior to LT. Fifty-two IMN and 49 CON patients received supplemental nutrition for a median (range) 56 (0-480) and 65 (0-348) days, respectively. Preoperative changes in TBP were not significant (IMN: 0.06 ± 0.15 [SEM]; CON: 0.12 ± 0.10 kg). Compared to baseline, a 0.7 ± 0.2 kg loss of TBP was seen in both groups at 30 days after LT (P < 0.0001) and, at 360 days, TBP had not increased significantly (IMN: 0.08 ± 0.19 kg; CON: 0.26 ± 0.23 kg). Infectious complications occurred in 31 (60%) IMN and 28 (57%) CON patients (P = 0.84). The median (range) postoperative hospital stay was 10 (5-105) days for IMN and 10 (6-27) days for CON patients (P = 0.68). CONCLUSION: In patients undergoing LT, perioperative IMN did not provide significant benefits in terms of preoperative nutritional status or postoperative outcome.