Identifying biomarkers of ventilator induced lung injury during one-lung ventilation surgery: a scoping review.

Background: Ventilator-induced lung injury (VILI) can occur as a result of mechanical ventilation to two lungs. Thoracic surgery often requires one-lung ventilation (OLV). The potential for VILI is likely higher in OLV. The impact of OLV on development of post-operative pulmonary complications is not well understood. We aimed to perform a scoping review to determine reliable biomarkers of VILI after OLV. Methods: A scoping review was performed using Cochrane Collaboration methodology. We searched Medline, EMBASE and SCOPUS. Gray literature was searched. Studies of adult human or animal models without pre-existing lung damage exposed to OLV, with biomarker responses analyzed were included. Results: After screening 5,613 eligible papers, 89 papers were chosen for full text review, with 29 meeting inclusion. Approximately half (52%, n=15) of studies were conducted in humans in an intra-operative setting. Bronchoalveolar lavage (BAL) & serum analyses with enzyme-linked immunosorbent assay (ELISA)-based assays were most commonly used. The majority of analytes were investigated by a single study. Of the analytes that were investigated by two or more studies (n=31), only 16 were concordant in their findings. Across all sample types and studies 84% (n=66) of the 79 inflammatory markers and 75% (n=6) of the 8 anti-inflammatory markers tested were found to increase. Half (48%) of all studies showed an increase in TNF-α or IL-6. Conclusions: A scoping review of the state of the evidence demonstrated that candidate biomarkers with the most evidence and greatest reliability are general markers of inflammation, such as IL-6 and TNF-α assessed using ELISA assays. Studies were limited in the number of biomarkers measured concurrently, sample size, and studies using human participants. In conclusion these identified markers can potentially serve as outcome measures for studies on OLV.

Genetic predictors of gene expression associated with psychiatric comorbidity in patients with inflammatory bowel disease - A pilot study.

BACKGROUND: Inflammatory bowel disease (IBD) affects millions of people in North America, and patients with IBD have a high incidence of psychiatric comorbidities (PC). The genetic mechanisms underlying the link are, in general, poorly understood. MATERIALS AND METHODS: A transcriptome-wide association study (TWAS) was performed using genetically regulated gene expression profiles imputed from the genetic profiles of 240 IBD patients in the Manitoba IBD Cohort Study. The imputation was performed using the 44 non-diseased human tissue-specific reference models from the GTEx database. Linear modeling and gene set enrichment analysis were performed to identify genes and pathways that are significantly associated with IBD patients with PC compared to IBD alone in each of the 44 non-diseased human tissues. Finally, an enrichment map was generated to investigate networks of the enriched gene sets associated with IBD patients with PC. RESULTS: The genes RBPMS in skeletal muscle (adjusted p = 0.05), KCNA5 in the cerebellar hemisphere of the brain (adjusted p = 0.09), GSR, SMIM34A, and LIPT2 in the frontal cortex of the brain (adjusted p = 0.09 for each) were the top genetically regulated genes with a suggestive association with IBD patients with PC. We identified three gene set networks, which include gene sets and pathways with a suggestive association with IBD patients with PC: one with 7 gene sets overlapping in apolipoprotein B mRNA editing subunit genes, one with 3 gene sets including pigmentation gene sets, and the other one with 3 gene sets including peptidyl tyrosine phosphorylation regulation related gene sets. CONCLUSIONS: Our TWAS analysis has identified genes and pathways with a suggestive association with IBD patients with PC. These findings can be potentially used for illustrating the mechanism of developing PC in the patients with IBD and developing diagnosis tool or drug targets for IBD patients with PC.

Postoperative but not intraoperative transfusions are associated with respiratory failure after pneumonectomy.

OBJECTIVES: Transfusion of blood products has been associated with increased risk of post-pneumonectomy respiratory failure. It is unclear whether intraoperative or postoperative transfusions confer a higher risk of respiratory failure. Our objective was to assess the role of transfusions in developing post-pneumonectomy respiratory failure. METHODS: We performed a retrospective cohort study using prospectively collected data on consecutive pneumonectomies between 2005 and 2015. Patient records were reviewed for intraoperative/postoperative exposures. Univariable and multivariable analyses were performed. RESULTS: Of the 251 pneumonectomies performed during the study period, 24 (9.6%) patients suffered respiratory failure. Ninety-day mortality was 5.6% (n = 14) and was more likely in patients with respiratory failure (7/24 vs 7/227, P < 0.001). Intraoperative and postoperative transfusions occurred in 42.2% (n = 106) and 44.6% (n = 112) of patients, respectively and were predominantly red blood cells. On univariable analysis, both intraoperative (P = 0.03) and postoperative transfusion (P = 0.004) were associated with a higher risk of respiratory failure. The multivariable model significantly predicted respiratory failure with an area under curve (AUC) = 0.88 (P = 0.001). On multivariable analysis, the only independent predictors of respiratory failure were postoperative transfusions [adjusted odds ratio (aOR) 6.54, 95% confidence interval (CI) 1.74-24.59; P = 0.005] and lower preoperative forced expiratory volume (adjusted OR 0.96, 95% CI 0.93-0.99; P = 0.03). Estimated blood loss was not significantly different (P = 0.91) between those with (median 800 ml, interquartile range 300-2000 ml) and without respiratory failure (median 800 ml, interquartile range 300-2000 ml). CONCLUSIONS: Respiratory failure occurred in 9.6% of patients post-pneumonectomy and confers a higher risk of 90-day mortality. Postoperative (but not intraoperative) transfusion was the strongest independent predictor associated with respiratory failure. Intraoperative transfusion may be in reaction to active/unpredictable blood loss and may not be easily modifiable. However, postoperative transfusion may be modifiable and potentially avoidable. Transfusion thresholds should be assessed in light of potential cost-benefit trade-offs.