Cohort profile of BIGPROMISE: a perioperative biobank of a high-risk surgical population.

PURPOSE: Postoperative complications increase mortality, disability and costs. Advanced understanding of the risk factors for postoperative complications is needed to improve surgical outcomes. This paper discusses the rationale and profile of the BIGPROMISE (biomarkers to guide perioperative management and improve outcome in high-risk surgery) cohort, that aims to investigate risk factors, pathophysiology and outcomes related to postoperative complications. PARTICIPANTS: Adult patients undergoing major surgery in two tertiary teaching hospitals. Clinical data and blood samples are collected before surgery, at the end of surgery and on the first, second and third postoperative day. At each time point a panel of cardiovascular, inflammatory, renal, haematological and metabolic biomarkers is assessed. Aliquots of plasma, serum and whole blood of each time point are frozen and stored. Data on severe complications are prospectively collected during 30 days after surgery. Functional status is assessed before surgery and after 120 days using the WHO Disability Assessment Schedule (WHODAS) 2.0. Mortality is followed up until 2 years after surgery. FINDINGS TO DATE: The first patient was enrolled on 8 October 2021. Currently (1 January 2024) 3086 patients were screened for eligibility, of whom 1750 (57%) provided informed consent for study participation. Median age was 66 years (60; 73), 28% were female, and 68% of all patients were American Society of Anaesthesiologists (ASA) physical status class 3. Most common types of major surgery were cardiac (49%) and gastro-intestinal procedures (26%). The overall incidence of 30-day severe postoperative complications was 16%. FUTURE PLANS: By the end of the recruitment phase, expected in 2026, approximately 3000 patients with major surgery will have been enrolled. This cohort allows us to investigate the role of pathophysiological perioperative processes in the cause of postoperative complications, and to discover and develop new biomarkers to improve risk stratification for adverse postoperative outcomes. TRIAL REGISTRATION NUMBER: NCT05199025.

Serum biomarker CA 15-3 as predictor of response to antifibrotic treatment and survival in idiopathic pulmonary fibrosis.

Aim: Cancer antigen 15-3 (CA 15-3) is a baseline biomarker in idiopathic pulmonary fibrosis (IPF), but its value during follow-up is unknown. Materials and methods: Associations between serum CA 15-3 and pulmonary function tests during 1-year follow-up were evaluated by a mixed model in 132 IPF treated with pirfenidone or nintedanib. Results: Increased baseline (median: 56 kU/l) and follow-up CA 15-3 levels were inversely associated with forced vital capacity and diffusing capacity of the lung for carbon monoxide (estimates respectively: -5.21 and -4.69; p < 0.001). Baseline and 6-month CA 15-3 above 58.5 (hazard ratio: 1.67; p = 0.031) and 50.5 kU/l (hazard ratio: 2.99; p < 0.001), respectively, showed impaired survival compared with lower levels. Conclusion: CA 15-3 is associated with pulmonary function test during follow-up in IPF on antifibrotic treatment. Higher (follow-up) values are related with poor survival. Therefore, CA 15-3 is a promising follow-up biomarker in IPF.

A genetic polymorphism in the CAV1 gene associates with the development of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Caveolin 1 (Cav-1) is the primary structural component of cell membrane invaginations called 'caveolae'. Expression of Cav-1 is implicated in the pathogenesis of pulmonary fibrosis. Genetic polymorphisms in the CAV1 gene influence the function of Cav-1 in malignancies and associate with renal allograft fibrosis. Chronic allograft rejection after lung transplantation, called 'bronchiolitis obliterans syndrome' (BOS), is also characterised by the development of fibrosis.In this study, we investigated whether CAV1 genotypes associate with BOS and whether Cav-1 serum levels are influenced by the CAV1 genotype and can be used as a biomarker to predict the development of BOS. METHODS: Twenty lung transplant recipients with BOS (BOSpos), ninety without BOS (BOSneg) and four hundred twenty-two healthy individuals donated DNA samples. Four SNPs in CAV1 were genotyped. Serial Cav-1 serum levels were measured in a matched cohort of 10 BOSpos patients and 10 BOSneg patients. Furthermore, single-time point Cav-1 serum levels were measured in 33 unmatched BOSneg patients and 60 healthy controls. RESULTS: Homozygosity of the minor allele of rs3807989 was associated with an increased risk for BOS (odds ratio: 6.13; P = 0.0013). The median Cav-1 serum level was significantly higher in the BOSpos patients than in the matched BOSneg patients (P = 0.026). Longitudinal analysis did not show changes in Cav-1 serum levels over time in both groups. The median Cav-1 serum level in the group of 43 BOSneg patients was lower than that in the healthy control group (P = 0.046).In lung transplant recipients, homozygosity of the minor allele of rs3807989 and rs3807994 was associated with increased Cav-1 serum levels. CONCLUSION: In lung transplant recipients, the CAV1 SNP rs3807989 was associated with the development of BOS and Cav-1 serum levels were influenced by the CAV1 genotype.