Publications

Background: Early detection of postoperative complications after colorectal cancer (CRC) surgery is associated with improved outcomes. The aim was to investigate early metabolomics signatures capable to detect patients at risk for severe postoperative complications after CRC surgery. Materials and methods: Prospective cohort study of patients undergoing CRC surgery from 2015 to 2018. Plasma samples were collected before and after surgery, and analyzed by mass spectrometry obtaining 188 metabolites and 21 ratios. Postoperative complications were registered with Clavien-Dindo Classification and Comprehensive Complication Index. Results: One hundred forty-six patients were included. Surgery substantially modified metabolome and metabolic changes after surgery were quantitatively associated with the severity of postoperative complications. The strongest positive relationship with both Clavien-Dindo and Comprehensive Complication Index (beta=4.09 and 63.05, P<0.001) corresponded to kynurenine/tryptophan, against an inverse relationship with lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs). Patients with LPC18:2/PCa36:2 below the cut-off 0.084 mu M/mu M resulted in a sevenfold higher risk of major complications (OR=7.38, 95% CI: 2.82-21.25, P<0.001), while kynurenine/tryptophan above 0.067 mu M/mu M a ninefold (OR=9.35, 95% CI: 3.03-32.66, P<0.001). Hexadecanoylcarnitine below 0.093 mu M displayed a 12-fold higher risk of anastomotic leakage-related complications (OR=11.99, 95% CI: 2.62-80.79, P=0.004). Conclusion: Surgery-induced phospholipids and amino acid dysregulation is associated with the severity of postoperative complications after CRC surgery, including anastomotic leakage-related outcomes. The authors provide quantitative insight on metabolic markers, measuring vulnerability to postoperative morbidity that might help guide early decision-making and improve surgical outcomes.

JTD Keywords: Acids, Anastomotic leakage, Bypass, Clinical-practice guidelines, Colon, Colorectal cancer, Metabolomics, Postoperative complications, Predict, Sepsis, Trauma, Tryptophan degradation

JTD Keywords: biochemical engineering, neurotrauma and neurodegenerative disease, optogenetics and dreadds, spinal cord injury (sci), Biochemical engineering, Neurotrauma and neurodegenerative disease, Optogenetics and dreadds, Sensorimotor, Spinal cord injury (sci)

Heterotopic ossification (HO) is a condition triggered by an injury leading to the formation of mature lamellar bone in extraskeletal soft tissues. Despite being a frequent complication of orthopedic and trauma surgery, brain and spinal injury, the etiology of HO is poorly understood. The aim of this study is to evaluate the hypothesis that a sustained local ionic homeostatic imbalance (SLIHI) created by mineral formation during tissue calcification modulates inflammation to trigger HO. This evaluation also considers the role SLIHI could play for the design of cell-free, drug-free osteoinductive bone graft substitutes. The evaluation contains five main sections. The first section defines relevant concepts in the context of HO and provides a summary of proposed causes of HO. The second section starts with a detailed analysis of the occurrence and involvement of calcification in HO. It is followed by an explanation of the causes of calcification and its consequences. This allows to speculate on the potential chemical modulators of inflammation and triggers of HO. The end of this second section is devoted to in vitro mineralization tests used to predict the ectopic potential of materials. The third section reviews the biological cascade of events occurring during pathological and material-induced HO, and attempts to propose a quantitative timeline of HO formation. The fourth section looks at potential ways to control HO formation, either acting on SLIHI or on inflammation. Chemical, physical, and drug-based approaches are considered. Finally, the evaluation finishes with a critical assessment of the definition of osteoinduction.

JTD Keywords: apatite, beta-tricalcium phosphate, bone, bone graft, bone morphogenetic protein, demineralized bone-matrix, experimental myositis-ossificans, extracellular calcium, heterotopic ossification, in-vitro, inflammation, multinucleated giant-cells, osteoinduction, spinal-cord-injury, total hip-arthroplasty, traumatic brain-injury, Apatite, Calcium-sensing receptor, Osteoinduction