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

Herein, an innovative self- and pressure-adhesive biomedical implant was developed. Tissue adhesion was achieved with a thermosensitive hydrogel based on poly-(N-isopropylacrylamide-co-acrylamide), PNIPAAm-co-PAAm, grafted on a substrate composed of knitted fibers of isotactic polypropylene mesh (PP), used as surgical mesh implants. The in vitro studies, carried out with porcine skin, showed an important role of the inclusion of acrylamide-based comonomer (AAm) in the thermosensitive hydrogel PNIPAAm matrix. The bonding, peeling, and shearing energies obtained for PNIPAAm-co-PAAm increased exponentially up to three, two, and six times, respectively, compared to the gel without AAm. The physisorption and mechanical interlocking mechanisms are responsible for such improvement due to the simultaneous creation of hydrophobic and hydrophilic interactions of the thermosensitive hydrogel at temperatures higher than the lower critical solution temperature (LCST), with the porcine tissue. In addition, our bioadhesives present excellent interfacial toughness (similar to 100 J/m(2)) when compared to commercial bioglues (similar to 50 J/m(2) or lower). The results obtained represent a very promising adhesive material that is extensible to other medical devices that require atraumatic fixation to avoid chronic pain related to other fixation approaches.

JTD Keywords: Bioadhesive, Complications, Hernia-repair, Interface adhesion, Mechanicalinterlocking, Physisorption, Poly(n-isopropylacrylamide), Polypropylene mesh, Surgicalmesh, Thermosensitive hydrogel

It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism.Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

JTD Keywords: complications, coronavirus, cultured-cells, disease, distal tubule, mouse, protein, reveals, spike, Ace2, Ace2 protein, human, Angiotensin-converting enzyme 2, Angiotensin-converting enzyme-2, Covid-19, Diabetes 2, Diabetes mellitus, Diabetic nephropathies, Human kidney organoids, Humans, Kidney, Organoids, Peptidyl-dipeptidase a, Sars-cov-2

It is about 20 years that tubular nerve guides have been introduced into clinical practice as a reliable alternative to autograft, in gaps not-longer-than 20 mm, bringing the advantage of avoiding donor site sacrifice and morbidity. There are limitations in the application of tubular guides. First, tubular structure in itself makes surgical implantation difficult; second, stitch sutures required to secure the guide may represent a site of unfavorable fibroblastic reaction; third, maximum length and diameter of the guide correlate with the occurrence of a poorer central vascularization of regenerated nerve. We report on the in vivo testing of a new concept of nerve-guide (named NeuroBox) which is double-halved, not-degradable, rigid, and does not require any stitch to be held in place, employing acrylate glue instead. Five male Wistar rats had the new guide implanted in a 4-mm sciatic nerve defect; two guides incorporated a surface constituted of microtrenches aligned longitudinally. Further five rats had the 4-mm gap left without repair. Contralateral intact nerves were used as controls. After 2 months, nerve regeneration occurred in all animals treated by the NeuroBox; fine blood vessels were well represented. There was no regeneration in the un-treated animals. Even if the limited number of animals does not allow to draw definitive conclusions, some result can be highlighted: an easy surgical technique was associated with the box-shaped guide and acrylate glue was easily applied; an adequate intraneural vascularization was found concurrently with the regeneration of the nerve and no adverse fibroblastic proliferation was present.

JTD Keywords: Peripheral-nerve, Polyglycolic acid, Guidance cues, Collagen tube, Median nerve, Repair, Growth, Cyanoacrylate, Complications, Anastomosis