Dataset Information

Serum 1,3-Beta-D-Glucan Values During and After Laparoscopic and Open Intestinal Surgery.

ABSTRACT: Background:1,3-beta-D Glucan (BDG) assay has good accuracy for distinguishing patients with invasive fungal infections from patients without. Some procedures and medications affect BDG levels, resulting in false-positive BDG results. The extent of intestinal surgery on BDG kinetics is unknown. We evaluated the influence of laparoscopic and open intestinal surgery on peri- and postsurgical serum BDG values. Methods:BDG was determined in 346 samples from 50 patients undergoing laparoscopic (24) or open (26) intestinal surgery at the following time points: after insertion of arterial but before skin incision, after skin incision but before dissection of the intestinal mucosa, after completion of anastomosis, after completion of skin sutures, in the evening after surgery, day 2 after surgery, 4-5 days after surgery. Results:BDG was positive (ie, concentration ?80 pg/mL) in 54% to 61% of patients during laparoscopic and open surgery (highest rates after completion of skin sutures). BDG was still positive in 12% (open) to 17% (laparoscopic) of patients without any suspected or proven fungal infection or anastomotic leakage 4-5 days after surgery. After completion of gut anastomosis, the BDG increase was higher in open compared with laparoscopic intestinal surgery. Conclusions:The value of positive BDG tests in the perioperative setting up to 5 days postsurgery seems to be limited due to BDG elevations from intestinal surgical procedures.

SUBMITTER: Szyszkowitz A

PROVIDER: S-EPMC6290064 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Serum 1,3-Beta-D-Glucan Values During and After Laparoscopic and Open Intestinal Surgery.

Szyszkowitz Alexander A Zurl Christoph C Herzeg Anna A Berger Anton A Gemes Geza G Mitteregger Martin M Prüller Florian F Prattes Juergen J Zollner-Schwetz Ines I Valentin Thomas T Hoenigl Martin M Krause Robert R

Open forum infectious diseases 20181108 12

<h4>Background</h4>1,3-beta-D Glucan (BDG) assay has good accuracy for distinguishing patients with invasive fungal infections from patients without. Some procedures and medications affect BDG levels, resulting in false-positive BDG results. The extent of intestinal surgery on BDG kinetics is unknown. We evaluated the influence of laparoscopic and open intestinal surgery on peri- and postsurgical serum BDG values.<h4>Methods</h4>BDG was determined in 346 samples from 50 patients undergoing lapar ...[more]

PMID: 30568978

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Project description:ImportanceSurgery represents the mainstay treatment of colorectal liver metastases. Indications for the laparoscopic approach in this setting have been widened and there is a need to confirm the benefits of minimally invasive liver surgery (MILS) in patients with complex disease states.ObjectiveTo compare outcomes of laparoscopic surgery with those of open surgery for liver metastases from colorectal cancer, focusing on the characteristics of modern MILS and therefore overcoming possible selection bias related to different policies for patients' eligibility for MILS over time.Design, setting, and participantsA cohort study of 885 resections performed for liver metastases from colorectal cancer between January 1, 2004, and June 30, 2017, at the Hepatobiliary Surgery Unit of San Raffaele Hospital, Milano, Italy, comprising 187 laparoscopic and 698 open resections. Procedures performed using the MILS approach with a ratio of MILS to total resections per year of more than 30% were considered and were matched by propensity scores (ratio of 1:4) to procedures performed using the open approach with a ratio of MILS to total resections per year of less than 30%.Main outcomes and measuresThe primary end point was short-term outcomes, including morbidity, mortality, functional recovery, and interval between surgery and adjuvant treatments; the secondary end point was long-term outcomes.ResultsAmong this cohort (104 patients in the MILS group; 46 women and 58 men; median age, 62 years [range, 35-81 years]; and 412 patients in the open group; 181 women and 231 men; median age, 60 years [range, 37-80 years]), primary end-point data showed a significantly higher incidence of postoperative morbidity in patients who underwent open resections compared with those who underwent MILS (94 [22.8%] vs 21 [20.2%]; P = .04). Patients in the MILS group had fewer major complications (Dindo-Clavien grades III-V) compared with patients in the open group (Dindo-Clavien grades III-V; 7 [6.7%] vs 35 [8.5%]; P = .03) as well as shorter lengths of stay (median [range] duration, 3 [2-35] vs 5 [4-37] days; P = .02). Oncologic results were not compromised by the laparoscopic approach.Conclusions and relevanceIn this study, the results of the propensity score matching analysis between modern laparoscopic surgery and previous open surgery appear to confer more comparable cohorts for complexity, further supporting the advantages of laparoscopy in the surgical treatment of liver metastases from colorectal cancer. The increase in use that laparoscopy has experienced appears to be based on increased feasibility, widening of eligibility criteria for patients, enhanced clinical effectiveness, and oncologic outcomes. All these elements together suggest that up to 70% of patients appear to be candidates for this minimally invasive surgical approach in high-volume centers.

Project description:Anti-beta-glucan antibodies elicited by a laminarin-conjugate vaccine confer cross-protection to mice challenged with major fungal pathogens such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. To gain insights into protective beta-glucan epitope(s) and protection mechanisms, we studied two anti-beta-glucan monoclonal antibodies (mAb) with identical complementarity-determining regions but different isotypes (mAb 2G8, IgG2b and mAb 1E12, IgM). C. albicans, the most relevant fungal pathogen for humans, was used as a model.Both mAbs bound to fungal cell surface and to the beta1,3-beta1,6 glucan of the fungal cell wall skeleton, as shown by immunofluorescence, electron-microscopy and ELISA. They were also equally unable to opsonize fungal cells in a J774 macrophage phagocytosis and killing assay. However, only the IgG2b conferred substantial protection against mucosal and systemic candidiasis in passive vaccination experiments in rodents. Competition ELISA and microarray analyses using sequence-defined glucan oligosaccharides showed that the protective IgG2b selectively bound to beta1,3-linked (laminarin-like) glucose sequences whereas the non-protective IgM bound to beta1,6- and beta1,4-linked glucose sequences in addition to beta1,3-linked ones. Only the protective IgG2b recognized heterogeneous, polydisperse high molecular weight cell wall and secretory components of the fungus, two of which were identified as the GPI-anchored cell wall proteins Als3 and Hyr1. In addition, only the IgG2b inhibited in vitro two critical virulence attributes of the fungus, hyphal growth and adherence to human epithelial cells.Our study demonstrates that the isotype of anti-beta-glucan antibodies may affect details of the beta-glucan epitopes recognized, and this may be associated with a differing ability to inhibit virulence attributes of the fungus and confer protection in vivo. Our data also suggest that the anti-virulence properties of the IgG2b mAb may be linked to its capacity to recognize beta-glucan epitope(s) on some cell wall components that exert critical functions in fungal cell wall structure and adherence to host cells.

Project description:In response to invading microorganisms, insect β-1,3-glucan recognition protein (βGRP), a soluble receptor in the hemolymph, binds to the surfaces of bacteria and fungi and activates serine protease cascades that promote destruction of pathogens by means of melanization or expression of antimicrobial peptides. Here we report on the nuclear magnetic resonance (NMR) solution structure of the N-terminal domain of βGRP (N-βGRP) from Indian meal moth (Plodia interpunctella), which is sufficient to activate the prophenoloxidase (proPO) pathway resulting in melanin formation. NMR and isothermal calorimetric titrations of N-βGRP with laminarihexaose, a glucose hexamer containing β-1,3 links, suggest a weak binding of the ligand. However, addition of laminarin, a glucose polysaccharide (~6 kDa) containing β-1,3 and β-1,6 links that activates the proPO pathway, to N-βGRP results in the loss of NMR cross-peaks from the backbone (15)N-(1)H groups of the protein, suggesting the formation of a large complex. Analytical ultracentrifugation (AUC) studies of formation of the N-βGRP-laminarin complex show that ligand binding induces self-association of the protein-carbohydrate complex into a macro structure, likely containing six protein and three laminarin molecules (~102 kDa). The macro complex is quite stable, as it does not undergo dissociation upon dilution to submicromolar concentrations. The structural model thus derived from this study for the N-βGRP-laminarin complex in solution differs from the one in which a single N-βGRP molecule has been proposed to bind to a triple-helical form of laminarin on the basis of an X-ray crystallographic structure of the N-βGRP-laminarihexaose complex [Kanagawa, M., Satoh, T., Ikeda, A., Adachi, Y., Ohno, N., and Yamaguchi, Y. (2011) J. Biol. Chem. 286, 29158-29165]. AUC studies and phenoloxidase activation measurements conducted with the designed mutants of N-βGRP indicate that electrostatic interactions involving Asp45, Arg54, and Asp68 between the ligand-bound protein molecules contribute in part to the stability of the N-βGRP-laminarin macro complex and that a decreased stability is accompanied by a reduced level of activation of the proPO pathway. An increased level of β-1,6 branching in laminarin also results in destabilization of the macro complex. These novel findings suggest that ligand-induced self-association of the βGRP-β-1,3-glucan complex may form a platform on a microbial surface for recruitment of downstream proteases, as a means of amplification of the initial signal of pathogen recognition for the activation of the proPO pathway.

Project description:BackgroundAnastomotic leakage (AL) is a dreaded complication following colorectal cancer surgery, impacting patient outcome and leads to increasing healthcare consumption as well as economic burden. Bowel perfusion is a significant modifiable factor for anastomotic healing and thus crucial for reducing AL.AimsThe study aimed to calculate a cut-off value for quantified laser speckle perfusion units (LSPUs) in order to differentiate between ischemic and well-perfused tissue and to assess inter-observer reliability.MethodsLSCI was performed using a porcine ischemic small bowel loop model with the PerfusiX-Imaging® system. An ischemic area, a well-perfused area, and watershed areas, were selected based on the LSCI colormap. Subsequently, local capillary lactate (LCL) levels were measured. A logarithmic curve estimation tested the correlation between LSPU and LCL levels. A cut-off value for LSPU and lactate was calculated, based on anatomically ischemic and well-perfused tissue. Inter-observer variability analysis was performed with 10 observers.ResultsDirectly after ligation of the mesenteric arteries, differences in LSPU values between ischemic and well-perfused tissue were significant (p < 0.001) and increased significantly throughout all following measurements. LCL levels were significantly different (p < 0.001) at both 60 and 120 min. Logarithmic curve estimation showed an R2 value of 0.56 between LSPU and LCL values. A LSPU cut-off value was determined at 69, with a sensitivity of 0.94 and specificity of 0.87. A LCL cut-off value of 3.8 mmol/L was found, with a sensitivity and specificity of 0.97 and 1.0, respectively. There was no difference in assessment between experienced and unexperienced observers. Cohen's Kappa values were moderate to good (0.52-0.66).ConclusionReal-time quantification of LSPUs may be a feasible intraoperative method to assess tissue perfusion and a cut-off value could be determined with high sensitivity and specificity. Inter-observer variability was moderate to good, irrespective of prior experience with the technique.

Dataset Information

Serum 1,3-Beta-D-Glucan Values During and After Laparoscopic and Open Intestinal Surgery.

Publications

Serum 1,3-Beta-D-Glucan Values During and After Laparoscopic and Open Intestinal Surgery.

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