The local effect of phospholipids on experimental postoperative adhesions

INTRODUCTION: Peritoneal adhesions as a consequence of operations or intra-abdominal inflammations consist an important cause of, usually medium-term, morbidity and mortality as well as repeated hospitalizations. They are formed as fibrous bands between injured surfaces and are considered to be part of the physiological healing process of the peritoneum. In-depth knowledge of their pathophysiology has led to a plethora of clinical and experimental studies, however, so far none of the tested substances was found to be effective in the long term, so as to be established as a reliable practice for adhesions prevention. On the other hand, phospholipids, which are natural constituents of biological membranes, seem to display excellent antiadhesive properties. PURPOSE: The aim of this study was to investigate the local effectiveness of phospholipids, when administered intraperitoneally, in the reduction of the inflammatory response due to surgical trauma during intra-abdominal procedures, in order to prevent formation of postoperative adhesions, as well as the possible underlying mechanisms. MATERIALS AND METHODS: Twenty male Wistar rats were subjected to a midline laparotomy and a standard peritoneal and cecum abrasion trauma. Before laparotomy closure, a bolus of 3mL of phospholipids [12 mg/mL] or NaCl [placebo] was given intraperitoneally. Seven days later, the quality and the quantity of adhesions, as well as proinflammatory and/or profibrotic serum mediators, were blindly assessed. Human colonic subepithelial myofibroblasts were isolated from normal controls and cultured with transforming growth factor-b1 [TGFb1, 5 ng/mL] in the presence of phospholipids in various concentrations [30 to 300 mg/mL]. Collagen production and migratory activity of myofibroblasts were also assessed. RESULTS: Phospholipids significantly reduced both the amount and density of intra-abdominal adhesions [p<0.01]. In addition, the levels of all measured cytokines in serum [IL-1β, IL-6, PDGF-1 and TGF-β1] were significantly reduced in the group receiving phospholipids [p<0.01]. Moreover, the presence of phospholipids significantly reduced [p<0.001] both the baseline collagen production and the one induced when TGF-β1 was administered to myofibroblasts cultures. Finally, using the scratch test, phospholipids were found to decrease both the baseline and the TGF-β1-induced migration of myofibroblasts in a concentration-dependent manner. CONCLUSION: Intraperitoneal application of phospholipids prior to closure of laparotomy may be involved in the prevention of postoperative adhesions formation via reduction of proinflammatory and/or profibrotic mediators and by inhibiting the fibrogenic properties of mesenchymal cells.ΕΙΣΑΓΩΓΗ: Οι περιτοναϊκές συμφύσεις ως συνέπεια εγχειρήσεων ή ενδοκοιλιακών φλεγμονών συνιστούν μια σημαντική αιτία μεσοπρόθεσμης, συνήθως, νοσηρότητας και θνητότητας καθώς και επαναλαμβανόμενων νοσηλειών στο νοσοκομείο. Οργανώνονται ως ινώδεις δεσμοί μεταξύ των τραυματισμένων επιφανειών και θεωρούνται ότι είναι μέρος της φυσιολογικής διαδικασίας επούλωσης του περιτοναίου. Η γνώση του μηχανισμού δημιουργίας τους οδήγησε σε πληθώρα κλινικών και πειραματικών μελετών, αλλά μέχρι σήμερα σχεδόν κανένα από τα προϊόντα που δοκιμάστηκαν δε φάνηκε να έχει την απαιτούμενη αποτελεσματικότητα και αξιοπιστία σε βάθος χρόνου ώστε να μπορέσει να καθιερωθεί στην καθ’ ημέρα κλινική πράξη. Ωστόσο, τα φωσφολιπίδια, ως φυσικά συστατικά των βιολογικών μεμβρανών, φαίνεται ότι επιδεικνύουν εξαιρετικές αντισυμφυτικές ιδιότητες. ΣΚΟΠΟΣ: Σκοπός της πειραματικής αυτής μελέτης είναι η διερεύνηση της τοπικής δράσης των φωσφολιπιδίων, όταν χορηγηθούν ενδοπεριτοναϊκά, στη μείωση της φλεγμονώδους αντίδρασης που οφείλεται στο εγχειρητικό τραύμα κατά τη διάρκεια ενδοκοιλιακών επεμβάσεων και στην αποτροπή σχηματισμού μετεγχειρητικών συμφύσεων, καθώς και των πιθανών μηχανισμών με τους οποίους συμβαίνει αυτό. ΥΛΙΚΟ ΚΑΙ ΜΕΘΟΔΟΣ: Είκοσι άρρενες επίμυες τύπου Wistar υποβλήθηκαν σε μέση λαπαροτομία και τυπικό τραυματισμό διά τριβής του περιτοναίου και του τυφλού. Πριν το κλείσιμο της κοιλίας, χορηγήθηκε ενδοπεριτοναϊκά εφάπαξ δόση 3mL φωσφολιπιδίων [12mg/mL] ή NaCl [εικονικό φάρμακο]. Μετά από επτά ημέρες, αξιολογήθηκαν η ποιότητα και η ποσότητα των σχηματιζόμενων συμφύσεων, καθώς και οι προφλεγμονώδεις και/ή προϊνωτικοί μεσολαβητές στον ορό. Ανθρώπινοι υποεπιθηλιακοί υοϊνοβλάστες παχέος εντέρου καλλιεργήθηκαν με μετατρεπτικό αυξητικό παράγοντα β1 [TGF-β1, 5ng/mL] και την παρουσία φωσφολιπιδίων σε διάφορες συγκεντρώσεις [30 ως 300 μg/mL] και υπολογίστηκαν η παραγωγή κολλαγόνου και η μεταναστευτική δραστηριότητα των μυοϊνοβλαστών. ΑΠΟΤΕΛΕΣΜΑΤΑ: Τα φωσφολιπίδια μείωσαν σημαντικά τόσο την ποσότητα όσο και την ποιότητα των σχηματιζόμενων ενδοκοιλιακών συμφύσεων [p<0.01]. Τα επίπεδα των IL-1β, IL-6, PDGF-1 και TGF-β1 στον ορό βρέθηκαν σημαντικά μειωμένα στην ομάδα που έλαβε φωσφολιπίδια [p<0.01] σε σχέση με την ομάδα ελέγχου. Επιπρόσθετα, η παρουσία φωσφολιπιδίων μείωσε σημαντικά [p<0.001] τόσο τη βασική παραγωγή κολλαγόνου όσο και αυτή που επάγεται όταν χορηγηθεί παράγοντας TGF-β1 στις καλλιέργειες μυοϊνοβλαστών. Τέλος, χρησιμοποιώντας την δοκιμασία επούλωσης τραύματος [scratch test], βρέθηκε ότι τα φωσφολιπίδια μειώνουν και τη βασική και την επαγόμενη από τον TGF-β1 μετανάστευση των μυοϊνοβλαστών, δοσοεξαρτώμενα. ΣΥΜΠΕΡΑΣΜΑΤΑ: Η ενδοπεριτοναϊκή χορήγηση φωσφολιπιδίων πριν τη σύγκλειση της λαπαροτομίας φαίνεται ότι συμβάλλει σημαντικά στην πρόληψη σχηματισμού μετεγχειρητικών συμφύσεων μέσω της μείωσης των προφλεγμονωδών και/ή προϊνωτικών μεσολαβητών και της αναστολής της επουλωτικής ικανότητας των μεσοθηλιακών κυττάρων

One-Dimensional Heterogeneous Reaction Model of a Drop-Tube Carbonator Reactor for Thermochemical Energy Storage Applications

Calcium looping systems constitute a promising candidate for thermochemical energy storage (TCES) applications, as evidenced by the constantly escalating scientific and industrial interest. However, the technologically feasible transition from the research scale towards industrial and highly competitive markets sets as a prerequisite the optimal design and operation of the process, especially corresponding reactors. The present study investigates for the first time the development of a detailed, one-dimensional mathematical model for the steady-state simulation of a novel drop-tube carbonator reactor as a core equipment unit in a concentrated solar power (CSP)-thermochemical energy storage integration plant. A validated kinetic mathematical model for a carbonation reaction (CaO(s) + CO2(g) &rarr; CaCO3(s)) focused on thermochemical energy storage conditions was developed and implemented for different material conditions. The fast gas&ndash;solid reaction kinetics conformed with the drop-tube reactor concept, as the latter is suitable for very fast reactions. Reaction kinetics were controlled by the reaction temperature. Varying state profiles were computed across the length of the reactor by using a mathematical model in which reactant conversions, the reaction rate, and the temperature and velocity of gas and solid phases provided crucial information on the carbonator&rsquo;s performance, among other factors. Through process simulations, the model-based investigation approach revealed respective restrictions on a tailor-made reactor of 10 kWth, pointing out the necessity of detailed models as a provision for design and scale-up studies

PERCUTANEOUS ENDOSCOPIC GASTROSTOMY IN DEMENTIA SUFFERING GREEK INDIVIDUALS

Dementia in geriatric patients is a major cause of malnutrition. In this article, the impact of Percutaneous Endoscopic Gastrostomy placed in these persons is explored in order to understand the choices of the relatives leading to their placement. A retrospective analysis of the epidemiologic, clinical and demographic data of 51 persons with PEG placement is performed. The patients’ mean age was 74 years, most of them came from another hospital department (64.71%), all returned home but three, who went to a rehabilitation center. All their relatives had a university education or higher, and in 26 cases the relative was a doctor. Lack of major common complications, easier and faster feeding has increased the decision of the PEG placement, according to the family, who can have more “constructive time” with their relative without great psychological burdens

Predicting adherence of patients with HF through machine learning techniques

International audienceHeart failure (HF) is a chronic disease characterised by poor quality of life, recurrent hospitalisation and high mortality. Adherence of patient to treatment suggested by the experts has been proven a significant deterrent of the above-mentioned serious consequences. However, the non-adherence rates are significantly high; a fact that highlights the importance of predicting the adherence of the patient and enabling experts to adjust accordingly patient monitoring and management. The aim of this work is to predict the adherence of patients with HF, through the application of machine learning techniques. Specifically, it aims to classify a patient not only as medication adherent or not, but also as adherent or not in terms of medication, nutrition and physical activity (global adherent). Two classification problems are addressed: (i) if the patient is global adherent or not and (ii) if the patient is medication adherent or not. About 11 classification algorithms are employed and combined with feature selection and resampling techniques. The classifiers are evaluated on a dataset of 90 patients. The patients are characterised as medication and global adherent, based on clinician estimation. The highest detection accuracy is 82 and 91% for the first and the second classification problem, respectively

Estimation of Heart Failure Patients Medication Adherence through the Utilization of Saliva and Breath Biomarkers and Data Mining Techniques

International audienceThe aim of this work is to estimate the medication adherence of patients with heart failure through the application of a data mining approach on a dataset including information from saliva and breath biomarkers. The method consists of two stages. In the first stage, a model for the estimation of adherence risk of a patient, exploiting anamnestic and instrumental data, is applied. In the second stage, the output of the model, accompanied with data from saliva and breath biomarkers, is given as input to a classification model for determining if the patient is adherent, in terms of medication. The method is evaluated on a dataset of 29 patients and the achieved accuracy is 96%

A four-probiotic preparation for ventilator-associated pneumonia in multi-trauma patients: results of a randomized clinical trial

The role of probiotics in the prevention of ventilator-associated pneumonia (VAP) remains inconclusive. The aim of this study was to assess the efficacy of a probiotic regimen for VAP prophylaxis in mechanically ventilated multi-trauma patients, intubated immediately after the injurious insult. In a randomized, placebo-controlled study enrolling multi-trauma patients, patients expected to require mechanical ventilation for &gt;10 days were assigned at random to receive prophylaxis with a probiotic formula (n= 59) or placebo (n= 53). The probiotic formula was a preparation of Lactobacillus acidophilus LA-5 [1.75 x10(9) colony-forming units (cfu)], Lactobacillus plantarum (0.5 x10(9) cfu), Bifidobacterium lactis BB-12 (1.75 x109 cfu) and Saccharomyces boulardii (1.5 x10(9) cfu) in sachets. Each patient received two sachets twice daily for 15 days: one through the nasogastric tube and one spread on the oropharynx. The incidence of VAP was the primary endpoint. The incidence of other infections and sepsis, and the duration of hospital stay were the secondary endpoints. Administration of probiotics reduced the incidence of VAP [11.9% vs 28.3%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.13-0.92; P=0.034] and sepsis [6.8% vs 24.5%, odds ratio 0.22, 95% CI 0.07-0.74: P= 0.016]. Furthermore, probiotic prophylaxis reduced the time of stay in the intensive care unit (ICU) and the length of hospital stay. The prophylactic use of probiotics with a combination of enteral and topical application to the oropharynx had a positive effect on the incidence of VAP and sepsis, as well as on ICU and total hospital stay in patients receiving protracted mechanical ventilation. (C) 2021 The Authors. Published by Elsevier Ltd

MicroRNA 31-3p expression and benefit from anti-EGFR inhibitors in metastatic colorectal cancer patients enrolled in the prospective phase II PROSPECT-C trial

PURPOSE: Anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibodies (mABs) are effective in the treatment of metastatic colorectal cancer (mCRC) patients. RAS status and tumour location (sidedness) are predictive markers of patients' response to anti-EGFR mABs. Recently, low microRNA-31-3p expression levels have been correlated with clinical benefit from the anti-EGFR mAb cetuximab. Here we aimed to validate the predictive power of microRNA-31-3p in a prospective cohort of chemo-refractory mCRC patients treated with single agent anti-EGFR mABs. EXPERIMENTAL DESIGN: microRNA-31-3p was tested by in-situ hybridization in ninety-one pre-treatment core biopsies from metastatic deposits of forty-five mCRC patients. Sequential tissue biopsies obtained before treatment, at the time of partial response, and at disease progression were tested to monitor changes in microRNA-31-3p expression over treatment. MicroRNA-31-3p expression, sidedness, and RAS status in pre-treatment cell-free DNA were combined in multivariable regression models to assess the predictive value of each variable alone or in combination. RESULTS: Patients with low microRNA-31-3p expression in pre-treatment biopsies showed better overall response rate, as well as better progression free and overall survival, compared to those with high microRNA-31-3p expression. The prognostic effect of microRNA-31-3p was independent from age, gender and sidedness. No significant changes in the expression of microRNA-31-3p were observed when sequential tissue biopsies were tested in long-term or poor responders to anti-EGFR mABs. MicroRNA-31-3p scores were similar when pre-treatment biopsies were compared with treatment-na\uefve archival tissues (often primary CRC).Conclusions: Our study validates the role of microRNA-31-3p as potential predictive biomarker of selection for anti-EGF mABs

Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer

Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS wild-type CRCs identified associations of NF1 and non-canonical RAS/RAF aberrations with primary resistance and validated transcriptomic CRC subtypes as non-genetic predictors of benefit. Sixty-four percent of biopsies with acquired resistance harbored no genetic resistance drivers. Most of these had switched from a cetuximab-sensitive transcriptomic subtype at baseline to a fibroblast- and growth factor-rich subtype at progression. Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PD-L1 and LAG3 immune checkpoint expression, potentially providing opportunities to treat cetuximab-resistant CRCs with immunotherapy.M.G., A.Woolston, L.J.B., and B.G. were supported by CRUK, a charitable donation from Tim Morgan, Cancer Genetics UK and the Constance Travis Trust. G.S. was funded by an Institute of Cancer PhD Studentship, R.G.E. by a Spanish Society of Medical Oncology (FSEOM) grant for Translational Research in Reference Centers. The study was also supported by the ICR/RMH NIHR Biomedical Research Center for Cancer, by the CRUK Immunotherapy Accelerator (ICR/RMH, UCL) and by a Wellcome Trust Strategic Grant (105104/Z/14/Z)