Κυκλοφορούντα miRNA σαν πιθανοί βιοδείκτες της ανταπόκρισης της θεραπείας με anti-TNF σε ασθενείς με ΙΦΝΕ

Εισαγωγή Οι Ιδιοπαθείς Φλεγμονώδεις Νόσοι του Εντέρου (ΙΦΝΕ) αποτελούν σημαντικό αίτιο νοσηρότητας στο σύγχρονο κόσμο, επηρεάζοντας κυρίως νέες και παραγωγικές ηλικιακές ομάδες. Η αιτιολογία τους δεν έχει αποσαφηνισθεί αλλά φαίνεται να προκύπτουν από ανώμαλη ανοσολογική απόκριση σε περιβαλλοντικά ερεθίσματα γενετικά προδιαθετιμένων ατόμων. Η είσοδος των βιολογικών παραγόντων στη φαρέτρα των θεραπευτικών επιλογών βελτιστοποίησε την πρόγνωση των ασθενών. Παρα ταύτα όμως παραμένει ένα όχι αμελητέο ποσοστό αυτών που δεν ανταποκρίνεται στη θεραπεία ταυτόχρονα όμως εκτίθεται στις ανεπιθύμητες δράσεις των φαρμάκων αυτών. Σε μια εποχή όπου οι -βιολογικές και μη- σύγχρονες θεραπείς αυξάνονται και στοχεύοντας στην επίτευξη του ιδανικού κλινικού αποτελέσματος με τις λιγότερες παρενέργειες για τον ασθενή, καθίσταται αναγκαία η ανεύρεση βιοδεικτών, εύκολων και επαναλήψιμων στη χρήση, για την πρόβλεψη της ανταπόκρισης στη θεραπεία. Με τους κλινικούς και ορολογικούς δείκτες να έχουν περιορισμένη τέτοια ικάνοτητα, η αναζήτηση στρέφεται προς γενετικούς και επιγενετικούς δείκτες. Σκοπός της μελέτης Η αναζήτηση συσχέτισης πολυμορφισμών σε microRNAs - rs2910164 , rs11 614913, rs113054794, και rs188519172- και της απάντησης στη θεραπεία με αντι-TNF ασθενών με νόσο Crohn. Μέθοδοι Ασθενείς με νόσο Crohn, βάσει κλινικών, ενδοσκοπικών, απεικονιστικών και ιστολογικών κριτηρίων, και οι οποίοι θα ελάμβαναν αντι-TNF παράγοντα συμπεριλήφθηκαν στη μελέτη. Έλαβαν όλοι infliximab ή adalimumab ενδοφλέβια/υποδόρια στις διεθνώς θεσμοθετημένες δόσεις και χρονικά διαστήματα. Η κλινική και ορολογική απάντηση ταυτοποιήθηκε με τους δείκτες Harvey-Bradshaw (ΗΒΙ) και CRP αντίστοιχα. Η ενδοσκοπική ανταπόκριση αξιολογήθηκε με ειλεοκολονοσκόπηση την εβδομάδα 12-20 μετά την έναρξη της θεραπείας. Οι αλλαγές στην ενδοσκοπική εικόνα συγκρινόμενες με αυτές της αρχικής ενδοσκόπησης κατηγοριοποιήθηκαν σε 4 κατηγορίες και οι ασθενείς χωρίσθηκαν σε ανταποκριθέντες και μη. Από περιφερικό αίμα εκχυλίστηκε γενωμικό DNA και ακολούθησε γενετική ανάλυση. Αποτελέσματα Εκατόν επτά ασθενείς συμπεριλήφθηκαν στη μελέτη. Εβδομήντα δύο (67.3%) ασθενείς θεωρήθηκαν ως πλήρως ανταποκριθέντες, 22 (20.5%) ως μερικώς ενώ 13 (12.1%) ως πρωτογενώς μη ανταποκριθέντες. Η ανταπόκριση στη θεραπεία με βιολογικό παράγοντα δεν διέφερε μεταξύ των ασθενών με διαφορετικά χαρακτηριστικά όπως ηλικία, φύλο, διάρκεια ή έκταση της νόσου ενώ υπήρξε συνάφεια μεταξύ του δείκτη ΗΒΙ και των επιπέδων της CRP με την απάντηση στη θεραπεία. Σχετικά με τη συχνότητα των πολυμορφισμών rs2910164, rs11614913, και rs188519172 των miR-146, miR-196a και miR-224 αντίστοιχα δεν αναδείχθηκε καμία στατιστικά σημαντική διαφορά μεταξύ των πλήρως, μερικώς και των μη ανταποκριθέντων ασθενών στη θεραπεία με αντι-TNF. Μάλιστα ο γονότυπος CC του rs2910164 δεν ανιχνεύθηκε σε κανέναν ασθνενή της μελέτης. Σχετικά με τον πολυμορφισμό rs113054794 του miR-221, ο φυσιολογικός γονότυπος CC ήταν ο μόνος που ανευρέθη σε όλους τους ασθενείς της μελέτης, υποδεικνύοντας ότι αυτός ο πολυμορφισμός πιθανώς είναι πολύ σπάνιος στους Καυκάσιους. Συμπέρασμα Καμία συσχέτιση δεν αναδείχθηκε μεταξύ των μελετώμενων πολυμορφισμών και της απάντησης στην αντι-TNF θεραπεία ασθενών με νόσο Crohn. Ο πολυμορφισμός rs113054794 δεν ανιχνεύθηκε στον πληθυσμό μας.Introduction Inflammatory bowel disease (IBD) constitutes an important cause of morbidity in the modern world, affecting mainly young and productive age groups. Their aitiology is partly unclear but it is hypothesized that it arises from a combination of genetic susceptibility and environmental factors that trigger an inappropriate mucosal inflammatory response. Anti-TNF agents have revolutionized IBD therapy nonetheless there still exists a non negligible percentage of patients who never respond but are exposed to biologic therapy side effects. In an era when biologic and non- biologic therapies are constantly increasing and while we aim at achieving the ideal clinical result with the least side effects for each patient, identification of new, easy to use biomarkers is considered almost mandatory. Clinical and serological biomarkers show limited such capability thus searching is headed towards genetic and epigenetic markers. Aim of study To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 miRNA polymorphisms and response to anti-TNF treatment in patients with Crohn's disease (CD). Methods One hundred seven patients with CD based on standard clinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the Harvey-Bradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Whole peripheral blood was extracted and genotyping was performed by PCR. Results One hundred and seven patients were included in the study. Seventy two (67.3%) patients were classified as complete responders, 22 (20.5%) as partial while 13 (12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients' characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to anti-TNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population. Conclusion No correlation was detected between studied polymorphisms and patients' response to anti-TNF treatment. Polymorphism rs113054794 was not detected in our population

Comparative performance and external validation of three different scores in predicting inadequate bowel preparation among Greek inpatients undergoing colonoscopy

Background Predictive scores aim to predict bowel preparation adequacy among hospitalized patients undergoing colonoscopy. We evaluated the comparative efficacy of these scores in predicting inadequate bowel cleansing in a cohort of Greek inpatients. Methods We performed a post hoc analysis of data generated from a cohort of inpatients undergoing colonoscopy in 4 tertiary Greek centers to validate the 3 models currently available (models A, B and C). We used the Akaike information criterion to quantify the performance of each model, while Harrell's C-index, as the area under the receiver operating characteristics curve (AUC), verified the discriminative ability to predict inadequate bowel prep. Primary endpoint was the comparison of performance among models for predicting inadequate bowel cleansing. 70.7 +/- 15.4 years-were included in the analysis. Model B showed the highest performance (Harrell's C-index: AUC 77.2% vs. 72.6% and 57.5%, compared to models A and C, respectively). It also achieved higher performance for the subgroup of mobilized inpatients (Harrell's C-index: AUC 72.21% vs. 64.97% and 59.66%, compared to models A and C, respectively). Model B also performed better in predicting patients with incomplete colonoscopy due to inadequate bowel preparation (Harrell's C-index: AUC 74.23% vs. 69.07% and 52.76%, compared to models A and C, respectively).Conclusions Predictive model B outperforms its comparators in the prediction of inpatients with inadequate bowel preparation. This model is particularly advantageous when used to evaluate mobilized inpatients

Association of miR-146 rs2910164, miR-196a rs11614913, miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn’s disease.

AIM: To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn’s disease (CD). METHODS: One hundred seven patients with CD based on standard clinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the Harvey-Bradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Whole peripheral blood was extracted and genotyping was performed by PCR. RESULTS: One hundred and seven patients were included in the study. Seventy two (67.3%) patients were classified as complete responders, 22 (20.5%) as partial while 13 (12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients’ characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to anti-TNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population. CONCLUSION: No correlation is detected between studied polymorphisms and patients’ response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population

Revealing Insights: A Comprehensive Overview of Gastric Outlet Obstruction Management, with Special Emphasis on EUS-Guided Gastroenterostomy

Gastric outlet obstruction (GOO) poses a common and challenging clinical scenario, characterized by mechanical blockage in the pylorus, distal stomach, or duodenum, resulting in symptoms such as nausea, vomiting, abdominal pain, and early satiety. Its diverse etiology encompasses both benign and malignant disorders. The spectrum of current treatment modalities extends from conservative approaches to more invasive interventions, incorporating procedures like surgical gastroenterostomy (SGE), self-expandable metallic stents (SEMSs) placement, and the advanced technique of endoscopic ultrasound-guided gastroenterostomy (EUS-GE). While surgery is favored for longer life expectancy, stents are preferred in malignant gastric outlet stenosis. The novel EUS-GE technique, employing a lumen-apposing self-expandable metal stent (LAMS), combines the immediate efficacy of stents with the enduring benefits of gastroenterostomy. Despite its promising outcomes, EUS-GE is a technically demanding procedure requiring specialized expertise and facilities

EUS-Guided Diagnosis of Gastric Subepithelial Lesions, What Is New?

: Gastric subepithelial lesions (SELs) are intramural lesions that arise underneath the gastric mucosa. SELs can be benign, but can also be malignant or have malignant potential. Therefore, correct diagnosis is crucial. Endosonography has been established as the diagnostic gold standard. Although the identification of some of these lesions can be carried out immediately, solely based on their echo characteristics, for certain lesions histological examination is necessary. Sometimes histology can be inconclusive, especially for smaller lesions. Therefore, new methods have been developed in recent years to assist decision making, such as contrast enhanced endosonography, EUS elastography, and artificial intelligence systems. In this narrative review we provide a complete overview of the gastric SELs and summarize the new data of the last ten years concerning the diagnostic advances of endosonography on this topic

Results of the Eighth Scientific Workshop of ECCO:Prevention and Treatment of Postoperative Recurrence in Patients With Crohn's Disease Undergoing an Ileocolonic Resection With Ileocolonic Anastomosis

Despite the introduction of biological therapies, an ileocolonic resection is often required in patients with Crohn's disease [CD]. Unfortunately, surgery is not curative, as many patients will develop postoperative recurrence [POR], eventually leading to further bowel damage and a decreased quality of life. The 8th Scientific Workshop of ECCO reviewed the available scientific data on both prevention and treatment of POR in patients with CD undergoing an ileocolonic resection, dealing with conventional and biological therapies, as well as non-medical interventions, including endoscopic and surgical approaches in case of POR. Based on the available data, an algorithm for the postoperative management in daily clinical practice was developed.</p

Prevention of Malaria Resurgence in Greece through the Association of Mass Drug Administration (MDA) to Immigrants from Malaria-Endemic Regions and Standard Control Measures.

Greece was declared malaria-free in 1974 after a long antimalarial fight. In 2011-2012, an outbreak of P. vivax malaria was reported in Evrotas, an agricultural area in Southern Greece, where a large number of immigrants from endemic countries live and work. A total of 46 locally acquired and 38 imported malaria cases were detected. Despite a significant decrease of the number of malaria cases in 2012, a mass drug administration (MDA) program was considered as an additional measure to prevent reestablishment of the disease in the area. During 2013 and 2014, a combination of 3-day chloroquine and 14-day primaquine treatment was administered under direct observation to immigrants living in the epicenter of the 2011 outbreak in Evrotas. Adverse events were managed and recorded on a daily basis. The control measures implemented since 2011 continued during the period of 2013-2014 as a part of a national integrated malaria control program that included active case detection (ACD), vector control measures and community education. The MDA program was started prior to the transmission periods (from May to December). One thousand ninety four (1094) immigrants successfully completed the treatment, corresponding to 87.3% coverage of the target population. A total of 688 adverse events were recorded in 397 (36.2%, 95% C.I.: 33.4-39.1) persons, the vast majority minor, predominantly dizziness and headache for chloroquine (284 events) and abdominal pain (85 events) for primaquine. A single case of primaquine-induced hemolysis was recorded in a person whose initial G6PD test proved incorrect. No malaria cases were recorded in Evrotas, Laconia, in 2013 and 2014, though three locally acquired malaria cases were recorded in other regions of Greece in 2013. Preventive antimalarial MDA to a high-risk population in a low transmission setting appears to have synergized with the usual antimalarial activities to achieve malaria elimination. This study suggests that judicious use of MDA can be a useful addition to the antimalarial armamentarium in areas threatened with the reintroduction of the disease