Search

Inflammatory bowel disease (IBD) comprising ulcerative colitis and Crohn’s disease is a chronic immune-mediated disease which affects the gastrointestinal tract with a relapsing and remitting course, causing lifelong morbidity. IBD pathogenesis is determined by multiple factors including genetics, immune and microbial factors, and environmental factors. Although therapy options are expanding, remission rates are unsatisfiable, and together with the disease course, response to therapy remains unpredictable. Therefore, the identification of biomarkers that are predictive for the disease course and response to therapy is a significant challenge. Extrachromosomal circular DNA (eccDNA) fragments exist in all tissue tested so far. These fragments, ranging in length from a few hundreds of base pairs to mega base pairs, have recently gained more interest due to technological advances. Until now, eccDNA has mainly been studied in relation to cancer due to its ability to act as an amplification site for oncogenes and drug resistance genes. However, eccDNA could also play an important role in inflammation, expressed both locally in the- involved tissue and at distant sites. Here, we review the current evidence on the molecular mechanisms of eccDNA and its role in inflammation and IBD. Additionally, the potential of eccDNA as a tissue or plasma marker for disease severity and/or response to therapy is evaluated., Inflammatory bowel disease (IBD) comprising ulcerative colitis and Crohn’s disease is a chronic immune-mediated disease which affects the gastrointestinal tract with a relapsing and remitting course, causing lifelong morbidity. IBD pathogenesis is determined by multiple factors including genetics, immune and microbial factors, and environmental factors. Although therapy options are expanding, remission rates are unsatisfiable, and together with the disease course, response to therapy remains unpredictable. Therefore, the identification of biomarkers that are predictive for the disease course and response to therapy is a significant challenge. Extrachromosomal circular DNA (eccDNA) fragments exist in all tissue tested so far. These fragments, ranging in length from a few hundreds of base pairs to mega base pairs, have recently gained more interest due to technological advances. Until now, eccDNA has mainly been studied in relation to cancer due to its ability to act as an amplification site for oncogenes and drug resistance genes. However, eccDNA could also play an important role in inflammation, expressed both locally in the- involved tissue and at distant sites. Here, we review the current evidence on the molecular mechanisms of eccDNA and its role in inflammation and IBD. Additionally, the potential of eccDNA as a tissue or plasma marker for disease severity and/or response to therapy is evaluated.

Personalised medicine and the identification of predictors of the efficacy of specific drugs represent the ultimate goal for the treatment of ulcerative colitis (UC) in order to break the current therapeutic ceiling. JAK inhibitors are a new class of advanced therapies, orally administered, showing a good profile of efficacy and safety in both randomised controlled trials (RCTs) and real-world studies. Unfortunately, to date, it is not possible to draw the ideal profile of a patient maximally benefiting from this class of drugs to guide clinicians' therapeutic choices. Baseline clinical activities and inflammatory biomarkers, as well as their early variation after treatment initiation, emerged as the main predictors of efficacy from post hoc analyses of RCTs with tofacitinib. Similar findings were also observed in the real-life studies including mainly patients with a history of pluri-refractoriness to biological therapies. At last, a few new biomarkers have been explored, even though they have not been validated in large cohorts. This paper provides a review of the current knowledge on clinical variables and biomarkers predicting response to JAK inhibitors in UC.

CMV infection is still a matter of concern in IBD patients, especially regarding the disease's relapse management. Why IBD patients, particularly those affected by ulcerative colitis, are more susceptible to CMV reactivation is not totally explained, although a weakened immune system could be the reason. Various techniques, ranging from serology to histology, can be employed to detect intestinal CMV infection; however, there is currently disagreement in the literature regarding the most effective diagnostic test. Furthermore, CMV involvement in steroid resistance has been broadly discussed, but whether CMV infection is a cause or consequence of the disease severity and, consequently, steroid refractoriness is still debated. Its potential contribution to the lack of response to advanced therapy and small molecules must be more valued and wholly explored. In this review, we look at the actual literature on CMV in IBD patients, and we suggest a pragmatic algorithm for clinical practice management of CMV infection.

Limited knowledge is available about the relationship between food allergies or intolerances and inflammatory bowel disease (IBD). Clinicians frequently encounter patients who report food allergies or intolerances, and gastroenterologists struggle distinguishing between patients with organic disorders and those with functional disorders, which the patients themselves may associate with specific dietary components. This task becomes even more arduous when managing patients with significant underlying organic conditions, like IBD. The aim of this review is to summarize and emphasize any actual associations between food allergies and intolerances and inflammatory diseases, such as ulcerative colitis and Crohn's disease. Through a narrative disceptation of the current literature, we highlight the increased prevalence of various food intolerances, including lactose, fructose, histamine, nickel, and non-celiac gluten sensitivity, in individuals with IBD. Additionally, we explore the association between increased epithelial barrier permeability in IBD and the development of food sensitization. By doing so, we aim to enhance clinicians' awareness of the nutritional management of patients with IBD when facing complaints or evidence of food allergies or intolerances.

The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNF alpha inhibitors, anti-alpha 4 beta 7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naive patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities.

Inflammatory bowel diseases (IBD), including Crohn’s Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from the origin cell and able to circulate into the bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also play a role in IBD. In this review, we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment., Inflammatory bowel diseases (IBD), including Crohn’s Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from the origin cell and able to circulate into the bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also play a role in IBD. In this review, we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment.

Lay Summary Psychiatric disorders are more prevalent in IBD patients than in general population. In this prospective cohort study, we found a correlation between active UC, peculiar psychiatric distress (anxiety and depression above all), and specific taxonomic gut microbiota signatures.Background Several patients with ulcerative colitis (UC) suffer from psychiatric disorders, such as major depressive disorder, anxiety, or bipolar disorder, and show specific personality traits. Despite this, there are few data about personality profiles' characterization in UC patients and about correlation of their psychopathological profile with their intestinal microbiota. The aim of our study is to analyze the psychopathological and personality profile of UC patients and correlate it with specific signatures of their gut microbiota. Methods This is a prospective interventional longitudinal cohort study. We enrolled consecutive patients affected by UC attending to the IBD Unit of Center for Digestive Disease of "A. Gemelli" IRCCS Hospital in Rome and a group of healthy subjects, matched for specific characteristics. Each patient was evaluated by a gastroenterologist and a psychiatrist. Moreover, all participants underwent psychological tests and a collection of stool samples. Results We recruited 39 UC patients and 37 healthy subjects. Most patients showed high level of alexithymia, anxiety symptoms, depressive symptoms, as well as neuroticism and hypochondria, with obsessive-compulsive features at the behavioral level, which significantly impaired their quality of life and abilities at work. Gut microbiota analysis in UC patients demonstrated an increase in actinobacteria, Proteobacteria and Saccharibacteria (TM7), with a reduction in verrucomicrobia, euryarchaeota and tenericutes. Conclusions Our study confirmed the presence of high levels of psycho-emotional distress in UC patients, alongside alterations of the intestinal microbiota, and highlighted some families and genera of

Acute pancreatitis (AP) is an acute inflammation of the pancreas caused by the activation of digestive enzymes in the pancreatic tissue. The main causes of AP are cholelithiasis and alcohol abuse; less commonly, it can be caused by drugs, with a prevalence of up to 5%. Causal associations between drugs and pancreatitis are largely based on case reports or case series with limited evidence. We reviewed the available data on drug-induced AP, focusing on antimicrobial drugs and antivirals, and discussed the current evidence in relation to the classification systems available in the literature. We found 51 suspected associations between antimicrobial and antiviral drugs and AP. The drugs with the most evidence of correlation are didanosine, protease inhibitors, and metronidazole. In addition, other drugs have been described in case reports demonstrating positive rechallenge. However, there are major differences between the various classifications available, where the same drug being assigned to different probability classes. It is likely that the presence in multiple case reports of an association between acute pancreatitis and a drug should serve as a basis for conducting prospective randomized controlled trials to improve the quality of the evidence.

Inflammatory bowel diseases (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from the origin cell and able to circulate into the bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also play a role in IBD. In this review, we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment.

Inflammatory bowel diseases (IBD) and microscopic colitis are chronic immune-mediated inflammatory disorders that affect the gastroenterological tract and arise from a complex interaction between the host's genetic risk factors, environmental factors, and gut microbiota dysbiosis. The precise mechanistic pathways interlinking the intestinal mucosa homeostasis, the immunological tolerance, and the gut microbiota are still crucial topics for research. We decided to deeply analyze the role of bile acids in these complex interactions and their metabolism in the modulation of gut microbiota, and thus intestinal mucosa inflammation. Recent metabolomics studies revealed a significant defect in bile acid metabolism in IBD patients, with an increase in primary bile acids and a reduction in secondary bile acids. In this review, we explore the evidence linking bile acid metabolites with the immunological pathways involved in IBD pathogenesis, including apoptosis and inflammasome activation. Furthermore, we summarize the principal etiopathogenetic mechanisms of different types of bile acid-induced diarrhea (BAD) and its main novel diagnostic approaches. Finally, we discuss the role of bile acid in current and possible future state-of-the-art therapeutic strategies for both IBD and BAD.

Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli. Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC (n = 16) were enrolled and compared with healthy female subjects (n = 15) and patients with chronic gastrointestinal (GI) disorders (n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections.

Negli ultimi anni il mondo della progettazione di opere civili ha visto la diffusione di un approccio innovativo, il Building Information Modeling un processo coordinato che agevola la gestione digitale di rappresentazioni virtuali delle caratteristiche fisiche e funzionali di un’opera. La soluzione BIM permette una perfetta condivisione delle informazioni nel processo costruttivo, dalla progettazione alla manutenzione, l’interoperabilità tra le varie figure coinvolte in un progetto e una riduzione di tempi e costi di realizzazione grazie alla possibilità di individuare e risolvere errori già in fase progettuale e non in quella esecutiva, dove eventuali modifiche in corso d’opera risultano onerose e complicate.L’obiettivo del presente elaborato consiste nell’implementazione della filosofia BIM nel processo di progettazione di infrastrutture stradali con l’intento di evidenziare i vantaggi e gli eventuali limiti emersi durante l’utilizzo dei software. Lo studio sul BIM effettuato in questo lavoro di tesi si è concentrato, in primo luogo, nel definire effettivamente cosa si intenda con il termine BIM; in particolare si sofferma l’attenzione sui concetti fondamenti dei modelli informativi, quali lo scambio di dati, l’interoperabilità ed i livelli di sviluppo. All'interno dell'elaborato viene esposto il caso di studio relativo al progetto di un sottopasso a spinta alla linea ferroviaria Castelfranco – Bassano mediante metodologia BIM. Infine si esegue il computo metrico estimativo di tutto il progetto, mediante il programma STR Vision CPM, un software utilizzato in logica BIM per il computo delle opere d’arte ed in tradizionale per il computo dei restanti materiali dell’infrastruttura.

Lo scopo di questa tesi è quello di analizzare a fondo il concetto sovrastruttura ferroviaria senza ballast e sottolinearne pregi e difetti rispetto a quella tradizionale con pietrisco, al fine di identificare chiaramente quando e dove i sistemi senza massicciata forniscono prestazioni migliori. L'aumento dei costi di manutenzione delle sovrastrutture ferroviarie al giorno d'oggi stanno aprendo la strada a nuovi sistemi, la maggior parte sviluppati in paesi che hanno linee di velocità elevate e tanti altri paesi si stanno preparando per aggiornare le proprie linee esistenti, nonché per creare nuove linee ferroviarie ad alta velocità. In molti casi i sistemi senza ballast sembrano avere le potenzialità per offrire un servizio per linee ad alta velocità più efficiente rispetto alle tracce tradizionali con ballast, soprattutto a causa della loro maggiore stabilità strutturale, del basso bisogno di manutenzione e del lungo ciclo di vita. Il primo capitolo è dedicato alla descrizione della struttura del binario tradizionale con ballast analizzando gli strati che formano la sovrastruttura. Il secondo capitolo è dedicato alla descrizione di varie tipologie, utilizzate nel mondo, di sovrastrutture ferroviarie senza ballast, di ognuna di esse sono state elencate le caratteristiche costruttive e prestazionali. Il terzo capitolo è dedicato al confronto tra le due tipologie di sovrastruttura, sono state descritte le capacità elastiche e deformative delle due soluzioni, il degrado cui incorrono le due soluzioni, gli stati sollecitanti a cui sono sottoposte e la risposta delle stesse. Di particolare importanza è il confronto di costo dei due sistemi e il rumore e le vibrazioni generate da questi; infatti negli ultimi anni questi sono gli aspetti fondamentali su cui si basa la scelta di un sistema costruttivo; a seguito di questo confronto è stato possibile trarre le conclusioni.

Negli ultimi anni il mondo della progettazione di opere civili ha visto la diffusione di un approccio innovativo, il Building Information Modeling un processo coordinato che agevola la gestione digitale di rappresentazioni virtuali delle caratteristiche fisiche e funzionali di un’opera. La soluzione BIM permette una perfetta condivisione delle informazioni nel processo costruttivo, dalla progettazione alla manutenzione, l’interoperabilità tra le varie figure coinvolte in un progetto e una riduzione di tempi e costi di realizzazione grazie alla possibilità di individuare e risolvere errori già in fase progettuale e non in quella esecutiva, dove eventuali modifiche in corso d’opera risultano onerose e complicate.L’obiettivo del presente elaborato consiste nell’implementazione della filosofia BIM nel processo di progettazione di infrastrutture stradali con l’intento di evidenziare i vantaggi e gli eventuali limiti emersi durante l’utilizzo dei software. Lo studio sul BIM effettuato in questo lavoro di tesi si è concentrato, in primo luogo, nel definire effettivamente cosa si intenda con il termine BIM; in particolare si sofferma l’attenzione sui concetti fondamenti dei modelli informativi, quali lo scambio di dati, l’interoperabilità ed i livelli di sviluppo. All'interno dell'elaborato viene esposto il caso di studio relativo al progetto di un sottopasso a spinta alla linea ferroviaria Castelfranco – Bassano mediante metodologia BIM. Infine si esegue il computo metrico estimativo di tutto il progetto, mediante il programma STR Vision CPM, un software utilizzato in logica BIM per il computo delle opere d’arte ed in tradizionale per il computo dei restanti materiali dell’infrastruttura.

Lo scopo di questa tesi è quello di analizzare a fondo il concetto sovrastruttura ferroviaria senza ballast e sottolinearne pregi e difetti rispetto a quella tradizionale con pietrisco, al fine di identificare chiaramente quando e dove i sistemi senza massicciata forniscono prestazioni migliori. L'aumento dei costi di manutenzione delle sovrastrutture ferroviarie al giorno d'oggi stanno aprendo la strada a nuovi sistemi, la maggior parte sviluppati in paesi che hanno linee di velocità elevate e tanti altri paesi si stanno preparando per aggiornare le proprie linee esistenti, nonché per creare nuove linee ferroviarie ad alta velocità. In molti casi i sistemi senza ballast sembrano avere le potenzialità per offrire un servizio per linee ad alta velocità più efficiente rispetto alle tracce tradizionali con ballast, soprattutto a causa della loro maggiore stabilità strutturale, del basso bisogno di manutenzione e del lungo ciclo di vita. Il primo capitolo è dedicato alla descrizione della struttura del binario tradizionale con ballast analizzando gli strati che formano la sovrastruttura. Il secondo capitolo è dedicato alla descrizione di varie tipologie, utilizzate nel mondo, di sovrastrutture ferroviarie senza ballast, di ognuna di esse sono state elencate le caratteristiche costruttive e prestazionali. Il terzo capitolo è dedicato al confronto tra le due tipologie di sovrastruttura, sono state descritte le capacità elastiche e deformative delle due soluzioni, il degrado cui incorrono le due soluzioni, gli stati sollecitanti a cui sono sottoposte e la risposta delle stesse. Di particolare importanza è il confronto di costo dei due sistemi e il rumore e le vibrazioni generate da questi; infatti negli ultimi anni questi sono gli aspetti fondamentali su cui si basa la scelta di un sistema costruttivo; a seguito di questo confronto è stato possibile trarre le conclusioni.