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Paolo Gionchetti, Carlo Calabrese, Silvio Laureti, Gilberto Poggioli, Fernando Rizzello IRCCS Azienda Ospedaliero-Universitaria di Bologna, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Bologna, ItaliaCorrespondence: Paolo GionchettiDIMEC, Via Massarenti 9, Bologna, 40138, ItaliaEmail paolo.gionchetti@unibo.itAbstract: Procto-colectomy with an ileal pouch anal anastomosis is the procedure of choice for ulcerative colitis patients that require colectomy. Pouchitis is a non-specific inflammation of the ileal reservoir, and the most common, inflammatory and long-term, complication after pouch surgery for ulcerative colitis. The aetiology is still unknown, but many risk factors have been individuated. Pouchitis can be classified based on aetiology, duration, clinical course, and response to antibiotic therapy. Accurate diagnosis and classification is the key factor for an adequate management, and exclusion of secondary causes of pouchitis is pivotal. Most of the patients consistently respond to antibiotic therapy, but management of the subgroup of patients with chronic-antibiotic-resistant-pouchitis is still challenging, being this entity one of the major causes of pouch failure.Keywords: pouchitis, chronic antibiotic refractory pouchitis, classification, diagnosis, management

ABSTRACT Cytomegalovirus (CMV) colitis is a serious concern worsening the prognosis of patients with ulcerative colitis (UC). We aimed to assess risk factors and prognostic impact of CMV colitis in patients with moderate-to-severe UC flare. We conducted a retrospective, observational, single-center study. Consecutive adult patients hospitalized for moderate-to-severe UC from January 2020 to June 2023 were included. The primary endpoint was a diagnosis of CMV-colitis according to immunohistochemistry on tissue biopsies. The secondary endpoint was the need for colectomy within 30 days. Overall, 135 patients were included. CMV colitis was diagnosed in n = 37 (27.4%): n = 19 (51.4%) endoscopically, the remaining on surgical specimens. Of them, n = 23 (62.2%) had positive CMV-DNAemia with a median value of 1,008 cp/mL (interquartile range 318–2,980). Differences between the two groups (CMV colitis vs non-CMV) included age (60 vs 41 years, P = 0.004), Charlson Comorbidity Index (1 vs 0, P = 0.003), steroid refractoriness (86.5% vs 62.2%, P = 0.007), and positive CMV-DNAemia (62.2% vs 10.1%, P < 0.001). At multivariable analysis, steroid-refractory disease, Charlson Comorbidity Index, and CMV-DNAemia were associated with CMV colitis. Overall, n = 54 (39.7%) patients underwent colectomy, and this was significantly more common in patients with CMV colitis vs non-CMV group (54.1% vs 34.4%, P = 0.049). Kaplan-Meier showed that antiviral therapy seems to have a relevant impact on colectomy (P < 0.001). CMV-DNA blood detection is independently associated with CMV-positive refractory UC. Since CMV colitis may increase the risk of colectomy and antiviral treatment seems to reduce such risk, prospective studies are needed to confirm the role of CMV-DNA blood detection to early diagnose CMV colitis.IMPORTANCECytomegalovirus (CMV) colonic reactivation worsens the prognosis of patients with active ulcerative colitis. Blood CMV-DNA reactivation is strongly associated with CMV colitis. Prompt diagnosis and treatment of CMV colitis can avoid surgery in most cases.

The aim of the present study was to test a new oral contrast medium composed of natural components for the magnetic resonance (MR) imaging of small bowel diseases. Between January 2018 and June 2019, 35 patients affected by ileocolic Crohn’s disease (CD) were enrolled in the present study. Each patient underwent two sequential MR enterographies, first with the standard polyethylene glycol (PEG) water solution and, after 3 weeks, with the new natural beverage designed by our team. At the end of the administration of each oral contrast, a satisfaction survey was given to the patients to assess the palatability of both beverages. The intestinal distention and the quality of images were evaluated by two expert radiologists for both studies and the interreader agreement was calculated. According to the satisfaction questionnaire, 97.1% of patients expressed positive judgments regarding the natural beverage (71.4% very good and 25.7% good) whereas only 8.6% of them appreciated the PEG water solution (8.6% good) (p = 0.0001). The degree of intestinal distention was excellent and good in 97.1% of patients after the administration of PEG and in 94.3% of the patients after the administration of the natural beverage, without significant differences between the two products and with almost perfect (k = 0.821) and substantial (k = 0.754) inter-observer variability, respectively. No statistical differences were observed between the two expert radiologists regarding the evaluation of the imaging quality; in particular, they were considered good and excellent in 100% of patients after the administration of PEG water solution and in 97.2% of those who took the natural beverage, with substantial (k = 0.618) and almost perfect (k = 0.858) inter-observer variability, respectively. The new natural beverage demonstrated the same intestinal distension and excellent image quality compared to the synthetic standard oral contrast administered during MRE for small bowel diseases, proving to be a valid alternative with better palatability.

BackgroundCOVID-19, whose causative pathogen is the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic in March 2020. The gastrointestinal tract is one of the targets of this virus, and mounting evidence suggests that gastrointestinal symptoms may contribute to disease severity. The gut–lung axis is involved in the immune response to SARS-CoV-2; therefore, we investigated whether COVID-19 patients’ bacterial and fungal gut microbiome composition was linked to disease clinical outcome.MethodsIn May 2020, we collected stool samples and patient records from 24 hospitalized patients with laboratory-confirmed SARS-CoV-2 infection. Fungal and bacterial gut microbiome was characterized by amplicon sequencing on the MiSeq, Illumina’s integrated next generation sequencing instrument. A cohort of 201 age- and sex-matched healthy volunteers from the project PRJNA661289 was used as a control group for the bacterial gut microbiota analysis.ResultsWe observed that female COVID-19 patients had a lower gut bacterial microbiota richness than male patients, which was consistent with a different latency in hospital admittance time between the two groups. Both sexes in the COVID-19 patient study group displayed multiple positive associations with opportunistic bacterial pathogens such as Enterococcus, Streptococcus, and Actinomyces. Of note, the Candida genus dominated the gut mycobiota of COVID-19 patients, and adult patients showed a higher intestinal fungal diversity than elderly patients. We found that Saccharomycetales unassigned fungal genera were positively associated with bacterial short-chain fatty acid (SCFA) producers and negatively associated with the proinflammatory genus Bilophila in COVID-19 patients, and we observed that none of the patients who harbored it were admitted to the high-intensity unit.ConclusionsCOVID-19 was associated with opportunistic bacterial pathogens, and Candida was the dominant fungal taxon in the intestine. Together, we found an association between commensal SCFA-producers and a fungal genus that was present in the intestines of patients who did not experience the most severe outcome of the disease. We believe that this taxon could have played a role in the disease outcome, and that further studies should be conducted to understand the role of fungi in gastrointestinal and health protection.

IntroductionWe evaluated baseline Clearance of anti-tumor necrosis factors and human leukocyte antigen variant (HLA DQA1*05) in combination as poor prognostic factors (PPF) of pharmacokinetic (PK) origin impacting immune response (formation of antidrug antibodies) and disease control of inflammatory bowel disease (IBD) patients treated with infliximab or adalimumab.MethodsBaseline Clearance was estimated in IBD patients before starting treatment using weight and serum albumin concentrations. HLA DQA1*05 carrier status (rs2097432 A/G or G/G variant) was measured using real time polymerase chain reaction. The outcomes consisted of immune response, clinical and biochemical remission (C-reactive protein0.326 L/day and HLA DQA1*05 carrier status were 2-fold more likely to have antidrug antibodies (OR=2.3, 95%CI: 1.7-3.4; p

Inflammatory bowel diseases comprise Crohn’s disease and ulcerative colitis, two chronic inflammatory disorders of the digestive tract that develop in adolescence and early adulthood and show a rising pattern in industrialized societies, as well as in developing countries, being strongly influenced by environmental pressures such as nutrition, pollution and lifestyle behaviors. Here, we provide a narrative review of the bidirectional link between nutritional factors and IBD, of dietary deficits observed in IBD patients due to both the disease itself and dietary habits, and of the suggested nutritional interventions. Research of the literature was conducted. Clinical and basic research studies consistently demonstrate that diet could alter the risk of developing IBD in predisposed individuals. On the other hand, dietary interventions represent a valid tool in support of conventional therapies to control IBD symptoms, rebalance states of malnutrition, promote/maintain clinical remission and improve patients’ quality of life. Although there are no official dietary guidelines for patients with IBD, they should receive nutritional advice and undergo oral, enteral, or parenteral nutritional supplementation if needed. However, the dietary management of malnutrition in IBD patients is complex; future clinical studies are required to standardize its management.

The terminal ileum is the most frequent site of Crohn's Disease (CD) that necessitates surgery. Of the postoperative complications (POCs) associated with ileocaecal resection for CD, intra-abdominal septic complications (IASCs) include anastomotic leak, abscesses, and entero-cutaneous fistula. We aimed to identify predictors of IASCs and severe POCs (Clavien-Dindo ≥3) after primary ileocaecal resection for CD. This is a retrospective single-centre cohort study including all consecutive primary ileocaecal resection for CD in a tertiary IBD centre between 2004 and 2021. A total of 853 patients underwent primary ileocaecal resection for CD. 307 (36.6 %) patients were receiving antibiotics, 253 (29.8 %), systemic steroids, and 178 (21.0 %) oral budesonide at surgery. At 90 days, 260 (30.8 %) patients developed POCs, 62 (7.3 %) severe POCs, and 56 (6.6 %) IASCs. At multivariate analysis, severe POCs were associated with lower preoperative albumin levels (OR1.58, 95 %CI 1.02–2.50, p = 0.040) and a history of cardiovascular diseases (OR2.36, 95 %CI 1.08–7.84, p = 0.030). IASCs were associated with lower preoperative albumin levels (OR1.81, 95 %CI 1.15–2.94, p = 0.011) and oral budesonide (OR2.07, 95 %CI 1.12–3.83, p = 0.021) with a dose-dependent effect. The independent association, dose-dependent effect, and biological plausibility of budesonide and IASCs suggest a robust causal effect. Oral budesonide should be carefully assessed before primary ileocaecal resection for CD. [ABSTRACT FROM AUTHOR]

Abstract Background A new capsule endoscopy (CE) system featuring two advanced optics for 344°-viewing and a prolonged operative time has been recently developed for Crohn’s disease (CD) patients. Hence, we evaluated, for the first time, the performance of this novel CE and the add-on value of the 344°-viewing in a multi-center real-life setting. Methods Consecutive patients with suspected or established CD received the PillCam™ Crohn’s System as supplementary diagnostic work-up focused on the small-bowel between June 2017 and June 2018. Technical and clinical data, including the panenteric CE diagnostic yield, the Lewis score and the impact of small-bowel findings on clinical management during a 6-months follow-up (new diagnosis, staging or treatment upgrade) were collected, thereby evaluating the added value of the 344° panoramic-view (lesions detected by camera A and B) over the standard 172°-view (lesions detected by one camera only). Results Among 41 patients (aged 43 ± 20 years), 73% underwent CE for suspected CD and 27% for established CD. The rate of complete enteroscopy was 90%. No technical failure or retention occurred. Compared to the standard 172° view, the panoramic 344°-view revealed a greater number of patients with a relevant lesion (56.1% vs. 39.0%; P = 0.023), resulting in higher Lewis score (222,8 vs. 185.7; P = 0.031), and improved clinical management (48.8% vs. 31.7%, P = 0.023). Conclusions The panoramic 344°-view increases small-bowel CE accuracy, thereby improving the clinical management of CD patients with mild small-bowel active disease. This system should be regarded as a new standard for both small-bowel diagnosis and monitoring in inflammatory bowel diseases.

Objective We postulated that adalimumab [ADA] drug clearance [CL] may be a more critical determinant of therapeutic outcome than ADA concentration. This was tested in Crohn's disease [CD] patients undergoing ADA maintenance treatment. Methods CD patients from four cohorts received ADA induction and started maintenance therapy. Therapeutic outcomes consisted of endoscopic remission [ER], sustained C-reactive protein [CRP] based clinical remission [defined as CRP levels below 3 mg/L in the absence of symptoms], and faecal calprotectin [FC] level below 100 µg/g. Serum albumin, ADA concentration, and anti-drug antibody status were determined using immunochemistry and homogeneous mobility shift assay, respectively. CL was determined using a nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Mann–Whitney test and logistic regression with calculation of odds ratio. Repeated event analysis was conducted using a nonlinear mixed effect model. Results In 237 enrolled patients [median age 40 years, 45% females], median CL was lower in patients achieving ER as compared with those with persistent active endoscopic disease [median 0.247 L/day vs 0.326 L/day, respectively] [ p  <0.01]. There was no significant difference in ADA concentration between patients in endoscopic remission compared with those with recurrence [median 9.3 µg/mL vs 11.7 µg/mL, respectively]. Sustained CRP-based clinical remission and FC levels below 100 µg/g were generally associated with lower CL and higher ADA concentration. Repeated event analysis confirmed those findings with better performances of CL than concentration in associating with ER and other outcomes. Conclusion Lower ADA clearance is associated with an improved clinical outcome for patients with Crohn's disease and may be a superior pharmacokinetic measure than concentration. [ABSTRACT FROM AUTHOR]

Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with a rapidly growing worldwide incidence. The last decades presented rapid progress in pharmacological treatment leading in many cases to clinical and endoscopic remission, including biological treatment with anti-TNF agents. The exact timing of introduction, optimization and maintenance of anti-TNF therapy in IBDs is not thoroughly covered in current guidelines. We used the Delphi panel methodology to gather the IBD experts' views and achieve consensus for clinical recommendations on introducing and maintaining anti-TNF therapy for patients with IBDs. Twelve recommendations achieved a high level of consensus in two assessment rounds by 52 (1st round) and 47 (2nd round) IBD experts. In many clinical situations, the early use of anti-TNF therapy is recommended. Nowadays, the cost-efficacy profile of anti-TNF biosimilars makes them the first-line drug in a substantial proportion of patients, thus providing the opportunity to increase access to biological therapy. [ABSTRACT FROM AUTHOR]

Background. The lifelong and remitting nature of ulcerative colitis results in considerable disability and a substantial negative impact on quality of life. The major goal of the therapy of ulcerative colitis is considered to be the modification of the course of the disease, so that the patient’s quality of life can be improved while minimising disease-related disability. Although considerable progress in understanding the molecular pathways involved in ulcerative colitis has led to improved treatment options, there is currently no definitive cure for ulcerative colitis, there remain considerable unmet needs in terms of long-term efficacy and safety, and there are many patients who continue to be burdened by physical and psychological symptoms. Defining unmet needs can help to increase the awareness of the shortcomings of current therapeutic management and highlight the need to achieve not only a control of clinical symptoms but also control of mucosal healing, in order to attain the best possible long-term outcomes. Methods. With the aim of providing a better understanding of the unmet needs of patients towards improving overall care, a Delphi process was used to obtain consensus among a group of Italian ulcerative colitis experts. The consensus group met with a major focus of delineating the unmet needs of current treatment strategies and overall management of ulcerative colitis, while also focusing on quality of life and patient care. Results. Three main areas were identified: (i) treatment, (ii) monitoring and risk management, and (iii) patient-related issues. A high level of consensus was reached on all but one of the statements identified. Conclusions. The findings arising from the Delphi process provide valuable insights into the unmet needs in the management of moderate-to-severe ulcerative colitis from the clinician’s perspective, while emphasising the benefits of therapeutic individualization and suggesting areas that need additional study with the aim of optimising the treatment of patients with ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammation of the coli mucosa clinically characterized by bloody diarrhea, abdominal pain and other systemic symptoms. The onset, as well as subsequent relapses, may occur with varying degrees of clinical and endoscopic activity and extent of disease. The clinical and endoscopic activity varies from mild to severe, while the extent of disease, without interruption, may involve from the rectum up to the entire colon. The severe form, when not properly and promptly treated, can be life-threatening and may determine various complications requiring urgent surgical treatment. Early recognition of severe forms, their treatment and patient monitoring can reduce morbidity and mortality, and improve surgical outcome. Since the 1950s, systemic corticosteroids have been the first-line treatment in severe active UC. Today, appropriate patient monitoring, and recognition of clinical, radiological and laboratory findings indicative of steroid failure guide the clinician in the use of immunomodulatory drugs or suggest indications for surgery. The aim of our study is to review the more recent data and guidelines that could be useful in clinical practice for the management of severe UC.

Ulcerative colitis (UC) is a chronic inflammatory condition that is confined to the colonic mucosa. Its main symptoms include diarrhea, rectal bleeding and abdominal pain. Approximately two-thirds of UC patients have disease confined distal to the splenic flexure, which can be treated effectively with topical therapy. This means the active drug can be delivered directly to the site of inflammation, limiting the systemic absorption and potential side effects. Topical treatment with aminosalicylates is the most effective approach in the treatment of these forms, provided that the formulation reaches the upper margin of the disease. Given this, the suppository formulation is the treatment of choice for proctitis and distal sigmoiditis. Thanks to their proximal spread, enemas, foams and gels represent the treatment of choice for proctosigmoiditis and for distal ulcerative colitis. Oral aminosalicylates are less effective than topical therapies in patients with active disease, while the combination of topical and oral treatment is more effective in patients refractory to topical or oral mono-therapy. Topically administered aminosalicylates play an important role in the maintenance of remission, but the long-term adhesion to therapy is poor. For this reason, the oral formulation is the first-line therapy in the maintenance of remission. Refractory patients can be treated with topical steroids or systemic steroids and TNF-alpha inhibitors in severe forms.

Background: The treatment of Inflammatory bowel disease comes from many years of esperience, clinical trials and mistakes. Discussion: In patients with active Crohn disease steroids are considerated the first choice, but recently, the introduction of anti-TNF alfa agents (infliximab and adalimumab) has changed the protocols. Anti-TNF are also used for closing fistula after surgical curettage. An efficently preventive treatment of Crohn disease still has not been found but hight dose of oral salicylates, azatioprine or 6-MP and antibiotics might be useful. In severe attacks of ulcerative colitis, high dose iv treatment of steroids are required for a few days. Later on, a further treatment with anti- TNF might delay the need of surgery. In patients with mild to moderate attacks of ulcerative colitis, topical treatment is preferred, it consists of enemas, suppositories or foams containing 5-aminosalycilic acid, traditional steroids, topical active steroids. Topical treatment can be associated with oral steroids or oral salicylates. Oral salicylates or azatioprine are used for prevention of relaps.