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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.

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.

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.

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

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]

BackgroundCrohn's disease (CD) is a potentially debilitating condition that burdens Italian healthcare substantially. The symptomatic management relies on prompt therapy adjustment to reduce flares and follow-up diagnostic inputs to maximise remission. Capsule endoscopy (CE) has introduced advantages in CD diagnostics, allowing the direct inspection of the entire gastrointestinal mucosa. The diagnostic procedure is comparable in effort to standard ileocolonoscopy (IC) but requires no anaesthesia. Whether CE follow-up improves clinical outcomes remains to be defined.ObjectivesTo provide a preliminary evaluation of CE in terms of clinical outcomes with respect to the standard of care ileocolonoscopy/MRE in Italy.MethodsThis retrospective analysis utilises anonymised, monocentric data from the S. Orsola-Malpighi Hospital IBD database in Bologna, Italy, collected between 1999 and 2019. Out of 421 adult patient records, 100 were included in the analysis (50 per arm, matched per demographic and clinical characteristics). The CE represented the intervention arm, whereas ileocolonoscopy/magnetic resonance enterography was the standard of care. The use of biologics, symptomatology course, and surgery were the outcomes.ResultsThe two techniques performed similarly overall. In general, no significant difference emerged in the use of biologics. The use of biologics appears reduced in the CE group, only in L4 patients after the first follow-up year. Similarly, surgery was seemingly less frequent among L4 patients in the CE group. No difference was found between groups in flare occurrence and duration. CE patients might have experienced longer and earlier first remissions, but no long-term difference persisted.ConclusionsThe CE group showed an apparent reduction in biologics and surgery, limiting to L4 diagnoses. More extensive, prospective, multicentre, randomised studies must corroborate these preliminary findings.

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

The knowledge that 5-aminosalicylic acid (5-ASA) is the active compound of sulphasalazine and that it acts topically has stimulated the use of 5-ASA containing enemas and ocher similar compounds such as olsalazine and 4-aminosalicylic acid (4-ASA). 5-ASA enemas have been shown to be effective in controlling active disease in clinical trials and have also been shown to be of benefit in prevention of relapses. Olsalazine enemas have not demonstrated significantly better results than placebo 4-ASA enemas are effective but the results obtained have differed as to effective dose

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.

Background and study aims Obesity represents a major health concern; bariatric surgery is the most effective treatment reducing and maintaining weight loss. The role of a routine esophagogastroduodenoscopy (EGD) prior bariatric surgery is still debated. Moreover, in this scenario of COVID-19 pandemic, EGD is even more questionable due to the procedural risk of viral transmission. A new model of video-endoscopic capsule (VEC) recently has been introduced as a good alternative to the EGD. The aim of this study was to determine if this new capsule is an adequate diagnostic alternative to EGD in the work-up of patients selected for bariatric surgery, particularly in the setting of COVID-19. Patients and methods From January to November 2020, 27 patients selected for bariatric surgery were enrolled in this pilot study to assess for noninferiority of VEC compared to EGD in detection of upper gastrointestinal disease. Results VEC had sensitivity, specificity, and positive and negative predictive values in identification of significant lesions of 91.3 %, 83.33 %, 98.01 %, and 51.57 %, respectively, compared with EGD as the standard criterion. The accuracy was 90.51 % (95 % CI, 73.75 %-98.18 %) and the chi-square statistic is 0.1153 (P = 0.73). Conclusions Our report confirms the diagnostic noninferiority of VEC in preoperative work-up of patients selected for bariatric surgery, compared to EGD. This is very important, particularly during the COVID-19 pandemic, given the high risk of contamination with EGD. Larger multicenter studies are required to confirm our preliminary results.

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]

Ustekinumab (UST) and vedolizumab (VDZ) are biologic therapies for moderate-to-severe Crohn's disease (CD) in patients who failed or had contraindication to anti-TNF treatment. To evaluate ustekinumab efficacy as third-line treatment after swapping from VDZ for failure. We conducted a monocentric, retrospective, observational study where CD patients were followed for 12 months from the beginning of UST therapy. We assessed clinical activity (HBI) and laboratory markers (CRP) at the initiation of UST therapy (T0) and after 2(T2), 6(T6) and 12(T12) months. Endoscopic activity was recorded at T0 and T12. We registered data regarding their clinical history and previous biologic treatments. Steroid-free clinical remission was defined as HBI ≤ 4 without need for steroids. Clinical response was defined as HBI reduction of at least three points or the suspension of steroids. 27 CD patients treated with UST after VDZ failure had a minimum follow up of 12 months and were included. All patients had previously been treated with anti-TNF agents. After 12 months, steroid-free clinical remission was evident in 15 (55.5%) patients, 5 (18.5%) had clinical response, while 7 (26%) had suspended for failure or persisted on treatment after optimization. Ustekinumab should be considered as third-line biologic treatment in multi-refractory CD patients. [ABSTRACT FROM AUTHOR]

This is the second of a series of two articles reporting the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management, and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimisation, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC. [ABSTRACT FROM AUTHOR]