Hocus Pocus: the Role of Hand-held Ultrasonography in Predicting Disease Extension and Endoscopic Activity in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis [UC] assessment still requires ileocolonoscopy [IC]. Intestinal ultrasound [IUS] has emerged as a non-invasive assessment tool, and the Milan Ultrasound Criteria [MUC] score has been validated to estimate and grade UC disease activity. Recently, hand-held IUS [HHIUS] has been used in several clinical settings, but data about its use in UC are limited. We aimed to evaluate the diagnostic accuracy of HHIUS compared with conventional IUS in detecting UC extension and activity. PATIENTS AND METHODS: From November 2021 to September 2022, we prospectively enrolled UC patients afferent to our third-level IBD Unit for IC evaluation. Patients underwent IC, HHIUS, and IUS. Ultrasound activity was defined by MUC >6.2, and endoscopic activity was defined by a Mayo endoscopic score [MES] >1. Cohen's k test was applied to test the concordance between IUS-MUC and HHIUS-MUC after MUC dichotomisation [MUC >6.2, yes/no]. RESULTS: In all, 86 patients with UC were enrolled. No significant difference was recorded between IUS and HHIUS at the per-segment extension [p = N.S.], and both procedures were comparable in terms of results of bowel wall thickness [BWT] and bowel wall stratification [BWS] assessment [p = N.S.]. IUS and HHIUS displayed excellent agreement when the MUC score system was applied [k = 0.86, p <0.01]. CONCLUSION: Hand-held intestinal ultrasound and IUS are comparable in UC extension definition and MUC evaluation. HHIUS could be reliable for detecting disease activity and estimating its extension, providing close monitoring. It also represents a non-invasive, easily practicable investigation, allowing immediate medical decisions with significant time and cost advantages.

Exploring the concept of deep remission in Crohn's disease: correlation between transmural healing and biomarkers.

Background: While mucosal healing (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn's disease (CD), little is known about the real significance and clinical impact of deep remission (DR). Objectives: To better explore the concept of DR, toward a direct correlation between MH, TH, and biomarkers. Design: Real-world observational longitudinal study to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive CD patients on biologics. Methods: A receiver operating characteristic (ROC) curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, patients achieving CR, MH, and TH, in association with the target FC/CRP values, were considered in DR. Results: Among 118 CD patients, CR, MH, and TH were achieved in 62.7, 44.1, and 32.2%, respectively. After 2 years, the mean FC levels decreased from 494 ± 15.4 µg/g to 260 ± 354.9 µg/g (p < 0.01). Using the ROC curve analysis, an FC cut-off value of 94 µg/g was associated with both MH [sensitivity: 94.2%, specificity: 84.8%, positive predictive value (PPV): 83.05%, negative predictive value (NPV): 94.92%, area under the curve (AUC): 0.95] and TH (sensitivity: 92.1%, specificity: 70%, PPV: 64.4%, NPV: 94.9%, AUC: 0.88). CRP < 5 mg/L was associated with both MH (sensitivity: 96.1%, specificity: 62.1%, PPV: 66.7%, NPV: 95.35%, AUC: 0.85) and TH (sensitivity: 97.4%, specificity: 52.5%, PPV: 52%, NPV: 95.35%, AUC: 0.78). When considering CD patients with concomitant CR, MH, and TH associated with an FC < 94 µg/g and CRP < 5 mg/L, this association was found identified in 33 patients (27.9%). Conclusion: An FC < 94 µg/g and a normal CRP are associated with CR, MH, and TH and could be included in the definition of DR in association. So by definition, DR could be achieved in approximately 30% of CD patients during maintenance treatment with biologics.

Incident Colorectal Cancer in Inflammatory Bowel Disease.

Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (≤40 years) in 25% of patients (median age 55.5 (22-76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn's disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn's Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with >40 years (p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients (p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1-68) vs. 14.5 (8-40); p = 0.85; IBD: 12 months (1-68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients.

Treatment-based risk stratification of infections in inflammatory bowel disease: A comparison between anti-tumor necrosis factor-α and nonbiological exposure in real-world setting.

BACKGROUND AND AIM: Infective issues about anti-tumor necrosis factor (TNF)-α agents in inflammatory bowel disease (IBD) remain controversial, especially when compared with nonbiological treatments. This study aimed to evaluate the incidence and prevalence of several infections in anti-TNF-α-exposed patients compared with nonbiological treatments. METHODS: All naïve IBD subjects treated with anti-TNF-α and matched nonbiologic-exposed patients were included. RESULTS: Among 3453 patients in the database, 288 anti-TNF-α-exposed subjects and 288 nonbiologic-exposed IBD controls met inclusion criteria. Fifty-eight infections (20.1%) occurred during anti-TNF-α treatment versus 23 (8%) in the matched group (odds ratio [OR] 2.9, P < 0.001) (incidence 5.72 vs 0.96/100 patient-years, incidence ratio [IR] 6, P < 0.001). IR was higher for anti-TNF-α versus mesalamine/sulfasalazine (IR 40.8, P < 0.001), similar to azathioprine/6-mercaptopurine/methotrexate (IR 0.78, P = 0.32) and lower than corticosteroids (IR 0.05, P < 0.001). The incidence rate of serious infections was 1.3 in the anti-TNF-α-exposed versus 0.38/100 patient-years in nonexposed subjects (IR 3.44, P = 0.002), without significant difference between anti-TNF-α and azathioprine/6-mercaptopurine/methotrexate (1.3 vs 3.03/100 patient-years, IR 0.43, P = 0.1). Predictors of infections in anti-TNF-α-exposed patients were concomitant use of systemic steroids (OR 1.9, P = 0.02) or azathioprine (OR 2.6, P = 0.01) and a body mass index < 18.5 at time of infection (OR 2.2, P = 0.01). CONCLUSIONS: The risk of developing infections during anti-TNF-α therapy remains high, although not dissimilar to that found for other immunosuppressants, while concomitant immunosuppression and malnutrition appear the most important causes of infection.

The impact of a dedicated contact centre on the clinical outcome of patients with inflammatory bowel disease during the COVID-19 outbreak.

BACKGROUND: With the interruption of elective activity during the coronavirus disease 2019 (COVID-19) pandemic, a reorganisation of health care for patients with inflammatory bowel disease (IBD) was warranted. We aimed to investigate the effectiveness of a dedicated contact centre service (CCS) on the reorganization of a high-volume IBD centre and on the continuity of care during the COVID-19 outbreak. METHODS: We compared the CCS services provided to 3680 IBD patients and clinical outcomes before (January-February 2020) and during (March-April 2020) the COVID-19 period. We further included, as comparator, data from March to April of the previous year (2019). RESULTS: During the outbreak, the CCS received an increase of 10.2% of contacts, from 881, in January-February 2020, to 971 (p = 0.02). An increase of 6% in CCS activities was also reported in comparison with March-April 2019 (from 914 to 971 in March-April 2020, p = 0.71). Before COVID-19, in both periods most contacts (67% in January-February 2020 and 60% in March-April 2019) required information about clinical activity, while fewer (33% in January-February 2020 and 40% in March-April 2019) requested logistic information. During the pandemic, most contacts (65.1%) asked to speak with a physician, 23.7% asked for information, while 11.1% wanted to cancel/postpone their appointments. Among all the information, 66% concerned COVID-19. In March-April 2020, 259 outpatient visits were booked, but were all replaced by phone consultations. No difference was detected in the number of intravenous biological administrations (307 versus 296, p = 0.64), surgeries (10 versus 9, p = 0.82) and urgent hospitalisations (10 versus 12, p = 0.67) before and during the COVID-19. CONCLUSION: The CCS was an effective tool in the reorganization of the IBD centre. Scheduled visits were replaced by phone calls. The main clinical outcomes were maintained in the COVID-19 period. Virtual follow-up using the CCS could be implemented after the pandemic to optimise the resources of the IBD centre.

Cancer Risk in Inflammatory Bowel Disease: A 6-Year Prospective Multicenter Nested Case-Control IG-IBD Study.

BACKGROUND: In a 6-year, multicenter, prospective nested case-control study, we aimed to evaluate risk factors for incident cancer in inflammatory bowel disease (IBD), when considering clinical characteristics of IBD and immunomodulator use. The secondary end point was to provide characterization of incident cancer types. METHODS: All incident cases of cancer occurring in IBD patients from December 2011-2017 were prospectively recorded in 16 Italian Group for the Study of Inflammatory Bowel Disease units. Each of the IBD patients with a new diagnosis of cancer was matched with 2 IBD patients without cancer, according to IBD phenotype (ulcerative colitis [UC] vs Crohn's disease [CD]), age (±5 years), sex. Risk factors were assessed by multivariate logistic regression analysis. RESULTS: Cancer occurred in 403 IBD patients: 204 CD (CD cases), 199 UC (UC cases). The study population included 1209 patients (403 IBD cases, 806 IBD controls). Cancer (n = 403) more frequently involved the digestive system (DS; 32%), followed by skin (14.9%), urinary tract (9.7%), lung (6.9%), genital tract (6.5%), breast (5.5%), thyroid (1.9%), lymphoma (2.7%, only in CD), adenocarcinoma of the small bowel (SBA; 3.9%, 15 CD, 1 pouch in UC), other cancers (15.9%). Among cancers of the DS, colorectal cancer (CRC) more frequently occurred in UC (29% vs 17%; P < 0.005), whereas SBA more frequently occurred in CD (13% vs 6.3% P = 0.039). In CD, perforating (B3) vs non-stricturing non-perforating (B1) behavior represented the only risk factor for any cancer (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.33-4.11). In CD, risk factors for extracolonic cancer (ECC) were a B3 vs B1 and a stricturing (B2) vs B1 behavior (OR, 2.95; 95% CI, 1.62-5.43; OR, 1.79; 95% CI, 1.09-2.98). In UC, risk factors for ECC and for overall cancer were abdominal surgery for UC (OR, 4.63; 95% CI, 2.62-8.42; OR, 3.34; 95% CI, 1.88-5.92) and extensive vs distal UC (OR, 1.73; 95% CI, 1.10-2.75; OR, 1.99; 95% CI, 1.16-3.47). Another risk factor for ECC was left-sided vs distal UC (OR, 1.68; 95% CI, 1.00-2.86). Inflammatory bowel disease duration was a risk factor for skin and urinary tract cancers. CONCLUSIONS: Perforating CD, extensive UC, and abdominal surgery for UC were identified as risk factors for overall incident cancer and for ECC. The clinical characteristics associated with severe IBD may increase cancer risk.

Real-Life Effectiveness and Safety of Golimumab and Its Predictors of Response in Patients with Ulcerative Colitis.

BACKGROUND: Golimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis. AIMS: To assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response. METHODS: Consecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system. RESULTS: A total of 196 patients were included. After 3 months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p < 0.001). Multivariate analysis revealed that a higher total Mayo score (p < 0.001, OR 1.5, 95% CI 1.2-1.8) and naïve status to anti-TNF-alpha (p = 0.015, OR 3.0, 95% CI 1.2-7.5) were predictive of a favorable response. Seventy-seven (39.3%) of the 130 responders maintained a response at month 12 of therapy. There were 17 adverse events, 28 patients needed hospitalization, and 15 patients underwent surgery. Self-administration of the drug was appreciated by most patients. CONCLUSIONS: The efficacy and safety of golimumab in daily clinical practice were confirmed for the short- and long-term treatment of patients with active ulcerative colitis. Patients naïve to the anti-TNF-alpha monoclonal antibody and those with a higher total Mayo score were more likely to respond to golimumab.

Pathophysiology of non-celiac gluten sensitivity: where are we now?

Non-celiac gluten sensitivity (NCGS) is the term used to describe individuals complaining of intestinal and extra-intestinal symptoms related to gluten ingestion and rapidly improving after its withdrawal, and in which both celiac disease (CD) and wheat allergy (WA) were properly ruled out. The prevalence of this condition remains unknown and a lot of questions about the possible pathogenetic mechanisms are still unclarified. It is believed that NCGS represents a heterogeneous condition with different subgroups potentially characterized by different pathogenesis, clinical history, and clinical course. Moreover, a possible overlap with irritable bowel syndrome (IBS) and other functional diseases could complicate patient selection for clinical studies, slowing down the understanding of this disorder. Last but not least, the lack of validated biomarkers remains a significant limitation in research studies on NCGS. Hence, there is a need for strict diagnostic criteria for NCGS.

The burden of anaemia in patients with inflammatory bowel diseases.

BACKGROUND: Anaemia (AN) is frequently associated with inflammatory bowel diseases (IBD) and can negatively influence the quality of life of patients. AIM: To evaluate the prevalence and causes of AN in IBD. METHODS: We prospectively performed a one-year multicentre observational study including all IBD cases attending six Units. We also investigated patients' main serological parameters. RESULTS: The study population included 965 IBD patients (582 CD; 383 UC), of whom 142 were in-patients and 823 out-patients. AN was diagnosed in 134 out of 965 IBD patients (14%). No significant difference in AN prevalence was observed between CD and UC. The prevalence of AN was higher in the hospitalized IBD (26% in- vs. 11.7% out-patients; p<0.01; OR 2.2) and in active disease (CD: 34% active vs. 16% inactive; p<0.01; OR 2.1 - UC: 26% active vs. 19% inactive; p=0.03; OR 1.3). Iron deficiency was present in 72 patients (53.7%), AN of chronic diseases in 12 (8.2%), mixed type AN in 11 (8.2%), thalassemia in 9 (6.7%), and macrocytic AN in 8 (5.9%). CONCLUSIONS: In Southern Italy, AN is common in IBD and is more frequent in active disease and hospitalized patients. Iron deficiency still remains the major cause of AN in IBD.

Fatigue in inflammatory bowel diseases: relationship with age and disease activity.

A higher rate of patients suffering from inflammatory bowel diseases (IBD) are reported to experience the symptom of fatigue compared with general population. Fatigue can impair quality of life of IBD patients by limiting their daily functioning. However, this problem is poorly understood and addressed. Our aim was to investigate the impact of fatigue in IBD patients compared with controls, and to seek for relation between age and disease activity. IBD patients aged between 16 and 75 years observed at our Unit from June 2011 through June 2012 were evaluated for fatigue. Patients were asked to fill the fatigue impact scale (FIS) questionnaire. A cohort of age- and sex-matched patients observed for other-than-IBD diseases were prospectively enrolled to act as controls. Patients diagnosed with malignancies were excluded from evaluation. Each group included 16 patients, of whom half aged over 65 years. Fatigue was more severe in IBD patients than in controls (p = 0.02), irrespective of age and disease activity. IBD patients with moderate to severe disease activity showed worse fatigue compared with controls at any age (p < 0.0001). Young IBD patients with low disease activity showed a trend toward worse FIS score when compared with old IBD counterparts (p = 0.06). IBD significantly impacted on fatigue in our series. Considering IBD patients in remission, younger patients may experience worse fatigue. Further studies are needed to explore the effects of fatigue on quality of life and the potential of appropriate intervention strategies.

Relatives of Crohn's disease patients and breast cancer: an overlooked condition.

Recent data suggest that patients suffering from Crohn's disease (CD) may be at higher risk of developing extra-intestinal malignancies. This is attributed to inflammation and immunodepression due to medications. However, a genetic predisposition cannot ruled out. In the present study we investigated the prevalence of breast cancer in first-degree female relatives of CD patients compared with relatives of patients without evidence of gastrointestinal diseases. A total of 1302 female first-degree relatives of CD patients and 1294 relatives of controls were included. We found that CD was an independent risk factor for breast cancer development (OR = 2.76, 95% CI = 1.2-6.2; p = 0.017), and this is particularly evident in mothers (3.6% vs 1%, p = 0.009 - OR = 3.7, 95% CI 1.4-10). Among CD group, smoking habit of CD patients was associated with increased risk of cancer compared with relatives of non-smokers (7.7% vs 2.9%, p = 0.01 - OR = 2.8 95% CI 1.2-6.6). Intriguingly, stage at diagnosis was significantly higher in CD relatives (p = 0.04). Our findings suggest that first-degree female relatives of CD patients are at higher risk of developing breast cancer but receive diagnosis at more advanced stages, therefore advocating the need of more active screening protocol in this population.