Noninvasive Assessment of Postoperative Disease Recurrence in Crohn's Disease: A Multicenter, Prospective Cohort Study on Behalf of the Italian Group for Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopy (CS) is the gold standard to assess postoperative recurrence (POR) in Crohn's disease (CD). However, CS is invasive and may be poorly tolerated by patients. The aim of this study was to prospectively assess the diagnostic accuracy of a noninvasive approach in detecting POR, using the endoscopic Rutgeerts' score (RS) as the reference standard. METHODS: Consecutive patients with CD who underwent ileo-cecal resection were prospectively enrolled in 3 referral Italian centers. Patients underwent CS and bowel ultrasound within 1 year of surgery. Uni- and multivariable analyses were used to assess the correlation between noninvasive parameters and endoscopic recurrence, defined by a RS ≥2. RESULTS: Ninety-one patients were enrolled. Sixty patients (66%) experienced endoscopic POR. The multivariable analysis identified bowel wall thickness (BWT) per 1-mm increase (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.21-4.89; P = .012), the presence of mesenteric lymph nodes (OR, 15.63; 95% CI, 1.48-164.54; P = .022), and fecal calprotectin (FC) values ≥50 mcg/g (OR, 8.58; 95% CI, 2.45-29.99; P < .001) as independent predictors for endoscopic recurrence. The presence of lymph nodes or the combination of BWT ≥3 mm and FC values ≥50 mcg/g correctly classified 56% and 75% of patients, with less than 5% of patients falsely classified as having endoscopic recurrence. Conversely, the combination of BWT <3 mm and FC <50 mcg/g correctly classified 74% of patients with only 4.5% of patients falsely classified as not having endoscopic recurrence. CONCLUSIONS: A noninvasive approach combining bowel ultrasound and FC can be used with confidence for detecting POR in patients with CD without the requirement for CS.

Incidence and Patterns of COVID-19 Among Inflammatory Bowel Disease Patients From the Nancy and Milan Cohorts.

The first cases of COVID-19 infection were reported in December, 2019, in Wuhan, China. Italy (in particular Lombardy) and France (in particular Northeast) have been gravely hit. Both physicians and inflammatory bowel disease (IBD) patients are deeply concerned that immunosuppressants or biologics may increase the risk of COVID-19 infection. IOIBD has put in place an international registry, SECURE-IBD, for tracking all the cases with IBDs infected by COVID-19 (SECURE-IBD registry: http://www.covidibd.org). It will describe the outcomes of infected patients and the association between IBD-related medications and these outcomes.

Maintaining the Quality Standards of Care for Inflammatory Bowel Disease Patients During the COVID-19 Pandemic.

Since February 20, 2020, the SARS-COV2 infection has spread in Lombardy, and in the rest of the Italian regions, forcing our government to impose a national lockdown.1 Hospitals have been forced to adapt and to restructure their units to cope with this urgent new critical situation.2 Alternative solutions have been found to manage patients with inflammatory bowel disease (IBD), including remote monitoring, drug home delivery, limitations for infusion units, and patient education on measures to prevent infection,3 to maintain high-quality care.4.

Absence of COVID-19 Infection in Patients Accessing IBD Unit at Humanitas, Milan: Implications for Postlockdown Measures.

INTRODUCTION: The risk of coronavirus disease-19 infection for healthcare professionals and patients in hospitals remains unclear. METHODS: We investigated whether precautions adopted in our inflammatory bowel disease (IBD) unit have minimized the risks of infection for all patients accessing our facilities in a 1-month period by assessing the rate of coronavirus disease-19 infection in the follow-up period. RESULTS: Three hundred-twenty patients with IBD were included. None were infected from severe acute respiratory syndrome-coronavirus 2 in the follow-up period. None of the IBD team members were infected. DISCUSSION: Neither pharmacological immunosuppression nor access to the hospital seem to be risk factors for infection in patients with IBD.

A prospective study evaluating IOP changes after switching from a therapy with prostaglandin eye drops containing preservatives to nonpreserved tafluprost in glaucoma patients.

PURPOSE: To compare the ocular hypotensive effect of tafluprost with prostaglandin analogues (PGAs) in glaucoma patients. METHODS: 89 primary open-angle glaucoma patients treated with bimatoprost, latanoprost, or travoprost for at least 3 months complaining for ocular discomfort were switched to tafluprost. IOP was assessed at baseline and 3 months after switching the therapy by daily curve. Primary outcome was to compare the mean daily IOP of tafluprost with PGAs. RESULTS: The mean daily IOP was 16 ± 2.1 and 16.6 ± 2.0 mm Hg at baseline and after switching to tafluprost, respectively (P > 0.05). When analysis was carried out between tafluprost and each previous PGAs, the comparison between latanoprost and tafluprost and travoprost and tafluprost did not show any statistically significant difference in mean daily IOP and at each time point. The comparison between bimatoprost and tafluprost showed a statistically significant difference in mean daily IOP (P < 0.05) and at each time point (P < 0.05). CONCLUSIONS: After 3 months of switching tafluprost showed an overall IOP lowering effect similar to others PGAs. When each PGA was compared with tafluprost, bimatoprost showed to provide a statistically significant additional IOP lowering effect.

New Paradigms to Help Decisions in Treatment Choice: Head to Head Trial of Biological Therapies in Inflammatory Bowel Diseases.

The increasing armamentarium of drugs for inflammatory bowel disease (IBD) requires a direct comparison of different therapeutic options in order to guide physicians in the choice of the most appropriate treatment for their patients. Head-to-head trials, considered the gold standard in comparative research in IBD, allow to compare different therapies in the same population and setting, but also to evaluate different treatment strategies. Although head-to-head trials including biologics and immunosuppressive therapy in IBD have been performed decades ago, the interest in these direct comparisons is growing since the publication of the first randomized controlled trial directly comparing biologic agents with different molecular targets. This review provides an overview of the past and current IBD head-to-head trials, considering their respective strengths and limitations in a real-life setting.

TL1A: A New Potential Target in the Treatment of Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory diseases of the gastrointestinal tract. In the last few years, the development of biological agents targeting cytokines and receptors involved in IBD pathogenesis has led to better outcomes and has improved the course of the disease. Despite their effectiveness, drugs such as tumor necrosis factor (TNF) inhibitors, anti-Interleukin-12/23 and anti-integrins, do not induce a response in about one-third of patients, and 40% of patients lose response over time. Therefore, more efficient therapies are required. Recent studies showed that TL1A (Tumor necrosis factor-like cytokine 1A) acts as a regulator of mucosal immunity and participates in immunological pathways involved in the IBD pathogenesis. In this review article, we analyze the role of TL1A as a new potential target therapy in IBD patients.

Rediscovering histology: what is new in endoscopy for inflammatory bowel disease?

The potential of endoscopic evaluation in the management of inflammatory bowel diseases (IBD) has undoubtedly grown over the last few years. When dealing with IBD patients, histological remission (HR) is now considered a desirable target along with symptomatic and endoscopic remission, due to its association with better long-term outcomes. Consequently, the ability of endoscopic techniques to reflect microscopic findings in vivo without having to collect biopsies has become of upmost importance. In this context, a more accurate evaluation of inflammatory disease activity and the detection of dysplasia represent two mainstay targets for IBD endoscopists. New diagnostic technologies have been developed, such as dye-less chromoendoscopy, endomicroscopy, and molecular imaging, but their real incorporation in daily practice is not yet well defined. Although dye-chromoendoscopy is still recommended as the gold standard approach in dysplasia surveillance, recent research questioned the superiority of this technique over new advanced dye-less modalities [narrow band imaging (NBI), Fuji intelligent color enhancement (FICE), i-scan, blue light imaging (BLI) and linked color imaging (LCI)]. The endoscopic armamentarium might also be enriched by new video capsule endoscopy for monitoring disease activity, and high expectations are placed on the application of artificial intelligence (AI) systems to reduce operator-subjectivity and inter-observer variability. The goal of this review is to provide an updated insight on contemporary knowledge regarding new endoscopic techniques and devices, with special focus on their role in the assessment of disease activity and colorectal cancer surveillance.

Application of Ultrasound Elastography for Assessing Intestinal Fibrosis in Inflammatory Bowel Disease: Fiction or Reality?

BACKGROUND: Intestinal fibrosis and subsequent strictures represent an important burden in inflammatory bowel disease (IBD). Both the detection and evaluation of the degree of fibrosis in stricturing Crohn's disease (CD) are important when deciding the best therapeutic strategy (medical anti-inflammatory therapy, endoscopic dilation, surgery). Ultrasound elastography (USE) is a non-invasive technique that has been proposed in the field of IBD for evaluating intestinal stiffness as a biomarker of intestinal fibrosis. OBJECTIVE: The aim of this review is to discuss the ability and current role of ultrasound elastography in the assessment of intestinal fibrosis. RESULTS AND CONCLUSION: Data on USE in IBD are provided by pilot and proof-of-concept studies with small sample size. The first type of USE investigated was strain elastography, while shear wave elastography has been introduced recently. Despite the heterogeneity of the methods of the studies, USE has been proven to be able to assess intestinal fibrosis in patients with stricturing CD. However, before introducing this technique in current practice, further studies with larger sample sizes are needed. In addition, the use of homogeneous parameters, the assessment of reproducibility, and the identification of validated cut-off values are essential.

Is there a role for therapeutic sphingolipids in inflammatory bowel disease?

Introduction: Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are lifetime chronic inflammatory disorders. Over the past few decades, new therapeutic approaches, including early and more effective intervention with immunomodulators and biological agents, increased the possibility of a favorable modification of the natural history of IBD. Despite this progress, there is still a need to explore new therapeutic options.Area covered: Here, we review the literature about the role of therapeutic sphingolipids in inflammatory bowel disease patients.Expert opinion: Despite the great increase of treatment options in the last 20 years, many patients still do not respond to the induction therapy (primary non-responders) or lose response over time (secondary responders). Small-molecule drugs are a promising group of drugs with low molecular weight, an oral route of administration, and low immunogenicity offering several advantages when compared to biologics such as anti-TNFs and anti-integrins. Sphingosine-1-phosphate (S1P) receptor modulators are some among the new small molecules currently under clinical investigation for the treatment of IBD.

Targeting the gut layers in Crohn's disease: mucosal or transmural healing?

INTRODUCTION: Although the landmark of Crohn's Disease (CD) is the transmural inflammation, mucosal healing (MH), which is assessed by colonoscopy, is currently the gold standard of CD management. Transmural healing (TH) is a new concept evaluated by cross-sectional imaging (CSI) techniques, such as bowel ultrasound (US), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). Little is known about the clinical significance of persisting mural disease and the predictive value of complete TH. AREAS COVERED: The authors reviewed the available literature on TH and its meaning as predictor of long-term outcomes in CD, to explore if TH may be a better target compared to MH in CD patients, in terms of disease outcome, such as medication changes, hospitalization, or surgery. EXPERT OPINION: Some evidence suggests that achieving TH has a predictive value in CD management and correlates with better disease outcome than MH, although existing studies are few and with limitations. A definitive definition of TH is not yet established and the frequency or the preferred modality of TH evaluation remains unclear. Implementing TH in treat-to-target approach may enable stricter disease monitoring with noninvasive methods and finally change the disease course, preventing irreversible bowel damage.

Modulation of sphingosine-1-phosphate in ulcerative colitis.

Introduction: Sphingosine-1-phosphate (S1P) is a membrane-derived lysophospholipid signaling molecule implicated in various physiological and pathological processes, such as regulation of the immune, cardiovascular, pulmonary, and nervous systems and theoretical cancer-related risks, through extracellular activation of S1P1-5 receptors.Areas covered: S1P receptor agonism is a novel strategy for the treatment of UC targeting lymphocyte recirculation, through blockade of lymphocyte egress from lymph nodes. We conducted an extensive literature review on PUBMED on currently available data on molecular aspects of S1P modulation, the mechanisms of action of S1PR agonists (fingolimod, ozanimod, etrasimod, and KRP-203), and their potential efficacy and safety for the treatment of patients with ulcerative colitis.Expert opinion: Selective S1P modulators have emerged to enlarge the efficacy and safety profile of this class of agents. Phase 3 programs should add the potential body of evidence to prove their benefit for the management of UC patients.

PK, PD, and interactions: the new scenario with JAK inhibitors and S1P receptor modulators, two classes of small molecule drugs, in IBD.

INTRODUCTION: Inflammatory bowel diseases (IBDs) are immune-mediated chronic inflammatory disorders of the gastrointestinal tract whose pathogenesis is not yet fully understood. Despite the advent of biological agents, there are still unmet needs for IBD patients, due to suboptimal rate of sustained remission achieved. Small molecule drugs (SMDs), the next generation of selective drugs in IBD, show promising results in ongoing trials. AREAS COVERED: We describe the pharmacodynamics and pharmacokinetic features of novel SMDs and their main differences with biologic agents. EXPERT OPINION: Small molecule drugs are a promising class of drugs for the treatment of ulcerative colitis and Crohn's disease with good results in inducing and maintaining remission. Hence, over the next few years physicians will have numerous options of small molecule drugs for the treatment of patients with IBD. This group of drugs are potentially easier to use over biological agents due to pharmacokinetic features such as oral administration, short half-life, high volume of distribution, and lack of immunogenicity. On the other hand, drug-drug interactions can happen with small-molecule drugs, principally due to competitive metabolic and clearance mechanisms.

Inflammatory Bowel Disease Care in the COVID-19 Pandemic Era: The Humanitas, Milan, Experience.

The outbreak of the COVID-19 caused by coronavirus SARS-CoV2, is rapidly spreading worldwide. This is the first pandemic caused by a coronavirus in history. More than 150 000 confirmed cases worldwide are reported involving the SARS-CoV2, with more than 5000 COVID-19-related deaths on March 14, 2020. Fever, chills, cough, shortness of breath, generalised myalgia, malaise, drowsiness, diarrhoea, confusion, dyspnoea, and bilateral interstitial pneumonia are the common symptoms. No therapies are available, and the only way to contain the virus spread is to regularly and thoroughly clean one's hands with an alcohol-based hand rub or wash them with soap and water, to maintain at least 1 m [3 feet] distance from anyone who is coughing or sneezing, to avoid touching eyes, nose, and mouth, and to stay home if one feels unwell. No data are available on the risk of COVID-19 and outcomes in inflammatory bowel disease [IBD] patients. Outbreak restrictions can impact on the IBD care. We aim to give a viewpoint on how operationally to manage IBD patients and ensure quality of care in the current pandemic era.

Validation of the Red Flags Index for Early Diagnosis of Crohn's Disease: A Prospective Observational IG-IBD Study Among General Practitioners.

INTRODUCTION: Diagnostic delay >12 months is frequent in Crohn's disease [CD]. Recently, the International Organization for Inflammatory Bowel Disease [IO-IBD] developed a tool to identify early CD and reduce diagnostic delay. Subjects with an index ≥8 are more likely to have suspected CD (odds ratio [OR] 205, p <0.0001). We aimed to validate this questionnaire at the community level in patients seen by the general practitioners [GPs] in two large areas of Lombardy, Italy. METHODS: Consecutive adult patients referring to the GP were screened. The GPs administered the Red Flags [RF] questionnaire to the eligible patients. All patients were referred to the nearest participating centre to confirm or exclude the diagnosis of CD. Sensitivity, specificity, and positive and negative predictive values [PPV, NPV] of the RF index [RFI] were calculated. Patients lost to follow-up after the first gastroenterological visit were analysed using a non-responder imputation, assuming they were negative for CD diagnosis. RESULTS: From November 2016 to November 2019, 112 patients were included. A total of 66 subjects [59%] completed the study after the first gastroenterological visit. The prevalence of CD was 3.6% in the study population [4/112]. The RF index had 50% sensitivity, 58% specificity, 4% PPV, and 97% NPV. A combined diagnostic strategy with faecal calprotectin [FC] [RFI ≥8 and/or FC >250 ng/g] resulted in significantly improved accuracy: sensitivity 100% [29-100%], specificity 72% [55-85%], PPV = 21% [5-51%], NPV = 100% [88-100%]. CONCLUSIONS: The RF Index combined with FC is a valid tool to identify patients with high probability of having CD at early stage.

Endoscopy after surgery in inflammatory bowel disease: Crohn's disease recurrence and pouch surveillance.

INTRODUCTION: Crohn's disease (CD) and ulcerative colitis (UC) are immune-mediated disorders characterized by a chronic inflammation, with intermittent exacerbations of symptoms and inflammation. In both diseases, medical treatment has made revolutionary steps forward. Nevertheless, surgery is still required in many cases due to inefficacy of multiple medical therapies. It is not clear whether surgery rates in inflammatory bowel diseases (IBD) are currently decreasing despite all improvements. AREAS COVERED: Multidisciplinary management is critical in surgical patients to improve long-term outcomes. Endoscopy plays a crucial role, both before and after surgery, in planning therapeutic strategies and stratifying risk of recurrence. Aim of this review is to provide a deeper insight into the central role of endoscopy in the postoperative management of IBD patients, focusing on recent research advances, future challenges and unresolved questions. EXPERT OPINION: Both UC and CD surgical patients need endoscopy to define the correct therapeutic choice, predict subsequent disease course and adopt the correct surveillance strategy. In the next future, newer endoscopic techniques could be systematically applied in IBD patients after surgery, to assess early postoperative inflammation, response to treatment, or, regarding UC, to provide enhanced pouch surveillance, allowing for early detection of inflammation and dysplasia.

SFED recommendations for IBD endoscopy during COVID-19 pandemic: Italian and French experience.

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has required a complete change in the management of patients with inflammatory bowel disease (IBD) who need to undergo endoscopic procedures. Several preventive measures must be taken to avoid the spread of infection among health-care professionals and patients with IBD, including the use of personal protective equipment, greater attention to endoscopic room hygiene and rescheduling of non-urgent procedures. This Perspective aims to provide a guide based on the Italian and French experience to better face the difficulties encountered by endoscopists during this global health emergency. In particular, recommendations regarding the use of personal protective equipment to prevent COVID-19 transmission, both for patients and health-care professionals, are proposed and different scenarios in endoscopic IBD management are evaluated to suggest when endoscopy could be rescheduled and replaced by alternative biomarkers.

Multidisciplinary management of the nocebo effect in biosimilar-treated IBD patients: Results of a workshop from the NOCE-BIO consensus group.

The high cost of biological drugs for patients with inflammatory bowel disease (IBD) considerably impacts on health-care budgets. Since the patent of biological products expired, cheaper biosimilars have entered the market. Available data coming from real-world cohorts and clinical trials indicate that the efficacy and safety of biosimilars is comparable to that of the originator drugs. Treating IBD patients with a biosimilar may be complicated by the risk of the nocebo effect, a negative effect of a pharmacological or non-pharmacological treatment, induced by patients's expectations and unrelated to the physiological action of the treatment. The nocebo effect can negatively affect treatment outcomes and hamper the cost-savings of biosimilars. Reducing the nocebo effect requires a multidisciplinary effort of all health-care providers in charge of biosimilar-treated IBD patients. The aim of the review is to reflect the key messages of an international workshop on this topic, including viewpoints from the perspective of physicians, nurses, psychologists, pharmacists and patients.

Quality of Care Standards in Inflammatory Bowel Diseases: a European Crohn's and Colitis Organisation [ECCO] Position Paper.

The management of inflammatory bowel disease [IBD] is complex, and requires tight control of disease activity, close monitoring to avoid treatment side effects, health care professionals with expertise in IBD, and an interdisciplinary, holistic approach. Despite various efforts to standardise structures, processes, and outcomes,1-8 and due to the high variability at the local, national, and international levels, there are still no clear definitions or outcome measures available to establish quality of care standards for IBD patients which are applicable in all contexts and all countries. For this reason, the European Crohn's and Colitis Organisation [ECCO] supported the construction of a list of criteria summarising current standards of care in IBD. The list comprises 111 quality standard points grouped into three main domains [structure n = 31, process n = 42, outcomes n = 38] and is based on scientific evidence, interdisciplinary expert consensus, and patient-oriented perspectives. The list of proposed criteria is intended to represent the position of ECCO regarding the optimum quality of care that should be available to patients. Since health care systems and regulations vary considerably between countries, this list may require adaptation at local and national levels. It is recognised that not all these criteria that have been identified as optimal will be available in every unit. However, ECCO will continue its efforts to develop and coordinate projects and initiatives that will help to guarantee optimal quality of care for all IBD patients.

Anti-fibrotic Drugs for Crohn's Disease: Ready for Prime Time?

Intestinal fibrosis, driven by chronic inflammation in Crohn's disease, can be defined as an excessive accumulation of extracellular matrix in the affected gut segment ultimately leading to an impaired wound healing and cumulative tissue damage, possibly resulting in organ dysfunction, formation of stenotic lesions and necessity of surgical intervention. Despite continuous advances in developing novel treatment modalities targeting different pathways to control chronic gut inflammation in CD, no effective anti-fibrotic agents have been released, to date. Thus, a better understanding of the molecular and cellular mechanisms underlying intestinal fibrosis is key to move this area of investigation forward.