Era Of Biology Research Articles

Temporary Faecal Diversion for Refractory Perianal and/or Distal Colonic Crohn's Disease in the Biologic Era: An Updated Systematic Review with Meta-analysis.

We evaluated short- and long-term outcomes of temporary faecal diversion [FD] for management of refractory Crohn's disease [CD], focusing on outcomes in the biologic era. Through a systematic literature review until March 15, 2023, we identified 33 studies [19 conducted in the biologic era] that evaluated 1578 patients with perianal and/or distal colonic CD who underwent temporary FD [with intent of restoring bowel continuity] and reported long-term outcomes [primary outcome: successful restoration of bowel continuity, defined as remaining ostomy-free after reconnection at a minimum of 6 months after diversion or at the end of follow-up]. We calculated pooled rates (with 95% confidence interval [CI]) using random effects meta-analysis, and examined factors associated with successful restoration of bowel continuity. Overall, 61% patients [95% CI, 52-68%; 50% in biologic era] experienced clinical improvement after FD. Stoma takedown was attempted in 34% patients [28-41%; 37% in biologic era], 6-18 months after diversion. Among patients where bowel restoration was attempted, 63% patients [54-71%] had successful restoration of bowel continuity, and 26% [20-34%] required re-diversion. Overall, 21% patients [17-27%; 24% in biologic era] who underwent FD were successfully restored; 34% patients [30-39%; 31% in biologic era] required proctectomy with permanent ostomy. On meta-regression, post-diversion biologic use and absence of proctitis was associated with successful bowel restoration after temporary FD in contemporary studies. In the biologic era, temporary FD for refractory perianal and/or distal colonic CD improves symptoms in half the patients, and bowel continuity can be successfully restored in a quarter of patients.

Dynamic In Silico Model of Type 2 Diabetes Treated With Metformin Combined With Exercise: A Sobol Sensitivity Analysis

Background: The widespread adoption of a sedentary lifestyle characterized by the consumption of a high-energy diet combined with a lack of physical activity has resulted in a rise in the prevalence of metabolic disorders like type 2 diabetes (T2D) globally. The data published by the International Diabetes Federation (IDF) every year catches the attention of the world. Insulin resistance results in the dysregulation of the control mechanism that leads to T2D. In addition to metformin as a globally prescribed drug, physical exercise is recommended for the treatment of T2D as an alternative therapy. In today’s systems biology era, sensitivity analysis plays a major role in providing deeper insights into the metabolic insulin signalling pathways (ISPs). Methods: Here, the complex in silico dynamic model of the effect of alternative therapies on T2D was examined. In order to obtain more quantitative information about the signal transduction network of the ISPs and their interaction, a global sensitivity analysis of the in silico model was carried out using the MATLAB tool. Results: This study sheds light on the effect of parameter perturbation on the ISP via GLUT4 translocation in T2D patients performing physical exercise and using metformin. It also allows for the selection of a variety of parameters for in vivo or in vitro studies in the future on the basis of the impact of parameter variations on each component of the pathway. Conclusion: The Sobol index for each condition was noted after introducing perturbations in the most sensitive parameters. These results can provide experimental guidance on how the variations in model inputs have affected the model outputs.

"Neuroimmunoendocrinology" in Children with Rheumatic Diseases: How Glucocorticoids Are the Orchestra Director.

The neural, the endocrine, and the immune systems are studied as distinct districts in physiological and pathological settings. However, these systems must be investigated with an integrative approach, while also considering that therapeutic agents, such as glucocorticoids, can induce a reversible or irreversible change of this homeostasis. Children and adolescents affected by rheumatic diseases frequently need treatment with corticosteroids, and the treatment must sometimes be continued for a long time. In the biological era, the treat-to-target strategy allowed a real revolution in treatment, with significant steroid dose sparing or, in many patients, steroid treatment withdrawal. In this review, the impact of glucocorticoids on endocrine, immune, and neurologic targets is analyzed, and the crosstalk between these systems is highlighted. In this narrative review, we explore the reasoning as to why glucocorticoids can disrupt this homeostasis, we summarize some of the key results supporting the impact of glucocorticoids treatment on endocrine, immune, and neurologic systems, and we discuss the data reported in the international literature.

Treatment strategy changes for inflammatory bowel diseases in biologic era: results from a multicenter cohort in Japan, Far East 1000

Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn’s disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation.

Proteomic Approach to Anemonia sulcata and Its Symbiont Symbiodinium spp. as New Source of Potential Biotechnological Applications and Climate Change Biomarkers.

Marine ecosystems are among the richest in terms of biodiversity, and at present, still remain largely unknown today. In the molecular biology era, several analyses have been conducted to unravel the biological processes in this ecosystem. These systems have provided biotechnological solutions to current problems, including the treatment of diseases, as well as for the development of new biotechnological tools with applications in biomedicine and/or agri-food. In addition, in the context of climate change and global warming, these studies become even more necessary for the development of molecular tools that allow a reliable follow-up of this situation to anticipate alterations and responses of bioindicator species and to create a database to prevent and predict the environmental and climatic changes before the damage is irreversible. Proteomics approaches have revealed their potential use to obtain the set of biological effectors that lead to the real biological station on a specific stage, the proteins. In addition, proteomics-based algorithms have allowed the discovery of proteins with new potential biotechnological applications from proteome data through "applied proteomics". In this project, the first proteome analysis of the sea anemone, Anemonia sulcata, and its symbiont has been developed. These organisms present a wide distribution sea ecosystem. In Spain, it is accepted as a fishing and aquaculture species. Moreover, Anemonia sulcate has a symbiotic relation with autotroph Dinoflagellates, Symbiodinium spp., that allows the study of its relation at the molecular level. For the first characterization of A. sulcata proteome, three independent biological replicates were used, and proteins were extracted and analyzed by LC-MS/MS, allowing the quantification of 325 proteins, 81 from Symbiodinium spp. proteins and 244 from A. sulcata proteins. These proteins were subjected to gene ontology categorization by Cellular Component, Molecular Function and Biological Process. These analyzes have allowed the identification of biomarkers of gene expression as potential powerful emerging diagnostic tools to identify and characterize the molecular drivers of climate change stresses and improve monitoring techniques. In addition, through the application of novel algorithms for the detection of bioactive compounds based on the analysis of molecules of marine origin, the proteome has allowed the identification of proteins with potential applications in the fields of biomedicine and agri-food.

Biomolecular NMR in the AI-assisted structural biology era: Old tricks and new opportunities

Over the last 40 years nuclear magnetic resonance (NMR) spectroscopy has established itself as one of the most versatile techniques for the characterization of biomolecules, especially proteins. Given the molecular size limitations of NMR together with recent advances in cryo-electron microscopy and artificial intelligence-assisted protein structure prediction, the bright future of NMR in structural biology has been put into question. In this mini review we argue the contrary. We discuss the unique opportunities solution NMR offers to the protein chemist that distinguish it from all other experimental or computational methods, and how it can benefit from machine learning.

E06 Does GGT level correlate with activity parameters in enthesitis-related arthritis?

Abstract Introduction Enthesitis-related arthritis (ERA) is one of the main subgroups of juvenile idiopathic arthritis. As in the adult population, monitoring of patients with ERA is based on clinical and laboratory evaluation. Some studies showed a correlation between Gamma-glutamyl transferase (GGT) levels and rheumatoid arthritis disease activity markers. Thus, we aimed to evaluate the correlation between GGT levels and ERA activity parameters. Methods This is a cross-sectional monocentric study including patients meeting the International League of Associations for Rheumatology (ILAR) 2001 criteria for ERA. We collected the demographic and clinical data. We assessed the ERA activity using clinical parameters including Patient Global Assessment (PGA), Visual Analogue Scale (VAS), Morning stiffness (MS), tender joint count (TJC), swollen joint count (SJC), active enthesitis count (AEC), clinical sacroiliitis, back mobility, and ocular involvement. We collected biological parameters such as the C-reactive protein (CRP) and the Erythrocyte sedimentation rate (ESR). We calculated the Juvenile spondyloarthritis disease activity (JSpADA). GGT level was measured on the same day. The correlation was evaluated using Spearman’s rho coefficient (r). r-value &amp;lt;0.3 was considered poor; between 0.3 and 0.39, moderate; between 0.4 and 0.69, strong; and &amp;gt;0.7 very strong. Results Thirty patients with a mean age of 15.1 ± 4.1 years, and a ratio-sex of 2.75 were included. The mean disease duration was 4.3 ± 3.2 years. The mean PGA and the mean VAS were 6.2 ± 7.1 and 8.9 ± 2.9 respectively. Mean TJC, mean SJC, and mean AEC were 1.53 ± 2.8, 0.18 ± 0.47, and 1.2 ± 1.6 respectively. Clinical sacroiliitis was found in eight patients, limited back mobility in six, and uveitis in three patients. The mean CRP and ESR were 15.1 ± 22.7 mg/l and 23.8 ± 21.2 mm, respectively. The mean JSpADA was 2.6 ± 1.7. Mean GGT was 14.3 ± 6.6 mg/l. A strong correlation was noted between the GGT level and both CRP (r = 0.504, P = 0.05) and ESR (r = 0.601, P = 0.01). However, no correlation was noted between GGT level and PGA (r = 0.107, P = 0.6), VAS (r = 0.03, P = 0.9), SJC (r = -0.17, P = 0.368), nor JSpADA (r = 0.323, P = 0.87). Conclusion Our results suggest a strong correlation between GGT level and biological ERA activity parameters, unlike clinical parameters and disease activity scores. More studies are needed to confirm these findings. Ethics The authors have no conflicts of interest to declare.

Risk of uterine cervical cancer in inflammatory bowel disease: a systematic review and meta-analysis

Background and aims There are limited data on the association between uterine cervical cancer (UCC) and inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC). Methods This systematic review and meta-analysis assessed the risk of UCC in patients with IBD. We searched MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, gray literature and conference proceedings for studies published before 21 January 2022. Two reviewers independently screened studies, extracted data and assessed quality using the Newcastle–Ottawa Scale. Subgroup analyses were based on IBD type, biologic era, immunosuppression status, study location and design, and publication status. Fifteen studies were included. Results The pooled relative risk (RR) of UCC in IBD was 1.34 (95% confidence interval [CI], 1.07–1.69; I 2 = 53.4%). In subgroup analyses, the pooled RRs of UCC in CD and UC were 1.18 (95% CI, 0.97–1.42) and 1.50 (95% CI, 1.01–12.21), respectively. The pooled RRs of UCC in pre-biologic and biologic eras were 1.36 (95% CI, 0.83–2.23) and 1.99 (95% CI, 1.03–3.86), respectively. The pooled RR of UCC in immunomodulator users was 2.18 (95% CI, 0.81–5.87). The pooled RRs of UCC in Asia, Europe and North America were 5.65 (95% CI, 2.65–12.07), 1.13 (95% CI, 0.96–1.34) and 1.38 (95% CI, 1.10–1.73), respectively. Conclusions The risk of UCC was significantly increased in IBD, particularly in UC but not in CD, suggesting that women with IBD should undergo regular UCC screening and consider vaccination.

Recent advances in in situ Notch signaling measurement.

Notch signaling is necessary for the development of many organ systems, including the nervous system, biliary system, and visual and auditory sensory systems. This signaling pathway is composed of DSL ligands and Notch receptors. Upon the interaction of those components between neighboring cells, the intracellular domain of the Notch receptor is cleaved from the cell membrane to act as a transcription factor. To date, many mechanistic insights, including lateral inhibition and lateral induction, have been proposed from observation of patterning morphogenesis and expression profiles of Notch signaling-associated molecules. The lack of a direct measurement method for Notch signaling, however, has impeded the examination of those mechanistic insights. In this mini-review, recent advances in the direct measurement of Notch signaling are introduced with a focus on the application of genetic modification of Notch receptors with the components of the Cre/loxP system and Gal4/UAS system. The combination of such conventional genetic techniques is opening a new era in Notch signaling biology by direct visualization of Notch "signaling" in addition to Notch signaling-associated molecules.

Managing psoriasis in HIV‐positive patients in the era of biologics

Managing psoriasis in <scp>HIV</scp>‐positive patients in the era of biologics

Factors Associated with Response to Systemic Corticosteroids in Active Ulcerative Colitis: Results from a Prospective, Multicenter Trial.

Among patients with ulcerative colitis, 30-50% receive corticosteroids within the first five years after diagnosis. We aimed to reconsider their effectiveness in the context of the biologic era. In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥ 4) were eligible if initiating systemic corticosteroids. The primary endpoint was clinical response (decrease in the Lichtiger score of ≥50%) at week 4. Secondary endpoints included combined response defined as clinical response and any reduction in elevated biomarkers (CRP and/or calprotectin). Steroid dependence was assessed after three months. A total of 103 patients were included. Clinical response was achieved by 73% of patients, and combined response by 68%. A total of 15% of patients were steroid-dependent. Activity of colitis did not influence short-term response to treatment but increased the risk for steroid dependence. Biologic-naïve patients responded better than biologic-experienced patients. Past smoking history (OR 5.38 [1.71, 20.1], p = 0.003), hemoglobin levels (OR 0.76 [0.57, 0.99] for higher levels, p = 0.045), and biologic experience (OR 3.30 [1.08, 10.6], p = 0.036) were independently associated with nonresponse. Disease activity was not associated with short-term response to systemic corticosteroids but was associated with steroid dependence in patients with active ulcerative colitis. Exposure to biologics negatively affects response rates.

What are the outcomes in patients referred to a tertiary referral centre for Crohn's rectovaginal fistula surgery?

Rectovaginal fistulas in patients with Crohn's disease are challenging to manage, and surgical treatment remains the best option for achieving permanent closure of the fistula. Biologicals are now used routinely for patients with Crohn's disease. The aim of this study was to investigate the surgical procedures used by us to treat rectovaginal fistula in patients with Crohn's disease in the era of biologicals. Patients with Crohn's disease who underwent surgery for a rectovaginal fistula between 2010 and 2020 were included in this retrospective study and were identified from a prospectively maintained institutional database. Collected variables included demographics, perioperative and operative variables and data regarding medications used. Success of the procedure was defined as no symptoms at least 6 months after definitive repair and/or stoma closure. Twenty patients (out of 80 referred for evaluation) underwent surgery with intent to close the fistula and had at least 6 months of follow-up. Mean age was 44 ± 12 years with a median follow-up duration of 33 months (range 6-130 months). Forty per cent of the patients had a history of at least two surgeries to close the fistula. The overall healing rate was 70% (14/20). The most performed procedure was a transanal rectal advancement flap (7/20), with a success rate of 85%. Rectovaginal fistula in Crohn's disease is difficult to cure; according to our results almost half of these patients have multiple surgeries due to recurrence. Multiple procedures may be offered for this challenging problem in motivated patients. Perioperative diversion should be strongly considered.

Protein structure and dynamics in the era of integrative structural biology

Proteins carry out their biological activity as dynamic structures and populate in solution or in biological membranes structural distributions with different degrees of heterogeneity. The central challenge in structural biology is to capture protein structural dynamics under equilibrium or kinetic conditions shifting from single, static pictures to movies of conformational ensembles. Ideally, this task should be pursued both in vitro and in vivo, under the influence of the native environment. The last decade has seen a tremendous development of biophysical methods for the investigation of protein structure and dynamics. However, each method has specific limitations and no single approach offers such a complex level of description. Nonetheless, the combination of experimental and computational, complementary methods is opening promising new avenues. Also the ambition of implementing structural studies on an “omic” scale is becoming more and more realistic. In spite of still major limitations, integrative structural biology is bringing dynamics into structural proteomics, with exciting perspectives for basic and applied sciences.

Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.

Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis. In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions. Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.

JAK Inhibition in Juvenile Idiopathic Arthritis (JIA): Better Understanding of a Promising Therapy for Refractory Cases.

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases with probably differential underlying physiopathology. Despite the revolutionary era of biologics, some patients remain difficult to treat because of disease severity, drug adverse events, drug allergy or association with severe comorbidities, i.e., uveitis, interstitial lung disease and macrophagic activation syndrome. Janus Kinase (JAK) inhibitors are small molecules that target JAK/Signal Transducers and Activators of Transcription (STAT) pathways, which could then prevent the activity of several proinflammatory cytokines. They may provide a useful alternative in these cases of JIA or in patients actually affected by Mendelian disorders mimicking JIA, such as type I interferonopathies with joint involvement, and might be the bridge for haematopoietic stem cell transplantation in these disabling conditions. As these treatments may have side effects that should not be ignored, ongoing and further controlled studies are still needed to provide data underlying long-term safety considerations in children and delineate subsets of JIA patients that will benefit from these promising treatments.

Declining Trends of Reoperations and Disease Behaviour Progression in Crohn's Disease over Different Therapeutic Eras-A Prospective, Population-Based Study from Western Hungary between 1977-2020, Data from the Veszprem Cohort.

Few population-based studies have investigated long-term surgery rates for Crohn's disease [CD]. Our aim was to analyse disease progression and surgery rates in a population-based cohort over different therapeutic eras, based on the time of diagnosis: cohort-A [1977-1995], cohort-B [1996-2008], and cohort-C [2009-2018]. A total of 946 incident CD patients were analysed (male/female: 496/450; median age at diagnosis: 28 years [y]; interquartile range [IQR]: 22-40]). Patient inclusion lasted between 1977 and 2018. Immunomodulators have become widespread in Hungary since the mid-1990s and biologic therapies since 2008. Patients were followed prospectively, with both in-hospital and outpatient records reviewed regularly. The probability of disease behaviour progression from inflammatory [B1] to stenosing or penetrating phenotype [B2/B3] significantly decreased (27.1 ± 5.3%/21.5 ± 2.5%/11.3 ± 2.2% in cohorts A/B/C, respectively, after 5 years; 44.3 ± 5.9%/30.6 ± 2.8%/16.1 ± 2.9% after 10 years, respectively; [pLogRank <0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3 ± 3.8%/26.5 ± 2.1%/28.1 ± 2.4%, respectively, after 5 years; 46.1 ± 4.1%/32.6 ± 2.2%/33.0 ± 2.7% after 10 years, respectively; and 59.1 ± 4.0%/41.4 ± 2.6% [cohorts A/B] after 20 years. There was a significant decrease in first resective surgery risk between cohorts A and B [plog rank = 0.002]; however, no further decrease between cohorts B and C [plog rank = 0.665]. The cumulative probability of re-resection in cohorts A/B/C was decreasing over time (17.3 ± 4.1%/12.6 ± 2.6%/4.7 ± 2.0%, respectively, after 5 years [plog rank = 0.001]). We report a continuous decline in reoperation rates and disease behaviour progression in CD over time, with the lowest values in the biologic era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era.

In Stanisław Lem's Orbit

In Stanisław Lem's Orbit

Novel Small Molecules in IBD: Current State and Future Perspectives.

Biologicals have dominated the therapeutic scenery in inflammatory bowel diseases (IBDs), namely ulcerative colitis (UC) and Crohn's disease (CD), for the past 20 years. The development of tofacitinib was the starting point for an era of small molecules after the era of biologicals. These new agents may challenge the use of biological agents in the future. They share properties that appeal to both patients and physicians. Low production costs, a lack of immunogenicity, and ease of use are only some of their benefits. On the other hand, patients and their physicians must manage the potential side effects of small molecules such as JAK inhibitors or S1P1R modulators. Here, we present agents that have already entered the clinical routine and those that are still being investigated in clinical trials.

Maximizing the benefits of using biosimilars in Egypt

BackgroundBiosimilars constitute a pathway for sustainable financing of healthcare systems in the era of expensive biologics. However, such a pathway is not free of challenges. Since the biosimilars market is expanding in Egypt, there is an urgent need for a policy framework to optimize their use and diffusion in the market. We aim to characterize a national framework based on the experiences of other countries and consultation with local experts.MethodsA narrative literature review was conducted to identify biosimilars’ policy elements worldwide. A workshop was organized with experts to discuss the narrative review findings and create consensus on recommendations.ResultsThe narrative literature review highlighted the need for biosimilar policy actions in four areas: market authorization, pricing, reimbursement, and uptake. Eighteen experts representing the Egyptian healthcare authorities attended the workshop. The most significant conclusions from the workshop included setting the price of the biosimilar at 30–40% less than its originator’s price and establishing financing protocols, in which the more expensive biologics with significant price premiums should be excluded from the formulary.ConclusionsA summarized national framework policy recommendation for biosimilars was created by local experts from the main public healthcare entities in Egypt. These recommendations coincide with the international policies adopted across different countries that aim to improve patient access while sustaining health expenditure.

Lack of Benefit for Early Escalation to Advanced Therapies in Ulcerative Colitis: Critical Appraisal of Current Evidence.

Although ulcerative colitis [UC] shares many common pathways and therapeutic options with Crohn's disease [CD], CD patients are four times more likely to undergo surgery 10 years into their disease in the biological era and are more likely to have extraintestinal manifestations than UC patients. Early treatment in CD has been demonstrated to modify the natural history of the disease and potentially delay surgery. Previous reviews on this topic have borrowed their evidence from CD to make UC-specific recommendations. This review highlights the emergence of UC-specific data from larger cohort studies and a comprehensive individual patient data systemic review and meta-analysis to critically appraise evidence on the utility of early escalation to advanced therapies with respect to short-, medium-, and long-term outcomes. In UC, the utility of the early escalation concept for the purposes of changing the natural history, including reducing colectomy and hospitalizations, is not supported by the available data. Data on targeting clinical, biochemical, endoscopic, and histological outcomes are needed to demonstrate that they are meaningful with regard to achieving reductions in hospitalization and surgery, improving quality of life, and minimizing disability. Analyses of different populations of UC patients, such as those with 'relapsing & remitting' disease or with severe or complicated disease course, are urgently needed. The costs and risk/benefit profile of some of the newer advanced therapies should be carefully considered. In this clinical landscape, it appears premature to advocate an indiscriminate 'one size fits all' approach to escalating to advanced therapies early during the course of UC.