VAC-Stent in the Treatment of Post-Esophagectomy Anastomotic Leaks: A New "Kid on the Block" Who Marries the Best of Old Techniques-A Review.

Esophagectomy, while a pivotal treatment for esophageal cancer, is not without adverse events. Among these, anastomotic leak (AL) is the most feared complication, threatening patient lives and incurring significant healthcare costs. The management of AL is complex and lacks standardization. Given the high morbidity and mortality rates associated with redo-surgery, which poses risks for already fragile patients, various endoscopic treatments have been developed over time. Self-expandable metallic stents (SEMSs) were the most widely used treatment until the early 2000s. The mechanism of action of SEMSs includes covering the wall defect, protecting it from secretions, and promoting healing. In 2010, endoscopic vacuum therapy (EVT) emerged as a viable alternative for treating ALs, quickly gaining acceptance in clinical practice. EVT involves placing a dedicated sponge under negative pressure inside or adjacent to the wall defect, aiming to clear the leak and promote granulation tissue formation. More recently, the VAC-Stent entered the scenario of endoscopic treatment of post-esophagectomy ALs. This device combines a fully covered SEMS with an integrated EVT sponge, blending the ability of SEMSs to exclude defects and maintain the patency of the esophageal lumen with the capacity of EVT to aspirate secretions and promote the formation of granulation tissue. Although the literature on this new device is not extensive, early results from the application of VAC-Stent have shown promising outcomes. This review aims to synthesize the preliminary efficacy and safety data on the device, thoroughly analyze its advantages over traditional techniques and disadvantages, explore areas for improvement, and propose future directions.

Attitudes, perceptions and barriers in implementing therapeutic drug monitoring for anti-TNFs in inflammatory bowel disease: a survey from the Middle East.

Background: A growing body of evidence underscores the beneficial impact of therapeutic drug monitoring (TDM) on the efficacy and cost-effectiveness of anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD). Objectives: We surveyed clinician attitudes, perceptions and barriers related to TDM in IBD in the Middle East. Design: A 15-question survey was distributed through national gastroenterological societies in five Middle Eastern countries (UAE, Saudi Arabia, Kuwait, Lebanon and Egypt). Methods: Data on clinician characteristics, demographics, utilization patterns and obstacles related to the adoption of TDM with anti-TNFs were gathered. Logistic regression analysis was used to predict factors influencing the utilization of TDM. Results: Among 211 respondents (82% male), 82% were consultants, 8% were physicians with an interest in gastroenterology (GI), and 6% were GI trainees. Of these, 152 met inclusion criteria, treating >5 IBD patients per month and ⩾1 with an anti-TNF per month. TDM was used in clinical practice by 78% (95% CI: 71-85) of respondents. TDM was utilized following the loss of response (LOR) in 93%, for primary non-response (PNR) in 40% and before restarting anti-TNF therapy after a drug holiday in 33% of respondents, while 34% used TDM proactively. No specific factors were associated with the use of TDM. Barriers to TDM use included cost (85%), time lag to results (71%) and lack of insurance reimbursement (65%). Overall knowledge of TDM (70%), interpretation and actioning of results (76%) or awareness of clinical guidelines (57%) were not perceived as barriers. If barriers were removed, 95% would use TDM more frequently; 93% for LOR, 60% for PNR, 50% when restarting after a drug holiday, and 54% would use TDM proactively. Conclusion: Most gastroenterologists use TDM for LOR, with cost, time lag and insurance reimbursement being significant barriers. Addressing these barriers would increase the judicious use of reactive and proactive TDM to optimize anti-TNF therapy in IBD.

Attitudes, perceptions, and barriers in implementing therapeutic drug monitoring for anti-TNFs in inflammatory bowel disease: a survey from Middle East Anti-TNF therapies are perhaps the most widely used and available biological therapies for the treatment of inflammatory bowel disease globally even though other agents have been licensed in recent years. The role of therapeutic drug monitoring to optimise outcomes and mitigate against immunogenicity with anti-TNF agents are now being appreciated. Our study investigates clinician attitudes, perceptions, and barriers related to therapeutic drug monitoring (TDM) in the context of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD) through a comprehensive survey distributed from five Middle Eastern countries. Among 211 respondents (82% male), 82% were consultants, 8% physicians with an interest in gastroenterology (GI), and 6% GI trainees. TDM was utilised following loss of response (LOR) in 93%, for primary non-response (PNR) in 40%, and before restarting anti-TNF therapy after a drug holiday by 33% of respondents, while 34% used TDM proactively. No specific factors were associated with the use of TDM. Barriers to TDM use included cost (85%), time lag to result (71%), and lack of insurance reimbursement (65%). Overall knowledge of TDM (70%), interpretation and actioning of results (76%), or awareness of clinical guidelines (57%) were not perceived as barriers. If barriers were removed, 95% would use TDM more frequently; 93% for LOR, 60% for PNR, 50% when restarting after a drug holiday and 54% would use TDM proactively. Most gastroenterologists use TDM for LOR, with cost, time lag, and insurance reimbursement being significant barriers. Addressing these barriers would increase judicious use of reactive and proactive TDM to optimise anti-TNF therapy in IBD.

10-year follow-up results of the European Achalasia Trial: a multicentre randomised controlled trial comparing pneumatic dilation with laparoscopic Heller myotomy.

OBJECTIVE: As achalasia is a chronic disorder, long-term follow-up data comparing different treatments are essential to select optimal clinical management. Here, we report on the 10-year follow-up of the European Achalasia Trial comparing endoscopic pneumodilation (PD) with laparoscopic Heller myotomy (LHM). DESIGN: A total of 201 newly diagnosed patients with achalasia were randomised to either a series of PDs (n=96) or LHM (n=105). Patients completed symptom (Eckardt score) and quality-of-life questionnaires, underwent functional tests and upper endoscopy. Primary outcome was therapeutic success defined as Eckardt score <3 at yearly follow-up. Secondary outcomes were the need for retreatment, lower oesophageal sphincter pressure, oesophageal emptying, gastro-oesophageal reflux and the rate of complications. RESULTS: After 10 years of follow-up, LHM (n=40) and PD (n=36) were equally effective in both the full analysis set (74% vs 74%, p=0.84) and the per protocol set (74% vs 86%, respectively, p=0.07). Subgroup analysis revealed that PD was superior to LHM for type 2 achalasia (p=0.03) while there was a trend, although not significant (p=0.05), that LHM performed better for type 3 achalasia. Barium column height after 5 min at timed barium oesophagram was significantly higher for patients treated with PD compared with LHM, while other parameters, including gastro-oesophageal reflux, were not different. CONCLUSIONS: PD and LHM are equally effective even after 10 years of follow-up with limited risk to develop gastro-oesophageal reflux. Based on these data, we conclude that PD and LHM can both be proposed as initial treatment of achalasia.

Precision Medicine in Inflammatory Bowel Disease.

Ulcerative colitis and Crohn's disease are traditionally defined as the two main subtypes of inflammatory bowel disease. However, a more recent view considers IBD as a spectrum of heterogeneous phenotypes with consistent differences in clinical presentation and behaviors, likely explained by differences in underlying pathogenetic mechanisms. The etiology is still elusive, and the suggested pathogenesis is a complex interplay among genetic predisposition and abnormal immune response at the mucosal intestinal level, activated by only partially identified environmental triggers leading to altered intestinal permeability and impaired handling of gut microbiota. The undeniable continuous progress of medical therapy with more frequent shifts from traditional to more advanced modalities also underlines the actual unmet needs. We are using medications with completely different mechanisms of action, with a lack of predictive factors of outcomes and response and still an unsatisfactory rate of success. In addition, we are missing still valuable and accurate markers to predict disease progression and severity in order to avoid under- or over-treatment. In such a complex scenario, it is undoubtful that the application of artificial intelligence and machine learning algorithms may improve the management and pave the way for precision and eventually personalized medicine in these patients; however, there are still several challenges that will be the focus of this review.

Immunoglobulin A Glycosylation Differs between Crohn's Disease and Ulcerative Colitis.

Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammations of the digestive tract with increasing prevalence, yet they have unknown origins or cure. CD and UC have similar symptoms but respond differently to surgery and medication. Current diagnostic tools often involve invasive procedures, while laboratory markers for patient stratification are lacking. Large glycomic studies of immunoglobulin G and total plasma glycosylation have shown biomarker potential in IBD and could help determine disease mechanisms and therapeutic treatment choice. Hitherto, the glycosylation signatures of plasma immunoglobulin A, an important immunoglobulin secreted into the intestinal mucin, have remained undetermined in the context of IBD. Our study investigated the associations of immunoglobulin A1 and A2 glycosylation with IBD in 442 IBD cases (188 CD and 254 UC) and 120 healthy controls by reversed-phase liquid chromatography electrospray-ionization mass spectrometry of tryptic glycopeptides. Differences of IgA O- and N-glycosylation (including galactosylation, bisection, sialylation, and antennarity) between patient groups were associated with the diseases, and these findings led to the construction of a statistical model to predict the disease group of the patients without the need of invasive procedures. This study expands the current knowledge about CD and UC and could help in the development of noninvasive biomarkers and better patient care.

The cost of inflammatory bowel disease in high-income settings: a Lancet Gastroenterology & Hepatology Commission.

The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers.

Composition of the gut microbiota in patients with inflammatory bowel disease in Saudi Arabia: A pilot study.

Conclusions: The results of this study provide an overview of the variations in microbiota diversity present in Saudi IBD patients compared to healthy controls. Results: The key finding was three negative bacterial biomarkers, Paraprevotellaceae, the Muribaculaceae families of Bacteroidetes phylum, and the Leuconostocaceae family of Firmicutes phylum, which had a higher relative abundance in healthy individuals compared to IBD patients. It was also found that primary microbiota signatures at certain genera and species levels, including Prevotella copri, Bifidobacterium adolescentis, Ruminococcus callidus, Coprococcus sp., Ruminococcus gnavus, Dorea formicigenerans, Leuconostoc, Dialister, Catenibacterium, Eubacterium biforme, and Lactobacillus mucosae, were absent in almost all IBD patients, while Veillonella dispar was absent in all healthy individuals. Methods: After obtaining an informed consent, fecal samples were collected from 11 participants with IBD (patients) and 10 healthy individuals (controls). The bacterial components of the microbial population were identified by next-generation sequencing of partial 16S rRNA. Statistically significant dissimilarities were observed between samples for all metrics. Background: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition attributed to a complex interaction between imbalances in the gut microbiome, environmental conditions, and a deregulated immune response. The aim of the study was to investigate the composition of the gut microbiome of Saudi patients with IBD.

Peroral Endoscopic Myotomy for the Treatment of Esophageal Diverticula: A Systematic Review and Meta-analysis.

BACKGROUND: There is limited evidence on the efficacy of peroral endoscopic myotomy (POEM) in patients with esophageal diverticula. AIMS: This meta-analysis aimed to assess the efficacy and safety profile of POEM in patients with Zenker (ZD) and epiphrenic diverticula. METHODS: With a literature search through August 2020, we identified 12 studies (300 patients) assessing POEM in patients with esophageal diverticula. The primary outcome was treatment success. Results were expressed as pooled rates and 95% confidence intervals. RESULTS: Pooled rate of technical success was 95.9% (93.4%-98.3%) in ZD patients and 95.1% (88.8%-100%) in patients with epiphrenic diverticula. Pooled rate of treatment success was similar for ZD (90.6%, 87.1%-94.1%) and epiphrenic diverticula (94.2%, 87.3%-100%). Rates of treatment success were maintained at 1 year (90%, 86.4%-97.4%) and 2 years (89.6%, 82.2%-96.9%) in ZD patients. Pooled rate of symptom recurrence was 2.6% (0.9%-4.4%) in ZD patients and 0% in patients with epiphrenic diverticula. Pooled rates of adverse events and severe adverse events were 10.6% (4.6%-16.6%) and 3.5% (0%-7.4%) in ZD and 8.4% (0%-16.8%) and 8.4% (0%-16.8%) in epiphrenic diverticula, respectively. CONCLUSION: POEM represents an effective and safe therapy for the treatment of esophageal diverticula.

Attributes of intestinal microbiota composition and their correlation with clinical primary non-response to anti-TNF-α agents in inflammatory bowel disease patients.

The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn's disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae-previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy.

ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment.

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.

Infliximab is more effective than cyclosporine as a rescue therapy for acute severe ulcerative colitis: a retrospective single-center study.

BACKGROUND: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening disease, and the best option in cases of steroid-refractory disease is still debated. We compared the early- and long-term efficacy and safety of the 2 available "rescue therapies", infliximab (IFX) and cyclosporine (CYS), in this setting. METHODS: We retrospectively evaluated patients admitted for ASUC and treated with "rescue therapy". The primary endpoint was early colectomy-free survival (30 days) and colectomy-free survival until the end of follow up. The secondary endpoints were predictors of colectomy and long-term maintenance of the treatment strategy over time. RESULTS: Of 129 patients admitted, 68 received rescue therapy (47 with IFX), whereas 7 underwent early colectomy (10.3%). At 30 days, fewer patients treated with IFX showed a need for colectomy (8.5% vs. 14.3%) compared to those in the CYS group, though the difference was non-significant (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.10-4.69; P=0.47). No severe side effects due to IFX and CYS were observed. During a mean follow up of 40 months, 23 additional patients (37.7%) underwent colectomy, and the rate was significantly lower in the IFX group (25.6%) than in the CYS group (66.7%) (hazard ratio 0.25, 95%CI 0.10-0.61; P=0.003). Colectomy-free survival was significantly higher in the IFX group than in the CYS group (P=0.018) at 12 months. CONCLUSIONS: In our setting, the early outcomes of IFX and CYS for ASUC were comparable. IFX was associated with significantly lower colectomy rates during the observation period and had a similar safety profile to CYS.

Systematic review with meta-analysis: safety and tolerability of immune checkpoint inhibitors in patients with pre-existing inflammatory bowel diseases.

BACKGROUND: Immune checkpoint inhibitors may variably impact patients with pre-existing autoimmune diseases. AIMS: To evaluate the risks and outcomes of adverse events in patients with pre-existing inflammatory bowel diseases treated with immune checkpoint inhibitors. METHODS: Through a systematic literature review up until July 31, 2020, we identified 12 studies reporting the impact of immune checkpoint inhibitors in 193 patients with inflammatory bowel disease. Outcomes of interest were relapse of inflammatory bowel disease, need for corticosteroids and/or biologics to manage inflammatory bowel disease relapse, and discontinuation of immune checkpoint inhibitors. We calculated pooled rates (with 95% confidence intervals [CI]) using random effects meta-analysis, and examined risk factors associated with adverse outcomes through qualitative synthesis of individual studies. RESULTS: On meta-analysis, 40% patients (95% CI, 26%-55%) experienced relapse of inflammatory bowel disease with immune checkpoint inhibitors. Among patients who experienced relapse, 76% (95% CI, 65%-85%) required corticosteroids, and 37% (95% CI, 22%-53%) required biologic therapy. Overall, 35% patients (95% CI, 17%-57%) with inflammatory bowel disease discontinued immune checkpoint inhibitors. Gastrointestinal perforation and abdominal surgery due to immune checkpoint inhibitor complications occurred in <5% patients. In a large study, inhibitors of cytotoxic T-lymphocyte antigen-4 (CTLA-4) were associated with a higher risk of relapse than programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors. CONCLUSIONS: Approximately 40% of patients with pre-existing inflammatory bowel diseases experience relapse with immune checkpoint inhibitors, with most relapsing patients requiring corticosteroids and one-third requiring biologics. CTLA-4 inhibitors may be associated with higher risk of relapse.

Prevalence and Predictors of Reduced Bone Density in Child and Adolescent Patients With Crohn's Disease.

Reduced bone mineral density (BMD) has broadly been found to be associated with inflammatory bowel disease across a number of geographical locations and cultures. We aimed to estimate the prevalence of reduced BMD and identify clinical predictors in a cohort of Crohn's disease patients (CD) in Saudi Arabia. We conducted a retrospective study involving children and adolescents with CD between 2013 and 2018. BMD was evaluated using dual-energy X-ray absorptiometry scans of the spine and body. A multivariate analysis was performed for the detection of predictors of low BMD. Sixty-four patients were enrolled. The median age was 16 years (range, 8-19 years) and 55% of patients were males. Total body BMD scanning identified 25 patients (39%) with osteoporosis. Twenty patients (31.3%) were found to have z scores consistent with osteopenia. A multivariate regression analysis identified a low weight-for-age z score (B coefficient = 0.347, 95% confidence interval [CI] = 0.211-0.482, p < 0.001 for Spine BMD and B coefficient = 0.321, 95% CI = 0.170-0.472, p < 0.001 for total body BMD), a low height-for-age z score (B coefficient = 0.187, 95% CI = 0.035-0.338, p = 0.017 for spine BMD and B coefficient = 0.0.258, 95% CI = 0.089-0.427, p = 0.004 for total body BMD), a low 25-hyroxyvitamin D level (B coefficient = 0.026, 95% CI = 0.013-0.038, p < 0.001 for spine BMD and B coefficient = 0.016, 95% CI = 0.002-0.031, p = 0.026 for total body BMD), and a higher number of corticosteroid induction courses (B coefficient = -0.567, 95% CI = -0.923 to -0.212, p = 0.003 for spine BMD and B coefficient = -0.566, 95% CI = 0.963-0.169, p = 0.007 for total body BMD) as predictors of low BMD. In the spine BMD analysis, older age at the time of presentation was identified as a significant predictor for low bone density (B coefficient = 0.254, 95% CI = 0.141-0.368, p < 0.001). In conclusion, Saudi Arabian children and adolescents with CD have a high prevalence rate of low bone density compared to Western populations. Several clinical characteristics are identified as significant predictors for low BMD.

Comparative efficacy of first-line therapeutic interventions for achalasia: a systematic review and network meta-analysis.

BACKGROUND: Several interventions with variable efficacy are available as first-line therapy for patients with achalasia. We assessed the comparative efficacy of different strategies for management of achalasia, through a network meta-analysis combining direct and indirect treatment comparisons. METHODS: We identified six randomized controlled trials in adults with achalasia that compared the efficacy of pneumatic dilation (PD; n = 260), laparoscopic Heller myotomy (LHM; n = 309), and peroral endoscopic myotomy (POEM; n = 176). Primary efficacy outcome was 1-year treatment success (patient-reported improvement in symptoms based on validated scores); secondary efficacy outcomes were 2-year treatment success and physiologic improvement; safety outcomes were risk of gastroesophageal reflux disease (GERD), severe erosive esophagitis, and procedure-related serious adverse events. We performed pairwise and network meta-analysis for all treatments, and used GRADE criteria to appraise quality of evidence. RESULTS: Low-quality evidence, based primarily on direct evidence, supports the use of POEM (RR [risk ratio], 1.29; 95% confidence intervals [CI], 0.99-1.69), and LHM (RR, 1.18 [0.96-1.44]) over PD for treatment success at 1 year; no significant difference was observed between LHM and POEM (RR 1.09 [0.86-1.39]). The incidence of severe esophagitis after POEM, LHM, and PD was 5.3%, 3.7%, and 1.5%, respectively. Procedure-related serious adverse event rate after POEM, LHM, and PD was 1.4%, 6.7%, and 4.2%, respectively. CONCLUSIONS: POEM and LHM have comparable efficacy, and may increase treatment success as compared to PD with low confidence in estimates. POEM may have lower rate of serious adverse events compared to LHM and PD, but higher rate of GERD.

Optimizing biologic therapy in inflammatory bowel disease: a Delphi consensus in the United Arab Emirates.

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic, relapsing-remitting inflammatory conditions with a substantial negative impact on health-related quality of life and work productivity. Treatment of IBD has been revolutionized by the advent of biologic therapies, initially with anti-TNF agents and more recently with multiple alternatives targets, and yet more under development. OBJECTIVES: Approximatively one third of patients do not respond to biologic therapy and more importantly a significant proportion experiences partial response or loss of response during treatment. The latter are common clinical situations and paradoxically are not addressed in the commercial drug labels and available guidelines. There is therefore a clinical need for physicians to understand when and how eventually to optimize the biologic therapy. DESIGN: This consensus using a Delphi methodology was promoted and supported by the Emirates Society of Gastroenterology and Hepatology to close this gap. DATA SOURCES AND METHODS: Following an extensive systematic review of over 60,000 studies, 81 studies with dose escalation and five addressing drug monitoring were selected and in addition five systematic reviews and three guidelines. RESULTS AND CONCLUSION: after three rounds of voting 18 statements were selected with agreement ranging from of 80% to 100.

First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus.

Ulcerative colitis and Crohn's disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.

Global variability of the human IgG glycome.

Immunoglobulin G (IgG) is the most abundant serum antibody which structural characteristics and effector functions are modulated through the attachment of various sugar moieties called glycans. Composition of the IgG N-glycome changes with age of an individual and in different diseases. Variability of IgG glycosylation within a population is well studied and is known to be affected by both genetic and environmental factors. However, global inter-population differences in IgG glycosylation have never been properly addressed. Here we present population-specific N-glycosylation patterns of IgG, analyzed in 5 different populations totaling 10,482 IgG glycomes, and of IgG's fragment crystallizable region (Fc), analyzed in 2,579 samples from 27 populations sampled across the world. Country of residence associated with many N-glycan features and the strongest association was with monogalactosylation where it explained 38% of variability. IgG monogalactosylation strongly correlated with the development level of a country, defined by United Nations health and socioeconomic development indicators, and with the expected lifespan. Subjects from developing countries had low levels of IgG galactosylation, characteristic for inflammation and ageing. Our results suggest that citizens of developing countries may be exposed to environmental factors that can cause low-grade chronic inflammation and the apparent increase in biological age.

Genetics and epigenetics of IBD.

Inflammatory bowel diseases (IBD) are chronic intermittent inflammatory disorders of the gastrointestinal tract of unknown etiology but a clear genetic predisposition. Prompted by the first investigations on IBD families and twins, the genetic and epigenetic studies have produced an unprecedented amount of information in comparison with other immune-mediated or complex diseases. New inflammatory pathways and possible mechanisms of action have been disclosed, potentially leading to new-targeted therapy. However, the identification of genetic markers due to the great disease heterogeneity and the overwhelming contribution of environmental risk factors has not modified yet the disease management. The possibility for the future of a better prediction of disease course, response to therapy and therapy-related adverse events may allow a more efficient and personalized strategy. This review will focus on more recent discoveries that may potentially be of relevance in daily clinical practice.