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Christoforos Vlachos,1 Georgios Gaitanis,1 Konstantinos H Katsanos,2 Dimitrios K Christodoulou,2 Epameinondas Tsianos,2 Ioannis D Bassukas1 1Department of Skin and Venereal Diseases, 2Division of Gastroenterology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece Abstract: Psoriasis and the spectrum of inflammatory bowel diseases (IBD) are chronic, inflammatory, organotropic conditions. The epidemiologic coexistence of these diseases is corroborated by findings at the level of disease, biogeography, and intrafamilial and intrapatient coincidence. The identification of shared susceptibility loci and DNA polymorphisms has confirmed this correlation at a genetic level. The pathogenesis of both diseases implicates the innate and adaptive segments of the immune system. Increased permeability of the epidermal barrier in skin and intestine underlies the augmented interaction of allergens and pathogens with inflammatory receptors of immune cells. The immune response between psoriasis and IBD is similar and comprises phagocytic, dendritic, and natural killer cell, along with a milieu of cytokines and antimicrobial peptides that stimulate T-cells. The interplay between dendritic cells and Th17 cells appears to be the core dysregulated immune pathway in all these conditions. The distinct similarities in the pathogenesis are also reflected in the wide overlapping of their therapeutic approaches. Small-molecule pharmacologic immunomodulators have been applied, and more recently, biologic treatments that target proinflammatory interleukins have been introduced or are currently being evaluated. However, the fact that some treatments are quite selective for either skin or gut conditions also highlights their crucial pathophysiologic differences. In the present review, a comprehensive comparison of risk factors, pathogenesis links, and therapeutic strategies for psoriasis and IBD is presented. Specific emphasis is placed on the role of the immune cell species and inflammatory mediators participating in the pathogenesis of these diseases. Keywords: psoriasis, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, immune cells, inflammation

Background: Inflammatory bowel disease (IBD) commonly affects patients of reproductive age. The effect of disease activity on the outcome of pregnancy and its impact on neonatal health are areas of intense research., Methods: Α national retrospective study of pregnancies in women with IBD between 2010 and 2020 was carried out in 22 IBD reference centers in Greece., Results in Total: 223 pregnancies in 175 IBD patients [122 Crohn's disease (CD)] were included. Mean age at diagnosis was 26 years (12-44) with a mean duration of 7.4 (0-23). Pregnancy as a result of IVF occurred in 15 cases (6.7%). At the beginning of gestation, 165 patients (74%) were under treatment: 48 (29%) with anti-tumor necrosis factor alpha agents, 43 (26%) with azathioprine, 101 (61%) with 5-aminosalicylates, and 12 (7%) with steroids. Forty-nine cases (22%) of IBD flares were recorded: Two-thirds (n = 30) were in clinical remission at the onset of pregnancy, whereas treatment with corticosteroids was required in 22 (45%). Patients with ulcerative colitis were at greater risk for flare compared to those with CD (P < 0.001). All but two pregnancies (99.1%) resulted in an uncomplicated delivery. In 147 cases (67.1%), c-section was performed. Two late fetal deaths (0.9%) were reported, both in patients with persistently active disease. After delivery, 75 patients (34%) presented with a disease flare, associated with active disease at the beginning of pregnancy (P < 0.001)., Conclusion: The majority of Greek patients with IBD have a favorable pregnancy outcome. Active inflammation during gestation and a diagnosis of ulcerative colitis are negatively associated with pregnancy outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed., Methods: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events., Results: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q 1 -q 3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11)., Conclusions: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background/Objectives: QRS fragmentation has not been linked with increased mortality in individuals without known cardiac disease. We aimed to investigate the physiological determinants of QRS fragmentation in individuals without cardiac disease. Methods: Study participants were 163 (54 athletes, 109 nonathletes) asymptomatic individuals with QRS fragmentation but without cardiac disease. QRS fragmentation was assessed in the supine position after deep inspiration or standing up and during exercise. The changes in QRS fragmentation were evaluated over a median follow-up period of 2.3 (0.8-4.9) years. Results: The most common lead with QRS fragmentation was III (63.0% in athletes, 61.5% in nonathletes), immediately followed by V1 (50.0%) and aVF (42.6%) in athletes and aVF (55.0%) in nonathletes. QRS fragmentation in V1 was more frequent in athletes compared to nonathletes ( p < 0.001). Among athletes, the presence of QRS fragmentation in V1 could be independently predicted by increased RVOTproxi (right ventricular outflow tract proximal diameter indexed to body surface area) ( p < 0.001). Among individuals with QRS fragmentation in V1, deep inspiration resulted in disappearance of QRS fragmentation more frequently in nonathletes compared to athletes (100% vs. 20%, p = 0.003). Deep inspiration resulted in disappearance of QRS fragmentation in aVF ( p < 0.001). The presence of QRS fragmentation in II or aVF was associated with increased body mass index (BMI) ( p = 0.003). Among athletes without QRS fragmentation in V1 at baseline, the appearance of QRS fragmentation in V1 at the end of follow-up was associated with greater training age ( p = 0.034). Among individuals with QRS fragmentation in aVF at baseline, the disappearance of QRS fragmentation in aVF at the end of follow-up was associated with greater reduction in BMI ( p = 0.008). Conclusions: The characteristic feature of QRS fragmentation in athletes was the presence of QRS fragmentation in V1, which was associated with RVOTproxi. The persistence of QRS fragmentation in V1 after deep inspiration could serve as a specific marker of exercise-training-related cardiac adaptation. The presence of QRS fragmentation in the leads of the frontal plane was influenced by BMI and respiration phase.

Background: This systematic review and meta-analysis aims to explore in heart failure (HF) patients with reduced ejection fraction (EF) undergoing exercise-based cardiac rehabilitation the following: 1) the comparison of temporal changes between peak oxygen uptake (VO2peak) and first ventilatory threshold (VO2VT1), 2) the association of VO2peak and VO2VT1 changes with physiological factors, and 3) the differential effects of continuous aerobic exercise (CAE) and interval training (IT) on VO2peak and VO2VT1., Methods: A systematic literature search was conducted in PubMed, CENTRAL, and Scopus. Inclusion criteria were 1) original research articles using exercise-based cardiac rehabilitation, 2) stable HF patients with reduced EF, 3) available values of VO2peak and VO2VT1 (in mL/kg/min) both at baseline and after exercise training with comparison between these time points., Results: Among the 30 eligible trials, 24 used CAE, 5 IT, and one CAE and IT. Multivariable meta-regression with duration of exercise training and percentage of males as independent variables and the change in VO2peak as a dependent variable showed that the change in VO2peak was negatively associated with duration of exercise training (coefficient=-0.061, p=0.027), implying the possible existence of a waning effect of exercise training on VO2peak in the long term. Multivariable meta-regression demonstrated that both age (coefficient=-0.140, p<0.001) and EF (coefficient=-0.149, p<0.001) could predict the change in VO2VT1, whereas only age (coefficient=-0.095, p=0.022), but not EF (coefficient = 0.082, p = 0.100), could predict the change in VO2peak. The posttraining peak respiratory exchange ratio, as an index of maximum effort during exercise testing, correlated positively with the change in VO2peak (coefficient=-0.021, p=0.044). The exercise-induced changes of VO2peak (p = 0.438) and VO2VT1 (p = 0.474) did not differ between CAE and IT groups., Conclusions: Improvement of endurance capacity during cardiac rehabilitation may be detected more accurately with the assessment of VO2VT1 rather than VO2peak., Competing Interests: Declaration of Competing Interest Declarations of interest: none., (Copyright © 2024 Hellenic Society of Cardiology. All rights reserved.)

Background: Managing complex perianal fistulizing Crohn's disease (CD) remains challenging, despite current medical and surgical treatment approaches. Darvadstrocel, a therapy utilizing adipose-derived stem cells, shows promise in promoting tissue regeneration and healing, offering a novel and effective treatment for fistula management., Method: A systematic literature search was conducted on PubMed and Scopus to identify studies involving patients with complex perianal fistulizing CD treated with darvadstrocel., Results: In total, 2 randomized controlled trials (RCT), 5 observational studies with retrospective data collection and 2 observational studies with prospective design were included in the final review. Data from the European ADMIRE-CD RCT demonstrated that darvadstrocel is superior to placebo in terms of clinical and imaging improvement over both the short and long term. These findings align with the prospective studies analyzed in this systematic review. The rate of treatment-emergent adverse events in the ADMIRE-CD trial's RCTs was similar in both the darvadstrocel and control groups, with perianal abscess being the most common adverse event up to 52 weeks after drug administration. Retrospective studies indicated no side-effects beyond 52 weeks., Conclusions: Darvadstrocel appears to be a new, potentially effective and safe treatment option for the management of complex perianal fistulas. However, more randomized clinical trials are needed to evaluate the efficacy and safety profile of the drug., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Despite rescue therapy, acute severe ulcerative colitis (ASUC) is associated with a high risk of colectomy, while treatment options remain limited. Tofacitinib, a rapidly acting Janus Kinase (JAK) inhibitor, is gaining ground as an effective alternative treatment option for the management of acute severe ulcerative colitis, which may prevent emergency colectomy., Methods: A systematic literature search of PubMed and Embase was undertaken for studies of adult patients with ASUC treated with tofacitinib., Results: In total, two observational studies, seven case series and five case reports incorporating 134 patients who received tofacitinib in ASUC were identified with a follow-up period ranging from 30 days to 14 months. Overall, the pooled colectomy rate was 23.9% (95% CI 16.6-31.2). The pooled 90-day and 6-month colectomy free rate were 79.9% (95% CI 73.1-86.7) and 71.6% (95% CI 64-79.2) respectively. The most frequent adverse event was C. Difficile infection., Conclusions: Tofacitinib appears to be a promising option for the treatment of ASUC. Randomized clinical trials are required to further access the efficacy, safety and optimal dose of tofacitinib in cases of ASUC., Competing Interests: Conflict of interest All authors declare no conflicts of interest and have approved the manuscript and agree with its submission to Digestive and Liver Disease. No funding has been received., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients., Methods: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency., Results: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86-0.91)]. Cronbach's coefficient alpha for all items achieved 0.90 (95%CI 0.88-0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score., Conclusions: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients.

Objective: Aim: The aim of the study was to investigate the incidence of IBD in gastrointestinal surgery patients and record the disease's characteristics and treatment., Patients and Methods: Materials and Methods: A search was carried out in the archives of the gastroenterology clinics of the University General Hospital of Ioannina and the General Hospital of Ioannina "G. Hatzikosta" in Greece. All cases of operated patients from 1980 to 2018 were examined. The duration of the study was 4 months. Data were analyzed with the SPSS program, v.28., Results: Results: The total sample consisted of 1464 patients (n=1464). Most of them (915-62.5%) came from the University General Hospital of Ioannina, while the rest (549-37.5%) came from the GHI hospital "G. Hatzikosta". The mean age of the patients was 47 years (M=47.26, SD=17.34, Min=<1 month, Max=95 years). From the total sample, 58 patients (4%) suffered from IBD; most were men (42-72.41%). Their mean age was approximately 50 years (M=49.63, SD=16.48, Min=25 years, Max=77 years, range=52 years) and most belonged to the age groups of 31-40 years (11 patients- 19.6%) and 21-30 years and 61-70 years (10 patients-17.9%). The perianal disease was present in 43.1% (25 patients). The most frequent type of operation was fistula resection, ligation, curettage-biopsy (24.1%) and opening-drainage (22.4%-13 patients) and the most frequent type of anesthesia was general anesthesia (93.1%-54 patients)., Conclusion: Conclusions: This long-term study of the patients' data followed up over time showed that the possibility of surgery in patients with IBD is mitigated through systematic monitoring and multifaceted therapeutic treatment.The perianal disease which appeared more often in men shows that it can be diagnosed early and at an early stage and with the new minimally invasive techniques the patient with IBD can be treated with a better quality of life.

The development of fibrostenotic intestinal disease occurs in approximately one-third of patients with Crohn's disease and is associated with increased morbidity. Despite introducing new biologic agents, stricturing Crohn's disease remains a significant clinical challenge. Medical treatment is considered the first-line treatment for inflammatory strictures, and anti-TNF agents appear to provide the most considerable benefit among the available medical treatments. However, medical therapy is ineffective on strictures with a mainly fibrotic component, and a high proportion of patients under anti-TNF will require surgery. In fibrotic strictures or cases refractory to medical treatment, an endoscopic or surgical approach should be considered depending on the location, length, and severity of the stricture. Both endoscopic balloon dilatation and endoscopic stricturoplasty are minimally invasive and safe, associated with a small risk of complications. On the other hand, the surgical approach is indicated in patients not suitable for endoscopic therapy. This review aimed to present and analyze the currently available medical, endoscopic, and surgical management of stricturing Crohn's disease.

Aim: To establish whether the addition of probiotics to a globally accepted Helicobacter pylori (H. pylori)-eradication scheme may reduce the rates of side effects and increase the eradication rates. Methods. Prospective, randomized, placebo-controlled trial of patients receiving eradication therapy for H. pylori in the eight participating centers. All patients received a 10-day proton pump inhibitor containing non-bismuth quadruple therapeutic regimen for H. pylori eradication (omeprazole 20 mg, amoxycillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg all twice daily orally) and were randomized to receive either probiotics (group A) or placebo (group B). The probiotic used combined four probiotic strains, i.e., Lactobacillus Acidophilus, Lactiplantibacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii. Results. Data were analyzed for 329 patients in group A and 335 patients in group B. Fifty six (17.0%) patients in group A and 170 (50.7%) patients in group B reported the occurrence of an H. pylori treatment-associated new symptom or the aggravation of a pre-existing symptom of any severity (p < 0.00001). H. pylori was successfully eradicated in 303 patients in group A (92.0%) and 291 patients in group B (86.8%), (p = 0.028). Conclusion: Adding probiotics to the 10-day concomitant non-bismuth quadruple H. pylori eradication regimen increases the eradication rate and decreases side effects.

The development of biological agents against tumor necrosis factor (TNF) has revolutionized the management of inflammatory bowel disease (IBD), frequently achieving induction and maintenance of remission in both ulcerative colitis and Crohn's disease. However, a loss of response due to the development of anti-drug antibodies (ADA) is seen annually in approximately 20% of IBD patients receiving anti-TNF therapy. Current evidence suggests that the use of immunomodulators (IMM), such as thiopurines (azathioprine and 6-mercaptopurine) or methotrexate, may prevent or suppress ADA formation. In this article, we present a comprehensive review of the available literature regarding the efficacy of IMM in the prevention and suppression of ADA development to anti-TNF therapy in patients with IBD., Competing Interests: Conflict of interest: Konstantinos Papamichael reports lecture fees from Mitsubishi Tanabe Pharma and Physicians Education Resource LLC; consultancy fee from Prometheus Laboratories Inc; and scientific advisory board fees from ProciseDx Inc. and Scipher Medicine Corporation. The remaining authors declare no conflict of interest, (Copyright: © Hellenic Society of Gastroenterology.)

Background: The physiological QT prolongation in athletes is expected to widen the gray zone between physiology and pathology of QT, increasing the diagnostic challenges encountered in athletes with QT prolongation., Summary: According to international recommendations for electrocardiogram in athletes, further evaluation for long QT syndrome (LQTS) is indicated in male athletes with corrected QT (QTc) ≥470 ms and in female athletes with QTc ≥480 ms. Apart from QTc ≥500 ms, diagnostic challenges arise in borderline cases of QTc prolongation, where further clinical investigations are needed to be performed to clarify whether LQTS exists. Clinical diagnostic investigations, including exercise testing, are more readily available, convenient, and easily interpretable, as well as less costly than genetic testing for LQTS. The main findings on exercise testing that are suggestive of LQTS can be the paradoxical prolongation of QTc during exercise and QTc ≥480 ms at fourth min of recovery., Key Messages: Exercise testing appears to have an important role in the diagnostic evaluation of athletes with prolonged QT interval, when genetic testing is not available., (© 2022 S. Karger AG, Basel.)

Objectives: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic., Methods: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death)., Results: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics., Conclusions: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: This real-world study assessed the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with ulcerative colitis over 12 months in Greece., Methods: GO-LIFE was a noninterventional, prospective, multicenter, 12-month study. Patients who had moderately-to-severely active ulcerative colitis were naïve to antitumor necrosis factor (anti-TNFα) therapy and had failed previous conventional therapy. Patients received golimumab as per label. The primary endpoint was patients achieving inflammatory bowel disease questionnaire 32-item (IBDQ-32) remission at 12 months. Secondary endpoints, at 6 and 12 months, included patients achieving IBDQ-32 response; the mean change in the treatment satisfaction questionnaire for medication (TSQM) and the work productivity and activity impairment in ulcerative colitis (WPAI:UC) questionnaires; changes in healthcare utilization; patients achieving clinical response and remission; adherence rates and the percentage of patients who discontinued golimumab., Results: IBDQ-32 remission was achieved by 76.9% of patients at 12 months. Mean changes in all TSQM and WPAI:UC domain scores at 12 months were statistically significant. Clinical remission was achieved by 49.4 and 50.6% of patients at 6 and 12 months, and clinical response by 59.3 and 56.8%, respectively. All patients but one (80/81) had high adherence (≥80%) to golimumab treatment over 12 months. Ulcerative colitis-related health care resource utilization was reduced during the follow-up period., Conclusions: In real-world settings, treatment with golimumab resulted in meaningful improvements in HRQoL and other PROs, and in disease activity at 6 and 12 months in patients with moderately-to-severely active ulcerative colitis who were naïve to anti-TNFa therapy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Crohn's disease (CD) is characterized by a remitting and relapsing course. Longstanding active CD may result in accumulating intestinal damage and disease-related complications. In contrast, mucosal healing is associated with significant improvement in the health-related quality of life, longer periods of disease remission and lower risk of disease progression, complications, hospitalizations, intestinal surgeries, as well as a lower risk of developing colorectal cancer. Mucosal healing, the new treatment endpoint in CD, made necessary the development of noninvasive, accurate, objective and reliable tools for the evaluation of CD activity. Ileocolonoscopy with biopsies remains the reference standard method for the evaluation of the colonic and terminal ileal mucosa. However, it is an invasive procedure with a low risk of complications, allowing the investigation of only a small part of the small bowel mucosa without being able to assess transmural inflammation. These disadvantages limit its role in the frequent follow up of CD patients. In this review, we present the currently available biomarkers and imaging modalities for the noninvasive assessment of CD activity., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Inflammatory bowel disease (IBD) is a multisystemic disease with a wide range of extraintestinal manifestations in both ulcerative colitis and Crohn's disease, while increasing evidence supports the interaction between gut and central nervous system, described as "gut-brain axis". According to epidemiological studies, it seems that patients with IBD present more frequently with impaired mental status compared to the general population, leading to diagnostic and management problems in this group of patients. The association between IBD and mental disorders, such as dementia and autism spectrum disorders, has not been fully clarified; genetic factors and the gut-brain axis seem to be involved. The purpose of this review is to present and analyze the epidemiological data about this issue, describe the possible pathogenetic mechanisms and discuss some considerations about the management of patients with IBD and impaired mental status., Competing Interests: All authors declare no conflict of interest., (Copyright 2021, Fousekis et al.)

Background: Anemia is a common extraintestinal manifestation of Inflammatory Bowel Disease (IBD) affecting negatively the patients' quality of life. The aim of this study was to determine the frequency and real-life management of anemia in IBD patients in Greece., Methods: This study was conducted in 17 Greek IBD referral centers. Demographic, clinical, laboratory, IBD and anemia treatment data were collected and analyzed retrospectively., Results: A total of 1394 IBD patients [560 ulcerative colitis (UC), 834 Crohn's disease (CD)] were enrolled. Anemia at any time was reported in 687 (49.3%) patients of whom 413 (29.6%) had episodic and 274 (19.7%) had recurrent/persistent anemia. Anemia was diagnosed before IBD in 45 (6.5%), along with IBD in 269 (39.2%) and after IBD in 373 (54.3%) patients. In the multivariate analysis the presence of extraintestinal manifestations (p = 0.0008), IBD duration (p = 0.026), IBD related surgeries and hospitalizations (p = 0.026 and p = 0.004 accordingly) were risk factors of recurrent/persistent anemia. Serum ferritin was measured in 839 (60.2%) IBD patients. Among anemic patients, 535 (77.9%) received treatment. Iron supplementation was administered in 485 (90.6%) patients, oral in 142 (29.3%) and intravenous in 393 (81%)., Conclusions: The frequency of anemia in IBD patients, followed at Greek referral centers, is approximately 50%. Development of recurrent/persistent anemia may be observed in 20% of cases and is independently associated with the presence of extraintestinal manifestations, IBD duration, IBD related surgeries and hospitalizations. Anemia treatment is administered in up to [Formula: see text] of anemia IBD patients with the majority of them receiving iron intravenously.

Serrated polyp associated colorectal cancer (CRC) develops from an alternative mechanism of colorectal carcinogenesis and accounts for 10-15% of all CRC. Serrated polyposis syndrome (SPS) occurs infrequently and is characterized by the occurrence of multiple serrated polyps (hyperplastic polyps, sessile serrated lesions and traditional serrated adenomas) throughout the colon and/or rectum and has been strongly associated with development of CRC. However, SPS is frequently unrecognized, due to application failure of the WHO criteria regarding diagnosis and/or missed serrated polyps during endoscopy. The management of SPS requires surveillance at regular intervals and removal of large serrated polyps. Endoscopic resection suitability and technique depends on lesion size and the endoscopist's experience. In this manuscript, we present an update regarding SPS epidemiology, molecular characteristics, management, surveillance strategies and endoscopic resection techniques., Competing Interests: None., (AJTR Copyright © 2021.)

Vaccines, cytokines, and adoptive cellular therapies (ACT) represent immuno-therapeutic modalities with great development potential, and they are currently approved for the treatment of a limited number of advanced malignancies. The most up-to-date knowledge on the regulation of the anti-cancer immune response has recently led to the development and approval of inhibitors of immune checkpoints, which have produced unprecedented clinical activity in several hard to treat solid malignancies. However, severe adverse events (AEs) represent a limitation to the use of these drugs. Currently approved checkpoint inhibitors block cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand (PD-L1), resulted in increased survival of patients with several solid and hematologic malignancies. The most common treatment AEs associated with these drugs are fatigue, rash, and auto-immune/inflammatory reactions. Many of the immune-related AEs are reversible and the strategies for their management include supportive care either with or without treatment withdrawal; nevertheless, in severe cases, hospitalization and treatment with immune suppressants, and/or immunomodulators may be required. Steroid therapy is a critical component of the treatment algorithm; nevertheless, the associated immunosuppression may compromise the antitumor response. This article provides a comprehensive and narrative review of luminal gastrointestinal and hepatic complications, including recommendations for their investigation and management., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7361). SB serves as an unpaid editorial board member of Annals of Translational Medicine from Nov 2019 to Oct 2021. The other authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Celiac disease (CD) is a chronic intestinal immune-mediated disease occurring in genetically susceptible individuals who are exposed to gluten. Although it primarily affects the small intestine, CD has been associated with a wide spectrum of extraintestinal manifestations, including thromboembolism and cardiovascular events. The risk of ischemic stroke, myocardial infarction, and thromboembolism, such as deep vein thrombosis and pulmonary embolism, is higher in patients with CD, while there is accumulating evidence that gluten-free diet in CD patients decreases the risk of these complications. The pathogenetic mechanism of increasing hypercoagulability in CD is multifactorial and involves hyperhomocysteinemia due to malabsorption of vitamins B12, B6, and folic acid; endothelial dysfunction; acceleration of atherosclerosis; chronic inflammation; thrombocytosis; and thrombophilia. Therefore, in cases of thromboembolic complications and cardiovascular disease of obscure etiology, clinicians' awareness of possible celiac disease is warranted.

Intestinal failure-associated liver disease (IFALD) remains one of the most common and serious complications of parenteral nutrition (PN), causing a wide spectrum of hepatic manifestations from steatosis and mild cholestasis to portal hypertension and end-stage liver failure. The prevalence of IFALD depends on the diagnostic criteria and ranges from 4.3% to 65%. Moreover, many factors are shown to contribute to its development, including nutrient deficiencies, toxicity of PN, infections, and alterations of bile acid metabolism and gut microbiota. Prevention and management of IFALD aim at ameliorating or eliminating the risk factors associated with IFALD. The use of PN formulations with a lower ratio omega-6-to-omega-3 polyunsaturated fatty acids, cycle PN, optimization of enteral stimulation and prevention and early treatment of infections constitute the main therapeutic targets. However, failure of improvement and severe IFALD with end-stage liver failure should be considered as the indications of intestinal transplantation. The aim of this review is to provide an update of the epidemiology, pathophysiology, and diagnosis of IFALD in the adult population as well as to present a clinical approach of the therapeutic strategies of IFALD and present novel therapeutic targets., Competing Interests: None

Background: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice., Aims: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease., Methods: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists., Results: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%))., Conclusion: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disorder in Western countries, comprises steatosis to nonalcoholic steatohepatitis (NASH), with the latter having the potential to progress to cirrhosis. The transition from isolated steatosis to NASH is still poorly understood, but lipidomics approach revealed that the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis and these alterations correlate with disease progression. Recent data suggest that both quantity and quality of the accumulated lipids are involved in pathogenesis of NAFLD. Changes in glycerophospholipid, sphingolipid, and fatty acid composition have been described in both liver biopsies and plasma of patients with NAFLD, implicating that specific lipid species are involved in oxidative stress, inflammation, and cell death. In this article, we summarize the findings of main human lipidomics studies in NAFLD and delineate the currently available information on the pathogenetic role of each lipid class in lipotoxicity and disease progression., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: To present a case series of two fraternal twin girls who passed away from brain and colorectal cancers attributed to Constitutional Mismatch Repair Deficiency syndrome (CMMRD). A review of literature for CMMRD-related pediatric malignancies is also presented., Methods: The two girls were diagnosed with cancer at the age of 11 and 13 respectively. The early onset of multiple malignancies in the family raised clinical suspicion for a potential genetic mutation. The presence of café-au-lait spots at clinical examination led to further investigations for neurofibromatosis., Results: Neurofibromatosis type 1 testing was negative in both children. Genetic analysis turned out positive for biallelic MSH6 mutations in the two girls, leading to CMMRD syndrome diagnosis. Both parents and two out of three alive siblings were diagnosed with Lynch syndrome., Conclusions: Colorectal cancer is a very rare finding in childhood and should raise suspicion for CMMRD syndrome and should be followed by regular screening., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Background: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up., Methods: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery., Findings: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (p<0·0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was €866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease (€1782 [SD 4370]) than in patients with ulcerative colitis (€286 [1427]) or IBD unclassified (€521 [2807]; p<0·0001)., Interpretation: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease., Funding: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To review and highlight the ocular manifestations associated with celiac disease (CD) and presentation of their pathogenetic mechanisms., Methods: A thorough review of the literature was performed using PubMed to identify articles about serrated polyposis syndrome. The search was performed using the search string: ("celiac disease" OR "coeliac disease") AND ("ocular manifestations" OR "eye" OR "orbitopathy" OR "uveitis" OR "neuro-ophthalmic manifestations"). Only articles in English were reviewed., Results: Several ocular symptoms and disorders have been associated with CD and are a result of defective intestinal absorption and immunological mechanisms. These include nyctalopia, dry eye, cataract, thyroid-associated orbitopathy, uveitis, central retinal vein occlusion and neuro-ophthalmic manifestations. In addition, CD-related ocular disease may represent the first manifestation of CD., Conclusion: CD may hold accountable for the development of ocular diseases of obscure etiology.

Introduction: Clostridium difficile infection (CDI) has been reported to be a cause of flare-ups in patients with inflammatory bowel disease (IBD). Cytomegalovirus (CMV) infection can cause severe disease and complications in immunocompromised patients in consequence of disease or therapy., Aim: Our aim was to describe the prevalence and clinical outcomes of CDI with concomitant CMV infection in IBD patients hospitalized for flare-ups in association with the disease itself and medication used., Methods: We prospectively identified consecutive patients referred for CDI management during 2015-2017. Stool samples were tested for Clostridium difficile toxin A and/or B and Glutamate Dehydrogenase in patients with clinical symptoms. CDI patients with IBD history were tested for anti-CMV IgG and IgM antibodies by chemiluminescent microparticle immunoassay and underwent histological analysis for CMV on colon biopsies. Data were collected for demographic characteristics, treatment and outcome., Results: 125 patients with CDI were enrolled. Among these patients, 14 (11.2%) were diagnosed with IBD. The mean patient age of IBD patients was 52.5±15.4 years at diagnosis of CDI, 85.7% had UC, 14.3% CD, while the age of patients was shared. Eleven of the total of 14 patients (78.6%) tested positive for anti-CMV IgG. Of these, 3 patients (21.4%) exhibited high CMV IgG avidity, without detectable anti-CMV IgM and biopsy-proven CMV colitis. Of the 14 IBD patients with CDI, 8 patients (57.1%) were receiving anti-tumor necrosis factor (anti-TNF) therapy (21.4 % infliximab or golimumab, 7.1% vedolizumab or adalimumab) and 43.5% of patients were being treated with systemic corticosteroids. Four UC patients (28.6%) on steroids of the 14 CDI patients underwent a colectomy whereas none of the not on steroids patients underwent colectomy (p=0.25). Among them, 1 patient (7.1%) had recurrent CDI after 5 months from the first episode of CDI.These patients were treated with vancomycin, metronidazole and fidaxomicin. The mean age of patients that had a colectomy 65.5±9.32 (n=4) was higher than the mean age of those 47.30±14.49 (n=10) who improved (U Mann-Whitney =6. p=0.04)., Conclusions: Immunosuppressive medications and older age are associated with increased risk of CDI and poor outcome. Although, CMV is a rare colonic pathogen in the immunocompetent patient, it should be included and screened when exacerbation of IBD occurs in patients receiving any type of immunosuppressive therapy., Competing Interests: None declared., (© 2020 Maria Kosmidou, Nicoletta T. Karavasili, Maria Saridi, Alexandros Skamnelos, Athanasios Kavvadias, Anna Batistatou, Konstantina G. Gartzonika, Stavroula Tsiara, Konstantinos H. Katsanos, Dimitrios K. Christodoulou.)

Hepatitis E virus (HEV) is a significant health problem with approximately 20 million individuals infected annually. HEV infection has been associated with a wide spectrum of extrahepatic manifestations, including neurological, hematological and renal disorders. Guillain-Barré syndrome and neuralgic amyotrophy are the most frequent neurological manifestations. In addition, HEV infection has been observed with other neurological diseases, such as encephalitis, myelitis and Bell's palsy. Hematologic manifestations include anemia due to glucose-6-phospate dehydrogonase deficiency, autoimmune hemolytic anemia and severe thrombocytopenia. Membranoproliferative glomerulonephritis and relapse IgA nephropathy with or without coexisting cryoglobulinemia appear to be the most common renal injuries related with HEV infection. Also, HEV infection has been associated with acute pancreatitis and other immune-mediated manifestations, such as arthritis and myocarditis. However, the pathophysiologic mechanisms of HEV-related extrahepatic manifestations are still largely unclear.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are well-described disease entities with unknown etiopathogenesis. Environmental, genetic, gut microbiota, and host immune response correlations have been implicated. The role of susceptibility gene polymorphisms, such as ATG16L1 T300A and ECM1 T130M and G290S, is well-described, although controversial findings have been reported., Methods: Two hundred five patients with inflammatory bowel disease (108 CD and 97 UC), and 223 healthy blood donors (control group) from the Northwest Greece region were genotyped for rs2241880 (T300A), rs3737240 (T130M) and rs13294 (G290S) single nucleotide polymorphisms. Genotyping was performed using the real-time polymerase chain reaction method., Results: The frequency of G allele was significantly higher in CD patients compared to the control group (P=0.029; odds ratio [OR] 1.45, 95% confidence interval [CI] 1.04-2.03). Carriers of two G alleles (T300A), compared to those carrying only one, were 1.3 times more susceptible to CD (P=0.022; OR 2.45, 95%CI 1.14-5.27). In CD patients, the presence of the T300A polymorphism indicates a possible protective effect against developing a penetrating (B3) phenotype, while in UC patients, presence of the T300A polymorphism, indicates a possible protective effect against developing joint-involving extraintestinal manifestations., Conclusion: Our study found a significant association of the T300A polymorphism with CD susceptibility, suggesting that CD occurrence in our population has a strong genetic background, with the T300A G allele having an additive effect., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Aim: To evaluate the uptake of screening colonoscopy among physicians as compared to the general population., Methods: Asymptomatic physicians, aged 45-67 years, at average risk for colorectal cancer (CRC), working in the participating National Health System hospitals were asked to complete a questionnaire regarding the uptake of screening colonoscopy. The results were compared to those in a background healthy population, aged 50-75 years, inhabitants of a Greek county, who were offered a free access to a screening colonoscopy program for CRC. High-risk adenomas were those ≥10 mm in diameter or any adenoma, regardless of size, with villous histology or high-grade dysplasia., Results: Overall, 267 of 782 physicians and 402 of 6,534 nonphysicians underwent a screening colonoscopy (uptake rates 34.2 and 6.2% respectively, p = 0.00001). Screening colonoscopy has yielded 4 adenocarcinomas (1.6%), 14 high-risk adenomas (5.5%), and 61 low-risk adenomas (25.7%) in the physicians' group. Corresponding figures in the nonphysician arm were 4 (1), 26 (6.5), and 107 (26.6%), respectively. The main reason among physicians for nonadherence was indifference/negligence (n = 213)., Conclusion: The proportion of physicians undergoing screening colonoscopy for CRC is significantly higher compared to the general population; however, it does remain suboptimal., (© 2019 S. Karger AG, Basel.)

Irritable bowel syndrome (IBS) is the most common reason to visit a gastroenterologist. IBS was believed to be a functional disease, but many possible pathophysiologic mechanisms can now explain the symptoms. IBS patients are classified into subtypes according to their predominant bowel habit, based on the Rome IV criteria. These include diarrhea-predominant and constipation-predominant IBS, as well as the mixed type, a combination of the two. Usually, IBS treatment is based on the predominant symptoms, with many options for each subtype. A new promising treatment option, fecal microbiota transplantation, seems to have beneficial effects on IBS. However, treating the pathophysiological causative agent responsible for the symptoms is an emerging approach. Therefore, before the appropriate therapeutic option is chosen for treating IBS, a clinical evaluation of its pathophysiology should be performed., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

The pharmacological management of inflammatory bowel disease (IBD) over the last two decades has transitioned from reliance on aminosalycilates, corticosteroids and immunomodulators to earlier treatment with anti-tumor necrosis factor (anti-TNF) therapy. Nevertheless, 20-30% of patients discontinue anti-TNF therapy for primary non-response and another 30-40% for losing response within one year of treatment. These undesirable therapeutic outcomes can be attributed to pharmacokinetic (anti-drug antibodies and/or low drug concentrations) or pharmacodynamic issues characterized by a non-TNF driven inflammation. The latter issues necessitate the use of medications with different mechanisms of action. Besides the biologics natalizumab, vedolizumab and ustekinumab that have already been approved for the treatment of IBD new non-anti-TNF therapies are currently under investigation including small molecule drugs against Janus kinase and sphingosine-1-phosphate receptors. This manuscript will review the medications that are in the later stages of development for the treatment of IBD and directed against immune targets other than TNF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and study aims  Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) improved the diagnostic performance and upgraded the role of endoscopic ultrasonography (EUS) into an interventional modality, able to guide patient management and treatment.This review aimed to highlight the advances, emerging practices, procedural techniques and technological innovations in EUS tissue acquisition in pancreatic diseases. Methods  A thorough review of the literature was performed using PubMed to identify articles that describe techniques, advances, and practices in EUS tissue acquisition in gastrointestinal diseases. Conclusion  Since the first EUS-FNA procedure, EUS guided-tissue acquisition has been evolving continuously. Development of needles with innovative tip design enabled procurement of larger samples with preserved histological architecture. Moreover, sampling techniques and complementary methods, such as contrast harmonic imaging and EUS-elastography, have been introduced in an effort to improve diagnostic performance and sample adequacy.

Patients with inflammatory bowel diseases (IBD) represent heterogeneous groups with different characteristics and different clinical course. A great deal of effort is made to discover proxies for more severe disease needing more intense treatment and early intervention to gain the maximum therapeutic benefit. Endoscopy remains an invaluable method in assessment of patients with IBD. Pseudopolyps are often encountered during endoscopy and, although they are a well described entity, their presence is of unclear importance. In one of our recent studies and in conjunction with one study with a large cohort of patients with IBD and pseudopolyps, patients with pseudopolyps were found to face a higher inflammatory burden in terms of receiving more intense biological treatment. This letter comes as a comment and proposition regarding the concept of re-evaluation of pseudopolyps as a promising marker in IBD scores., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest.

Background and Aim: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years., Methods: The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period., Results: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU., Conclusions: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Inflammatory bowel disease (IBD) consists of two disorders: Crohn's disease (CD) and ulcerative colitis (UC). Over the past few decades, a great body of knowledge has accumulated regarding the pathogenesis of IBD, and effective pharmaceutical agents, such as inhibitors of tumor necrosis factor (anti-TNF), have been introduced. Although these agents have dramatically improved the outcome of IBD, up to 70% of patients with CD and 10-30% of those with UC still undergo surgery within 10 years from diagnosis. Because of their young age and high recurrence rates, these patients are appropriate candidates for laparoscopic surgery as an alternative to laparotomy. Recently, considerable attention has been focused on perioperative outcomes of patients who are receiving anti-TNF agents and require surgery. The aim of this narrative review is to discuss the current evidence regarding the impact of perioperative anti-TNF treatment on post-operative complication rates with a special focus on laparoscopic surgery.