Cutaneous Eruption in a Crohn's Disease Patient Under Tumor Necrosis Alpha Inhibitor Treatment: A Rare Case of Syphilis.

Reaching a diagnosis of a cutaneous eruption in a Crohn's disease (CD) patient treated with anti-tumor necrosis factor alpha (anti-TNFα) can be challenging. Differential diagnosis must include extra-intestinal manifestations of CD, adverse reactions to the therapy itself as well as infectious diseases with cutaneous manifestations. We report the case of a 28-year-old man on infliximab for Crohn's colitis, who presented with painless, non-pruritic genital and body exanthema. After a thorough evaluation, early secondary syphilis was confirmed with a fluorescent treponemal antibodies-absorbed test. Intramuscular (IM) benzathine penicillin G 2.4 million units in a single dose was administered and clinical manifestations resolved completely within a couple of weeks.

Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

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 (q1 -q3, 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.

Sedation during endoscopic procedures: a Hellenic Society of Gastroenterology Position Statement.

Administration of sedation by non-anesthesiologists during gastrointestinal endoscopy remains highly controversial in Greece. The aim of this set of 16 position statements prepared by experts in the field on behalf of the Hellenic Society of Gastroenterology is to aid gastroenterologists in their everyday clinical practice and provide evidence for the best use of drugs for the sedation of patients who undergo an endoscopy. The statements address issues such as the level of sedation required, the best drugs used, their mode of action, their side-effects and possible ways to counter their action, and were adopted if at least 80% of all participants agreed upon them.

The Inflammatory Bowel Disease-Disk Tool for Assessing Disability in Inflammatory Bowel Disease Patients: Validation of the Greek Version.

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.

Signaling pathways associated with bone loss in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized in many patients by extraintestinal manifestations. One of the most common comorbidities seen in IBD patients is a significant reduction in their bone mass. The pathogenesis of IBD is mainly attributed to the disrupted immune responses in the gastrointestinal mucosa and putative disruptions in the gut microbiomes. The excessive inflammation of the gastrointestinal tract activates different systems, such as the RANKL/RANK/OPG and the Wnt pathways linked with bone alterations in IBD patients, thereby suggesting a multifactorial etiology. The mechanism responsible for the reduced bone mineral density in IBD patients is thought to be multifactorial, and, so far, the principal pathophysiological pathway has not been well established. However, in recent years, many investigations have increased our understanding of the effect of gut inflammation on the systemic immune response and bone metabolism. Here, we review the main signaling pathways associated with altered bone metabolism in IBD.

Prevalence and predictors of arthralgia after initiation of vedolizumab in patients with inflammatory bowel disease: a retrospective cohort study.

OBJECTIVES: Vedolizumab is a mAb used for the treatment of moderate to severe ulcerative colitis and Crohn's disease. There is evidence that administration of vedolizumab has been associated with either new onset or reactivation of extra-intestinal manifestations, among which arthralgia is the most prominent. We aimed to study the incidence, characteristics and predictors for the occurrence of arthralgias in patients with inflammatory bowel disease (IBD) who receive vedolizumab. METHODS: A retrospective cohort study was implemented in patients with IBD. The occurrence of new-onset and recurrent arthralgias were recorded. Multivariate Cox proportional-hazards models were used to identify factors associated with the endpoints of interest. RESULTS: A total of 115 vedolizumab-treated IBD patients (male = 50.4%; ulcerative colitis = 70.4%; median follow-up = 12.7 months) participated. New-onset arthralgia occurred in 20.9%, and recurrent in 46.7% (45 patients at risk). Among patients with ulcerative colitis, multivariate Cox's proportional-hazards models showed, that new onset arthralgia was significantly associated with extensive colitis (hazard ratio = 2.91; 95% confidence interval, 1.04-8.12). Of 15 patients with concomitant treatment of azathioprine, no one manifested new-onset arthralgia (X2P = 0.03; Fisher's exact test P = 0.038). No predictors were identified for recurrent arthralgia. CONCLUSION: Arthralgias is a common manifestation of vedolizumab treatment. Patients with extensive ulcerative colitis demonstrate a higher risk for new-onset arthralgia, whereas, concomitant treatment with azathioprine appears to be protective. These associations may be mediated by re-directed lymphocyte trafficking and may support concomitant immunomodulator administration in specific patient subpopulations who commence treatment with vedolizumab.

Patients With Inflammatory Bowel Diseases Have Impaired Antibody Production After Anti-SARS-CoV-2 Vaccination: Results From a Panhellenic Registry.

BACKGROUND: Four EMA-approved vaccines against SARS-CoV-2 are currently available. Data regarding antibody responses to initial vaccination regimens in patients with inflammatory bowel diseases (IBD) are limited. METHODS: We conducted a prospective, controlled, multicenter study in tertiary Greek IBD centers. Participating patients had completed the initial vaccination regimens (1 or 2 doses, depending on the type of COVID-19 vaccine) at least 2 weeks before study enrolment. Anti-S1 IgG antibody levels were measured. Demographic and adverse events data were collected. RESULTS: We tested 403 patients (Crohn's disease, 58.9%; male, 53.4%; median age, 45 years) and 124 healthy controls (HCs). Following full vaccination, 98% of patients seroconverted, with mRNA vaccines inducing higher seroconversion rates than viral vector vaccines (P = .021). In total, IBD patients had lower anti-S1 levels than HCs (P < .001). In the multivariate analysis, viral vector vaccines (P < .001), longer time to antibody testing (P < .001), anti-TNFα treatment (P = .013), and age (P = .016) were independently associated with lower anti-S1 titers. Vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or anti-interleukin-12/IL-23 monotherapy (P = .023 and P = .032). All anti- SARS-CoV-2 vaccines were safe. CONCLUSIONS: Patients with IBD have impaired antibody responses to anti-SARS-CoV-2 vaccination, particularly those receiving viral vector vaccines and those on anti-TNFα treatment. Older age also hampers antibody production after vaccination. For those low-response groups, administration of accelerated or prioritized booster vaccination may be considered.

Thisis a multicenter study on IBD patients after COVID-19 vaccination and anti-S1 IgG antibody levels measurement. Patients with IBD have lower antibody responses than healthy controls, particularly those receiving viral vector vaccines and those on anti-TNFα or combination treatment.

Assessment of Dietary Adequacy and Quality in a Sample of Patients with Crohn's Disease.

Both under-and over-nutrition are prevalent in patients with Crohn's Disease (CD). The aim of the present study was to evaluate dietary intake and compare it with relevant recommendations during active disease and remission, also taking into consideration the adequacy of energy reporting. Dietary quality was assessed through adherence to the Mediterranean diet and to the European dietary guidelines for cardiovascular disease prevention (CVD-score). Malnutrition was diagnosed with the GLIM criteria. There were 237 patients evaluated (54.9% males, 41.3 ± 14.1 years and 37.6% with active disease). In the total sample, high prevalence of overweight/obesity (61.6%) and low prevalence of malnutrition (11.4%) were observed, whereas 25.5% reported low protein intake in the sub-sample of adequate energy reporters. The mean MedDietScore was 28.0 ± 5.5 and the mean CVD-score was 5.25 ± 1.36, both reflecting moderate dietary quality. Patients with active disease reported higher prevalence of low protein intake, lower carbohydrate, fibers, fruits, vegetables, legumes, and sweets consumption and a lower MedDietScore compared to patients in remission. Consumption of fibers, fruits, vegetables, and legumes while in remission did not result in reaching the recommended intakes, and dietary quality was low as reflected by the MedDietScore. In conclusion, both protein undernutrition and energy overconsumption were prevalent in the current sample and overall patients adhered to a moderate quality diet irrespective of disease stage.

Poor performance of predictive equations to estimate resting energy expenditure in patients with Crohn's disease.

Studies exploring the accuracy of equations calculating Resting Energy Expenditure (REE) in patients with Crohn's disease are lacking. The aim of this study was to investigate the accuracy of REE predictive equations against indirect calorimetry in Crohn's disease patients. REE was measured using indirect calorimetry (mREE) after an overnight fasting. Fourteen predictive equations, with and without body composition analysis parameters, were compared with mREE using different body weight approaches. Body composition analysis was performed using dual X-ray absorptiometry. 186 Crohn's disease outpatients (102 males) with mean age 41.3±14.1 years and 37.6% with active disease were evaluated. Mean mREE in the total sample was 1734±443 kcal/day. All equations under-predicted REE and showed moderate correlations with mREE (Pearson's r or Spearman's rho 0.600-0.680 for current weight, all p-values<0.001). Accuracy was low for all equations at the individual level (28-42% and 25-40% for current and adjusted body weight, respectively, 19-33% for equations including body composition parameters). At the group level, accuracy showed wide limits of agreement and proportional biases. Accuracy remained low when sample was studied according to disease activity, sex, body mass index and medication use. All predictive equations underestimated REE and showed low accuracy. Indirect calorimetry remains the best method for estimating REE of patients with Crohn's disease.

Real-World Use and Adverse Events of SARS-CoV-2 Vaccination in Greek Patients with Inflammatory Bowel Disease.

Since inflammatory bowel disease (IBD) patients were excluded from vaccine authorization studies, limited knowledge exists regarding perceptions and unfavorable effects of COVID-19 vaccination in this group. We aimed to investigate the real-world use and adverse events (AEs) of COVID-19 vaccines in Greek IBD patients. Fully vaccinated IBD patients followed in Greek centers were invited to participate. All patients filled out an anonymous online survey concerning the vaccination program, which included information regarding demographics, clinical characteristics, treatment, vaccination perceptions and potential AEs. Overall, 1007 IBD patients were included. Vaccine hesitancy was reported by 49%. Total AEs to vaccination were reported by 81% after dose 1 (D1) and 76% after dose 2 (D2), including isolated injection site reactions (36% and 24% respectively). Systemic AEs were more common after D2 (51%, D2 vs. 44%, D1, p < 0.0001). Very few patients reported new onset abdominal symptoms (abdominal pain 4% (D1), 6% (D2) and diarrhea 5% (D1), 7% (D2)). There were no serious AEs leading to emergency room visit or hospitalization. In multivariate analysis, AEs occurrence was positively associated with young age and female gender (p < 0.0005 for both doses), whereas inactive disease was negatively associated with AE in D1 (p = 0.044). SARS-CoV-2 vaccination in Greek IBD patients demonstrated a favorable and reassuring safety profile.

Response to Anti-α4ß7 Blockade in Patients With Ulcerative Colitis Is Associated With Distinct Mucosal Gene Expression Profiles at Baseline.

BACKGROUND: Improving treatment outcomes with biological therapy is a demanding current need for patients with inflammatory bowel disease. Discovery of pretreatment prognostic indicators of response may facilitate patient selection and increase long-term remission rates. We aimed to identify baseline mucosal gene expression profiles with predictive value for subsequent response to or failure of treatment with the monoclonal antibody against integrin α4ß7, vedolizumab, in patients with active ulcerative colitis (UC). METHODS: Mucosal expression of 84 immunological and inflammatory genes was quantified in RNA extracted from colonic biopsies before vedolizumab commencement and compared between patients with or without response to treatment. Significantly differentiated genes were further validated in a larger patient cohort and within available public data sets, and their functional profiles were studied accordingly. RESULTS: In the discovery cohort, we identified 21 genes with a statistically significant differential expression between 54-week responders and nonresponders to vedolizumab. Our validation study allowed us to recognize a "core" mucosal profile that was preserved in both discovery and validation cohorts and in the public database. The applied functional annotation and analysis revealed candidate dysregulated pathways in nonresponders to vedolizumab, including immune cell trafficking, TNF receptor superfamily members mediating noncanonical NF-kB pathway, in addition to interleukin signaling, MyD88 signaling, and toll-like receptors (TLRs) cascade. CONCLUSIONS: Nonresponse to vedolizumab in UC is associated with specific pretreatment gene-expression mucosal signatures and dysregulation of particular immunological and inflammatory pathways. Baseline mucosal and/or systemic molecular profiling may help in the optimal stratification of patients to receive vedolizumab for active UC.

Predictors of Response to Vedolizumab in Patients with Ulcerative Colitis: Results from the Greek VEDO-IBD Cohort.

BACKGROUND: Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. AIMS: We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. METHODS: Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. RESULTS: We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. CONCLUSIONS: Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.

Irrigating Acetic Acid Solution During Colonoscopy for the Detection of Sessile Serrated Neoplasia: A Randomized Controlled Trial.

BACKGROUND: Misdiagnosed sessile serrated lesions (SSLs) are important precursors for interval colorectal cancers. AIMS: We investigated the usage of acetic acid (AA) solution for improving the detection of SSLs in the right colon in a randomized controlled trial. METHODS: A tandem observation of the right colon was performed in 412 consecutive patients. A first inspection was performed under white light high-definition endoscopy. In the AA group, a low concentration vinegar solution (AA: 0.005%) irrigated by a water pump in the right colon was compared with a plain solution of normal saline (NS) in the diagnostic yield of SSLs during the second inspection. Secondary outcomes in overall polyp detection were measured. RESULTS: Qualitative comparisons showed significant differences in the detection rates of all polyps except adenomas, with remarkable improvement in the demonstration of advanced (> 20 mm), SSLs, and hyperplastic polyps during the second inspection of the right colon using the AA solution. Significant improvement was also noted in the AA group, as far as the mean number of polyps/patient detected, not only in SSLs (AA group: 0.14 vs. NS group: 0.01, P < 0.001), but also in all histological types and all size-categories in the right colon. Small (≤ 9 mm) polyps were detected at a higher rate in the sigmoid colon expanding the effect of the method in the rest of the colon. CONCLUSION: AA-assisted colonoscopy led to a significant increase in SSLs detection rate in the right colon in a safe, quick, and effective manner.

A rare case of duodenal-type follicular lymphoma in rectum appearing as hyperplastic polyp with metachronous appearance in duodenum and stomach.

Hyperplastic polyps consist a very frequent finding in colonoscopy having a very low potential to malignancy. According to the international guidelines, it is recommended that all polyps should be resected except for diminutive (≤ 5 mm) rectal and rectosigmoid polyps which are predicted with confidence to be hyperplastic. Therefore, in departments where optical diagnosis can be ensured, a "resect and discard" strategy may be implemented for diminutive polyps. In our case, a duodenal-type follicular lymphoma was detected in a 5 mm rectum polyp with hyperplastic appearance. After 4 months, the lymphoma was detected also in stomach and duodenum. Under therapy with Rituximab, she is in remission. To our knowledge, there has never been reported such a case in the literature. Furthermore, it alerts us that we should be very cautious with the optical diagnosis and the "resect and discard strategy".

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

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.

The burden and management of anemia in Greek patients with inflammatory bowel disease: a retrospective, multicenter, observational study.

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.

Effect of golimumab on health-related quality of life, other patient-reported outcomes and healthcare resource utilization in patients with moderate-to-severe ulcerative colitis: a real-world multicenter, noninterventional, observational study in Greece.

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.