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Background & Aims: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. Methods: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. Results: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. Conclusions: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high. [ABSTRACT FROM AUTHOR]

Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with an unpredictable course and a remitting–relapsing evolution. Fatigue is a frequent complaint in patients with IBD, affecting approximately half of the newly diagnosed patients with IBD. The aim of this study was to analyze fatigue in patients with IBD in remission. Materials and Methods: One hundred nineteen consecutive outpatients diagnosed with IBD for over 3 months that were in corticosteroid-free clinical and biochemical remission at the time of assessment were included in this cross-sectional study. Out of them, 72 (60.5%) were male; the median age was 39 years (IQR 30–47). Seventy-seven patients (64.7%) were diagnosed with Crohn's disease and forty-two (35.3%) with ulcerative colitis, with a median disease duration of 6 years (IQR 2–10). Fatigue, health-related quality of life (HR-QoL), anxiety and depression were evaluated using the following self-administered questionnaires: FACIT Fatigue, IBDQ 32 and HADS. Results: The mean FACIT-Fatigue score was 41.6 (SD ± 8.62), and 38.7% of patients were revealed as experiencing fatigue when a cut-off value of 40 points was used. The mean IBDQ 32 score was 189.4 (SD ± 24.1). Symptoms of anxiety and depression were detected in 37% and 21% of the patients, respectively. In the multivariate analysis, fatigue was significantly associated with lower HR-QoL (OR 2.21, 95% CI: 1.42–3.44, p < 0.001), symptoms of anxiety (OR 5.04, 95% CI: 1.20–21.22, p = 0.008), female sex (OR 3.32, 95% CI: 1.02–10.76, p = 0.04) and longer disease duration (OR 1.13, 95% CI: 1.01–1.27, p = 0.04). Conclusions: Fatigue is highly prevalent even in patients with inactive IBD and is correlated with lower HR-QoL and anxiety, as well as with clinical factors such as longer disease duration and female sex. [ABSTRACT FROM AUTHOR]

Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with an unpredictable evolution that can have a negative impact on patients' quality of life (QoL). Even though patients in remission have a better QoL compared to patients with active disease, they still have a lower QoL compared to healthy people. The aim of this study is to identify the factors that are associated with a lower QoL in patients with IBD in clinical remission, in a tertiary IBD center in Romania. Materials and Methods: Ninety-seven adult patients with a current diagnosis of IBD for over 3 months who were in clinical remission were enrolled in this study. Pregnant women, patients with ostomy, perianal disease, extraintestinal manifestations or other significant comorbidities were excluded. Out of the 97 patients, 63.9% were men. The median age was 39 years (IQR 29–47), and the median disease duration was 5 years (IQR 2–10). Disease activity was assessed using the SCCAI score for ulcerative colitis and HBI score for Crohn's disease. Remission was defined for SCCAI score ≤ 1 and HBI score ≤ 4. The health-related quality of life (HR-QoL) was assessed using the IBDQ32 score. FACIT-Fatigue was used to evaluate the level of fatigue. Patients with symptoms of anxiety or depression were identified with the HADS score. Symptoms of anxiety were considered when HADS-A >7 points and symptoms of depression when HADS-D >7 points. Results: Sixty-five patients (67%) were diagnosed with CD and the remaining 32 (33%) with UC. Ninety-three patients (95.9%) were on biological therapy. The mean IBDQ score (total score) was 190.54 points (SD +/− 8.2). The mean FACIT Fatigue score was 42.5 (SD +/− 8.2), with 6.2% of patients suffering from severe fatigue (FACIT Fatigue < 30 points). A total of 33% of patients had symptoms of anxiety and 16.5% of depression. Exposure to more than one biologic therapy (p = 0.02), fatigue (p < 0.001) and symptoms of anxiety (p < 0.001) were associated with a lower HR-QoL in the multivariate analysis. Female patients, patients with Crohn's disease, patients with anemia and patients with symptoms of depression also had a lower HR-QoL, but this did not reach statistical significance in our study. Conclusions: Exposure to a higher number of biological agents (patients that switched multiple biologics), the presence of fatigue and symptoms of anxiety impair the HR-QoL of patients with IBD in clinical remission. Further studies should assess in a prospective manner whether early identification of these factors with prompt clinical interventions could lead to a better HR-QoL in these patients. [ABSTRACT FROM AUTHOR]

CONVENTIONALLY, UC IS RECOGNIZED AS A DISEASE WITH CONTINUOUS MUCOSAL INFLAMMATION THAT EXTENDS FROM THE RECTUM TO THE PROXIMAL PART OF THE COLON, BUT DURING THE LAST DECADE, A PARTICULAR PATTERN OF COLITIS THAT INVOLVES THE DISTAL COLON WITH A NORMAL APPEARANCE MUCOSA INTERPOSED AND A WELL DEFINED AREA OF INFLAMMATION AROUND THE APPENDIX HAS BEEN HIGHLIGHTED. WE USED A TERTIARY CARE CENTER EVIDENCES TO ANALYZE THE CHARACTERISTICS OF UC PATIENTS WITH PARP. WE EVALUATED 76 PATIENTS WHO WENT TO OUR CLINIC FOR INVESTIGATING CHRONIC DIARRHEA SYNDROME BETWEEN JANUARY 2018-DECEMBER 2020 AND FOR WHOM A DIAGNOSIS OF ULCERATIVE COLITIS WAS ESTABLISHED. ONLY 7 PATIENTS HAD ENDOSCOPICALLY ASPECT OF PARP (THIS HAPPENED DURING FOLLOW-UP ENDOSCOPY), ASPECT SUPPORTED ALSO BY THE HISTOLOGICAL DESCRIPTION (NANCY INDEX SCORE). DURING FOLLOW-UP, MOST PATIENTS WITH PARP KEPT THE SAME EXTENT OF LESIONS. CONCLUSIONS: WE CONFIRM THE PRESENCE OF PARP AS A "SKIP LESION" IN DISTAL UC, DIAGNOSTIC SUPPORTED ALSO BY THE HISTOPATHOLOGIST, AND EVEN THOUGH WE ARE CONFIDENT IN THE DIAGNOSIS OF ULCERATIVE COLITIS, ONE PATIENT HAD A CROHN'S DISEASE PHENOTYPE SWITCH DURING THE EVOLUTION. NONETHELESS, WE CANNOT CONCLUDE THAT PARP HAS A ROLE IN THE EXTENSION OF LESIONS, REMISSION OR RELAPSE OF DISEASE, GIVEN THE FACT THAT WE DO NOT HAVE A SUFFICIENT GROUP OF ELIGIBLE PATIENTS, FOR WHICH REASON DETAILED STUDIES ARE NEEDED. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness and safety of biosimilar infliximab (CT-P13) in a real-life setting in adults with moderate-to-severe active Crohn's disease (CD) or ulcerative colitis (UC). Methods: This multi-centre, observational cohort study was conducted at medical centres in Romania, Czech Republic, and Bulgaria. Effectiveness was measured using the Crohn's Disease Activity Index (CDAI) for CD or partial Clinical Activity Index (pCAI) for UC. Quality-of-life (QoL) was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Safety was assessed according to treatment withdrawals and adverse events (AEs) monitoring. Analyses were performed in the safety population and were reported based on the observed case (OC) or last observation carried forward (LOCF) method. Results: Altogether, 85 patients with CD (n = 38) or UC (n = 47) received biosimilar infliximab for up to 30 weeks. Most patients (n = 68; 80.0%) had no prior exposure to infliximab. At the end of treatment, 65.8% (95% CI = 49.8–78.9) of CD patients and 55.3% (95% CI = 41.2–68.6) of UC patients showed a clinical response, and 47.4% (95% CI = 32.5–62.7) and 48.9% (95% CI = 35.3–62.8), respectively, were in remission. Statistically significant (p < 0.0001) improvements from baseline were observed in CDAI and pCAI scores (both LOCF). In the combined CD and UC population, SIBDQ was significantly improved (p < 0.0001) from baseline to end of treatment (OC). Two AEs (moderately severe infusion reactions) were judged by investigators to be definitely related to treatment, one of which led to treatment withdrawal. Conclusion: Results align with those of previous studies demonstrating the effectiveness and safety of biosimilar infliximab in CD and UC. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Cytokines and their receptors play a critical role in the pathogenesis of the inflammatory bowel disease (IBD). The aim of this study was to investigate the expression profiles of inflammatory genes in inflamed and non-inflamed colonic tissue samples in patients with Crohn's disease (CD) and ulcerative colitis (UC), and to identify molecular signatures for different IBD phenotypes. Methods: Seventy-one patients diagnosed with IBD (38 CD, 33 UC) and 15 non-IBD controls have been included in the study. For each patient, biopsy samples were obtained during colonoscopy from inflamed (L) and healthy (N) mucosa. We investigated by commercially available reverse-transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) kit the mRNA expression of a set of 40 genes involved in inflammation: cytokines, chemokines, receptors, signal transduction molecules and transcription factors. Results: In L biopsies from patients with CD, higher expression levels were found for IL-4 (p=0.009) and IL-12p35 (p=0.0005), whereas in L biopsy samples from patients with UC higher expression levels were found for IL-8 (p=0.03), chemokines SCYA3 (p=0.05), SCYA4 (p=0.01) and glutathione S-transferase P1 (p=0.01). In N biopsies of patients with CD higher expression levels were found for IL-1R (p=0.01) and IL-12p35 (p=0.007), whereas in N biopsies of patients with UC higher expression levels were found for IL-15 (p=0.009) and SCYA8 (p=0.001). The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD. Conclusions: RT-MLPA is a sensitive and effective method for the evaluation of the profiles of inflammatory genes in IBD, with potential future applications for diagnosis, phenotypic stratification and targeted therapy. [Copyright &y& Elsevier]

Summary: Background & aims: Malnutrition is variably encountered in adult patients with Crohn’s disease. We evaluated the nutritional status at the beginning and during Infliximab treatment in patients with Crohn’s disease. Methods: Patients with moderate/severe flares of disease treated with Infliximab for induction and maintenance of remission were included in a prospective observational study. Body Mass Index and Nutritional Risk Index were calculated in each patient at 0, 6 weeks and than every 8 weeks for one year. Results: From 30 patients treated with Infliximab 59.3% had low BMI, 35.7% being undernourished. The severity of Crohn’s disease did not correlate with low BMI but did correlate with Nutritional Risk Index (p = 0.001). In all patients that responded to Infliximab treatment progressive weight gain was observed, all but one patient reaching normal BMI after one year. Mean weight gain was significantly more elevated (p = 0.001) and time needed to reach normal BMI was longer in the undernutrition group (p = 0.01). Clinical remission was the principal factor associated with weight gain (p = 0.001), while there was no influence of endoscopic remission on nutritional status. Conclusions: In patients with moderate/severe forms of Crohn’s disease malnutrition is frequently encountered. Induction and maintenance treatment with Infliximab determines weight gain and corrects malnutrition in all patients with clinical remission. [Copyright &y& Elsevier]

Introduction. Crohn's disease (CD) and ulcerative colitis (UC), can resemble similarities regarding endoscopic/histologic aspects, which carry different outcomes. The definitive diagnosis of IBD requires corroboration of multiple datas, upper and lower endoscopy playing an important role for the positive diagnostic and for excluding other causes of diarrhea. Study objective: This work is a single-center study with retrospective recruitment of patients with first diagnosis of IBD and its primary objective is to analyze whether or not there is a relationship between the macroscopic diagnosis and the histopathological one. As secondary objectives we analized epidemiological data, symptoms, macroscopic appearence of the lessions and the existence of microscopic lessions and we calculated histopathological scores (GHAS for CD and Geboes for UC). Materials and Methods. A retrospective recruitment of patients newly diagnosed with IBD has been made, within 4 years. 174 patients were eligible and were distributed into two groups: 80 patients with exclusive colonic CD and 94 patients with pancolitis. Patients with ileal involvement, fistulizing pattern, or who were already diagnosticated and treated were excluded. Results. We had a slightly male preponderance (52.9% versus 47.1%) with a mean age of disease onset of 38.0 years; we had 68.7% patients with CD inflammatory pattern, respectively 31.3% with stenosing one. Most of the patients had moderate disease (34 -CD and 57-UC). Most commonly reported macroscopic appearance was erythema and oedema in both groups: 76.4% (CD) and 87.4% (UC). In terms of histological severity, severe forms (translated by Geboes score >3.1 and GHAS > 10) are overwhelmingly found in both groups. Conclusions. The concordance between the macroscopic appearance reported by the endoscopist and the microscopic appearance concluded by the pathologist, correlated positively with the degree of chronic inflammation for patients with UC, but we did not obtain similar results for those with CD, partialy reflecting the discontinuous nature of the lessions. The results of the correlation between Mayo score and Geboes score demonstrated that any increase in the degree of chronic inflammation, architectural changes, presence of eosinophils or neutrophils in the lamina propria, or erosions/ulcerations were associated with an increase in Mayo score. Concerning a possible correlation between the severity of CD and histopathological appearance, we had a striking observation, namely that no statistically significant association between predictors and the degree of severity of CD was evident. In conclusion, we hypothesized that a possible influence of histopathological lesions on disease severity is small. [ABSTRACT FROM AUTHOR]

Background & Aims: Bowel ultrasound (BU) is a non-invasive, inexpensive, widely available tool, valuable for inflammatory bowel disease (IBD) assessment. The aim of the present study was to investigate the clinical utility of BU to predict the need to intensify therapy in IBD patients. Methods: One hundred seventeen IBD patients (89 Crohn's disease, and 28 ulcerative colitis) diagnosis established at least 6 months before enrolment, undergoing maintenance therapy were prospectively included in the study. Bowel ultrasound investigated the following parameters: the bowel wall thickness (BWT), loss of wall stratification, the presence of the bowel wall Doppler signal, the visible lymph nodes, the mucosal hyperechoic spots, and the irregular external bowel wall. The patients were followed-up for 6 months, registering the need to escalate the treatment regimen. Subgroup analyses were conducted for patients requiring immediate treatment intensification (37 subjects), due to active disease at baseline and patients with subsequent treatment intensification, in the 6 months follow-up period (21 cases) in comparison to patients that required no therapeutic optimization (59 cases). Results: During the follow-up, 49.6% of patients needed treatment escalation. All the investigated BU variables were significantly associated with the main outcome. In the multivariate analysis, the mean BWT (p<0.0001), and the presence of the bowel wall Doppler signal (p=0.007) were independent predictors of the main outcome. For the subgroup analyses: mean BWT (p=0.0001) and the presence of the bowel wall Doppler signal (p=0.01) were independent predictors for immediate treatment intensification (active disease at baseline) and mean BWT (p=0.0003) and the lack of bowel wall stratification (p=0.05) were independent predictors for the need of subsequent therapeutic optimization. Logistic regression prediction models and prediction scores (BU score) had the best AUROC values (>0.91) when compared to traditional biomarkers of active inflammation, such as C reactive protein or fecal calprotectin. Conclusion: Bowel ultrasound could be used as a non-invasive, easy to use diagnostic tool to predict the need to intensify therapy in patients with IBD. [ABSTRACT FROM AUTHOR]

Background & Aims: Identifying the risk factors for extraintestinal manifestations (EIMs) in inflammatory bowel diseases (IBD) may optimize the therapeutic decision. We aimed to assess the prevalence of EIMs in IBD patients in Romania and to determine the risk factors. Methods: We analyzed 2,626 patients registered in the Romanian IBD Prospect National Registry. We performed a descriptive cross-sectional study to assess the point prevalence of EIMs, calculating global prevalence and analyzing the different types of EIMs and their respective frequencies were carried out. Demographic and clinical risk factors were researched as possible predictors for EIMs development, based on the results of the univariate and multivariate logistic regression analysis. Results: The overall point prevalence of EIMs was 16.3%. A significantly higher frequency of EIMs in Crohn's disease (CD) was noted in comparison to ulcerative colitis (UC) and IBD unclassified (IBDU) (23.2% vs 11.3% and 16.3%, respectively, p<0.001). The most frequent type of EIM was peripheral arthropathy (8.3%), significantly associated with CD (p<0.001). Univariate analysis highlighted the significant independent common predictive risk factors for EIMs, in both CD and UC patients: female gender, patient's urban area of origin, anemia, hypoalbuminemia, and high level of C-reactive protein (CRP), while significant independent IBD phenotype-related risk factors were ileocolonic location and concomitant involvement of upper gastrointestinal tract for CD, non-smoker status and both moderate and severe disease activity for UC (p<0.05). Multivariate analysis determined that female CD patients with moderate or severe disease activity, with other than isolated ileal disease, and female UC patients with moderate or severe extensive colitis are the most likely to develop EIMs. Conclusions: IBD patients are experiencing EIMs in a large proportion, with higher rates for CD. As EIMs negatively affect patient outcomes, foreseeing the risk by identifying independent and associated predictive factors could be a first step to optimal work-up and treatment [ABSTRACT FROM AUTHOR]

Background & Aims: Prevalence of malnutrition in inflammatory bowel diseases (IBD) varies between 16% and 75%. Data on the nutritional status at initial diagnosis of ulcerative colitis (UC) or Crohn's Disease (CD) are scarce. It is believed that more than 50% of IBD patients suffer significant weight loss prior to diagnosis. The aims of our study were to assess malnutrition in patients recently diagnosed with IBD and to determine its predictive factors. Methods: We retrospectively included 625 IBD patients registered in the Romanian "IBD Prospect" database between January 2006 and July 2017. All patients were diagnosed within 6 months prior to registration. We defined malnutrition as weight loss of more than 5% of the initial weight during the 3 months prior to registration. Results: There were 361 new cases of UC, 241 CD and 23 cases of unclassified IBD. There was a slight male predominance (M/F=1.2). Prevalence of overall malnutrition was 36.3%. It was significantly more frequent in CD than in UC patients (41.1% vs. 32.4%, p=0.031). In multivariate analysis, malnutrition in UC patients was associated with male gender (p=0.001), more severe disease (p<0.0001) and more extensive disease (p=0.027), while in CD it was associated with younger age (p=0.013) and more severe disease (p<0.0001). Conclusions: About 1 in 3 newly diagnosed IBD patients presents with malnutrition at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Background and aim. In spite of prolonged disease remission of IBD patients, induced by the new biological molecules, a significant number of them suffer from persistent debilitating symptoms with major impact on the quality of life. Frequently, these symptoms are due to post-inflammatory motility changes and misinterpreted as functional disorders. Our aim is to identify and characterize the anorectal motility dysfunction in IBD patients. Method. We are conducting an ongoing prospective study started in August 2019, which includes the IBD patients admitted in a Tertiary Gastroenterology Centre in Bucharest, with specific symptoms (anorectal pain, incontinence, difficult defecation). We perform high resolution anorectal manometry using Sandhill Scientific systems, the parameters being analysed using InSIGHT software. The manometric testing comprise measurements of anorectal pressure at rest, during squeeze, simulated evacuation, rectoanal inhibitory reflex (RAIR) and rectal sensory testing, in compliance with International Anorectal Physiology Working Group protocol. Results. We studied 21 patients (12 patients with Ulcerative Colitis and 9 patients with Crohn's Disease, 15 females and 6 males, mean age 40 (±11.43) years. Only 23.1% (5 patients) had rectal active involvement. Symptoms were reported by 81.0% (17) patients: pain (57.1%), anal incontinence (94.1%), difficult evacuation (29.4%), urgency (64.7%) and intolerance of rectal therapies (35.3%); rectal inflammation was not correlated with the presence of symptoms in our study group (p= 0.53). Modified manometric parameters were found in 81.0% patients and were associated with previous pelvic surgical interventions (p<0.05); although, the latter does not seem to increase the risk of incontinence (p= 0.33). In 61.9% cases the manometric measurements correlated with the symptoms. 85% of the patients with passive incontinence presented lower resting pressure and 57.1% of those with active incontinence were found with lower squeeze pressures. Changes compatible with dyssynergia were detected in 61.9% of the cases. Sensory testing revealed alterations in 46.2% of patients, and RAIR was negative in 33.3% of the cases. Conclusions. There was a considerable number of patients with anorectal motility changes. Therefore, pelvic floor investigation is an essential tool in the management of IBD patients with anorectal syptoms. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence and mildness of inflammatory bowel diseases (IBD) in South Eastern Europe. The authors had reported the low incidence and low prevalence of IBD in Romania. They compare the characteristic of IBD in Romania and Turkey and noted that most patients had ulcerative colitis and some had Crohn's disease.

Background & Aims. Serological markers have been widely used for diagnostic purposes and disease stratification in inflammatory bowel diseases (IBD). The aim of this study was to investigate the seroprevalence and the correlations of anti-Saccharomyces cerevisiae antibodies (ASCA) titers with different clinical phenotypes in Romanian patients with Crohn's disease (CD). Methods. The study included 107 CD and 86 ulcerative colitis (UC) patients from the Gastroenterology Departments of three University Hospitals, and 60 healthy subjects. ASCA IgA and IgG titers were determined using ELISA test. For CD patients the phenotype was established according to the Montreal classification. The differences in ASCA titers for different CD phenotypes were assessed using the Mann-Whitney U test. Results. ASCA prevalence was 33.6% in CD group, 12.8% in UC group and 6.6% in the control group. Significantly higher IgA (p=0.05) and IgG (p=0.03) titers were found in patients from the Montreal A1+A2 groups (age at onset below 40) compared with the older patients (A3). Higher titers were found in patients with extensive ileo-colonic lesions (L3) and upper gastrointestinal tract involvement (L4) than in patients having only colonic disease (L2). Significantly higher IgA (p=0.03) and IgG (p=0.03) titers were observed in patients with stenosing (B2) and penetrating (B3) disease compared with the nonstricturing, nonpenetrating (B1) phenotype. No correlation between ASCA titers and disease duration was found. Conclusion. ASCA seropositivity in Romanian CD patients is lower than in Western Europe. Higher ASCA IgA and IgG titers are associated with a younger age at diagnosis and more aggressive phenotypes. [ABSTRACT FROM AUTHOR]