Diagnosis and Medical Treatment of Acute and Chronic Idiopathic Pouchitis in Inflammatory Bowel Disease.

Despite the decreased rates in inflammatory bowel disease (IBD) colectomies due to high advances in therapeutic options, a significant number of patients still require proctocolectomy with ileal pouch-anal anastomosis (IPPA) for ulcerative colitis (UC). Pouchitis is the most common complication in these patients, where up to 60% develop one episode of pouchitis in the first two years after UC surgery with IPAA with severe negative impact on their quality of life. Acute cases usually respond well to antibiotics, but 15% of patients will still develop a refractory disease that requires the initiation of advanced immunosuppressive therapies. For chronic idiopathic pouchitis, current recommendations suggest using the same therapeutic options as for IBD in terms of biologics and small molecules. However, the available data are limited regarding the effectiveness of different biologics or small molecules for the management of this condition, and all evidences arise from case series and small studies. Vedolizumab is the only biologic agent that has received approval for the treatment of adult patients with moderately to severely active chronic refractory pouchitis. Despite the fact that IBD treatment is rapidly evolving with the development of novel molecules, the presence of pouchitis represents an exclusion criterion in these trials. Recommendations for the approach of these conditions range from low to very low certainty of evidence, resulting from small randomized controlled trials and case series studies. The current review focuses on the therapeutic management of idiopathic pouchitis.

Treatment of antibiotic refractory chronic pouchitis with JAK inhibitors and S1P receptor modulators: an ECCO CONFER Multicentre Case Series.

BACKGROUND AND AIMS: Data regarding effectiveness and safety of JAK inhibitors and S1P receptor modulators in antibiotic refractory chronic pouchitis (CARP) are lacking. METHODS: This ECCO-CONFER project retrospectively collected JAK inhibitors or S1P receptor modulators treatments for CARP with at least 3-months follow up. The outcomes included corticosteroid and antibiotics-free clinical response and remission at three and twelve months, trend in mPDAI, endoscopic PDAI, CRP and calprotectin. RESULTS: Seventeen treatments in 15 patients were collected. Previous pouchitis treatments included infliximab (5/15), adalimumab (4/15), vedolizumab (9/15), and ustekinumab (5/15). Pooling data on JAK inhibitors (8 tofacitinib, 1 filgotinib and 6 upadacitinib), after 3 months (T3), steroid and antibiotics-free clinical response was achieved in 53.3% (8/15), steroid and antibiotics-free clinical remission was achieved in 40% (6/15). Of the patients with at least 12 months of follow-up, steroid and antibiotics-free clinical response was achieved in 50% (3/6) and remission in one patient (16.7%), endoscopic response in 50% (3/6), endoscopic remission in 50% (3/6). Of the two ozanimod treatments at T3, steroid and antibiotics-free clinical response was achieved in one patient, without remission; both discontinued ozanimod before T12. No side effects reported. CONCLUSIONS: Small molecules may represent a suitable option for CARP refractory to multiple biologics, deserving further investigation.

Rotational Thromboelastometry Coagulation Parameters (ROTEM®) May be Discriminative for Active Inflammatory Bowel Disease: A Prospective Observational Study.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is associated with increased risk of thromboembolic events. The rotational thromboelastometry (ROTEM®) is a validated integrative assessment of coagulation, but it has never been studied in IBD patients. METHODS: We performed a monocentric prospective observational study in a national tertiary center. Adult IBD patients underwent ROTEM® analysis on admission to our IBD Department. Parameters evaluated with ROTEM® tests (INTEM, EXTEM and FIBTEM) were clotting time (CT), the time of clot formation (CFT), clot firmness amplitude after 5 and 10 minutes (A5 and A10) and maximum clot firmness (MCF). ROC curves were performed in order to evaluate the ability of ROTEM® to predict active IBD. RESULTS: Several ROTEM® parameters were significantly associated with active IBD compared to patients in remission, towards a hypercoagulable status for patients with active disease: CT, CFT, A5, A10, MCF. ROC analysis demonstrated that parameters related to clot robustness showed a very good prediction ability of active IBD (AUC >0.8): A5, A10, MCF in INTEM (p<0.001), in EXTEM (p<0.001) and MCF in FIBTEM (p<0.001). ROTEM® parameters showed high correlations with inflammation markers as C-reactive protein (CRP) and faecal calprotectin (FC). CONCLUSIONS: Our study showed that ROTEM® parameters are modified in patients with active IBD, being correlating with inflammation markers and demonstrating a high prediction ability of active IBD. Future research is needed to validate ROTEM® as a method to discriminate patterns of active IBD and to guide anticoagulant therapy in patients with active IBD.

Impact of Dietary Patterns in Inflammatory Bowel Disease Subtypes Versus Healthy Subjects: a Retrospective Cohort Study.

Objectives:Inflammatory bowel diseases (IBD) have been associated with multiple environmental factors, including diet. A dietary pattern characterized by low fiber content, high fat content and high carbohydrate content has been linked to the development of IBD. The objective of the current investigation is to examine the potential link between dietary patterns and the occurrence of IBD and to investigate whether there are any differences in relation to the type of IBD and specific food groups. Material and methods:We conducted an observational retrospective comparative study using three cohorts: 89 Crohn's disease (CD) patients, 40 ulcerative colitis (UC) patients and 64 healthy subjects. All participants underwent structured interviews and were required to complete a questionnaire regarding their dietary habits either prior to the onset of IBD or within the last year for control subjects. Results:A higher proportion of CD patients reported a higher rate of salt intake (71.9% vs. 53.1%, p-value = 0.043), sweetened beverages (38.2% vs. 17.2%, p-value=0.022), processed meat (66.3% vs. 40.6%, p-value=0.007), fatty meat (50.6% vs. 28.1%, p-value=0.021), fried foods (47.2% vs. 9.4%, p-value<0.001) and mayonnaise (21.3% vs. 6.2%, p-value=0.032) and a lower intake of nuts and seeds (20.2% vs. 43.8%, p-value=0.004) and yogurt (23.6% vs. 43.8%, p-value=0.030) compared to healthy subjects. Compared to controls, in the UC group there was a higher consumption of salt (85% vs. 53.1%, p-value=0.003), sweetened beverages (47.5% vs. 17.2%, p-value=0.005), fatty meat (55% vs. 28.1%, p-value=0.025) and fried foods (55% vs. 9.4%, p-value<0.001) and a lower intake of nuts and seeds (10% vs. 43.8%, p-value=0.001). Conclusion:Diet patterns before the onset of the disease are similar in patients with Crohn's disease and patients with ulcerative colitis: increased consumption of sweetened beverages, processed and fatty meat, fried food, salt, store-bought ice cream, and mayonnaise, and decreased intake of seeds, nuts, and yogurt.

Fatigue Is Associated with Anxiety and Lower Health-Related Quality of Life in Patients with Inflammatory Bowel Disease in Remission.

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.

Surgery for Inflammatory Bowel Disease in the Era of Biologic Therapy: A Multicenter Experience from Romania.

Background and Objectives: Biologic therapy has fundamentally changed the opportunity of medical treatment to induce and maintain remission in inflammatory bowel disease (IBD). Nevertheless, the rate of surgery is still at a very high rate, profoundly affecting the quality of life. We aimed to analyze surgical cases at three major IBD units in order to identify the main risk factors and the impact of biologic therapy on pre- and postsurgical outcomes. Material and Methods: This was a multicenter retrospective cohort study that included 56 patients with IBD-related surgical interventions from 3 tertiary care hospitals in Bucharest, Romania. The study was conducted between January 2017 and June 2021. All data were retrospectively collected from the medical records of the patients and included the age at diagnosis, age at the time of surgery, IBD type and phenotype, biologic therapy before or/and after surgery, timing of biologic therapy initiation, extraintestinal manifestations, type of surgery (elective/emergency), early and long-term postoperative complications and a history of smoking. Results: A low rate of surgical interventions was noted in our cohort (10.3%), but half of these occurred in the first year after the IBD diagnosis. A total of 48% of the surgical interventions had been performed in an emergency setting, which seemed to be associated with a high rate of long-term postoperative complications. We found no statistically significant differences between IBD patients undergoing treatments with biologics before surgery and patients who did not receive biologics before the surgical intervention in terms of the IBD phenotype, type of surgery and postoperative complications. Conclusion: Our study showed that biologics initiated before the surgical intervention did not influence the postoperative complications. Moreover, we demonstrated that patients with Crohn's disease and no biologics were the most susceptible to having to undergo surgery. Conclusion: In conclusion, the management of patients with IBD requires a multidisciplinary approach that considers an unpredictable evolution.

Health-Related Quality of Life in Patients with Inflammatory Bowel Disease in Clinical Remission: What Should We Look For?

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.

Efficacy and Safety of Ledispavir/Sofosbuvir with or without Ribavirin in patients with Decompensated Liver Cirrhosis and Hepatitis C Infection: a Cohort Study.

BACKGROUND AND AIMS: Ledipasvir/Sofosbuvir (LDV/SOF) with or without Ribavirin (RBV) has shown good results in terms of efficacy and safety in clinical trials in advanced liver cirrhosis, but real-life data are still needed in order to confirm this profile. We investigated the efficacy and safety of LDV/SOF in a large Romanian population with liver cirrhosis and genotype 1b hepatitis C virus (HCV). METHODS: We analyzed a multicentric retrospective cohort enrolling 349 patients with decompensated liver cirrhosis due to HCV who received LDV/SOF±RBV 12/24 weeks (301/48). Patients were included between 2017-2018, all with genotype 1b. Main inclusion criteria were liver cirrhosis and detectable HCV RNA. The cases were followed-up monthly during therapy and 12 weeks after the end of therapy. RESULTS: The cohort included 60% females with a median age of 61, 16% interferon (IFN) pre-treated, 53% with comorbidities, 40/53/7 % with Child Pugh A/B/C, 4% with virus B co-infection and 8% with previously treated hepatocellular carcinoma. Mean initial MELD score was 11.92 (6.82÷ 24.5). Six patients were lost during follow-up. Sustained virologic response (SVR) in intention-to-treat was reported in 85.1%. Predictive factors of SVR in decompensated cirrhosis were female gender (p=0.01), advanced age (p<0.001), lower bilirubin levels (p=0.002) and lower CTP score (p=0.02). In patients with CTP score B or C low bilirubin levels (p=0.003), low INR (p<0.001), increased platelet count (p=0.04), low CTP score (p<0.001), lack of encephalopathy (p=0.02), serum albumin >3.5g/dl (p=0.002) predicted improvement of liver function. Serious adverse events were reported in 16/349 (4.6%), most of them due to severe liver decompensation (9/16). CONCLUSIONS: LDV/SOF±RBV proved to be highly efficient in our difficult to treat population with 85.1% SVR.

Fecal Microbiota Transplantation in Recurrent NAP1/B1/027 Clostridium Difficile Infection (CDI) Resistant to Vancomycin and Metronidazole in a Patient with Ulcerative Colitis (UC): A Case Report.

Most of the studies showed that IBD patients inflammatory bowel diseases (IBD) with CDI have more of the whole range of short- and long-term worst outcomes than those without CDI. Initial infection with the BI/NAP1/027 epidemic clone was found to be a significant risk factor for relapse. However, current literature is suggesting increasingly that for patients with infections that fail to resolve with traditional antibiotic regimens, FMAT's average cure rate of >90%. We report a case of a 40-year-old man, diagnosed with ulcerative colitis (UC) in 2012 who presented in our clinic for 20 watery stools per day with mucus and blood, hypogastric pain, pyrexia and chills. Rectosigmoidoscopy and histopathological examination diagnosed a ctive lesions of ulcerative colitis with Clostridium difficile toxins A/B enzyme immunoassays (EIA) testing initially negative. The patient was non-responder at day 10 of intravenous (iv) corticotherapy and received induction therapy with Infliximab 5 mg/kg. EIA testing for Clostridium difficile was repeated at day 12 of hospitalization with positive results for toxins A/B, and associated oral therapy with Vancomycin and Metronidazole was initiated without clinical response in day 7, reasons for what intravenously therapy with Tigecycline was started with good response. Patient was discharged after 10 days of Tigecycline, but came back twice for two relapses of Clostridium difficile colitis treated successfully with Tigecycline, reasons for what fecal transplantation was performed in Matei Bals Institute, which induced remission of both CDI and UC.