Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn's disease: The HEAL study from GETECCU.

BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. METHODS: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. CONCLUSION: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

Psychological burden and quality of life in newly diagnosed inflammatory bowel disease patients.

Objective: Psychological factors, such as stress, anxiety, and depression, are frequently related to inflammatory bowel disease (IBD). However, few studies have examined these factors in patients newly diagnosed with IBD. The aim of the present study was to test the psychological burden in patients with a recent diagnosis of IBD and the factors related to this psychological burden. Methods: We performed a prospective, multi-center, observational study in patients with a new diagnosis of IBD (≤6 months). The patients were recruited from four different Spanish hospitals. Clinical and demographic characteristics were collected. Patients were evaluated using the Hospital Anxiety and Depression Scale and quality of life questionnaire for patients with inflammatory bowel disease (IBDQ-32). The Scale of Stress Perceived by the Disease was used to assess stressful life events. Results: We included 156 patients newly diagnosed with IBD [69 women; 80 Crohn's disease (CD) and 76 ulcerative colitis (UC)], with a mean age of 42.3 (SD 16.21) years. A total of 37.2% of patients had symptoms of anxiety and 17.3% had symptoms of depression. Quality of life was affected in 30.1% of patients. Factors related to anxiety in early IBD were being a woman and having CD. The only factor related to depression was the presence of comorbidity. Being a woman and having suffered previous stressful life events were factors related to impaired quality of life. Conclusion: Anxiety, depression, and impaired quality of life are frequent in patients with a recent diagnosis of IBD. This psychological burden is greater in women.

Gastric variceal bleeding as a form of presentation of a pancreatic neuroendocrine tumor / Sangrado por varices gástricas como forma de presentación de un tumor neuroendocrino pancreático

NETs (neuroendocrine tumors) constitute a heterogeneous group of epithelial-type neoplasms with a predominantly neuroendocrine differentiation. Although the most common locations are the pancreas, digestive tract, and lung, this type of neoplasm can arise in virtually any organ in the body. They are rare tumors with a wide variety of clinical presentations. Symptomatic tumors are more frequent in younger patients and present at more advanced pathological stages. We present the case of a 42-year-old male with idiopathic splenomegaly and bicytopenia (anaemia and thrombocytopenia) under study by haematology department who was admitted due to an episode of melena and hemoglobin of 4.5 mg/dl. Isolated gastric varices (IGV1) with red spots were confirmed at gastroscopy and endoscopic variceal obturation using cyanoacrylate was performed in two sessions. An endoscopic ultrasonography was performed, showing thrombosis of the splenic vein extending towards the splenoportal confluence with anechoic serpiginous structures outside and inside the gastric wall suggestive of collateral circulation with gastric varices (GV). An increase in portal caliber was observed, with no signs of liver cirrhosis. Computed tomography confirms the findings. Two months/week/days later he was readmitted with rebleeding signs after starting anticoagulant treatment, so it was decided to perform a splenectomy due to failure of the endoscopic treatment. Histology revealed infiltration of the spleen by a well-differentiated neuroendocrine tumor (NET). Gallium PET/CT and Octreotid scan showed uptake in the body and tail of the pancreas with positivity for somatostatin receptors previously undetected by other means. Finally, treatment was completed with distal pancreatectomy and splenoportal axis trombectomy with vascular esplenic resection and the patient was discharged from hospital.(AU)

Gastric variceal bleeding as a form of presentation of a pancreatic neuroendocrine tumor.

NETs (neuroendocrine tumors) constitute a heterogeneous group of epithelial-type neoplasms with a predominantly neuroendocrine differentiation. Although the most common locations are the pancreas, digestive tract, and lung, this type of neoplasm can arise in virtually any organ in the body. They are rare tumors with a wide variety of clinical presentations. Symptomatic tumors are more frequent in younger patients and present at more advanced pathological stages. We present the case of a 42-year-old male with idiopathic splenomegaly and bicytopenia (anaemia and thrombocytopenia) under study by haematology department who was admitted due to an episode of melena and hemoglobin of 4.5 mg/dl. Isolated gastric varices (IGV1) with red spots were confirmed at gastroscopy and endoscopic variceal obturation using cyanoacrylate was performed in two sessions. An endoscopic ultrasonography was performed, showing thrombosis of the splenic vein extending towards the splenoportal confluence with anechoic serpiginous structures outside and inside the gastric wall suggestive of collateral circulation with gastric varices (GV). An increase in portal caliber was observed, with no signs of liver cirrhosis. Computed tomography confirms the findings. Two months/week/days later he was readmitted with rebleeding signs after starting anticoagulant treatment, so it was decided to perform a splenectomy due to failure of the endoscopic treatment. Histology revealed infiltration of the spleen by a well-differentiated neuroendocrine tumor (NET). Gallium PET/CT and Octreotid scan showed uptake in the body and tail of the pancreas with positivity for somatostatin receptors previously undetected by other means. Finally, treatment was completed with distal pancreatectomy and splenoportal axis trombectomy with vascular esplenic resection and the patient was discharged from hospital.

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case-Control Study (COVID-19-EII).

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case−control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March−July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3−5.9), occupational risk (OR: 2.9; 95%CI: 1.8−4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2−2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09−0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution.

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU.

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-×¥-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18−20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50−0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66−0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20−22%] vs. 14% [95% CI 13−16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM.

Nationwide COVID-19-EII Study: Incidence, Environmental Risk Factors and Long-Term Follow-Up of Patients with Inflammatory Bowel Disease and COVID-19 of the ENEIDA Registry.

We aim to describe the incidence and source of contagion of COVID-19 in patients with IBD, as well as the risk factors for a severe course and long-term sequelae. This is a prospective observational study of IBD and COVID-19 included in the ENEIDA registry (53,682 from 73 centres) between March-July 2020 followed-up for 12 months. Results were compared with data of the general population (National Centre of Epidemiology and Catalonia). A total of 482 patients with COVID-19 were identified. Twenty-eight percent were infected in the work environment, and 48% were infected by intrafamilial transmission, despite having good adherence to lockdown. Thirty-five percent required hospitalization, 7.9% had severe COVID-19 and 3.7% died. Similar data were reported in the general population (hospitalisation 19.5%, ICU 2.1% and mortality 4.6%). Factors related to death and severe COVID-19 were being aged ≥ 60 years (OR 7.1, 95% CI: 1.8-27 and 4.5, 95% CI: 1.3-15.9), while having ≥2 comorbidities increased mortality (OR 3.9, 95% CI: 1.3-11.6). None of the drugs for IBD were related to severe COVID-19. Immunosuppression was definitively stopped in 1% of patients at 12 months. The prognosis of COVID-19 in IBD, even in immunosuppressed patients, is similar to that in the general population. Thus, there is no need for more strict protection measures in IBD.

Upper gastrointestinal bleeding due to duodenum diverticulum: a challenge for the endoscopist.

An 80-year-old female with a mechanic mitral valve treated with acenocumarol was admitted to the hospital due to tarry stools over the last two days and hemoglobin levels of 5.6 g/dl. She had not biliary pathology. An emergency esophagogastroduodenoscopy showed lots of fresh clots over the second part of the duodenum that seemed to come from the major papilla. A duodenoscopy was performed in order to obtain a direct view, showing a huge clot near the papilla. Its removal with a polypectomy snare revealed a large duodenum diverticulum with little saculations inside, one of which showed a visible, actively bleeding vessel. Sclerosis with epinephrine was performed and subsequently, two through-the-scope Cook® 11 mm clips were placed, achieving the cessation of the hemorrhage. Several attempts with different clips were needed since they were separated by the elevator nail of the duodenoscope. No complications developed during the procedure or once anticoagulation was restarted.

Inflammatory bowel disease new-onset during secukinumab therapy: real-world data from a tertiary center.

Secukinumab is a monoclonal antibody that inhibits interleukin-17A. It is currently prescribed for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis, which are immune-mediated diseases that show significant co-heritability with inflammatory bowel disease (IBD). Although this treatment appears to be well tolerated by patients, several cases of new-onset IBD after secukinumab have been reported during the last years.

Acute neutrophilic gastritis induced by nivolumab used as treatment for non- metastatic malignant melanoma.

We present the case of a 47-year-old male with a personal history of radically removed malignant melanoma (pT3bN2M0) who was receiving adjuvant nivolumab for the prevention of recurrence. He was admitted to our service complaining of epigastric pain and hyporexia after receiving the ninth dose of nivolumab. He underwent a preferential esophagogastroduodenoscopy, which showed intense inflammation limited to the stomach.

What are the odds? Duodenum adenocarcinoma as a primary metachronic neoplasia.

We present the case of an 81-year-old male with a history of surgically resected colorectal and bladder cancer, who was admitted to our hospital with a urinary infection. A routine renal ultrasound showed a pelvic cyst and a CT scan confirmed a non-complicated cyst, but a lesion was observed in the left lung. He underwent a PET-CT in which an unexpected enhancement of the small bowel attracted our attention.

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry.

BACKGROUND: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. METHODS: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. RESULTS: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. CONCLUSIONS: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Cuff-assisted versus cap-assisted colonoscopy for adenoma detection: results of a randomized study.

BACKGROUND: The adenoma detection rate (ADR) is the most important marker of colonoscopy quality. Devices to improve adenoma detection have been developed, such as the Endocuff and transparent cap. The aim of the current study was to examine whether there was a difference in ADR between Endocuff-assisted (EAC) and cap-assisted colonoscopy (CAC). METHODS: A randomized prospective trial was conducted. Eligible patients included adults ≥ 18 years referred because of symptoms, surveillance, or colonoscopies as part of the Bowel Cancer Screening Programme (BCSP). The primary outcome measure was ADR. Secondary outcomes included mean number of adenomas, mean number of polyps, polyp detection rate, cecal intubation rate, and time to cecal intubation. Procedural measures, device removal rate, and adverse events were also recorded. RESULTS: A total of 711 patients (51.1 % men; median age 63 years) were included, of whom 357 patients were randomized to EAC and 354 patients to CAC. In the intention-to-treat analysis, the ADR was similar in both groups: EAC 50.4 % (95 % confidence interval [CI] 45.1 - 55.7) vs. CAC 50.6 % (95 %CI 45.2 - 55.9). Similar results were obtained in the per-protocol analysis: EAC 51.6 % (95 %CI 46.2 - 57) vs. CAC 51.4 % (95 %CI 46 - 56.8). There were no differences between the two devices in ADR according to the mean number of adenomas and polyps per procedure, polyp detection rate, cecal intubation rate, and time to cecal intubation. Device removal rate and adverse events were also similar. CONCLUSION: In this randomized study, no differences in ADR were found between Endocuff- and cap-assisted colonoscopy.

The Colonoscopy Satisfaction and Safety Questionnaire (CSSQP) for Colorectal Cancer Screening: A Development and Validation Study.

Colonoscopy services working in colorectal cancer screening programs must perform periodic controls to improve the quality based on patients' experiences. However, there are no validated instruments in this setting that include the two core dimensions for optimal care: satisfaction and safety. The aim of this study was to design and validate a specific questionnaire for patients undergoing screening colonoscopy after a positive fecal occult blood test, the Colonoscopy Satisfaction and Safety Questionnaire based on patients' experience (CSSQP). The design included a review of available evidence and used focus groups to identify the relevant dimensions to produce the instrument (content validity). Face validity was analyzed involving 15 patients. Reliability and construct and empirical validity were calculated. Validation involved patients from the colorectal cancer screening program at two referral hospitals in Spain. The CSSQP version 1 consisted of 15 items. The principal components analysis of the satisfaction items isolated three factors with saturation of elements above 0.52 and with high internal consistency and split-half readability: Information, Care, and Service and Facilities features. The analysis of the safety items isolated two factors with element saturations above 0.58: Information Gaps and Safety Incidents. The CSSQP is a new valid and reliable tool for measuring patient' experiences, including satisfaction and safety perception, after a colorectal cancer screening colonoscopy.

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.

Does "responsive insertion technology" improve practice of colonoscopy? Results of a randomized study.

OBJECTIVE. During colonoscopy, advancing the endoscope can sometimes be difficult due to the appearance of loops or bends in the insertion tube. Therefore, research continues toward improving colonoscope technology. The aim of this study is to compare the use of colonoscopes equipped with "responsive insertion technology" (RIT) versus regular non-RIT colonoscopes. MATERIALS AND METHODS. Prospective, comparative and randomized trials that included patients submitted to colonoscopy. In group I, RIT colonoscopes were used, while in group II, colonoscopies with variable stiffness but without the other components of the RIT technology were used. Demographic variables and variables related to colonoscopy, as well as the pain perceived by the patient and the difficulty in performing endoscopy were recorded. RESULTS. A total of 122 patients were included in group I and 120 patients in group II. The cecal intubation rate was similar in both groups. The use of the RIT colonoscopes was associated with a lower cecal intubation time (4.4 ± 2.0 vs. 5.4 ± 3.5, p = 0.005) and a lower difficulty in performing examinations for both the endoscopist (19.1 ± 20.0 vs. 27.7 ± 22.2, p = 0.002) and the nursing staff (20.8 ± 17.0 vs. 26.3 ± 19.6, p = 0.04). No significant differences were found between both groups in the need for ancillary maneuvers or in the pain perceived by the patient. CONCLUSIONS. RIT colonoscopes allow cecal intubation in a shorter time compared to variable stiffness colonoscopes, and are associated with a greater level of ease of the procedure.

Factors associated with non-attendance at outpatient endoscopy.

OBJECTIVE: Non-attendance at endoscopy procedures leads to wasted resources and increased costs. The purpose of this study was to investigate the factors associated with non-attendance. MATERIAL AND METHODS: All patients who attended the outpatient clinic for gastroscopy or colonoscopy examinations were included in the study. Patients who missed their appointment were identified and their data were collected prospectively. Patients who kept their appointment in the same period of time served as controls. RESULTS: Between August 2002 and February 2003, 1051 gastroscopies and 756 colonoscopies were scheduled. A total of 265 patients (14.7%) missed their appointment. No significant differences were found between attendees and non-attendees for mean age, gender, type of examination and day of the week on which the examination was scheduled. The time on the waiting list was longer in patients who did not keep their appointment than in those who did. Fewer appointments were missed in patients with a preferent referral, and among patients referred by their general practitioner a higher percentage failed to keep their appointment compared with those referred by a specialist. In the multivariate analysis, length of time on the waiting list and the source of referral were the only two independent predictive factors for non-attendance. CONCLUSIONS: A longer time on the waiting list and referral by a general practitioner are factors associated with patients failing to keep their endoscopy appointment.