Severe outbreak of ulcerative colitis and cerebral neoplasia. Difficult management in COVID time.

A 61-year-old male diabetic patient, diagnosed with ulcerative colitis (UC) 30 years ago, currently under treatment with mesalazine is presented. He was admitted to the emergency department due to a severe outbreak of UC, with 15 depositions daily, rectal bleeding and poor general condition. A brain CT-scan was carried out in the emergency department due to a sudden self-limited aphasia. A left frontal lesion of 45x38 mms with a prominent perilesional edema and with a displacement of the midline was reported. This was believed to be a meningioma (figure 1A). Urgent neurosurgery was not performed, prioritizing the severe flare-up UC. Based on this, full-dose metilprednisolone was administered.

GIST. Duodenopancreatectomía. Tumor neuroendocrino no funcionante.

Zollinger Ellison syndrome is an unusual entity. This termn is used to describe the clinical manifestations of a gastrin-synthesizing neoplasm. Gastrinomas occur mainly in the duodenum and pancreas. Primary gastrinomas are rarely found in other intra-abdominal sites, such as the ovary, bile ducts, spleen or kidney, or even more unusual in extra-abdominal locations. Several studies provide strong evidence that gastrinomas can also occur in the lymph nodes. However, the existence of primary lymph node gastrinomas is controversial.

Switch to subcutaneous infliximab during the SARS-CoV-2 pandemic: preliminary results.

A new subcutaneous formulation of the infliximab biosimilar CT-P13 has recently been developed for the treatment of inflammatory bowel disease (IBD), providing response rates similar to intravenous treatment. The use of this new formulation was requested, in an effort to limit patient attendance at intravenous infusion centers and to maintain biological treatment during the COVID-19 pandemic. The objective of this observational, retrospective and descriptive study was to assess CT-P13 efficacy and safety after switching from intravenous to a subcutaneous formulation in patients with IBD receiving maintenance therapy. This article shows preliminary results after six months of follow-up.

An extremely uncommon complication of acute pancreatitis: spontaneous pancreatic cutaneous fistula.

We report the case of a 67-year-old male who was referred to our hospital due to severe abdominal pain and fever. His past medical history included a total gastrectomy surgery for stomach cancer. Abdominal examination showed intense pain on deep palpation in the epigastric region. Laboratory test revealed elevated C-reactive protein (235 mg/l) and amylase (1,789 U/l). Computerized tomography reported a pancreatic collection with the presence of air bubbles inside and areas of necrotic pancreatic parenchyma.

Views of patients with inflammatory bowel disease during the COVID-19 pandemic: ACCU survey results.

INTRODUCTION AND OBJECTIVES: the SARS-COV-2 pandemic has forced a substantial change in the care of patients with digestive pathologies, especially for inflammatory bowel disease (IBD) patients taking immunosuppessive medications. In this regard, some national and international guidelines have indicated the standards to be taken into account. However, few studies have evaluated how patients have dealt with this infection. Therefore, this study was performed with the aim to determine how the SARS-COV-2 pandemic has affected our IBD patients. MATERIAL AND METHODS: an online survey was performed among the members (295) of the Association of Crohn's Disease and Ulcerative Colitis (ACCU), which consisted of 19 questions. Finally, it was completed by 168 patients. RESULTS: fifty-eight per cent of cases were female, 63.7 % had Crohn's disease (CD) and 53 % received biologic therapy. Five per cent were infected by SARS-CoV-2 and were male. The main concern of the patients was the fear of acquiring the infection (80.9 %). More than 90 % continued their treatments and half of the patients worked from home during the pandemic period. CONCLUSIONS: the perspective of the patients is necessary to achieve an adequate management and evolution of the disease. More studies are needed to assess the impact that exceptional situations, such as the COVID-19 pandemic, may have on IBD patients in order to improve adherence and control of the disease.

Cut-off ranges of infliximab serum levels in Crohn's disease in the clinical practice.

INTRODUCTION: between 30 % and 40 % of patients treated with infliximab lose response during maintenance. Therapeutic drug monitoring could be used to optimize management in these situations. However, infliximab serum levels are not well defined. The aim of this study was to determine the cut-off range of infliximab serum levels in Crohn's disease patients in remission in the clinical practice. METHODS: an observational retrospective study was performed from 2016 to 2017. Patients were included with established Crohn's disease, who had been on a maintenance dose schedule of infliximab. Infliximab levels and antibodies to infliximab were measured at least twice in all patients, after induction and after six months of treatment. Clinical remission was defined as ≤ 4 using the Harvey-Bradshaw index. Cluster analysis was used to analyze the results. RESULTS: one hundred and five Crohn's disease patients were included in the study; 57.1 % were male with a mean age of 39 years (SD ± 12.9). The median (range) time of the disease was eleven years (7-15) and the median (range) time of follow-up was 32 months (22-38). Patients who achieved remission had infliximab serum levels between 4.26-8.26 ug/ml versus 0.06-1.43 ug/ml in patients who did not achieve remission after induction. Infliximab serum levels were 2.84-7.75 ug/ml and 0.05-2.69 ug/ml in patients who achieved remission versus those who did not achieve remission after six months of treatment. Overall, 4.26-8.26 ug/ml was found to be the best cut-off range for remission. CONCLUSIONS: in our clinical practice, serum levels of infliximab in Crohn's disease patients should be higher than 4 ug/ml to achieve clinical remission.

Index of the Mayo Endoscopy and Ulcerative Colitis Endoscopy Index of Severity: are they equally valid?

INTRODUCTION: endoscopy plays an essential role in the management of patients with ulcerative colitis (UC), as it allows us to visualize and assess the severity of the disease. Different scores have been devised to standardize the findings because such assessments are not always objective. AIMS: the aim of this study was to assess the interobserver variability between the Index of Mayo Endoscopy (IME) and the Ulcerative Colitis Endoscopy Index of Severity (UCEIS), analyzing the severity of the endoscopic lesions in patients with UC. The secondary aim was to analyze if the cathartic preparation affected the degree of concordance amongst the endoscopists. MATERIAL AND METHODS: this was a single-cohort observational, comparative study in which a colonoscopy was performed in patients with UC, as the normal clinical practice. The results were classified according to the IME and the UCEIS by three endoscopic specialists. In order to assess the degree of interobserver correlation, the Kappa index for IME was used and the intraclass correlation coefficient was used for UCEIS. RESULTS: sixty-seven patients were included in the study. The average age was 51 (SD ± 16.7) and the average Mayo Clinic index was 3.07 (SD ± 2.54). The weighted Kappa index between endoscopists A and B for the IME was 0.8, 0.52 between A and C and 0.49 between B and C. The intraclass correlation coefficient for UCEIS was 0.922 between the three endoscopists (95 % CI: 0.832-0.959). A better interobserver correlation was found when the cathartic preparation was ≥ 8 based on the Boston Scale. CONCLUSIONS: there was a higher correlation between the different endoscopists for the UCEIS than for the IME. Thus, this should be considered to be the best index to use in the clinical practice. A good cleansing preparation is important to improve the interobserver correlation.

Late migration of a metal stent after EUS-drainage of a pancreatic pseudocyst abscess.

Endoscopic ultrasound (EUS)-guided drainage of pancreatic collections has replaced surgery as the first line of treatment due its accuracy and safety profile. A higher success rate and fewer adverse events has been observed using fully covered metal stent for the drainage. However, complications of EUS-guided drainage can appear. We present a case of late migration of the stent.

Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: results of a multicenter study after 12 months.

BACKGROUND AND AIMS: infliximab has changed the natural history of inflammatory bowel disease (IBD). The advent of biosimilar treatments such as CT-P13 will hopefully improve the availability of biological therapies. Data with regard to drug switching are currently limited. The objective of the study was to assess the effectiveness and safety of switching from the reference product (RP), infliximab, to CT-P13 in patients with IBD. METHODS: this was a multicenter prospective observational study in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients had switched from infliximab RP (Remicade®) to CT-P13 treatment and were followed up for 12 months. The efficacy endpoint was the change in clinical remission assessed at 0 and 12 months, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. Adverse events were monitored and recorded throughout the study. RESULTS: a total of 167 patients (116 CD/51 UC) were included; 88.8% (103/116) of patients with CD were in remission at the time of the drug switch and 69.7% were in remission at 12 months. The Harvey-Bradshaw (HB) score significantly changed at 12 months (p = 0.001); 84.3% (43/51) of patients with UC were in remission at the time of the drug switch and 76.7% were in remission at 12 months. No significant changes in the median partial Mayo score (p = 0.87) were observed at 12 months. Serious adverse events related to medication were reported in 12/167 (7.2%) cases. CONCLUSION: switching from infliximab RP to CT-P13 is safe and effective at 12 months. The loss of efficacy at 12 months was 15.7%.

Carriage of the HLA-DQA1⋆05 haplotype is associated with a higher risk of infratherapeutic drug concentration and higher immunogenicity in patients undergoing treatment with anti-TNF for inflammatory bowel disease.

Background: The success of anti-tumor necrosis factor (TNF) drug strategies in the treatment of inflammatory bowel disease (IBD) is altered by the development of anti-drug antibodies that reduce their efficacy. Studies have shown that the HLA-DQA1⋆05 allele increases the risk of immunogenicity to anti-TNF drugs approximately twofold. Objective: Analyze whether the presence of the HLA-DQA1⋆05 allele is associated with the development of immunogenicity and to evaluate the disease response to anti-TNF drugs (infliximab (IFX) and adalimumab (ADA)), according to the presence of this allele. Design: This is an observational retrospective cohort study, single center, to determine the impact of HLA-DQA1⋆05 on disease activity in patients with IBD at the Hospital Universitario Virgen Macarena. Methods: In total, 200 IBD patients were included: 109 treated with IFX and 91 with ADA. Data were collected using the computerized medical records from the DIRAYA program of the Servicio Andaluz de Salud. Response-defined as improvement-and remission-defined as the disappearance of symptoms and analytical/endoscopic signs-were assessed using activity indices (partial Mayo, Harvey-Bradshaw) in all patients. Anti-TNF drug levels were also determined, as well as the presence or absence of anti-IFX and anti-ADA antibodies. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology statement. Results: The HLA-DQA1⋆05 haplotype was present in 70 (35%) patients, including 39 (36%) treated with IFX and 31 (34%) with ADA. The risk of withdrawal, intensification, as well as antibody development, was higher in patients carrying the allele and on treatment with IFX or ADA. Conclusion: In our study, we demonstrated that there is an increased risk of immunogenicity in patients carrying the HLA-DQA1⋆05 genotype, which would support the idea of screening for this genetic variant before starting anti-TNF therapy, as its prevalence is high in the general population and increases the risk of treatment discontinuation due to loss of response.

Carriage of HLA-DQA1⋆05 haplotype is associated with higher risk of infratherapeutic drug concentration and higher immunogenicity in patients undergoing treatment with anti-TNF for inflammatory bowel disease Anti-TNF drugs are commonly used to treat inflammatory bowel disease (IBD), but their effectiveness can be reduced if patients develop antibodies against them. This study investigated whether a specific gene, HLA-DQA1⋆05, increases the likelihood of forming these antibodies and affects the response to anti-TNF drugs, such as infliximab (IFX) and adalimumab (ADA).The study analyzed 200 IBD patients, including those treated with IFX and ADA. Researchers assessed drug levels, the presence of antibodies, and how well patients responded to the treatment. They found that 35% of the patients carried the HLA-DQA1⋆05 gene. Those with this gene had a higher risk of treatment issues, such as needing to stop or switch medications, and were more likely to develop antibodies.The findings suggest that screening for the HLA-DQA1⋆05 gene before starting anti-TNF therapy could be beneficial. Identifying patients with this gene might help predict who is at higher risk for treatment failure and allow for better management of their care.

Long-Term Outcomes of Intravenous Ustekinumab Maintenance Treatment in Patients With Loss of Response to Subcutaneous Dosing.

BACKGROUND: Ustekinumab (UST) is commonly used to treat Crohn's disease and ulcerative colitis. However, some patients may experience diminishing response or require increased dosage. Intravenous (IV) UST maintenance is explored as a solution. OBJECTIVES: We sought to evaluate IV UST maintenance effectiveness and safety in inflammatory bowel disease patients with partial or lost subcutaneous UST response. METHODS: This was a multicenter retrospective study of inflammatory bowel disease patients on IV UST maintenance. Clinical response and remission at weeks 12 and 52, defined as Harvey-Bradshaw Index ≤4 for Crohn's disease or partial Mayo score ≤2 for ulcerative colitis. Objective markers reduction (fecal calprotectin, C-reactive protein), UST trough levels pre- and post-IV maintenance, and adverse events were assessed. RESULTS: A total of 59 patients were included. Clinical remission at weeks 12 and 52 achieved by 47.5% and 64.3% respectively. 96.6% continued IV UST at follow-up. UST serum levels quadrupled. No adverse events reported. CONCLUSIONS: IV UST maintenance effectively sustained remission in most patients at 52 weeks.

When patients lose response to subcutaneous ustekinumab, strategies include reinduction, interval shortening, and less explored intravenous maintenance. Its high rescue rate and safety profile make it a valuable option for managing active inflammatory bowel disease.

High serum levels of ustekinumab are associated with better clinical outcomes during maintenance treatment for inflammatory bowel disease.

Background: Ustekinumab (UST) is an effective treatment option in Crohn's disease (CD) and ulcerative colitis (UC). However, it still remains unclear if therapeutic drug monitoring could be helpful to guide clinicians. Objectives: The aim of our study was to analyze the relationship between UST through levels (USTTL) and clinical outcomes in real-world inflammatory bowel disease (IBD) patients. Design: We performed a unicentric retrospective study including patients with IBD under UST treatment with at least one level determination. Methods: The following variables were analyzed at the initiation of UST and at each USTTL measurement: clinical response and remission using the Harvey-Bradshaw Index (HBI) for CD and the Partial Mayo Score (pMayo) for UC; biochemical response and remission using fecal calprotectin and C-reactive protein, among others. Two periods were considered: P1 (time between induction and the first determination of USTTL) and P2 (time between USTTL1 and the second determination of USTTL). Results: We included 125 patients, 117 with CD. In P1, 62.4% of patients were on subcutaneous maintenance, and the median USTTL1 was 3.1 µg/mL (1.6-5.3). In 44.8% of CD patients (48/117), clinical remission was achieved, with USTTL1 significantly higher than those who did not achieve remission (3.7 µg/mL (2.3-5.4) vs 2.3 µg/mL (1.1-5.2); p = 0.04). In the 46 patients with two determinations, statistically significant differences were found between variables in P2 versus P1: clinical remission (73.9% vs 21.7%; p = 0.001); USTTL (7.2 µg/mL (4.7-11.7) vs 3.4 µg/mL (1.9-6.4); p < 0.001), HBI (4 (4-4.3) vs 8 (4-9); p < 0.001), pMayo (1 (1-3.3) vs 4.5 (3-5); p = 0.042), and corticosteroid use (26.1% vs 41.3%; p = 0.024). Receiver-Operating-Characteristic (ROC) curves were calculated for clinical remission in P2, with USTTL cutoff value of 6.34 µg/mL for clinical remission and a high rate of intensified patients (98%). Conclusion: High serum levels of UST were associated with clinical remission during treatment for IBD under intensification treatment, with a cutoff point of 6.3 µg/mL.

Intravenous ustekinumab maintenance treatment in patients with loss of response to subcutaneous dosing.

Background: Ustekinumab (UST) is indicated for the treatment of Crohn's disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world, some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed. Objectives: The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous (SC) UST. Design: We performed a monocentric observational retrospective study including patients with active IBD on maintenance treatment with IV UST. Methods: The clinical response and remission was analyzed at week 12, defined as either Harvey-Bradshaw Index ⩽ 4 for CD or partial Mayo Score ⩽ 2 for UC. The reduction of objective markers of disease activity, fecal calprotectin, and C-reactive protein was evaluated. Moreover, UST trough levels were measured pre- and post-UST IV maintenance and any adverse events were assessed. Results: We included 23 patients. Clinical remission at week 12 was achieved by 43.5% of the patients. The proportion of patients in clinical response after 12 weeks on UST IV maintenance was 82.6%. After a median follow-up of 9.3 months all patients remained on IV UST maintenance. No adverse events were recorded in any patient for the duration of the study. Conclusions: IV UST maintenance treatment was able to recapture response in most of the patients who had lost response to SC maintenance.

Comparison of the Mayo Endoscopy Score and the Ulcerative Colitis Endoscopy Index of Severity and the Ulcerative Colitis Colonoscopy Index of Severity.

Background and study aims: Endoscopy plays an essential role in managing patients with ulcerative colitis (UC), as it allows us to visualize and assess the severity of the disease. As such assessments are not always objective, different scores have been devised to standardize the findings. The main aim of this study was to assess the interobserver variability between the Mayo Endoscopy Score (MES), Ulcerative Colitis Endoscopy Index of Severity (UCEIS) and Ulcerative Colitis Colonoscopy Index of Severity (UCCIS) analyzing the severity of the endoscopic lesions in patients with ulcerative colitis. Patients and methods: This was a single-cohort observational study in which a colonoscopy was carried out on patients with UC, as normal clinical practice, and a video was recorded. The results from the video were classified according to the MES, UCEIS and UCCIS by three endoscopic specialists independently, and they were compared to each other. The Mayo Endoscopy Score (MES) was used to assess the clinical situation of the patient. The therapeutic impact was analyzed after colonoscopy was carried out. Results: Sixty-seven patients were included in the study. The average age was 51 (SD ±â€Š16.7) and the average MES was 3.07 (SD ±â€Š2.54). The weighted Kappa index between endoscopists A and B for the MES was 0.8; between A and C 0.52; and between B and C 0.49. The intraclass correlation coefficient for UCEIS was 0.92 among the three endoscopists (CI 95 %: 0.83-0.96) and 0.96 for UCCIS among the three endoscopists (CI 95 % 0.94-0.97). A change in treatment for 34.3 % of the patients was implemented on seeing the results of the colonoscopy. Conclusions: There was an adequate, but not perfect, correlation between the different endoscopists for MES, UCEIS, UCCIS. This was higher with the last two scores. Thus, there is still some subjectivity to be minimized through special training, on assessing the seriousness of the endoscopic lesions in patients with UC.

Erythema Nodosum: As an Extraintestinal Manifestation or Complication in Ulcerative Colitis?

In our case, we want to highlight the importance of screening for opportunistic infectious diseases in these immunosuppressed patients. We present the case of an erythema nodosum triggered by reactivation of Herpes Simplex Virus (HSV) in a patient with ulcerative colitis.

Long-term follow up after switching from original infliximab to an infliximab biosimilar: real-world data.

BACKGROUND: Several studies have reported positive efficacy outcomes for patients with inflammatory bowel disease treated with CT-P13, an infliximab biosimilar. Data from follow-up periods longer than 1 year are still scarce. Here, we assessed the long-term efficacy data, loss of response and safety after switching from infliximab to CT-P13 in patients with inflammatory bowel disease. METHODS: This was a prospective single-center observational study involving patients with moderate-to-severe Crohn's disease and ulcerative colitis switched from infliximab to CT-P13 treatment and reviewed up to 24 months. Efficacy and loss of response were measured using the Harvey-Bradshaw (HB) index and partial Mayo score for patients with Crohn's disease and ulcerative colitis respectively. C-reactive protein, infliximab drug levels, adverse events and antidrug antibodies were also monitored throughout the study. RESULTS: A total of 64 patients with Crohn's disease and 36 patients with ulcerative colitis were included. Most of them (72%) remained on CT-P13. Overall, 28% of patients discontinued the therapy due to loss of response, adverse events or long-lasting clinical remission. Remission at 18 and 24 months occurred in 69.9% and 68.5% of patients, respectively. Dose increase was performed in 22% of patients, with remission being reached in 60% of them. HB index, partial Mayo score, C-reactive protein and infliximab drug levels did not show significant changes. Serious adverse events were reported in 14% of patients. Overall, two patients developed low levels of antidrug antibodies. CONCLUSIONS: Most of the patients switching from original infliximab were maintained on CT-P13 at 2 years of follow up with a good profile of efficacy and safety.

Loss of efficacy and safety of the switch from infliximab original to infliximab biosimilar (CT-P13) in patients with inflammatory bowel disease.

BACKGROUND: Infliximab original has changed the natural history of inflammatory bowel diseases (IBD) over the past two decades. However, the recent expiration of its patent has allowed the entry of the first Infliximab biosimilar into the European and Spanish markets. Currently switching drugs data in IBD are limited. AIM: To compare the efficacy of infliximab biosimilar, CT-P13, against infliximab original, analyzing the loss of response of both at the 12 mo follow-up in patients with IBD. METHODS: An observational study of two cohorts has been conducted. One retrospective cohort that included patients with IBD treated with Infliximab original, and a prospective cohort of patients who were switching from infliximab original to infliximab biosimilar (CT-P13). We had analyzed the overall efficacy and loss of efficacy in patients in remission at the end of one year after treatment with the original drug compared to the results of the year of treatment with the biosimilar. RESULTS: 98 patients (CD 67, CU 31) were included in both cohorts. The overall efficacy for infliximab original per year of treatment was 71% vs 68.2% for infliximab biosimilar (P = 0.80). The loss of overall efficacy at 12 mo for infliximab original was 6.6% vs 14.5% for infliximab biosimilar (P = 0.806). The loss of efficacy in patients who were in basal remission was 16.3% for infliximab original vs 27.1% for infliximab biosimilar. Adverse events were 9.2% for infliximab original vs 11.2% for infliximab biosimilar. CONCLUSION: The overall efficacy and loss of treatment response with infliximab biosimilar (CT-P13) is similar to that observed with infliximab original in patients who were switching at the 12 mo follow-up. There is no difference in the rate of adverse events.

Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: 12 months results.

BACKGROUND: Biological agents, such as infliximab, have transformed the outcomes of patients with immune-mediated inflammatory diseases. The advent of biosimilar treatment options such as CT-P13 promises to improve the availability of biological therapy, yet real-world switching data are currently limited. Here, we assess the effectiveness and safety of switching to CT-P13 from infliximab reference product (RP) in patients with inflammatory bowel disease. MATERIALS AND METHODS: This was a prospective single-center observational study in patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade) to CT-P13 treatment and followed up for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 3-monthly intervals, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. C-reactive protein (CRP) was also measured. Adverse events were monitored and recorded throughout the study. RESULTS: A total of 98 patients with inflammatory bowel disease (67 CD/31 UC) were included. A total of 83.6% (56/67) of patients with CD were in remission at the time of the switch and 62.7% were in remission at 12 months. The Harvey-Bradshaw score showed a significant change at 12 months (P=0.007) but no significant change was observed in median CRP at this timepoint (P=0.364). A total of 80.6% (25/31) of patients with UC were in remission at the time of the switch and 65.3% (18/28) were in remission at 12 months. No significant changes in the median partial Mayo score (P=0.058) or CRP (P=0.329) were observed at 12 months. Serious adverse events related to medication were reported in 11 (11.2%) patients. CONCLUSION: Switching from infliximab RP to CT-P13 is efficacious and well tolerated in patients with CD or UC for up to 12 months.