The Utility of Magnetic Resonance Enterography and Double Balloon Enteroscopy-Assisted Endoscopic Balloon Dilatation for Small Bowel Strictures in Crohn's Disease: A Retrospective Observational Study.

Introduction: Crohn's disease (CD) of the small bowel is associated with a severe course and increased risk of complications. Strictures at this location are challenging to diagnose and out-of-reach of colonoscopy. We aimed to evaluate the detection rate of small bowel strictures with magnetic resonance enterography (MRE) and assess the efficacy of double balloon enteroscopy-assisted endoscopic balloon dilatation (DBE-assisted EBD) in managing these strictures. Methods: A retrospective study included all patients with DBE-assisted EBD of small bowel strictures in CD in our facility. All patients had MRE to detect strictures prior to the dilatation. Sequential dilatation protocol was performed using through-the-scope (TTS) working channel balloons. The outcomes included technical success defined by the passage of the enteroscope post-dilatation, resolution of symptoms, and the requirement of repeated procedures or surgery during 12 months of follow-up. Results: Twenty DBE-assisted EBDs of small bowel strictures were attempted during 13 DBE procedures in 10 patients (6 males, median age 42). MRE identified 75% of the strictures with 100% accuracy in localisation. Retrograde DBE was the approach in 16/20 (80%) strictures. Anaesthetic intubation was used in 8/20 (40%). DBE reached 19/20 strictures. All the reached strictures were dilated successfully; the technical success following dilatation was 72.2%. The median DBE insertion time with TTS balloon dilatation was 66 min. Three patients required follow-up dilatations within 2-3 months. Surgery was not needed during the follow-up period. Conclusions: MRE is essential in diagnosing and localising small bowel strictures in CD. DBE reached 95% of strictures with successful dilatation. Immediate technical success was high, and safety was demonstrated. Planned repeat procedures for sequential dilatation were performed in a few patients. Surgical resection was avoided in all patients.

A Displaced Intrauterine Device Eroding Into the Sigmoid Colon.

A 36-year-old female presented to the gynecology office eight weeks after the placement of a ParaGard intrauterine device (IUD). Upon gynecologic examination, the strings of the IUD were not found. Magnetic resonance imaging was performed which reported the IUD embedded in the sigmoid colon. Initial diagnostic laparoscopy was done without bowel preparation and revealed an IUD embedded within the sigmoid colon and mesocolon. Colonoscopy did not reveal any breach of the colonic lumen. A second diagnostic laparoscopy was planned with the robotic-assisted technique after bowel preparation. Intraoperative findings during the second operation identified the IUD embedded in the antimesenteric side of the sigmoid colon with surrounding scar tissue to the uterus. The IUD was sharply freed using robotic scissors and the resulting serosal defect was sutured in layers with buttress made of appendices epiploica. The patient recovered well and had an excellent outcome. Our article highlights the minimally invasive method of dealing with a displaced IUD. The use of the robotic technique was helpful in our case to achieve an excellent outcome.

First-trimester exposure to tofacitinib in ulcerative colitis: A case report of a healthy newborn and literature review.

Tofacitinib is contraindicated in pregnancy. We present a patient with ulcerative colitis on tofacitinib who had an unplanned pregnancy. Tofacitinib was ceased, switched to vedolizumab, and she gave birth to a healthy newborn at term. Case reports of reassuring outcomes provide real-world data that assists decision-making for future patients.

Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities.

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4+ and CD8+ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.

The Effects of the COVID Pandemic on Patients with IBD: Lessons Learned and Future Directions.

The COVID-19 pandemic has caused extended global disruption and changed healthcare behaviour and delivery in patients with inflammatory bowel disease, many of whom take immune modifying treatment. Although there were fears about the vulnerability of IBD patients to SARS-CoV-2 infection, we have learnt that overall IBD patients are equivalent to the general population in both viral acquisition and infection outcomes. Overall IBD patients obtain effective vaccine-induced immune responses, although in some groups an additional vaccine dose is required to constitute a primary course. The pandemic has led to significant changes in healthcare delivery, some of which will be enduring. As we grapple with the challenges of recovery, the lessons learnt will continue to be important in optimising outcomes in future outbreaks.

Misconceptions Drive COVID-19 Vaccine Hesistancy in Individuals with Inflammatory Bowel Disease.

Background: Vaccination is an effective public health measure to combat the SARS-CoV-2 pandemic. However, vaccine "hesitancy" has limited uptake in some, including inflammatory bowel disease (IBD) patients who may have unique concerns influencing uptake. Aim: The aim of the study is to explore attitudes, concerns, and the influence of different sources of information on COVID-19 vaccine uptake in IBD patients. Methods: Patients from a specialist IBD clinic at a tertiary hospital in Australia and a national IBD patient society were invited to complete an anonymous online survey regarding COVID-19 vaccination. Demographic characteristics, attitudes towards vaccination, and trust in sources of information were explored. Logistic regression was used to identify variables associated with vaccine uptake. Results: Of 441 respondents, 93% of respondents had received at least 1 dose of COVID-19 vaccination. Self-perceived risk of being more unwell with COVID-19 infection due to IBD (AOR 5.25, 95% CI 1.96-14.04, p < 0.001) was positively associated with vaccine uptake. Concerns regarding the safety of vaccination in pregnancy (OR 0.22, 95% CI 0.08-0.65, p=0.006) and of causing an IBD flare (OR 0.28, 95% CI 0.10-0.77, p=0.01) were negatively associated with vaccine uptake. In total, 282 (73.7%) responders ranked healthcare workers the most trusted source to obtain information surrounding vaccination. Conclusion: Vaccine hesitancy in IBD patients is low. Concerns about the safety of vaccination in pregnancy and in causing an IBD flare are both associated with vaccine hesitancy. Healthcare providers play a key role in proactively addressing these misconceptions particularly in the context of emerging virus variants and the availability of boosters.

Review article: latent tuberculosis in patients with inflammatory bowel diseases receiving immunosuppression-risks, screening, diagnosis and management.

BACKGROUND: One quarter of the world's population has latent tuberculosis infection (LTBI). Systemic immunosuppression is a risk factor for LTBI reactivation and the development of active tuberculosis. Such reactivation carries a risk of significant morbidity and mortality. Despite the increasing global incidence of inflammatory bowel disease (IBD) and the use of immune-based therapies, current guidelines on the testing and treatment of LTBI in patients with IBD are haphazard with a paucity of evidence. AIM: To review the screening, diagnostic practices and medical management of LTBI in patients with IBD. METHODS: Published literature was reviewed, and recommendations for testing and treatment were synthesised by experts in both infectious diseases and IBD. RESULTS: Screening for LTBI should be performed proactively and includes assessment of risk factors, an interferon-gamma releasing assay or tuberculin skin test and chest X-ray. LTBI treatment in patients with IBD is scenario-dependent, related to geographical endemicity, travel and other factors. Ideally, LTBI therapy should be used prior to immune suppression but can be applied concurrently where urgent IBD medical treatment is required. Management is best directed by a multidisciplinary team involving gastroenterologists, infectious diseases specialists and pharmacists. Ongoing surveillance is recommended during therapy. Newer LTBI therapies show promise, but medication interactions need to be considered. There are major gaps in evidence, particularly with specific newer therapeutic approaches to IBD. CONCLUSIONS: Proactive screening for LTBI is essential in patients with IBD undergoing immune-suppressing therapy and several therapeutic strategies are available. Reporting of real-world experience is essential to refining current management recommendations.

SARS-CoV-2 vaccination in patients with inflammatory bowel disease.

BACKGROUND: The current COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has drastically impacted societies worldwide. Vaccination against SARS-CoV-2 is expected to play a key role in the management of this pandemic. Inflammatory conditions such as inflammatory bowel disease (IBD) often require chronic immunosuppression, which can influence vaccination decisions. AIM: This review article aims to describe the most commonly available SARS-CoV-2 vaccination vectors globally, assess the potential benefits and concerns of vaccination in the setting of immunosuppression and provide medical practitioners with guidance regarding SARS-CoV-2 vaccination in patients with IBD. METHODS: All published Phase 1/2 and/or Phase 3 and 4 studies of SARS-CoV-2 vaccinations were reviewed. IBD international society position papers, safety registry data and media releases from pharmaceutical companies as well as administrative and medicines regulatory bodies were included. General vaccine evidence and recommendations in immunosuppressed patients were reviewed for context. Society position papers regarding special populations, including immunosuppressed, pregnant and breast-feeding individuals were also evaluated. Literature was critically analysed and summarised. RESULTS: Vaccination against SARS-CoV-2 is supported in all adult, non-pregnant individuals with IBD without contraindication. There is the potential that vaccine efficacy may be reduced in those who are immunosuppressed; however, medical therapies should not be withheld in order to undertake vaccination. SARS-CoV-2 vaccines are safe, but data specific to immunosuppressed patients remain limited. CONCLUSIONS: SARS-CoV-2 vaccination is essential from both an individual patient and community perspective and should be encouraged in patients with IBD. Recommendations must be continually updated as real-world and trial-based evidence emerges.

Calcineurin inhibitors in steroid and anti-TNF-alpha refractory immune checkpoint inhibitor colitis.

BACKGROUND AND AIM: Immune checkpoint inhibitor (ICI) colitis is an increasingly common problem encountered as the use of checkpoint inhibitors (CPIs) grows in the management of cancers. Corticosteroids and tumour necrosis factor (TNF)-alpha inhibitors are widely recommended in the management of ICI colitis; however, the experience is limited when patients are refractory. Different authors have reported success with vedolizumab, mycophenolate, and cyclosporine. This case series describes our experience with calcineurin inhibitors in the management of corticosteroid and anti-TNF-alpha refractory ICI colitis. METHODS: Data from electronic medical records were identified and reviewed retrospectively from a cohort of patients treated at a single oncology center. All patients who were identified between March 2018 and May 2020 with ICI colitis refractory to treatment with infliximab and corticosteroids were included. RESULTS: There were 11 patients who developed ICI colitis after receiving CPIs for advanced melanoma and required rescue therapy with either cyclosporine or tacrolimus after treatment failure of infliximab. Median age was 53 (±8.48) years, with nine patients (81%) receiving combination Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) / programmed cell death protein 1 (PD-1) immunotherapy. Median time after first CPI infusion to ICI colitis was 4.43 (±19.53) weeks. The median time from onset of symptoms to commencement of rescue therapy with calcineurin inhibitors was 70 days (±66.06). Eight of the 11 patients (72.7%) responded to calcineurin inhibition. In patients who responded, calcineurin inhibitors were continued for a median of 54 (±28.96) days. CONCLUSION: The calcineurin inhibitors cyclosporine and tacrolimus appear to be a safe and effective option for the management of patients with infliximab-refractory ICI colitis. The therapeutic benefit is observed rapidly, and adverse effects appear to be limited with close monitoring.

Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment-free and overall survival in Chronic Lymphocytic Leukaemia.

Immune dysfunction attributed to hypogammaglobulinaemia is common in chronic lymphocytic leukaemia (CLL) and infection is a major contributor to morbidity and mortality. A higher incidence of multiple immunoglobulin and immunoglobulin G (IgG) subclass deficiency was associated with more advanced disease (P < 0·001 and P < 0·001, respectively) in a cohort of 147 CLL patients. Multiple immunoglobulin and IgG subclass deficiency were significantly associated with shorter treatment-free survival (TFS) (P < 0·001 and P = 0·006, respectively). The association between disease stage and immune dysfunction demonstrated by these data suggest aspects of immune deficiency correlate with disease severity and may be associated with shorter TFS in CLL.