An immunohistochemical atlas of necroptotic pathway expression.

Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators - Caspase-8, RIPK1, RIPK3 and MLKL - in formalin-fixed mouse and human tissues. We observed surprising heterogeneity in protein expression within tissues, whereby short-lived immune barrier cells were replete with necroptotic effectors, whereas long-lived cells lacked RIPK3 or MLKL expression. Local changes in the expression of necroptotic effectors occurred in response to insults such as inflammation, dysbiosis or immune challenge, consistent with necroptosis being dysregulated in disease contexts. These methods will facilitate the precise localisation and evaluation of necroptotic signaling in vivo.

Treat to transmural healing: how to incorporate intestinal ultrasound into the treatment of inflammatory bowel disease.

Intestinal ultrasound (IUS) is emerging as a key tool to achieving the therapeutic target of transmural healing in inflammatory bowel disease (IBD). IUS is a non-invasive, radiation-free, imaging modality comparable to MRI, CT and ileocolonoscopy (IC). With the appropriate training and equipment, IUS can be an easily repeatable bedside test for IBD diagnosis and disease monitoring, including treatment response. Core to successful high quality IUS employment are appropriate training and expert techniques; however, the training pathway will not be explored in this review. Given the increasing shift towards objective assessment for tight disease control, gastroenterologist-led IUS should be incorporated into the armamentarium of imaging modalities alongside radiologists, to enhance our diagnostic and monitoring toolbox. This comprehensive review aims to outline the current literature around IUS and propose the placement of IUS in a treat-to-target algorithm in IBD. Ultimately, IUS facilitates timely management decisions to optimise patient care with potential to revolutionise patient outcomes, moving towards transmural healing as the holy grail of therapy in IBD.

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.

Review article: prevention, diagnosis and management of COVID-19 in the IBD patient.

BACKGROUND: The current COVID-19 pandemic, caused by SARS-CoV-2, has emerged as a public health emergency. All nations are seriously challenged as the virus spreads rapidly across the globe with no regard for borders. The primary management of IBD involves treating uncontrolled inflammation with most patients requiring immune-based therapies. However, these therapies may weaken the immune system and potentially place IBD patients at increased risk of infections and infectious complications including those from COVID-19. AIM: To summarise the scale of the COVID-19 pandemic, review unique concerns regarding IBD management and infection risk during the pandemic and assess COVID-19 management options and drug interactions in the IBD population. METHODS: A literature review on IBD, SARS-CoV-2 and COVID-19 was undertaken and relevant literature was summarised and critically examined. RESULTS: IBD patients do not appear to be more susceptible to SARS-CoV-2 infection and there is no evidence of an association between IBD therapies and increased risk of COVID-19. IBD medication adherence should be encouraged to prevent disease flare but where possible high-dose systemic corticosteroids should be avoided. Patients should exercise social distancing, optimise co-morbidities and be up to date with influenza and pneumococcal vaccines. If a patient develops COVID-19, immune suppressing medications should be withheld until infection resolution and if trial medications for COVID-19 are being considered, potential drug interactions should be checked. CONCLUSIONS: IBD patient management presents a challenge in the current COVID-19 pandemic. The primary focus should remain on keeping bowel inflammation controlled and encouraging medication adherence.