What to do when traditional rescue therapies fail in acute severe ulcerative colitis.

Acute severe ulcerative colitis (ASUC) is a medical emergency that affects approximately 25% of patients with ulcerative colitis at some point in time in their lives. Outcomes of ASUC are highly variable. Approximately 30% of patients do not respond to corticosteroids and up to 50% of patients do not respond to rescue therapy (infliximab or cyclosporin) and require emergency colectomy. Data are emerging on infliximab dosing strategies, use of cyclosporin as a bridge to slower acting biologic agents and Janus kinase inhibition as primary and sequential therapy. In this review, we outline contemporary approaches to clinical management of ASUC in the setting of failure to respond to traditional rescue therapies.

Pneumocystis jirovecii Pneumonia Complicating Use of Upadacitinib in a Patient With Ulcerative Colitis and Primary Sclerosing Cholangitis: A Case Report.

Pneumocystis jirovecii is a ubiquitous, unicellular fungus that can cause pneumonia (PJP) in immunosuppressed individuals. We report the first case of PJP complicating upadacitinib use for ulcerative colitis. This report is of clinical relevance given the widespread uptake of JAK inhibition.

Safety and effectiveness of Janus kinase inhibitors in the management of inflammatory bowel disease following liver transplantation.

BACKGROUND: The management of inflammatory bowel disease (IBD) patients with concurrent liver transplantation is challenging, and data regarding the safety and efficacy of Janus kinase (JAK) inhibitors with anti-rejection medications are required. We report the experience of all liver transplant recipients receiving tofacitinib and/or upadacitinib for IBD across three states in Australia. METHODS: All liver transplant recipients from the Australian states of Victoria, New South Wales and Tasmania who required tofacitinib or upadacitinib for the treatment of IBD were identified using prospectively maintained liver transplant databases. Patients were followed up until medication cessation or last follow up. Clinical safety and efficacy data were collected. RESULTS: Eight patients (median age 30 years) were included, seven of whom received first-line JAK inhibition with tofacitinib. All patients had failed one or more biologic therapies prior to commencing JAK inhibition, including six patients who had failed two or more agents. JAK inhibition was continued for a median of 17 months, with 143 patient-months of combined follow-up. The anti-rejection medication tacrolimus was prescribed in all patients. Overall, seven (88%) patients achieved clinical remission, including all three patients who were switched from tofacitinib to upadacitinib. One patient required colectomy after 1 month of treatment. There were no other cases of serious infection, venous thromboembolism or major adverse cardiovascular events during follow-up. CONCLUSIONS: As the largest case series to-date, these data indicate that combining JAK inhibition with transplant anti-rejection medication may be a safe and clinically effective method of treating IBD in patients with prior biologic failure.

How do medical students want to learn ENT? Perspectives from a consensus forum.

OBJECTIVE: The UK Medical Licensing Assessment curriculum represents a consensus on core content, including ENT-related content for newly qualified doctors. No similar consensus exists as to how ENT content should be taught at medical school. METHOD: A virtual consensus forum was held at the 2nd East of England ENT Conference in April 2021. A syllabus of ENT-related items was divided into 'Presentations', 'Conditions' and 'Practical procedures'. Twenty-seven students, 11 foundation doctors and 7 other junior doctors voted via anonymous polling for the best three of nine methods for teaching each syllabus item. RESULTS: For 'Presentations' and 'Conditions', work-based or clinical-based learning and small-group seminars were more popular than other teaching methods. For 'Practical procedures', practical teaching methods were more popular than theoretical methods. CONCLUSION: Students and junior doctors expressed a clear preference for clinical-based teaching and small-group seminars when learning ENT content. E-learning was poorly favoured despite its increasing use.

Spectral Grouping of Electrically Encoded Sound Predicts Speech-in-Noise Performance in Cochlear Implantees.

OBJECTIVES: Cochlear implant (CI) users exhibit large variability in understanding speech in noise. Past work in CI users found that spectral and temporal resolution correlates with speech-in-noise ability, but a large portion of variance remains unexplained. Recent work on normal-hearing listeners showed that the ability to group temporally and spectrally coherent tones in a complex auditory scene predicts speech-in-noise ability independently of the audiogram, highlighting a central mechanism for auditory scene analysis that contributes to speech-in-noise. The current study examined whether the auditory grouping ability also contributes to speech-in-noise understanding in CI users. DESIGN: Forty-seven post-lingually deafened CI users were tested with psychophysical measures of spectral and temporal resolution, a stochastic figure-ground task that depends on the detection of a figure by grouping multiple fixed frequency elements against a random background, and a sentence-in-noise measure. Multiple linear regression was used to predict sentence-in-noise performance from the other tasks. RESULTS: No co-linearity was found between any predictor variables. All three predictors (spectral and temporal resolution plus the figure-ground task) exhibited significant contribution in the multiple linear regression model, indicating that the auditory grouping ability in a complex auditory scene explains a further proportion of variance in CI users' speech-in-noise performance that was not explained by spectral and temporal resolution. CONCLUSION: Measures of cross-frequency grouping reflect an auditory cognitive mechanism that determines speech-in-noise understanding independently of cochlear function. Such measures are easily implemented clinically as predictors of CI success and suggest potential strategies for rehabilitation based on training with non-speech stimuli.

Factors Associated With Response to Rescue Therapy in Acute Severe Ulcerative Colitis.

BACKGROUND: Acute severe ulcerative colitis (ASUC) is a medical emergency for which colectomy is required in patients who do not respond to rescue therapy. While previous studies have predominantly focused on predicting outcome to first-line corticosteroid therapy, there is a need to understand the factors associated with response to rescue therapies in order to improve clinical outcomes. We reviewed the evidence regarding factors associated with response to rescue therapy in adults with ASUC and identified future directions for research. METHODS: A systematic search of the literature was conducted, and 2 reviewers independently assessed studies for inclusion. RESULTS: Of 3509 records screened, 101 completed studies were eligible for inclusion. We identified 42 clinical, hematological, biochemical, endoscopic, or pharmacological factors associated with response to rescue therapy. Older age (≥50 years), thiopurine experience, and cytomegalovirus or Clostridioides difficile infection were associated with a higher risk of nonresponse to rescue therapy. Biochemical factors associated with poorer response included an elevated C-reactive protein (CRP) ≥30mg/L on admission, hypoalbuminemia and an elevated ratio of CRP to albumin. Severe endoscopic findings, including a Mayo endoscopic score of 3 or Ulcerative Colitis Endoscopic Index of Severity ≥5, portended poorer outcomes. The role of fecal calprotectin and therapeutic value of measuring infliximab drug levels in ASUC remain to be defined. CONCLUSIONS: Response to rescue therapy can be predicted by several specific factors, which would aid clinical decision-making. Existing and emerging factors should be integrated within predictive and prognostic models to help improve clinical outcomes.

In this review, we summarize the clinical, hematological, biochemical, radiological, endoscopic, and drug-related factors that predict or are associated with response to rescue therapy in patients with acute severe ulcerative colitis. We also provide a clinical algorithm for clinicians.

Outcomes out to 12 months after sequential use of high-dose tofacitinib following infliximab in acute severe ulcerative colitis.

Acute severe colitis (ASUC) remains a significant cause of morbidity in up to 25% of patients with ulcerative colitis during their disease course. We present the outcomes out to 12 months following the use of high-dose tofacitinib, 10 mg three times daily (TDS), in patients with steroid and infliximab refractory ASUC. A total of 11 patients with ASUC who were treated with high-dose tofacitinib after failing sequential infliximab therapy between 2019 and 2021 were identified at an Australian tertiary centre. Ten of 11 patients demonstrated clinical and biochemical response to treatment during admission. Two of 11 patients required colectomy, one during the index admission and the other during re-admission 10 days after the index presentation. Nine of the initial responders had a median Mayo score of 1 (IQR 0-4) at both 6 and 12 months, and all remained colectomy-free out to 12 months. Neither venous thromboembolic events nor major infective complications were observed. Tofacitinib may be a safe and effective induction and maintenance agent in the treatment of steroid and infliximab refractory ASUC. Prospective studies with long-term follow-up are required to explore the use of tofacitinib in ASUC before it can be routinely recommended as salvage therapy.

Novel Use of the Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition for the Treatment of Crohn's Disease During Pregnancy.

The Crohn's Disease Exclusion Diet (CDED) with partial enteral nutrition (PEN) is an emerging treatment option for Crohn's disease (CD). A 35-year-old pregnant woman presented with newly diagnosed ileal CD. At 14/40 gestation, CDED + PEN was prescribed without drug therapy. Outcomes included Harvey-Bradshaw Index, weight, and bowel wall thickness/Limberg score measured on intestinal ultrasound (IUS). In this patient, CDED + PEN achieved clinical and biochemical remission, improvements on IUS, gestational weight gain, and healthy birth weight without drug therapy. Sustained remission was achieved postpartum. Our case highlights the potential effectiveness of CDED + PEN to induce remission for active CD during pregnancy.

DECIDE: Delphi Expert Consensus Statement on Inflammatory Bowel Disease Dysplasia Shared Management Decision-Making.

BACKGROUND AND AIMS: Inflammatory bowel disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients. METHODS: Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders, and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement. RESULTS: In all, 31 members [15 gastroenterologists, 14 colorectal surgeons and two nurse specialists] from nine countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting. CONCLUSIONS: By consolidating evidence for best practice using literature review and key stakeholder and decision-making expert consultation, we have developed international consensus recommendations to support health care professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making.

Upadacitinib in end stage renal disease: A case of acute severe ulcerative colitis.

Recent data, indicating that inflammatory bowel disease (IBD) may be a risk factor for future chronic kidney disease, highlight the need to study the safety and clinical effectiveness of advanced IBD therapies in patients with end stage renal disease (ESRD), defined as an eGFR <15 mL/min/1.73m2. Upadacitinib, a selective oral Janus kinase (JAK) 1 inhibitor, has demonstrated efficacy in the management of moderate to severe ulcerative colitis. There is also emerging data indicating that JAK inhibition may be clinically effective in the setting of steroid-refractory acute severe ulcerative colitis (ASUC). There is, however, a lack of "real-world" data documenting the use of JAK inhibitors in patients with ESRD. Here, we report the use of upadacitinib in a patient with ESRD for the management of steroid-refractory ASUC, demonstrating, for the first time, the safe and clinically effective use of upadacitinib in this population.

Frailty predicts poor longer-term outcomes in patients following lower limb open surgical revascularization.

BACKGROUND: Frailty in vascular surgery patients is increasingly recognized as a marker of poor outcome. This provides particular challenges for patients with lower limb peripheral arterial disease who require surgical revascularization. This study aimed to assess the impact of frailty on short- and long-term outcome in this specific patient group using a specialty specific frailty score. METHODS: Patients undergoing open surgical revascularization for chronic limb ischemia (January 2015-December 2016) were assessed. Demographics, mode of admission, diagnosis, and site of surgery were recorded alongside a variety of frailty-specific characteristics. We calculated the previously validated Addenbrookes Vascular Frailty Score (AVFS) and Long AVFS (LAVFS). Primary outcome was 3-year mortality. RESULTS: Two hundred and sixty-one patients (75% men, median age 69 years) were studied. The median length of stay was 6 days with a 3-year mortality of 23%. The predictive power of vascular frailty scores showed that for 3-year mortality, area under the receiver operator curve values (AUROC) were specific for both the AVFS score (AUROC: 0.724, 95% CI: 0.654-0.794) and LAVFS Score (AUROC: 0.741, 95%CI: 0.670-0.813). Furthermore, the cumulative AVFS and LAVFS scores both predicted mortality over the follow-up period (P=0.0001) with increased mortality among patients with higher scores. CONCLUSIONS: Incremental worsening of frailty, determined using a specialty specific frailty score, predicts mortality risk in patients undergoing lower limb surgical revascularization.

Sequential Use of High-Dose Tofacitinib After Infliximab Salvage Therapy in Acute Severe Ulcerative Colitis.

BACKGROUND AND AIMS: Preliminary data regarding the effectiveness of tofacitinib in acute severe ulcerative colitis [ASUC] have been presented in two previous case series. We aimed to describe the novel use of high-dose tofacitinib immediately following non-response to infliximab in the setting of steroid-refractory ASUC. METHODS: Five patients who received high-dose tofacitinib 10 mg three times a day immediately following non-response to infliximab for steroid-refractory ASUC were identified at an Australian tertiary inflammatory bowel disease centre. RESULTS: Four of the five patients demonstrated clinical response to high-dose tofacitinib induction during their inpatient admission, with one patient requiring colectomy owing to a lack of clinical response. At 90 days, all four initial responders remained colectomy-free, with two patients achieving combined clinical and endoscopic remission. No adverse events directly attributable to high-dose tofacitinib were identified. CONCLUSIONS: High-dose tofacitinib may have a role as salvage therapy in the setting of steroid-refractory ASUC. Prospective studies are required to determine the safety and efficacy of high-dose tofacitinib to determine whether it can be routinely recommended as primary or sequential salvage therapy in the setting of steroid-refractory ASUC.

'Case of the month': a novel way to learn from endoscopy-related patient safety incidents.

Patient safety incidents (PSIs) are unintended or unexpected incidents which can or do lead to patient harm. The Joint Advisory Group on Gastrointestinal Endoscopy (JAG) acknowledges that PSIs should be reviewed by endoscopy services and learning shared among staff. It is recognised that more could be done to promote shared learning as outlined by the JAG 'Improving Safety and Reducing Error in Endoscopy' strategy. The 'Case of the month' series aims to provide a broad selection of cases and subsequent learning that can be shared among services and their workforce. This review focuses on five case vignettes that highlight a variety of PSIs in endoscopy. A structured approach, based on incident analysis methodology, is applied to each case to categorise PSIs and develop learning points. Learning is directed toward the individual, team and healthcare organisation. A selection of methods to disseminate learning at local, regional and national levels are also described.

Evaluating the Epley Canalolith Repositioning Procedure With and Without a Visual Assistive Device.

HYPOTHESIS: The primary goal of this study was to examine how accuracy is affected when we employ a guidance device to assist with the execution of the Epley canalolith repositioning procedure. BACKGROUND: Benign paroxysmal positional vertigo is a common cause of vestibular vertigo. Treatment is noninvasive and generally effective when performed correctly. Deficiencies in clinical application result in unnecessary failures in response for those affected. METHODS: Ten participants were each taken through six iterations of the Epley canalolith repositioning procedure. Iterations were divided evenly between those conducted with and without the use of a guidance device. One clinician performed all 60 procedures. Head movements were recorded using motion capture cameras and strategically placed motion tracking markers. RESULTS: Results showed that the guidance device significantly improved the latter phase maneuver accuracy. Rotation error was significantly reduced for hold3 with-device (M = 20.23°, SD = 12.08°) versus without-device (M = 40.13°, SD = 14.62°, p  =  0.001). Maximal rotation error during rotation4 of the maneuver demonstrated a similar reduction of error with-device (M = 24.44°, SD = 10.43°) versus without-device (M = 41.36°, SD = 12.89°, p  =  0.002). CONCLUSION: A simple visual guidance device can increase the execution accuracy of canalith repositioning procedures. Further research is required to show how such improvements influence treatment efficacy.

Diagnostic ileocolonoscopy: getting the basics right.

Proficient colonoscopy technique that optimises patient comfort while simultaneously enhancing the timely detection of pathology and subsequent therapy is an aspirational and achievable goal for every endoscopist. This article aims to provide strategies to improve colonoscopy quality for both endoscopists and patients.