Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response.

OBJECTIVES: We aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission. DESIGN: Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015-2020, n=110; All India Institute of Medical Sciences, New Delhi 2018-2020, n=62). RESULTS: In the 2015-2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992-1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992-1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%-11%. CONCLUSIONS: Emergency colectomy rates for ASC have halved in 25 years to 8%-15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.

Patient-reported Outcomes: the ICHOM Standard Set for Inflammatory Bowel Disease in Real-life Practice Helps Quantify Deficits in Current Care.

BACKGROUND: Patient-reported outcome measures [PROMs] are key to documenting outcomes that matter most to patients and are increasingly important to commissioners of health care seeking value. We report the first series of the ICHOM Standard Set for Inflammatory Bowel Disease [IBD]. METHODS: Patients treated for ulcerative colitis [UC] or Crohn's disease [CD] in our centre were offered enrolment into the web-based TrueColours-IBD programme. Through this programme, e-mail prompts linking to validated questionnaires were sent for symptoms, quality of life, and ICHOM IBD outcomes. RESULTS: The first 1299 consecutive patients enrolled [779 UC, 520 CD] were studied with median 270 days of follow-up (interquartile range [IQR] 116, 504). 671 [52%] were female, mean age 42 years (standard deviation [sd] 16), mean body mass index [BMI] 26 [sd 5.3]. At registration, 483 [37%] were using advanced therapies. Median adherence to fortnightly quality of life reporting and quarterly outcomes was 100% [IQR 48, 100%] and 100% [IQR 75, 100%], respectively. In the previous 12 months, prednisolone use was reported by 229 [29%] patients with UC vs 81 [16%] with CD, p <0.001; 202 [16%] for <3 months; and 108 [8%] for >3 months. An IBD-related intervention was reported by 174 [13%] patients, and 80 [6%] reported an unplanned hospital admission. There were high rates of fatigue [50%] and mood disturbance [23%]. CONCLUSIONS: Outcomes reported by patients illustrate the scale of the therapeutic deficit in current care. Proof of principle is demonstrated that PROM data can be collected continuously with little burden on health care professionals. This may become a metric for quality improvement programmes or to compare outcomes.

Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets.

Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal TRM cells remains undefined. Here, we investigate transcriptional and functional heterogeneity of human TRM cells through study of donor-derived TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identifies two transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We define a transcriptional signature discriminating these populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft, and lymphocytes from healthy gut, confirm these CD8+ TRM phenotypes. CD8+ CD69+CD103+ TRM cells produce interleukin-2 (IL-2) and demonstrate greater polyfunctional cytokine production, whereas ß2-integrin+CD69+CD103- TRM cells have higher granzyme expression. Analysis of intestinal CD4+ T cells identifies several parallels, including a ß2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ TRM cells.

Fatal breakthrough mucormycosis in a multivisceral transplant patient receiving micafungin: Case report and literature review.

Introduction: Antifungal agents are routinely used in the post-transplant setting for both prophylaxis and treatment of presumed and proven fungal infections. Micafungin is an echinocandin-class antifungal with broad antifungal cover and favorable side effect profile but, notably, it has no activity against molds of the order Mucorales. Presentation of case: A 47-year-old woman underwent multivisceral transplantation for intestinal failure-associated liver disease. She had a prolonged post-operative recovery complicated by invasive candidiasis and developed an intolerance to liposomal amphotericin B. In view of her immunosuppression, she was commenced on micafungin as prophylaxis to prevent invasive fungal infection. However, she developed acute graft versus host disease with bone marrow failure complicated by disseminated mucormycosis which was only diagnosed post mortem. Discussion: Non-Aspergillus breakthrough mold infections with micafungin therapy are rare with only eight other cases having been described in the literature. Breakthrough infections have occurred within one week of starting micafungin. Diagnosis is problematic and requires a high degree of clinical suspicion and microscopic/histological examination of an involved site. The management of these aggressive infections involves extensive debridement and appropriate antifungal cover. Conclusion: A high level of suspicion of invasive fungal infection is required at all times in immunosuppressed patients, even those receiving antifungal prophylaxis. Early biopsy is required. Even with early recognition and aggressive treatment of these infections, prognosis is poor.

Spinal Infections Among Patients With Long-Term Central Venous Catheters for Home Parenteral Nutrition.

Spinal infections are a rare yet serious metastatic complication of bacteremia among patients with long-term central venous catheters (CVCs) for which clinicians must remain vigilant. We performed a retrospective review of all cases of spinal infection occurring in the context of a CVC for long-term parenteral nutrition (PN) managed in our department between January 2010 and October 2013, a cohort of 310 patients over this time period. Six patients were identified (mean age, 65 years; 5 male). One hundred percent of patients presented with spinal pain (5/6 cervical, 1/6 thoracic). Organisms were cultured from the CVC in 5 of 6 patients. In all cases, the white blood cell count was normal, and in 5 of 6, C-reactive protein was normal. All diagnoses were confirmed on magnetic resonance imaging (MRI), and in 3 of 6 cases, an MRI was repeated (on the advice of neurosurgical colleagues) to confirm resolution of changes after a period of antimicrobial therapy. There was no clear correlation between duration of PN or number of days following CVC insertion and onset of infection. The CVC was replaced in 4 of 6 patients at the time of diagnosis, delayed removal in 1 of 6, and salvaged in the remaining case. Although rare, a high index of suspicion is needed in patients receiving long-term PN who present with spinal pain. Peripheral inflammatory markers may not be elevated. MRI should be performed and patients should be treated with antibiotics alongside involvement of local microbiology and neurosurgical teams. Multidisciplinary discussion on CVC salvage in these cases is important, especially in cases of challenging vascular anatomy.

Spinal Infections Among Patients With Long-Term Central Venous Catheters for Home Parenteral Nutrition: A Descriptive Case Series.

Spinal infections are a rare yet serious metastatic complication of bacteremia among patients with long-term central venous catheters (CVCs) for which clinicians must remain vigilant. We performed a retrospective review of all cases of spinal infection occurring in the context of a CVC for long-term parenteral nutrition (PN) managed in our department between January 2010 and October 2013, a cohort of 310 patients over this time period. Six patients were identified (mean age, 65 years; 5 male). One hundred percent of patients presented with spinal pain (5/6 cervical, 1/6 thoracic). Organisms were cultured from the CVC in 5 of 6 patients. In all cases, the white blood cell count was normal, and in 5 of 6, C-reactive protein was normal. All diagnoses were confirmed on magnetic resonance imaging (MRI), and in 3 of 6 cases, an MRI was repeated (on the advice of neurosurgical colleagues) to confirm resolution of changes after a period of antimicrobial therapy. There was no clear correlation between duration of PN or number of days following CVC insertion and onset of infection. The CVC was replaced in 4 of 6 patients at the time of diagnosis, delayed removal in 1 of 6, and salvaged in the remaining case. Although rare, a high index of suspicion is needed in patients receiving long-term PN who present with spinal pain. Peripheral inflammatory markers may not be elevated. MRI should be performed and patients should be treated with antibiotics alongside involvement of local microbiology and neurosurgical teams. Multidisciplinary discussion on CVC salvage in these cases is important, especially in cases of challenging vascular anatomy.

Obesity: a window of opportunity to intervene? Characteristics and management of morbidly obese adult inpatients in three trusts in Southern England.

Obesity affects 22% of men and 24% of women over the age of 16 years in the general population of the UK and is associated with multiple comorbidities. Little is known about the magnitude of the obesity problem among hospitalised adults and, although significant focus has been given to the identification and treatment of the malnourished inpatient, it is not known to what extent obese inpatients are equally -targeted. National guidelines for consideration of bariatric surgery exist, but it is not known to what extent potentially eligible individuals are referred. This multi-centre study -demonstrates a significant burden of obesity (defined as body mass index [BMI] ≥30 kg/m(2)) among those in hospital, affecting 22% of patients. This was more marked among orthopaedic patients and all-comers to intensive care units than on medical or surgical wards. Of those with BMI ≥35 kg/m(2), only 21% had been reviewed by dietetics and only 10% of patients who were potentially eligible for bariatric surgery had been referred to bariatric services. This study shows that there is an opportunity to recognise obesity and intervene in its management during hospital admission.

Case report: recurrent acute pancreatitis secondary to papillary somatostatinoma--a new association.

Acute pancreatitis may rarely be caused by papillary mass lesions such as adenocarcinomas and neuroendocrine tumours. Occasionally these papillary lesions may cause recurrent episodes of acute pancreatitis and patients presenting in this way require further pancreatic investigation. We believe this to be the first reported case of a duodenal papillary somatostatinoma causing recurrent acute pancreatitis. The patient was investigated with multiple imaging modalities, both at endoscopy and with more traditional radiology, and treated with resection by Whipple's pancreaticoduodenectomy. If diagnosed early in the absence of distant metastases the prognosis of papillary somatostatinoma with tumour resection is excellent.

A rare cause of haematemesis and chest pain.

This article discusses an elderly woman presenting with haematemesis and chest pain who underwent urgent oesophago-gastroduodenoscopy. This revealed a large dissecting intramural oesophageal haematoma, initially mistaken for a varix. This is a rare cause of haematemesis and chest pain but has characteristic endoscopic findings. It is a benign condition that may be managed conservatively and both clinicians and endoscopists should be aware of its classical presentation. Misdiagnosis of the chest pain as cardiac ischaemia may have an adverse outcome if antiplatelet or anticoagulation therapy is commenced. Follow up endoscopy a week later showed complete resolution of the lesion leaving a linear mucosal defect.