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.

An International Survey of Clinicians' Experience Caring for Patients Receiving Home Parenteral Nutrition for Chronic Intestinal Failure During the COVID-19 Pandemic.

BACKGROUND: This survey of centers caring for patients receiving home parenteral nutrition (HPN) was conducted to assess the impact of the coronavirus disease 2019 (COVID-19) crisis on the management of these patients regarding provision of care, monitoring, regular follow-up, and any changes to service infrastructure. METHODS: A survey was devised and publically published on the Research Electronic Data Capture database management system, with individual centers responding to a public link. RESULTS: A total of 78 adult and pediatric centers worldwide contributed to the survey, representing ≥3500 patients' experiences. Centers reported infrastructure maintenance for Parenteral Nutrition (PN) bag deliveries to patients (60, 76.92%) or delivery of ancillary items (57, 73.08%), home delivery and HPN administration (65, 83.33%), and home care nurse shortages (25, 32.05%). Routine follow-up of HPN patients changed to either all telemed or mixed with emergency clinic review (70, 89.74%). In 26 centers (33.33%), HPN for newly discharged patients with benign conditions was reduced or stopped. Based on clinical history, the centers reported psychological distress for patients (52, 66.67%), with anxiety, worry, concern, and apprehension reported most frequently (37 of 52, 71.15%) but also fear (10 of 52, 19.23%), depression (5 of 52, 9.62%), and issues related to isolation/confinement (12 of 52, 23.08%). CONCLUSIONS: The COVID-19 pandemic was reported by clinicians to have had a far-reaching adverse impact on patients receiving HPN, especially their safety in terms of provision of personal protective equipment, PN bags, available nursing staff, and psychological well-being. Healthcare systems responded to the challenge and presented new ways of working.

The impact of intestinal transplantation on quality of life.

INTRODUCTION: Intestinal failure (IF) and intestinal transplant (ITx) are associated with poor quality of life (QoL). Disease-specific assessment of QoL for IF and ITx is challenging, owing to the different problems encountered. We have sought to compare QoL pre-ITx with post-ITx and have compared generic QoL with a stable IF population. METHODS: Two prospectively maintained databases of patients referred for and undergoing ITx and a chronic (Type 2 & 3) IF cohort were interrogated. QoL instruments used were generic (EQ-5D-5L and SF-36) and disease-specific (HPN-QOL and ITx-QOL). Analysis used Student's t-test and one-way ANOVA with Bonferroni correction for multiple comparisons. Data were collected pre- and post-ITx at 3, 6, 12-months and yearly thereafter. RESULTS: All QoL instruments improved following ITx to levels comparable with a cohort of stable IF patients not requiring ITx. Both the visual analogue score component (EQ-5D-5L) and the effect of underlying illness on QoL (HPN-QOL/ITx-QOL) were higher following ITx than either pre-ITx or when compared with the IF cohort. Effects on general health, ability to eat and drink, to holiday and travel were improved as early as 3 months post-ITx. Other components did not before 6-12 months following ITx, but were maintained to at least 24 months. Patient personal financial pressures are greater following ITx, even in a publicly funded healthcare system. CONCLUSION: ITx has beneficial effects on QoL compared to those assessed for or awaiting ITx. QoL following ITx is similar to patients with IF not requiring ITx. A QoL instrument that covers the journey of patients from IF through ITx would assist longitudinal analysis of the value and timing of ITx at an individual level.

Application of quality improvement techniques to reduce parenteral nutrition wastage in a national intestinal failure unit.

OBJECTIVES: Parenteral nutrition (PN) costs approximately £80 per day per bag. Unpredictable changes in patients' clinical condition, venous access loss or reasons related to the processes involved in administering PN can lead to PN wastage. Cost efficiencies are imperative to optimise limited resource utilisation in all current healthcare economies. We undertook a quality improvement (QI) project to reduce PN wastage in an adult acute hospital setting. The project SMART's (specific, measurable, achievable, realistic, time-based) objective was reducing in-patient PN wastage by 10% in 9 months using QI methodology on a national intestinal failure unit (IFU). METHOD: Wastage reasons were evaluated through pareto charts to target waste reduction using 'Plan, Do, Study, Act' (PDSA) cycles. Variation was mapped using c-charts. RESULTS: 12-week baseline wastage data predicted 1000 bags wasted per annum (p.a.). PDSA cycles actioned included: regular enhanced clinical team awareness of wastage; unused PN bags redistributed within expiry date; stock bag rotation; critical path analysis of PN bag journey; enhanced discharge planning/coordination; reorganisation of fridge PN storage according to weekday; changing ordering frequency and bag type (from tailored to standard) to increase flexibility around discharge date and PN weaning. Implementation of PDSA cycles led to a 34% reduction in PN wastage in 9 months. CONCLUSION: In a high-use IFU, PN wastage is common and costly. Using a QI approach with concurrent PDSA cycles and a motivated multidisciplinary team, high levels of wastage reduction are possible with associated significant cost savings and from this study a predicted cost saving of approximately £30 000 p.a.

A risk stratifying tool to facilitate safe late-stage percutaneous endoscopic gastrostomy in ALS.

BACKGROUND: The safety of percutaneous endoscopic gastrostomy (PEG) insertion in amyotrophic lateral sclerosis (ALS) patients with significant respiratory compromise has been questioned. OBJECTIVES: To review the characteristics of an ALS clinic patient cohort undergoing PEG, and the introduction of a risk stratification tool with procedural adaptations for higher-risk individuals. METHODS: Patients undergoing PEG insertion were analysed (n = 107). Cases stratified as higher-risk underwent insertion in a semi-recumbent position, minimising sedation, with the option of nasal non-invasive ventilation. RESULTS: All underwent successful PEG. One-third had pre-procedure FVC ≤50% (mean, 64 ± 22%). Of those who underwent PEG insertion after introduction of risk stratification (n = 58), 39 (67%) met criteria for being higher risk, 16 (41%) of whom had FVC ≤50% (p = 0.005). High-risk patients received lower sedative doses vs. the low-risk group (midazolam 2.1 ± 1.1 vs.2.8 ± 0.95mg, p = 0.021; fentanyl 42 ± 16 vs. 60 ± 21µg, p = 0.015). Four deaths occurred within one month of insertion (attributable to the natural disease course). CONCLUSIONS: Risk stratification identified a greater number of patients with evidence of respiratory compromise than using the sole criterion of FVC ≤50%. A modified PEG procedure enabled safe insertion despite respiratory compromise, in those who might not have tolerated attempted insertion by alternative means such as radiologically-inserted gastrostomy.