NHS GRAMPIAN REVIEW OF NEW GUIDANCE FOR VARICEAL SCREENING

Introduction Covid-19 pandemic caused significant disruption to elective endoscopy services nationally. This paved way to endoscopy minimised management pathways for patients with liver cirrhosis. Standard pathway pre-COVID19 was as set out in Baveno VI consensus guidelines and involved variceal screening endoscopy for all patients with clinically significant portal hypertension. We adopted the new pathway as suggested by the national clinical forum, endorsed by the Scottish Government, which proposes the use of Carvedilol in patients with clinically significant portal hypertension and endoscopy reserved for patients who are intolerant of carvedilol or have contraindications to beta-blocker use. The rationale behind new guidance is the improvement in survival with Carvedilol and its efficacy in reducing hepatic venous pressure gradient and preventing decompensation. The recent Baveno VII consensus also suggests patients established on Carvedilol therapy do not need endoscopy as it is unlikely to change clinical management. We aim to assess the impact of applying the new guidance on the variceal screening/surveillance endoscopy waiting list. Methods 243 patients were identified on our variceal endoscopy waiting list who were due an endoscopy between 2019 and 2024. Patients on variceal banding programme have been excluded from this analysis. Data collected included their Childs Pugh score, fibroscan score, medications, platelet count and previous endoscopy results if applicable. Patients were then categorised into three groups. 1. Clinical monitoring of blood tests and fibroscan yearly without endoscopy 2. Carvedilol therapy indicated 3. To continue with endoscopic screening. Results 26/243 (10.6%) patients were removed from the waiting list with plan for yearly monitoring. 10/243 (4%) patients were to continue with endoscopic screening due to Carvedilol intolerance. 207 patients met the criteria to commence Carvedilol without the need for endoscopy. Therefore, 207/233 (88%) patients could be removed from the waiting list by applying the new guidance. This would free up approximately 29 endoscopy lists which can be utilised to address other areas within gastroenterology and hepatology service with longer waiting times. Conclusions The impact on variceal endoscopy waiting times by adopting the new guidance is significant. It provides opportunity to utilise the resources more effectively. From patient's perspective, endoscopy is an invasive procedure and anxiety provoking to some patients resulting in failure to attend endoscopy appointments. As the requirement for endoscopy is considerably low, the new guidance may be more acceptable to patients who prefer to avoid endoscopy. Patient compliance and tolerance to Carvedilol will be recorded prospectively to assess the overall impact on the service.

NURSE LED CLOSE MONITORING CLINIC FOR PATIENTS WITH DECOMPENSATED LIVER DISEASE OR DERANGED LIVER FUNCTION

Introduction Emergency admission to hospital with decompensated liver disease (DLD) is a common medical presentation and carries a high mortality (10-20%)(1). Due to the nature of the disease and the associated complexities, the Close Monitoring Clinic (CMC) was set up to facilitate appropriate review post discharge with the aim of allowing early discharge, reducing re-admission rates and to provide education and support to patients. Aims and objectives To effectively manage and support patients with features of decompensated liver disease following discharge from the Gastroenterology Ward. The clinic also has capacity to review patients with other liver conditions who require close monitoring. Reduce the workload of medical staff and ensure patients are seen within 1-2 weeks post discharge in an attempt to reduce the readmission rate. Methods Clinic Commenced in 02/07/2019, half hour appointments were allocated to each patient. Nurses have completed clinical examination skills training and are independent prescribers. An MDT was introduced for discussion of patients with medical, pharmacy, nursing staff the following day when blood results available. It is planned the Palliative care team will join this MDT. It was initially thought that 4 clinic slots per week would be sufficient to accommodate all patients, however we had to increase this according to demand. Results To date (14/02/2022) there have been 500 appointments offered, only 42 appointments were not attended, giving an attendance rate of 92%. There have been 174 individuals offered appointments for the clinic, with a mean number of appointments per patient being 2 (range 1-28). The demographics show that 102 (58%) patients are male, the average age of those offered appointments was 58years old (range22-89). The aetiology of the need for an appointment can be seen in Chart 4. The time from discharge and appointment request (1-2 weeks) to time of actual appointment offered in a 20% sample is 85% of patients offered an appointment within the requested time frame. Conclusion The close monitoring clinic is an invaluable service, reducing the number of appointments required by medical staff. During the COVID-19 pandemic, we continued to see these patients face to face and if required arrange planned admissions mainly for ascitic drainage, reducing the workload on emergency care staff and GPs. These patients whilst in hospital are in a critical condition and often have had a near death experience have found the psychological support and the availability of telephone advice between appointments invaluable. The 'did not attend' rate is extremely low at 8%, which is incredible given the high number of patients with alcohol related aetiology.

MANUFACTURING FRESHLY CULTURED UMBILICAL CORD-DERIVED MESENCHYMAL STROMAL CELLS (UC-MSCS) FOR A PHASE 1, MULTIPLE-DOSE CLINICAL TRIAL FOR COVID-19-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

Background & Aim: The Cellular Immuno-Therapy for COVID-19 related ARDS (CIRCA-19) was a phase 1, single site, dose escalation trial using a 3+3+3 design to determine the safety and maximum feasible tolerated dose of intravenously delivered, freshly cultured UC-MSCs. Nine patients, each receiving repeated unit doses of UC-MSCs over 3 consecutive days, were enrolled into 3 dose panels: Panel 1: 25×106 cells/dose (cumulative dose: 75×106 MSCs);Panel 2: 50×106 cells/dose (cumulative dose: 150×106 MSCs);Panel 3: up to 90×106 cells/dose (cumulative dose: 270×106 MSCs). Methods, Results & Conclusion: UC-MSCs were isolated from cords of healthy term pregnancies delivered by C-section. Cords were mechanically and enzymatically digested, and UC-MSCs were propagated in xeno-free conditions for 2 weeks prior to cryopreservation in a cord specific cell bank. One fully validated cell bank was used in CIRCA-19 that was free of adventitious agents (HBV, HCV, HSV1/2, Parvo B19 and Retroviruses), had high viability (>95%) and MSC identity with positive expression (>95%) of CD73, CD90 and CD105 and negative expression (<5%) of CD14, CD19, CD34, CD45 and HLA-DR. UC-MSCs also demonstrated high proliferative capacity (EdU+ >45%;DBT = 22h) and enhanced IDO expression (ΔΔCq?>18) when treated with IFN-γ. For the final product, UC-MSCs were thawed, plated and cultured for 24 to 120 h before harvesting to produce a batch of the final drug product formulated as 2.5×106 fresh UC-MSCs/mL suspended in PlasmaLyte A containing 5% Human Albumin, to be infused within 48h. Batches were tested for viability, endotoxin level, ACE-2 expression, tissue factor activity, sterility and mycoplasma. Sixteen batches of UC-MSCs were produced for a total of 41 cell doses (16 doses of 25M;13 doses of 50M;12 doses of 90M cells each). Twenty-seven of the 41 doses (9 doses of 25M, 50M and 90M cells each) were used to treat trial participants. The remaining doses were used for stability studies. All drug products had high viability (> 95%), endotoxin levels of <0.2 EU/mL and tested negative for mycoplasma and bacterial contaminants. All UC-MSC batches were negative for ACE-2 expression (Cq?>35;GAPHD Cq: 15±2;no detectable levels by western blotting) and had tissue factor activity levels between 250-310pM. UC-MSC drug product was stable for up to 96h (>80% viability) and had?>90% viability up to 48h in all 3 dose panels. This study demonstrates the feasibility of manufacture and delivery of a multi-dose fresh cell product in an emergent ICU setting.

Virtual fracture liaison clinics in the COVID era: an initiative to maintain fracture prevention services during the pandemic associated with positive patient experience.

We introduced virtual fracture liaison clinics during the COVID-19 pandemic in order to support clinical care while DXA services were down-turned. We observed that virtual FLS clinics are effective in delivering fracture risk assessment, health promotion, and clinical management and are well received by patients with positive patient experience. INTRODUCTION: We examined the impact of virtual FLS telephone clinics, as an alternative to face-to-face clinics during the COVID-19 lockdown. METHODS: Patients presenting with low trauma fracture were recruited according to standard criteria. A structured telephone clinic appointment was offered, which included fracture risk and health promotion assessment and a treatment plan. Risk factors, demographics, fracture type, FRAX scores, and outcomes were analysed. We assessed patient experience with an anonymised patient survey. RESULTS: Clinical outcomes from virtual clinics were assessed (77F/33M; mean age 65.7 years). The mean 10-year observed fracture risk for major osteoporotic fracture was 18.2% and 7.0% for hip fracture. We observed high 'attendance' rates at 79%; however, a significant number were still not available for telephone review (11%) or cancelled their appointment (10%). A recommendation for bisphosphonate treatment was made in 54% of the cohort based on National Osteoporosis Guidelines Group (NOGG) criteria. Follow-up DXA assessment is planned for 64%, according to fracture risk and NOGG guidance. We received 60 responses from the initial patient survey. Ninety percent rated their overall experience of service at 4 or 5 (very good to excellent). Ninety-eight indicated they would recommend the service to others. CONCLUSIONS: Virtual clinics are effective in delivery of fracture risk assessment and clinical management with positive patient experience. While a significant proportion will require DXA follow-up to complete the clinical assessment, virtual clinics have mitigated delays in fracture prevention interventions during the COVID-19 pandemic.

Radical radiotherapy (RT) and chemoradiotherapy (CRT) in non-small cell lung cancer (NSCLC): Outcomes from a regional cancer network

Background: This is a retrospective review of outcomes and predictive factors for radical RT for NSCLC in our network. Technological advancement in RT has enabled treatment of larger tumours. SOCCAR (55Gy in 20 fractions) is the most used regime at our centre. This is a timely review in the context of COVID-19, with a renewed interest in shorter RT schedules. Methods: Data for patients who received RT or CRT for Stage I-III NSCLC from 2016-2018 (prior to introduction of adjuvant Durvalumab – NICE approved in 2018) was reviewed at North Middlesex University Hospital, London. Data included smoking history, lung function, planning parameters (PTV, Mean heart dose (MHD), V20 and V5 lung), relapses and deaths. Outcomes were demonstrated as overall survival (OS) and progression free survival (PFS) through Kaplan-Meier analyses. Progression was defined from follow-up imaging or clinical documentation. Results: 90 patients were analysed. Median follow-up time was 16 months. Median age was 72. 60 patients received 55Gy (66%) and 30 received 60-66Gy (33%). 32 patients received concurrent CRT (cCRT-36%), 13 received sequential CRT (sCRT-14%) and 45 received RT alone (50%). 21 patients had early disease (Stage I+II,23%) and 69 had Stage III disease (77%). Median PTV was 304 mm3 and median MHD was 6.65Gy. For all patients, median OS (mOS) was 23 months. Median PFS (mPFS) was 12 months. 1, 2 and 3 year OSR was 72%, 47% and 30% respectively. In those aged over 70, mOS was 23 months and mPFS was 12. For cCRT, mOS was 26 months and mPFS was 14. For sCRT, mOS was 13 months and mPFS was 13. RT alone mOS was 22 months and mPFS was 10. mOS for the cCRT group using 60-66Gy was 26 months and was not reached for 55Gy. mPFS for 60-66Gy and 55Gy was 12 and 15 months respectively. In those aged over 70-1,2 and 3 year OSR was 83%,70% and 50% respectively. FEV1% predicted was associated with OS (HR 0.98, 95% CI 0.97-0.99, p=0.04). Further analysis was performed looking at smoking history, performance status, pathology and gender. Conclusions: Our data confirms that cCRT is an effective treatment for NSCLC (regardless of schedule and age) with comparable outcomes to contemporary CRT trials. Patient screening and regimen choice is key to good outcomes, as apparent in the trends within our data. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.