Standard Of Care Research Articles

Economic evaluation of the Liverpool heart failure virtual ward model.

A virtual ward (VW) supports patients who would otherwise need hospitalisation by providing acute care, remote monitoring, investigations, and treatment at home. By March 2024 the VW programme had treated 10 950 patients across six speciality VWs, including heart failure (HF). This evaluation presents the economic assessment of the Liverpool HF VW. A comprehensive economic cost comparison model was developed by York Health Economics Consortium (University of York) to compare the costs of the VW to standard hospital inpatient care (SC). The model included direct VW costs and additional costs across the care pathway. Costs and resource use for 648 patients admitted to the HF VW were calculated for 30 days post discharge and total cohort costs were extrapolated to a full year. Primary outcomes included costs related to length of stay, readmissions, and NHS 111 contact. The total cost for the HF VW pathway, including set-up costs, was £467 524. This results in an incremental net cost benefit of £735 512 compared to the total SC cost of £1 203 036, indicating a substantial net cost benefit of £1 135 per patient per episode (PPPE). This advantage remains despite initial setup expenses and ongoing costs such as home visits, virtual consultations, point-of-care (POC) testing and home monitoring equipment. Our HF VW model offers a substantial net cost benefit, driven by reduced hospital stays, fewer emergency department visits, and lower readmission rates. The study highlights the importance of considering system-wide impacts and continuous monitoring of VWs as they develop.

The Impact of Hierarchical Chain Nursing Model on the Resolution Time of Fever and Cough in Children with Pneumonia

Objective: This study investigates the effects of a hierarchical chain nursing model on the resolution time for fever and cough in children diagnosed with pneumonia. Methods: Eighty children with pneumonia admitted to our hospital between March 2021 and January 2022 were enrolled in this study. The participants were divided into two groups: the observation group and the experimental group, each containing 40 patients, based on the nursing interventions provided. The observation group received standard nursing care, while the experimental group was treated with the hierarchical chain nursing model. We compared clinical outcomes, including the resolution times for symptoms (fever, cough, pulmonary rales), length of hospitalization, pulmonary function indicators [such as peak expiratory flow (PEF), functional residual capacity (FRC), and forced expiratory flow rate at 25% of vital capacity (FEF25%)], the mental health of family members, and their satisfaction with nursing care. Results: The total effective treatment rate was 77.5% in the observation group and 97.5% in the experimental group, with the latter significantly higher (P<0.05). The duration of pulmonary rales and the length of hospitalization were significantly less in the experimental group (all, P<0.05). Post-intervention, the levels of PEF, FRC, and FEF25% showed substantial improvement in the experimental group compared to the observation group (all, P<0.05). Moreover, the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores for family members in the experimental group were significantly lower than those in the observation group (all, P<0.05). Family satisfaction rates were 75.0% for the observation group and 97.5% for the experimental group, with the latter demonstrating significantly greater satisfaction with nursing care (P<0.05). Conclusion: The hierarchical chain nursing model proves to be highly effective in managing pneumonia in children. This model not only enhances clinical outcomes and expedites the resolution of symptoms such as fever, cough, and pulmonary rales but also improves lung function and reduces psychological stress among family members. Consequently, this model significantly increases family satisfaction with nursing services.

BS SO09 - Use of ursodeoxycholic acid in preventing gallstone formation after bariatric surgery – introduction of a new clinical pathway

Abstract Background Rapid weight loss is a risk factor for symptomatic gallstone formation. Managing gallstone disease such as choledocholithiasis can be more challenging after Bariatric Surgery (BS) due to altered anatomy. Ursodeoxycholic acid (UDCA) is a low-cost and low-risk method of reducing the risk of symptomatic gallstone disease and cholecystectomy by almost a third in patients who have had BS. However, it is not yet included in national guidelines for bariatric surgery. We audited prescription rates of UDCA in patients who underwent BS with a view to introducing it into our standard post BS care bundle. Method Data was collected from 30 consecutive patients who underwent a sleeve gastrectomy or Gastric bypass in November and December 2023. The results informed our practice and a UDCA prescribing pathway was developed using evidence from randomized trials. The pathway was circulated to all members of the bariatric service on 17/1/2024 and discussed at the departmental meeting. The audit loop was closed by collecting data from a further 30 consecutive patients. Demographic data, type of operation, BMI, history of gallstone disease, prescribing data and reasons for non-compliance were collected. The compliance rate to the UCDA pathway was expected to be 100%. Results Data was collected from 60 patients (85% female; median BMI 49; median age 45). No patient who could have benefited received UDCA prior to the intervention. After the intervention, 15/30 (50%) of patients were correctly prescribed UDCA. Therefore, correct prescription of UDCA did not meet target compliance rates. No patient was incorrectly prescribed UCDA. Reasons for non-compliance include human error, concern about the size of the tablet, inadequate knowledge about how to administer (e.g. crushing in liquid) and misconceptions of oral intake after BS. Conclusion UCDA can reduce incidence of symptomatic gallstones following BS, yet use of UDCA in bariatric centres in the UK is thought to be low. We discovered that more time should be dedicated to educating the team about administration methods and how it interacts with the current postoperative diet plan. A UCDA pathway and education of bariatric teams can improve compliance with appropriate UDCA prescribing. Further intervention is required and planned in our centre such as utilising e-prescribing as a prompt to include UDCA in the discharge prescription and considering the use of the drug's liquid form in the short term.

Can Digital Technology Revolutionize Continuous Education in Diabetes Care?

Rapid technological advancements, such as artificial intelligence, wearable technologies, and telehealth with remote monitoring, are transforming continuous education for health care providers (HCPs) in diabetes management. These technologies improve patient care and necessitate innovative educational approaches to prepare HCPs for clinical integration. Digital education offers real-time, scalable, and cost-effective solutions, especially in areas with health care workforce shortages. However, the effect of digital education on HCPs' knowledge, skills, attitudes, and patient outcomes remains under-researched and necessitates further study. As technologies advance, achieving precision in diabetes continuous education becomes feasible. The 2024 ADA Standards of Care emphasize early adoption of advanced technologies and proficiency among HCPs. This commentary explores transformative trends, discussing limitations and proposing solutions to revolutionize continuous education in diabetes care.

Prospective Screening of Cancer Syndromes in Patients with Mesenchymal Tumors

Background: The etiology of most mesenchymal tumors is unknown, and knowledge about syndromes with an increased risk of tumors in bone or soft tissue is sparse. Methods: We present a prospective germline analysis of 312 patients with tumors suspected of being sarcomas at a tertiary sarcoma center. Germline and tumor whole genome sequencing, tumor transcriptome, and methylome analyses were performed. Results: Germline pathogenic or likely pathogenic variants associated with an increased risk of tumors were detected in 24 patients (8%), of which 11 (4%) harbored a detectable second hit in the tumor. Second hits were confirmed in genes with (NF1, RB1, TP53, EXT2, and SDHC) and without (ATM, CDC73, MLH1, MSH6, POLG, and KCNQ1) known association with mesenchymal tumor predisposition. Sarcomas from two Lynch syndrome patients showed mismatch repair deficiency, predicting a treatment response to immune checkpoint inhibitors (Level 1 biomarker according to the FDA (Federal Drug Administration) and ESMO (European Society for Medical Oncology)). None of the three CHEK2 carriers had a second hit in the tumor, suggesting a weak link to sarcoma. Conclusions: We conclude that second-hit analyses can be used in standard of care to identify syndrome-related tumors. This approach can help distinguish true manifestations of tumor syndromes from unrelated germline findings and enhance the understanding of germline predisposition in soft tissue tumors. Prospective screening using germline whole genome sequencing should be considered when comprehensive somatic sequencing is introduced into clinical practice.

AI-Enhanced Predictive Analytics for Proactive Healthcare Management: Leveraging Machine Learning to Improve Patient Care and Operational Efficiency

As healthcare changes quickly, combining artificial intelligence (AI) and machine learning (ML) technologies has become a major force that can change things. This is because it improves predictive analytics for proactive healthcare management. This essay looks at how AI-powered predictive analytics might be able to help healthcare systems provide better care to patients and run more smoothly. Machine learning algorithms can find patterns and trends in huge amounts of patient data that traditional analysis methods might miss. This lets healthcare workers make smart decisions before big problems happen. The study looks into many uses of AI-enhanced prediction analytics, such as figuring out which patients are at the highest risk, finding diseases early, and making treatment plans work better. Using past patient data and real-time tracking, predictive models can figure out how likely it is that a person will develop a chronic condition. This lets doctors act quickly and make personalized care plans for each person. This cautious method not only improves the health of patients, but it also makes healthcare systems less busy by cutting down on hospital readmissions and trips to the emergency room. The paper also looks at how predictive analytics can help healthcare groups streamline their working processes. Healthcare facilities can better arrange staff and tools, making sure that resources are available where and when they are needed, by predicting how many patients will be admitted and how resources will be used. This speed makes patients happier, cuts down on wait times, and raises the standard of care generally. The study also looks at the problems that come with using AI and predictive analytics in healthcare, such as worries about data privacy, integrating new systems with old ones, and the need for strong algorithms that can handle a wide range of patients. It stresses how important it is for lawmakers, healthcare workers, and data scientists to work together to make ethical rules for the use of AI in healthcare situations.

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.

Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

BN SO13 - Re-Audit of Biliary Pancreatitis Management: Enhancing Compliance with Timely Laparoscopic Cholecystectomy

Abstract Background Biliary acute pancreatitis requires timely management to prevent complications. Guidelines recommend laparoscopic cholecystectomy within two weeks of admission. A previous audit in our surgery department showed only 32.6% compliance with this guideline. This re-audit aimed to evaluate improvements in compliance, identify barriers, and provide insights for enhancing patient care. By retrospectively analyzing patient data from January to November 2023, we assessed progress and highlighted areas needing further improvement to align with established guidelines and ensure better patient outcomes. Method A retrospective analysis was conducted on a cohort of 32 patients admitted to the general surgery department with a diagnosis of biliary acute pancreatitis between January 2023 and November 2023. Patient records were reviewed to gather data on the timing of laparoscopic cholecystectomy performed within two weeks of the index admission. The compliance rate from this period was compared to a previous audit to assess improvements. Key barriers to timely intervention, such as the availability of ultrasound slots, hot gallbladder lists, and pre-assessment clinics, were also identified and analyzed. Statistical methods were used to confirm the significance of observed changes. Results he re-audit revealed a significant improvement in compliance with guidelines for the management of biliary acute pancreatitis. The percentage of patients undergoing laparoscopic cholecystectomy within two weeks of admission increased from 32.6% in the initial audit to 64.5% in the re-audit. However, the analysis identified persistent barriers to timely intervention, including limited availability of ultrasound slots, insufficient "hot gallbladder" surgical lists, and fear of difficulty of acute laparoscopic cholecystectomy. These findings highlight both the progress made and the areas needing further attention to enhance compliance and patient care. Conclusion The re-audit demonstrated a notable improvement in adherence to guidelines for the management of biliary acute pancreatitis, with a significant increase in timely laparoscopic cholecystectomy. Despite this progress, persistent barriers such as limited ultrasound availability, insufficient "hot gallbladder" lists, and pre-assessment clinics need to be addressed. Continuous evaluation and targeted interventions are essential to further enhance compliance, reduce complications, and improve patient outcomes. Ongoing efforts to refine clinical practices will help achieve the highest standards of care for patients with biliary pancreatitis.

Case report: The effect of induction targeted therapies in stage III driver mutants non-small cell lung cancer

BackgroundOver the past decade, progress in the diagnosis and treatment of Non-Small Cell Lung Cancer (NSCLC) has led to the identification of many targeted mutations. This has enhanced PFS and OS in both advanced and early-stage NSCLC. The current standard of care for stage III NSCLC varies, and it may combine chemotherapy with either immunotherapy or radiotherapy. This study evaluated the role of induction targeted therapies in patients with driver mutations and inoperable NSCLC.MethodsThis is a single-center, retrospective study assessing the efficacy of targeted therapy in resectable stage III NSCLC patients who are EGFR or ALK-positive, using patient records, PET-CT, brain MRI staging, and mediastinal lymph node evaluation.ResultsBetween January 2020 and February 2024, we identified four patients with either EML4-ALK fusions (2/4) or EGFR mutations (2/4) who underwent treatment with brigatinib or osimertinib before surgery. All patients experienced clinical benefits. Of the two patients with ALK fusion, one responded almost completely, while the other exhibited a notable partial response. Among the patients with EGFR mutations, one had a complete response and the other displayed a significant partial response. All four patients subsequently underwent lobectomy surgical resection.ConclusionsThis case series highlights the potential of targeted therapies for resectable NSCLC in the neoadjuvant setting. Further research is required to confirm their benefits, assess their safety and efficacy, and determine optimal timing and sequencing.

Abstract B009: Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers

Abstract While the use of ctDNA-based minimal residual disease (MRD) monitoring is gaining popularity in adult cancers, this approach is not yet widely adopted in pediatric cancers (PCs). We developed a robust and sensitive assay to monitor ctDNA in PCs, which overcomes PC-specific challenges including low tumor mutational burden, paucity of hotspot mutations and low blood volume. To address these challenges, our innovations include personalized panel design that targets primary tumor mutations from each patient, a fixed panel targeting hotspot mutations, error suppression from duplex deep sequencing and customized pipeline for tumor burden estimation. We retrospectively analyzed 661 blood or cerebrospinal fluid (CSF) samples from 168 patients. We achieved an average detection limit of 0.005% ctDNA purity leading to MRD detected ranging from 0.001% to 100% with brain tumor consistently showing a low MRD. At disease diagnosis, progression and relapse, our assay identified ctDNA in over 93% of extra- cranial solid tumors, 90% of leukemia, 89% of sarcoma, and 90% of neuroblastoma. For brain tumors, we detected MRD in ∼90% of CSF samples, and in ∼60% of blood samples, a major advance over previous approaches. Importantly, we detected MRD in ∼ 20% of cases with a clinically complete response, predicting relapse up to 6 months before clinical confirmation. Overall, these results demonstrate that our monitoring assay for PCs is an important addition to standard of care for precision-guided treatment. Citation Format: Rob Salomon, Wenhan Chen, Charles Shale, Mojgan Toumari, Aileen Lowe, Wenyan Li, Jingwei Chen, Sajad Razavi-Bazaz, Paulette Barahona, Louise Cui, Chelsea Mayoh, Sam El-Kamand, Vanessa Tyrrell, Marie Wong-Erasmus, Loretta MS Lau, Noemi Fuentes-Bolanos, Edwin Cuppen, Dong-Anh Khoung-Quang, Jordan Staunton, Marion K Mateos, Toby Trahair, Michelle Haber, David S Ziegler, Paul Ekert, Peter Priestley, Mark Cowley. Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B009.

Overcoming immunosuppression in cancer: how ketogenic diets boost immune checkpoint blockade.

Immune checkpoint blockade (ICB) is now part of the standard of care in the treatment of many forms of cancer, yet it lacks efficacy in some patients, necessitating adjunct therapies to support the anti-tumor immune response. Ketogenic diets (KDs), i.e., high-fat low-carbohydrate diets, have been shown to have antiproliferative and immunomodulatory effects in various preclinical cancer studies. Here, we review current knowledge of the complex interplay of KDs and the anti-tumor immune response in the context of ICB therapy, to update our understanding of diet-induced immunometabolic reprogramming in cancer. Preclinical cancer studies have revealed increased activation of and infiltration by tumor-fighting immune cells, especially CD8+ T cells, but also M1 macrophages and natural killer cells, in response to a KD regimen. In contrast, immune-suppressive cells such as regulatory CD4+ T lymphocytes, M2 macrophages, and myeloid-derived suppressor cells were reported to be decreased or largely unaffected in tumors of KD-fed mice. KDs also showed synergism with ICB therapy in several preclinical tumor studies. The observed effects are ascribed to the ability of KDs to improve immune cell infiltration and induce downregulation of immune-inhibitory processes, thus creating a more immunogenic tumor microenvironment. The studies reviewed herein show that altering the metabolic composition of the tumor microenvironment by a KD can boost the anti-tumor immune response and diminish even immunotherapy-resistant as well as immunologically "cold" tumors. However, the exact underlying mechanisms remain to be elucidated, requiring further studies before KDs can be successfully implemented as an adjunct tumor therapy to improve survival rates for cancer patients.

HPB SO22 - Clinical outcomes following radical cholecystectomies, a single centre experience in review

Abstract Background Gallbladder carcinoma (GBC) is a rare disease with dismal prognosis. The majority of cases are identified at an advanced state that preclude curative approaches which would usually necessitate removal of the gallbladder with en-block wedge hepatectomy of segment 4b/5 as well as periportal lymphadenectomy. The purpose of this study was to analyze our outcomes for patients undergoing a radical cholecystectomy for suspected GBC. Method A retrospective analysis of patients who underwent radical cholecystecomies at Queen’s Medical Centre, Nottingham, UK between 1st January 2014 and October 2023 was performed. Patients with concomitant primaries, incidental GBC or completion liver resection following index cholecystectomy were excluded. Results 41 patients were eligible for analysis, those were comprised of 13 males and 28 females with a median age of 67 (IQR 57-72) years. The incidence of malignancy on histology was 31.7% (GBC n=11, metastatic renal carcinoma n=1, metastatic melanoma n=1). Cystic margin assessment by frozen section was performed in 41% of cases. In cases with confirmed gallbladder cancer, the median tumour size was 30mm, positive periportal lymph nodes were identified in two patients while R0 resection was achieved in all cases. The median length of stay following surgery was 5 days (IQR 5-7) while Clavien Dindo complication grade ≥ III were experienced in 12% ( return to theatre for leak from repaired cholecysto-duodenal fistula n=1, IR drainage of post operative collection n=3, ITU stay for cardiac arrhythmia n=1). The pathologies encountered in benign cases (n=28) were compatible with chronic cholecystitis (53.5%, n=15), concurrent chronic cholecystitis and adenomyomatosis (21.4%, n=6), xanthogranulomatous cholecystitis (10.7%, n=3), adenomyomatosis (7.1%, n=2), follicular cholecystitis (3.5%, n=1), benign GB polyps (3.5%, n=1). Conclusion Radical cholecystectomy remains the standard of care for suspected GBC however sufficient preoperative counselling is prudent given likelihood of benign disease on histology.

The European Rare Kidney Disease Reference Network

Rare kidney diseases encompass awide range of congenital, inherited and acquired conditions. Two million Europeans are affected by rare kidney diseases. The European Rare Kidney Disease Reference Network (ERKNet) aims to improve the clinical management of patients with these diseases. ERKNet encompasses 95highly specialized adult and pediatric nephrology units at 72sites in 24European Union (EU) member states, as well as agroup of patient advocates (European Patient Advocacy Group, ePAG). ERKNet centers care for more than 65,000 rare kidney disease patients and pursues avariety of activities. An online consultation service helps improve the management of complex cases. Expert working groups develop clinical practice guidelines for individual groups of rare kidney diseases. In a3-year postgraduate program, junior physicians at ERKNet centers are trained by experts in the diagnosis and treatment of rare kidney diseases through webinars and case-based eLearning modules. Information brochures and online texts on rare kidney diseases for patients, relatives and the general public are produced and disseminated. Clinical research is supported by aEuropean Registry for Rare Kidney Diseases (ERKReg), which provides important information on demographics and disease progression and facilitates the identification of patient cohorts for therapeutic studies. In addition, the registry provides clinical performance statistics of reference centers and allows benchmarking to promote the harmonization and standardization of care for rare kidney disease patients across Europe.

MicroRNAome profiling of breast cancer unveils hsa-miR-5683 as a tumor suppressor microRNA predicting favorable clinical outcome.

Breast cancer is a heterogeneous disease with diverse molecular subtypes, underscoring a better understanding of its molecular features and underlying regulatory mechanisms. Therefore, identifying novel prognostic biomarkers and therapeutic targets is crucial for advancing the current standard of care for breast cancer patients. Ninety-six formalin-fixed paraffin-embedded (FFPE) breast cancer samples underwent miRNAome profiling using QIAseq microRNA library kit and sequencing on Illumina platform. Mature miRNA quantification was conducted using CLC Genomics Workbench v21.0.5, while Relapse-free survival (RFS) analysis was conducted using RStudio 2023.09.1. Gain-of-function studies were conducted using miRNA mimics, while the effects of miRNA exogenous expression on cancer hallmark were assessed using 2-dimentional (2D) proliferation assay, three-dimensional (3D) organotypic culture, and live-dead staining. TargetScan database and Ingenuity Pathway Analysis (IPA) were used for miRNA target identification. Hierarchical clustering based on miRNA expression revealed distinct patterns in relation to PAM50 classification and identified miRNAs panels associated with luminal, HER2, and basal subtypes. hsa-miR-5683 emerged as a potential prognostic biomarker, showing a favorable correlation with RFS and suppressing tumorigenicity under 2D and 3D conditions in triple-negative breast cancer (TNBC) models. Findings were further extended to the MCF7 hormone receptor positive (HR+) model. Transcriptomic profiling of hsa-miR-5683 overexpressing TNBC cells revealed its potential role in key oncogenic pathways. Integration of downregulated genes and CRISPR-Cas9 perturbational effects identified ACLY, RACGAP1, AK4, MRPL51, CYB5B, MKRN1, TMEM230, NUP54, ANAPC13, PGAM1, and SOD1 as bona fide gene targets for hsa-miR-5683. Our data provides comprehensive miRNA expression atlas in breast cancer subtypes and underscores the prognostic and therapeutic significance of numerous miRNAs, including hsa-miR-5683 in TNBC. The identified gene targets unravel the intricate regulatory network in TNBC progression, suggesting promising avenues for further research and targeted therapeutic interventions.

Abstract B048: Microfluidic isolation of immune cell-derived extracellular vesicles in head and neck cancer patients on immune-checkpoint blockade

Abstract Background: Immune-checkpoint blockade (ICB), with or without chemotherapy, is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). However, only a minority of patients get clinical benefit from it. The combined expression of PD-L1 in a tumor section is currently the only biomarker approved for response prediction. Yet, its invasive nature and suboptimal predictive performance underscores the need for new, non- invasive surrogates of immune activity in patients undergoing ICB. Extracellular vesicles (EVs) carry key molecules critical for cell-cell communication and have the potential to be used as a non-invasive, real-time biomarker of systemic immune activity, essential for success in ICB- based therapy. Methods: We used a multichannel, microfluidic device that employs an immune- affinity approach, ‘herringbone chip’ (EVHB-Chip), to retrospectively isolate EVs from twelve HNSCC patients before and after the first cycle of ICB. One mL of plasma was used per patient per time point. For each patient, two devices were serially used, with each sample continuously following through each chip in a non-destructive manner—the first device aimed to isolate B cell EVs (antibodies against CD19 and CD20). The second device was optimized to capture T cell EVs (against CD274/PD-L1). Digital-droplet PCR was performed after EVs were isolated to detect the RNA transcripts in the EV cargo. Serial sampling was performed for six out of the twelve patients. Response assessment was conducted via RECIST1.1 criteria or clinical evaluation. Results: Most of our cohort was male 7/12 (57%) and had oral cavity 4/12 (33%) or oropharynx 4/12 (33%) tumors. Additionally, 11/12 (91%) patients received ICB monotherapy. Most of the cohort had a PD-L1 ≤ 1 (7/12; 58%), 7/12 patients experienced disease progression (PD), 4/12 experienced stable disease (SD), and one patient had a partial response (PR). Most of the RNA signal in pre-ICB samples was obtained from CD20 (12/12; 100%), followed by CD45 (10/12; 83%), CD19 (9/12; 75%), and CD274/PD-L1 (5/12; 41%). No difference was found in the RNA signal pre-ICB between responders and non-responders (p=0.1). For the patients with serial sampling available, the signal from CD274/PD-L1 increased after one infusion of ICB in 4/6 patients and remained negative in one. A trend towards a high amount of T cell-derived EVs was observed for the entire cohort (p=0.07; p=0.08) when comparing the amount of RNA via our EV marker (GAPDH, ACTB) between T and B cell devices. Patients with higher than 11.4/mL copies of CD19 (median value for the cohort) in the pre-ICB plasma sample tended to have a higher overall survival (HR 0.26, 95% CI: 0.06-1.13; p-value: 0.05) and progression-free survival (HR 0.28, 95% CI: 0.07-1.16; p-value: 0.06). Conclusion: The EVHB-Chip allowed for the detection and profiling of T and B cell-derived EVs in pre-ICB plasma samples of HNSCC patients undergoing ICB in this pilot cohort. Higher CD19 signal pre-ICB could potentially impact response and survival outcomes in ICB-based therapies. Citation Format: Andrew R. Levy, Daniel A Ruiz Torres, Uma Paithankar, Raheel Ahmad, Daniel C Rabe, Daniel L Faden, Shannon L Stott. Microfluidic isolation of immune cell-derived extracellular vesicles in head and neck cancer patients on immune-checkpoint blockade [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B048.

Cost-effectiveness of faecal microbiota transplantation compared with vancomycin monotherapy for early Clostridioides difficile infection: economic evaluation alongside a randomised controlled trial.

For Clostridioides difficile infection (CDI), faecal microbiota transplantation (FMT) is currently recommended for patients with three or more CDI episodes. A recent randomised controlled trial (RCT) show that FMT may be considered early, defined as intervention during the first or second CDI episode. Compared with standard care for first or second CDI, patients randomised to FMT had €1,645 lower hospital costs over 26 weeks owing to fewer admissions and hospital contacts and less medication use.

Short-Term Impact of Digital Mental Health Interventions on Psychological Well-Being and Blood Sugar Control in Type 2 Diabetes Patients in Riyadh

Background: Type 2 diabetes (T2D) management is complicated by psychological factors, yet mental health interventions are not routinely integrated into diabetes care. This study investigated the impact of a digital mental health intervention on psychological well-being and glycemic control in T2D patients. Methods: A quasi-experimental study was conducted with 120 T2D patients divided into intervention (n = 60) and control (n = 60) groups. The intervention group received a one-month digital mental health intervention alongside standard care. Psychological well-being (PHQ-9, GAD-7, and DDS) and glycemic control (HbA1c) were assessed at baseline and post-intervention. Results: The intervention group showed significant improvements in HbA1c levels (−0.5%, p = 0.032), PHQ-9 (−3.1, p = 0.001), GAD-7 (−2.8, p = 0.006), and DDS (−7.7, p = 0.012) scores compared to the control group. Strong correlations were observed between psychological improvements and HbA1c reductions. Higher engagement with the digital platform was associated with greater improvements in both psychological and glycemic outcomes. Conclusions: Integrating digital mental health interventions into T2D care can significantly improve both psychological well-being and glycemic control. These findings support a more holistic approach to diabetes management that addresses both mental and physical health aspects.

Abstract A060: Identification of tumour-specific variants from pleural effusion cell-free DNA as diagnostic markers of cancers affecting the lungs

Abstract Background: Pleural mesothelioma (PM) can be difficult to diagnose due to a combination of the growth pattern of the tumour, the invasive nature of the biopsy procedure and the frailty of the patient. Some patients with PM develop a build-up of fluid around their lungs as their first clinical symptom. This fluid can make breathing difficult and is routinely drained as part of standard care. Currently, a cytological test can be performed to identify if PM cells are present in the fluid, however, while this is a specific test, it lacks sensitivity. We examined if (a) cell-free DNA (cfDNA) originating from tumours affecting the lung could be detected in this fluid and (b) if this cfDNA could be determined as coming from PM compared to non-small cell lung cancer (NSCLC), due to changes in genes that only occur in these types of tumours. Methods: Using the QIAamp MinElute ccfDNA Kit, we were able to isolate sufficient concentrations of cfDNA from pleural effusions (n=80) derived from patient samples procured by our colleagues at Southmead Hospital with either PM or NSCLC to perform gene panel sequencing. Using the QIAseq Targeted DNA Pro Human Lung Cancer Research Panel, with additional booster primers covering BAP1 and SETD2, we performed the library preparation in-house. Data analysis was carried out using the QIAGEN CLC Genomics Workbench, with the specific workflows for the gene panels and results were filtered by QC, proportion of variant reads and variant read count. Data were compared to expected variant frequencies published in TCGA. Results: Tumour-specific cfDNA was isolated from pleural effusions in the majority of samples tested. In a proportion of these, variants indicative of a specific type of tumour (PM or NSCLC) were readily detectable, at slightly lower than the expected frequencies than reported in TCGA. Conclusions and future work: This approach can act as a 'rule-in' clinically diagnostic test for the presence of PM or NSCLC in a higher proportion of people that can currently be identified through cytology testing. These individuals could be spared from receiving an invasive biopsy to diagnose their tumour. We are currently working on (i) increasing the sensitivity of this approach to identify more cases and (ii) if a bioinformatic method can identify tumour-specific copy number alterations from the gene panel sequencing data. Citation Format: Connie MacKinnon, Dr Colette Mustard, Dr Nicole Brace, Dr Beth Sage, Jenny Symonds, Colin Nixon, Dr Anna Bibby, A/Prof Antonia Pritchard. Identification of tumour-specific variants from pleural effusion cell-free DNA as diagnostic markers of cancers affecting the lungs [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A060.

Improved kidney function is associated with Colchicine treatment in COVID-19 patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause of significant morbidity and mortality. Acute kidney injury (AKI) has been seen in COVID-19-infected subjects, and it has frequently resulted in an abnormal estimated glomerular filtration rate. Colchicine, an immunomodulatory drug, was used in several studies in the early stages of the pandemic. Colchicine has been shown to prevent the development of renal failure in patients with Familial Mediterranean Fever (FMF). It has also been reported to reduce fibrosis, which plays a role in chronic kidney disease. We, therefore, aimed to investigate whether using Colchicine, in addition to standard care, was associated with better renal function in patients with severe COVID-19 infection. This retrospective cohort study comprised 118 out of 605 hospitalized COVID-19 subjects. Some of the subjects (n = 50) received oral Colchicine plus standard care, called the Col ( +) group. The others (n = 68) received only the standard care, called the Col (-) group. The estimated glomerular filtration rate (eGFR) and other laboratory findings, including lymphocytes, D-dimer, and CRP, were analyzed. The D-dimer and serum creatine levels were significantly reduced in both groups. The number of lymphocytes showed a significant increase in both groups at discharge. The level of C-reactive protein (CRP) was significantly higher in the Col ( +) group than in the Col (-) group at admission. The reduction of SCr was considerably higher in the Col ( +) group than in the Col (-) group. Similarly, the improvement of eGFR was higher in the Col ( +) group than in the Col (-) group at discharge and 6-12 mounts follow-up. Our findings indicated the use of Colchicine plus standard care was associated with improved renal function in hospitalized patients with severe COVID-19 infection.

Abstract 4140111: Impact of Digital Health Tools on Patients Undergoing Cardiac Rehabilitation

Digital health apps are novel tools that have the potential to enhance patient care. However, their benefits in the context of cardiac rehabilitation (CR) are not well studied. This study aims to examine an app’s effectiveness in enhancing exercise performance. The app (KardioPAC) connects to both Bluetooth and cellular-enabled BP devices, which allows providers to monitor and communicate with patients remotely. We aim to assess the app’s impact on functional capacity (metabolic equivalents /METs) compared to standard of care (SOC) CR. This study took place at UC San Diego. Participants were recruited from CR, and randomized in a 1:1 ratio to the two study arms (KardioPAC+CR vs SOC CR). The intervention group was requested to take BP at home and upload via KardioPAC. They additionally received a BP reminder daily and got an intra-app call from the care team at least every 1-2 weeks and when needed. All patients, including SOC arm, were asked to complete a pre- and post-CR visit. In each visit, several measurements (including blood pressure, METs, and quality of life questionnaires) were recorded. The study was approved by the UCSD IRB. All statistical analyses were performed on Python 3.11.8. From Jan 2023 to Mar 2024, 43 patients were enrolled. Table 1 shows their demographics. The mean METs changes are 3.68 vs 2.97 (Intervention vs Control, p=0.052). The mean METs percent changes are 104.39% vs 81.22% (Intervention vs Control, p=0.042), as plotted in Figure 1. Our study found that digital tools significantly enhance CR patients’ performance, even with a small sample size. Furthermore, we found positive signals of digital tools in reducing patients’ blood pressure and improving their quality of life. Patients’ behavior could be changed by incorporating digital tools into daily practice. Our study warrants large-scale studies to investigate the underlying mechanisms and verify the broader benefits of digital tools, including physical, mental, and social improvements.