Multicenter Study Research Articles

EGS SO13 - Evaluation of Different Surgical Risk Prediction Models in Predicting Morbidity and Mortality in Giant Hiatus and Diaphragmatic Hernia Repairs

Abstract Background Emergency giant hiatus hernia and diaphragmatic hernia repairs are associated with high rates of mortality and morbidity; different studies reported variable outcomes. Accurate risk assessment empowers patients to provide informed consent and also serves as a valuable tool for identifying individuals who may require enhanced postoperative care, such as respiratory support and critical care admission. Various risk prediction tools have been developed to assist clinicians in making decisions to aid in stratifying the risk of surgical management. We aimed to assess the effectiveness of different risk prediction models in predicting mortality and morbidity in this patient cohort. Method Retrospective analysis performed on cases between May, 2010 and January, 2021 in a tertiary adult upper gastro-intestinal centre. The outcomes from the operations were assessed and compared with the predicted morbidity and mortality for different risk prediction models. Including the Surgical Outcome Risk Tool (SORT), the National Emergency Laparotomy Audit (NELA), parsimonious NELA and the American College of Surgeons National Surgical Quality Improvement Programme (ACS-NSQIP). The models were compared using the area under the curve (AUC). Morbidity models included Portsmouth Physiological and Operative Severity Score (P-POSSUM) and the ACS-NSQIP. Morbidity was evaluated by calculating the comprehensive complication index (CCI). Results A total of 108 patients met the criteria and were included in the analysis. Among these 50.9% were females. The median age was 69 (IQR 59-78). The 30-day mortality rate was 6.93% (7 patients), six patients died during the same admission, and one patient died during a re-admission. ACS-NQSIP had the highest predictive power for mortality (AUC = 0.6344), in comparison to NELA (AUC=0.5665), parsimonious NELA (AUC=0.4866) and SORT (AUC = 0.4342). Both ACS-NSQIP and P-POSSUM showed moderate correlation to CCI (rho = 0.489, p<0.001 and 0.446, p<0.001 respectively). Conclusion ACS-NSQIP is a better predictor of both mortality and morbidity in emergency giant hiatus and diaphragmatic hernia repairs when compared to NELA, parsimonious NELA, P-POSSUM and SORT. Interestingly, parsimonious NELA had a lower prediction rate when compared with the older NELA model. ACS-NSQIP may have a role in pre-assessment and consenting of emergency hiatus and diaphragmatic hernia repairs. Multi-centre prospective studies could be used to validate these findings.

Healthcare costs in relation to kidney function among older people: the SCOPE study.

In this study, a comprehensive analysis of costs of chronic kidney disease (CKD) was performed, to understand factors associated with the economic burden of the disease in a multicentre international framework. The impact on costs of demographics, socio-economics, clinical, and functional variables was tested in 2204 subjects aged 75years or more attending outpatient clinics in Europe using a multicentre 2-year prospective cohort study. By means of collected resources consumption and unit cost data a comprehensive cost database was built and then investigated using multilevel regression modeling. Overall, hospitalization, medications and specialist visits were the main cost items, with a notable variability among countries. Estimated yearly costs were 4478€ ± 9804€, rising up to 6683€ ± 10,953€ for subjects with estimated Glomerular Filtration Rate (eGFR) < 30. Costs increased significantly according to the severity of the disease, gender and age. Clinical and functional covariates were also significantly associated with CKD-related total costs, even after correcting for the inter-country variability. Findings corroborate the importance of multidimensional assessment of participants with CKD, as multimorbidity and functional disability produce a detrimental impact on participant's prognosis and cost of care. Preservation of functional impairment and adequate management of comorbidities may thus help decreasing the overall consumption on health care resources in CKD patients, especially in older people.

Abstract B013: An mDETECT assay for monitoring treatment response in metastatic breast cancer patients

Abstract Metastatic breast cancer treatment response is currently assessed every 3-6 months and this long delay results in many patients undergoing ineffective and toxic treatments for long periods of time. We have developed the methylation DETEction of Circulating Tumour DNA (mDETECT) assay, a targeted DNA methylation-based Next Generation Sequencing liquid biopsy that detects cancer-specific patterns in all subtypes of breast cancer. The assay targets 60 differentially hypermethylated regions in breast cancer across the genome and assesses over 400 individual CpGs with an average of 8 CpGs per target amplicon. The assay has been assessed on DNA from 73 breast cancer tumour samples which on average had 40 regions hypermethylated per patient with similar rates across all subtypes. We will present results from plasma samples from locally advanced and metastatic breast cancer patients along with plasma from age-matched, healthy female controls. A prospective, multi-centre observational cohort study to monitor metastatic breast cancer patients using the mDETECT liquid biopsy as they undergo treatment is active and recruiting patients. Blood is drawn with every standard-of-care blood draw for up to 3 years. Plasma has been assessed using the mDETECT assay to determine the methylation status of the DNA at each time point. 35 patients have been enrolled to date with ongoing recruitment up to 150 patients. Patients are being monitored with the mDETECT assay for earlier detection of disease progression on a treatment. They will also be monitored through treatment changes to assess a patient’s initial response to a given treatment. Changes in mDETECT levels will be correlated with clinical response to determine if the mDETECT breast cancer assay can detect a response to treatment at an earlier timepoint. This assay could allow for improved monitoring of treatment response allowing clinicians to make informed decisions, improving outcomes and prolonging patient’s lives. Citation Format: Keira Frosst, Brooke Wilson, Katrina Cristall, Catherine Crawford-Brown, Christopher R Mueller. An mDETECT assay for monitoring treatment response in metastatic breast cancer patients [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 B013.

HPB SO03 - Preoperative biliary drainage prior to pancreaticoduodenectomy for pancreatic head malignancy: Guidelines versus the reality

Abstract Background British guidelines currently advise against routine preoperative biliary stenting (PBS) unless patients have cholangitis or organ failure secondary to biliary obstruction. If stenting is required, self-expanding metal stents are advocated. Using a large multicentre cohort, this study aimed to investigate the proportion of patients who underwent PBS prior to pancreatoduodenectomy (PD) and describe the approach used. Method Data were extracted from the Recurrence After Whipple’s (RAW) study, a multicentre retrospective cohort study of outcomes of PD performed for histologically confirmed pancreatic head malignancy (29 centres from 8 countries, n=1484). Patients who underwent PBS were identified and the details surrounding this were obtained. Results 1482 patients had data on use of PBS. 427 didn't undergo PBS, 1055 underwent attempted PBS. Of the latter, 989 had a stent placed successfully, 38 had PBS failed , and 28 had an external biliary drain . when PBS performed, Among 857 were primary endoscopically placed , 75 had percutaneously placed PBS having failed endoscopy , and 50 had a primary percutaneously placed PBS . 755 patients known stent material ( 66% were plastic, 34% metal). In 671 who had data regarding cytology from PBS known, 48% had cytology suggestive/diagnostic of malignancy, 25% had inadequate histology, and 28% did not send a cytology sample. Conclusion Despite guidelines advising against routine PBS, over two thirds of PD patients in our study underwent stenting. Despite guidelines advocating metal stents when PBS is necessary, two thirds of the stents deployed were plastic. Stent cytology has a low sensitivity for pancreatic head malignancy.

HPB SO41 - Does Adjuvant Chemotherapy Provide a Survival Benefit in Elderly Patients (≥70 years) with Pancreatic Cancer? A Retrospective Cohort-study

Abstract Background There is currently conflicting evidence surrounding the use of adjuvant chemotherapy (AC) for elderly patients (over 70 years) with pancreatic adenocarcinoma. Limited existing studies debate its effect on overall survival (OS) and relapse-free survival (RFS). The aim of this study is to assess whether adjuvant chemotherapy following pancreaticoduodenectomy provides a survival benefit in elderly patients with pancreatic cancer. Method A retrospective review including elderly adult patients, seventy years and older, who underwent a Whipple’s pancreatoduodenectomy for pancreatic adenocarcinoma between 1st January 2015 and 31st December 2020, at a tertiary HPB centre was performed. Information on baseline characteristics, preoperative assessment, histopathology, postoperative complications and course, and adjuvant chemotherapy were collected. Elderly patients who received AC were compared to those who did not undergo AC. Statistical analysis was performed using Jamovi 2.3. Results Sixty-eight patients were included with 44 (65%) receiving AC. There was no difference in age (p=0.72), sex (p=0.19), preoperative characteristics (all p&amp;lt;0.05), and resection margin (p=0.67) between the groups. There was no difference in complication rates (p=0.20), including Clavien-Dindo3+ (p=0.68). The length of hospital stay was shorter in the AC group, without statistical significance (15.7±11.9 vs 23.2±20.3 days, p=0.06). There was no difference in RFS between the groups (22.7±20 vs 15.4±23.6 months, p=0.18). However, patients who received AC had a significantly greater OS compared to those who did not (30.7±18.2 vs 18.6±22.2 months, p=0.02). Conclusion AC improved overall survival in elderly (≥70 years) patients with pancreatic adenocarcinoma. Whilst many elderly patients may not receive adjuvant chemotherapy due to postoperative complications and/or longer hospital stay, our study suggests age alone should not be a deciding factor when considering adjuvant chemotherapy in this cohort. A future large, multicentre prospective study is needed to further examine OS with the use of AC in elderly patients with pancreatic adenocarcinoma.

Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation.

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis, we identify a CR-related activity pattern underlying successful memory encoding that moderates the detrimental effect of AD pathological load on cognitive performance. CR is mainly represented by a more pronounced expression of the task-active network encompassing deactivation of the default mode network (DMN) and activation of inferior temporal regions including the fusiform gyrus. We devise personalized fMRI-based CR scores that moderate the impact of AD pathology on cognitive performance and are positively associated with years of education. Furthermore, higher CR scores attenuate the effect of AD pathology on cognitive decline over time. Our findings primarily provide evidence for the maintenance of core cognitive circuits including the DMN as the neural basis of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.

Real-World Comparative Effectiveness and Safety of Filgotinib and Upadacitinib for Ulcerative Colitis: A Multicentre Cohort Study.

Janus kinase (JAK) inhibitors, filgotinib (FIL) and upadacitinib (UPA) have emerged as promising treatments for ulcerative colitis (UC). However, a comparative analysis of these JAK inhibitors, particularly in patients previously treated with tofacitinib (TOF), has not been performed. To compare the efficacy and safety of FIL and UPA in patients with UC, including those previously exposed to TOF. A multicentre retrospective cohort study was conducted to compare the effectiveness and safety of FIL and UPA in patients with UC whose treatment was initiated between March 2022 and December 2023. The co-primary outcomes were clinical response and remission at week 8. The secondary outcomes included treatment persistence and adverse events (AEs). Modified Poisson and Cox regression models with multivariable analysis to adjust for confounders and propensity score matching were conducted. Subgroup analyses stratified by previous exposure to TOF and biologics were also conducted. In total, 168 patients (98 treated with FIL and 70 treated with UPA) were enrolled in this study, with a median follow-up period of 181days. The clinical response/remission rates at week 8 were 55.1/46.9% for FIL and 71.4/65.7% for UPA, respectively. UPA was associated with significantly higher rates of clinical response (adjusted risk ratio [RR] 1.40 [95% confidence interval [CI], 1.09 to 1.80]) and clinical remission (adjusted RR 1.54 [95% CI, 1.16 to 2.05]) compared with FIL. This result was consistent across subgroup analyses based on previous exposure to TOF or biologics, except for bio-naive patients. There was no significant difference in the treatment persistence. AEs were more frequent with UPA (45.7%) than with FIL (24.5%) (p=0.0049). Propensity score matching confirmed the superior overall effectiveness of UPA. UPA demonstrated better short-term effectiveness than FIL, with a higher incidence of AEs.

BN SO44 - Is routine histological analysis of excised gallbladders necessary?

Abstract Background Gallbladder cancer is rare representing &amp;lt;1% of annual cancer diagnoses in the UK. It is more common in females (2.4/100,000 vs 1/100,000) with a peak age incidence of 85–89-years. Our trust routinely histologically analyses all resected gallbladders, over 1000 per year, regardless of indication. Our pathologists estimate that each specimen costs £75 to analyse, reflecting an annual cost of over £80,000. A 2021 systematic review suggested selective histological analysis is safe, reduces laboratory burden and costs. We aimed to assess our centre’s cholecystectomy specimens to ascertain the incidental gallbladder cancer diagnoses and explore the possibility of selective analysis. Method A retrospective search of our pathology database was carried out for the terms “cancer” and “gallbladder” from 2015 to 2018 inclusive. After exclusion of non-gallbladder primary cancers, all selected cases electronic notes were retrospectively reviewed. The primary outcome was the incidental findings of gallbladder cancer. Secondary outcomes were the indications for surgery, intraoperative findings, histological macroscopic description, final diagnosis and further management where applicable. Results We identified 4421 gallbladder specimens of which 12 (0.27%) identified cancer. The ratio of female to male diagnoses was 5:1 and the median age was 73.5 years. Of the 12 cancers, 7 (0.16%) of these were incidental findings, with 5 having surgery for symptomatic gallstones and 2 for gallbladder polyps. The 5 symptomatic gallstones patients all had grossly abnormal macroscopic appearances of the serosa, dense adhesions or exudate; all were confirmed as gallbladder adenocarcinoma. Three patients were fit enough for limited liver resection. Conclusion Our results demonstrate that across four years the rate of incidental gallbladder adenocarcinoma diagnosed by cholecystectomy was 0.16%. In all non-polypoidal cases (0.11%), the gallbladder was macroscopically abnormal. This suggests that with careful criteria, selective gallbladder histological analysis may reduce laboratory burden and therefore costs associated with elective gallbladder surgery. With increasing emphasis to improve efficiency and rationalise healthcare spending, our results suggest that selective histological analysis may be safe and effective. However, given the consequences of missing a cancer diagnosis it would require a larger scale multi centre study to support a move in this direction.

LeAf Trauma- an intersectoral prospective multicenter study assessing quality of life and return to work after majortrauma-study protocol.

With increasing survival rates, the functional outcome and quality of life of trauma patients are gaining more importance. Survivors suffer from chronic pain, psychosomatic disorders, and unemployment as well as increased post-traumatic morbidity, which can lead to an impaired quality of life. So far, the TraumaRegister DGU® records patient data during in-hospital treatment. In this study severely injured patients after major trauma are assessed when discharged from hospital, as well as 6, 12 and 18 months after trauma. The aim is to document cross-sector patient pathways and to identify and quantify the factors influencing the health-related quality of life (hrQoL) and the return to work (RTW), using patient-reported experience measures (PREM) and patient reported outcome measures (PROM). Patients are recruited in certified trauma centers of the German Society for Trauma Surgery (DGU). This study protocol describes the methodology of the prospective multicentre study of LeAf Trauma. Translation of the results will be implemented by using the network structures of the German Society for Trauma Surgery (DGU) for the treatment of patients with major trauma.

Abstract A074: Early detection of breast implant associated anaplastic large cell lymphoma by multiplex lateral flow assay of CD30 and IL-10

Abstract Introduction: More than 1300 women have developed a unique breast implant associated anaplastic large cell lymphoma (BIA-ALCL) around breast implants. BIA-ALCL presents as an accumulation of fluid (seroma) a median of 9 years after implant placement. When detected early, survival with surgery alone is nearly 100%. Remaining patients present with masses and/or lymph node metastases requiring radiation, chemotherapy and/or immunotherapy and fatalities have occurred. Methods: Preliminary studies identified CD30 and IL-10 as the most sensitive and specific biomarkers for BIA-ALCL in seroma fluids. Therefore, we constructed a multiplex LFA to detect both CD30 and IL-10 in 30 mL seroma fluid within 20 minutes. LFA is a point of care immunoassay using capture and detection antibodies that detect separate epitopes of the target molecule. The detection antibody is linked to a colored particle; in this multiplex assay CD30 antibody was linked to blue and IL-10 to red particles. Separate positive test lines (blue and red) indicate presence of CD30 or IL-10. A control line confirms migration of the seroma fluid past the test lines. To determine the dynamic range of sensitivity we spiked recombinant CD30 and IL-10 into benign seromas. Test and control lines were quantitated with NIH Image J software and ratios of test line to control line calculate for each sample. Forty-eight hour supernatants of supernatants of BIA-ALCL lines TLBR1 and TLBR2 were tested for IL-10 and CD30. Fifteen patients, 8 with BIA-ALCL and 7 with benign seromas provided consent for testing of their seroma fluids. Results: Multiplex CD30/IL10 LFA produced positive test lines for neat and 1:10 dilutions of 48 hour supernatnats of BIA-ALCL lines TLBR1 and TLBR2. Both IL-10 and CD-30 could be detected on the multiplex LFA strip using a 1:3 dilution of seroma fluids. The multiplex LFA shows both IL-10 and CD30 are significantly higher in malignant samples (IL-10 TL/CL: malignant, 0.2±0.16 n=8 vs benign, 0.004±0.007 n=7, p&amp;lt;0.05; CD30 TL/CL: malignant, 0.38±0.2 vs benign, 0.02±0.02, p&amp;lt;0.001, two-way ANOVA). Importantly, when either IL-10 or CD30 yields a faint positive test line, the other is not detected reducing the possibility of false positives. Conclusions: The CD30/IL-10 multiplex LFA had 100% positive and negative predictive value in this pilot study. The assay was able to distinguish lymphoma from recurrent breast cancer and more common benign seromas. The use of this multiplex assay mitigates positive false positive results from more sensitive CD30 LFA which has been detected in some benign seromas. This LFA will potentially allow early pre-operative detection of ALCL allowing surgeons to plan their surgical approach. The LFA can replace more costly time-consuming flow cytometry, immunohistochemistry, cyto- and histopathologic studies which require at least 10 ml of fluid. The LFA can be performed outside of medical centers in rural and underserved areas. A larger prospective multicenter study including intra-operative sampling is planned to validate these results. Citation Format: Peng Xu, Katerina Kourentzi, Richard Willson, Marshall Kadin. Early detection of breast implant associated anaplastic large cell lymphoma by multiplex lateral flow assay of CD30 and IL-10 [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 A074.

Characteristics of Side Effects in Non-Emergency Indications Using Computer-Controlled Pressurized Monoplace Hyperbaric Chambers: A Retrospective Multicenter Study

Background: Hyperbaric oxygen therapy (HBOT) involves inhaling nearly 100% oxygen in a pressurized environment and is commonly used to treat various diseases and injuries. Despite its well-known safety, HBOT is associated with side effects, with frequent middle ear barotrauma (MEB) and oxygen toxicity. Understanding the characteristics and risk factors associated with these side effects is critical for improving patient compliance and treatment outcomes. Methods: This retrospective multicenter study aimed to analyze the characteristics and factors associated with side effects during HBOT using a computer-controlled pressurized monoplace hyperbaric chamber. We conducted a retrospective observational study across the two tertiary hospitals in Korea, involving patients who received HBOT from October 2016 for one hospital and October 2017 for another hospital to June 2020. Data were extracted from electronic medical records and hyperbaric chamber logs, including patient demographics, medical history, HBOT indications, and details of side effects. Statistical analyses, including chi-square and t-tests, were used to compare variables. Results: A total of 247 patients (mean age: 59.35 ± 15.05 years, 63.56% male) were included. The most common indications for HBOT were sudden sensorineural hearing loss (27.94%) and post-graft/flap (24.29%). Hypertension (46.15%) and diabetes mellitus (39.27%) were the most frequent comorbidities. Otalgia was the most prevalent side effect (33.20%), followed by chest discomfort (2.02%) and headache (1.62%). A significant proportion of patients (11.74%) terminated HBOT due to side effects, with most pauses occurring at pressures between 1.2 and 1.4 ATA (26.67%). Side effects, particularly otalgia, significantly impact patient compliance with HBOT. Conclusions: The incidence of side effects varies by pressure level during treatment, suggesting the need for tailored strategies to minimize side effects. This study highlights the importance of patient monitoring and education to improve the safety and efficacy of HBOT in monoplace chambers.

Targeted antimicrobial regimens for Gram-negative prosthetic joint infections: a prospective multicenter study.

Fluoroquinolones (FQs) are considered the most effective antimicrobial treatment for Gram-negative prosthetic joint infection (GN-PJI). Alternatives are needed due to increasing FQ resistance and side effects. We aimed to compare different targeted antimicrobial strategies for GN-PJI managed by debridement, antibiotics, and implant retention (DAIR) or one-stage revision surgery (1SR) and to review the literature of oral treatment options for GN-PJI. In this prospective, multicenter, registry-based study, all consecutive patients with a PJI caused by a Gram-negative microorganism (including mixed infections with Gram-positive microorganisms), managed with DAIR or 1SR from 2015 to 2020, were included. Minimum follow-up was 1 year. Patients underwent targeted therapy with oral FQ, oral cotrimoxazole, or intravenous or oral β-lactams. Survival analysis was performed with use of Kaplan-Meier and Cox proportional hazards models to identify factors potentially associated with treatment failure. Seventy-four patients who received either FQ (n = 47, 64%), cotrimoxazole (n = 13, 18%), or β-lactams (n = 14, 18%) were included. Surgical strategy consisted of DAIR (n = 72) or 1SR (n = 2). Median follow-up was 449 days (interquartile range 89-738 days). Failure free survival did not differ between the FQ (72%) and cotrimoxazole (92%) groups (log rank, P = 0.13). This outcome did not change when excluding all pseudomonal PJI in the FQ group. Cotrimoxazole is a potential effective targeted antimicrobial therapy for patients with GN-PJI. A randomized controlled trial is needed to confirm the findings of this study.

Religiosity, perceived family support, and gender disclosure of LGBTQ + medical students in Thailand.

The well-being of LGBTQ + medical students can be influenced by religiosity, family support, and the disclosure of their gender identity or sexual orientation. These factors have frequently been overlooked and warrant further consideration in creating a supportive environment for all students. This multicenter study investigated two main outcomes including the differences in religiosity and perceived family support between LGBTQ + and non-LGBTQ + medical students in Thailand, and the gender disclosure to family among LGBTQ + medical students. It was conducted among students from five medical schools across Thailand, using online questionnaires during the academic year 2021-2022. Data were collected on demographic characteristics, religiosity, gender identity/sexual orientation disclosure to family, and perceived family support. Comparisons between groups were conducted using chi-square test and Wilcoxon rank-sum test. Of the 1,322 participants, 31.2% identified themselves as LGBTQ+, among whom 81.8% were Buddhists. The proportion of non-religious LGBTQ + students was significantly higher (vs. non-LGBTQ+; 15.0% vs. 8.4%, respectively; p = 0.001). However, there was no statistical difference in religiosity between LGBTQ + and non-LGBTQ + students as well as between LGBTQ + subgroups. Although, 74% of LGBTQ + students reported good family support, significantly more LGBTQ + students perceived poor family support (vs. non-LGBTQ+, 7.0% vs. 4.7%; p = 0.002). Regarding the disclosure of gender identity or sexual orientation to the family, the majority of LGBTQ + individuals indicated either a non-disclosure or uncertainty. There were significant associations between perceived family support and the likelihood of disclosing one's identity to family members, as better perceived support was associated with higher disclosure rates. No statistically significant difference in religiosity was found between LGBTQ + and non-LGBTQ + students. The majority of LGBTQ + medical students reported receiving good family support; however, among those who perceived their family's support to be lacking, there was a greater tendency to conceal their gender identity from their families. For future studies, it is crucial to investigate whether this concealment extends to other spheres of their lives and to assess the potential impact on their well-being, including mental health and quality of life.

Predicting adverse drug event using machine learning based on electronic health records: a systematic review and meta-analysis

IntroductionAdverse drug events (ADEs) pose a significant challenge in current clinical practice. Machine learning (ML) has been increasingly used to predict specific ADEs using electronic health record (EHR) data. This systematic review provides a comprehensive overview of the application of ML in predicting specific ADEs based on EHR data.MethodsA systematic search of PubMed, Web of Science, Embase, and IEEE Xplore was conducted to identify relevant articles published from the inception to 20 May 2024. Studies that developed ML models for predicting specific ADEs or ADEs associated with particular drugs were included using EHR data.ResultsA total of 59 studies met the inclusion criteria, covering 15 drugs and 15 ADEs. In total, 38 machine learning algorithms were reported, with random forest (RF) being the most frequently used, followed by support vector machine (SVM), eXtreme gradient boosting (XGBoost), decision tree (DT), and light gradient boosting machine (LightGBM). The performance of the ML models was generally strong, with an average area under the curve (AUC) of 76.68% ± 10.73, accuracy of 76.00% ± 11.26, precision of 60.13% ± 24.81, sensitivity of 62.35% ± 20.19, specificity of 75.13% ± 16.60, and an F1 score of 52.60% ± 21.10. The combined sensitivity, specificity, diagnostic odds ratio (DOR), and AUC from the summary receiver operating characteristic (SROC) curve using a random effects model were 0.65 (95% CI: 0.65–0.66), 0.89 (95% CI: 0.89–0.90), 12.11 (95% CI: 8.17–17.95), and 0.8069, respectively. The risk factors associated with different drugs and ADEs varied.DiscussionFuture research should focus on improving standardization, conducting multicenter studies that incorporate diverse data types, and evaluating the impact of artificial intelligence predictive models in real-world clinical settings.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024565842, identifier CRD42024565842.

The Genomic Landscape of Wilson Disease in a Pan India Disease Cohort and Population-Scale Data.

Wilson's disease (WD) results from pathogenic ATP7B gene variations, causing copper accumulation mainly in the liver, brain, and kidneys. In India, despite studies on ATP7B variants, WD often goes undiagnosed, with the prevalence, carrier rate, and mutation spectrum remaining unknown. A multicenter study examined genetic variations in WD among individuals of Indian origin via whole exome sequencing. The study used the InDelible structural variants calling pipeline and conducted molecular dynamic simulations on variants of uncertain significance (VUS) in ATP7B AlphaFold protein structures. Additionally, a high-throughput gene screening panel for WD was developed. This study examined 128 clinically diagnosed cases of WD, revealing 74 genetically confirmed cases, 22 with ATP7B variants, and 32 without. Twenty-two novel ATP7B gene variants were identified, including a 322 bp deletion classified as a structural variant. Molecular dynamics simulations highlighted the potential deleterious effects of 11 ATP7B VUS. Gene burden analysis suggested associations with ANO8, LGR4, and CDC7. ATP7B gene hotspots for pathogenic variants were identified. Prevalence and carrier rates were determined as one in 18,678 and one in 67, respectively. A multiplex sequencing panel showed promise for accurate WD diagnosis. This study offers crucial insights into WD's genetic variations and prevalence in India, addressing its underdiagnosis. It highlights the novel genetic variants in the ATP7B gene, the involvement of other genes, a scalable, cost-effective multiplex sequencing panel for WD diagnosis and management and promising advancements in WD care.

EGS SO26 - Back Under the Knife: Unveiling the Fate of non-trauma Patients Returning to the Emergency Theatre

Abstract Background Offering a planned or unplanned second operation in emergency general surgery is not uncommon. However, there is a scarcity of data in this context. This study aims to evaluate the outcomes of patients who were offered two emergency operations to those who required one operation, focusing on complications, increased level of care at discharge and mortality rates. Method We identified those patients who underwent planned and unplanned revisits to the emergency theatre between July 2020 and July 2023. Inclusion criteria were consistent with the established UK National Emergency Laparotomy Audit (NELA at our centre over three years.. We examined demographics, ASA (American Society of Anesthesiologists) classification, indications and outcomes in terms of complications, increased post-operative care levels and mortality rates. Results 390 patients (89.3%) required one operation (1OP) and 47 (10.7%)patients underwent two operations (2OP) . The median age was 70 years for 1OP and 71 years for 2OP, with a male-to-female ratio of 192:198 in 1OPG and 22:25 in 2OP. The median ASA score (2 vs. 3), median frailty score (3 vs. 4) and the median Clavien-Dindo classification (2 vs. 4), and length of stay in days (12 vs. 21) were significantly higher for the 2OP. The increase in the level of care at discharge (30.6% vs. 59%) and the mortality (7.4% vs. 32%) were higher in the 2OP. Conclusion Our study shows that non-trauma patients requiring a second emergency operation face significantly worse outcomes compared to those undergoing only one surgery. Specifically, the group needing two operations experienced higher rates of complications, increased levels of post-operative care, and significantly higher mortality rates. These findings underscore the critical need for close monitoring and a multidisciplinary approach perioperatively. Moreover, these insights can help provide patients and their families with informed decision-making regarding the potential risks and benefits of additional surgical interventions. A prospective multicentre study would be valuable in providing further insights into this subgroup of patients.

Operationalisation of post-COVID condition case definition in a comprehensive research protocol.

Post-COVID-19 condition (PCC) is a prevalent and high-burden sequela of SARS-CoV-2 infection. Because of the complexity of its manifestations, PCC case definition currently lacks standardisation and reproducibility. We aimed to devise a simple screening tool to boost reproducibility and comparability of PCC case definition across PCC studies, and to provide a framework in which to reliably identify suspected PCC cases. We also developed a comprehensive assessment protocol based on the most frequently reported PCC characteristics. Within a European multi-centre study and based on the conclusions of a previous systematic review, we devised a checklist to assess the presence of PCC-associated symptoms and their temporal relationship with COVID-19. The checklist was developed to include three symptom cores (cognitive, psychiatric, and general). For each symptom, onset is assessed within 3 months after COVID-19 resolution and persistence for at least 2 months. Any symptom fulfilling this criterion is sufficient to prompt suspicion of PCC. At least one symptom is required in the cognitive or psychiatric domains to suspect PCC with neuropsychiatric involvement. Our protocol features an extensive neuropsychological evaluation and self-administered scales for mood, anxiety, stress-related symptoms, sleep disorders, quality of life, disability, mental health, and personality traits; scales for quantitative assessment of fatigue and headache are also included. Consistent identification of PCC cases is crucial to correctly include patients in research and clinical studies. We propose a simple, reproducible, and flexible screening tool and a proposal for a comprehensive assessment that could be employed to enhance standardisation and comparability.

Abstract 4115645: NLRP3 Inflammasome Inhibition With Dapansutrile in Type 2 Diabetes and Elevated Systemic Inflammation: Rationale and Design of the DAPAN-DIA study

Background: Monoclonal antibodies against IL-1β decrease inflammation, improve insulin secretion and glycaemia, and reduce residual CV risk, but must be injected and are associated with higher incidence of fatal infection. There remains an unmet need for an oral treatment for T2D patients at risk for cardiometabolic complications to safely reduce IL-1β-mediated inflammation chronically&amp;with low risk of immunosuppression. In an initial dose-range finding study in heart failure patients with T2D, we reported evidence of anti-hyperglycaemic efficacy and improvement in LVEF with dapansutrile an oral specific inhibitor of the NLRP3 inflammasome. Objectives: To investigate the potential of preventing the transition to organ complications, The EU funded consortium INTERCEPT-T2D in collaboration with US based biotech Olatec Therapeutics has launched a clinical trial of anti-inflammatory therapy with dapansutrile targeting T2D patients with low-grade inflammation. Methods: Dapansutrile in Diabetes and Complications (DAPAN-DIA, NCT06047262) aims to determine whether NLRP3 inhibition with dapansutrile has the potential to not only improve glycaemia but also reduce micro- and macro-vascular risk and complications from diabetes. DAPAN-DIA is a multicenter, pbo-controlled, prospective, randomized, double-blind trial conducted in Switzerland, France, Belgium and Germany. A total of 300 patients with T2D, HbA1c &gt;7.5% and hsCRP&gt;1.5 mg/L are being randomized to either dapansutrile 1000 mg BID or matching PBO tablets for 6 months (2:1 ratio dapansutrile: pbo). The primary endpoint is change from baseline HbA1c. Secondary endpoints include biomarkers associated with diabetic complications, progression of MASLD as well as chronic inflammation (IL-1 β, IL-6 and hsCRP). A subject-assessed QoL questionnaire is also collected. To detect an absolute difference of 0.5% in HbA1c between groups, approximately 300 subjects will be randomized 2:1 ratio to achieve 80% power, assuming a standard deviation of 1.2% in change from baseline in HbA1c at week 26. Results: The trial has launched and currently is enrolling subjects. Conclusions: DAPAN-DIA is the first placebo-controlled, adequately powered, large, multi-center study with an oral NLRP3-specific Inhibitor, dapansutrile. The trial will generate important data on a new clinically relevant dimension in T2D care where consideration at diagnosis of inflammatory parameters are of importance for the transition to T2D-related complications.

Comprehensive analysis of psychological symptoms and quality of life in early patients with IBD: a multicenter study from China.

To investigate the prevalence and risk factors of psychological symptoms and quality of life (QoL) in early patients with inflammatory bowel disease (IBD). From September 2021 to May 2022, a unified questionnaire was developed to collect clinical data from early patients with IBD from 42 tertiary care hospitals. The influencing factors of psychological symptoms and poor QoL are screened by logistic regression analysis for constructing model in predicting poor QoL. The consistency index, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the model. A total of 939 early patients with IBD were surveyed, Among them, 20.3% exhibited anxiety, 21.7% had depression, 57.3% experienced sleep disturbance, and 41.9% reported poor QoL. The factors influencing psychological symptoms varied between ulcerative colitis (UC) and Crohn's disease (CD) patients. The QoL was primarily affected by disease activity, income level and depression. The AUC value of the model in the training group was 0.781 (95% CI: 0.748-0.814). The calibration diagram of the model closely matched the ideal curve. Compared to other prediction models, our model showed superior predictive capability, with NRI and IDI values of 0.324 (95%CI:0.196-0.4513) and 0.026 (95%CI:0.014-0.038), respectively. DCA indicated that the nomogram model could provide clinical benefits. Early patients with IBD exhibit a high prevalence of psychological symptoms and poor QoL. The nomogram prediction model we constructed demonstrates high accuracy and performance in predicting QoL in early patients with IBD.

Pre-transplant metabolic tumor volume predicts recurrence following liver transplantation for colorectal metastasis: A multicenter study.

Liver transplant (LT) for colorectal cancer liver metastases (CRLM) is increasingly popular, yet the ideal selection criteria remain unknown. Pre-transplant PET metabolic tumor volume (MTV) has been described as predicting recurrence, with a proposed cut-off of MTV ≥70cm3. This approach has not been validated. Patients undergoing LT for CRLM at two academic transplant centers (1/1/2017-12/1/2023) were included. PET-MTV was calculated by a staff radiologist from the most recent PET-scan before LT using the published protocol. Twenty-six patients were included. Median follow-up was 609 days (IQR 320-1069) and from PET to LT was 1.9 months (1.3-2.6). Nearly all (n=24, 92.3%) received living donor transplantation. Absolute recurrence rate was 30.8% (n=8). Actuarial unadjusted 1-, and 2-year RFS were 83% (n=15/18), and 62% (n=8/13); 1- and 2-year OS were 100% (n=18/18), and 85% (n=11/13).The incidence of recurrence-per-year follow-up was 0.35 when MTV ≥70cm3 versus 0.10 if MTV <70cm3 (P<0.001). Median RFS using Kaplan-Meier product-estimate was 0.83 years (95%CI 0.43-1.23) in MTV≥70cm3 versus 4.1 years (95%CI 2.90-5.22) when MTV<70cm3 (P<0.001); this was also associated with improved OS (P=0.003). MTV>70cm3 demonstrated HR=2.42 (95%CI 2.2-62.2, P=0.006) for association with RFS on univariate Cox-proportional hazards analysis, and an Area-Under-the-Curve (AUC)=0.771 (95%CI 0.560-0.981) for predicting recurrence (P=0.030)Nineteen patients (69.2%) had histologically viable tumor, which was associated with recurrence (43% vs. 0%, P=0.039) and reduced RFS (log-rank P=0.019). PET-MTV was associated with presence of histologically-viable tumor (AUC=0.763, 95%CI 0.583-0.944). PET-MTV ≥70cm3 was associated with reduced RFS and OS after LT for CRLM, confirming findings from the Norway group. This is likely due to its' ability to identify residual viable tumors, which are independently associated with recurrence. PET-MTV should be a key selection criterion prior to LT for CRLM.