Median Delay Research Articles

Impact of Sensitive Circulating Tumor DNA Monitoring on CT Scan Intervals During Postoperative Colorectal Cancer Surveillance

Objective: This study investigated whether digital polymerase chain reaction (dPCR)-based circulating tumor DNA (ctDNA) monitoring can allow longer intervals between computed tomography (CT) scans during postoperative surveillance of colorectal cancer (CRC). Background: Practical guidelines still recommend intensive postoperative surveillance of CRC using periodical CT scans and serum carcinoembryonic antigen testing. Methods: The longitudinal dynamics of ctDNA for 52 patients with CRC as measured by dPCR using probes targeting 87 individual tumor-specific mutations (1–5 per patient) were compared with results from conventional (ie, clinical) surveillance using serum tumor markers and CT. Results: A total of 382 CT procedures were carried out for the patient cohort (3.3/year per patient) and the median lead time from ctDNA relapse to clinical relapse was 182 days (range, 0–376 days). If the CT interval was annual, potential delays in the detection of clinical relapse would have occurred for 7 of the 10 patients who experienced clinical relapse (9 of 13 events), with a median delay of 164 days (range, 0–267 days). If annual CT surveillance was performed together with ctDNA monitoring, 218 (57.1%) CTs would not have been needed to detect the first clinical relapse. In addition, the ctDNA monitoring would have provided a lead time of 339 days for detection of clinical relapse (range, 42–533 days). Conclusions: Our findings suggest that the ctDNA monitoring as part of postoperative surveillance and clinical relapse detection for patients with CRC could allow the CT interval to be lengthened. Trial Registration: This trial was registered with University Hospital Medical Information Network Clinical Trial Registry (UMIN000045114).

Multicenter Retrospective Registry Study on BCG Use in Non-Muscle Invasive Bladder Cancer in Latin America: BLATAM (Bladder Cancer in Latin America) Group.

This study, conducted by the Bladder Cancer in Latin America (BLATAM) group, aims to analyze epidemiological and therapeutic data on non-muscle invasive bladder cancer (NMIBC) in Latin American patients. It seeks to identify factors contributing to suboptimal responses to Bacillus Calmette-Guérin (BCG) therapy and assess areas for improvement in regional treatment practices. A multicenter retrospective study was carried out in collaboration with reference Urology Departments across Latin America. Data were collected using an electronic Case Report Form (CRF) from 2011 to 2021, capturing demographics, clinical presentation, treatment details, and follow-up of NMIBC patients treated with BCG. Statistical analyses included Kaplan-Meier survival analysis for relapse-free survival (RFS). Data from 292 patients across five countries were analyzed, with a mean age of 70.3 years and a male prevalence of 74%. Smoking history was reported in 70.6% of patients. The mean time to the first BCG dose was 2.4 months post-TURBT, with 26.7% of patients exceeding the recommended 60-day window for induction initiation. While 84% of patients completed BCG induction, only 45.9% followed the recommended Lamm maintenance schedule. Delays in starting maintenance cycles were observed, with a median delay of over 36 days for the first cycle and 65 days for the second cycle. RFS at 1 year and 5 years for high-risk patients was 87.3% and 53.3%, respectively. This study highlights critical deviations from recommended NMIBC management protocols in Latin America, including delayed BCG initiation and inconsistencies in maintenance therapy. These findings emphasize the need for standardized treatment protocols and improved adherence to international guidelines, which could enhance NMIBC patient outcomes in the region. Collaborative efforts are essential to develop region-specific strategies, improve data collection, and ultimately provide better care for bladder cancer patients in Latin America.

Trends to shorter diagnostic delay in spondyloarthritis patients during the last decades and association with clinical presentation: data from ASAS-COMOSPA study

BackgroundDiagnostic delay is one of the greatest challenges in spondyloarthritis (SpA). Better disease knowledge and more accessibility to new image technology could have a positive impact on time to diagnosis.ObjectivesThe...

214. Clinical Characteristics and Outcomes of Patients Treated with Tecovirimat for Mpox Disease: A Large Cohort in New York City

Abstract Background Clinical characteristics and outcomes in patients with mpox treated with tecovirimat are not well described. Methods We requested retrospective deidentified data from healthcare systems in New York City (NYC) with >50 tecovirimat prescriptions. Patients with probable or confirmed mpox initiating tecovirimat from May–December 2022 were included. We used a survey tool to extract demographic and clinical data from medical records. Patients reporting tecovirimat initiation at a different institution or with unknown HIV status were excluded. We used multivariable Poisson regression models with robust standard errors to examine factors associated with hospitalization and treatment delays. Results Of 751 eligible records, we excluded 41, leaving 708 patients in the analysis; median age was 36 years (IQR 31–43); 694 (98%) were assigned male at birth; 566 (80%) were cisgender men who have sex with men; 399 (56%) were living with HIV; and 232 (33%), 195 (28%), and 182 (26%) identified as Hispanic, non-Hispanic (NH) white, and NH Black, respectively. Reasons for treatment included proctitis (n=376, 53%), lesion type (confluent, location) (335, 47%), HIV (237, 33%), and bacterial superinfection (58, 8%). Side effects (100, 14%) and severe adverse events (7, 1%) were rare. The most common long-term sequela was scarring (69,10%) (Table 1). Of 100 (14%) hospitalized patients, reasons for hospitalization included pain (25%), bacterial superinfection (22%), and dysphagia (13%) (Table 2). Median delay from symptom onset to treatment initiation was 8 days (IQR 6–11). NH Black patients had higher risk of initiating ≥8 days after symptom onset (adjusted relative risk [aRR]=1.4, 95%CI: 1.2–1.7) and being hospitalized (aRR=2.2, 95%CI: 1.4–3.5) compared with Hispanic patients, adjusting for HIV and insurance status (Tables 3,4). Conclusion We described common reasons for tecovirimat initiation and hospitalization. There were racial and ethnic disparities in hospitalization and treatment delays that may have been due to late presentation to care or provider-related delayed testing. More research and focused efforts to mitigate these disparities are needed. These findings may better inform decisions for treatment initiation and hospitalization for mpox. Disclosures Ofole Mgbako, MD MS, Gilead: Advisor/Consultant

505. Real-World Use of Cabotegravir Long-Acting for Pre-Exposure Prophylaxis: Data from Trio Health Cohort

Abstract Background Cabotegravir (CAB) long acting (LA) for pre-exposure prophylaxis (PrEP) was approved in the US in Dec 2021 to reduce the risk of sexually acquired HIV-1 infection. The Centers for Disease Control and Prevention (CDC) guidelines state that both HIV antigen (Ag)/antibody (Ab) and HIV RNA testing should be conducted prior to every injection. This analysis presents data on testing practices, effectiveness, adherence, and persistence in real world setting in the US.Table 1:Baseline Characteristics for those with at least 1 injection of CAB LA PrEP Methods Individuals initiating CAB LA PrEP were identified from electronic health records in the Trio Health cohort between Dec 2021- Jan2024. HIV testing within ±7 days of injection and HIV incidence were assessed among individuals with ≥ 1 injection of CAB LA. Incident HIV was defined as detectable HIV RNA +/- positive HIV Ag/Ab test. Adherence was assessed among those with ≥ 2 injections of CAB LA. As per label, the first 2 initiation injections are to be administered monthly followed by continuation injections every 2 months. On-time injections were defined as occurring within ±7 days of target date and discontinuations as 127 days without injections.Table 2:HIV Testing during Follow-up among Individuals with ≥1 injection of CAB LA for PrEP (N=526) Results Among the 526 individuals with ≥ 1 injections (median 5 [IQR: 3-8]; median follow-up 7 months [IQR: 3-14] [Table 1]), 34% had both HIV RNA and HIV Ag/Ab tests performed, and 63% had either test prior to all injections [Table 2]. HIV RNA tests were used less frequently than HIV Ag/Ab tests. Of 474 with ≥ 2 CAB LA injections, 76 (16%) had a delayed 2nd injection with a median of 22 days delay [IQR: 9-33] [Table 3]. Of 396 with continuation injections, 131 (33%) had delays with median of 1 delayed injection and median delay of 12 days [IQR: 3-29]. Ten (3%) individuals had 1 missed injection and none missed ≥ 2 injections. No incident HIV diagnoses were identified. The majority were persistent at 6 months (92%) and at 12 months (85%).Table 3:Delayed Injections among Individuals with ≥2 Injections of CAB LA for PrEP Conclusion These real-world data with long duration of follow-up and a large sample size further support that CAB LA for PrEP remains effective at preventing HIV acquisition. Injections were administered on time among the majority of initiators. HIV testing practices in this real-world setting did not align with the CDC testing guidelines among a significant proportion of users. No incident HIV diagnoses were identified, regardless of testing approach or injection timing. Disclosures Moti Ramgopal, MD, FACP, FIDSA, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Carolyn A. Brown, MSPH, PhD, ViiV Healthcare/GSK: Stocks/Bonds (Public Company) Andrew Frick, MS, Trio Health: Employee Janna Radtchenko, MBA, Trio Health: Employee Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds (Public Company)|ViiV Healthcare: Full Time Employee Leigh Ragone, MS, GlaxoSmithKline: Stocks/Bonds (Public Company)|ViiV Healthcare: Full time employee Jean A. van Wyk, MBChB, MFPM, ViiV Healthcare: Employee|ViiV Healthcare: Stocks/Bonds (Public Company) Karam Mounzer, MD, Epividian: Board Member|Epividian: Honoraria|GS: Advisor/Consultant|GS: Grant/Research Support|GS: Honoraria|Merck: Advisor/Consultant|THERA Technologies: Grant/Research Support|ViiV healthcare: Advisor/Consultant|ViiV healthcare: Grant/Research Support|ViiV healthcare: Honoraria Paul Benson, DO, ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Steven Santiago, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|Janssen: Honoraria Gregory Huhn, MD, MPHTM, Eli Lilly: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|ViiV Healthcare: Grant/Research Support Kenneth H. Mayer, MD, MPH, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|ViiV Healthcare: Grant/Research Support Rick A. Elion, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Honoraria|Proteus: Grant/Research Support|Trio Health: Employee|ViiV Healthcare: Advisor/Consultant Vani Vannappagari, MBBS, MPH, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Full time Employee|ViiV Healthcare: Stocks/Bonds (Public Company)

Impact of mechanical ventilation on severe acute kidney injury in critically ill patients with and without COVID-19 – a multicentre propensity matched analysis

BackgroundAcute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Its complications often require renal replacement therapy (RRT). Invasive mechanical ventilation (IMV) and infections are considered risk factors for the occurrence of AKI. The use of IMV and non-invasive ventilation (NIV) has changed over the course of the pandemic. Concomitant with this change in treatment a reduction in the incidences of AKI and RRT was observed. We aimed to investigate the impact of IMV on RRT initiation by comparing critically ill patients with and without COVID-19. Furthermore, we wanted to investigate the rates and timing of RRT as well as the outcome of patients, who were treated with RRT.ResultsA total of 8,678 patients were included, of which 555 (12.8%) in the COVID-19 and 554 (12.8%) in the control group were treated with RRT. In the first week of ICU stay the COVID-19 patients showed a significantly lower probability for RRT initiation (day 1: p < 0.0001, day 2: p = 0.021). However, after day 7 a reversed HR was found. In mechanically ventilated patients the risk was significantly higher for the initiation of RRT over the entire stay. While in non-COVID-19 patients this was a non-significant trend, in COVID-19 patients the risk for RRT was significantly increased. The median delay between initiation of IMV and requirement of RRT was observed to be longer in COVID-19 patients (5 days [IQR: 2–11] vs. 2 days [IQR: 1–5]). The analysis restricted to patients with RRT showed a significantly higher risk for ICU death in patients requiring IMV compared to patients without IMV.ConclusionThe analysis demonstrated that IMV as well as COVID-19 are associated with an increased risk for initiation of RRT. The association between IMV and risk of RRT initiation was given for all investigated time intervals. Additionally, COVID-19 patients showed an increased risk for RRT initiation during the entire ICU stay within patients admitted to an ICU due to respiratory disease. In COVID-19 patients treated with RRT, the risk of death was significantly higher compared to non-COVID-19 patients.

Delayed Surgery Increases the Rate of Infection in Closed Diaphyseal Tibial and Femoral Fractures.

Although delays in musculoskeletal care in low- and middle-income countries (LMICs) are well documented in the open fracture literature, the impact of surgical delays on closed fractures is not well understood. This study aimed to assess the impact of surgical delay on the risk of infection in closed long-bone fractures treated with intramedullary nailing in LMICs. Using the SIGN (Surgical Implant Generation Network) Surgical Database, patients ≥16 years of age who were treated with intramedullary nailing for closed diaphyseal femoral and tibial fractures from January 2018 to December 2021 were identified. Infection was diagnosed based on the assessment by the treating surgeon. A logistic regression model, adjusting for potential confounders, was used to analyze the association between delays to surgery (in weeks) and infection. Of the 9,477 closed fractures that were included in this study, 58% were femoral fractures and 42% were tibial fractures. The mean age was 35 years, and 76.2% of the patients were men. The mean delay to surgery was 10.5 days, and the median delay to surgery was 6 days. The overall infection rate was 3.1%. The odds of developing an infection increased by 9.2% with each week of delayed surgical treatment (odds ratio,1.092; 95% confidence interval, 1.042 to 1.145). Increasing delays were also associated with longer surgery duration and higher rates of open reduction. Surgical delays in LMICs were associated with an increased risk of infection in closed long-bone fractures. This study quantified the increased risk of infection due to delays in receiving care, highlighting the importance of timely surgery for closed fractures in LMICs. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Educational attainment, Aβ, tau, and structural brain reserve in Alzheimer's disease.

Alzheimer's disease (AD) patients with higher educational attainment (EA) often exhibit better cognitive function. However, the relationship among EA status, AD pathology, structural brain reserve, and cognitive decline requires further investigation. We compared cognitive performance across different amyloid beta (Aβ) positron emission tomography (A±) statuses and EA levels (High EA/Low EA). We examined the effects of Aβ plaques, tau tangles, and gray matter volume (GMV) on the relationship between EA and domain-specific cognitive decline. A+/High-EA individuals exhibited slower cognitive decline in global cognition and language domains than A+/Low-EA individuals. This cognitive benefit was independently and synergistically explained by reduced AD pathology, including lower Aβ and tau burdens, as well as preserved GMV. Additionally, High-EA individuals experienced a median delay of 1.9 years in the onset of significant brain atrophy among A+ individuals. These findings highlight the independent and synergistic contributions of EA-associated AD pathology and GMV alterations to longitudinal cognitive decline. Alzheimer's disease (AD) individuals with high educational attainment (EA) show slower declines in global cognition and language. EA-related slower cognitive decline is linked to reduced tau and greater gray matter volume in AD. AD individuals with high EA show a median 1.9 year delayed onset of brain atrophy.

Efficacy and complications of the induced membrane technique for immediate bone reconstruction in complex hand injuries.

To report the radiological outcomes and complications of the Masquelet induced membrane technique (IMT) for acute bone reconstruction in complex hand injuries. We retrospectively reviewed 22 patients treated primarily by the IMT for bone defect of the phalanx and/or metacarpals bones in 26 injured digits. The median bone defect length was 17mm (IQR 13-25). Given the severity and variability of the lesions, revision parameters focused on bone healing and postoperative complications. At the median follow-up of nine months (IQR, 6-14 months), bone union was achieved in 25 digits (96%) with a median delay of three months (IQR, 2.5-3.5 months) after stage 2. Postoperative complications occurred in 11 of 26 digits requiring revision surgery in nine of 26 digits (35%). Soft tissue coverage failure and infection were the main complications. A patient underwent a late amputation through the metacarpophalangeal joint due to an uncontrolled bone infection. Despite a significant rate of complications, bone reconstruction using the IMT is a reliable procedure for achieving bone healing of phalanx or metacarpal bone defects in complex hand injuries.

DOP087 Characterization of a European population with recently diagnosed Crohn’s Disease: results from the prospective Crohn´s Disease Cohort (CROCO) Study

Abstract Background Crohn’s disease (CD) is a chronic and progressive condition with a growing global prevalence, leading to potential bowel damage and disability. Data on the clinical presentation, outcomes, and treatment options in newly diagnosed CD patients in Europe in the current era are essential to guide physicians. The aim is describe the clinical characteristics of a contemporary European cohort of recently diagnosed CD patients. Methods The Crohn's Disease Cohort (CROCO) is an ongoing, multicenter, European prospective study of CD patients diagnosed within the last 12 months, aimed at tracking bowel damage progression and disability. This report presents the baseline characteristics at study inclusion. Results From August 2021 to October 2024, 399 patients (56% male, 46% current or former smokers) with a median age at diagnosis of 33.7 years (IQR 24.6; 49.2) were recruited across 18 centers. The median delay between symptom onset and diagnosis was 6.2 months (IQR 2; 15.4), and the median disease duration at inclusion was 3.8 months (IQR 1.6; 7.4). Ileal involvement (L1/L3) was reported in 85% of patients. Overall, 15% had perianal disease and 28% had extraintestinal manifestations, predominantly arthritis/arthralgia. Complicated disease behavior was observed in 32% of patients at diagnosis (stricturing: 17%; penetrating: 15%); 6% had undergone intestinal surgery, and 3% perianal surgery from diagnosis to inclusion. CD-related hospitalizations were reported by 22% of patients. Regarding treatments, 51% received steroids (28% systemic steroids), 17% 5-ASA, 1% immunosuppressants monotherapy, and 44% initiated biological therapy (168 anti-TNF, 8 anti-IL 12/23, and 6 anti-integrin, representing 42%, 2% and 2% of the cohort, respectively). A total of 31% were managed with a combination of biologic and immunosuppressant therapies. Disability assessment showed that 48% of patients reported no disability, 24% mild disability, and 28% moderate to severe disability. Conclusion In this prospective European cohort of newly diagnosed CD patients, nearly one-third had a complicated disease phenotype and moderate to severe disability, despite a relatively short diagnostic delay. While steroid use remains common, early initiation of biological therapy in 44% of patients reflects a shift in CD management strategies.

P0993 Prevention of Postoperative Recurrence of Crohn’s Disease: Comparison of Two Therapeutic Strategies

Abstract Background Postoperative recurrence of Crohn’s disease affects half of patients within 10 years, making prevention crucial. The ECCO recommends immediate postoperative prophylactic treatment for patients with at least one risk factor for recurrence. While this strategy is proven effective for those with multiple risk factors, data on its benefits compared to endoscopy-guided prophylaxis in patients with only one risk factor is lacking. The study aimed to compare immediate postoperative prophylactic treatment with endoscopy-guided prophylaxis in patients with a single risk factor Methods This retrospective bicentric study included patients who underwent ileocolic resection for Crohn’s disease between January 2011 and December 2021, each with one risk factor for postoperative recurrence. Patients were divided into two groups G1 received immediate postoperative prophylactic treatment, while G2 received prophylactic treatment guided by colonoscopy within the first year after surgery. The primary outcome was the frequency of endoscopic recurrence within one year :Rutgeerts score ≥ i2. Secondary outcomes included severe endoscopic recurrence (i4) within 12 months and clinical recurrence at 6 and 24 months. Statistical analysis was conducted using SPSS26 Results This study included 41 patients divided into two groups. Group 1 (24 patients) had an average age of 34 years, with 58.33% being active smokers.Postoperative treatments were as follows: infliximab (4 patients), infliximab-azathioprine combination (3 patients), adalimumab (4 patients), ustekinumab (1 patient), and azathioprine monotherapy (12 patients). A Rutgeerts score of i2 or higher was found in 13 patients after a median of 9 months post-surgery, with an average follow-up of 3 years Group 2 (17 patients) had an average age of 38 years, with 64.7% being active smokers. Postoperative colonoscopy was performed after a median delay of 8 months. A Rutgeerts score of i2 or higher was found in 10 patients. The treatments initiated after colonoscopy were as follows: infliximab (3 patients), infliximab-azathioprine combination (2 patients), adalimumab (7 patients), azathioprine monotherapy (4 patients), and ustekinumab (1 patient). The average follow-up after surgery was 3 years No significant differences were observed between the groups in terms of endoscopic or severe endoscopic recurrence, or clinical recurrence at 6 and 24 months post-surgery Conclusion In our study, early initiation of prophylactic postoperative treatment for patients with a single risk factor did not reduce clinical or endoscopic recurrence rates. This suggests that avoiding such early treatment could help prevent unnecessary exposure to immunosuppressants and biologics, thereby reducing risks of side effects and high costs

P0552 Incisional and parastomal hernia after surgical management of inflammatory colitis: a common complication presenting a real therapeutical challenge in a tertiary expert center

Abstract Background Surgical management of inflammatory colitis often requires a staged approach involving multiple interventions with or without stoma creation. Data on the incidence, risk factors, impact and management of incisional and parastomal hernias (IH and PSH) in UC patients are limited. This study aims to assess the incidence of IH and PSH after surgical completion in colitis patients and to identify associated risk factors. Methods All patients undergoing surgical management for inflammatory colitis between March 2010 and May 2024 were eligible. The primary endpoint was the incidence of IH and/or PSH and/or and/or stoma prolapse. Risk factors of hernia (IH and/or PSH) were analysed using univariate and multivariate analyses. Results A hundred and nine patients had surgical management for inflammatory colitis and were included in the analysis (87 UC [80%], 6 Crohn’s disease [5.5%], 14 indeterminate [13%], 2 drug-induced [1.8%]). Mean age was 46 ± 17 years. Indications included refractory colitis (n=32, 29%), severe acute colitis (n=58, 54%), and dysplasia (n=19, 17%). Procedures performed were ileal pouch anal anastomosis (IPAA) in 73(67%) patients, ileorectal anastomosis (IRA) in 23(21%), and non-restorative proctocolectomy with end ileostomy in 13(12%). Patients underwent a mean of 2.7±0.96 procedures with 99 patients requiring 2 or more procedures. Temporary stomas were created in 84(77%), and 19(17%) had permanent stomas. Median follow-up time was 44[21-91] months. 25(23%) patients had parietal complications after a median delay of 25[11-35] months following the last procedure: 22(20%) IH, 4(3.6%) PSH, and 3(2.8%) stomas prolapse*. None of the 4 patients with prophylactic biological mesh placement during stoma closure developed complications. Among 25 patients with parietal complications, 20 underwent abdominal wall repair. Of these, 6(30%) had recurrence requiring redo abdominal wall surgery in 3(15%). Adjusted risk factors for parietal complications included BMI≥25 (OR=3.13;95%CI=1.11-8.82;p=0.031) and permanent stoma (OR=5.86;95%CI=1.83-18.80; p=0.003). The type and number of procedures, and surgical indications were not associated with parietal complications. * Several patients had several complications Conclusion Parietal complications represent a major clinical challenge in the surgical management of inflammatory colitis. Nearly one-quarter of patients develop abdominal incisional or parastomal hernias, and one-third of patient experience recurrence following abdominal wall repair. Prophylactic mesh placement at the stoma closure site should be studied as an option to reduce this risk. References None

P0295 Histological healing reduces the risk of relapse in ulcerative colitis: results of a prospective study

Abstract Background The STRIDE II guidelines recognize endoscopic mucosal healing (MH), defined by a UCEIS score ≤1 or a Mayo endoscopic subscore = 0 (MES), as one of the main therapeutic goals in ulcerative colitis (UC). Nevertheless, histological healing (HH) could reduce the risk of long-term complications in UC. The aim of this study was to assess the risk of relapse in UC depending on the degree of remission achieved. Methods We conducted a prospective study including all consecutive UC patients in clinical remission and endoscopic MH (MES 0 or 1) between January 2021 and January 2024. The primary endpoint was UC relapse, defined as the need for treatment intensification and/or corticosteroids initiation and/or UC-related hospitalization and/or colectomy. Patients were followed up every 6 months for two years. HH was defined as a Nancy index ≤ 1 (blinded double reading). Results A total of 75 patients were included. The median disease duration was 12 years (IQR [7.5-19.0]) and 66 (82%) patients had a left side colitis (E2) or pancolitis (E3). Patients were treated for a median of 3 years (IQR [1.2 - 6.9]) prior to colonoscopy. Mayo=0 and HH were observed in 49 (65%) and 55 (79%) patients, respectively. After a median follow-up of 21.0 months (IQR [12.0 - 26.5]), relapse was observed in 13 patients (17%) after a median delay of 11 months (IQR [6.0 - 18.0]). There was no significant difference in the risk of relapse between MES 1 and MES 0 patients (13.6% vs. 30.7% respectively p = 0.27). The risk of relapse in patient with MES 1 was significantly higher among patient with absence of HH (39.7% versus 20.1% respectively p = 0.04). Similarly, in patients with MES 0, the risk of relapse was significantly higher among patients without HH (70.0% versus 27.4% respectively, p = 0.023). No UC-related hospitalizations or colectomy were reported during follow-up. In multivariate analysis, only absence of HH was associated with disease relapse (HR = 6.1, 95% CI = [1.6 - 23.1], p = 0.01). The degree of correlation between rectal biopsies and whole-colon biopsies was almost perfect (к 0.84 (%-agree 93.1, p &amp;lt; 0.001)) for HH assessment. Conclusion In this prospective study, histological healing was associated with improved long-term outcome in UC patients whatever the degree of endoscopic mucosal healing. Rectal biopsies were effective in identifying HH.

P0842 Paediatric Inflammatory Bowel Diseases: novel agents on the therapeutic horizon

Abstract Background The therapeutic landscape for inflammatory bowel disease (IBD) has advanced considerably over the past two decades with the development of monoclonal antibodies and advanced small molecules. However, only one advanced therapy class is approved for children with IBD. Long delays exist following adult approval, with a median delay of over seven years to paediatric approval (Figure 1).1 With the recent circulation of draft guidance for industry on drug development in paediatric IBD (pIBD) by the US Food and Drug Administration (FDA),2 an opportunity exists to improve clinical trial processes for drug approval in pIBD. The aim of this study is to summarize the landscape of pIBD clinical trials through a review of trial registries. Methods We conducted a cross-sectional review of publicly accessible data from Clinicaltrials.gov and ClinicalTrialsRegister.eu to identify investigational therapeutic agents as well as approved therapeutic agents for the treatment of pIBD. All interventional pIBD studies (&amp;lt;18 years and/or included a paediatric population) listed from the database’s inception to May 13, 2024, were considered for inclusion. Results A total of 3,493 records were identified from Clinicaltrials.gov (2,758) and ClinicalTrialsRegister.eu (735). One-hundred and sixteen completed trials were included in the review. Of those completed trials, 34 studies focused on biologic agents (29%). Novel small molecule agents (spingosine-1-phosphate agonists and Janus kinase inhibitors) were examined in 7 studies (6%). A further 118 IBD trials are actively recruiting paediatric patients. Sixty-five studies are randomised controlled trials and 53 are open-label studies. With regards to biologic agents, 17 trials are exploring the use of approved biologic agents in children and 34 trials are focusing on novel biologic agents. These include etrolizumab, golimumab, guselkumab, mirikizumab, risankizumab, ustekinumab, and vedolizumab. Sixteen trials are recruiting, examining small molecule therapies in pediatrics, to include upadacitinib, tofacitinib, etrasimod, and ozanimod. Conclusion Efforts to hasten the approvals of novel agents in pIBD is paramount to ensure timely access to effective medications. Whilst there is increasing trial activity in the pIBD landscape, approval by regulatory bodies continue to pose barriers. Consideration for novel trial designs and collaboration between research networks could reduce the delay in paediatric marketing approvals. Continued engagement with regulatory bodies and the international pIBD community offers a critical opportunity to advance drug approvals in children with IBD.

Swallowed Topical Tacrolimus Induces Clinical and Histological Remission in a Subset of Patients with Severe Lymphocytic Esophagitis

Introduction: Lymphocytic esophagitis (LyE) represents a chronic inflammatory disease of the esophagus with low response rates to topical steroids. Thus, novel treatment options such as swallowed topical tacrolimus, particularly for refractory cases, are urgently needed. Methods: We retrospectively analyzed patients with LyE enrolled in the Swiss eosinophilic esophagitis database that received treatment with a swallowed tacrolimus syrup (1 mg bid). We compared clinical (visual analogue scale [VAS] 0–10), endoscopic (VAS, Endoscopic Reference Score [EREFS]), and histological (peak lymphocyte count) disease activity before versus after treatment. Results: Out of 17 LyE patients, we identified a total of 7 patients undergoing tacrolimus treatment (4 males, median age 71.3 years, IQR: 61.3–76.5, median diagnostic delay of 51.0 months, IQR: 24.5–62.0). Six patients had been previously treated with PPI, five with topical and/or systemic steroids. All patients were treated with topical tacrolimus corresponding to 1 mg bid (for a median of 13 weeks, IQR: 11–15). All patients had clinically, and histologically active disease at baseline. Topical tacrolimus treatment resulted in histological remission (<30 lymphocytes/hpf) in 3/7 patients (42.9%), while 4/7 patients achieved symptomatic remission (VAS for dysphagia ≤2, 57.1%). Overall, clinical (VAS 5 vs. 2, p = 0.0625) and endoscopic activity (VAS 5 vs. 2, p = 0.0625, and EREFS 3 vs. 2, p = 0.125) decreased. Measurement of tacrolimus trough levels in 4/7 patients (range 2.1–3.9 μg/L) revealed some degree of systemic absorption. Mild adverse events to the tacrolimus treatment were seen in 2 patients (esophageal candidiasis, hyposensitivity around lips). No impact on kidney function was observed during the treatment period. Conclusion: Topical tacrolimus appears to be a potential treatment option for severe LyE, particularly after failure of PPI and/or topical steroids. Further studies are needed, in particular regarding the optimal galenic formulation to avoid systemic absorption. Introduction: Lymphocytic esophagitis (LyE) represents a chronic inflammatory disease of the esophagus with low response rates to topical steroids. Thus, novel treatment options such as swallowed topical tacrolimus, particularly for refractory cases, are urgently needed. Methods: We retrospectively analyzed patients with LyE enrolled in the Swiss eosinophilic esophagitis database that received treatment with a swallowed tacrolimus syrup (1 mg bid). We compared clinical (visual analogue scale [VAS] 0–10), endoscopic (VAS, Endoscopic Reference Score [EREFS]), and histological (peak lymphocyte count) disease activity before versus after treatment. Results: Out of 17 LyE patients, we identified a total of 7 patients undergoing tacrolimus treatment (4 males, median age 71.3 years, IQR: 61.3–76.5, median diagnostic delay of 51.0 months, IQR: 24.5–62.0). Six patients had been previously treated with PPI, five with topical and/or systemic steroids. All patients were treated with topical tacrolimus corresponding to 1 mg bid (for a median of 13 weeks, IQR: 11–15). All patients had clinically, and histologically active disease at baseline. Topical tacrolimus treatment resulted in histological remission (<30 lymphocytes/hpf) in 3/7 patients (42.9%), while 4/7 patients achieved symptomatic remission (VAS for dysphagia ≤2, 57.1%). Overall, clinical (VAS 5 vs. 2, p = 0.0625) and endoscopic activity (VAS 5 vs. 2, p = 0.0625, and EREFS 3 vs. 2, p = 0.125) decreased. Measurement of tacrolimus trough levels in 4/7 patients (range 2.1–3.9 μg/L) revealed some degree of systemic absorption. Mild adverse events to the tacrolimus treatment were seen in 2 patients (esophageal candidiasis, hyposensitivity around lips). No impact on kidney function was observed during the treatment period. Conclusion: Topical tacrolimus appears to be a potential treatment option for severe LyE, particularly after failure of PPI and/or topical steroids. Further studies are needed, in particular regarding the optimal galenic formulation to avoid systemic absorption.

Unexpected Clinically Relevant Findings Detected via Computed Tomography in Patients with Severe Aortic Stenosis Who Are Candidates for Transcatheter Aortic Valve Replacement.

Background: The detection of unexpected findings (UF) during CT scans of patients undergoing TAVR is frequent; however, it is unclear whether such findings have a clinical impact on the TAVR pathway. Methods: We conducted a retrospective, single-center observational study enrolling patients who were candidates for TAVR. All enrolled patients underwent a CT scan before valve implantation. The primary outcome of this study was all-cause mortality, while the secondary outcome was to determine whether the diagnosis of clinically relevant UF on CT scans results in a significant delay in the TAVR procedure. Results: A total of 284 patients were enrolled. Clinically relevant UF were identified in 15% of the patients, with the most common types being pulmonary masses or nodules. During the follow-up period, 83 patients (29.2%) died. The prognosis was worsened by chronic kidney disease (HR 1.76, p = 0.03) and left ventricular dilatation (HR 1.74, p = 0.04), while the diagnosis of clinically relevant UF did not impact all-cause mortality (p = 0.38). No statistically significant differences were found in the delay from the diagnosis of severe aortic stenosis to TAVR between patients with and without clinically relevant UF (p = 0.07), although patients with clinically relevant UF experienced a median delay of approximately 37 days in the TAVR procedure. Conclusions: The presence of clinically relevant UF on preoperative CT scans does not affect all-cause mortality but shows a trend toward increasing the time from diagnosis to the procedure in patients with severe aortic stenosis undergoing TAVR. Further studies are required to confirm these findings in larger patient cohorts.

A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency.

Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterisation of the AAE-C1-INH cohort in UK is required to inform management. To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical and treatment profiles of AAE-associated diseases in UK. Retrospective data on 117 AAE-C1-INH patients were collected using a national survey proforma across 25/34 Adult Clinical Immunology and Allergy centres in UK. Other European cohorts were compared. Median age at AAE-C1-INH diagnosis was 65 years with 3.4% of patients diagnosed below 40 years. The median delay in diagnosis was one year. Antifibrinolytics and attenuated androgens showed comparable efficacy as LTP 88.9% and 89.5%, respectively. A haematological disorder was identified in 83.8% AAE-C1-INH patients compared to 3.4% autoimmune diseases. The predominant haematological disorders were splenic marginal zone lymphoma (SZL) 34% followed by MGUS 16%. The severity of angioedema did not depend on the associated disease. Anti-C1INH-autoantibodies testing was limited at 23.1%. Rituximab monotherapy was effective in treating 9/9 SZL and 1/2 MGUS-associated AAE-C1-INH. Rituximab efficacy was independent of anti-C1INH-autoantibodies detection with response in 3/3 seronegative and 4/4 seropositive patients. The diagnosis of AAE-C1-INH should not be overlooked below the age of 40 years. The choice of oral LTP should be informed by propensity to side-effects. B-cell depletion could be considered in treating monoclonal B cell disorder-associated-AAE-C1-INH in the absence of haematological indications. Further studies are required to address the clinical utility of anti-C1INH-autoantibodies.

Timing of rejection events preceded by Covid-19 mRNA vaccination in recipients of solid organ transplants.

SARS-CoV-2 mRNA vaccine reactogenicity has raised concerns regarding the risk of rejection in solid organ transplant recipients. We explored whether SOT recipients diagnosed with acute rejection had previously received a vaccine injection within a timeframe consistent with a causal link. We identified all SOT recipients with a diagnosis of acute rejection from 2020 to 2022 and who had previously received a SARS-CoV-2 vaccination, and analysed whether the delay between vaccination and rejection was constant. In the 45 identified patients, median delay between the last SARS-CoV-2 vaccination and the rejection was 102days [IQR 48-178]; the continuous distribution of this delay, with no identifiable time pattern, is not in favor of a role of vaccination in rejection. SARS-CoV-2 mRNA vaccination is unlikely to trigger rejection in SOT recipients.

Causes and determinants of infant mortality using verbal autopsy and social autopsy methods in a rural population of Odisha: a community-based matched case-control study

BackgroundThe avoidable causes of infant mortality should be identified, and interventions should be made to improve the infant mortality rate. The cause of infant deaths should be assessed in both...

Healthcare-seeking delays and associated factors among immigrant patients with acute ischaemic stroke in Shenzhen: a retrospective observational study

ObjectiveTo examine healthcare-seeking delays among immigrant patients with acute ischaemic stroke (AIS), identifying key factors contributing to these delays and proposing evidence-based interventions for policy formulation and research.DesignA retrospective observational...