Median Rate Research Articles

Checkpoint Inhibition in Addition to Dabrafenib/Trametinib for BRAFV600E-Mutated Anaplastic Thyroid Carcinoma.

Background: The dabrafenib plus trametinib combination (DT) has revolutionized the treatment of BRAFV600E-mutated anaplastic thyroid carcinoma (BRAFm-ATC). However, patients eventually develop resistance and progress. Single-agent anti-PD-1 inhibitor spartalizumab has shown a median overall survival (mOS) of 5.9 months. Combination of immunotherapy with BRAF/MEK inhibitors (BRAF/MEKi) seems to improve outcomes compared with BRAF/MEKi alone, although no direct comparison is available. BRAF-targeted therapy before surgery (neoadjuvant approach) has also shown improvement in survival. We studied the efficacy and safety of DT plus pembrolizumab (DTP) compared with current standard-of-care DT alone as an initial treatment, as well as in the neoadjuvant setting. Methods: Retrospective single-center study of patients with BRAFm-ATC treated with first-line BRAF-directed therapy between January 2014 and March 2023. Three groups were evaluated: DT, DTP (pembrolizumab added upfront or at progression), and neoadjuvant (DT before surgery, and pembrolizumab added before or after surgery). The primary endpoint was mOS between DT and DTP. Secondary endpoints included median progression-free survival (mPFS) and response rate with DT versus DTP as initial treatments, and the exploratory endpoint was mOS in the neoadjuvant group. Results: Seventy-one patients were included in the primary analysis: n = 23 in DT and n = 48 in DTP. Baseline demographics were similar between groups, including the presence of metastatic disease at start of treatment (p = 0.427) and prior treatments with surgery (p = 0.864) and radiation (p = 0.678). mOS was significantly longer with DTP (17.0 months [confidence interval CI, 11.9-22.1]) compared with DT alone (9.0 months [CI, 4.5-13.5]), p = 0.037. mPFS was also significantly improved with DTP as the initial treatment (11.0 months [CI, 7.0-15.0]) compared with DT alone (4.0 months [CI, 0.7-7.3]), p = 0.049. Twenty-three patients were in the exploratory neoadjuvant group, where mOS was the longest (63.0 months [CI, 15.5-110.5]). No grade 5 adverse events (AEs) occurred in all three cohorts, and 32.4% had immune-related AEs, most frequently hepatitis and colitis. Conclusions: Our results show that in BRAFm-ATC, addition of pembrolizumab to dabrafenib/trametinib may significantly prolong survival. Surgical resection of the primary tumor after initial BRAF-targeted therapy in selected patients may provide further survival benefit. However, conclusions are limited by the retrospective nature of the study. Additional prospective data are needed to confirm this observation.

Reduction of Urinary Tract Infection in Pediatric Surgical Patients Using NSQIP-P and Quality Improvement Methodology.

Hospital-acquired urinary tract infections (UTIs) have a detrimental effect on patients, families, and hospital resources. The Sydney Children's Hospital Network (SCHN) participates in the NSQIP-Pediatric (NSQIP-P) to monitor postoperative complications. NSQIP-P data revealed that the median UTI rate at SCHN was 1.75% in 2019, 3.5 times higher than the NSQIP-P target rate of 0.5%. Over three quarters of the NSQIP-P identified patients with UTI also had a urinary catheterization performed intraoperatively. A quality improvement project was conducted between mid-2018 and 2021 to minimize catheter-associated UTIs (CAUTIs) at SCHN. NSQIP-P samples include pediatric (younger than 18 years) surgical patients from an 8-day cycle operative log. NSQIP-P data are statistically analyzed by the American College of Surgeons and provide biannual internationally benchmarked reports. The project used clinical redesign methodology with a 6-phase process for quality improvement projects. The objectives of the project were to reduce urinary catheter duration of use, educate parents or carers, and improve catheter care and insertion technique by health staff. The duration of a urinary catheter in situ reduced from a median of 4.5 to 3 days from 2017 to 2021. The median NSQIP-P UTI rate at SCHN was reduced by 47.4% from 1.75% in 2019 to 0.9% in 2022. A multifactorial approach in quality improvement has been shown to be an effective strategy to reduce UTI rates at SCHN, and patient outcomes were improved within a 3-year timeframe. Although this project has reduced UTI rates at SCHN, there remain opportunities for further improvement.

Kidney scoring surveillance: predictive machine learning models for clear cell renal cell carcinoma growth using MRI.

Classification of clear cell renal cell carcinoma (ccRCC) growth rates in patients with Von Hippel-Lindau (VHL) syndrome has several ramifications for tumor monitoring and surgical planning. Using two separate machine-learning algorithms, we sought to produce models to predict ccRCC growth rate classes based on qualitative MRI-derived characteristics. We used a prospectively maintained database of patients with VHL who underwent surgical resection for ccRCC between January 2015 and June 2022. We employed a threshold growth rate of 0.5cm per year to categorize ccRCC tumors into two distinct groups-'slow-growing' and 'fast-growing'. Utilizing a questionnaire of qualitative imaging features, two radiologists assessed each lesion on different MRI sequences. Two machine-learning models, a stacked ensemble technique and a decision tree algorithm, were used to predict the tumor growth rate classes. Positive predictive value (PPV), sensitivity, and F1-score were used to evaluate the performance of the models. This study comprises 55 patients with VHL with 128 ccRCC tumors. Patients' median age was 48years, and 28 patients were males. Each patient had an average of two tumors, with a median size of 2.1cm and a median growth rate of 0.35cm/year. The overall performance of the stacked and DT model had 0.77 ± 0.05 and 0.71 ± 0.06 accuracies, respectively. The best stacked model achieved a PPV of 0.92, a sensitivity of 0.91, and an F1-score of 0.90. This study provides valuable insight into the potential of machine-learning analysis for the determination of renal tumor growth rate in patients with VHL. This finding could be utilized as an assistive tool for the individualized screening and follow-up of this population.

Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport.

Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photodynamic therapy (PDT) via a laser coupled balloon device, is demonstrated. To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome. We use Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. Treatment parameters (laser power, photosensitizer concentration, and irradiation time) are considered, as well as PDT's impact on brain tissue temperature. The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence = at balloon wall) and assuming an initial photosensitizer concentration of . Increases in treatment time and light power (light fluence = at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the p hotosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration to and keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. To improve treatment outcome, focus should be placed on improving the photosensitizer. With further development and optimization, the simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.

Current Photodynamic Therapy for Glioma Treatment: An Update.

Research on the development of photodynamic therapy for the treatment of brain tumors has shown promise in the treatment of this highly aggressive form of brain cancer. Analysis of both in vivo studies and clinical studies shows that photodynamic therapy can provide significant benefits, such as an improved median rate of survival. The use of photodynamic therapy is characterized by relatively few side effects, which is a significant advantage compared to conventional treatment methods such as often-used brain tumor surgery, advanced radiotherapy, and classic chemotherapy. Continued research in this area could bring significant advances, influencing future standards of treatment for this difficult and deadly disease.

(327) Adverse Event Reporting in Testosterone Therapy Randomized Controlled Trials (RCT)

Abstract Introduction Testosterone (T) therapy (TTH) is associated with well recognized adverse events (AEs) such as: polycythemia (PCT), major adverse cardiac events (MACE), gynecomastia (GYN), worsening obstructive sleep apnea (OSA). Objective We aimed to critically analyze published TTH RCTs with regard to how well TTH AEs were reported. Methods A literature review was performed of all TTH RCTs listed on PUBMED that had been published between 1997-2021. We describe sample size, trial duration, industry funding, T assay used, baseline and on-treatment total and free T, TTH modality, and mean follow-up during the RCTs. We also describe the reporting of PCT, GYN, MACE, OSA and the definitions used in these RCTs. Results 29 trials were reviewed (Table 1), 55% reported on transdermal T, 41% intramuscular T, 7% enclomiphene, 7% human chorionic gonadotropin and 7% other oral treatments (aromatase inhibitor, tamoxifen). 17% compared two TTH modalities. Median sample size was 73 [41, 189]. Median age was 63 [58, 67] years. Median follow-up in the RCT reported was 8 [6, 12] months. 55% had the support of pharmaceutical companies. The total T (TT) assay used was immunoassay (IA 59%), LCMS (24%), other (10%), while 7% did not report on the assay type, and only 55% reported free T level (79% calculate by Vermeulen formula, and 21% equilibrium dialysis). Median baseline TT level was 248 [227, 320] ng/dL; on TTH it was 528 [460, 621] ng/dL. Median baseline free T level was 5.4 [5, 6.3] ng/dL, on TTH it was 11.1 [9.3, 15.5] ng/dL. 83% measured HCT levels at any point, only 21% reported baseline levels, 24% reported post treatment. Median baseline HCT 43 [42, 46]%, post-TTH median HCT increase of 2.4[-2.5, +3]%. 52% reported on PCT rates (45% defined HCT >52%, 7% HB >17 g/dL). Median PCT rate was 2%, none mentioned phlebotomy. 17% of RCTs reported on GYN, with a median rate of 1.5%, while none mentioned GYN grade or if mammography had been performed. 17% of trials mentioned MACE, but only 2 defined MACE. Median MACE rate was 2%. 10% reported OSA, but none mentioned the type of assessment; the median rate was OSA 2%. Conclusions This analysis showed that the majority TTH RCTs have sub-optimal reporting of TTH safety. Disclosure No.

Central Arctic Ocean surface–atmosphere exchange of CO2 and CH4 constrained by direct measurements

Abstract. The central Arctic Ocean (CAO) plays an important role in the global carbon cycle, but the current and future exchange of the climate-forcing trace gases methane (CH4) and carbon dioxide (CO2) between the CAO and the atmosphere is highly uncertain. In particular, there are very few observations of near-surface gas concentrations or direct air–sea CO2 flux estimates and no previously reported direct air–sea CH4 flux estimates from the CAO. Furthermore, the effect of sea ice on the exchange is not well understood. We present direct measurements of the air–sea flux of CH4 and CO2, as well as air–snow fluxes of CO2 in the summertime CAO north of 82.5∘ N from the Synoptic Arctic Survey (SAS) expedition carried out on the Swedish icebreaker Oden in 2021. Measurements of air–sea CH4 and CO2 flux were made using floating chambers deployed in leads accessed from sea ice and from the side of Oden, and air–snow fluxes were determined from chambers deployed on sea ice. Gas transfer velocities determined from fluxes and surface-water-dissolved gas concentrations exhibited a weaker wind speed dependence than existing parameterisations, with a median sea-ice lead gas transfer rate of 2.5 cm h−1 applicable over the observed 10 m wind speed range (1–11 m s−1). The average observed air–sea CO2 flux was −7.6 mmolm-2d-1, and the average air–snow CO2 flux was −1.1 mmolm-2d-1. Extrapolating these fluxes and the corresponding sea-ice concentrations gives an August and September flux for the CAO of −1.75 mmolm-2d-1, within the range of previous indirect estimates. The average observed air–sea CH4 flux of 3.5 µmolm-2d-1, accounting for sea-ice concentration, equates to an August and September CAO flux of 0.35 µmolm-2d-1, lower than previous estimates and implying that the CAO is a very small (≪ 1 %) contributor to the Arctic flux of CH4 to the atmosphere.

Abstract TP131: Computed Tomography Perfusion Imaging Patterns Are Similar Before and After Interfacility Transfer of Ischemic Stroke Patients

Background: Large vessel occlusion (LVO) stroke patients are often transferred from regional hospitals to comprehensive stroke centers (CSC) for thrombectomy. The need for repeat imaging at CSCs prior to intervention is unclear. We compared regional hospital and CSC perfusion imaging results for interfacility transfers in a single health system. Methods: We analyzed a cohort of patients in western Michigan who received CT perfusion imaging before and after transfer to a CSC. Perfusion mismatch (MM), core infarct volume (CIV), and favorability of imaging for mechanical thrombectomy (MT) candidacy were compared between the regional and CSC studies. A favorable imaging profile was defined as the presence of LVO, MM volume >10 mL, and MM/CIV ratio of >1.2. Linear regression was used to examine predictors of infarct growth during transfer. Results: Over a 10-month period, 25 patients met inclusion criteria. The median age was 76 (IQR 66-81), 60% were male, median NIHSS was 11 (IQR 2-18), and most patients had occlusion of the internal carotid or middle cerebral arteries (72%). The median time from last known well to initial CT was 250 minutes (IQR 85-620). Regional median MM volume was 52 mL (IQR 8-97), CIV was 0 mL (IQR 0-13), and hypoperfusion intensity ratio (HIR) was 0.25 (IQR 0-0.34). The median time between CTs was 152 minutes (IQR 139-226). The median change in MM volume was -3 mL (IQR -27-3) and median CIV growth rate was 0 mL/hr (IQR 0-2.0). In a multivariable regression model, higher HIR (β=23.2, p=0.012) and minutes between imaging studies (β=0.10, p=0.021) were associated with CIV growth. Sixteen patients (64%) had favorable imaging profiles for MT at the regional hospital. Of these, 15 (93.8%) continued to have a favorable CSC imaging profiles and 9 (56.2%) underwent MT. Of the 9 patients without favorable regional imaging profiles, 1 (11.1%) had a favorable CSC imaging profile and 2 (22.2%) underwent MT. Conclusion: In our sample, regional and CSC perfusion imaging patterns were similar and patients infrequently crossed thresholds for MT candidacy between studies. Initial HIR and longer delays between were independently associated with infarct growth during transfers, however overall infarct growth was very small.

Is it resectable? A survey regarding tumor classification and vascular involvement

IntroductionThe anatomic location of the pancreas can result in involvement of major vasculature, which may act as a contraindication to resection. Several classification systems have been developed. We sought to discover the variations in the HPB community determining PDAC resectability. MethodsThe multiple-choice survey was distributed to all full members of the IHPBA. Questions were asked regarding demographics and clinical scenarios regarding tumor resectability. Results164 responses were submitted. Most of the respondents were male and had been in practice for over 10 years. The median age range was 40–50 years old. Most practiced in either Asia (n = 57,35.9%), North America (n = 52,32.7%), or Europe (n = 32,20.1%).Classification systems used to determine resectability were: NCCN (n = 42,26.3%), JPS (n = 35,21.9%), International consensus (n = 33,20.6%), AHPBA/SSO (n = 23,14.4%), Alliance (n = 3,1.9%), and other/no-classification (n = 23,14.5%).There was significant variation in the frequency of the most common answer within the scenarios (84.7%–33.5%). Participant concordance with their stated classification system found a median rate of 62.5%. Participant decision of tumor resectability was not dependent on their adopted classification system. ConclusionWhen classifying PDAC resectability, there is significant variation between surgeons as to how they would classify a specific tumour, independent of the classification system they use. In addition, surgeons do not show high concordance with the definitions within that classification system.

Recurrence following Resection of Intraductal Papillary Mucinous Neoplasms: A Systematic Review to Guide Surveillance

Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies based on the risk of recurrence. We performed a systematic review of the current literature regarding recurrence patterns following resection of non-invasive IPMN to summarize evidence-based recommendations for surveillance. Among the 61 studies reviewed, a total of 8779 patients underwent resection for non-invasive IPMN. The pooled overall median follow-up time was 49.5 months (IQR: 38.5–57.7) and ranged between 14.1 months and 114 months. The overall median recurrence rate for patients with resected non-invasive IPMN was 8.8% (IQR: 5.0, 15.6) and ranged from 0% to 27.6%. Among the 33 studies reporting the time to recurrence, the overall median time to recurrence was 24 months (IQR: 17, 46). Existing literature on recurrence rates and post-resection surveillance strategies for patients with resected non-invasive IPMN varies greatly. Patients with resected non-invasive IPMN appear to be at risk for long-term recurrence and should undergo routine surveillance.

Fish stranding in relation to river bar morphology and baseflow magnitude: Combining field surveys and hydrodynamic–numerical modelling

AbstractHydropeaking mitigation based on down‐ramping thresholds is crucial to avoid stranding of fish and ensure sustainable hydropower production. However, the risk of stranding is influenced by several biotic and abiotic factors that interact with the ramping rate, including river morphology and baseflow magnitude. Also, at the river bar scale, the lateral or horizontal down‐ramping velocity may be of even greater importance than the vertical one as the prior integrates bar morphology. This study investigates the connection between ecologically relevant hydraulic parameters (vertical and lateral ramping velocity, dewatered river bar width) and the stranding of young‐of‐the‐year European grayling (Thymallus thymallus) due to down‐ramping, based on field observations of stranded fish at the hydropeaked Drava River in Austria combined with hydrodynamic–numerical modelling. We also examine the interplay between baseflow conditions and river topography in the dewatered areas. Stranding observations in spring and summer found a median rate of 90 individuals per 100 m, ranging from 50 to 500 fish per 100 m shoreline. Stranding rates were three times higher at night than during the day. Our data revealed a positive relationship between stranded fish and down‐ramping hydraulics, with higher intensity resulting in more stranded fish. This association was stronger for the lateral than the vertical ramping velocity, presumably because the former accounts for bar morphology, suggesting that the lateral dewatering velocity is a better indicator to assess fish stranding at the bar scale than the vertical velocity. We also found a negative relationship between the extent of the dewatered area and baseflow magnitude, indicating that the stranding risk is higher during down‐ramping at low flow conditions.

P903 Persistence, efficacy and tolerance of subcutaneous Infliximab after switch from intravenous infliximab in IBD patients in remission: one-year results from a multicenter prospective cohort

Abstract Background Prospective data after switch from intravenous infliximab (IV-IFX) to subcutaneous (SC-IFX) in Inflammatory Bowel Disease (IBD) is needed. The aim of this prospective multicenter cohort was to describe SC-IFX persistence, efficacy and tolerance after switch from IV-IFX. Methods IBD patients in steroid-free clinical remission (defined by a Harvey Bradshaw index (HBI) ≤ 4 for Crohn’s disease (CD), and partial Mayo Score (PMS) ≤ 2 with no subscore >1 for ulcerative colitis UC)) for at least 6 months on IV-IFX, were enrolled in this prospective cohort if they switched to SC-IFX. Clinical (HBI, PMS), biological (CRP, fecal calprotectin (FC)) and pharmacokinetic evaluations were performed at 3, 6, 12 and 24 months from switch. In case of clinical or biological relapse, as per physicians’ judgement, SC-IFX dose could be increased, or drug changed. Primary endpoint was SC-IFX persistence at week 48 (W48). Secondary endpoints comprised steroid-free clinical remission at W48, proportion of patients who switched back to IV-IFX, HBI and PMS changes and FC, CRP and infliximab serum level changes. Statistical comparisons were performed using Fisher’s exact test. Survival without treatment discontinuation was analysed using a Kaplan-Meyer curve. Results 426 patients were included (72.4% CD, 45.1% female, median age 37 years), with a median time from diagnosis of 143 months in CD, 154 months in UC. At baseline, 74% were on IV-IFX standard dose (5mg/kg every 8-week) and 68 (16%) received combination therapy with an immunosuppressant. Among patients with complete data until W48, SC-IFX persistence was 95.3% (CI, 93.2-97.5). 319/367 (89.9%) were on steroid-free clinical remission. From baseline to W48, median HBI and PMS scores were 0, CRP did not change significantly, median FC rate decreased significantly from 52µg/g to 36 µg/g (p=0.015). Mean Infliximab trough level at inclusion was 7.97µg/mL, while it reached 17.96µg/mL at W48 (p<0.0001). 23 (5.4%) patients had an increase of SC-IFX dose and 22 (5.2%) stopped SC-IFX, of which 6 patients switched back to IV-IFX. SC-IFX persistence was significantly higher among patients treated with SC-IFX monotherapy (98.8%) as compared to those on combination therapy (90.0%) (HR=0.14 [0.04-0.53]). Adverse events were reported in 181/426 patients (42.4%), 12 led to treatment discontinuation. Nine severe adverse events (2%) were reported. Three patients (0.7%) had IBD-related surgery and 8 (1.9%) IBD-related hospitalization. Conclusion In this large multicenter prospective cohort of IBD patients in remission, one-year persistence of SC-IFX after switch from IV-IFX was 95.3%, supporting excellent efficacy and tolerance of SC-IFX.

P763 Rare and severe adverse events in pediatric inflammatory bowel disease: identification of safety signals through the international prospective PIBD-SETQuality Safety Registry

Abstract Background Rare but severe adverse events (AEs) can occur in pediatric inflammatory bowel disease (PIBD) due to ongoing inflammation, secondary to immunosuppressive drugs or as coincidental finding. These events can lead to significant disability or even death. Limited prospective research hampers the understanding of the incidences, risk factors, and outcomes associated with these events. Methods As part of the ongoing international PIBD-SETQuality Safety Registry, participating pediatric gastroenterologists prospectively reported the occurrence of any of 10 listed rare and severe AEs in their PIBD patient population (<19 years) via monthly electronic surveys since October 2016. Additionally, physicians could report ‘other rare and severe AEs’. Participants received an annual denominator survey, to report the number of PIBD patients under their care. Incidence rates (IRs) were calculated for each AE using Poisson regression models and were compared between countries. Upon reporting AEs, participants received specific follow-up forms to collect patient and IBD characteristics, as well as complication details (diagnosis, risk factors, management, outcome). Results Over a 77-month study period (October 2016 to April 2023), 222 pediatric gastroenterologists from 167 centers across 36 countries actively contributed to the registry, completing 7,975 monthly surveys with a median response rate of 86% [IQR 82%-88%]. On average, participants contributed for 53 months [IQR 25-72]. They covered 30,192 PIBD patients, with 114,528 patient-years (PY) of follow-up. In total, 285 listed complications were reported, alongside 117 uncategorized ‘other rare and severe AEs’. The highest IRs (95%CI) per 10,000 PY were found for VTE (IR 5.50 [2.74-4.99]), renal failure (IR 3.67 [2.67-4.89]), opportunistic infections (IR 2.88 [2.01-3.98]), and cancer (IR 2.71 [1.86-3.77]) (Figure 1). The lowest IRs (95%CI) per 10,000 PY were found for liver failure (IR 0.35 [0.11-0.81]) and HLH (IR 0.52 [0.21-1.06]). Combined IRs of the listed AEs did not differ among the five countries with the highest contribution of PY (p=0.18). Conclusion Through international collaboration among a large network of PIBD specialists, the Safety Registry has confirmed the increased incidence of several AEs in PIBD, including VTE, cancer and renal failure. Clinical characterization of these events may lead to a better understanding of their underlying etiologies and outcomes. This improves patient care by providing guidance for management development, facilitating well informed clinical decision making and may lead to prevention of these rare and severe events.

Examining County-Level Associations between Federally Qualified Health Centers and Sexually Transmitted Infections: A Political Ecology of Health Framework.

Federally Qualified Health Centers (FQHCs) are the largest providers of healthcare for sexually transmitted infections (STIs) in medically underserved communities in the United States (US). Through the Affordable Care Act (ACA), FQHCs have grown in number, but the impact of this growth on STIs is poorly understood. This ecological study seeks to quantify the association between FQHCs and STI prevalence in all US counties. Variables were described utilizing medians and interquartile ranges, and distributions were compared using Kruskal-Wallis tests. Median rates of chlamydia in counties with high, low, and no FQHCs were 370.3, 422.6, and 242.1 cases per 100,000 population, respectively. Gonorrhea rates were 101.9, 119.7, and 49.9 cases per 100,000 population, respectively. Multivariable linear regression models, adjusted for structural and place-based characteristics (i.e., Medicaid expansion, social vulnerability, metropolitan status, and region), were used to examine county-level associations between FQHCs and STIs. Compared to counties with no FQHCs, counties with a high number of FQHCs had chlamydia rates that were an average of 68.6 per 100,000 population higher (β = 68.6, 95% CI: 45.0, 92.3) and gonorrhea rates that were an average of 25.2 per 100,000 population higher (β = 25.2, 95% CI: 13.2, 37.2). When controlled for salient factors associated with STI risks, greater FQHC availability was associated with greater diagnosis and treatment of STIs. These findings provide empirical support for the utility of a political ecology of health framework and the critical role of FQHCs in confronting the STI epidemic in the US.

P413 Bowel Urgency in patients with Ulcerative Colitis: prevalence and association with clinical, endoscopic data and disability

Abstract Background Bowel urgency (BU), identified as the sudden need for bowel movements, is increasingly being recognized as an impactful symptom in patients with ulcerative colitis (UC), distinct from stool frequency (SF) and rectal bleeding (RB). We aimed to assess the association of BU with patient-reported outcomes (PRO), including SF and RB, as well as clinical and endoscopic activity and disability in a real-world setting, using data from the IBD-Disk:Italian translation and validation study. Methods We conducted a cross-sectional multicentre study, consecutively including ≥ 18yo UC patients between February 2023 and October 2023. Demographic, clinical and endoscopic data were collected. Clinical remission was defined as partial Mayo score ≤ 1 and endoscopic activity as MES ≥ 1. All patients completed the following questionnaire for disability IBD-Disk and IBD Questionnaire-32 (IBDQ-32) for quality of life. BU was assessed using the question about regulating defecation in the past 7 days using a 10-point NRS ranging from 0 (absolutely disagree) to 10 (totally agree) from the IBD-DISK. RB was measured from question 22 of IBDQ and SF from question 1 of IBDQ-32, both using a 7-point NRS ranging from 0 (always) to 7 (never). Results 209 UC patients with a median age of 37(IQR 28-52) were enrolled, 111(53.1%) being female. Overall, 31 (14.8%) had proctitis, 91(45.5%) had left colitis and 87(41.6%) had extended/pancolitis. The median pMAYO score was 4(IQR=2-6), while the median MES was 2(IQR=1-2). 75% patients (35.9%) reporting BU were more likely to have moderate clinical (pMAYO=5; IQR=3-6) and endoscopic activity of disease (median MES=2; IQR=1-2) compared to those without urgency (p< .0001). Additionally, BU was associated with a higher median rate of hospitalizations in the previous 12 months (Δ=1; p<0.001).Patients with BU reported a higher degree of RB(33.3%) and SF(50,7%) than patients without BU (p< .0001).Noteworthy, individuals with BU had higher median IBD-DISK total score (29; IQR=9-52) and lower scores for IBDQ-32 (168;IQR=138-196) compared to patients without BU [median IBD-DISK=17(IQR=5-39); median IBDQ-32=181,IQR=158-202), p<0.001]. In the univariate analysis, BU was associated with a higher IBD-DISK total score (OR=1.04,CI=1.02-1.06; p<0.001) and SF (OR=0.59,CI=0.45-0.78; p=0.001), without being associated with RB (p=0.57) and IBD-Q32 total score (p=0.84). Conclusion BU can be a surrogate marker for UC clinical and endoscopic activity. Our findings suggest that it is an independent factor from RB and it is associated with disability. Hence, it can be considered as an additional key PRO in UC. However, a systematic standardized approach for BU definition and assessment is strongly awaited to incorporate it as treat-to-target measure

A Systematic Review on Clinical and Health-Related Quality of Life Outcomes following Total Gastrectomy in Patients with Hereditary Diffuse Gastric Cancer

Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant syndrome associated with early onset diffuse gastric cancer. Definitive treatment is prophylactic total gastrectomy (PTG) associated with significant morbidity. Studies published from January 2000 to December 2022 reporting clinical, histopathological or health-related quality of life outcomes in HDGC patients undergoing PTG were identified. The study quality was assessed by the “Newcastle–Ottawa scale”. Of the 257 articles screened, 21 were selected. A total of 353 patients were examined in 15 studies that reported surgical outcomes. The median age was 42 years old. The median major complication and mortality rates were 19.2% and 0.3%, respectively. The most common complications were wound infection at 4.8% followed by anastomotic leak and pulmonary complications at 4.5% each. Following PTG, 88.6% of patients had early lesions amongst 414 patients. The mean/median number of signet ring cell carcinoma foci in the gastrectomy specimens was from 2 to 78. All cases were stage 1 with no lymph node involvement. There was a wide range of psychosocial effects following PTG closely related to the physical symptoms. It is imperative for patients to receive comprehensive preoperative counselling to make an informed decision and be followed up under the care of a multidisciplinary team.

1877 Recruitment to a phase 3, RCT in Parkinson’s: strategies and association between participant characteristics and PI specialty

Abstract Introduction Falls are a common complication of Parkinson’s disease, driven in part by an underlying cholinergic deficit that contributes to gait and cognitive impairment. Phase 2 studies have established that amelioration of this deficit using cholinesterase inhibitors may reduce falls. Methods CHIEF-PD (CHolinesterase Inhibitor to prEvent Falls in Parkinson's Disease) is a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease that recruited from NHS sites. Relationships between the Principal Investigators’ specialty and the participants baseline characteristics were evaluated using linear, logistic and ordinal logistic regression. Cognitive impairment was defined as MoCA ≤26, while falls in the prior 12 months were separated into ordinal quartiles (1-2, 3-5, 6-12, 13+). Results Recruitment to CHIEF-PD commenced in January 2020 and completed in April 2023. Recruitment increased up until the start of the pandemic and thereafter there were 2 peaks. Potential participants were identified through clinic lists, databases, via national and local media and charities. 600 participants were enrolled across 38 sites. Sites enrolled between 1 and 74 participants, each. The median recruitment rate was 19 participants per month (IQR 6-27). 14 (37%) sites had Principal Investigators that were neurologists and 24 (63%) sites had PIs that were geriatricians. Most participants (76%) were over the age of 65 years. Compared with neurologists, geriatricians recruited older patients (difference in means 2.08 (95% CI 0.68, 3.48); p=0.004), with similar levels of cognitive impairment (OR 1.20 (95% CI 0.85, 1.69); p=0.293) and a lower fall rate (OR 0.46 (95% CI 0.34, 0.62); p<0.001) at baseline. Conclusion Recruitment of older participants to a Clinical Trial of an Investigational Medicinal Product (CTIMP) trial throughout the Covid-19 pandemic across 38 UK centres was feasible using multiple strategies. Characteristics of participants varied according to the sub-speciality of the Principal Investigator at the site.

Efficacy and pharmacoeconomic advantages of Fufang Huangbai Fluid hydropathic compress in diabetic foot infections: a comparative clinical study with antimicrobial calcium alginate wound dressing.

Objective: To compare the intervention effects and pharmacoeconomic advantages of Fufang Huangbai Fluid (FFHB) hydropathic compress versus Antimicrobial Calcium Alginate Wound Dressing (ACAWD) in the treatment of diabetic foot infections (DFI). Methods: Patients with DF who were hospitalized in the peripheral vascular Department of Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2020 to February 2022 and met the inclusion and excluding criteria were allocated into the experimental group and control group through minimization randomization. The experimental group was treated with FFHB hydropathic compress for 2weeks, while the control group was treated with ACAWD for the same duration. The wound healing of both groups was monitored for 1month post-discharge. Clinical data from all eligible patients were collected, and differences in various indices between cohorts were analyzed. Results: 22 in the experimental group (including two fell off) and 20 in the control group. After the treatment, the negative rate of wound culture in the experimental group was 30% and that in the control group was 10%, There was no significant difference in the negative rate of wound culture and change trend of minimum inhibitory concentration (MIC) value of drug sensitivity (p > 0.05). The infection control rate of the experimental group was 60%, and that of the control group was 25%. The difference between the two groups was statistically significant (χ2 = 5.013, p = 0.025). The median wound healing rate of the experimental group was 34.4% and that of the control group was 33.3%. There was no significant difference between the two groups (p > 0.05). During the follow-up 1month later, the wound healing rate in the experimental group was higher, and the difference was statistically significant (p = 0.047). Pharmacoeconomic evaluations indicated that the experimental group had greater cost-effectiveness compared to the control group. Conclusion: In the preliminary study, FFHB demonstrated comparable pathogenic and clinical efficacy to ACAWD in the treatment of mild DF infection, and exhibited superior pharmacoeconomic advantages. With the aid of infection control, the wound healing rate in the FFHB group showed notable improvement. Nevertheless, due to the limited sample size, larger-scale studies are warranted to further validate these findings. Clinical Trial Registration: (https://www.chictr.org.cn/showproj.aspx?proj=66175), identifier (ChiCTR2000041443).

Identification of Glandular (Acinar)/Tubule Formation in Invasive Carcinoma of the Breast: A Study to Determine Concordance Using the World Health Organization Definition.

The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

A phase I/II study of antroquinonol in combination with nab-paclitaxel and gemcitabine for patients with metastatic pancreatic cancer.

648 Background: The survival of metastatic pancreatic cancer (mPC) is still disappointing though advancement in recent regimens. Antroquinonol, a new chemical entity, has been proposed for the treatment of neoplasms. In this phase I/II trial, we investigated the dose and efficacy of antroquinonol combined with gemcitabine and nab-paclitaxel (Gem/Nab-P) on mPC patients. Methods: Patients with chemo-naive, metastatic PDAC were enrolled. In the phase I, run-in drug-drug interaction (DDI) and dose escalation in a 3 + 3 designed to determine the maximal tolerated dose (MTD) of antroquinonol for phase II study. Gem/Nab-P (gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8, and 15 every 4 weeks) was given from cycle 0 in phase I. The dose of antroquinonol was escalated from 200mg orally three times a day since the first cycle of Gem/Nab-P. The primary end points were median PFS and 6-month PFS rate. This trial is registered at ClinicalTrials.gov: NCT03310632. Results: In the phase I study of 15 patients, the MTD of antroquinonol was 300mg tid. In the phase II study of 40 patients, the median PFS was 5.3 (95% CI: 3.7–7.5) months and 6-month PFS rate was 40% (95% CI: 21%–57%), whereas median OS was 12.6 (95% CI: 8.8–15.8) months and12-month OS rate was 59.9% (95% CI: 37.8%–76.4%), respectively. The adverse events including hematological and non-hematological classes were decreased in the antroquinonol plus Gem/Nab-P, the GI discomforts were increased but manageable. Conclusions: In this phase I/II trial, antroquinonol plus Gem/Nab-P showed good efficacy in survival and less adverse events than a first-line strategy of Gem/Nab-P for mPC patients. Clinical trial information: NCT03310632 . [Table: see text]