Increase In Grade Research Articles

Hepatotoxicity following external radiotherapy in patients with hepatocellular carcinoma treated with or without prior yttrium-90 radioembolization.

564 Background: A variety of local therapy options exist to treat Hepatocellular Carcinoma (HCC) including external radiotherapy (EBRT). Prior yttrium-90 (Y90) delivered transarterially is often a contraindication to EBRT in clinical trials and guidelines due to concerns of cumulative hepatotoxicity, though clinical data to suggest higher rates of hepatotoxicity is limited. This study examines hepatotoxicity profiles after EBRT with and without prior Y90 treatment using the ALBI grading system. Methods: Patients treated for HCC with EBRT from 2016 to 2024 with sufficient laboratory follow-up were retrospectively reviewed. Patients were classified into three ALBI grades based on ALBI scores: 1 (< -2.6), 2 (-2.6 < x < -1.39), and 3 (> -1.39). The total EBRT dose was defined using the EQD2 method (α/β = 10). The ALBI scores at 3- and 6-months post-EBRT were compared to baseline for patients with or without prior Y90 using paired t-tests. The main RT planning goal was ≥700 cc liver- (tumor volume+ Y90 volume) receiving ≤15 Gy. Results: 62 patients were treated with EBRT with (n=14) or without (n=48) prior Y90. At 6-months post-EBRT, 11 patients with prior Y90 and 39 patients without prior Y90 had appropriate laboratory follow-up. EBRT dose, technique, and baseline liver function are outlined in Table 1. The median time from Y90 to EBRT was 12.3 months (range 4-61 months). In patients with prior Y90, ALBI scores were similar at 3-mo (mean = -2.4 SD = 0.8, vs mean= -2.4 SD = 0.7, p= 0.60) and 6-mo (mean= -2.3 SD= 0.9, vs mean = -2.4 SD = 0.6, p= 0.653) post-EBRT compared to baseline, respectively. In patients without Y90, ALBI scores were clinically similar at 3-mo (mean = -2.2 SD = 0.7, vs mean= -2.3 SD = 0.6, p= 0.15) and 6-mo (mean= -2.1 SD= 0.8, vs mean = -2.3 SD = 0.7, p=0.021) post-EBRT compared to baseline, respectively. The proportion of patients with an increase in ALBI grade at 3- and 6-mo post-EBRT was similar regardless of prior Y90 treatment. In patients treated with Y90, 14.3% and 36.4% had an increase in ALBI grade at 3- and 6-months, respectively. In those treated without prior Y90, 21.3% and 35.9% had an increase in ALBI grade at 3- and 6-months, respectively. Conclusions: Patients with HCC treated with EBRT after Y90 appear to have a similar rate of hepatotoxicity defined by the ALBI grading system compared to patients treated without prior Y90. In well-selected patients, prior Y90 should not be an absolute contraindication for EBRT. Demographics and ALBI changes post-EBRT. EBRT alone (n = 48) EBRT after Y90 (n = 14) Median Age Years (range) 67.6 (17.9-84.3) 65.6 (55.1-85.2) Proton, IMRT/SBRT 22 (46%), 26 (54%) 9 (64%), 5 (36%) Baseline Child Pugh Score (A, B, C) 34 (70.8%), 10 (20.8%), 4 (8.4%) 11 (78.6%), 3 (21.4%), 0 (0%) Median EBRT EQD2 (range) 82 Gy (44-99) 82 Gy (67-86) Baseline ALBI Grade (1, 2, 3) 23 (47.9%), 20 (41.7%), 5 (10.4%) 6 (42.9%), 7 (50%), 1 (7.1%)

« Augmented radiotherapy » in the management of high-risk prostate cancer (PCa): A systematic review.

In patients with high-risk (HR) prostate cancer (PCa) treated with radiotherapy and androgen deprivation therapy (ADT), intensification with androgen receptor pathway inhibitor (ARPI) improves overall survival (OS), at the cost of significant side-effects. We hypothesized that "augmented RT" schedules (defined as either dose-escalation on the prostate gland over 78 Gy and/or addition of whole pelvic radiotherapy (WPRT)), combined with long-term ADT can reach excellent prostate cancer specific survival (PCSS) in this population with little detrimental impact on quality of life. We searched Pubmed database until February 8, 2024. Studies reporting both oncological and toxicity outcomes after "augmented RT" were deemed eligible. Studies without ADT or with ARPI intensification were deemed ineligible. Dose-escalation within the prostate gland at doses over 78 Gy halved the risk of biochemical recurrence at 5 years, with however no impact on PCSS. The addition of WPRT provides a 5-year disease-free survival (DFS) reaching 89.5 % at 5 years, with no significant increase in late grade≥ 2 genito-urinary (GU) or gastrointestinal (GI) toxicity. Combined approaches result in 9-year PCSS ranging between 96.1 % and 100 %. Most approaches demonstrated excellent safety profiles. "Augmented RT" reached excellent oncological outcomes, with minimal additional toxicity. The development of biomarkers might lead to further treatment personalization, in the rapidly evolving landscape of systemic therapies.

Studies of the expansion mechanism on different pellets under hydrogen-rich reducing atmosphere

ABSTRACT In response to the need to develop green low-carbon iron smelting technology, blast furnace hydrogen reduction technology is of great significance for reducing CO2 emissions from the ironmaking system. This study focuses on the change in swelling behaviour of different types of pellets during the blast furnace hydrogen smelting process. It analyses the reduction swelling index (RSI/%) and compression strength before and after reduction at 900°C in a variety of reduction gas atmospheres, among other indices. The results show that under the condition of ore grade, the reduction expansion rate of pellet increases with the increase of grade. With the increase of basicity (R) (0 ∼ 0.25) and the Mg-Al ratio (M/A) (0.4 ∼ 1.4), the reduction in expansion of the pellet shows an upward trend. However, the RSI/% shows a downward trend with the increase of the synergistic effect of ore silicon and aluminium (S + A). The compression strength after reduction increases to different degrees with the increase of the proportion of hydrogen in the reduction atmosphere; the maximum increase was about 0.591 KN. SEM-EDS detection was carried out on pellet in different reduction atmospheres, and the structure and component changes of various regions during the reduction process were analysed.

Feasibility study for evaluating cervical intervertebral disc degeneration using axial diffusion tensor imaging.

Intervertebral disc (IVD) degeneration is the main cause of neck pain. Although conventional magnetic resonance imaging can detect morphological changes in intervertebral disc degeneration, it cannot provide accurate and objective evaluations. Magnetic resonance diffusion tensor imaging (DTI) reflects the microstructural changes in tissues by describing the diffusion of water molecules. It was initially applied to the evaluation of lumbar disc degeneration; however, no study has used DTI to evaluate cervical disc degeneration. To conduct a prospective study to evaluate the efficacy and feasibility of DTI in quantifying cervical disc degeneration by correlating the main parameters of axial DTI of intervertebral discs, namely fractional anisotropy (FA) and mean diffusivity (MD) values, using the Pfirrmann grade. The cervical discs of 30 symptomatic volunteers with neck pain and 20 asymptomatic volunteers were assessed using a 3.0 T magnetic resonance scanner. We evaluated intervertebral discs from C3/4 to C6/7 in each volunteer. The Pfirrmann grades, FA value, and MD value on the conventional magnetic resonance imaging were evaluated. The Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare the FA and MD values of subjects with different degeneration levels. Statistical analysis showed that the FA value of the nucleus pulposus in patients group was significantly higher than that in the asymptomatic volunteers, and the MD value of the nucleus pulposus was significantly lower than that in the asymptomatic volunteers, and the difference was significant (P < 0.05). In the study group, with an increase in cervical intervertebral disc grade, the FA value of the nucleus pulposus also showed a gradual upward trend, and this difference was significant (P < 0.05). The MD value of the nucleus pulposus showed a gradual downward trend, except between grades I and II, which indicates that the axial FA value can better show the early pathological changes of the cervical intervertebral disc. The FA and MD values of the cervical intervertebral disc can quantitatively evaluate the degree of degeneration of the cervical intervertebral disc; axial DTI imaging technology can provide a good theoretical basis for the imaging diagnosis of cervical intervertebral disc degeneration and has important clinical application value.

Northern Scandinavian mountains supported by a low-grade eclogitic crustal keel

Plate tectonics predicts that mountain ranges form by tectono-magmatic processes at plate boundaries, but high topography is often observed along passive margins far from any plate boundary. The high topography of the Scandes range at the Atlantic coast of Fennoscandia is traditionally assumed isostatically supported by variation in crustal density and thickness. Here we demonstrate, by our Silverroad seismic profile, that the constantly ~44 km thick crust instead is homogenous above the Moho, and Pn-velocity abruptly change from 7.6 km s−1 below the Scandes to >8.2 km s−1 below the Proterozoic shield. By modelling gravity anomalies and topography, based on the seismic model, we demonstrate that this change corresponds to an increase in metamorphic eclogitic grade from 35% below the high-topography Scandes to 70% below the low-topography shield. The sharp contrast between the low-grade, reduced-density and the high-grade, high-density eclogitic bodies below the uniform seismological Moho explains the enigmatic topography of the mountain range without a crustal root.

Automated quantification of anterior chamber cells using swept-source anterior segment optical coherence tomography

PurposeTo validate automated counts of presumed anterior chamber (AC) cells in eyes with histories of uveitis involving the anterior segment using swept-source (SS) anterior segment optical coherence tomography (AS-OCT) against manual counts and compare automated counts against Standardized Uveitis Nomenclature (SUN) criteria.MethodsEyes were imaged with the ANTERION SS AS-OCT device (Heidelberg Engineering). A fully automated custom algorithm quantified the number of hyper-reflective foci (HRF) in line-scan images. Automated and manual counts were compared using interclass correlation (ICC) and Pearson correlation coefficient. Automated counts were compared to SUN grades using a mixed-effects linear regression model.Results90 eyes (54 participants) were included; 67 eyes (41 participants) had histories of uveitis, while 23 eyes (13 healthy participants) served as controls. ICC comparing automated to manual counts was 0.99 and the Pearson correlation coefficient was 0.98. Eyes at each SUN grade with corresponding median HRF (interquartile range [IQR]) were: Grade 0, 42 eyes, 2 HRF (0,4); 0.5+, 10 eyes, 10 HRF (8,15); 1+, 9 eyes, 22 HRF (15,33); 2+, 3 eyes, 27 HRF; 3+, 2 eyes, 128 HRF; 4+, 1 eye, 474 HRF. For every 1-step increase in grade, automated count increased by 38 (p < 0.001) or 293% (Pearson correlation coefficient 0.80, p < 0.001). Automated counts differed significantly between clinically inactive eyes (2 HRF [0,4]) and controls (0 HRF [0,1], p = 0.02).ConclusionsOur algorithm accurately counts HRF when compared to manual counts, with strong correlation to SUN clinical grades. SS AS-OCT offers the advantage of imaging of the entire AC and may allow detection of subclinical inflammation in eyes that appear clinically inactive.

Preoperative comprehensive risk estimation for axillary lymph node metastasis in breast cancer: development and verification of a network-based prediction model

To prevent the overaggressive treatment of axillary lymph nodes (ALNs) in breast cancer, it is necessary to develop a convenient analysis method that accurately and comprehensively reflects whether ALNs are metastatic or nonmetastatic. We retrospectively analyzed data from patients who underwent surgery for breast cancer at the Weifang Hospital of Traditional Chinese Medicine between January 2019 and June 2023. Binary logistic regression analysis was used to predict the metastasis status of ALNs. The developmental data set included 531 patients (January 2019–June 2023). The validation set included separate data points (n = 178, January 2019–June 2023). Multivariate analysis revealed that positive findings on breast physical examination, ultrasound grades of ALNs, lymphovascular invasion, and Her-2 status had significant predictive value for metastatic ALNs. Based on these findings, a 5-grade risk scoring system and 3-level management recommendations were developed. The risk of metastasis ranged from 11.25 to 93.46%, which was positively correlated with an increase in risk grade. The areas under the curve of the development and validation sets were 0.895 and 0.865, respectively. Ultimately, a convenient, accurate and comprehensive web-based predictive model was constructed using various breast cancer clinical, imaging and pathological criteria to stratify ALNs according to the metastasis probability.

Risk factors for low back pain after oblique lumbar interbody fusion in patients with low-grade degenerative lumbar spondylolisthesis: a retrospective study.

To investigate the risk factors of low back pain after oblique lumbar interbody fusion (OLIF) in patients with low grade degenerative lumbar spondylolisthesis (DLS). This retrospective study included 116 patients with single-level low-grade lumbar spondylolisthesis with low back pain who underwent OLIF surgery in our hospital from December 2017 to October 2020. Demographic, clinical, surgical, and radiological characteristics of this population were analyzed to determine the relationship between these characteristics and the degree of low back pain relief after OLIF. A total of 116 patients (average age 58.61 ± 7.01 years) were included in this study. Among them, 33 patients had poor improvement of low back pain after surgery, and 83 patients had satisfactory effect after surgery with obvious relief of low back pain. Postoperative disc height increase ≤2.5 mm (P = 0.000) was most correlated with poor improvement of low back pain symptoms after OLIF. The factors positively correlated with poor improvement of low back pain symptoms after OLIF in patients with low-grade degenerative lumbar spondylolisthesis included the increase of spondylolisthesis grade (OR = 17.665; 95%CI: 3.262-95.678 P = 0.001), disc height increase ≤2.5 mm (OR = 34.377; 95%CI: 5.632-209.818 P = 0.000). The factors negatively correlated with poor improvement of low back pain symptoms after OLIF in patients with low-grade degenerative lumbar spondylolisthesis included no osteoporosis (OR = 0.067; 95%CI: 0.013-0.350 P = 0.001), no cage subsidence (OR = 0.208; 95%CI: 0.048-0.903 P = 0.036), duration of preoperative low back pain symptoms ≤36 months (OR = 0.045; 95%CI: 0.007-0.277 P = 0.001). OLIF can significantly improve the low back pain symptoms in patients with low-grade degenerative lumbar spondylolisthesis. High grade of spondylolisthesis before operation, duration of low back pain symptoms more than 36 months, osteoporosis, postoperative cage subsidence, and postoperative segmental disc height improvement less than 2.5 mm are risk factors for low back pain after operation.

Temporal increase in Ki-67 index in patients with pancreatic neuroendocrine tumours.

Pancreatic neuroendocrine tumours (PanNETs) have intra-tumour heterogeneity, notably regarding the Ki-67 index, which is a major prognostic factor. The temporal evolution of PanNET biology is poorly known. We aimed to study the prognostic impact of the temporal evolution of Ki-67 and other molecular markers (MEN1, ATRX/DAXX, PDX1/ARX) in PanNETs. We retrospectively studied 109 patients with sporadic PanNETs and serial tumour samples (n=286), on which we measured the Ki-67 index and the expression of the other markers. Variables associated with shorter overall survival [OS] and Ki-67 increase over time were explored using multivariable analyses. The median time between the initial and last samples was 49.4 months, with a median variation in Ki-67 of +4% (interquartile range [IQR], -1 to +15%; p<0.001) and +0.5%/year (IQR -0.2 to +3.3%). Tumour grade increased in 36% of cases. At multivariable analysis, increase of Ki-67 ≥ 2%/year was associated with shorter OS (HR 1.96, 95% CI [1.02-3.73], p=0.041). This variation was more common in patients who received alkylating agents (OR 4.47, 95%CI [1.48-15.38, p=0.011) and was less common in those who achieved tumour control with somatostatin analogues (OR 0.27, 95%CI [0.08-0.82], p=0.027). MEN1 and ATRX/DAXX expressions were stable over time while the proportion of alpha-like signature (PDX1-/ARX+) decreased (p=0.016); none was associated with Ki-67 nor influenced prognosis. Overall, an increase of PanNET grade and Ki-67 index is frequent over time, indicates poorer prognosis, and is promoted by alkylating agents. Rebiopsy during PanNET evolution seems relevant to adjust prognosis evaluation and therapeutic strategy.

Impact of Referential Questions on Students' Oral Participation and Academic Performance in English

Referential questions are designed to elicit open-ended responses, allowing students to express their understanding in a way that is meaningful to them. This paper investigates the impact of the teachers' use of referential questions on the students' oral participation and academic performance in an English class. Using a quasi-experimental research design, the study investigated the Grade 10 students' level of oral involvement in terms of frequency and fluency. It used a researcher-made oral participation rubric and class records to gather the necessary data. The study's results revealed improved student oral participation after the teacher consistently used referential questions. Additionally, an increase in the student's grades in English was also seen in the class record after one grading period of using referential questions in the classroom. Finally, the statistical data showed a positive relationship between the students’ frequency of oral participation and academic performance in English but no direct correlation between the quality of their oral participation and their academic performance in English. This study recommends that teachers incorporate referential questions regularly in English classes to enhance students' oral participation and engagement.

Influence of selenium additives on butter quality and storage stability

The study's results showed that using Selenium preparations in butter production inhibited oxidative processes occurring during butter storage. In such a product, the oxidative changes of the butter were slowed down, resulting in the product's quality parameters being preserved longer. Before storage, the butter was evaluated in the 45 to 43 points range. After 15 days of storage, the taste and odour scores of the oil ranged from 44 to 40 points. The highest score was assigned to samples with high fat content stored at minus 5°C. The 62.5 per cent fat samples stored at 15°C had the lowest score for this storage period. When stored for more than 30 days, there was a further decrease in the taste and odour score of the oil. It scored between 41 and 37 points during this storage period. In addition, only sweet butter stored at minus temperature remained in the high grade. At the last storage stage (60 days), the butter scored from 38 to 35 points. Summarising the presented data, it should be noted that using selenium in butter production inhibits the development of oxidative processes and slows the deterioration of organoleptic characteristics during product storage. The rate of these processes depends on the storage temperature and the amount of oil in the butter. Due to the use of Selenium at the temperature of Minus 5 °C the shelf life of butter of the highest grade increases by 1.6-2.0 times, at 5 °C, by 1.8-2.4 times and at 15 °C, by 2.4-3.0 times. The non-infinite fatty acids in the milk fat of the cows we study are less than infinite acids, as indicated by the value of glyceride solid fractions and the amount of iodine. The iodine index in cows of the Alatau breed was 28.62, while for those in the third lactation and beyond, it was 28.45. The iodine index values for Holstein cows were 28.86 and 28.7, respectively.

The impacts of 2,4-D herbicide DMA® 4 IVM on reproductive health and gene expression along the hypothalamic-pituitary-gonad-liver [HPGL] axis in the fathead minnow (Pimephales promelas).

Aquatic herbicides are commonly used to control a variety of non-native plants. One common active ingredient used in commercial herbicide formulations globally is 2,4-dichlorophenoxyacetic acid (2,4-D). Though 2,4-D is used in aquatic ecosystems, no studies have investigated cellular, biochemical, and transcriptional effects or mechanisms of 2,4-D exposure on fathead minnows (Pimephales promelas) throughout juvenile development. Herein, we aim to evaluate the impacts of chronic ecologically relevant 2,4-D exposure on reproductive systems of fathead minnow. Juvenile fathead minnows were exposed to ecologically relevant concentrations of 2,4-D in DMA4 herbicide under laboratory conditions in a flow through system. Male plasma testosterone concentrations, testicular and ovarian histology, and differential gene expression along the HPGL axis in three tissue types (brain, liver, and gonad) were assessed after a chronic 120 day exposure period. We observed significantly decreased plasma testosterone concentration in male fish exposed to environmentally relevant concentrations (0.50, 2.00, and 4.00 mg/L) of 2,4-D. We observed a significant increase in ovarian severity grading and oocyte atresia in female fish exposed to 4.00 mg/L. Of differential expression analysis in fish exposed to 2.00 mg/L 2,4-D in DMA4, we identified significantly decreased expression of the steroid hormone receptors ESR1, ESR2b, and AR in males. Expression of male steroidogenic genes 3βHSD and 11βHSD2 along with expression of genes regulating steroid metabolism, SULT1st2 and CBR1l were increased. Altogether, these data suggest that 2,4-D could act as an endocrine disrupting chemical that alters expression of primary genes regulating hormone receptors, steroidogenesis, and steroid metabolism along the hypothalamic-pituitary-gonad-liver (HPGL) axis. The use of 2,4-D herbicides for weed control in aquatic ecosystems could present risks to the reproductive health of non-target aquatic species.

The efficacy of a reporting and data system for computed tomography imaging in assessing the likelihood of malignancy in submandibular salivary gland tumors: a preliminary study.

To establish a submandibular gland imaging reporting and data system (SI-RADS) and explore its value in diagnosing submandibular gland (SMG) tumors. Patients with primary SMG tumors who underwent enhanced computed tomography (CT) scanning and surgical intervention at Peking University Hospital of Stomatology (2013-2022) were retrospectively included. The imaging data were assessed for acquisition of the relevant imaging features, including lesion boundary, shape, enhancement, calcification, lymph node, and adjacent tissue involvement, and vascular invasion. Thereafter, these lesions were categorized into 6 grades: RADS 1, normal; RADS 2, benign; RADS 3, probably benign; RADS 4a, low probability of malignancy; RADS 4b, moderate probability of malignancy; RADS 5, high probability of malignancy. In total, 336 SMG lesions (272 benign and 64 malignant) were included. The proportions of malignant tumors were 0%, 5.1%, 33.3%, 63.0%, and 100% for SI-RADS 2, 3, 4a, 4b, and 5 lesions, respectively. With an increase in SI-RADS grading, the proportion of malignancy increased significantly. Significant differences in malignancy proportions were observed between adjacent grades. The SI-RADS based on enhanced CT images exhibits significant importance for preoperative differentiation between benign and malignant SMG tumors. By precisely delineating the imaging characteristics, it provides clinicians with a tool for more accurate preoperative diagnosis and treatment planning.

Efficacy and safety of adding immune checkpoint inhibitors to first-line standard therapy for recurrent or advanced cervical cancer: a meta-analysis of phase 3 clinical trials.

Immune checkpoint inhibitors (ICIs) combined with standard therapy (ST) have emerged as a novel treatment strategy for recurrent or advanced cervical cancer (r/a CC). However, the available data from phase 3 clinical trials have yielded mixed results. This study aims to evaluate the therapeutic efficacy and safety of adding ICIs to ST in the treatment of r/a CC. Data from four phase 3 clinical trials (KEYNOTE-826, CALLA, BEATcc, and ENGOT-cx11/GOG-3047/KEYNOTE-A18), involving 2,857 patients, were analyzed. Meta-analyses were conducted to combine hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), odds ratios (ORs) for the objective response rate (ORR), and relative risks (RRs) for adverse events (AEs). The addition of ICIs to ST significantly improved PFS (HR, 0.67; 95% CI, 0.60-0.75), OS (HR, 0.66; 95% CI, 0.58-0.75), and ORR (OR, 1.48; 95% CI, 1.13-1.94) compared to ST alone. However, there was a modest increase in grade 3-5 AEs (RR, 1.08; 95% CI, 1.03-1.13) with the combined therapy. This meta-analysis indicates that the combination of ICIs with ST in the treatment of r/a CC not only demonstrates superior efficacy over ST alone but also maintains a comparable toxicity profile, offering strong evidence for an effective and relatively safe treatment approach for managing this disease. https://www.crd.york.ac.uk/prospero/, identifier CRD42024593895.

Evaluating the Impact of Combined Clinical and Genetic Risk Factors on Dementia Onset

AbstractBackgroundIntegrating clinical and genetic risk factors for dementia in a precision medicine framework can play a crucial role in primary prevention. Here, we ascertained the proportion of individuals who are at heightened risk of developing dementia based on their family history, genetic, and clinical risk factors and evaluated how the additive burden of these risk indicators is associated with incident dementia.MethodWe analyzed longitudinal data from 3,395 diverse older adults, dementia‐free at baseline with follow‐up and whole genome sequencing, enrolled in the National Alzheimer’s Co‐coordinating Center and the Alzheimer’s Disease Neuroimaging Initiative (Table 1). Our risk indicators comprised: 1) self‐reported first‐degree relative with cognitive impairment; 2) carriage of the APOE*e4 allele; 3) an AD polygenic risk score, incorporating 24 variants and normalized for genetic ancestry, ranking in the top 2% (AD‐PRS); 4) presence of dominantly inherited AD mutations in PSEN1, PSEN2, or APP; and 5) a score of ≥6 on a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (mCAIDE), comprised of age, sex, education, obesity, hypertension, and hypercholesterolemia. We calculated the total risk burden as the sum of these indicators. Cox proportional hazard models were employed to estimate the risk of dementia progression associated with increasing risk burden.ResultsAmong participants, 55% had a family history of dementia, 36% were APOE*e4 carriers, 33% had high mCAIDE scores, 2.2% had extreme AD‐PRS, and none had ADAD mutations. Distribution of risk indicators was as follows: 20% had none, 41% one, 32% two, 7.5% three, and 0.2% four (Figure 1). Our analysis revealed a graded increase in dementia risk with more indicators: compared to those with none, individuals with one, two, three, or four indicators had 1.67, 3.14, 4.41, and 15.22 times increased dementia risk, respectively (Figure 2).ConclusionThe majority of our cohort exhibited at least one dementia risk indicator, with a higher risk burden markedly increasing dementia risk. These findings underscore the value of integrating genetic and clinical risk factors in predicting dementia, highlighting the potential of precision medicine in guiding preventive strategies for at‐risk individuals.

HPB SO10 - Evaluation of the impact of an Enhanced Recovery Pathway on clinical outcomes after Pancreaticoduodenectomy

Abstract Background Southampton General Hospital (SGH) is a high-volume HPB centre with a well-established Enhanced Recovery After Surgery pathway (ERAS). Despite the morbidity associated with pancreatic surgery, there is a large body of evidence supporting the use of a multi-modal approach to accelerate patient recovery. Within SGH, ERAS is utilised for all patients undergoing Pancreaticoduodenectomy (PD). Initial assessment of the pathway in SGH demonstrated a reduction in length of stay. Since its implementation, ERAS has been modified to optimise the pathway. The aim of this study was to assess whether the impact of ERAS had progressed over time. Method Single centre retrospective analysis of patients undergoing open PD from 2007-2023. Pancreatic reconstruction was with pancreaticojejunostomy. Pre and Post ERAS data were analysed. Post ERAS data was subdivided into Early, Middle and Late implementation time phases. Length of Stay, Complications (Clavien-Dindo Grade 3 and above), Readmissions and Mortality were all examined. Non-parametric data analysis was undertaken with Kruskal-Wallis, Spearman rank correlation and Wilcoxon rank-sum tests. Significance further assessed with Multi-variate regression (MVR). All Data were analysed using STATA. Results Overall, 861 patients underwent an open PD, the yearly volume increasing with time. Mean age was 66 years, which did not change with time. With ERAS implementation, Median Length of Stay (LOS) fell 13 to 9 days (p&amp;lt;0.01) and there was no statistically significant increase in Grade 3 complications or Readmissions (p=0.931, p=0.163). Grade 3 complications increased LOS (p&amp;lt;0.01). Increased age led to a small increase in LOS (p&amp;lt;0.01). Median LOS across Early, Middle and Late ERAS periods was 10, 9 and 9 respectively. LOS did not consistently demonstrate a statistically significant improvement across ERAS phases (MVR p=0.387, K-Wallis p&amp;lt;0.05). Conclusion The implementation of ERAS significantly reduced the median LOS for patients undergoing PD, without increasing their risk of complications or readmissions. This benefit has also been safely maintained across the period of its implementation.

Abstract 4136712: Fontan-specific morbidities impact on heart transplant outcomes: a multicenter study

Introduction: Fontan circulatory failure (FCF) is associated with poor long-term survival. The impact of Fontan-specific morbidities on outcomes in those evaluated for heart transplant (HT) are not well understood. Hypothesis: FCF-specific morbidities, their degree of severity, and the accumulation of morbidities are associated with mortality in individuals undergoing HT. Methods: This 20 center, retrospective cohort study of individuals with FCF from 2008-2023 collected data on FCF-specific morbidities, waitlist (WL), and post-HT outcomes. Each unique FCF morbidity was defined with graded severities (absent, mild, moderate, severe, and life-threatening) via a prior effort. The primary outcome was survival from WL to 1-year post-HT. Appropriate 2-group statistics and multivariable logistic regression compared surviving with those who died. Receiver operating characteristic curve determined the most discriminating value of total cumulative morbidities on mortality. Results: Of the 340 patients included, 51(15%) died between WL and 1 year post-HT. On univariate analysis, 7 of 27 FCF morbidities were associated with the mortality (p &lt; 0.2) including: anatomic Fontan pathway obstruction, clinical hypoxia, chronic pleural effusions, sleep apnea, portal variceal disease, acute kidney injury within 1 year prior to WL, and mental health disorders. On multivariable analysis, only clinical hypoxia and portal variceal disease emerged as independent risk factor for mortality (adjusted odds ratio [aOR]: 2.48, p = 0.03 and aOR 2.74 P=0.02 respectively). When assessing the impact of increasing severity of each morbidity, again worsening clinical hypoxia (aOR 1.42 increase with each increase in grade, p=0.01) and portal variceal disease (aOR 1.80 with each increase in grade, p=0.01) had differential effects on mortality. Risk of death increased with greater number of FCF morbidities. Having 2 or more of the 7 univariately significant morbidities was the value best discriminating survivors from those who died (Area under the curve 0.67; sensitivity 78%, negative predictive value 93%). Conclusion: Clinical hypoxia and portal variceal disease confer independent risk for non-survival in patients with Fontan from WL to 1 year after HT. Additionally, the magnitude of mortality risk for both hypoxia and varices worsens as disease severity worsens. Given the impact, consistent evaluation for these morbidities and timely referral for heart failure evaluation is warranted.

Abstract 4134345: Diastolic Dysfunction And The Risk Of Stroke And Major Bleeding

Background: Diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident ischemic stroke/transient ischemic attack (TIA) and with bleeding events is not well established. Aims: To examine the association of presence and severity of DD with the risk of incident ischemic stroke/TIA and major bleeding. Methods: A total of 219,667 patients who underwent at least one echocardiogram between 2010 and 2022 at a large academic institution and were followed for at least 3 months were included. Patients with prior history of stroke or TIA (n=21,505, 10%) were excluded. Smart key-phrase search was applied to echocardiographic reports to classify patients into 4 groups, based on the most severe DD assessment: Normal (n=113,265), grade I (n=21,981), grade II (n=7,215), and grade III (n=1,627). Patients in whom the presence of DD could not be determined (n=54,074) were excluded. The final study cohort (n=144,088) was followed to the endpoint of hospital admission for ischemic stroke/TIA or for major bleeding. Results: Over a median follow-up of 3.4 years, 3482 (2.4%) patients were hospitalized for stroke/TIA and 6994 (4.9%) for major bleeding. After adjusting for several confounding variables (Table), DD remained a strong predictor of incident stroke/TIA (hazard ratio (HR)=1.34 per grade increase in DD, p&lt;0.001, Figure) and of major bleeding (HR=1.32 per grade increase in DD, p&lt;0.001, Figure). These results were similar in patients with (n=11,508, 8%) or without prior history of atrial fibrillation. Conclusions: Patients with DD have a heightened risk of ischemic cerebrovascular accidents and major bleeding independent of the presence of atrial fibrillation. These risks escalate with the severity of DD. DD should be considered when counseling patients regarding their risk profile and management options.

Analysis of Key Environmental Variables Affecting Fish Communities and Species Distribution in Asian Lotic Ecosystems

In 2011, Korea installed artificial structures on four rivers to secure water resources and reduce flood damage; however, these structures have altered ecosystems and aquatic communities. This study analyzed fish communities and environmental variables at 72 sites in the Geumgang River. Fish communities and environmental variables before weir installation were examined using site data from 2008 to 2009. The results showed that Cyprinidae dominated the 70 observed species. A self-organizing map categorized the 72 sites into four groups based on fish communities. Sensitive and insectivorous species decreased, whereas tolerant and omnivorous species increased from Groups I to IV. Twenty-one indicator species were identified, with fewer and less distinct distribution patterns in Groups II and III than in Groups I and IV. The fish assessment index (FAI) showed a decline in grades A and B and an increase in grades C and D from Groups I to IV. Correlation analysis between the FAI and environmental variables indicated that fish communities in the Geumgang River were mainly influenced by water quality, reflecting altitude gradients and pollution levels. This study’s findings are anticipated to significantly inform water management strategies for the Geumgang, Yeongsangang, Nakdonggang, and Hangang Rivers.

Abstract 4137883: Association of Pre-Donation Blood Pressure with Hypertension in Living Kidney Donors

Background: Living kidney donors (LKD) are at risk for developing hypertension (HTN); however, the levels of pre-donation blood pressure (BP) that may predict post-donation BP are unknown. Hypothesis: Higher pre-donation BP is associated with a greater risk of developing post-donation HTN. Goals: We aim to examine the association between pre-donation BP and the risk of developing HTN in LKD. Methods: A retrospective cohort study using OPTN/SRTR included adult LKD undergoing donation between 6/1972 and 9/2022. Systolic and diastolic hypertension (SHTN and DHTN) were defined by SBP ≥130 and DBP ≥80 mmHg, respectively. Multiple Cox regression was utilized to examine the association between decile of pre-donation BP and time-to-event of developing post-donation SHTN and DHTN. Results: Of 174,311 adult LKD, the mean±SD age was 41±12 years and 60% were female. Mean pre- and post-donation SBP and DBP and deciles of BP are shown in Table 1 and Figure 1, respectively. The median time to follow-up for developing SHTN was 13.2 (IQR 6.8, 24.4) and DHTN was 12.2 months (IQR 6.3, 24.1). The incidence rate of developing SHTN and DHTN was 0.020 and 0.03 person-months, respectively. After adjusting for age (&lt;65 vs. ≥65 y/o), gender, race, U.S. citizenship, education level, history of pre-donation HTN, diabetes, pre-donation BMI, DBP, eGFR, urine protein:creatinine ratio, and the interaction term between decile of pre-donation SBP and age, LKD in deciles 5 to 10 (SBP 119–200 mmHg) had significantly graded increased risk for developing SHTN compared to LKD in decile 4 (SBP 115-118 mmHg; HR decile10 4.82, 95%CI 3.37, 6.91), while those in deciles 1 to 3 had a graded decrease in the risk but were non-significant (HR decile1 0.68, 95CI% 0.42, 1.11). In addition, there was a decreased risk of SHTN observed in elderly LKD (≥65 y/o) in deciles 5 and 10 (P interaction 0.041 and 0.009). The pattern of pre-donation DBP decile – DHTN association was similar to the SBP – SHTN association, but only DBP deciles 8-10 (DBP 81–195 mmHg) were significant (HR decile10 2.10, 95%CI 1.31, 3.34); Figur 2. There was no interaction between pre-donation DBP and age. Conclusions: Elevated pre-donation SBP or DBP greater than 118 or 80 mmHg is associated with a graded increase in developing post-donation SHTN or DHTN, respectively especially in the non-elderly (&lt;65 years old) LKD. BP control during the pre-donation period should be achieved to mitigate the risk of post-donation HTN.