Sample Median Research Articles

Controlling Nutritional Status (CONUT) Score: a new tool for characterization and prognosis of patients with infective endocarditis

Abstract Background malnutrition is a marker of unfavorable prognosis in different medical conditions, however, the association between new objective immunonutritional indexes and outcomes for patients with infective endocarditis (IE) is not fully studied. Purpose the aim of this study was to assess the role of the Controlling Nutritional Status (CONUT) Score in the characterization of patients with IE and its association with prognostic outcomes. Methods a total of 184 cases of confirmed IE were consecutively collected and followed during one year after diagnosis in two tertiary hospitals. CONUT score was calculated using serum albumin, total cholesterol and lymphocyte count [(range 0-12), the higher, the worse] at diagnosis, and patients were categorised as CONUT-high (>=6, n=98), and CONUT-low (<6, n=86) based on the sample median value. Results mean age was 70 [SD 15] years, 64% were men and community-acquired infections were 69%. Median score value was 6 (4). As shown in Table 1 and 2, diabetes and frailty were more prevalent in CONUT-high group, who showed a worse profile of nutritional biomarkers. Overall, the most frequent pathogen was S. viridans (n=43). By groups, S. aureus was predominantly isolated in CONUT-high (20 vs 8%; p 0.02), and non-viridans streptococci in CONUT-low (9 vs 2%, p 0.03). Regarding infection site, IE of aortic bioprostheses was more common in CONUT-high, whereas mechanical aortic valves and mitral bioprostheses were more frequently involved in CONUT-low. Larger vegetations [14 (11) vs 11 (7) mm, p 0.02], and more periannular abscesses (25 vs 13%, p 0.04) were detected in CONUT-high, who presented more acute kidney injury and septic shock during hospitalization. Despite higher predicted surgical risk in CONUT-high, neither the proportion of patients who underwent surgery nor in-hospital mortality, differed between groups. When analyzing according to the therapeutic approach, only among those medically managed patients without surgical indication, in-hospital mortality was higher in CONUT-high. At 1-year follow-up, rehospitalization rate tended to be lower in those with a better nutritional status (35% vs 51%, p 0.07). Conclusions in patients with IE and a high CONUT score, diabetes and frailty were more prevalent. In addition, virulent pathogens, larger vegetations and periannular complications were more frequently reported. Although surgery performance and in-hospital mortality did not differ between groups, a worse nutritional status was associated with a higher rate of clinical complications and higher mortality among patients with conservative management who did not meet surgical criteria.

Associations of "Weekend Warrior" Physical Activity With Incident Disease and Cardiometabolic Health.

Achievement of guideline-recommended levels of physical activity (≥150 minutes of moderate-to-vigorous physical activity per week) is associated with lower risk of adverse cardiovascular events and represents an important public health priority. Although physical activity commonly follows a "weekend warrior" pattern, in which most moderate-to-vigorous physical activity is concentrated in 1 or 2 days rather than spread more evenly across the week (regular), the effects of physical activity pattern across a range of incident diseases, including cardiometabolic conditions, are unknown. We tested associations between physical activity pattern and incidence of 678 conditions in 89 573 participants (62±8 years of age; 56% women) of the UK Biobank prospective cohort study who wore an accelerometer for 1 week between June 2013 and December 2015. Models were adjusted for multiple baseline clinical factors, and P value thresholds were corrected for multiplicity. When compared to inactive (<150 minutes moderate-to-vigorous physical activity/week), both weekend warrior (267 total associations; 264 [99%] with lower disease risk; hazard ratio [HR] range, 0.35-0.89) and regular activity (209 associations; 205 [98%] with lower disease risk; HR range, 0.41-0.88) were broadly associated with lower risk of incident disease. The strongest associations were observed for cardiometabolic conditions such as incident hypertension (weekend warrior: HR, 0.77 [95% CI, 0.73-0.80]; P=1.2×10-27; regular: HR, 0.72 [95% CI, 0.68-0.77]; P=4.5×10-28), diabetes (weekend warrior: HR, 0.57 [95% CI, 0.51-0.62]; P=3.9×10-32; regular: HR, 0.54 [95% CI, 0.48-0.60]; P=8.7×10-26), obesity (weekend warrior: HR, 0.55 [95% CI, 0.50-0.60]; P=2.4×10-43, regular: HR, 0.44 [95% CI, 0.40-0.50]; P=9.6×10-47), and sleep apnea (weekend warrior: HR, 0.57 [95% CI, 0.48-0.69]; P=1.6×10-9; regular: HR, 0.49 [95% CI, 0.39-0.62]; P=7.4×10-10). When weekend warrior and regular activity were compared directly, there were no conditions for which effects differed significantly. Observations were similar when activity was thresholded at the sample median (≥230.4 minutes of moderate-to-vigorous physical activity/week). Achievement of measured physical activity volumes consistent with guideline recommendations is associated with lower risk for >200 diseases, with prominent effects on cardiometabolic conditions. Associations appear similar whether physical activity follows a weekend warrior pattern or is spread more evenly throughout the week.

Natural history of autologous sperm cryostorage.

What is the natural history of elective autologous sperm cryostorage prior to gonadotoxic treatment? We estimate large sample median times to transfer for use, to the man's death or to discard of sperm, and their determinants, as the key operational outcomes of sperm cryostorage. No large sample studies of the natural history of sperm cryostorage prior to gonadotoxic treatment are reported. This observational single-centre study covered 45 years of outcomes with a survival analysis for sperm cryostorage prior to scheduled gonadotoxic treatment, and its determinants. This study included 3923 men (mean age 30 years) who sought sperm cryostorage for a wide range of cancers and other diseases requiring gonadotoxic treatments. The median time to transfer for use (n = 371 men 9%) was 2.4 years (quartiles 1.0, 6.0), the median time to death (n = 553 men, 14%) was 1.7 (0.9, 3.3) years, and the median time to discard (n = 1807 men, 46%) was 7.7 (1.7, 11.1) years. In multivariate Cox model regression, the underlying disease, number of storage visits and follow-up visits, and whether sperm were seen at follow-up visits were consistent predictors of times to outcomes. This study did not investigate sperm cryostorage for reasons other than gonadotoxic treatment, nor the fertilization outcomes of the cryostored sperm. These data provide estimates of the key operational factors for sperm cryostorage programs, prior to potentially sterilizing gonadotoxic treatments, and free from financial or insurance restrictions. There was no specific funding for this study. D.J.H. has provided expert witness testimony to antidoping and professional standards tribunals and is supported by an NHMRC Investigator Grant. The other authors have no disclosures. N/A.

Selection Bias in Reporting of Median Waiting Times in Organ Transplantation

Median organ waiting times published by transplant organizations may be biased when not appropriately accounting for censoring, death, and competing events. This can lead to overly optimistic waiting times for all transplant programs and, consequently, may deceive patients on the waiting list, transplant physicians, and health care policymakers. To apply competing-risk multistate models to calculate probabilities for transplantation and adverse outcomes on the Swiss national transplant waiting list. The WAIT (Waitlist Analysis in Transplantation) study was a retrospective cohort study of all transplant candidates in Switzerland listed from January 1, 2018, or later and observed until December 31, 2023. Transplant candidates were listed in 1 of the 6 transplant centers (Basel, Bern, Geneva, Lausanne, St Gallen, and Zurich) for heart, liver, lungs, kidney, or pancreas and/or islet transplant. A total of 4352 candidates were listed during the study period, of whom 709 (16.3%) were excluded due to living-donor transplant (691 in the kidney program and 18 in the liver program). Waiting for organ transplant. Time to transplantation, death, or delisting. Competing-risk multistate models were used to analyze time-to-event data from the national organ waiting list with the Aalen-Johansen estimator to compute probabilities for both transplant and adverse outcomes. Results were compared with the sample median among only those undergoing transplant and the Kaplan-Meier method with censoring of competing events. Data from 3643 transplant candidates (2428 [66.6%] male; median age, 56 [range, 0-79] years) were included in the analysis. The median time to transplantation (MTT) was 0.91 (95% CI, 0.83-1.07) years for heart, 3.10 (95% CI, 2.57-3.77) years for kidney, 1.32 (95% CI, 0.76-1.55) years for liver, 0.80 (95% CI, 0.37-1.12) years for lung, and 1.62 (95% CI, 0.91-2.17) years for pancreas and/or islet programs. Alternative estimation methods introduced bias to varying degrees: the sample median among only persons undergoing transplantation underestimated the waiting time by 38% to 61% and the Kaplan-Meier method by 2% to 12% compared with the MTT. In this cohort study of transplant candidates in Switzerland, the MTT, the duration at which the transplant probability is 0.50, was used as a measure of average waiting time. Suboptimal methods led to biased and overly optimistic waiting time estimations; thus, applying appropriate competing-risk methods to address censoring and competing events is crucial.

Two-Decade Changes in the Ciliate Assemblage Feeding Pattern Reflect the Reservoir Nutrient Load

The perception of the importance of ciliate in freshwater has changed dramatically since the “microbial loop” conceptualisation, reflecting methodological attempts. The data from two decades (1994–2018) on the surface (0–3 m) ciliate assemblage in the Slapy reservoir (Vltava River, Czech Republic) during two different nutrient-load defined periods were analysed. We grouped the identified, quantified, and biomass-evaluated ciliates in the quantitative protargol-impregnated preparations according to their feeding behaviour. The sampling median and interquartile range data of the ciliates were plotted; the modelled water age, nutrients, bacteria, heterotrophic nanoflagellates, and Rhodomonas spp. were applied as the main explanatory background variables. We validated the differences between the periods, engaging multivariate analyses. The picoplankton-filtering species dominated the assemblages in an annual mean (halteriids and minute strobilidiids followed by peritrichs). Algae hunting urotrichs, Balanion planctonicum, and nanoplankton filtering tintinnids were significant before the spring phytoplankton peak when a maximum of ciliate biomass reflected mixotrophic nanoplankton filtering pelagostrombidiids. Only there did ciliate biomass tightly follow their quantified prey. Heterotrophic and mixotrophic Askenasia and Lagynophrya were typical raptorial/flagellate-hunting cilates; only Mesodinium spp. reached the maximum during autumn. The observed oligotrophication of the reservoir increased the ciliate assemblage biomass in the surface layer during stratification in concordance with the Plankton Ecology Group (PEG) model.

Acrylamide and HMF occurrence and bioaccessibility in instant coffee and coffee substitutes. A study on isolated and milk-combined beverages

This research evaluated the occurrence and bioaccessibility of acrylamide and HMF in commercial instant coffees (IC) and coffee substitutes (CS), considering both isolated consumption and combination with milk. There were no significant differences in acrylamide content between IC and CS samples (median: 589 vs. 671 µg/kg), but higher variability was reported for CS, probably due to their varied composition (roasted cereals, nuts, honey, dehydrated fruits, and/or chicory). Acrylamide level were always below the EU benchmark for each category. HMF contents were similar between both groups (1354–5127 mg/kg for IC and 735–7134 mg/kg for CS; median: 2890 vs. 2960 mg/kg), with no clear ingredient relationship. Since IC consumption by the Spanish population is ten times higher than that of CS, exposure to acrylamide and HMF was higher from IC (6.8 vs. 1.07 ng/kg body weight/day for acrylamide; 39.1 vs. 4.2 µg/kg body weight/day for HMF). The standardized in vitro gastrointestinal digestion protocol (INFOGEST) was used. The gastrointestinal process reduced the bioaccessibility of acrylamide up to 27.2 % in IC and to 22.4 % in CS, regardless of the presence of milk. HMF bioaccessibility from IC significantly dropped after the gastrointestinal digestion, whereas it greatly increased for CS. The presence of milk did not affect HMF bioaccessibility. These results highlight the importance of assessing food bioaccessibility in typical consumption scenarios, providing a holistic view and a realistic evaluation of the potential risks associated with acrylamide and HMF exposure in the diet.

THE EFFECT OF EDUCATIONAL BACKGROUND ON THE QUALITY OF LIFE OF THE PRE-ELDERLY POPULATION

The quality of life of the pre-elderly population is the key to readiness to enter the stages of old age to realize a prosperous life. Previous research has extensively studied the condition of the elderly population in various scientific disciplines and still minimally examines the quality of life of the pre-elderly population, especially regarding educational background as an indicator of human resource development. This research aims to measure and analyze the influence of educational background on the quality of life of the pre-elderly population as they enter old age. This research method is quantitative with the instrument used being a questionnaire. This research population was residents in Timbangan Sub District, Ogan Ilir Regency aged 45-59 years. The sample calculation used the Isaac and Michael formula with a sampling error of 5% so that the sample size for this study is 310 residents. Data analysis used in this research is the independent sample median K test, Tukey test, and ordinal regression test using SPSS version 20 and STATA version 17 software. The results show that there is a significant influence between educational background and the quality of life of the pre-elderly population in Timbangan Sub District, Ogan Ilir Regency, it was 7,16%. Thus, educational background variables can contribute to improving the quality of life of the pre-elderly population in Timbangan Sub District, Ogan Ilir Regency.

Investigation and improvement of spill quality at XiPAF synchrotron

The Xi’an 200 MeV Proton Application Facility (XiPAF) is a specialized facility designed to simulate space radiation environments. To meet the requirements of space radiation simulation, the proton accelerator must provide a quasi-continuous spill. The facility has achieved this goal by implementing third-order resonance and RF knockout (RF-KO) slow extraction. In this study, the source of the spill ripple at the XiPAF synchrotron was analyzed and a method was developed to calculate the fluctuation ratio of the spill from the spill spectrum. According to the experimental results, the spill quality at XiPAF is mainly affected by the ripple of the magnet power supply. To improve the spill quality, the frequency spectrum of the excitation signal was optimized to suppress the influence of the power supply ripple. We found that the dual-frequency signal, which consists of the two sinusoidal waves corresponding to the extraction and diffusion regions in the third-order resonance, can significantly reduce the influence of the magnet power supply ripple. After adopting the optimized dual-frequency signal, the fluctuation ratio of the spill is reduced from about 0.15 to 0.092 (sample median) at a sampling frequency of 1.24 kHz.

Shewhart Type Control Chart Based on Median for Location Parameter

Control charts are prominent tools in monitoring various variables of manufacturing processes. In this paper, the control chart based on sample median is proposed for process location parameter using Shewhart?s approach. The proposed control chart is developed under some distributions including normal distribution. Its performance is studied in terms of power, average run length (ARL) and standard deviation of run length (SDRL). Also, the effect of non normality on this control chart is discussed.. KEYWORDS :ARL, Control limits, Location parameter, Median, Non-normality, Power.

Ultra-sensitive ctDNA mutation tracking to identify molecular residual disease and predict relapse in patients with early breast cancer.

1010 Background: Circulating tumor DNA (ctDNA) based detection of Molecular Residual Disease (MRD) in breast cancer patients presents a strategy to identify patients at high risk of relapse, although current assays have limited sensitivity for low level ctDNA detection. In this study we profile early breast cancer patients with an ultra-sensitive, whole genome sequencing-based, tumor-informed ctDNA platform, and correlate the findings with clinical outcomes. Methods: We analysed 598 plasma samples (median 8 samples/patient, range 2-14) from 76 patients with early breast cancer (23 TNBC, 33 HER2+, 16 HR+ and 4 unknown) enrolled in the ChemoNEAR study. Samples were collected at diagnosis before therapy, at Cycle 2 of neoadjuvant chemotherapy (NAC), post-surgery after neoadjuvant therapy if administered, and every 3 months during follow-up for the first year, and subsequently every 6 months for up to five years. Plasma cfDNA was analysed using the NeXT Personal ctDNA based MRD platform, a tumour-informed approach leveraging whole-genome sequencing of tumor and normal samples to produce personalised ctDNA sequencing panels, with each bespoke panel consisting of up to ~1,800 selected variants that enable ultra-sensitive MRD detection. MRD detection was correlated with clinical outcomes and histopathological data. Results: We detected a broad range of ctDNA levels ranging from 204,900 PPM to 2.2 PPM (median 296 PPM). 40% of all ctDNA detections were in the ultra-low range of &lt;100 PPM. 97.8% (45/46) of patients had ctDNA detected at baseline prior to treatment, including 100% TNBC, 100% HER2+, and 83% of HR+ patients. At a median follow-up of 76 months (range 5-113) from study entry, detection of ctDNA associated with high risk of future relapse (HR undefined, p&lt;0.0001; log-rank test) and shortened overall survival (p&lt;0.0001; log-rank test) with median lead-time from ctDNA detection to clinical relapse of 12.5 months (range 1-60). MRD was identified in 100% (10/10) of patients who relapsed. Of the relapsed patients, the median level of ctDNA at first MRD detection was 18.5 PPM. No ctDNA undetected patients relapsed throughout follow up (58/58). Three patients had ctDNA detected in follow-up but had not relapsed at the time of data cut off. For patients that were ctDNA undetected at post-surgical landmark, 94% (31/33) patients did not relapse. Conclusions: NeXT Personal detected breast cancer relapse with a long lead-time over clinical relapse, and strongly associated with relapse free survival. The assay demonstrated high rates of ctDNA detection at diagnosis. The strong negative predictive value at landmark suggests potential use in de-escalation studies. Several prospective, interventional trials are being conducted to assess whether treatment based on MRD detection improves outcome.

Association between circulating tumor DNA (ctDNA) and recurrence-free survival (RFS) in patients (pts) with resected stage III melanoma: An exploratory analysis of SWOG S1404.

9564 Background: Our exploratory study aimed to understand the association between the presence of ctDNA after definitive surgical resection and RFS in pts with stage III melanoma treated with adjuvant immunotherapy. Methods: This study included 92 pts with resected stage III melanoma enrolled in a phase 3 trial (NCT02506153) that evaluated the efficacy of adjuvant pembrolizumab compared to interferon alfa-2b or ipilimumab in pts with stage IIIA(N2a)-IV resected melanoma. Personalized, tumor-informed ctDNA assays (Signatera) were run on banked plasma samples (median: 3.8 mL) collected at up to 5 time points after resection: pre-adjuvant treatment (pre-Tx), 1, 3, 6, or 12 months after Tx initiation and at recurrence. RFS was measured from randomization (pre-Tx) to first recurrence or death. A case-control design was used: 50% with recurrence within 2 yrs of randomization and 50% alive without recurrence for &gt; 2 yrs. Conditional logistic regression compared the presence of ctDNA at pre-Tx between case-control groups. Results: Of the 92 pts, samples from 10 did not pass quality control. This study analyzed a total of 245 plasma samples from 82 pts. No significant differences in demographics, including stage, number of + lymph nodes, and BRAF status, existed between pts who were ctDNA+ or ctDNA- pre-Tx. 7 of 10 pts (70.0%) who were ctDNA+ pre-Tx had disease recurrence within 2 yrs compared to 33 of 72 pts (45.8%) who were ctDNA- (p = 0.19). 2-yr RFS was 30% in pts who were ctDNA+ pre-Tx and 54% in pts who were ctDNA- (HR 1.75; 95% CI: 0.78, 3.94; p = 0.18). Of the 7 pts who were ctDNA+ pre-Tx and had disease recurrence within 2 yrs, 5 were ctDNA+ at all time points assessed. The other 2 pts transiently cleared ctDNA during Tx, turning back ctDNA+ prior to recurrence. Of the 3 pts who were ctDNA+ pre-Tx and did not recur within 2 yrs, 2 cleared ctDNA during immunotherapy and remained ctDNA- at later time points. All 39 pts who were ctDNA- pre-Tx and did not recur within 2 yrs remained ctDNA- at later time points. Among 29 pts having ctDNA timepoints available for analysis near the time of recurrence (end-of-Tx or on-progression timepoints), 22 (75.9%) were ctDNA+. Conclusions: In this study, pre-Tx incidence of ctDNA+ after surgical resection was low, potentially related to limited plasma yield. However, the ctDNA positivity rate increased in subsequent serial testing. ctDNA might help identify early disease recurrence in patients with melanoma in the adjuvant setting, but further studies of larger cohorts accounting for treatment effect with more uniform pre-analytic collection are needed.

Diagnostic Utility of Cytomegalovirus (CMV) DNA Quantitation in Ulcerative Colitis.

Cytomegalovirus (CMV) colitis is a critical condition associated with severe complications in ulcerative colitis (UC). This study aimed to investigate the diagnostic value of the presence of CMV DNA in intestinal mucosa tissue and blood samples in patients with active UC. This study included 81 patients with exacerbated symptoms of UC. Patient data were obtained from the Hospital Information Management System. CMV DNA in colorectal tissue and plasma samples were analyzed using a real-time quantitative PCR assay. CMV markers were detected using immunohistochemistry and hematoxylin-eosin staining. Immunohistochemistry positivity was observed in tissue samples from eight (9.9%) patients. Only one (1.2%) patient showed CMV-specific intranuclear inclusion bodies. CMV DNA was detected in 63.0% of the tissues (median: 113 copies/mg) and in 58.5% of the plasma samples (median: 102 copies/mL). For tissues, sensitivity and the negative predictive value (NPV) for qPCR were excellent (100.0%), whereas specificity and the positive predictive value (PPV) were low (41.9% and 15.7%, respectively). For plasma, sensitivity and NPV were high (100.0%) for qPCR, whereas specificity and PPV were low (48.6% and 24.0%, respectively). CMV DNA ≥392 copies/mg in tissue samples (sensitivity 100.0% and specificity 83.6%) and ≥578 copies/mL (895 IU/mL) in plasma samples (sensitivity 66.7% and specificity 100.0%) provided an optimal diagnosis for this test. The qPCR method improved patient management through the early detection of CMV colitis in patients with UC. However, reliance on qPCR positivity alone can lead to overdiagnosis. Quantification of CMV DNA can improve diagnostic specificity, although standardization is warranted.

Super-polynomial accuracy of multidimensional randomized nets using the median-of-means

We study approximate integration of a function f f over [ 0 , 1 ] s [0,1]^s based on taking the median of 2 r − 1 2r-1 integral estimates derived from independently randomized ( t , m , s ) (t,m,s) -nets in base 2 2 . The nets are randomized by Matousek’s random linear scramble with a random digital shift. If f f is analytic over [ 0 , 1 ] s [0,1]^s , then the probability that any one randomized net’s estimate has an error larger than 2 − c m 2 / s 2^{-cm^2/s} times a quantity depending on f f is O ( 1 / m ) O(1/\sqrt {m}) for any c &gt; 3 log ⁡ ( 2 ) / π 2 ≈ 0.21 c&gt;3\log (2)/\pi ^2\approx 0.21 . As a result, the median of the distribution of these scrambled nets has an error that is O ( n − c log ⁡ ( n ) / s ) O(n^{-c\log (n)/s}) for n = 2 m n=2^m function evaluations. The sample median of 2 r − 1 2r-1 independent draws attains this rate too, so long as r / m 2 r/m^2 is bounded away from zero as m → ∞ m\to \infty . We include results for finite precision estimates and some nonasymptotic comparisons to taking the mean of 2 r − 1 2r-1 independent draws.

Is alcohol and psychoactive medication use associated with excess hospital length-of-stay and admission frequency? A cross-sectional, observational study

BackgroundHospital length-of-stay and admission frequency are commonly used indicators of disease burden and health resource expenditures. However, the impact of psychoactive prescription medication use and harmful alcohol consumption on both the duration and frequency of hospital admissions is under-explored.MethodsWe conducted an analysis of data gathered from 2872 patients admitted to the Emergency Department at Lovisenberg Diaconal Hospital in Oslo, Norway. Psychoactive medicines (benzodiazepines, opioids, and z-hypnotics) were detected via liquid chromatography-mass spectrometry analysis of whole blood, while alcohol consumption was self-reported through the Alcohol Use Disorder Identification Test-4 (AUDIT-4). Using logistic regression, we examined associations with our primary outcomes, which were excess length-of-stay and admission frequency, defined as exceeding the sample median of 3.0 days and 0.2 admissions per year, respectively.ResultsCompared to the absence of psychoactive medication, and after adjusting for age, gender, malignant disease, pre-existing substance use disorder and admission due to intoxication, the detection of two or more psychoactive medicines was associated with both excess length-of-stay (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.20 to 2.14) and yearly hospitalization rate (OR, 3.72; 95% CI, 2.64 to 5.23). This association persisted when increasing the definition for excess length-of-stay to 4 and 5 days and to 1.0 and 1.5 admissions per year for admission frequency. Harmful alcohol consumption (AUDIT-4 scores of 9 to 16) was not associated with excess length-of-stay, but with excess admission frequency when defined as more than 1.0 admission per year when compared to scores of 4 to 6 (OR, 2.68; 95% CI, 1.58 to 4.57).ConclusionsPsychoactive medication use is associated with both excess length-of-stay and increased antecedent admission frequency, while harmful alcohol consumption may be associated with the latter. The utility of our findings as a causal factor should be explored through intervention-based study designs.

Understanding the Relationship Between Wealth and Cognitive Function by Race/Ethnicity Among Older United States Adults with Diabetes.

The prevalence of type 2 diabetes is increasing with the burden disproportionately falling on older adults and racial/ethnic minorities. Older adults with diabetes show greater cognitive decline and there are disparities in cognitive function by race/ethnicity that can be explained by social determinants such as wealth. To understand whether there is a differential relationship between wealth and cognitive function by race/ethnicity among older U.S. adults with diabetes. Data on 9,006 adults aged 50+ with diabetes from the Health and Retirement Study (2006-2016) were analyzed. The primary outcome, cognitive function, was a score ranging from range 0-27 categorized as: normal [12-27], mild cognitive impairment (MCI) [7-11], and dementia including Alzheimer's disease [0-6]. Three modeled outcomes were: 1) normal versus MCI, 2) normal versus dementia, 3) MCI versus dementia. Wealth was log transformed and used as continuous and binary (≥median, <median). Logistic generalized estimating equation models were used to examine the relationship between wealth and cognitive function and models were stratified by race/ethnicity. Models were adjusted for demographics, lifestyle, functional limitations, and comorbidities. In adjusted models, greater wealth was significantly associated with lower odds of MCI and dementia for all groups. Similarly, having wealth less than the sample median was associated with higher odds of MCI and dementia compared to wealth≥sample median. Increased wealth was significantly protective against MCI and dementia for all ethnic groups. Wealth less than the sample median was associated with greater odds of dementia for NHB and NHW.

Endoscopic submucosal dissection and endoscopic mucosal resection for esophageal and gastric lesions: A comparison of procedures

ObjectiveEsophageal and gastric lesions are effectively managed with minimally invasive upper endoscopic procedures such as endoscopic mucosa resection (EMR) and endoscopic submucosal dissection (ESD), offering patients alternatives to invasive interventions. While ESD is well established in Eastern Asia, its adoption in Denmark for superficial esophageal cancer is recent. This study presents real-world data on the feasibility, safety, and hospitalization duration associated with ESD and EMR for esophageal and gastric lesions. MethodsA retrospective analysis was conducted on patients who underwent ESD or EMR at a specialized center in Denmark from October 2016 to June 2022. Data on treatment, indication, lesion location, hospitalization duration, procedure duration, specimen size, complications, recurrence, and one-year overall survival were collected. Statistical comparisons utilized the Mann–Whitney U test, independent sample median test, and chi-squared test. ResultsThe study included 130 patients (144 procedures): 72 underwent ESD and 58 underwent EMR. Compared with EMR, ESD resulted in greater percentages of en bloc and R0 resections (98.8% vs. 64.1%, p < 0.001; and 83.9% vs. 23.8%, p < 0.001), greater complication rates (28.7% vs. 3.1%, p < 0.001) and longer procedure times (119.5 min vs. 37.0 min, p < 0.001). The ESD procedure time significantly decreased over time (p = 0.01). The local recurrence rates were 14.5% for ESD and 23.8% for EMR (p = 0.767). The one-year overall survival rates were similar between the groups (95.8% vs. 94.8%, p = 0.553). ConclusionBoth ESD and EMR are safe and viable for treating esophageal and gastric lesions. ESD offers advantages but requires more time and skill. These findings support the literature, emphasizing the importance of considering patient-specific factors and surgeon proficiency in selecting the appropriate procedure.

The Impact of the Comprehensive Unit-Based Safety Program on the Perioperative Efficiency and Patient Safety of Adult Hip and Knee Arthroplasty Procedures: Retrospective Comparative Study

BackgroundThe complexity of health care delivery systems presents a unique challenge for the perioperative space. In the area of arthroplasty procedures, the shift of complex patients into ambulatory surgery centers and reimbursement that is no longer commensurate with the inflated costs of performing these procedures have created difficulties for hospitals and physicians alike. Thus, there is a critical need to optimize perioperative workflows while maintaining high-quality care provision. MethodsOur institution implemented the Comprehensive Unit-based Safety Program (CUSP) to improve the quality and efficiency of total knee and hip arthroplasties (TKAs and THAs). This initiative involved extensive collaboration with clinical and administrative teams, as well as 5 intervention-driven workgroups. First-case on-time start rates and duration of first-case delays, case length, anesthesia preparation, in-room patient preparation, operation, patient exit, and room turnover after CUSP implementation were analyzed using independent samples median testing, Mann-Whitney U testing, and a percentage-point difference calculation. ResultsAfter CUSP arthroplasty implementation, first-case on-time start rates increased from 43 to 81%. Statistically significant decreases were observed in median times for first-case delays, case length, in-room patient preparation, operation, patient exit, and room turnover for TKAs and THAs, but not anesthesia preparation. ConclusionsThe implementation of CUSP arthroplasty for TKAs and THAs resulted in significant improvements in nearly all efficiency metrics, as well as preventions of patient safety missteps. These results exemplify the versatility of CUSP as a quality improvement method that can maintain patient safety and perioperative efficiency in the arthroplasty service of a large-scale medical center. Level of EvidenceIII.

Abstract 3928: Genomic landscape and estimation of immune infiltration of soft tissue sarcoma histology subtypes from the ORIEN network

Abstract Sarcomas encompass a group of malignant diseases arising from mesenchymal origins. Given their rarity and diversity, a fundamental understanding of the genomic underpinnings for many sarcoma subtypes is still lacking. Studies are often limited to one or several of the more common subtypes or a narrow evaluation of a broader sampling. We therefore report on one of the largest comprehensive omics evaluation in sarcomas to date, including whole exome sequencing (WES; n = 1170) and RNA-sequencing (n = 983) of tissues from 29 different sarcoma histologic subtypes collected at 13 institutions in the US as part of the Oncology Research Information Exchange Network (ORIEN). We identified recurrent somatic mutations previously identified in sarcomas (e.g. TP53, KIT) as well as other cancer types (e.g. BRCA1). The burden of putatively pathogenic driver point mutations was higher in metastatic samples (median = 3) as compared to primary tumor samples (median = 2; p &amp;lt; 0.001). We observed frequent copy number alterations including whole genome doubling more commonly in metastatic compared to primary tumors (23.4% vs. 16.9%; p = 0.0.25). Inspection of gene expression dimensionality reduction (UMAP) showed separation of gastrointestinal stromal tumors (GISTs), leiomyosarcomas, myxoid liposarcomas, and well/de-differentiated liposarcomas from the other histologies. Differential expression analysis for these four histologies with gene set enrichment analysis highlights the diversity of disease-specific pathways and need for sarcoma subtype-specific translational focus. Estimation of immune cell abundances based on RNA-seq followed by hierarchical clustering identified five immune subtypes. The subtypes ranged from low (clusters A, B) to high (clusters D, E) immune infiltration with higher abundance of T, B, Natural Killer (NK), and myeloid cells (FDR &amp;lt; 0.01). Intermediate immune group C was predominantly composed by GISTs and marked by an enrichment for NK cells (FDR &amp;lt; 0.01) compared to all groups except the immune “hot” group E; however, this immune group exhibited modest infiltration by other immune cell types. Notably, we observed significant differences in the overall survival of patients with sarcomas in immune enriched (C, D, E) compared to immune depleted clusters (A, B; p = 0.002). In summary, we report the genomic and expressional landscape of over 1000 sarcomas, representing one of the largest comprehensive profiling efforts in this disease. We identify the mutational and copy number variation landscape and observe differences between primary and metastatic samples. We highlight expression pathways that are enriched in histologic subtypes that cluster most distinctly from others, providing a subtype-specific roadmap for further translational efforts. Finally, we define immune enriched or depleted sarcoma subgroupings that carry a prognostic impact. Citation Format: Alex C. Soupir, Oscar E. Ospina, Dale Hedges, Jamie K. Teer, Michael D. Radmacher, David M. McKean, Nathan Seligson, Martin McCarter, Breelyn Wilkey, Greg Riedlinger, John Groundland, Benjamin J. Miller, Bryan Schneider, Reema Patel, Abdul Rafeh-Naqash, Stephen Edge, Bodour Salhia, Chris Moskaluk, Maggy Johns, Michelle L. Churchman, Oliver Hampton, David Liebner, Brooke L. Fridley, Andrew S. Brohl. Genomic landscape and estimation of immune infiltration of soft tissue sarcoma histology subtypes from the ORIEN network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3928.

Abstract 1075: Buccal mucosal remodeling predicts esophageal cancer risk

Abstract Lifestyle habits, including alcohol consumption, tobacco smoking, and germline variants of ALDH2 and ADH1B, increase the risk of developing esophageal squamous cell carcinoma (ESCC). However, current prediction methods that rely on self-reported lifestyle information lack accuracy. We previously demonstrated that driver-mutated clones remodel the esophageal epithelium with age and that this remodeling is accelerated in heavy drinkers and smokers. Nonetheless, predicting cancer from clonal expansion in normal tissues remains challenging, due to limited sample availability beyond the blood. The squamous epithelium continuously covers the esophagus, throat, and oral cavity. Therefore, we evaluated buccal mucosal remodeling by mutant clones and its potential as a predictive biomarker of ESCC. A total of 387 buccal mucosa samples were collected from 110 subjects, including 62 with ESCC and 48 without, using swabs of three different sizes, followed by error-corrected sequencing targeting 26 driver genes that showed positive selection in samples from ESCC and physiologically normal esophageal tissues, as well as ALDH2 and ADH1B. Somatic mutations were detected in all samples (median, 27 (1-134)). In total, 13,235 mutations, including 12,085 nonsynonymous and 1,150 synonymous mutations, with VAFs ranging from 0.0016-0.12 (median, 0.0025), were detected. Ten of the 26 genes, TP53, CHEK2, NOTCH1, CDKN2A, NOTCH2, FAT1, AJUBA, PPM1D, ARID1A, and ZNF750 showed positive selection (dN/dS &amp;gt;1, q&amp;lt;0.1). Correlation analysis demonstrated that driver mutations in TP53, FAT1, and PPM1D were positively correlated with not only germline risk variants of ALDH2 but also alcohol consumption. The impact of alcohol consumption on the number and sum of VAFs of mutations in each of the three genes was analyzed and stratified by the presence or absence of the germline risk variant of ALDH2, and positive correlations were observed only among subjects with risk variants. Compared to subjects without ESCC, patients with early-stage or advanced ESCC displayed significantly higher numbers and sums of VAFs of driver mutations (p&amp;lt;0.05). These results indicated that buccal mucosal remodeling driven by positively selected mutations is associated with lifestyle and germline risk factors for ESCC, thus motivating the establishment of a predictive model for ESCC using genetic swab data. The prediction model for ESCC using sequencing data outperformed a model using self-reported lifestyle and alcohol flushing reaction and a model using lifestyle and germline risk variants (AUC of 0.94, 0.72, and 0.88, respectively). In conclusion, this is the first study to use clonal expansion in normal tissues to predict the presence of solid organ cancer, and our study successfully established a prediction model for ESCC based on buccal mucosal remodeling and germline variants. Citation Format: Akira Yokoyama, Tomonori Hirano, Koichi Watanabe, Masashi Tamaoki, Kenshiro Hirohashi, Yoshihiro Ishida, Yoshikage Inoue, Yasuhide Takeuch, Yo Kishimoto, Soo Ki Kim, Chikatoshi Katada, Yasuhito Nanya, Hiroshi Seno, Seishi Ogawa, Manabu Muto, Nobuyuki Kakiuchi. Buccal mucosal remodeling predicts esophageal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1075.

Abstract 6299: Psychometric evaluation of the FACIT-SP 12 in a primary brain tumor patient population

Abstract Spirituality is a social determinant of health associated with psychosocial adjustment to serious illnesses including cancer but is not often assessed in clinical care. Here we perform psychometric evaluation of a tool developed to report spiritual well-being in chronic illness in a cohort of 248 patients with primary brain tumors (PBT) enrolled in a natural history study (NCT02851706, PI: T. Armstrong). Participants completed the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (FACIT-SP 12) as part of yearly clinical outcome assessments. Total score, Meaning/Peace and Faith scores were calculated. Internal consistency (Cronbach’s alpha) and construct validity (principal components analysis with varimax rotation) evaluated psychometric properties of the FACIT-SP 12; one-way ANOVAs, one-sample t-test and Wilcoxon signed rank tests evaluated group differences (sig. p&amp;lt;0.05) on patient report of spirituality/beliefs including belief in god(s)/higher power, being religious, and prayer and in comparison to scores of previously reported studies. Participants were majority male (57%), white (79%) with high grade tumor (59%) and a median age of 48 (range: 20-82). Seven different religions were reported (majority Christianity [55%]) but also spiritual non-religious (9%), no beliefs (13%), and 6% preferring not to answer. The principal components analysis confirmed the original 2 factor solution (Meaning/Peace and Faith) and explained 66.8% of the variance (KMO =0.87, 43% of residuals &amp;lt; 0.05), with one item not loading cleanly on either factor (“I know that whatever happens with my illness, things will be okay”). Cronbach’s alphas were 0.90, 0.90, and 0.89, for the total, Meaning/Peace, and Faith scales, respectively. For all three spiritual/belief questions, patients who responded “yes” had higher total and faith scores than those who responded “no"; but not in the Meaning/Peace score when reporting religion (p=0.108). This cohort reported lower total scores (mean=32.5), Meaning/Peace scores (mean=23.4, median=24.0) and Faith scores (mean=9.2, median=10.0) compared to the initial validation in other solid tumors and HIV/AIDs (means=38.5, 25.2, 13.6, respectively) and to a smaller, less diverse PBT sample (medians: Meaning/Peace=25.8, Faith=14.0). The FACIT-SP 12 demonstrated internal consistency and construct validity, with lower scores in comparison to populations in prior studies. More diverse belief systems than previously reported may contribute to differences among studies. Future analysis should explore the increased percentage of “prefer not to answer” respondents compared to earlier reports, associations with clinical and self-reported outcomes including symptoms and quality of life, evaluation of illness-related factors that contribute to poor spiritual well-being, and a longitudinal look at spiritual well-being. Citation Format: Elizabeth Vera, Byram Ozer, Alvina Acquaye-Mallory, Valentina Pillai, Anna Choi, Ewa Grajkowska, Tricia Kunst, Hope Miller, Kimberly Reinhart, Terri S. Armstrong, Macy Stockdill. Psychometric evaluation of the FACIT-SP 12 in a primary brain tumor patient population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6299.