Unadjusted Values Research Articles

Monitoring of prostate-specific antigen in men with benign prostate enlargement receiving 5-alpha reductase inhibitors: a non-interventional, cross-sectional study of real-world practice of urologists in Spain and Brazil

BackgroundInconsistent monitoring of prostate-specific antigen in patients receiving 5-alpha reductase inhibitors for lower urinary tract symptoms/benign prostate enlargement may affect prostate cancer outcomes. This study evaluated real-world practice among urologists treating patients receiving 5-alpha reductase inhibitors.MethodsThis non-interventional, cross-sectional study collected data from urologists in Spain (N = 100) and Brazil (N = 100) via a self-reporting questionnaire and patient record forms. Endpoints included: frequency/methodology of prostate-specific antigen monitoring, concerns about the effect of 5-alpha reductase inhibitors on prostate-specific antigen monitoring, triggers of prostate biopsy, and concerns when switching 5-alpha reductase inhibitor formulation.ResultsOver half of urologists monitored prostate-specific antigen every 6 months (Spain 59%, Brazil 58%). Preferred methods were the “doubling rule” (Spain 66%, Brazil 41%) and “increase from nadir” (Spain 28%, Brazil 43%). A minority of urologists monitored unadjusted values (Spain 3%, Brazil 11%) or did not monitor prostate-specific antigen (Spain 1%, Brazil 3%). Most urologists ranked the potential for 5-alpha reductase inhibitors to mask prostate cancer as their top concern (Spain 65%, Brazil 56%). The most selected trigger for prostate biopsy was “if doubled (adjusted) prostate-specific antigen level after 6 months of treatment is > 4 ng/mL” (Spain 39%, Brazil 37%). Many urologists were moderately/very concerned about the effect on prostate-specific antigen when switching 5-alpha reductase inhibitor formulation.ConclusionsAn unmet need exists for standard guidance and continuous education to support optimal monitoring and interpretation of prostate-specific antigen in patients with lower urinary tract symptoms/benign prostate enlargement treated with 5-alpha reductase inhibitors.

Trajectory of health-related quality of life during and after hospitalisation due to worsening of heart failure.

This study aimed to examine the trajectory in health-related quality of life (HRQoL) during and after hospitalisation for worsening of heart failure (HF) in Malaysia. 200 patients with heart failure and reduced ejection fraction (HFrEF) admitted into two hospitals in Malaysia due to worsening of HF were surveyed using the EQ-5D-5L questionnaire. The primary outcomes were utility values at admission, discharge and 1-month post-discharge (1MPD). Secondary outcomes included the visual analogue scores (VAS) and the proportion of patients reporting each EQ-5D-5L dimension levels. Missing data were imputed using multiple imputation, and generalised linear mixed models were fitted. At admission, the unadjusted mean utility values and VAS scores for HFrEF patients in Malaysia were as low as 0.150 ± 0.393 and 38.2 ± 20.8, respectively. After a median hospital stay of 4 days, there was a significant improvement in utility values and VAS scores by 0.510 (95% CI: 0.455-0.564) and 28.8 (95% CI: 25.5-32.1), respectively. The utility value and VAS score at 1-month post-discharge were not significantly different from discharge. The proportion of HFrEF patients reporting problems and severe problems in mobility, self-care, usual activities, and anxiety/depression, pain/discomfort reduced at varying degree from admission to discharge and 1MPD. HF is a progressive condition with substantial variation in HRQoL during the disease trajectory. During hospitalisation due to worsening of HF, HFrEF population has unfavourable HRQoL. Rapid and significant HRQoL improvement was observed at discharge, which sustained over one month. The study findings can inform future cost-effectiveness analyses and policies.

Habitual coffee consumption and risk of cardiovascular and all-cause mortality in the PAMELA hypertensive population

Background and aimsEvidence has been provided that in the normotensive population chronic coffee consumption does not adversely affect cardiovascular and total mortality. Whether and to what extent this is the case also in high risk cardiovascular patients such as those with elevated blood pressure (BP) is largely debated. Methods and resultsWe analyzed data collected in 943 hypertensive patients belonging to the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, which were classified as coffee consumers and non-consumers (self report). Cardiovascular and total mortality were evaluated at the 25 year follow-up taking into account a number of variables including office and 24-h ambulatory BP. When data were analyzed as unadjusted values no significant difference in hazard ratios for cardiovascular and total mortality was detected in coffee consumers and non-consumers considering office (0.85 and 0.83 respectively, PNS) or 24-h (1.08 vs 0.80 respectively, PNS) BP. This was the case also when the data were adjusted for confounders (age, sex, BP, lipid profile, plasma glucose and cholesterol levels, renal function, previous cardiovascular events) or when analyzed according to presence or absence of antihypertensive treatment. ConclusionsThus in mild-to-moderate hypertensive patients chronic coffee consumption does not exert deleterious long-term effects on cardiovascular and total mortality. This is the case in both genders and in treated and untreated hypertensive patients.

Exploring the role of body mass index-adjusted calf circumference within the SARC-CalF screening tool among older patients with cancer

ObjectivesThis study aimed to assess and compare the frequency of positive scores using unadjusted SARC-CalF with the scores derived from SARC-CalF after adjusting calf circumference (CC) for body mass index (BMI). The secondary aim was to assess the prognostic value of SARC-CalF after BMI adjustment, for length of hospital stay (LOS) and mortality. Design, Setting, and ParticipantsThis secondary analysis of a prospective cohort study, included both outpatients and inpatients of an oncology unit hospital in Brazil. MeasurementsBMI and CC were measured. Patients with excess weight had their CC adjusted for BMI by subtracting 3 cm, 7 cm, and 12 cm from the unadjusted CC values for respective BMI categories. SARC-CalF was used to screen for sarcopenia. Scores ≥11 were indicative of sarcopenia, considering both unadjusted and BMI-adjusted CC values. Clinical outcomes included prolonged LOS and both short- and long-term mortality. ResultsOur study included 206 subjects, with a median age of 69 years, and the majority were males (52.1%). The prevalence of low CC increased from 65% to 84% after BMI adjustment. Positive unadjusted SARC-CalF scores (≥11) were observed in 51% of the population and this prevalence increased to 65% using BMI-adjusted SARC-CalF criteria (≥11). Higher scores on BMI-adjusted SARC-CalF but not unadjusted SARC-CalF were independently associated with prolonged LOS [adjusted HR: 1.26 (1.03–1.53)], and 6-month mortality [adjusted HR: 1.42 (1.07–1.87)]. Both unadjusted and BMI-adjusted SARC-CalF were independently associated with 12-month mortality. ConclusionBMI-adjusted SARC-CalF may be a promising strategy to enhance the detection of older patients with cancer and excess weight at risk of sarcopenia, and it may serve a dual role as a prognostic tool, as it was independently associated with prolonged LOS and mortality.

Declining Inflation-Adjusted Medicare Physician Fees: An Unsustainable Trend in Hip Arthroscopy.

Although hip arthroscopy continues to be one of the most used arthroscopic procedures, no focused, comprehensive evaluation of reimbursement trends has been conducted. The purpose of this study was to analyze the temporal Medicare reimbursement trends for hip arthroscopy procedures. From 2011 to 2021, the Medicare Physician Fee Schedule Look-Up Tool was queried for Current Procedural Terminology (CPT) codes related to hip arthroscopy (29860 to 29863, 29914 to 29916). All monetary data were adjusted to 2021 US dollars. The compound annual growth rate and total percentage change were calculated. Mann-Kendall trend tests were used to evaluate the reimbursement trends. Based on the unadjusted values, a significant increase in physician fee was observed from 2011 to 2021 for CPT codes 29861 (removal of loose or foreign bodies; % change: 3.49, P = 0.03) and 29862 (chondroplasty, abrasion arthroplasty, labral resection; % change: 3.19, P = 0.03). The remaining CPT codes experienced no notable changes in reimbursement based on the unadjusted values. After adjusting for inflation, all seven of the hip arthroscopy CPT codes were observed to experience a notable decline in Medicare reimbursement. Hip arthroscopy with acetabuloplasty (CPT: 29915) and labral repair (CPT: 29916) exhibited the greatest reduction in reimbursement with a decrease in physician fee of 24.69% ( P < 0.001) and 24.64% ( P < 0.001), respectively, over the study period. Medicare reimbursement for all seven of the commonly used hip arthroscopy services did not keep up with inflation, demonstrating marked reductions from 2011 to 2021. Specifically, the inflation-adjusted reimbursements decreased between 19.23% and 24.69% between 2011 and 2021.

Abstract 15486: In-Hospital Outcomes After Cardiac Transplantation in Patients With Autism Spectrum Disorders: Insights From the National Inpatient Sample 2011-2019

Introduction: Many governing bodies and major international societies recommend against heart transplantation (HTx) in patients with severe cognitive-behavioral disabilities, however no clear criteria are offered to define severity. Patients with Autism Spectrum Disorders (ASD) may face systematic discrimination when being evaluated for HTx. There is a lack of data regarding outcomes after HTx in patients with ASD. Methods: The NIS was queried from 2011-2019 for relevant ICD-9 and ICD-10 codes to identify patients with and without ASD who underwent HTx. Baseline characteristics and in-hospital outcomes between patients were compared. Binary logistic regression was used to adjust outcomes for significantly different baseline characteristics (p&lt;0.05). Results: We identified a weighted sample of 25,456 patients who underwent HTx, of which 80 had a concurrent diagnosis of ASD. Because less than .05% of the adult HTx population had ASD, the outcome analysis was restricted to the pediatric population. After restriction there were 3,769 pediatric patients who underwent HTx, of which 70 had a diagnosis of ASD. There were no significant differences in mortality, transplant related complications (acute graft rejection, acute graft failure, acute cardiac allograft vasculopathy and unspecified complications), cardiac arrest, periprocedural sepsis, mechanical circulatory support, stroke and bleeding/vascular complications between groups. While unadjusted values signaled a difference in the rate of complete heart block (CHB), there was no significant difference after application to a binary logistic regression model (CHB aOR: 1.83, 95% CI .70 to 4.77, p=0.22) Total cost of stay was significantly higher in the ASD group ($2,017,389±$2,136,742 versus $1,675,459±$1,604,926, p&lt;0.05) while total length of stay was higher in the non ASD group (79.6±72 days versus 64.8±53.7 days, p&lt;0.05). Conclusion: There are no significant differences in outcomes after HTx between pediatric patients with and without ASD. The exclusion of patients with ASD from some transplant programs represents a major disparity in healthcare and transplant teams should consider a multidisciplinary approach to evaluating ASD patients for Htx.

Using Days Alive and Out of Hospital to measure inequities and possible pathways for them after cardiovascular surgery in Aotearoa New Zealand: study protocol for a secondary data analysis

IntroductionIn Aotearoa New Zealand (NZ), socioeconomic status and being of Māori ethnicity are often associated with poorer health outcomes, including after surgery. Inequities can be partially explained by differences in...

728-P: Biomarkers of Low-Grade Inflammation in Novel Subtypes of Patients at Risk for Diabetes

In the Tübingen Family Study recently 6 subtypes of prediabetic metabolism were identified. Cluster 3, 5 and 6 have a moderate to high risk for T2D or its associated complications. Cluster 3 is characterized by low insulin secretion, cluster 5 by insulin resistance and high liver fat content. Individuals in cluster 6 have an elevated risk of nephropathy despite a delayed diabetes development. Low-grade inflammation has been implicated in the development of T2D and cardiorenal complications. We hypothesized that the subtypes differ in levels of inflammatory biomarkers. Thus, we measured 31 inflammatory biomarkers associated with metabolic disease. We used Bio-Plex® multiplex immunoassays in 145 individuals who were recruited in Tübingen from the Prediabetes Lifestyle Intervention Study (PLIS) - a multicenter study conducted in individuals with ADA-defined prediabetes. Cluster comparison was done using ANOVA models, raw unadjusted values are reported. We identified eight biomarkers which differed among diabetes-risk subtypes, namely MIP1a, MIP1b, IL18, Osteopontin (OPN), IFNy, TNFb, and soluble TNFa-Receptor (sTNF-R)- 1 and -2. High risk cluster 3, 5 and 6 had significantly elevated levels of several inflammatory biomarkers compared to low risk cluster 2 with the lowest levels of these biomarkers. Within the high-risk groups, cluster 5 had increased biomarker levels compared to cluster 3 (e.g., IL-18: cluster 5: 86.2 pg/ml ± 3.9 vs cluster 3: 66.8 pg/ml ± 4.8, p=0.018; OPN: 16.8 ng/ml ± 1.0 vs. 12.8 ng/ml ± 0.8, p = 0.022; MIP1a 2.2 pg/ml ± 0.1 vs. 1.6 pg/ml ± 0.1, p &amp;lt; 0.001). Cluster 6 showed lower levels of IFNy than cluster 3 (2.2pg/ml ± 0.3 vs 3.5pg/ml ± 0.2, P=0.019). Our data show that the novel T2D risk subtypes differ in inflammatory biomarkers. This suggests that a low-grade inflammation may be involved in the progression from prediabetes to T2D and complications. A more precise mechanistic understanding is needed in order to establish precise preventive strategies for different risk phenotypes. Disclosure S.Katzenstein: None. J.Szendroedi: None. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. L.Fritsche: None. N.Stefan: Advisory Panel; Pfizer Inc., Research Support; Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. A.L.Birkenfeld: None. R.Jumpertz von schwartzenberg: Other Relationship; Sanofi, Amgen Inc., Lilly, Novo Nordisk. A.Sandforth: None. V.Minelli faiao: None. J.Seissler: None. S.R.Bornstein: None. N.Perakakis: Advisory Panel; Bayer Inc., Other Relationship; Novo Nordisk, Novo Nordisk. A.Schürmann: None. S.Kabisch: Other Relationship; Berlin-Chemie AG, Sanofi, Lilly, Boehringer Ingelheim Inc., JuZo Akademie, Research Support; J. Rettenmaier / Söhne, Wilhelm-Doerenkamp Foundation, German Center of Diabetes Research. M.Blüher: Advisory Panel; Boehringer Ingelheim Inc., Lilly, Novo Nordisk, Consultant; Novo Nordisk Foundation, Speaker's Bureau; Amgen Inc., AstraZeneca, Bayer Inc., Daiichi Sankyo, Novartis, Sanofi-Aventis Deutschland GmbH.

Estimating baseline creatinine to detect acute kidney injury in patients with chronic kidney disease.

Accurately estimating baseline kidney function is essential for diagnosing acute kidney injury (AKI) in patients with chronic kidney disease (CKD). We developed and evaluated novel equations to estimate baseline creatinine in patients with AKI on CKD. We retrospectively analysed 5649 adults with AKI out of 11 254 CKD patients, dividing them evenly into derivation and validation groups. Using quantiles regression, we created equations to estimate baseline creatinine, considering historical creatinine values, months since measurement, age, and sex from the derivation dataset. We assessed performance against back-estimation equations and unadjusted historical creatinine values using the validation dataset. The optimal equation adjusted the most recent creatinine value for time since measurement and sex. Estimates closely matched the actual baseline at AKI onset, with median (95% confidence interval) differences of just 0.9% (-0.8% to 2.1%) and 0.6% (-1.6% to 3.9%) when the most recent value was within 6 months to 30 days and 2 years to 6 months before AKI onset, respectively. The equation improved AKI event reclassification by an additional 2.5% (2.0% to 3.0%) compared to the unadjusted most recent creatinine value and 7.3% (6.2% to 8.4%) compared to the CKD-EPI 2021 back-estimation equation. Creatinine levels drift in patients with CKD, causing false positives in AKI detection without adjustment. Our novel equation adjusts the most recent creatinine value for drift over time. It provides more accurate baseline creatinine estimation in patients with suspected AKI on CKD, which reduces false-positive AKI detection, improving patient care and management.

P142 Cytomegalovirus seropositivity is associated with an increased frequency of highly differentiated T effector memory cells re-expressing CD45RA (Temra) and persistent disease refractory to anti-TNF therapy in rheumatoid arthritis

Abstract Background/Aims The role of highly differentiated T effector memory re-expressing CD45RA (Temra) in rheumatoid arthritis (RA) is unclear, including whether they can be used as a marker of persistent disease activity. Our aim was to investigate whether peripheral blood Temra frequency can be used to identify RA patients with active disease refractory to anti-TNF therapy. As cytomegalovirus (CMV) has been reported to be associated with the expansion of Temra as well as implicated in RA pathogenesis, we also explored the relationship between serum CMV immunoglobulin (IgG) status, Temra, and remission status. Methods A cross-sectional cohort of RA patients on anti-TNF therapy were recruited. Patients were stratified based on remission status. Remission was defined as no recorded DAS28-CRP≥2.4, no swollen joints, no C-reactive protein (CRP) &amp;gt;5mg/L, and on a stable DMARD dose and no reported disease flare/loss of remission in the last 6 months before recruitment. Patients on abatacept or on conventional DMARDs only were recruited as comparison groups. Peripheral blood mononuclear cells (PBMC) were analysed by flow cytometry. Serum CMV IgG was analysed by ELISA. Two-tailed Mann-Whitney U test or unpaired t-test were used to obtain unadjusted values, analysis of variance (ANOVA) of log-transformed data to obtain age-adjusted values, Spearman’s rank correlation to compare correlation between two variables, Fisher’s exact test to compare proportions. Results Thirty-six anti-TNF, 12 abatacept, and 16 patients on conventional synthetic DMARDs (csDMARDs) only were recruited. A higher proportion of CD4 and CD8 Temra (age-adjusted p = 0.004 and p = 0.0007 respectively) was observed in RA patients on anti-TNF with persistent disease compared to those in remission. This difference in Temra frequency was not observed in patients treated with csDMARDs only or abatacept. CD4 and CD8 Temra frequency correlated positively with CMV IgG levels (Spearman r = 0.8987, p &amp;lt; 0.0001 and Spearman r = 0.7211, p &amp;lt; 0.0001 respectively). There was a strikingly high proportion of anti-TNF patients with persistent disease who were CMV seropositive compared to anti-TNF patients in remission (93% versus 42%, Fisher’s exact test, p = 0.009). This difference was less marked and not significant in the other treatment groups. Conclusion The increased CMV seropositivity and Temra frequency in the context of persistent disease only in anti-TNF treated patients may provide a causal link between Temra and RA pathogenesis refractory to anti-TNF treatment. Disclosure S. Yeoh: Grants/research support; S.A.Y. has received funding for research from Versus Arthritis, Royal College of Physicians, Rosetrees Trust, University College London Hospitals NIHR BRC and UCLH charities. J. Kimpton: None. M. Shipa: Grants/research support; M.S. has received funding for research from Versus Arthritis and GSK. E. Hawkins: None. A. Akbar: Grants/research support; A.A. has received funding for research from the Medical Research Council and the Leo Skin Foundation (Denmark). M. Ehrenstein: None.

Bovine colostrum as a fortifier to human milk in very preterm infants – A randomized controlled trial (FortiColos)

Human milk for very preterm infants need fortification for optimal growth and development but the optimal fortification product remains to be identified. To investigate feasibility, safety and preliminary efficacy on growth and blood biochemistry when using intact bovine colostrum (BC) as a fortifier to human milk in very preterm infants. In an open-label, multicenter, randomized controlled pilot trial (infants 26-31 weeks' gestation), mother's own milk or donor human milk was fortified with powdered BC (n=115) or a conventional fortifier (CF, bovine-milk-based, n=117) until 35 weeks' postmenstrual age. Fortifiers and additional micronutrients were added to human milk according to local guidelines to achieve optimal growth (additional protein up to+1.4g protein/100mL human milk). Anthropometry was recorded weekly. Clinical morbidities including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) were recorded. Clinical biochemistry included plasma amino acid (AA) levels to assess protein metabolic responses to the new fortifier. A total of 232 infants, gestational age (GA) 28.5±1.4 (weeks+days), fulfilled inclusion criteria. Birthweight, GA and delta Z scores from birth to end of intervention on weight, length or head circumference did not differ between groups, nor between the subgroups of small for gestational age infants. Likewise, incidence of NEC (BC: 3/115 vs. CF: 5/117, p=0.72, unadjusted values), LOS (BC: 23/113 vs. CF: 14/116, p=0.08) and other morbidities did not differ. BC infants received more protein than CF infants (+10%, p<0.05) and showed several elevated AA levels (+10-40%, p<0.05). Infants fortified with BC showed similar growth but received more protein and showed a moderate increase in plasma AA-levels, compared with CF. Adjustments in protein composition and micronutrients in BC-based fortifiers may be required to fully suit the needs for very preterm infants.

Reactive Extraction of Betaine from Sugarbeet Processing Byproducts.

Betaine from natural sources is still preferred over its synthetic analogue in secondary industries. It is currently obtained by expensive separation means, which is one of the main reasons for its high cost. In this study, reactive extraction of betaine from sugarbeet industry byproducts, that is, molasses and vinasse, was investigated. Dinonylnaphthalenedisulfonic acid (DNNDSA) was used as the extraction agent, and the initial concentration of betaine in the aqueous solutions of byproducts was adjusted to 0.1 M. Although maximum efficiencies were obtained at unadjusted pH values (pH 6, 5, and 6 for aqueous betaine, molasses, and vinasse solutions, respectively), the effect of aqueous pH on betaine extraction was negligible in the range of 2-12. The possible reaction mechanisms between betaine and DNNDSA under acidic, neutral, and basic conditions were discussed. Increasing the extractant concentration significantly increased (especially in the range of 0.1-0.4 M) the yields, and temperature positively (but slightly) affected betaine extraction. The highest extraction efficiencies (∼71.5, 71, and 67.5% in a single step for aqueous betaine, vinasse, and molasses solutions, respectively) were obtained with toluene as an organic phase solvent, and it was followed by dimethyl phthalate, 1-octanol, or methyl isobutyl ketone, indicating that the efficiency increased with decreasing polarity. Recoveries from pure betaine solutions were higher (especially at higher pH values and [DNNDSA] < 0.5 M) than those from vinasse and molasses solutions, indicating the adverse influence of byproduct constituents; however, the lower yields were not due to sucrose. Stripping was affected by the type of organic phase solvent, and a significant amount (66-91% in single step) of betaine in the organic phase was transferred to the second aqueous phase using NaOH as the stripping agent. Reactive extraction has a great potential for use in betaine recovery due to its high efficiency, simplicity, low energy demand, and cost.

Quantifying health-related quality of life in Malaysian type 2 diabetes: focusing on complication types and severity.

There is a knowledge gap of health utility values for Type 2 Diabetes Mellitus (T2DM) complications in Malaysia. This study aimed to estimate EQ-5D-5L utility values and evaluate health-related quality of life (HRQoL) for Malaysian T2DM associated with complications and clinical characteristics. A cross-sectional study was conducted on T2DM patients at a tertiary hospital outpatient using the Malay and English version of the EQ-5D-5L questionnaire. Health utility values were derived using the Malaysian EQ-5D-5L value set. Ordinary least squares (OLS) multivariable regression model was used to estimate the health utility decrements associated with T2DM-related complications and clinical characteristics. A total of 513 T2DM patients were recruited. Overall, pain was the most affected of all five EQ-5D-5L dimensions. Patients with foot ulcer, amputation, severe heart failure and frequent hypoglycemia reported more problems collectively in all EQ-5D-5L dimensions. Older age, lower education level, longer duration of T2DM, urine protein creatine index (UPCI) > 0.02g/mmol, and injection therapy were significantly associated with lower EQ-5D-5L utility values (p < 0.004, Bonferroni adjusted). The lowest unadjusted utility values were reported for severe heart failure 0.65 (interquartile range, IQR 0.50), frequent hypoglycemia 0.74 (0.22) and being amputated 0.78 (0.47). In the multivariable regression model after controlling for sociodemographic and clinical characteristics, the largest utility value decrement was observed for amputation (-0.158, SE 0.087, p = 0.05), frequent hypoglycemia (-0.101, SE 0.030, p = 0.001), myocardial infarction (-0.050, SE 0.022, p = 0.022) and obesity (-0.034, SE 0.016, p = 0.029). Larger utility value decrements were found for severe stages of complications. These findings suggest the value of defining severity of complications in utility elicitation studies. The utility decrement quantified for different T2DM complication severity will be useful for economic evaluations within diabetic-related fields.

Detection of microplastics in human saphenous vein tissue using μFTIR: A pilot study.

Microplastics (MPs) are ubiquitous in the environment, in the human food chain, and have been recently detected in blood and lung tissues. To undertake a pilot analysis of MP contamination in human vein tissue samples with respect to their presence (if any), levels, and characteristics of any particles identified. This study analysed digested human saphenous vein tissue samples (n = 5) using μFTIR spectroscopy (size limitation of 5 μm) to detect and characterise any MPs present. In total, 20 MP particles consisting of five MP polymer types were identified within 4 of the 5 vein tissue samples with an unadjusted average of 29.28 ± 34.88 MP/g of tissue (expressed as 14.99 ± 17.18 MP/g after background subtraction adjustments). Of the MPs detected in vein samples, five polymer types were identified, of irregular shape (90%), with alkyd resin (45%), poly (vinyl propionate/acetate, PVAc (20%) and nylon-ethylene-vinyl acetate, nylon-EVA, tie layer (20%) the most abundant. While the MP levels within tissue samples were not significantly different than those identified within procedural blanks (which represent airborne contamination at time of sampling), they were comprised of different plastic polymer types. The blanks comprised n = 13 MP particles of four MP polymer types with the most abundant being polytetrafluoroethylene (PTFE), then polypropylene (PP), polyethylene terephthalate (PET) and polyfumaronitrile:styrene (FNS), with a mean ± SD of 10.4 ± 9.21, p = 0.293. This study reports the highest level of contamination control and reports unadjusted values alongside different contamination adjustment techniques. This is the first evidence of MP contamination of human vascular tissues. These results support the phenomenon of transport of MPs within human tissues, specifically blood vessels, and this characterisation of types and levels can now inform realistic conditions for laboratory exposure experiments, with the aim of determining vascular health impacts.

NEUROFILAMENT LIGHT CHAIN (NFL) AND GENERAL COGNITIVE ABILITY IN ADULTS APPROACHING MIDLIFE

Abstract Neurofilament light chain (NfL) is a biomarker indexing axonal integrity where small NfL variations may be associated with cognitive performance in early adulthood and high values associated with neurodegenerative disorders such as Alzheimer’s disease. In the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife1) individuals were tested at 28–49 years (M=33.1, SD=4.9). Quanterix Simoa assays of plasma NfL (pNfL) were measured in duplicate, and we included values for 1159 individuals where 1098 had available general cognitive ability scores and sociodemographic covariates. Unadjusted NfL values were consistent with other studies of early-mid adulthood (M = 5.9, SD = 3.1, range = 1.14 – 40.1 pg/mL) and 6% showed values outside expected normal reference limits (&amp;gt;10 pg/mL). After adjusting for technical covariates and skew, higher natural log-transformed pNfL was associated with age (r = 0.27) and female sex (r = 0.07). Moreover, adjusting for sociodemographic covariates, higher pNfL was associated with lower general cognitive ability (GCA) (r = -.06), where associations were more pronounced above the mean pNfL value (r = -.08). Multi-level regression analyses suggested that GCA-NfL associations were modified by age, whereby the worse performance was observed at higher ages and pNfL values (p &amp;lt;= 0.03), accounting for sibling relatedness and sociodemographic covariates. We observed small negative associations of higher plasma NfL and lower cognitive performance, where associations may become magnified with increasing age in early- to mid-adulthood.

Neuroimaging Findings in a Racially and Ethnically Diverse Cohort of Oldest‐Old Individuals: The LifeAfter90 Study

AbstractBackgroundNeuroimaging biomarkers are important and widely used in dementia research. Such studies, however, are rare in the oldest‐old and essentially non‐existent in ethnically diverse oldest‐old populations where the prevalence of cognitive impairment is greatest and dementia due to multiple pathologies. Here we present initial neuroimaging findings in the LifeAfter90 Study, a racially and ethnically diverse cohort of oldest‐old individuals.MethodsLifeAfter90 is a cohort of long‐term members of a health‐care system aged 90+ without a dementia diagnosis in their medical record at recruitment and clinical assessments every 6 months. Of the &gt;800 participants enrolled, a subset agreed to brain imaging (MRI and amyloid PET). Hippocampal volume (HV) and white matter hyperintensities (WMH) were normalized to intracranial volume and WMH was log transformed. Amyloid burden was quantified as the mean SUVR values of 4 regions and dichotomized with an SUVR cutpoint of 1.10. Mean neuroimaging marker levels were compared between ethnoracial groups with analysis of covariance adjusting for age.ResultsTo date, 99 individuals have undergone an MRI and 90 an amyloid PET scan. The average age at the time of scan was 93 years, 60% of participants were women, and 43% had college education or higher (Table 1). Unadjusted values of neuroimaging findings are in Table 1 and adjusted means in Table 2 and Figure. In our preliminary data, we see 44% amyloid positivity overall. Black individuals have the lowest proportion of amyloid positivity (32%) but among the highest WMH mean volume, whereas Latino individuals have the highest proportion of amyloid positivity (64%) and lowest WMH mean volume. Asian individuals had the highest mean hippocampal volume. Except for SUVR differences in Black vs Latino individuals (p=.04), there were no group differences in mean levels (Figure).ConclusionsWe present neuroimaging findings from a first‐of‐its kind multi‐ethnic cohort study of oldest‐old individuals. Although too early to test for differences due to the small number of individuals, we have indications of ethnoracial differences in levels of neuropathologies consistent with those of younger elderly. Determining the utility of neuroimaging biomarkers for identifying future disease in these individuals is essential for advancing cognitive research.

Long-term regional trends of nitrogen and sulfur deposition in the United States from 2002 to 2017

Abstract. Atmospheric deposition of nitrogen (N) and sulfur (S) compounds from human activity has greatly declined in the United States (US) over the past several decades in response to emission controls set by the Clean Air Act. While many observational studies have investigated spatial and temporal trends of atmospheric deposition, modeling assessments can provide useful information over areas with sparse measurements, although they usually have larger horizontal resolutions and are limited by input data availability. In this analysis, we evaluate wet, dry, and total N and S deposition from multiyear simulations within the contiguous US (CONUS). Community Multiscale Air Quality (CMAQ) model estimates from the EPA's (Environmental Protection Agency) Air QUAlity TimE Series (EQUATES) project contain important model updates to atmospheric deposition algorithms compared to previous model data, including the new Surface Tiled Aerosol and Gaseous Exchange (STAGE) bidirectional deposition model which contains land-use-specific resistance parameterization and land-use-specific deposition estimates needed to estimate the differential impacts of N deposition to different land use types. First, we evaluate model estimates of wet deposition and ambient concentrations, finding underestimates of SO4, NO3, and NH4 wet deposition compared to National Atmospheric Deposition Program observations and underestimates of NH4 and SO4 and overestimates of SO2 and TNO3 (HNO3+NO3) compared to the Clean Air Status and Trends Network (CASTNET) ambient concentrations. Second, a measurement–model fusion approach employing a precipitation and bias correction to wet-deposition estimates is found to reduce model bias and improve correlations compared to the unadjusted model values. Model agreement of wet deposition is poor over parts of the West and Northern Rockies, due to errors in precipitation estimates caused by complex terrain and uncertainty in emissions at the relatively coarse 12 km grid resolution used in this study. Next, we assess modeled N and S deposition trends across climatologically consistent regions in the CONUS. Total deposition of N and S in the eastern US is larger than the western US with a steeper decreasing trend from 2002–2017; i.e., total N declined at a rate of approximately −0.30 kg N ha−1 yr−1 in the Northeast and Southeast and by −0.02 kg N ha−1 yr−1 in the Northwest and Southwest. Widespread increases in reduced N deposition across the Upper Midwest, Northern Rockies, and West indicate evolving atmospheric composition due to increased precipitation amounts over some areas, growing agricultural emissions, and regional NOx/SOx emission reductions shifting gas–aerosol partitioning; these increases in reduced N deposition are generally masked by the larger decreasing oxidized N trend. We find larger average declining trends of total N and S deposition between 2002–2009 than 2010–2017, suggesting a slowdown of the rate of decline likely in response to smaller emission reductions. Finally, we document changes in the modeled total N and S deposition budgets. The average annual total N deposition budget over the CONUS decreases from 7.8 in 2002 to 6.3 kg N ha−1 yr−1 in 2017 due to declines in oxidized N deposition from NOx emission controls. Across the CONUS during the 2002–2017 time period, the average contribution of dry deposition to the total N deposition budget drops from 60 % to 52 %, whereas wet deposition dominates the S budget rising from 45 % to 68 %. Our analysis extends upon the literature documenting the growing contribution of reduced N to the total deposition budget, particularly in the Upper Midwest and Northern Rockies, and documents a slowdown of the declining oxidized N deposition trend, which may have consequences on vegetation diversity and productivity.

166. A STUDY OF THE LEARNING CURVE FOR LAPAROSCOPIC-ASSISTED SINGLE-PORT MEDIASTINOSCOPIC ESOPHAGECTOMY

Abstract Laparoscopic-assisted single-port mediastinoscopic esophagectomy is a safe and effective emerging minimally invasive esophagectomy. However, nothing has been reported about the learning curve for this technique. The goal of this study was to analyze the learning curve of this technique and to determine the number of procedures performed to achieve different levels of proficiency to improve surgeons’ understanding of the learning process of this new technique. This study retrospectively collected clinical data on consecutive laparoscopic-assisted single-port mediastinoscopic esophagectomies performed by the same surgeon at our center from October 2016 to August 2021. A simple scatter plot of the number of procedures versus procedure time and its trend line were plotted, using procedure time as an indicator of efficiency. Learning curves were quantitatively assessed by unadjusted cumulative sum values using the cumulative summation method, different segments were derived using joint point linear regression analysis, and variables were compared between subgroups using trend analysis. The survival analysis was performed using the Kaplan–Meier method. The learning curve could be divided into 3 different stages: the 1st–91st, 91st-125th, and 125th-182nd procedures comprised the preliminary, transition, and proficient stages, respectively. Compared with the preliminary stage, the procedure time, bleeding volume, postoperative hospital stays, and the incidence of anastomotic fistula were significantly lower in the proficiency stage, whereas the number of harvested lymph nodes and the rate of recurrent laryngeal nerve lymph node harvest was significantly higher. Additionally, there were no significant differences in overall survival and disease-free survival at different stages for patients with all, different T stages, and different N stages within 1 year postoperatively. In this study, there may be 3 stages of varying proficiency in the learning curve of laparoscopic-assisted single-port mediastinoscopic esophagectomy. Approximately 91 consecutive procedures were required to overcome the preliminary stage, whereas proficiency in this technique required approximately 125 consecutive procedures. Moreover, as the learning curve reached the proficiency stage, the perioperative indicators tended to stabilize. Furthermore, the short-term survival of patients might not be influenced by technical proficiency.

Calendar effects on surface air temperature and precipitation based on model-ensemble equilibrium and transient simulations from PMIP4 and PACMEDY

Abstract. Numerical modeling enables a comprehensive understanding not only of the Earth's system today, but also of the past. To date, a significant amount of time and effort has been devoted to paleoclimate modeling and analysis, which involves the latest and most advanced Paleoclimate Modelling Intercomparison Project phase 4 (PMIP4). The definition of seasonality, which is influenced by slow variations in the Earth's orbital parameters, plays a key role in determining the calculated seasonal cycle of the climate. In contrast to the classical calendar used today, where the lengths of the months and seasons are fixed, the angular calendar calculates the lengths of the months and seasons according to a fixed number of degrees along the Earth's orbit. When comparing simulation results for different time intervals, it is essential to account for the angular calendar to ensure that the data for comparison are from the same position along the Earth's orbit. Most models use the classical calendar, which can lead to strong distortions of the monthly and seasonal values, especially for the climate of the past. Here, by analyzing daily outputs from multiple PMIP4 model simulations, we examine calendar effects on surface air temperature and precipitation under mid-Holocene, Last Interglacial, and pre-industrial climate conditions. We came to the following conclusions. (a) The largest cooling bias occurs in boreal autumn when the classical calendar is applied for the mid-Holocene and Last Interglacial, due to the fact that the vernal equinox is fixed on 21 March. (b) The sign of the temperature anomalies between the Last Interglacial and pre-industrial in boreal autumn can be reversed after the switch from the classical to angular calendar, particularly over the Northern Hemisphere continents. (c) Precipitation over West Africa is overestimated in boreal summer and underestimated in boreal autumn when the classical seasonal cycle is applied. (d) Finally, month-length adjusted values for surface air temperature and precipitation are very similar to the day-length adjusted values, and therefore correcting the calendar based on the monthly model results can largely reduce the artificial bias. In addition, we examine the calendar effects in three transient simulations for 6–0 ka by AWI-ESM, MPI-ESM, and IPSL-CM. We find significant discrepancies between adjusted and unadjusted temperature values over continents for both hemispheres in boreal autumn, while for other seasons the deviations are relatively small. A drying bias can be found in the summer monsoon precipitation in Africa (in the classical calendar), whereby the magnitude of bias becomes smaller over time. Overall, our study underlines the importance of the application of calendar transformation in the analysis of climate simulations. Neglecting the calendar effects could lead to a profound artificial distortion of the calculated seasonal cycle of surface air temperature and precipitation.

Identifying Age Based Maturation in the ERP Response to Faces in Children With Autism: Implications for Developing Biomarkers for Use in Clinical Trials.

Recent proposals have suggested the potential for neural biomarkers to improve clinical trial processes in neurodevelopmental conditions; however, few efforts have identified whether chronological age-based adjustments will be necessary (as used in standardized behavioral assessments). Event-related potentials (ERPs) demonstrate early differences in the processing of faces vs. objects in the visual processing system by 4 years of age and age-based improvement (decreases in latency) through adolescence. Additionally, face processing has been proposed to be related to social skills as well as autistic social-communication traits. While previous reports suggest delayed latency in individuals with autism spectrum disorder (ASD), extensive individual and age based heterogeneity exists. In this report, we utilize a sample of 252 children with ASD and 118 children with typical development (TD), to assess the N170 and P100 ERP component latencies (N170L and P100L, respectively), to upright faces, the face specificity effect (difference between face and object processing), and the inversion effect (difference between face upright and inverted processing) in relation to age. First, linear mixed models (LMMs) were fitted with fixed effect of age at testing and random effect of participant, using all available data points to characterize general age-based development in the TD and ASD groups. Second, LMM models using only the TD group were used to calculate age-based residuals in both groups. The purpose of residualization was to assess how much variation in ASD participants could be accounted for by chronological age-related changes. Our data demonstrate that the N170L and P100L responses to upright faces appeared to follow a roughly linear relationship with age. In the ASD group, the distribution of the age-adjusted residual values suggest that ASD participants were more likely to demonstrate slower latencies than would be expected for a TD child of the same age, similar to what has been identified using unadjusted values. Lastly, using age-adjusted values for stratification, we found that children who demonstrated slowed age-adjusted N170L had lower verbal and non-verbal IQ and worse face memory. These data suggest that age must be considered in assessing the N170L and P100L response to upright faces as well, and these adjusted values may be used to stratify children within the autism spectrum.