95th Percentile Research Articles

Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography

BackgroundCardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. MethodsThe study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. ResultsDetectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45–1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39–1.90) for the first tertile to 2.02 (95 % CI 1.74–2.35) for the third tertile. ConclusionsDetectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.

Application timing as a mitigation tool for pesticide leaching to drains in northwest Europe

Study regionArtificially drained agricultural land in northwest Europe. Study focusThe use of application timing as a mitigation tool for pesticide leaching to drains was investigated by simulating pesticide fate after application every day in a pesticide-specific application window, using the agro-hydrological model DAISY. The simulations were carried out for six combinations of pesticide-crop-seasons using three synthetically generated climate series and 800 soil profiles. The simulated drain concentrations were transformed to normalized pesticide concentrations in a hypothetical adjacent stream. Each application day was then characterized by the maximum normalized hourly pesticide concentration in the stream, expressed as the maximum hourly toxic unit (mTU), occurring within 300 days after application. New hydrological insights for the regionThe result showed that if the pesticide was applied consistently every year at the best application day, pesticide leaching, in terms of the 90th percentile of mTU, could be reduced by up to 62% compared to a random application. If the pesticide application day was restricted to vary in a five-day period, the 90th percentile of mTU could be reduced by up to 21%. Thus, our study shows that there is a significant mitigation potential for reducing pesticide leaching to drains by tailoring the timing of pesticide application to weather conditions.

The association of the dietary inflammatory potential with risk of overall and site-specific cancers: A community-based longitudinal study in the UK Biobank

ObjectivesThe association of the dietary inflammatory potential with cancer risk remains uncertain. We examined the relationship of the dietary inflammatory potential with risk of overall and site-specific cancers and explored its sex and age differences. DesignA community-based longitudinal study. SettingParticipants from the UK Biobank completed baseline surveys during 2006–2010 and were followed for up to 15 years to detect incident cancer. Participants170,899 cancer-free participants with dietary data available (mean age: 55.73 ± 7.95, 54.10% female). MeasurementsAt baseline, dietary intake was assessed with a 24-h dietary record for up to 5 times. The inflammatory diet index (IDI) was calculated to assess the dietary inflammatory potential as a weighted sum of 31 food groups (including 14 anti-inflammatory and 17 pro-inflammatory) based on plasma high-sensitivity C-reactive protein (hsCRP) levels, and tertiled as low (indicating low-inflammatory diet), moderate, and high IDI (as reference). Overall and site-specific cancers were ascertained via linkage to routine hospital admission, cancer registry, and death certificate data. Data were analyzed using Cox regression and Laplace regression. ResultsDuring the follow-up (median 10.32 years, interquartile range: 9.95–11.14 years), 18,884 (11.05%) participants developed cancer. In multi-adjusted Cox regression, low IDI scores were associated with decreased risk of rectal cancer (hazard ratio [95% confidence interval, CI] 0.76 [0.61, 0.94]), thyroid cancer [0.45 (0.27, 0.74)], lung cancer [0.73 (0.61, 0.88)]. However, the association between IDI score and the risk of overall cancer was not significant. Laplace regression analysis showed that 10th percentile differences (95% CIs) of cancer onset time for participants with low IDI scores was prolonged by 1.29 (0.32, 2.27), 1.44 (0.58, 2.30), and 2.62 (0.98, 4.27) years for rectal cancer, thyroid cancer, and lung cancer, respectively, compared to those with high IDI scores. Stratified analysis revealed that low IDI scores were associated with a lower risk of rectal cancer (p interaction between IDI score and sex = 0.035) and lung cancer in males, but not in females, and with a reduced risk of thyroid cancer in females, but not in males. Moreover, low IDI scores were associated with a reduced risk of rectal cancer and lung cancer in the participants aged ≥60 years, but not in those <60 years, and with a reduced risk of thyroid cancer in those aged ≥60 years and <60 years. ConclusionsA low-inflammatory diet is associated with decreased risk and prolonged onset time of rectal cancer and lung cancer, especially among males and individuals aged ≥60 years, and thyroid cancer among females.

Compound and consecutive drought-flood events at a global scale

Flooding during or after droughts poses significant challenges to disaster risk management. However, interactions between droughts and floods are often overlooked as studies typically analyse these events in isolation. Here we explore historical occurrences of compound and consecutive drought-flood events and drought effects on flood severity and timing by analysing global datasets of hydrometeorological and biophysical variables for 8255 catchments worldwide. These data show that 24% of floods globally (anomalies above the 85th percentile) are preceded by, or happen during, drought conditions. Flood events occurring during drought conditions are typically of lower magnitude, especially in arid regions, while floods following drought events have a severity distribution comparable to single flood events. For most drought-flood events, flood timing appears relatively unaffected by drought conditions, but almost a quarter of the drought-flood events had flood timings occurring two to three months later than expected. These shifts in flood timing suggest droughts potentially affect flood-generating processes. As both drought and flood occurrences are projected to increase in a warming climate, interactions between them may become more common and need to be accounted for in flood risk assessment and management.

Effects of Coexposure to Air Pollution from Vegetation Fires and Extreme Heat on Mortality in Upper Northern Thailand.

Background: understanding the effects of coexposure to compound extreme events, such as air pollution and extreme heat, is important for reducing current and future health burdens. This study investigated the independent and synergistic effects of exposure to air pollution from vegetation fires and extreme heat on all-cause mortality in Upper Northern Thailand. Methods: we used a time-stratified case-crossover study design with a conditional quasi-Poisson model to examine the association between mortality and coexposure to air pollution due to vegetation fire events (fire-PM2.5) and extreme heat. Extreme heat days were defined using the 90th and 99th percentile thresholds for daily maximum temperature. Results: we observed a significant positive excess risk of mortality due to independent exposure to fire-PM2.5 and extreme heat, but not an interactive effect. All-cause mortality risk increased by 0.9% (95% confidence interval (CI): 0.1, 1.8) for each 10 μg/m3 increase in fire-PM2.5 on the same day and by 12.8% (95% CI: 10.5, 15.1) on extreme heat days (90th percentile) relative to nonextreme heat days. Conclusion: this study showed that exposure to PM2.5 from vegetation fires and extreme heat independently increased all-cause mortality risk in UNT. However, there was no evidence of a synergistic effect of these events.

Analytical validation of the Mindray CL1200i analyzer high sensitivity cardiac troponin I assay: MERITnI study.

This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies.

Associations between peak expiratory flow and frailty in olderly individuals: findings from the China health and retirement longitudinal study

PurposePeak Expiratory Flow (PEF) is associated with a variety of adverse health outcomes in older adults; however, the relationship between PEF and frailty remains uncertain, and this study investigated the relationship between PEF and frailty within an olderly Asian demographic.MethodsData were sourced from the Chinese Health and Retirement Longitudinal Study (CHARLS). Individuals in the study, all 60 years or older, underwent baseline PEF assessments quantified as standardized residual (SR) percentile values. The evaluation of frailty was conducted based on the criteria established by Fried. Participants without frailty at the outset were tracked over a four-year period, during which the relationships between PEF and frailty were examined through logistic regression and discrete-time Cox regression analyses.ResultsAmong 5,060 participants, cross-sectional analysis revealed that the prevalence of frailty was 2–3 times higher in the lower 10–49th and &amp;lt; 10th SR percentile groups compared to the 80–100th SR percentile group. The longitudinal study corroborated these results, showing an adjusted hazard ratio (HR) of 2.01 (95% CI, 1.15–3.51) for PEF SR percentiles below the 10th, in contrast to those between the 80th and 100th percentiles.ConclusionPEF independently predicts and determines frailty in older adults. Declines in PEF greater than expected are associated with the development of frailty. Subsequent studies are encouraged to delve deeper into the connection between respiratory function and frailty in diverse contexts.

Analysis of Autism Incidence in High IQ Societies

This study investigates the prevalence of autistic traits among individuals with high IQ, specifically in populations whose admission to high-IQ societies requires a score in the 98ᵗʰ percentile or above. The investigation incorporates a meticulous bibliographic review, complemented by interviews with representatives from high-IQ societies such as Intertel, Infinity International Society (IIS), ePiq, and ISI Society. These societies report the absence of an explicit criterion for autism diagnosis during the admission process, which is based solely on supervised psychometric IQ tests. Nonetheless, these organizations acknowledge a notable incidence of IQ reports coinciding with preexisting autism diagnoses but do not believe they constitute the majority or even half of the individuals. A survey conducted with members of the “Gifted” group, represented by high-IQ individuals from various nationalities with a predominance of Europeans and Brazilians, revealed that while the majority of participants had taken IQ tests, those diagnosed with autism did not constitute the majority. This phenomenon suggests a significant barrier in the comprehensive assessment of autism in contexts where the primary focus is intelligence measurement. This study implies the need for a deeper integration of neuropsychological diagnoses into the admission processes of these societies for a more precise mapping of the intersections between high IQ and autistic traits.

Effect of genotyping density on the detection of runs of homozygosity and heterozygosity in cattle.

Runs of homozygosity (ROHom) are contiguous stretches of homozygous regions of the genome. In contrast, runs of heterozygosity (ROHet) are heterozygosity-rich regions. The detection of these two types of genomic regions (ROHom and ROHet) is influenced by the parameters involved in their identification and the number of available single nucleotide polymorphisms (SNP). The present study aimed to test the effect of chip density in detecting ROHom and ROHet in the Italian Simmental cattle breed. A sample of 897 animals were genotyped at low-density (50k SNP; 397 individuals), medium-density (140k SNP; 348 individuals), or high-density (800k SNP; 152 individuals). The number of ROHom and ROHet per animal (nROHom and nROHet, respectively) and their average length were calculated. ROHom or ROHet shared by more than one animal and the number of times a particular SNP was inside a run were also computed (SNPROHom and SNPROHet). As the chip density increased, the nROHom increased, whereas their average length decreased. In contrast, the nROHet decreased and the average length increased as the chip density increased. The most repeated ROHom harbored no genes, whereas in the most repeated ROHet four genes (SNRPN, SNURF, UBE3A and ATP10A) previously associated with reproductive traits were found. Across the three datasets, 31 SNP, located on Bos taurus autosome (BTA) 6, and 37 SNP (located on BTA21) exceeded the 99th percentile in the distribution of the SNPROHom and SNPROHet, respectively. The genomic region on BTA6 mapped the SLIT2, PACRGL, and KCNIP4 genes, whereas 19 and 18 genes were mapped on BTA16 and BTA21, respectively. Interestingly, most of genes found through the ROHet analysis were previously reported to be related to health, reproduction, and fitness traits. The results of the present study confirm that the detection of ROHom is more reliable when the chip density increases, whereas the ROHet trend seems to be the opposite. Genes and Quantitative Trait Loci (QTL) mapped in the highlighted regions confirm that ROHet can be due to balancing selection, thus related to fitness traits, health, and reproduction, whereas ROHom are mainly involved in production traits. The results of the present study strengthened the usefulness of these parameters in analyzing the genomes of livestock and their biological meaning.

The Relationship between Physical Activity and Motor Competence of Foundation Phase Children in Wales during the School Day

Early childhood is a crucial time for children to develop their fundamental motor skills (FMS), serving as a foundation for engagement in lifelong physical activity (PA). With increasing concerns over the declining levels of PA and motor competence (MC), the aim of this study was to explore the predictors of PA in children in a play-based curriculum. A secondary purpose was to explore levels of PA and MC during the school day. The final aim was to explore whether there were sex differences. Children (N = 94; Mage = 68.96 months, SD = 8.25) in five classes from four different schools in Wales were tested on the TGMD-2, standing long jump, and MABC-2. Levels of PA were measured using ActiGraph GT3X-BT accelerometers, and 85 children met the wear time criteria. Object control (OC) skills, standing long jump, and age significantly predicted the percentage of time spent performing sedentary behaviours F(10,73) = 3.026, p = 0.003, R2 = 0.29 (adj R2 = 0.20) and time spent on MVPA F(10,73) = 3.597, p &lt; 0.001, R2 = 0.33 (adj R2 = 0.24). Children spent an average of 48.7% of the school day performing sedentary behaviours and 9.1% performing moderate to vigorous physical activity (MVPA) and did not achieve 60 min of MVPA. The MABC revealed that 67% were below the 15th percentile. Girls spent more time than boys performing sedentary behaviours (p = 0.014), and boys spent more time than girls on MVPA (p = 0.004). Boys outperformed girls at OC skills (p &lt; 0.001), while girls outperformed boys at locomotor skills (p &lt; 0.001). These findings reinforce the pivotal role teachers and parents play in providing opportunities for children to be PA. OC skills and jump were positively associated with PA, emphasising the importance of developing FMS in early childhood. There were also sex disparities for both PA and MC, along with low levels of MC, highlighting the need for investing in comprehensive programmes and initiatives that prioritise the development of FMS during early childhood.

#1323 Kidney health in children with X-linked hypophosphatemia: lessons from the prospective multicenter study in Germany and Switzerland

Abstract Background and Aims X-linked hypophosphatemia (XLH) is the most common genetic cause of hypophosphatemia. Mutations in the PHEX gene cause elevated circulating levels of fibroblast growth factor 23 (FGF23), phosphaturia, rickets and osteomalacia. Conventional treatment with phosphate salts and active vitamin D is associated with nephrocalcinosis and preclinical studies in mice have shown that a chronic high phosphate load causes proximal tubular injury and fibrosis. There is no detailed analysis on kidney health in XLH patients yet. Method We conduct a prospective observational multicenter study in Germany and Switzerland to evaluate kidney health in pediatric XLH patients. Patients receive conventional therapy or burosumab, a fully humanized anti-FGF23 antibody. Clinical and biochemical data, blood and urine samples are collected annually. Results To date, 137 patients (80 girls, mean age 10.5 years) from 40 centers are included. 22% of patients have been treated conventionally for 7.5 years, 78% of patients have received burosumab for 2.3 years with 3.7 years of conventional therapy beforehand. Children with XLH show increased systolic blood pressure and body mass index (BMI), and overweight (BMI &amp;gt;90th percentile) and hypertension (systolic blood pressure &amp;gt;95th percentile) were each found in 20% of patients. A reduced eGFR (&amp;lt;90 ml/min/1.73 m2) and/or nephrocalcinosis was noted in 7% and 28% of patients, respectively. Microalbuminuria is twice as prevalent in children with XLH as in healthy children (14% vs 7%). Urinary lithogenic substances (calcium, oxalate, glycolate) are increased in 1.8-22.8%, and citrate is decreased in 12.3% of XLH patients. Tubular injury markers neutrophil gelatinase-associated lipocalin (NGAL) and Dickkopf-3 (DKK3) are elevated in urine of children with XLH, Chitinase 3-like 1 (CHl3L1) is comparable to children with chronic kidney disease, while kidney injury molecule-1 (Kim-1), indicating proximal tubule cell injury, is within a normal range. The renal inflammation marker monocyte chemoattractant protein-1 (MCP-1) is elevated in children with XLH, and epidermal growth factor (EGF), a marker of tubular cell repair, is decreased compared to healthy adults. Conclusion Pediatric XLH patients on conventional or burosumab therapy show enhanced systolic blood pressure slightly associated with elevated BMI, and significant renal comorbidity, i.e. reduced eGFR, nephrocalcinosis, increased urinary lithogenic substances, elevated urinary markers of glomerular and tubular injury and inflammation. The impact of conventional versus burosumab treatment are still being investigated.

#1564 Clinical implication of hyperfiltration and metabolic syndrome on the cardiovascular events, kidney failure, and all-cause mortality

Abstract Background and Aims Renal hyperfiltration (RHF) and metabolic syndrome (MetS) increase the risk of cardiovascular disease, end stage kidney disease (ESKD), and all-cause mortality. While RHF is strongly related to the metabolic risk, it is little known how the combined association of these two factors affects the risk of MetS-related complication, cardiovascular disease, and all-cause mortality. Method We reviewed the National Health Insurance Service database of Korea for people who received national health screenings between 2009 and 2011. RHF was defined as estimated glomerular filtration rate (eGFR) &amp;gt; 95th percentile after stratification for age, sex, height and weight, and normal renal filtration defined as eGFR 25-75th percentile. MetS was considered as the presence of three or more of the metabolic risks. Individuals were compared based on the presence of RHF and MetS. Age, sex, and Charlson comorbidity index matching were performed to reduce the selection bias in the study population. Finally, a total of 276,952 patients were matched, with 69,238 patients in each group, in a 1:1:1:1 ratio based on both their metabolic status and the presence of RHF. Results In multivariate Cox analysis, in comparison to normal renal filtration without MetS, RHF without MetS does not increase the risk of progression to ESKD. RHF patients increased the risk of progression to ESKD (aHR 2.75, 95% CI 1.38-5.50) only when combined with MetS. Moreover, irrespective of metabolic status, the risk of cardiovascular events (without MetS: aHR 1.08, 95% CI 1.00-1.17), (with MetS: aHR, 1.49; 95% CI, 1.38-1.60) and all-cause mortality (without MetS: aHR 1.29, 95% CI 1.20-1.40), (with MetS: aHR, 1.49; 95% CI, 1.37-1.62) increases significant in RHF patients. Notably, RHF synergistically increases the risk of cardiovascular events when accompanied with MetS (p for interaction = 0.041). However, RHF increases the risk of all-cause mortality more significantly without MetS than with MetS (p for interaction = 0.005). Conclusion The clinical implication of RHF is dependent on MetS status, and a significant interaction between the two factors is observed. To establish a treatment strategy for patients with RHF, MetS status must be considered.

#1458 Adverse muscle composition predicts all-cause mortality in CKD

Abstract Background and Aims Sarcopenia is common in CKD and associates with morbidity and mortality. A rapid and standardized MRI (Magnetic Resonance Imaging) scan protocol allows an accurate muscle composition analysis by quantification of skeletal muscle volume and muscle fat infiltration (MFI). The combined observation of low muscle volume and high muscle fat infiltration, i.e. adverse muscle composition (AMC), is a prevalent muscle composition phenotype within CKD and associates to poor function, high prevalence of comorbidity, and an increased risk for coronary heart disease (CHD). It has also been shown that AMC is an independent predictor of all-cause mortality in patients with non-alcoholic fatty liver disease and in general population. In this study we aimed to investigate muscle composition as predictor of all-cause mortality within participants with CKD in the UK Biobank imaging study (UKB). Method This is a prospective study including UKB participants with CKD defined as having an eGFR cystatin C &amp;lt; 60 ml/min/1, 73 m2. A control group was created by matching each participant with CKD for sex, age, and BMI to four participants with normal eGFR. Cystatin C was analyzed based on blood samples at time of study enrolment 7-9 years prior to the MRI. Fat-tissue free thigh muscle volume and MFI were quantified using a rapid neck-to-knee water and fat separated MRI protocol and automated image analysis (AMRA® Researcher). For each participant, a personalized muscle volume z-score (sex- and body size-specific) was calculated and combined with MFI to divide the participants into four muscle composition phenotype groups; 1) normal muscle composition, 2) only low muscle volume, 3) only high MFI and 4) AMC, using previously published thresholds based on the whole UKB cohort. The thresholds were the 25th percentile (&amp;lt; -0.68 SD) for muscle volume z-score and the 75th percentile (men &amp;gt;7.69%; women &amp;gt;8.82%) for MFI. The mortality data were obtained through the UKB´s linkage to national death registries. All-cause mortality was investigated using Kaplan-Meier curves and Cox regression. Models within participants with CKD were crude and subsequently adjusted for sex, age, BMI, low hand grip strength (&amp;lt;16/27 kg for females/males), physical activity, smoking, alcohol, and previous diagnosis of cancer, prevalent CHD and type 2 diabetes, all assessed at the time of imaging. Results Conclusion AMC, determined by standardized MRI, was a strong predictor of all-cause mortality in CKD. The study results indicate that CKD patients with poor muscle health, identified as having both low muscle volume z-score and high MFI, have a significantly higher mortality risk. This vulnerable group would potentially benefit from targeted interventions and is also of specific interest when evaluating new treatments for CKD.

#933 Serum and kidney complement and severity of ANCA associated vasculitis in the kidney

Abstract Background and Aims Kidney involvement in ANCA associated vasculitis (AAV) is commonly described as pauci-immune based on histological characteristics. However, we now know that the complement system is activated and contributes to the pathogenesis of AAV – with Avacopan (C5a inhibitor) demonstrating superior efficacy in maintenance of remission over Prednisolone in the ADVOCATE trial. Our aim was to evaluate if there is an association between kidney disease severity and the presence of serum and histological complement activation markers. Method Retrospective cohort study of 59 patients with AAV diagnosed between November 2015 and May 2019. Complement activation markers were serum complements (C3 and C4) levels and presence of complement (C3, C1q and C4) in glomerular capillary walls in immunofluorescence with intensity of 2+ and 3+. Kidney disease severity markers were peak serum creatinine value at presentation, anti-MPO or anti-PR3 levels, and number and proportion of glomeruli with crescents on kidney biopsy. Associations were evaluated using Spearman correlation or Mann Whitney U test as appropriate Results Among 59 patients with biopsy-proven AAV in the kidney, the median (25th percentile, 75th percentile) age was 68.8 (60.7, 73.4) years, serum creatinine was 263 (156, 560) µmol/L, and anti-MPO and anti-PR3 levels were 100.0 (81.5, 199.2) and 128.8 (22.9, 200) in 41 and 7 patients, respectively. respectively. The number and proportion of glomeruli with crescents were 6 (3, 12) and 33.3% (12.0%, 42.6%), respectively. Serum C3 and C4 were performed in 41 patients and the median levels were 1.00 (0.83, 1.14) and 0.24 (0.18, 0.31), respectively. Serum C3 level did not correlate with serum creatinine, anti-MPO or anti-PR3 titers, and number and proportion of glomeruli with crescents. Serum C4 level was negatively correlated with anti-MPO titer (34 patients; r = −0.393, p = 0.02) but did not correlate with serum creatinine or number or proportion of crescents. Complement in the glomerular capillary wall was present in 8 patients (13.6%): C3, C1q and C4 were present in 8, 3 and 1 patients, respectively. Serum creatinine [median 299 (IQR 133, 998) µmol/L versus 261 (156, 359) µmol/L, p = 0.39], anti-MPO titer [100 (88.3, 200) IU/ml versus 100 (79.4, 198) IU/ml, p = 0.74], number of crescents [14 (4, 21) versus 5 (3, 12), p = 0.90] and proportion of crescents [38.9% (12.5%, 42.3%) versus 31.3% (11.1%, 44.3%), p = 0.59] were not different in those with and without complement in the kidney biopsy. Conclusion The presence of complement activation markers was not associated with kidney disease severity in AAV. However, the detection of clinically significant associations may have been limited by our cohort size.

#723 The impact of kidney function on arterial stiffness in COVID-19 survivors: an analysis from CARTESIAN Study

Abstract Background and Aims SARS-CoV-2 pandemic has been linked to an increased incidence of cardiovascular events, potentially due to accelerated vascular aging [1]. Conversely, impaired kidney function is known to contribute to the pathogenesis of heightened arterial stiffness, independent of traditional cardiovascular risk factors [2]. This study aimed to assess the impact of COVID-19 on arterial stiffness among a cohort of survivors of the first pandemic wave, with varying degrees of infection severity. The assessment was conducted at 6 ± 3 (T1) and 12 ± 3 months (T2) post-infection, with the population stratified based on kidney function. Method the CARTESIAN study, a large international multicenter cohort study, was designed to assess the long-term effects of COVID-19 on vascular aging. A total of 938 subjects were stratified into three groups based on their estimated glomerular filtration rate (eGFR) percentiles using the CKD-EPI_2021 equation: 1) &amp;gt;75th percentile, 2) 75th-25th percentile, and 3) &amp;lt;25th percentile, respectively. The same population was further categorized based on the severity of COVID-19 into three groups: 1) patients who were not hospitalized (No-Hosp), 2) subjects requiring hospitalization in a medical unit (Hosp), or 3) those in an intensive care unit (ICU). Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). A hierarchical repeated measures mixed model analysis was conducted to compare cf-PWV across these groups (&amp;gt;75th, 75th-25th, and &amp;lt;25th groups, respectively). Results in the cross-section analysis (T1) &amp;lt;25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the &amp;gt;75th group. Using hierarchical linear modeling, the &amp;lt;25th exhibited higher cf-PWV than the &amp;gt;75th group, even after adjusting for both all the random and fixed variables, included the three COVID-19 group (+0.51 m/s, p = 0.013). In longitudinal analysis, globally, no substantial changes were found in the cf-PWV between T1 and T2, remained significantly higher in the &amp;lt;25th group compared to the &amp;gt;75th group (p = 0.003), in a linear mixed model adjusted for all the random and fixed variables. Interestingly, a significant interaction between eGFR groups* COVID-19 groups was found in repeated measures analysis (p = 0.039). In particular, within ICU group, we found a significant increase of cf-PWV between 6- and 12-months in &amp;lt;25th group, from 8.64 [7.59-9.31] to 9.41 [8.89-10.41] m/s, p = 0.021) (Fig. 1). Conclusion the findings suggest that individuals with both lower eGFR and a history of severe COVID-19 may be at a heightened risk of accelerated arterial aging. Understanding these dynamics is crucial for targeted interventions to mitigate long-term cardiovascular consequences in COVID-19 survivors with kidney disease.

#2832 Lean tissue mass is associated with mortality across different stages of chronic kidney disease: a systematic review and meta-analysis

Abstract Background and Aims Loss of lean tissue mass (LLTM) commonly occurs in multiple long-term conditions (LTC), including chronic kidney disease (CKD), and is thought to be associated with adverse outcomes including mortality, frailty surrogates and poor quality of life. It remains unclear whether LLTM is directly associated with mortality in CKD after adjusting for the severity of CKD or the degree of multimorbidity, and whether such associations remain in other LTC with similar levels of multimorbidity, such as heart failure (HF). Method A systematic review was conducted in adult CKD [kidney transplant (KT), CKDG3-5 or dialysis treated kidney failure (D-KF)] and HF patients who had whole body bioimpedance defined lean tissue mass (BI-LTM). The primary outcome was mortality, with secondary outcomes including hospitalisation and health related quality of life (HRQoL). The review was registered with PROSPERO (CRD42021240688) and was conducted according to PRISMA guidelines. Electronic database searches of MEDLINE, EMBASE, AMED, CINAHL, PsychInfo, Web of Science, CENTRAL, ICTRP and ISRCTN were searched from inception until June 2023. Data extraction and risk of bias assessments, using the Quality in Prognosis Studies (QUIPS) tool, was performed by two independent reviewers. Random effects meta-analysis was conducted using STATA SE16.2 using restricted maximum likelihood (REML) estimation. Results From 10,024 citations, 126 studies were identified (100 D-KF, 12 CKDG3-5, 2 KT, 3 mixed CKD and 9 HF) reporting outcomes on 143,053 D-KF, 15,164 CKDG3-5, 346 KTR and 3716 HF patients respectively. There were 1,227 deaths (over 2-5 years) in the HF studies and 16,471 deaths (over 1-20 years) in the CKD studies. The weighted mean eGFRCreat was 54 and 42 ml/min/1.73 m2 in the KT and CKDG3-5 studies, with only 3 HF studies reporting any measure of renal function (all using categorical cut offs). In 87 studies survival analyses of all-cause mortality (ACM) showed that BI-LTM was associated with mortality in 67%, 100%, 85% and 74% of the HF, KT, CKDG3-5 and D-KF studies respectively after adjusting for age, sex, diabetic status, comorbidity score, CRP / IL-6, albumin and bioimpedance defined fluid measures in 93%, 77%, 64%, 17%, 32%, 59% and 24% of analyses. Meta-analysis within D-KF studies reporting MVA revealed a 1-degree decrease in phase angle (pooled HR 1.82, 95% CI 1.50-2.20: Fig. 1A) and lean tissue index &amp;lt;10th percentile (pooled HR 1.48, 95% CI 1.31-1.66: Fig. 1B) was associated with ACM. Leave one out meta-analysis and sensitivity analyses removing studies at high-risk of statistical analysis and study confounding bias confirmed these pooled estimates were robust. Of the studies reporting secondary outcomes including hospitalisation and HRQoL (including the Short Form-36 and Kidney Disease Quality of Life Instrument), 67% showed associations with BI-LTM. Conclusion LLTM is associated with mortality across all stages of CKD and in heart failure. Furthermore, LLTM is associated with adverse outcomes such as hospitalisation and poor quality of life. This study confirms that LLTM potentially has an important role in the explanatory pathway for adverse outcomes in patients with LTCs, including CKD. Using BI-LTM may provide a way to identify early LLTM and target interventions to reduce the risk of adverse outcomes in these multimorbid cohorts.

#3109 Sarcopenia in peritoneal dialysis patients

Abstract Background and Aims Sarcopenia is considered a frequent cause of morbidity and mortality among patients with chronic kidney disease (CKD). In clinical practice, tools such as handgrip strength and bioelectrical impedance analysis (BIA) can help us diagnose sarcopenia and possibly predict clinical outcomes. However, the outcomes associated with this diagnosis in the population of patients under peritoneal dialysis (PD) and the consequent importance of the implementation of these tools is not clear. Method Single-centre retrospective study with patients who started peritoneal dialysis (PD) between January 1st 2017 and December 31st 2023, with a follow-up of 18 months or until technique dropout. Demographic, clinical data and outcomes were collected. Muscle strength (measured by handgrip strength with a dynamometer) and muscle mass (estimated through BIA-derived lean tissue index (LTI)) were also evaluated. Sarcopenia was considered when low strength (handgrip strength values &amp;lt;27 kg and &amp;lt;16 kg for men and women, respectively) and loss of muscle mass (LTI &amp;lt;10th percentile, relative to an age and gender-matched healthy population) were present. Results Fifty-three patients were included, with 66% male and a mean age of 58 ± 15 years. Comorbidities included hypertension in 88.7%, diabetes mellitus (DM) in 26.4% and coronary artery disease (CAD) in 17.0%. PD vintage was 23 months (IQR 21) and most were on continuous ambulatory peritoneal dialysis (75.5%). Median Clinical Frailty Score (CFS) was 2 (IQR 1). Mean LTI was 13.2 ± 2.7 kg/m2 and average handgrip strength was 28.4 ± 8.8 kg in the right arm and 26 kg (IQR 13) in the left. Reported outcomes of number of peritonitis, outer peritoneal catheter infection, hospitalizations and MACE (Major Adverse Cardiovascular Events) episodes were low. There were 3 reported deaths during follow-up. Six patients were considered sarcopenic, with 66% male and a mean age of 58.1 ± 14.9 years, with DM in 50%, hypertension in 100% and CAD in 33.3%. Median LTI was 9.4 (IQR 1.2), with left and right median hand grip of 24 (IQR 10) and 26 (13), respectfully. Outcomes were also low, with no statistically significant difference between sarcopenic and non-sarcopenic patients. Conclusion Despite being considered an indication of higher morbidity and mortality, the diagnosis of sarcopenia was not associated with worse outcomes in patients under peritoneal dialysis.

High variability in self-pay pricing for vasectomy and vasectomy reversal in the United States.

In the United States (US) men who undergo vasectomy and/or vasectomy reversal (vasovasotomy) are likely to pay out-of-pocket for these procedures. We characterized the publicly disclosed pricing of both procedures with a focus on variability in self-pay prices. We queried all US hospitals for publicly disclosed prices of vasectomy and vasovasotomy. We assessed interhospital variability in self-pay pricing and compared hospitals charging high (≥75th percentile) and low (≤25th percentile) self-pay prices for either procedure. We also examined trends in pricing after the 2022 US Supreme Court decision that allowed individual states to ban abortion. Of 6692 hospitals, 1375 (20.5%) and 281 (4.2%) disclosed self-pay prices for vasectomy and vasovasotomy, respectively. There was a 17-fold difference between the 10th and 90th percentile self-pay prices for vasectomy ($421-$7147) and a 39-fold difference for vasovasotomy ($446-$17,249). Compared with hospitals charging low (≤25th percentile) self-pay prices for vasectomy or vasovasotomy, hospitals charging high (≥75th percentile) prices were larger (median 150 vs. 59 beds, p < 0.001) and more likely to be for-profit (31.2% vs. 7.8%, p < 0.001), academic-affiliated (52.7% vs. 23.1%, p < 0.001), and located in an urban zip code (70.1% vs. 41.3%, p < 0.001). From October 2022 to April 2023, the median self-pay price of vasectomy increased by 10% (from $1667 to $1832) while the median self-pay price of vasovasotomy decreased by 16% (from $3309 to $2786). We found large variability in self-pay pricing for vasectomy and vasectomy reversal, which may serve as a barrier to the accessibility of male reproductive care.

Variation in the Cost of Hip Arthroscopy for Labral Pathological Conditions: A Time-Driven Activity-Based Costing Analysis.

Despite growing interest in delivering high-value orthopaedic care, the costs associated with hip arthroscopy remain poorly understood. By employing time-driven activity-based costing (TDABC), we aimed to characterize the cost composition of hip arthroscopy for labral pathological conditions and to identify factors that drive variation in cost. Using TDABC, we measured the costs of 890 outpatient hip arthroscopy procedures for labral pathological conditions across 5 surgeons at 4 surgery centers from 2015 to 2022. All patients were ≥18 years old and were treated by surgeons who each performed ≥20 surgeries during the study period. Costs were normalized to protect the confidentiality of internal hospital cost data. Descriptive analyses and multivariable linear regression were performed to identify factors underlying cost variation. The study sample consisted of 515 women (57.9%) and 375 men (42.1%), with a mean age (and standard deviation) of 37.1 ± 12.7 years. Most of the procedures were performed in patients who were White (90.6%) or not Hispanic (93.4%). The normalized total cost of hip arthroscopy per procedure ranged from 43.4 to 203.7 (mean, 100 ± 24.2). Of the 3 phases of the care cycle, the intraoperative phase was identified as the largest generator of cost (>90%). On average, supply costs accounted for 48.8% of total costs, whereas labor costs accounted for 51.2%. A 2.5-fold variation between the 10th and 90th percentiles for total cost was attributed to supplies, which was greater than the 1.8-fold variation attributed to labor. Variation in total costs was most effectively explained by the labral management method (partial R2 = 0.332), operating surgeon (partial R2 = 0.326), osteoplasty type (partial R2 = 0.087), and surgery center (partial R2 = 0.086). Male gender (p < 0.001) and younger age (p = 0.032) were also associated with significantly increased costs. Finally, data trends revealed a shift toward labral preservation techniques over debridement during the study period (with the rate of such techniques increasing from 77.8% to 93.2%; Ptrend = 0.0039) and a strong correlation between later operative year and increased supply costs, labor costs, and operative time (p < 0.001 for each). By applying TDABC to outpatient hip arthroscopy, we identified wide patient-to-patient cost variation that was most effectively explained by the method of labral management, the operating surgeon, the osteoplasty type, and the surgery center. Given current procedural coding trends, declining reimbursements, and rising health-care costs, these insights may enable stakeholders to design bundled payment structures that better align reimbursements with costs. Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.

#1462 Muscle mass, muscle strength, and health-related quality of life in kidney transplant recipients results of the TransplantLines Biobank &amp; cohort study

Abstract Background and Aims Muscles play a vital role in nearly every aspect of daily living, and kidney transplant recipients (KTR) often experience reduced muscle mass and strength, potentially contributing to their diminished health-related quality of life (HRQoL). We aimed to investigate the potential relationship of muscle mass and muscle strength with physical HRQoL in KTR. Method Data of stable KTR (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Studies were used. Muscle mass was assessed using both appendicular skeletal muscle mass (via bioimpedance analysis) indexed to height squared (ASMI) and 24-hour urinary creatinine excretion rate indexed to height squared (CERI). Muscle strength was assessed using handgrip strength indexed to height squared (HGSI). HRQoL was assessed using the physical component score derived from the Short Form 36 questionnaire. Results A total of 751 KTR (61% male, mean age 56 ± 13 years) at a median of 3 years after transplantation were included. Mean ASMI was 7.5 ± 1.2 kg/m2, mean CERI was 4.1 ± 1.1 mmol/24 h/m2 and mean HGSI was 12.4 ± 3.4 kg/m2. The mean physical HRQoL score was 70 ± 21. Lower ASMI, CERI and HGSI were all associated with lower physical HRQoL, independent of potential confounders. Both associations were best characterized by a significant non-linear relationship (see Figure). Below median values, ASMI, CERI and HGSI were each associated with physical HRQoL, whereas above median values, associations were far less pronounced. When associations of ASMI, CERI and HSGI were adjusted for each other, associations of below median values of ASMI and CERI with physical HRQoL materially weakened, while those of HGSI remained strongly associated. Compared to the 50th percentile, a decrease to the 10th percentile was associated with a decrease in physical HRQoL of 6.0% for ASMI (P = 0.006), of 5.1% for CERI (P = 0.006) and 13.2% for HGSI (P &amp;lt; 0.001), whereas an increase to the 90th percentile was associated with an increase in physical HRQoL of only 1.3% for ASMI (P = 0.22), of 3.6% for CERI (P = 0.05) and −0.4% for HGSI (P = 0.73). Conclusion Our findings suggest that low muscle mass and muscle strength are potentially modifiable risk factors for impaired physical HRQoL. Both muscle mass and muscle strength were complementarily associated with HRQoL. However, muscle strength was most strongly associated with physical HRQoL. The non-linear nature of the associations implies that KTR with low muscle mass or strength may particularly benefit from (p)rehabilitation interventions to improve HRQoL.