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ABSTRACT Oxidative stress, involved in many diseases, is defined as an impaired balance between reactive oxygen species (ROS) production and antioxidant defences. Antioxidant enzymes such as superoxide dismutase (SOD) play a key role in diminishing oxidative stress. Thus, the removal of ROS by exogenous SODs could be an effective preventive strategy against various diseases. The poor bioavailability of exogenous SODs has been criticized. However, improvements in SOD formulation may overcome this limitation and boost interest in its therapeutic properties. Here, we provide a review of animal and human studies about SODs supplementation in order to evaluate their therapeutic value. Protective effects have been observed against irradiation, carcinogenesis, apoptosis and neurodegeneration. SODs administration has also been reported to alleviate inflammatory, infectious, respiratory, metabolic and cardiovascular diseases and genitourinary and fertility disorders, raising the question of its mechanism of action in these diverse situations. Some authors have shown an increase in endogenous antioxidant enzymes after exogenous SODs administration. The induction of endogenous antioxidant defence and, consequently, a decrease in oxidative stress, could explain all the effects observed. Further investigations need to be carried out to test the hypothesis that SODs supplementation acts by inducing an endogenous antioxidant defence.

Recent studies suggest that high-dose hemodiafiltration (HDF) may reduce mortality more effectively than high-flux hemodialysis (HD), though the mechanisms remain unclear. Traditional metrics such as Kt/V and convective volume do not fully capture overall dialysis efficiency. This study proposes a novel approach using circulating beta-2-microglobulin (ß2M) levels to estimate an equivalent Continuous Dialytic Clearance (eCDC ß2M ), reflecting an equivalent glomerular filtration rate. Using data from the FRENCHIE study, we calculated eCDC ß2M and assessed its association with patient outcomes, including all-cause and cardiovascular mortality, in comparison with traditional dialysis dose metrics. Our analysis showed that HDF achieved higher treatment efficiency than high-flux HD, with a mean increase of + 1.5 ml/min in eCDC ß2M . Moreover, eCDC ß2M demonstrated superior predictive value for mortality risk compared to Kt/V. These findings support eCDC ß2M as a meaningful and physiologically relevant measure of dialysis efficiency and adequacy. By better reflecting the continuous function of the native kidney, this approach may improve patient stratification and outcome prediction across all forms of kidney replacement treatment schedule. Further validation in independent patient cohorts is warranted.

Aims Inflammation and cardiac remodelling are common and synergistic pathways in heart failure (HF). Emerging biomarkers such as soluble suppression of tumorigenicity 2 (sST2) and growth differentiation factor‐15 (GDF‐15), which are linked to inflammation and fibrosis process, have been proposed as prognosis factors. However, their potential additive values remain poorly investigated. Methods and results Here, we aimed at evaluating inflammatory and remodelling biomarkers to predict both short‐term and long‐term mortality in a population with chronic HF in comparison with other classical clinical or biological markers (i.e. N terminal pro brain natriuretic peptide, hs‐cTnT, C‐reactive protein) alone or using meta‐analysis global group in chronic HF risk score in a cohort of 182 patients followed during 80 months (interquartile range: 12.3–90.0). Proportional hazard assumption does not hold for sST2 and C‐reactive protein, and follow‐up was split into short term (less than 1 year), midterm (between 1 and 5 years), and long term (after 5 years). In univariate analysis, C‐reactive protein and sST2 were predictive of short‐term mortality but not of middle term and long term whereas GDF‐15 was predictive of short and mid‐term but not of long‐term mortality. In a multivariate model after adjustment for meta‐analysis global group in chronic HF score including the three markers, only sST2 was predictive of short‐term mortality (P = 0.0225), and only GDF‐15 was predictive of middle term mortality (P = 0.0375). None of the markers was predictive of long‐term mortality. Conclusions Our results demonstrate that both sST2 and GDF‐15 significantly improve the prognosis evaluation of HF patients and suggest that the value of GDF‐15 is more sustained overtime and could predict middle term events.

Background. The prognostic value of vitamin B12 blood levels remains controversial. An association between elevated vitamin B12 and mortality has been reported, particularly among elderly patients with cancers and liver or blood diseases. The present study explored the relationship between mortality and elevated vitamin B12 levels in a population of unscheduled inpatients in an internal medicine unit. Methods. This retrospective observational analysis was conducted between August 2014 and December 2018. We compared 165 patients with elevated plasma vitamin B12 levels (>600 pmol/l) with a random sample of 165 patients with normal B12 levels who were hospitalized during the same period. Demographic, clinical, and biological characteristics were assessed during hospitalization. The primary endpoint was all-cause death at 1 year. Results. Patients with elevated B12 were younger, with a lower body mass index and lower plasma albumin than those with normal B12 (75 ± 16 years vs 79 ± 13 years, p = 0.047; 23 ± 5 vs 26 ± 7 kg/m2, p < 0.001; and 33 ± 5 vs 35 ± 5 g/l, p < 0.001, respectively). The prevalence of auto-immune disease and referral from an intensive care unit was higher among patients with elevated B12 (11% vs 5%, p = 0.043 and 36% vs 10%, p < 0.001, respectively). After 1 year of follow-up, 64 (39%) patients with elevated B12 had died compared to 43 (26%) patients with normal B12 (p = 0.018). Multivariate analysis using the Cox proportional hazards regression model adjusted for age, gender, body mass index, intensive care unit hospitalization, albumin level, and the presence of solid cancer or autoimmune disease revealed elevated B12 to be associated with a significant risk of death in the first year of follow-up (hazard ratio: 1.71 [1.08–2.7], p = 0.022). Conclusion. Elevated B12 is an early warning indicator of increased short-term mortality, such as independently of age, cancer, or comorbidities, in patients hospitalized in an internal medicine department.

BACKGROUND Alzheimer disease (AD), the leading cause of dementia, has increased interest in the development of blood‐based biomarkers for early diagnosis and monitoring. The plasma amyloid beta (Aβ)42/Aβ40 ratio and phosphorylated tau (p‐tau) isoforms closely align with cerebrospinal fluid and positron emission tomography markers. The recent approval of the plasma p‐tau217/Aβ42 ratio marks a key step toward non‐invasive diagnostics. However, known Aβ42's preanalytical and analytical challenges raise concerns about the reliability of this ratio in routine clinical practice. METHODS Using the ALZAN prospective cohort of cognitively impaired individuals, we examined how delays between blood collection and laboratory processing affected the performance of plasma biomarkers in detecting. RESULTS The preanalytical delay has a significant impact for Aβ40 and Aβ42. However, the performance of p‐tau217 and p‐tau217/Aβ42 ratio were similar, thereby supporting the use of the ratio as a robust and efficient marker for AD diagnosis. DISCUSSION Our findings reinforce the high diagnostic accuracy of the p‐tau217/Aβ42 ratio in AD, regardless of preanalytical delays. Highlights Blood‐based biomarkers are playing an increasingly important role in the routine clinical management of AD. A significant advancement in this field was marked by the FDA's recent approval of the Lumipulse immunoassay, which measures the plasma p‐tau217/Aβ42 ratio for AD diagnosis. However, this development has sparked notable concern among researchers. One major issue is that the p‐tau217/Aβ42 ratio has not been extensively investigated. Only recently have studies begun to show that it offers slightly better diagnostic performance than p‐tau217 alone (https://doi.org/10.1101/2024.12.07.24318640). In addition, the known instability of Aβ42 under different preanalytical conditions could potentially compromise the reliability of the ratio in routine clinical settings. Using data from the ALZAN cohort, where we previously confirmed the enhanced diagnostic value of the p‐tau217/Aβ42 ratio, we specifically examined how preanalytical factors, specifically delays in blood sample processing, might affect its performance. Our results highlight the limited effect of this preanalytical parameter on clinical performance of the ratio, thereby supporting its robustness and practical value for routine use in AD diagnostic and care.

Glomerular filtration rate (GFR) is a crucial parameter in post-transplant follow-up (PTF). CKD-EPI 2009 creatinine-based equation remains the most used estimated GFR (eGFR) and only few data are available on the other equations, based on creatinine, cystatin C or their combination. We evaluated 10 GFR estimation equations on 242 kidney-transplant recipient patients having measured GFR (mGFR) determination (urinary clearance of 99m Tc-DTPA) with simultaneous plasma enzymatic creatinine and serum cystatin C (immunoturbidimetry or immunonephelemetry) assessments. Five creatinine (MDRD 2006, CKD-EPI 2009 and 2021, EKFC 2021, KRS 2023), two cystatin C (CKD-EPI 2012, EKFC 2023) and three combined eGFR (CKD-EPI 2012 and 2021, combined EKFC) were evaluated. All equations were significantly correlated with mGFR (R² = 0.672–0.745) with a low median bias (+4.2 to −1.1 mL/min/1.73 m²). Chronic kidney disease staging agreements were all above 68% (maximum: 79.3% for CKD-EPI comb 2021). Percentages of eGFR comprised in between 30% of the mGFR ranged from 85.5% to 87.6% (combined equations), from 83.1% to 84.3% (cystatin C equations) and from 75.2% to 81.4% (creatinine equations). Combined creatinine/cystatin C eGFR equations with a P30 value greater to 85% of transplant recipients appeared closer to mGFR than cystatin C or creatinine eGFR.

Serum creatinine (SCr) is the main variable for estimating glomerular filtration rate (GFR). Due to inter-assay differences, the prevalence of chronic kidney disease (CKD) varies according to the assay used, and calibration standardization is necessary. For SCr, isotope dilution mass spectrometry (IDMS) is the gold standard. Systematic differences are observed between Jaffe and enzymatic methods. Manufacturers subtract 0.30 mg/dl from Jaffe results to match enzymatic results (‘compensated Jaffe method’). The analytical performance of enzymatic methods is superior to that of Jaffe methods. In the original Modification of Diet in Renal Disease (MDRD) equation, SCr was measured by a Jaffe Beckman assay, which was later recalibrated. A limitation of this equation was an underestimation of GFR in the high range. The Chronic Kidney Disease Epidemiology (CKD-EPI) consortium proposed an equation using calibrated and IDMS traceable SCr. The gain in performance was due to improving the bias whereas the precision was comparable. The CKD-EPI equation performs better at high GFR levels (GFR >60 ml/min/1.73 m 2 ). Analytical limitations have led to the recommendation to give a grade (>60 ml/min/1.73 m 2 ) rather than an absolute value with the MDRD equation. By using both enzymatic and calibrated methods, this cutoff-grade could be increased to 90 ml/min/1.73 m 2 (with MDRD) and 120 ml/min/1.73 m 2 (with CKD-EPI). The superiority of the CKD-EPI equation over MDRD is analytical, but the precision gain is limited. IDMS traceable enzymatic methods have been used in the development of the Lund–Malmö (in CKD populations) and Berlin Initiative Study equations (in the elderly). The analytical errors for cystatin C are grossly comparable to issues found with SCr. Standardization is available since 2011. A reference method for cystatin C is still lacking. Equations based on standardized cystatin C or cystatin C and creatinine have been proposed. The better performance of these equations (especially the combined CKD-EPI equation) has been demonstrated.

Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies based on in-depth literature analysis that may help healthcare systems face these challenges, with a focus on digital health technologies (DHTs), to enhance removal and ensure better control of broader spectrum of uremic toxins, to optimize resources, improve care and outcomes, and empower patients. Therefore, alternative strategies, such as self-care dialysis, home-based dialysis with the support of teledialysis, need to be developed. Managing ESKD requires an improvement in patient management, emphasizing patient education, caregiver knowledge, and robust digital support systems. The solution involves leveraging DHTs to automate HD, implement automated algorithm-driven controlled HD, remotely monitor patients, provide health education, and enable caregivers with data-driven decision-making. These technologies, including artificial intelligence, aim to enhance care quality, reduce practice variations, and improve treatment outcomes whilst supporting personalized kidney replacement therapy. This narrative essay offers an update on currently available digital health technologies used in the management of HD patients and envisions future technologies that, through digital solutions, potentially empower patients and will more effectively support their HD treatments.

Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology. Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3) activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP) and orosomucoid. In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003) whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001) and orosomucoid (p = 0.01). In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology.

Natriuretic peptides (BNP and NT-proBNP) are recognized as gold-standard predictive markers in Heart Failure (HF). However, currently ST2 (member of the interleukin 1 receptor family) has emerged as marker of inflammation, fibrosis and cardiac stress. We evaluated ST2 and CRP as prognostic markers in 178 patients with chronic heart failure in comparison with other classical markers such as clinical established parameters but also biological markers: NT-proBNP, hs-cTnT alone or in combination. In multivariate analysis, subsequent addition of ST2 led to age, CRP and ST2 as the only remaining predictors of all-cause mortality (HR 1.03, HR 1.61 and HR 2.75, respectively) as well as of cardiovascular mortality (HR 1.00, HR 2.27 and HR 3.78, respectively). The combined increase of ST2 and CRP was significant for predicting worsened outcomes leading to identify a high risk subgroup that individual assessment of either marker. The same analysis was performed with ST2 in combination with Barcelona score. Overall, our findings extend previous data demonstrating that ST2 in combination with CRP as a valuable tool for identifying patients at risk of death.