Lactoferrin efficacy in treating hyperferritinemia in patients suffering from pathologies unrelated to hereditary hemochromatosis.

Ferritin (Ftn), a globular protein, sequesters 4500 atoms of iron per molecule. Elevated serum Ftn levels (hyperferritinemia) is an indicator of iron homeostasis disorders. We present the results of an observational study involving 17 patients with hyperferritinemia unrelated to hereditary hemochromatosis (HH). All participants received treatment with 200 mg of bovine lactoferrin (bLf) once (n = 14) or twice (n = 3) a day before meals. The patients, treated with 200 mg/day of bLf, exhibited a significant increase in red blood cells (+10%, p < 0.001), hemoglobin (+4%, p < 0.001), and hematocrit (+15%, p = 0.004), accompanied by a significant reduction in serum Ftn levels (-52%, p < 0.001), C-reactive protein (CRP) (-85.0%, p < 0.001), and D-dimers (-19%, p < 0.001). Among the three patients treated with 400 mg/day of bLf, two had effects similar to those of patients bLf-treated with 200 mg/day and one experienced a strong reduction of Ftn, CRP, and erythrocyte sedimentation rate (from -97% to -75%). The decrease in serum Ftn levels due to bLf treatment was largely independent of gender (p = 0.78), age (p = 0.66), baseline symptoms (p = 0.20), and concomitant acute (p = 0.34) and chronic (p = 0.53) infections. Although this observational pilot study yields positive effects in patients with hyperferritinemia unrelated to HH treated with bLf, a larger sample size is needed for conclusive results.

Assessment of cephalometric parameters and correlation with the severity of the obstructive sleep apnea syndrome.

BACKGROUND: In individuals diagnosed with obstructive sleep apnea syndrome (OSAS), variations in craniofacial structure have been inconsistently documented, showing differing degrees of alteration between obese and nonobese patients. In addition, sleep disturbance has also been shown to induce disequilibrium in this population of patients. This pilot observational study aimed to assess craniofacial values in obese and nonobese subpopulations of patients with OSAS and their correlation and association with the severity of OSAS. We also assessed whether OSAS patients are characterized by an impaired equilibrium in relation to and associated with the severity of OSAS. METHODS: We included all consecutive adult patients with OSAS. Through cephalometry, we assessed the upper (UPa-UPp) and lower (LPa-LPp) pharynx diameters, superior anterior facial height (Sor-ANS), anterior facial height (ANS-Me), anterior vertical dimension (Sor-Me), posterior facial height (S-Go) and craniovertebral angle (CVA). Furthermore, we analyzed postural equilibrium through a stabilometric examination. RESULTS: Forty consecutive OSAS patients (45% female with a mean age of 56 ± 8.2 years) were included. The subgroup of nonobese patients had a reduced UPa-UPp (p = 0.02). Cephalometric measurements were correlated with the severity of OSAS in nonobese patients, whereas only Sor-ANS was correlated with the severity of OSAS in the obese subpopulation. In the overall population, altered craniofacial values are associated with severe OSAS. Although there are differences in equilibrium between obese and nonobese OSAS patients, the stabilometric measurements were not correlated or associated with OSAS severity. CONCLUSION: Altered craniofacial values and compromised equilibrium in OSAS patients are linked to OSAS severity. Therefore, the management of OSAS should be tailored not only to weight management but also to craniofacial and postural rehabilitation to enhance patient outcomes.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies. METHODS: The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis. RESULTS: During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HRfor1ln unit increase: 1.23, 95% CI 1.06-1.43, p =.008) and CV mortality (HRfor1ln unit increase: 1.26, 95% CI 1.03-1.54, p =.03). After multivariate adjustment, these associations were no longer significant (all-cause mortality, HRfor 1 ln unit increase: 1.16, 95% CI .99-1.36, p =.07; CV mortality, HRfor1ln unit increase: 1.18, 95% CI .95-1.46, p =.14). However, in fully adjusted interaction analyses, a doubling in the risk of this outcome in women was registered (Women, HRfor1ln unit increase: 1.88, 95% CI 1.27-2.78, p =.002; Men, HRfor1ln unit increase: 1.07, 95% CI .83-1.38, p =.61; p for effect modification: .02). CONCLUSIONS: PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.

When impact trials are not feasible: alternatives to study the impact of prediction models on clinical practice.

Patients with kidney disease have an uncertain future with prognosis varying greatly per patient. To get a better idea of what the future holds and tailor interventions to the individual patient, prediction models can be of great value. Before a prediction model can be applied in practice, its performance should be measured in target populations of interest (i.e., external validation) and whether it helps improve clinical practice (i.e., whether it impacts clinical practice) should be determined. The impact would ideally be determined using an impact trial, but such a trial is often not feasible, and the impact of prediction models is therefore rarely assessed. As a result, prediction models that may not be so impactful may end up in clinical practice and impactful models may not be implemented due to a lack of impact studies. Ultimately, many prediction models end up never being implemented, resulting in much research waste. To allow researchers to get an indication of a prediction model's impact on clinical practice, alternative methods to assess a prediction model's impact are important. In this paper, we discuss several alternatives, including interviews, case-based surveys, decision comparisons, outcome modelling, before-after analyses, and decision curve analyses. We discuss the general idea behind these approaches, including what information can be gathered from such studies and important pitfalls. Lastly, we provide examples of the different alternatives.

Tubular phosphate transport: a comparison between different methods of urine sample collection in FGF23-dependent hypophosphatemic syndromes.

OBJECTIVES: Tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) is used to evaluate renal phosphate reabsorption and it is a useful tool for the differential diagnosis of hypophosphatemic syndromes. TmP/GFR is typically calculated from fasting plasma and second morning void urine samples, obtained 2 h after the first void (TmP/GFR 2 h). The purpose of this study was to evaluate if TmP/GFR calculated from 24 h urine collection (TmP/GFR 24 h) can be used as an alternative for TmP/GFR 2 h in patients with urine phosphate wasting. METHODS: We enrolled adult patients with X-linked hypophosphatemia (XLH) or tumor-induced osteomalacia (TIO). All patients underwent blood and urine sample collections, to calculate TmP/GFR 24 h and TmP/GFR 2 h. RESULTS: Twenty patients (17 XLH and 3 TIO), aged 24-78 years, were included. All patients had low TmP/GFR 2 h (0.35 mmol/L, IQR 0.24-0.47 mmol/L) and TmP/GFR 24 h (0.31 mmol/L, IQR 0.22-0.43 mmol/L). The concordance correlation coefficient between TmP/GFR 2 h and TmP/GFR 24 h was 0.86 (95 % CI: 0.69-0.93), with a systematic bias of 0.05 mmol/L (95 % limits of agreement: -0.10 to 0.20). Furthermore, in 70 % (i.e., 14 patients out of 20) and 80 % (i.e., 16 patients out of 20) of cases the difference between TmP/GFR 2 h and TmP/GFR 24 h was within ±30 % and ±35 %, respectively. CONCLUSIONS: Despite TmP/GFR 2 and 24 h show a relatively suboptimal agreement, the difference between the two parameters appears to be small and not clinically significant in the setting of adult patients with FGF23-dependent urine phosphate wasting and secondary hypophosphatemia.

Comparative Effectiveness of Combined IgM-Enriched Immunoglobulin and Extracorporeal Blood Purification Plus Standard Care Versus Standard Care for Sepsis and Septic Shock after Cardiac Surgery.

Background: The combination of surgery, bacterial spread-out, and artificial cardiopulmonary bypass surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyper-inflammatory condition frequently associated with compromised hemodynamics and organ dysfunction. A promising approach could be extracorporeal blood purification therapies in combination with IgM enriched immunoglobulin. This approach might perform a balanced control of both hyper and hypo-inflammatory phases as an immune-modulating intervention. Methods: We performed a retrospective observational study of patients with proven infection after cardiac surgery between January 2020 and December 2021. Patients were divided into two groups: (1) the first group (Control Group) followed a standard care approach as recommended by the Surviving Sepsis Campaign Guidelines; The second group (Active Group) underwent extracorporeal blood purification therapy (EBPT) in combination with intravenous administration of IgM enriched immunoglobulin 5 mL/kg die for at least three consecutive days, in conjunction with the standard approach (SSC Guidelines). In addition, ventriculo-arterial (V/A) coupling, Interleukin 6 (IL-6), Endotoxin Activity Assay (EAA), Procalcitonin, White Blood Cells (WBC) counts, Sequential Organ Failure Assessment (SOFA) Score and Inotropic Score were assessed in both two groups at different time points. Results: Fifty-four patients were recruited; 25 were in the Control Group, while 29 participants were in the Active Group. SOFA score significantly improved from baseline [12 (9-16)] until at T 3 [8 (3-13)] in the active group; it was associated with a median EAA reduction from 1.03 (0.39-1.20) at T 0 to 0.41 (0.2-0.9) at T 3 in the active group compared with control group 0.70 (0.50-1.00) at T 0 to 0.70 (0.50-1.00) at T 3 (p < 0.001). V/A coupling tended to be lower in patients of the active arm ranging from 1.9 (1.2-2.7) at T 0 to 0.8 (0.8-2.2) at T 3 than in those of the control arm ranging from 2.1 (1.4-2.2) at T0 to 1.75 (1.45-2.1) at T 3 (p = 0.099). The hemodynamic improvement over time was associated with evident but no significant decrease in inotropic score in the active group compared with the control group. Changes in EAA value from T 0 to T 4 were directly and significantly related (r = 0.39, p = 0.006) to those of V/A coupling. Conclusions: EBPT, in combination with IgM enriched immunoglobulin, was associated with a mitigated postoperative response of key cytokines with a significant decrease in IL-6, Procalcitonin, and EAA and was associated with improvement of clinical and metabolic parameters.

Risk Factors of Chronic Kidney Disease Progression: Between Old and New Concepts.

Chronic kidney disease (CKD) is a condition characterized by the gradual loss of kidney function over time and it is a worldwide health issue. The estimated frequency of CKD is 10% of the world's population, but it varies greatly on a global scale. In absolute terms, the staggering number of subjects affected by various degrees of CKD is 850,000,000, and 85% of them are in low- to middle-income countries. The most important risk factors for chronic kidney disease are age, arterial hypertension, diabetes, obesity, proteinuria, dyslipidemia, and environmental risk factors such as dietary salt intake and a more recently investigated agent: pollution. In this narrative review, we will focus by choice just on some risk factors such as age, which is the most important non-modifiable risk factor, and among modifiable risk factors, we will focus on hypertension, salt intake, obesity, and sympathetic overactivity.

Lactoferrin in the Prevention of Recurrent Respiratory Infections in Preschool Children: A Prospective Randomized Study.

Few studies have evaluated the effect of bovine lactoferrin (bLf) on reducing respiratory infections in preschool children. This randomized controlled trial evaluated the effect of bLf in preschool children with recurrent respiratory infections. Participants were randomly assigned bLf (n = 25) or control (n = 25). Outcomes included respiratory infection episodes (RIEs), symptom duration, school absence and medication. Fifty children aged 4.2 ± 0.1 years were included. During the active 4-month phase, median number of RIEs was reduced by 50% in the bLf group [1-episode, interquartile range (IQR): 0-2] vs. control (2, IQR: 1-3; p = 0.02). The proportion of participants with >3 RIEs was significantly lower in bLf (n = 1, 4%) vs. control (n = 7, 28%) with 80% lower odds of upper RIEs in the bLf arm (odds ratio: 0.20, 95% CI:0.06-0.74, p = 0.015). The duration of symptoms (3 vs. 6, p = 0.009) and days absent from school (3 vs. 6, p = 0.15) were lower in the active arm. Over the 2-month follow-up, no significant differences were observed between groups for infection episodes, symptom duration or school absence. However, bLf-treated children received significantly less corticosteroids over the entire 6-month study period (32% vs. 60%; p = 0.047). bLf supplementation significantly reduced the frequency and duration of RIEs in children with decreased corticosteroid use.

Biomarkers in clinical epidemiology studies.

This paper discusses the use of biomarkers in clinical practice and biomedical research. Biomarkers are measurable characteristics that can be used to indicate the presence or absence of a disease or to track the progression of a disease. They can also be used to predict how a patient will respond to a particular treatment. Biomarkers have enriched clinical practice and disease prognosis by providing measurable characteristics that indicate biological processes. They offer valuable insights into disease susceptibility, progression, and treatment response, aiding drug development and personalized medicine. However, developing and implementing biomarkers come with challenges that must be addressed. Rigorous testing, standardization of assays, and consideration of ethical factors are crucial in ensuring the reliability and validity of biomarkers. Reliability is vital in biomarker research. It ensures accurate measurements by preventing biases and facilitating robust correlations with outcomes. Conversely, validation examines which and how many biomarkers correspond to theoretical constructs and external criteria, establishing their predictive value. Multiple biomarkers are sometimes necessary to represent the complex relationship between exposure and disease outcomes accurately. Susceptibility factors are pivotal in disease states' complex interaction among genetic and environmental factors. Gaining a comprehensive understanding of these factors is essential for effectively interpreting biomarker data and maximizing their clinical usefulness. Using well-validated biomarkers can improve diagnoses, more effective treatment evaluations, and enhanced disease prediction. This, in turn, will contribute to better patient outcomes and drive progress in medicine.

Socioeconomic Status and Clinical Outcomes in Chronic Kidney Disease: Bootstrap Validation of a Simple Indicator.

Background: Chronic Kidney Disease (CKD) is a complex health condition that interacts significantly with socioeconomic determinants, particularly income status and education. This study developed a simple indicator of socioeconomic status (SES), which is composed of income status and education in CKD patients, and evaluated its impact on health outcomes in this population. Methods: This study was conducted on 561 CKD patients, stages 2-5. The composite SES score was developed by combining the regression coefficients of income and education as predictors of the study endpoint in a multivariable Cox model, normalizing these coefficients to derive weights, and then using these weights to calculate an individual percentage score based on each person's income and education. The composed SES indicator was internally validated through bootstrap analysis. Over a median follow-up time of 36 months, we tracked all-cause death and non-fatal cardiovascular events. Results: Both lack of income (p = 0.020) and low educational level (p = 0.034) were independently related to the combined endpoint. Based on these covariates' regression coefficients, a composite socioeconomic score considering income and educational level was generated. In a Cox regression model, a 10% increase in this composite risk score entailed a 25% increase in the hazard ratio (HR) of the combined endpoint [HR (10% increase): 1.25], and the internally validated 95% CI ranged from 1.14 to 1.41 (p < 0.001). Conclusions: This study underscores the significant impact of a simple, bootstrap-validated composite SES indicator on CKD patients' health outcomes. These findings highlight the importance of considering education and socioeconomic factors in managing and treating CKD patients and inform future research and policy considerations for this population.

Role of kidney function on Nrf2 mRNA levels in type 2 diabetes.

INTRODUCTION: Diabetic kidney disease (DKD) is a major complication in patients with diabetes and the main contributor to the chronic kidney disease (CKD) global burden. Oxidative stress is a crucial factor in DKD pathogenesis but the role of the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) and its molecular regulators has been poorly investigated in man. RESEARCH DESIGN AND METHODS: In this case-control study, we analyzed the roles of Nrf2, a transcription factor shielding cells from oxidative stress, its repressor Kelch-like ECH-associated protein 1 (Keap1) and six microRNAs (miRNAs) that potentially suppress Nrf2. We categorized 99 participants into 3 groups: 33 non-dialysis patients with type 2 diabetes with DKD, 33 patients with type 2 diabetes without DKD and 33 control subjects and quantified the gene expression (messenger RNA (mRNA)) levels of Nrf2, Keap1 and 6 miRNAs. Moreover, we studied the correlation between gene expression levels and clinical indicators of kidney health. RESULTS: In patients with diabetes with DKD, Nrf2 mRNA levels were significantly lower than in patients without DKD (p=0.01) and controls (p=0.02), whereas no difference in Nrf2 expression levels existed between patients without DKD and controls. Conversely, in patients with and without DKD, Keap1 expression levels were significantly higher than in controls. Of the six miRNAs studied, miRNA 30e-5p showed differential expression, being markedly reduced in patients with DKD (p=0.007). Nrf2 mRNA levels directly correlated with estimated glomerular filtration rate (eGFR) in patients with DKD (r=0.34, p=0.05) and in a formal mediation analysis the eGFR emerged as the first factor in rank for explaining the difference in Nrf2 mRNA levels between patients with and without DKD. CONCLUSIONS: The observed dysregulation in the Nrf2-Keap1 axis and the unique expression pattern of miRNA30e-5p in DKD underscore the need for more focused research in this domain that can help identify novel intervention strategies for DKD in patients with type 2 diabetes.

Effect of early administration of tetracosactide on mortality and host response in critically ill patients requiring rescue surgery: a sensitivity analysis of the STOPSHOCK phase 3 randomized controlled trial.

BACKGROUND: Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction. This was a sensitivity analysis of a drug (tetracosactide; TCS10) targeting melanocortin receptors (MCRs) in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders. METHODS: Sensitivity analysis was based on a randomized, two-arm, multicenter, double-blind, controlled trial. The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs-outputs in 100 consecutive cases (from August to September 2013 from Emilia Romagna region, Italy). Patients included an agent-based TCS10 group (10 mg, single intravenous bolus before surgery; n = 56) and control group (n = 44) and the association with cytokines, lactate, and bleeding-blood transfusion episodes with the prior-risk log-odds for mortality rate in time-to-event was analyzed. RESULTS: Thirty-day mortality was significantly improved in the TCS10 group vs. control group (0 vs. 8 deaths, P < 0.0001). Baseline levels of interleukin (IL)-6, IL-10, and lactate were associated with bleeding episodes, independent of TCS10 treatment [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.39-2.79; OR = 1.53, 95%CI 1.17-2.12; and OR = 2.92, 95%CI 1.40-6.66, respectively], while baseline level of Fms-like tyrosine kinase 3 ligand (Flt3L) was associated with lower bleeding rates in TCS10-treated patients (OR = 0.31, 95%CI 0.11-0.90, P = 0.03). For every 8 TCS10-treated patients, 1 bleeding case was avoided. Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group (OR = 0.32, 95%CI 0.14-0.73, P = 0.01). For every 4 TCS10-treated patients, 1 transfusion case was avoided. CONCLUSIONS: Sensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care. To introduce the technology readiness level in real-life critically ill patients, further large-scale studies are required. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT Number: 2007-006445-41 ).

Common mistakes in biostatistics.

Biostatistics plays a pivotal role in developing, interpreting and drawing conclusions from clinical, biological and epidemiological data. However, the improper application of statistical methods can lead to erroneous conclusions and misinterpretations. This paper provides a comprehensive examination of the most frequent mistakes encountered in the biostatistical analysis process. We identified and elucidated 10 common errors in biostatistical analysis. These include using the wrong metric to describe data, misinterpreting P-values, misinterpreting the 95% confidence interval, misinterpreting the hazard ratio as an index of prognostic accuracy, ignoring the sample size calculation, misinterpreting analysis by strata in randomized clinical trials, confusing correlation and causation, misunderstanding confounders and mediators, inadequately codifying variables during the data collection, and bias arising when group membership is attributed on the basis of future exposure in retrospective studies. We discuss the implications of these errors and propose some practical strategies to mitigate their impact. By raising awareness of these pitfalls, this paper aims to enhance the rigor and reproducibility of biostatistical analyses, thereby fostering more robust and reliable biomedical research findings.

ROC curve analysis: a useful statistic multi-tool in the research of nephrology.

In the past decade, scientific research in the area of Nephrology has focused on evaluating the clinical utility and performance of various biomarkers for diagnosis, risk stratification and prognosis. Before implementing a biomarker in everyday clinical practice for screening a specific disease context, specific statistic measures are necessary to evaluate the diagnostic accuracy and performance of this biomarker. Receiver Operating Characteristic (ROC) Curve analysis is an important statistical method used to estimate the discriminatory performance of a novel diagnostic test, identify the optimal cut-off value for a test that maximizes sensitivity and specificity, and evaluate the predictive value of a certain biomarker or risk, prediction score. Herein, through practical examples, we aim to present a simple methodological approach to explain in detail the principles and applications of ROC curve analysis in the field of nephrology pertaining diagnosis and prognosis.

Effects of working from home on lifestyle behaviors and mental health during the COVID-19 pandemic: A survey study.

The COVID-19 outbreak has led to relevant changes in everyday life worldwide. One of these changes has been a rapid transition to and an increasing implementation of working from home (WH) modality. This study aimed to evaluate the impact of mandatory WH during the COVID-19 pandemic on lifestyle behaviors, Mediterranean diet adherence, body weight, and depression. An online cross-sectional survey was conducted in the early 2022 at the National Research Council of Italy using ad hoc questions and validated scales collecting information on physical activity, sedentary behavior, hobbies/pastimes, dietary habits including adherence to the Mediterranean diet, body weight, and depression during WH compared with before WH. 748 respondents were included in the study. An increased sedentary lifetime was reported by 48% of respondents; however, the subsample of workers who previously performed moderate physical activity intensified this activity. Body weight gain during WH was self-reported in 39.9% of respondents. Mediterranean diet adherence increased (p≪0.001) during WH compared with before WH. The average level of mental health did not record an overall variation; however, the proportion of subjects with mild and moderate depression increased (p = 0.006), while workers who reported values indicative of depression before the transition declared an improvement. These findings highlight health-related impact of WH during the COVID-19 pandemic that may inform future strategies and policies to improve employees' health and well-being.

Association of vitamin D and bisphenol A levels with cardiovascular risk in an elderly Italian population: results from the InCHIANTI study.

Few studies have evaluated the association between circulating levels of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and the endocrine disruptor bisphenol A (BPA), with risk of cardiovascular (CV) disease in elderly individuals. This was a cross-sectional study in a subgroup of elderly people from the InCHIANTI Biobank in Italy. We examined the association between circulating serum vitamin D metabolites, 1,25(OH)2D, 25(OH)D, and the endocrine disrupting agent BPA, with an arbitrary CV risk score and the European Society of Cardiology-based 10-year CV risk (SCORE2/SCORE2-OP) using univariate and multiple regression. In 299 individuals, blood samples were tested for serum values of 25(OH)D, 1,25(OH)2D and urinary BPA levels. One hundred eighty individuals (60.2%) were deficient (< 20 ng/ml) in 25(OH)D. Levels of 25(OH)D and 1,25(OH)2D were negatively correlated with CV risk score (p < 0.0001 for both) as well as SCORE2/SCORE2-OP (p < 0.0001 for both) while BPA levels were positively correlated with both CV risk scores (p < 0.0001 for both). In a logistic regression model, male gender (odds ratio; OR: 2.1, 95% CI:1.1-3.8, p = 0.022), obesity (OR:2.8, 95% CI:1.2-6.5, p = 0.016) and BPA levels ≥ 110 ng/dl (OR:20.9, 95% CI:9.4-46.8, p < 0.0001) were associated with deficient levels of 25(OH)D. 1,25(OH)2D levels < 41 ng/dl and 25(OH)D levels < 20 ng/ml were associated with CV risk score ≥ 3 (OR: 4.16, 95% CI: 2.32-7.4, p < 0.0001 and OR: 1.86, 95% CI: 1.02-3.39, p = 0.044) respectively and 1,25(OH)2D levels < 41 ng/dl were associated with SCORE2/SCORE2-OP of ≥ 20% (OR:2.98, 95% CI: 1.7-5.2, p = 0.0001). In this cross-sectional analysis, BPA exposure was associated with significantly reduced levels of vitamin D that in turn were significantly associated with increased CV risk.

Plasma levels of myeloperoxidase and resistin independently predict mortality in dialysis patients.

BACKGROUND: In patients with kidney failure (KF) undergoing dialysis, neutrophils are dysfunctionally activated. Such chronic activation does not correspond to increased protection against infections and is thought to cause direct vascular damage accounting for the higher incidence of cardiovascular (CV) events. We hypothesized that circulating levels of neutrophil degranulation products (i.e. myeloperoxidase (MPO) and resistin) can predict overall and CV-specific mortality in dialysis patients. METHODS: MPO and resistin levels were assessed in plasma samples from n = 1182 dialysis patients who were followed-up for median 2.9 years (IQR: 1.7-4.2). RESULTS: Patients were 65 ± 14 (SD) years old and 36 % women. Median value of MPO and resistin were 78 ng/mL (IQR: 54 - 123) and 72 ng/mL (IQR: 46 - 110), respectively. MPO and resistin levels correlated with biomarkers of organ damage, nutritional status and inflammation. Both MPO and resistin levels predicted all-cause mortality even after adjustment for traditional risk factors and inflammation, nutritional and KF-related indexes (MPO, HRfor 1 ln unit increase: 1.26, 95 %CI 1.11 - 1.42, P < 0.001; Resistin, HRfor 1 ln unit increase: 1.25, 95 %CI 1.09 - 1.44, P = 0.001). Similarly, their predictive ability held true also for CV death (MPO, HRfor 1 ln unit increase: 1.19, 95 %CI 1.01 - 1.41, P = 0.04; Resistin, HRfor 1 ln unit increase: 1.29, 95 %CI 1.07 - 1.56, P = 0.007). CONCLUSION: Plasma levels of MPO and resistin correlate with prospective overall and CV-specific mortality risk in KF patients undergoing dialysis and might be useful prognostic tools. Mediators of inflammation may be potential target to improve survival of those patients.

Leadless pacemakers in patients with different stages of chronic kidney disease: Real-world data from the updated i-LEAPER registry.

BACKGROUND: Limited data are available on leadless pacemaker (LPM) outcomes according to different stages of chronic kidney disease (CKD). OBJECTIVE: The purpose of this study was to investigate differences in the safety and efficacy of LPMs among patients stratified per different stages of renal function. METHODS: Consecutive patients enrolled in the multicenter international i-LEAPER registry (International LEAdless PacemakEr Registry) were analyzed. Patients were divided into 3 groups according to CKD stage. The primary end point was the comparison of LPM-related major complication rate at implantation and during follow-up. Differences in electrical performance were deemed secondary outcomes. RESULTS: Of the 1748 patients enrolled, 33% were in CKD stage G3a/G3b and 9.4% were in CKD stage G4/G5. Patients with CKD presented cardiovascular comorbidities more frequently. During a median follow-up of 39 months (interquartile range [IQR] 18-59 months), major complication rate did not differ between groups (normal kidney function [NKF] group 1.8% vs CKD stage G3a/G3b group 2.9% vs CKD stage G4/G5 group 2.4%; P = .418). All-cause mortality resulted higher in the CKD stage G4/G5 group than in the NKF group (19.5% vs 9.8%; adjusted hazard ratio 1.9; 95% confidence interval 1.25-2.89; P = .003). LPM electrical performance was comparable between groups, except for patients with CKD who showed a slightly higher pacing threshold during 1-month follow-up (NKF group 0.50 V [IQR 0.35-0.70 V] vs G3a/G3b group 0.56 V [IQR 0.38-0.81 V] vs G4/G5 group 0.51 V [0.38-0.84 V] @ 0.24 ms; P < .001). CONCLUSION: In a real-world setting, patients with advanced CKD who underwent LPM implantation were underrepresented. Although all-cause mortality was higher in end-stage CKD, periprocedural complications and LPM performance were overall comparable between NKF and different stages of CKD, except for higher values of pacing threshold in patients with CKD up to first-month follow-up.