Clinical Implications of Estimating Glomerular Filtration Rate with Different Equations in Heart Failure Patients with Preserved Ejection Fraction.

INTRODUCTION: The prognostic values of estimated glomerular filtration rate (eGFR) calculated by different formulas have not been adequately compared in patients with heart failure with preserved ejection fraction (HFpEF). AIM: We compared the predictive values of serum creatinine-based eGFRs calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, Modification of Diet in Renal Disease Study (MDRD) formula, and full-age-spectrum creatinine (FAS Cr) equation in 1751 HFpEF patients. METHODS: The area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were employed. RESULTS: eGFR values were lowest calculated with FAS Cr equation (p < 0.001). When patients were classified into 4 subgroups (eGFR ≥ 90, 89-60, 59-30, and  < 30 ml/min/1.73 m2) or only 2 subgroups (≥ 60 or  < 60 ml/min/1.73 m2), the 3 formulas correlated significantly, with the best correlation found between the MDRD and CKD-EPI formulas (kappa = 0.871 and 0.963, respectively). The 3 formulas conveyed independent prognostic information. After adjusting for potential cofounders, risk prediction for all-cause mortality was more accurate (p = 0.001) using the CKD-EPI equation than MDRD formula as assessed by AUC. Compared with MDRD formula, CKD-EPI equation exhibited superior predictive ability assessed by IDI and NRI of 0.32% (p < 0.001)/10.4% (p = 0.010) for primary endpoint and 0.37% (p = 0.010)/10.8% (p = 0.010) for HF hospitalization. The risk prediction for deterioration of renal function was more accurate (p ≤ 0.040) using the CKD-EPI equation than FAS Cr equation as assessed by AUC, IDI, and NRI. CONCLUSION: The CKD-EPI formula might be the preferred creatinine-based equation in clinical risk stratification in HFpEF patients.

Remnant cholesterol is an effective biomarker for predicting survival in patients with breast cancer.

BACKGROUND: Breast cancer is the most common malignancy in women worldwide. The relationship between remnant cholesterol (RC) and the prognosis of patients with breast cancer has not been clearly reported. This study investigated the prognostic value of RC in predicting mortality in patients with breast cancer. METHODS: This study prospectively analysed 709 women patients with breast cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. Restricted cubic splines were used to analyse the dose-response relationship between RC and breast cancer mortality. The Kaplan-Meier method was used to evaluate the overall survival of patients with breast cancer. A Cox regression analyses was performed to assess the independent association between RC and breast cancer mortality. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. Sensitivity analysis was performed after excluding patients with underlying diseases and survival times shorter than one year. RESULTS: A linear dose-response relationship was identified between RC and the risk of all-cause mortality in patients with breast cancer (p = 0.036). Kaplan-Meier survival analysis and log-rank test showed that patients with high RC levels had poorer survival than those with low RC levels (p = 0.007). Univariate and multivariate Cox regression analyses showed that RC was an independent risk factor for mortality in women patients with breast cancer. IPTW-adjusted analyses and sensitivity analyses showed that CR remained a prognostic factor. CONCLUSIONS: RC is an independent risk factor for the prognosis of patients with breast cancer, and patients with higher RC levels have poorer survival.

Assessment of Serum Atherogenic Indices and Insulin Resistance in Retinal Vein Occlusion.

Objectives: This study aimed to investigate serum atherogenic indices as novel cardiovascular risk factors associated with retinal vein occlusion (RVO). Materials and Methods: This retrospective case-control study included 57 patients with newly diagnosed RVO whose plasma lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and insulin resistance were examined. Serum atherogenic indices (LDL-C/HDL-C, TC/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios) and presence of insulin resistance were compared between the patients and 63 healthy subjects. Cut-off values were determined by receiver operating characteristic curve analysis. Results: The mean age of the RVO patients was 63.7±9.4 years. Plasma levels of LDL-C, HDL-C, TC, and TG showed no significant difference between the patient and control groups (p>0.05). However, LDL-C/HDL-C, non-HDL-C/HDL-C, and TC/HDL-C ratios were higher in the RVO group compared to healthy subjects (p=0.015, p=0.036, and p=0.015, respectively). Fasting insulin concentrations, plasma insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were higher in the RVO patients compared to controls (p=0.003, p=0.001, and p=0.001, respectively). Conclusion: LDL-C/HDL-C, TC/HDL-C, and non-HDL-C/HDL-C ratios were found to be increased in RVO. Compared to the traditional plasma lipid profile, serum atherogenic indices were found to be superior predictors of RVO development. Measurement of HOMA-IR index should be taken into consideration in the evaluation of insulin resistance. High serum atherogenic indexes in RVO patients reveal the need to take precautions against the risk of cardiovascular disease and stroke.

Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men.

Introduction: Azoospermia, characterized by an absence of sperm in the ejaculate, represents the most severe form of male infertility. While surgical sperm retrieval in obstructive azoospermia (OA) is successful in the majority of cases, patients with non-obstructive azoospermia (NOA) show retrieval rates of only about 50% and thus frequently have unnecessary surgery. Surgical intervention could be avoided if patients without preserved spermatogenesis are identified preoperatively. This prospective study aimed to discover biomarkers in seminal plasma that could be employed for a non-invasive differential diagnosis of OA/NOA in order to rationalize surgery recommendations and improve success rates. Methods: All patients signed written informed consent, underwent comprehensive andrological evaluation, received human genetics to exclude relevant pathologies, and patients with azoospermia underwent surgical sperm retrieval. Using label-free LC-MS/MS, we compared the proteomes of seminal plasma samples from fertile men (healthy controls (HC), n=8) and infertile men diagnosed with 1) OA (n=7), 2) NOA with successful sperm retrieval (mixed testicular atrophy (MTA), n=8), and 3) NOA without sperm retrieval (Sertoli cell-only phenotype (SCO), n=7). Relative abundance changes of two candidate markers of sperm retrieval, HSPA2 and LDHC, were confirmed by Western Blot. Results: We found the protein expression levels of 42 proteins to be significantly down-regulated (p ≤ 0.05) in seminal plasma from SCO NOA patients relative to HC whereas only one protein was down-regulated in seminal plasma from MTA patients. Analysis of tissue and cell expression suggested that the testis-specific proteins LDHC, PGK2, DPEP3, and germ-cell enriched heat-shock proteins HSPA2 and HSPA4L are promising biomarkers of spermatogenic function. Western blotting revealed a significantly lower abundance of LDHC and HSPA2 in the seminal plasma of men with NOA (SCO and MTA) compared to controls. Discussion: The results indicate that certain testis-specific proteins when measured in seminal plasma, could serve as indicators of the presence of sperm in the testis and predict the success of sperm retrieval. Used in conjunction with conventional clinical assessments, these proteomic biomarkers may assist in the non-invasive diagnosis of idiopathic male infertility.

Free triiodothyronine to free thyroxine ratio as a marker of poor prognosis in euthyroid patients with acute coronary syndrome and diabetes after percutaneous coronary intervention.

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI.

Plasma GFAP, NfL and pTau 181 detect preclinical stages of dementia.

Background: Plasma biomarkers are preferable to invasive and expensive diagnostic tools, such as neuroimaging and lumbar puncture that are gold standard in the clinical management of Alzheimer's Disease (AD). Here, we investigated plasma Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NfL) and Phosphorylated-tau-181 (pTau 181) in AD and in its early stages: Subjective cognitive decline (SCD) and Mild cognitive impairment (MCI). Material and methods: This study included 152 patients (42 SCD, 74 MCI and 36 AD). All patients underwent comprehensive clinical and neurological assessment. Blood samples were collected for Apolipoprotein E (APOE) genotyping and plasma biomarker (GFAP, NfL, and pTau 181) measurements. Forty-three patients (7 SCD, 27 MCI, and 9 AD) underwent a follow-up (FU) visit after 2 years, and a second plasma sample was collected. Plasma biomarker levels were detected using the Simoa SR-X technology (Quanterix Corp.). Statistical analysis was performed using SPSS software version 28 (IBM SPSS Statistics). Statistical significance was set at p < 0.05. Results: GFAP, NfL and pTau 181 levels in plasma were lower in SCD and MCI than in AD patients. In particular, plasma GFAP levels were statistically significant different between SCD and AD (p=0.003), and between MCI and AD (p=0.032). Plasma NfL was different in SCD vs MCI (p=0.026), SCD vs AD (p<0.001), SCD vs AD FU (p<0.001), SCD FU vs AD (p=0.033), SCD FU vs AD FU (p=0.011), MCI vs AD (p=0.002), MCI FU vs AD (p=0.003), MCI FU vs AD FU (p=0.003) and MCI vs AD FU (p=0.003). Plasma pTau 181 concentration was significantly different between SCD and AD (p=0.001), MCI and AD (p=0.026), MCI FU and AD (p=0.020). In APOE ϵ4 carriers, a statistically significant increase in plasma NfL (p<0.001) and pTau 181 levels was found (p=0.014). Moreover, an association emerged between age at disease onset and plasma GFAP (p = 0.021) and pTau181 (p < 0.001) levels. Discussion and conclusions: Plasma GFAP, NfL and pTau 181 are promising biomarkers in the diagnosis of the prodromic stages and prognosis of dementia.

Early dynamic changes to monocytes following major surgery are associated with subsequent infections.

Background: Post-operative infections are a common cause of morbidity following major surgery. Little is understood about how major surgery perturbs immune function leading to heightened risk of subsequent infection. Through analysis of paired blood samples obtained immediately before and 24 h following surgery, we evaluated changes in circulating immune cell phenotype and function across the first 24 h, to identify early immune changes associated with subsequent infection. Methods: We conducted a prospective observational study of adult patients undergoing major elective gastrointestinal, gynecological, or maxillofacial surgery requiring planned admission to the post-anesthetic care unit. Patients were followed up to hospital discharge or death. Outcome data collected included mortality, length of stay, unplanned intensive care unit admission, and post-operative infections (using the standardized endpoints in perioperative medicine-core outcome measures for perioperative and anesthetic care criteria). Peripheral blood mononuclear cells were isolated prior to and 24 h following surgery from which cellular immune traits including activation and functional status were assessed by multi-parameter flow cytometry and serum immune analytes compared by enzyme-linked immunosorbent assay (ELISA). Results: Forty-eight patients were recruited, 26 (54%) of whom developed a post-operative infection. We observed reduced baseline pre- and post-operative monocyte CXCR4 and CD80 expression (chemokine receptors and co-stimulation markers, respectively) in patients who subsequently developed an infection as well as a profound and selective post-operative increase in CD4+ lymphocyte IL-7 receptor expression in the infection group only. Higher post-operative monocyte count was significantly associated with the development of post-operative infection (false discovery rate < 1%; adjusted p-value = 0.001) with an area under the receiver operating characteristic curve of 0.84 (p < 0.0001). Conclusion: Lower monocyte chemotaxis markers, higher post-operative circulating monocyte counts, and reduced co-stimulatory signals are associated with subsequent post-operative infections. Identifying the underlying mechanisms and therapeutics to reverse defects in immune cell function requires further exploration.

Association of two novel systemic inflammatory biomarkers and frailty based on NHANES 2007-2018.

Background: Frailty is a significant concern in the field of public health. However, currently, there is a lack of widely recognized and reliable biological markers for frailty. This study aims to investigate the association between systemic inflammatory biomarkers and frailty in the older adult population in the United States. Methods: This study employed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 and conducted a rigorous cross-sectional analysis. We constructed weighted logistic regression models to explore the correlation between the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and frailty in the population aged 40 to 80 years. Using restricted cubic spline (RCS), we successfully visualized the relationship between SII, SIRI, and frailty. Finally, we presented stratified analyses and interaction tests of covariates in a forest plot. Results: This study involved 11,234 participants, 45.95% male and 54.05% female, with an average age of 64.75 ± 0.13 years. After adjusting for relevant covariates, the weighted logistic regression model indicated an odds ratio (OR) and 95% confidence interval(CI) for the correlation between frailty and the natural logarithm (ln) transformed lnSII and lnSIRI as 1.38 (1.24-1.54) and 1.69 (1.53-1.88), respectively. Subsequently, we assessed different levels of lnSII and lnSIRI, finding consistent results. In the lnSII group model, the likelihood of frailty significantly increased in the fourth quartile (OR = 1.82, 95% CI: 1.55-2.12) compared to the second quartile. In the lnSIRI group model, the likelihood of frailty significantly increased in the third quartile (OR = 1.30, 95% CI: 1.10-1.53) and fourth quartile (OR = 2.29, 95% CI: 1.95-2.70) compared to the second quartile. The interaction results indicate that age and income-to-poverty ratio influence the association between lnSIRI and frailty. RCS demonstrated a nonlinear relationship between lnSII, lnSIRI, and frailty. Conclusion: The results of this cross-sectional study indicate a positive correlation between systemic inflammatory biomarkers (SII, SIRI) and frailty.

Can the Glasgow prognostic score predict ischemic stroke in patients with infective endocarditis?

OBJECTIVE: The Glasgow prognosis score is a simple parameter calculated using serum levels of albumin and C-reactive protein. The aim of this study was to examine whether this parameter may predict ischemic stroke in patients with infective endocarditis. METHODS: A total of 80 patients who were diagnosed with definitive infective endocarditis according to Duke criteria between 2016 and 2023 were included in the study. Glasgow prognosis score was based on serum levels of albumin and C-reactive protein. In imaging methods, patients were divided into two groups according to whether they had a stroke or not. These two groups were compared in terms of biochemical parameters, and infective endocarditis findings on echocardiography and Glasgow prognosis score. RESULTS: We found that the results were statistically similar except for serum C-reactive protein (Group 1: 54.9±71.1 and Group 2: 39±70.7; p=0.03), neutrophil (Group 1: 19.8±10.8*109/L and Group 2: 13.3±7.3*109/L; p=0.014), albumin (Group 1: 2.3±0.6 and Group 2: 2.8±0.5; p=0.03), and Glasgow prognosis score (Group 1: median 2, min.-max. (1-2) and Group 2: median 1, min.-max. (0-1); p=0.004). In the receiver operating characteristics analysis, Glasgow prognosis score had 82.4% sensitivity and 58.3% specificity in predicting ischemic stroke if the Glasgow prognosis score cutoff was ≥1. In multivariate logistic regression analysis, chronic renal failure [odds ratio (OR): 1.098; 95% confidence interval: 1.054-1.964; p=0.044], age (OR: 1.050; 95%CI 1.006-1.096; p=0.024), and Glasgow prognosis score (OR: 0.695; 95%CI 0.411-0.949; p=0.035) were independent variables in predicting ischemic stroke. CONCLUSION: High Glasgow prognosis score is an independent predictor of ischemic stroke in patients with infective endocarditis. Glasgow prognosis score, determined using albumin and C-reactive protein levels, is a simple and practical index for predicting the prognosis of patients hospitalized with infective endocarditis.

Comparison of HIF-1α and survivin levels in patients with diabetes and retinopathy of varying severity.

PURPOSE: This study measured serum hypoxia--inducible factor-1 (HIF-1α) and survivin levels in patients with diabetes and investigated their association with the severity of retinopathy. METHODS: This study included 88 patients with type 2 diabetes mellitus who underwent routine eye examinations. Three groups were created. Group 1 consisted of patients without diabetic retinopathy. Group 2 included patients with non-proliferative diabetic retinopathy. Group 3 included patients with proliferative diabetic retinopathy. To measure serum HIF-1α and survivin levels, venous blood samples were collected from patients. RESULTS: The mean HIF-1α levels in groups 1, 2, and 3 were 17.30 ± 2.19, 17.79 ± 2.34, and 14.19 ± 2.94 pg/ml, respectively. Significant differences were detected between groups 1 and 3 (p=0.01) and between groups 2 and 3 (p=0.01). The mean survivin levels in groups 1, 2, and 3 were 42.65 ± 5.37, 54.92 ± 5.55, and 37.46 ± 8.09 pg/ml, respectively. A significant difference was only detected between groups 2 and 3 (p=0.002). CONCLUSION: The present study revealed that serum HIF-1α and survivin levels are increased in patients with non-proliferative diabetic retinopathy compared to those in patients without diabetic retinopathy.

The association of fibrinogen-albumin ratio and neutrophil-lymphocyte ratio with the severity of respiratory syncytial virus infection in children.

Respiratory syncytial virus (RSV) is a common cause of respiratory infections. It is responsible for more than half of lower respiratory tract infections in infants requiring hospitalization. This study aimed to investigate the correlation between the fibrinogen-albumin ratio (FAR) and the severity of RSV infection and to compare its effectiveness with the neutrophil-lymphocyte ratio (NLR). This was a retrospective cohort study with patients aged from 29 days to two years who had been admitted to the pediatric clinic of our hospital. Patients were divided into four groups: group 1 (mild disease), group 2 (moderate disease), group 3 (severe disease), and group 4 (control). FAR and NLR were measured in all groups. FAR was significantly higher in group 3 than in the other groups, in group 2 than in groups 1 and 4, and in group 1 than in group 4 (p<0.001 for all). NLR was significantly higher in group 4 than in the other groups and in group 3 than in groups 1 and 2 (p<0.001 for all). FAR totaled 0.078 ± 0.013 in patients with bronchiolitis; 0.099 ± 0.028, in patients with bronchopneumonia; and 0.126 ± 0.036, in patients with lobar pneumonia, all with statistically significant differences (p<0.001). NLR showed no significant statistical differences. This study found a statistically significant increase in FAR in the group receiving invasive support when compared to that receiving non-invasive support (0.189 ± 0.046 vs. 0.112 ± 0.030; p=0.003). Mechanical ventilation groups showed no differences for NLR. FAR was used to identify severe RSV-positive patients, with a sensitivity of 84.4%, a specificity of 82.2%, and a cutoff value of >0.068. This study determined a cutoff value of ≤1.49 for NLR, with a sensitivity of 62.2% and a specificity of 62.2% to find severe RSV-positive patients. Also, statistically significant associations were found between FAR and hospitalization and treatment length and time up to clinical improvement (p<0.001 for all). NLR and hospitalization and treatment length showed a weak association (p<0.001). In children with RSV infection, FAR could serve to determine disease severity and prognosis and average lengths of hospitalization, treatment, and clinical improvement. Additionally, FAR predicted disease severity more efficiently than NLR.

The application of plasma circRAD18 in the prediction of gestational diabetes mellitus (GDM) and its adverse effects.

BACKGROUND: In cancer biology, circRAD18 promotes glucose metabolism, potentially indicating its involvement in glucose metabolism-related disorders, such as gestational diabetes mellitus (GDM). The present study investigated the predictive role of circRAD18 in GDM and its potential adverse effects. METHODS: A total of 482 women who intended to get pregnant in short-term were enrolled. For those who successfully conceived, plasma samples were collected and followed up until delivery to monitor the occurrence of GDM and its associated adverse events. The accumulation of circRAD18 in plasma was analyzed using RT-qPCR. GDM-free curves and ROC curves were plotted to assess the predictive value of plasma circRAD18 for GDM. RESULTS: After admitting 482 female patients, 388 of them achieved pregnancy within half a year. During the follow-up period, 52 cases were diagnosed with GDM. Compared to non-GDM group (n = 336), the GDM group (n = 52) had a lower accumulation level of circRAD18 on the day of pregnancy confirmation. In addition, low levels of circRAD18 accumulation on that day distinguished potential GDM patients from non-GDM cases. The 388 cases were divided into high and low circRAD18 level groups (n = 194). GDM-free curve analysis showed that patients in the low circRAD18 level group had a higher incidence of GDM compared to the high level group (43/194 vs. 9/194). A close association was found between low levels of plasma circRAD18 and hypertension, but not premature delivery, intrauterine death, malformation, intrauterine infection, miscarriage, macrosomia or intrauterine distress. CONCLUSION: The reduction in the accumulation of plasma circRAD18 is predictive of GDM and hypertension in pregnant women.

Systolic blood pressure status modifies the associations between the triglyceride-glucose index and incident cardiovascular disease: a national cohort study in China.

BACKGROUND: The triglyceride-glucose (TyG) index and blood pressure (BP) are correlated and serve as risk factors for cardiovascular disease (CVD). The potential impact of BP status on the association between the TyG index and CVD risk remains uncertain. This study aims to investigate the relationships between the TyG index and incident CVD in Chinese middle-aged and elderly adults, considering variations in BP status among participants. METHODS: 6558 participants (mean age: 58.3 (± 8.7) years; 46.0% were men) without prevalent CVD were recruited from the China Health and Retirement Longitudinal Study. Participants were divided into three groups according to their systolic blood pressure (SBP) levels (< 120mmHg, 120 ∼ 129mmHg, ≥ 130mmHg). The TyG index was computed as ln[triglyceride (mg/dl) * fasting blood glucose (mg/dl)/2]. The primary outcome was CVD (heart disease and stroke), and the secondary outcomes were individual CVD components. Cox regression models and restricted cubic splines were performed to investigate the associations between continuous and categorical TyG with CVD. RESULTS: 1599 cases of CVD were captured during 58,333 person-years of follow-up. Per 1-SD higher TyG index was associated with a 19% (HR: 1.19; 95% CI: 1.12, 1.27) higher risk for incident CVD, and the participants with the highest quartile of TyG index had a 54% (HR: 1.54; 95% CI: 1.29, 1.84) higher risk of CVD compared to those in the lowest quartile. SBP significantly modifies the association between the TyG index and CVD, with higher HRs for CVD observed in those with optimal and normal SBP. SBP partially mediated the associations between the TyG index with CVD. The results were generally consistent among participants with varying pulse pressure statuses rather than diastolic BP statuses. CONCLUSIONS: The associations between the TyG index and CVD were modified by BP status, with greater HRs for CVD observed among those who had SBP < 130mmHg. SBP can partially mediate the association between the TyG index with CVD, highlighting the importance of early screening for the TyG index to identify at risk of hypertension and CVD.

The effect of obesity and subsequent weight reduction on cardiac morphology and function in cats.

BACKGROUND: In people, obesity is a risk factor for cardiovascular disease, associated with systemic hypertension, cardiac remodelling and systolic and diastolic dysfunction. Weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. In cats, far less is known regarding the effects of obesity and subsequent weight reduction on cardiovascular morphology and function. This prospective study aimed to assess cardiac morphology and function, heart rate variability, cardiac biomarkers and body composition before and after controlled weight reduction in cats with obesity. Body composition analysis (by dual energy x-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, systemic arterial systolic blood pressure, electrocardiography, plasma cardiac biomarkers) were performed prior to weight management in twenty cats with obesity. These investigations were repeated in eleven cats that reached target weight. RESULTS: At baseline, systemic hypertension was not documented, but the majority of cats with obesity (15 out of 19) showed echocardiographic evidence of diastolic dysfunction. Eleven of 20 cats had increased maximal end-diastolic septal or left ventricular free wall thickness (≥ 6.0 mm) at baseline. Median (interquartile range) percentage of weight lost in the cats reaching target weight was 26% (17-29%), with a median reduction in body fat mass of 45% (26-64%). Both the end-diastolic left ventricular free wall (median magnitude of change -0.85 mm, IQR -0.05 mm to -1.55 mm, P = 0.019; median percentage reduction 14.0%) and end-diastolic interventricular septum (median magnitude of change -0.5 mm, IQR -0.2 mm to -1.225 mm, P = 0.047; median percentage reduction 7.9%) thickness decreased after weight reduction. Following weight reduction, pulsed wave tissue Doppler imaging of the left ventricular free wall was consistent with improved diastolic function in 4 out of 8 cats, however there was no significant difference in overall diastolic function class. Further, there was no change in heart rate variability or cardiac biomarkers with weight reduction. CONCLUSION: An increase in left ventricular wall thickness and diastolic dysfunction were common echocardiographic features in cats with obesity within our study and may be reversible with successful weight and fat mass loss. Further studies are required to clarify the clinical consequences of these findings.

Association between triglyceride-glucose related indices with the all-cause and cause-specific mortality among the population with metabolic syndrome.

BACKGROUND: Triglyceride-glucose (TyG) index has been determined to play a role in the onset of metabolic syndrome (MetS). Whether the TyG index and TyG with the combination of obesity indicators are associated with the clinical outcomes of the MetS population remains unknown. METHOD: Participants were extracted from multiple cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 years. Three indicators were constructed including TyG index, TyG combining with waist circumference (TyG-WC), and TyG combining with waist-to-height ratio (TyG-WHtR). The MetS was defined according to the National Cholesterol Education Program (NCPE) Adult Treatment Panel III. Kaplan-Meier (KM) curves, restricted cubic splines (RCS), and the Cox proportional hazard model were used to evaluate the associations between TyG-related indices and mortality of the MetS population. The sensitive analyses were performed to check the robustness of the main findings. RESULTS: There were 10,734 participants with MetS included in this study, with 5,570 females and 5,164 males. The median age of the study population was 59 years old. The multivariate Cox regression analyses showed high levels of TyG-related indices were significantly associated with the all-cause mortality of MetS population [TyG index: adjustedhazard ratio (aHR): 1.36, 95%confidence interval (CI): 1.18-1.56, p < 0.001; TyG-WHtR index: aHR = 1.29, 95%CI: 1.13-1.47, p < 0.001]. Meanwhile, the TyG-WC and TyG-WHtR index were associated with cardiovascular mortality of the MetS population (TyG-WC: aHR = 1.45, 95%CI: 1.13-1.85, p = 0.004; TyG-WHtR: aHR = 1.50 95%CI: 1.17-1.92, p = 0.002). Three TyG-related indices showed consistent significant correlations with diabetes mortality (TyG: aHR = 4.06, 95%CI: 2.81-5.87, p < 0.001; TyG-WC: aHR = 2.55, 95%CI: 1.82-3.58, p < 0.001; TyG-WHtR: aHR = 2.53 95%CI: 1.81-3.54, p < 0.001). The RCS curves showed a non-linear trend between TyG and TyG-WC indices with all-cause mortality (p for nonlinearity = 0.004 and 0.001, respectively). The sensitive analyses supported the positive correlations between TyG-related indices with mortality of the MetS population. CONCLUSION: Our study highlights the clinical value of TyG-related indices in predicting the survival of the MetS population. TyG-related indices would be the surrogate biomarkers for the follow-up of the MetS population.

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease.

BACKGROUND: Population of patients with inflammatory bowel disease (IBD) is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality. Growth-differentiation factor-15 (GDF-15) is often over-expressed under stress conditions, such as inflammation, malignancies, heart failure, myocardial ischemia, and many others. AIM: To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases. An additional aim was to determine possible associations between GDF-15 and multiple clinical, anthropometric and laboratory parameters in patients with IBD. METHODS: This cross-sectional study included 90 adult patients diagnosed with IBD, encompassing both Crohn's disease (CD) and ulcerative colitis (UC), and 67 healthy age- and sex-matched controls. All patients underwent an extensive workup, including colonoscopy with subsequent histopathological analysis. Disease activity was assessed by two independent gastroenterology consultants specialized in IBD, employing well-established clinical and endoscopic scoring systems. GDF-15 serum concentrations were determined following an overnight fasting, using electrochemiluminescence immunoassay. RESULTS: In patients with IBD, serum GDF-15 concentrations were significantly higher in comparison to the healthy controls [800 (512-1154) pg/mL vs 412 (407-424) pg/mL, P < 0.001], whereas no difference in GDF-15 was found between patients with CD and UC [807 (554-1451) pg/mL vs 790 (509-956) pg/mL, P = 0.324]. Moreover, multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age, sex, and C-reactive protein levels (P = 0.016 and P = 0.049, respectively). Finally, an association between GDF-15 and indices of anemia was established. Specifically, negative correlations were found between GDF-15 and serum iron levels (r = -0.248, P = 0.021), as well as GDF-15 and hemoglobin (r = -0.351, P = 0.021). Accordingly, in comparison to IBD patients with normal hemoglobin levels, GDF-15 serum levels were higher in patients with anemia (1256 (502-2100) pg/mL vs 444 (412-795) pg/mL, P < 0.001). CONCLUSION: For the first time, we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls, and the results imply that GDF-15 might be involved in IBD pathophysiology. Yet, it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Blood-based biological ageing and red cell distribution width are associated with prevalent Parkinson's disease: findings from a large Italian population cohort.

Background: Aging clocks tag the actual underlying age of an organism and its discrepancy with chronological age and have been reported to predict incident disease risk in the general population. However, the relationship with neurodegenerative risk and in particular with Parkinson's Disease (PD) remains unclear, with few discordant findings reporting associations with both incident and prevalent PD risk. Objective: To clarify this relationship, we computed a common aging clock based on blood markers and tested the resulting discrepancy with chronological age (ΔPhenoAge) for association with both incident and prevalent PD risk. Methods: In a large Italian population cohort - the Moli-sani study (N=23,437; age ≥ 35 years; 52% women) - we carried out both Cox Proportional Hazards regressions modelling ΔPhenoAge as exposure and incident PD as outcome, and linear models testing prevalent PD as exposure and ΔPhenoAge as outcome. All models were incrementally adjusted for age, sex, education level completed and other risk/protective factors previously associated with PD risk in the same cohort (prevalent dysthyroidism, hypertension, diabetes, use of oral contraceptives, exposure to paints, daily coffee intake and cigarette smoking). Results: No significant association between incident PD risk (209 cases, median (IQR) follow-up time 11.19 (2.03) years) and PhenoAging was observed (Hazard Ratio [95% Confidence Interval] = 0.98 [0.71; 1.37]). However, a small but significant increase of ΔPhenoAge was observed in prevalent PD cases vs healthy subjects (ß (Standard Error) = 1.39 (0.70)). An analysis of each component biomarker of PhenoAge revealed a significant positive association of prevalent PD status with red cell distribution width (RDW; ß (SE) = 0.46 (0.18)). All the remaining markers did not show any significant evidence of association. Conclusion: The reported evidence highlights systemic effects of prevalent PD status on biological aging and red cell distribution width. Further cohort and functional studies may help shedding a light on the related pathways altered at the organism level in prevalent PD, like red cells variability, inflammatory and oxidative stress mechanisms.

Associations of sex hormone ratios with metabolic syndrome and inflammation in US adult men and women.

Background: Sex hormones play a critical role in sex differences and cardiovascular disease risk associated with metabolic syndrome (MS) and inflammation. However, the associations of sex hormone ratios with metabolic and inflammatory markers are unclear according to sex and age differences. We evaluated the associations of sex hormone ratios with MS and inflammation among males and females. Methods: A retrospective cross-sectional study was conducted by including all adults from the National Health and Nutrition Examination Survey cycles 2013-2016 and excluding any pregnant women, heart disease, diabetes, and those currently taking insulin. MS was defined using the National Cholesterol Education Program criteria and a high-sensitivity C-reactive protein (CRP) level>3 mg/L was defined as a high CRP. Measures of MS components and CRP concentrations were also analyzed. The primary exposures were testosterone to estradiol (excess androgen index), testosterone to sex hormone-binding globulin (free androgen index), and estradiol to sex hormone-binding globulin (free estradiol index). The adjusted associations were summarized with a relative risk (RR) and 95% confidence interval (CI). Results: This study included 9167 subjects with 4360 males and 4807 females. Increases in free estradiol index were positively associated with MS (RR=1.48; 95%CI: 1.39, 1.58; RR=1.31; 95%CI: 1.22, 1.40) and high CRP (RR=1.49; 95%CI: 1.25, 1.77; RR=1.26; 95%CI: 1.06, 1.50) in men with age<50 years and age≥50 years, respectively. Similarly, higher free estradiol index was also robustly associated with increased prevalence of MS (RR=1.22; 95%CI: 1.15, 1.28) and high CRP (RR=1.68; 95%CI: 1.48, 1.90) in women with age ≥50 years. Among women with age<50 years, a higher free androgen index was associated with MS (RR=1.34; 95%CI: 1.25, 1.42) and high CRP (RR=1.13; 95%CI: 1.02, 1.25). These associations were unchanged even after adjusting for all sex hormones. Conclusion: Free estradiol index was consistently and positively associated with MS and high CRP in males of all ages and older females. Free androgen index was positively associated with MS and high CRP in females with age<50 years.

Association of glycogen synthase kinase-3ß with cognitive impairment in type 2 diabetes patients: a six-year follow-up study.

Background: Our previous multicenter case-control study showed that aging, up-regulation of platelet glycogen synthase kinase-3ß (GSK-3ß), impaired olfactory function, and ApoE ϵ4 genotype were associated with cognitive decline in type 2 diabetes mellitus (T2DM) patients. However, the causal relationship between these biomarkers and the development of cognitive decline in T2DM patients remains unclear. Methods: To further investigate this potential relationship, we designed a 6-year follow-up study in 273 T2DM patients with normal cognitive in our previous study. Baseline characteristics of the study population were compared between T2DM patients with and without incident mild cognitive impairment (MCI). We utilized Cox proportional hazard regression models to assess the risk of cognitive impairment associated with various baseline biomarkers. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic accuracy of these biomarkers in predicting cognitive impairment. Results: During a median follow-up time of 6 years (with a range of 4 to 9 years), 40 patients (16.13%) with T2DM developed MCI. Participants who developed incident MCI were more likely to be older, have a lower education level, have more diabetic complications, a higher percentage of ApoE ϵ4 allele and a higher level of platelet GSK-3ß activity (rGSK-3ß) at baseline (P<0.05). In the longitudinal follow-up, individuals with higher levels of rGSK-3ß were more likely to develop incident MCI, with an adjusted hazard ratio (HR) of 1.60 (95% confidence interval [CI] 1.05, 2.46), even after controlling for potential confounders. The AUC of the combination of age, rGSK-3ß and ApoEϵ4 allele predicted for incident MCI was 0.71. Conclusion: Platelet GSK-3ß activity could be a useful biomarker to predict cognitive decline, suggesting the feasibility of identifying vulnerable population and implementing early prevention for dementia.

Correlation Between the 8-hydroxy-2'-deoxyguanosine Level in the Peritoneal Solution of Patients Undergoing Peritoneal Dialysis and the Peritoneal Equilibration Test, Kt/V, Ferritin, and Albumin Levels.

INTRODUCTION: Peritoneal dialysis (PD) is an effective treatment  modality for advanced kidney failure, offering patients a significant  degree of independence. However, the long-term use of PD is  limited due to the degeneration of the peritoneal membrane,  resulting in reduced dialysis adequacy. Evaluating the peritoneal  membrane condition in patients with advanced kidney failure  who are undergoing PD is challenging with existing methods.  Therefore, this study aimed to investigate the correlation between  8-hydroxy-2'-deoxyguanosine (8OHDG) levels in the peritoneal  solution of patients undergoing PD and various factors, such  as peritoneal equilibration test (PET), dialysis adequacy (Kt/V),  underlying diseases, serum ferritin, and albumin levels. 8OHDG  is a sensitive marker of oxidative stress caused by DNA damage. METHODS: A total of 56 patients were included in this cross-sectional  study. Five milliliters of PD fluid were collected from the patients,  and 8-OHdG levels were measured using ELISA method. Then, they  were compared with PET, Kt/V, albumin, and ferritin markers in  the patients' files, and the results were analyzed by statistical tests. RESULTS: The study examined the correlation between 8OHDG  and other markers. It was found that this index had significant  associations with PET and underlying HTN (P < .05), whereas no  significant associations were identified with the other markers. CONCLUSION: The results of the present study demonstrate that  the level of 8OHDG, as one of the oxidative stress markers, could  be used to evaluate the function of the peritoneum in patients  undergoing PD. DOI: 10.52547/ijkd.7654.