This study examines global trends in cardiovascular disease (CVD) associated with kidney dysfunction (KD) from 1990 to 2021 and projects future trends through 2050.

This study analyzed the 2021 Global Burden of Disease (GBD) database, focusing on age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years rate (ASDR), absolute numbers, estimated annual percentage change, and average annual percent change. A Bayesian age-period-cohort model was employed to project global trends from 2022 to 2050. Variables included age, gender, national levels, and Socio-demographic Index (SDI) regions.

From 1990 to 2021, the CVD burden from KD increased, with deaths rising from 1,312,393 to 2,095,800 and DALYs from 27,382,767 to 41,589,861. However, the ASMR decreased from 40.58 per 100,000 in 1990 to 25.55 in 2021, while ASDR fell from 742.17 to 489.81 during the same period. The burden was higher in men, peaking at ages 70-74 and in women at ages 85-89. Regions with lower-middle and low SDI recorded the highest CVD burden, inversely related to SDI levels. Geographically, Central Asia and Eastern Europe recorded the highest rates, while high-income Asia Pacific and Southern Latin America had the lowest. Projections suggest a sustained decline in global CVD burden due to KD from 2022 to 2050, although disparities between sexes are expected to persist, with men bearing a heavier burden.

CVD attributable to KD remains a major global public health challenge, especially for men, the elderly, and low SDI regions. These spatial and temporal variations highlight the need for region-specific healthcare strategies.

Biomarkers are pivotal in the management of heart failure (HF); however, their lack of cardiac specificity could limit clinical utility. This study aimed to investigate the transcoronary changes and intracardiac production of these biomarkers.

Transcoronary gradients for B-type natriuretic peptide (BNP) and five novel biomarkers-galectin-3 (Gal-3), soluble suppression of tumourigenicity 2 (sST2), tissue inhibitor of metalloproteinase 1 (TIMP-1), growth differentiation factor 15 (GDF-15) and myeloperoxidase (MPO)-were determined using femoral artery (FA) and coronary sinus (CS) samples from 30 HF patients and 10 non-HF controls. Intracardiac biomarker production was assessed in an HF canine model using real-time quantitative PCR (qPCR) and western blot (WB) analysis.

Compared with the control group, levels of all detected biomarkers were significantly elevated in the HF group, while transcoronary gradients were only observed for BNP, Gal-3 and TIMP-1 levels in the HF group (BNP: FA: 841.5 ± 727.2 ng/mL vs. CS: 1132.0 ± 959.1 ng/mL, P = 0.005; Gal-3: FA: 9.5 ± 3.0 ng/mL vs. CS: 19.7 ± 16.4 ng/mL, P = 0.002; and TIMP-1: FA: 286.7 ± 68.9 ng/mL vs. CS: 377.3 ± 108.9 ng/mL, P = 0.001). Real-time qPCR and WB analysis revealed significant elevation of BNP, Gal-3 and TIMP-1 in the cardiac tissues of the HF group relative to other groups.

This study provided evidence of transcoronary changes in BNP, Gal-3 and TIMP-1 levels in HF patients, offering insights into their intracardiac production. These findings enhance the understanding of the biology of these biomarkers and may inform their clinical application.

Although the neurocardiac axis is central to cardiovascular homeostasis, its dysregulation drives heart failure and cardiometabolic diseases. This review examines the bidirectional interplay between the autonomic nervous system and the heart, highlighting the role of this interplay in disease progression and its therapeutic potential. The autonomic nervous system modulates cardiac function and vascular tone through its sympathetic and parasympathetic branches. However, in heart failure, chronic sympathetic overdrive and parasympathetic withdrawal exacerbate myocardial remodeling and metabolic dysfunction, both of which are exacerbated by cardiometabolic conditions such as obesity and diabetes. These conditions are increasingly recognized to impair neurocardiac regulation, thereby promoting inflammation and adverse outcomes. An important emerging area concerns neuroimmune control, in which the brain orchestrates systemic inflammation through circuits involving the bone marrow, spleen, and other organs, thereby amplifying cardiovascular damage. This neuroimmune axis integrates peripheral signals to influence immune responses that contribute to disease progression. Lifestyle factors, such as stress, sleep, exercise, and diet, affect autonomic and immune balance and, thus, cardiovascular disease. Therapeutically, targeting neurocardiac and neuroimmune pathways pharmacologically or via neuromodulation (eg, vagal or splenic nerve stimulation) offers promise although the clinical translation of the latter remains challenging. In this review, we synthesize preclinical and clinical data to highlight the neurocardiac axis as a critical nexus in heart failure and cardiometabolic disease. Harnessing neuroimmune and neurocardiac interactions may inform precision approaches to reduce the burden of these conditions.

Dilated cardiomyopathy is an important contributor to heart failure burden worldwide. With an aging population and rising multimorbidity, in this review, we describe the prevalence of metabolic syndrome and renal failure in patients with dilated cardiomyopathy and focus on common underlying mechanisms, evaluate outcomes in these patients and highlight newer therapeutic strategies.

A significant proportion of patients with dilated cardiomyopathy has concomitant metabolic syndrome and renal disease. This combination of multimorbidity portends worse prognosis and often presents unique challenges in treatment given the complex interplay and shared pathophysiological pathways. Optimization of the cardio-renal-metabolic profile should be a key consideration in the management of patients with dilated cardiomyopathy. Therapeutic strategies targeting common pathophysiological pathways are needed in order to improve overall outcomes.

Type 2 diabetes (T2DM) co-existing with pulmonary tuberculosis (PTB) is associated with increased rates of treatment failure and mortality. Therefore, greater understanding of the occurrence and prevalence of this comorbidity and research to address the prevention and treatment of PTB in patients with T2DM (PTB + T2DM) have become paramount. Weighted gene co-expression network analysis (WGCNA) and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were employed to identify key gene modules and functions related to PTB + T2DM. Immune cell infiltration and drug sensitivity were compared between PTB + T2DM patients and healthy controls (HCs), with a bioinformatic approach. Several key genes were chosen for in vitro expression assays using quantitative real-time PCR (qRT-PCR), western blotting (WB), and enzyme-linked immunosorbent assay (ELISA). Compared to HCs and T2DM-only patients, PTB + 2DM patients showed upregulated expression of complement component C1q. WGCNA identified five crucial genes associated with PTB + T2DM: C1QA, CD248, LINC00278, MMP8, and MMP9. Multiscale embedded gene co-expression network analysis further identified FN1. The main KEGG pathways in PTB + T2DM patients were related to extracellular matrix-receptor interaction, the interleukin-17 signaling pathway, the AGE-RAGE signaling pathway in diabetic complications, the PI3K-Akt signaling pathway, and neutrophil extracellular trap formation. Receiver operating characteristic (ROC) analysis indicated that CD248, MMP8, MMP9, LINC00278, and C1QA have potential as diagnostic markers for PTB + T2DM. The expression levels of C1QA, LINC00278, MMP8, and MMP9 were significantly higher, and that of CD248 was significantly lower, in PTB + T2DM patients than in HCs. A network comprising highly correlated hub genes and microRNAs revealed the following interactions: C1QA with hsa-miR-363-5p, hsa-miR-671-5p, and hsa-miR-25-5p; CD248 with COL1 A2, COL1 A1, and COL4 A1; MMP8 with hsa-miR-539-5p, MMP9, and CEACAM8; and MMP9 with FN1, MMP8, hsa-miR-29b-3p, hsa-miR-942-3p, hsa-miR-302-5p, and hsa-miR-133a-5p. Seven drugs (ERK_440_1713, JAK_8517_1739, Palbociclib_1054, PLX.4720_1036, Savolitinib_1936, Selumetinib_1736, and VX.11e_2096) exhibited significant sensitivity in patients with high-expression or low-expression of C1QA. ELISA, qRT-PCR, and WB analyses confirmed the upregulated expression of C1QA, MMP8, and MMP9 in the peripheral blood of PTB + T2DM patients. This study elucidated the intricate molecular connections between PTB and T2DM and identified potential shared targets. Five genes (C1QA, MMP8, MMP9, CD248, and LINC00278) have potential as diagnostic markers for PTB + T2DM, and three genes (C1QA, MMP8, and MMP9) were upregulated in the peripheral blood of PTB + T2DM patients. Our findings may serve as a valuable reference for future research and clinical applications.

Diabetic cardiomyopathy (DbCM) is characterized by subclinical abnormalities in cardiac structure/function and is associated with a higher risk of overt heart failure (HF). However, there are limited data on optimal strategies to identify individuals with DbCM in contemporary health systems. The aim of this study was to evaluate the prevalence of DbCM in a health system using existing data from the electronic health record (EHR).

Adult patients with type 2 diabetes mellitus free of cardiovascular disease (CVD) with available data on HF risk in a single-center EHR were included. The presence of DbCM was defined using different definitions: (1) least restrictive: ≥1 echocardiographic abnormality (left atrial enlargement, left ventricle hypertrophy, diastolic dysfunction); (2) intermediate restrictive: ≥2 echocardiographic abnormalities; (3) most restrictive: 3 echocardiographic abnormalities. DbCM prevalence was compared across age, sex, race, and ethnicity-based subgroups, with differences assessed using the chi-squared test. Adjusted logistic regression models were constructed to evaluate significant predictors of DbCM.

Among 1921 individuals with type 2 diabetes mellitus, the prevalence of DbCM in the overall cohort was 8.7% and 64.4% in the most and least restrictive definitions, respectively. Across all definitions, older age and Hispanic ethnicity were associated with a higher proportion of DbCM. Females had a higher prevalence than males only in the most restrictive definition. In multivariable-adjusted logistic regression, higher systolic blood pressure, higher creatinine, and longer QRS duration were associated with a higher risk of DbCM across all definitions.

In this single-center, EHR cohort, the prevalence of DbCM varies from 9% to 64%, with a higher prevalence with older age and Hispanic ethnicity.

The 4-dimensional automated left atrial quantification (4D Auto LAQ) technology for the left atrium was recently available. We aimed to evaluate LA function using 4D Auto LAQ in patients with type 2 diabetes mellitus (T2DM) and investigate its value in predicting left ventricular remodeling (LVR).

A total of 106 T2DM patients (56 with left ventricular [LV] remodeling and 50 with normal geometry) and 46 age- and sex-matched controls were enrolled. LA total emptying fraction (LATEF), LA active emptying fraction (LAAEF), LA passive emptying fraction (LAPEF), and strain parameters, including LA reservoir longitudinal/circumferential strain (LASr/LASr-c), LA conduit longitudinal/circumferential strain (LAScd/LAScd-c), and LA contraction longitudinal/circumferential strain (LASct/LASct-c), were assessed with 4D Auto LAQ.

Compared to controls, LASr, LAScd, and LAPEF significantly decreased in both groups of T2DM patients (p < 0.001). T2DM patients with LVR had significantly lower LASr and LAScd than those with normal geometry (p < 0.001). LATEF was also reduced in T2DM patients with LVR compared to the control group (p < 0.05). Among the 4D-LAQ parameters, only LASr (odds ratio [OR]: 0.860, p = 0.016) was associated with LV remodeling (LVR) in multivariate analysis. Receiver operating characteristic (ROC) curves identified a LASr value of ≤22.5% as the optimal cutoff point to predict LVR in the T2DM cohort (sensitivity, 86.0%; specificity, 64.3%; area under the curve [AUC], 0.770; p < 0.001). In addition, LASr was found to be negatively correlated with both LV mass index (LVMI) and relative wall thickness (RWT) but positively correlated with the absolute value of the LV global longitudinal strain (LVGLS).

Impairment of LA reservoir and conduit functions can be observed in patients with T2DM, particularly in those with LVR. LASr may serve as a predictor of LVR in patients with T2DM.

Type 2 diabetes mellitus (T2DM) is closely associated with an increased risk and adverse event of acute coronary syndrome (ACS). The present study aims to investigate the association between differential urinary metabolites and major adverse cardiovascular events (MACEs) in patients with ACS co-morbid T2DM with preserved renal function, and to explore the potential value of the metabolites as prognostic biomarkers in this population. Ultra-high performance liquid chromatography-mass spectrometry (UHPLC/MS) was used to analyze urine samples from ACS co-morbid T2DM. Spearman's correlation was used to examine the association between differential metabolites and serum fasting blood glucose (FBG), glycated hemoglobin (HbA1c), Syntax score I, and MACE. The Cox proportional hazards models and Kaplan-Meier survival curves were used to identify MACE risk factors. A total of 101 differential urinary metabolites were identified, of which seven showed a correlation with FBG, HbA1c, Syntax score I and MACE. In particular, myo-inositol and (E)-Monocrotophos emerged as significant indicators of poor prognosis in ACS co-morbid with T2DM. Urinary metabolomic alteration is closely associated with clinical manifestation of ACS co-morbid T2DM. Urinary myo-inositol and (E)-Monocrotophos may be considered as prognostic biomarkers of ACS co-morbid T2DM.

To investigate the association between the Weekend Warrior (WW) pattern and diabetes prevalence in American adults.

Cross-sectional analysis of data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES).

We examined the relationship between four physical activity (PA) patterns-inactive, insufficiently active, WW, and regularly active-and diabetes prevalence. Multivariable logistic regression, marginal average population effects (MAPE), subgroup, and sensitivity analyses were performed to assess these associations. Odds ratios (ORs) and average marginal effects (AME), along with 95 % confidence intervals (CIs) were calculated.

Individuals engaging in the WW pattern (OR = 0.60, 95 % CI: 0.40 to 0.89, p = 0.013; AME = -0.05, 95 % CI: -0.09 to -0.02, p = 0.004) and the regularly active pattern (OR = 0.69, 95 % CI: 0.60 to 0.80, p < 0.001; AME = -0.04, 95 % CI: -0.06 to -0.03, p < 0.001) showed significantly lower diabetes prevalence than those classified as inactive. Compared to individuals classified as inactive, those categorized as insufficiently active demonstrated no significant difference in diabetes prevalence. No significant difference was observed between the WW and regularly active patterns (OR = 0.86, 95 % CI: 0.56 to 1.35, p = 0.5; AME = -0.01, 95 % CI: -0.06 to 0.03, p = 0.501). Subgroup interaction analyses revealed no significant effect modification (all p for interaction >0.05), and sensitivity analyses confirmed the robustness of these findings.

Both the WW and regularly active patterns are associated with a lower prevalence of diabetes compared with inactive individuals.

This study assesses success and methodological implications of linking IQVIA's Electronic Medical Records (EMR) of type 2 diabetes (T2D) patients with the National Health Data System (SNDS) database, a cornerstone process in healthcare research.

The OREOT cohort was constituted by T2D patients identified in the IQVIA EMR from 2014 to 2018 and linked indirectly to SNDS database. The EMR database contains clinical records from general practitioner consultations, representing ~2.8% of the French population and the SNDS claims database covers over 99% of the French population's healthcare activities. Linkage success was evaluated by the linkage rate. Baseline patients' characteristics were described for both linked and non-linked patients.

Of the 291 408 T2D patients identified in the EMR, 244 656 (84%) were successfully linked. After technical data cleaning, 239 141 (82%) were finally linked. Linked and non-linked patients (n = 52,267) were aged 65 years and more frequently male (57% and 59%); half were obese, and most of comorbidities were consistent. Linked patients had more EMR consultations (median 32 vs 16), and more cardiovascular events (12% vs 7%) or chronic kidney disease (10% vs 7%).

The successful linkage of EMR and SNDS databases provides valuable insights for future research in T2D and other chronic diseases requiring clinical data. This study demonstrates the feasibility of such data alignments, particularly in patients with complex health profiles or extensive medical records, and linkage potential to enhance real-world research quality. Despite higher prevalence of baseline comorbidities among linked patients, patients' characteristics were consistent with French T2D population.

To assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD) among patients with type 2 diabetes (T2D) in Belgium. To analyze trends in medication use and adherence to guidelines from 2019 to 2023.

We conducted a retrospective cross-sectional analysis using data from the Intego primary care database, encompassing records from 431 general practitioners. We identified adults with T2D through diagnostic codes and glycated hemoglobin levels and analyzed subgroups with ASCVD, HF, and CKD for trends in medication use, particularly SGLT2 inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP-1).

The T2D population increased from 20,766 in 2019 to 21,764 in 2023. The prevalence of ASCVD, HF, and CKD among T2D patients slightly increased to 27 %, 6.7 %, and 23.7 % by 2023 (from 25.2 %, 4.9 % and 21.5 % respectively). Medication prescription trends showed a tripling of SGLT2-i and GLP-1 prescribing in the study period to 6.2 % and 11.5 % respectively. Despite these increases, only 7.5 % of eligible patients received these medications as of 2023.

The study highlights a growing burden of ASCVD, HF, and CKD among T2D patients in Belgium and an increase in the use of guideline-recommended medications. However, there remains a substantial gap in the optimal use of these therapies, indicating a need for improved implementation of clinical guidelines in primary care.

Diabetic cardiomyopathy (DCM) is one of the most prevalent and severe complications associated with diabetes mellitus (DM). The onset of DCM is insidious, with the symptoms being obvious only in the late stage. Consequently, the early diagnosis of DCM is a formidable challenge which significantly influences the treatment and prognosis of DCM. Thus, it becomes imperative to uncover innovative approaches to facilitate the prompt identification and diagnosis of DCM. On the traditional clinical side, we tend to use serum biomarkers as well as imaging as the most common means of diagnosing diseases because of their convenience as well as affordability. As we delve deeper into the mechanisms of DCM, a wide variety of biomarkers are becoming competitive diagnostic indicators. Meanwhile, the application of multiple imaging techniques has also made efforts to promote the diagnosis of DCM. Besides, the spurt in sequencing technology has made it possible to give hints about disease diagnosis from the genome as well as the transcriptome, making diagnosis less difficult, more sensitive, and more predictive. Overall, sequencing technology is expected to be the superior choice of plasma biomarkers for detecting lesions at an earlier stage than imaging, and its judicious utilization combined with imaging technologies will lead to a more sensitive diagnosis of DCM in the future. Therefore, this review meticulously consolidates the progress and utilization of various biomarkers, imaging methods, and sequencing technologies in the realm of DCM diagnosis, with the aim of furnishing novel theoretical foundation and guide future research endeavors towards enhancing the diagnostic and therapeutic landscape of DCM.

Lately, numerous researches have portrayed stress hyperglycemia ratio (SHR) is predominantly connected with short-term adverse prognosis among individuals who have acute coronary syndrome. Nevertheless, the relation of SHR with prolonged effects and the value of SHR in predicting in coronary artery disease (CAD) patients with or lacking chronic kidney disease (CKD) remain unclear. The present study was designed to elucidate the relation of SHR with prolonged prognosis and the value of SHR in predicting the long-term all-cause and cardiovascular death of CAD patients with CKD or non-CKD.

We assessed 45,780 adults with CAD from a Chinese multi-center registry. SHR was computed via a formula [SHR = (admission glucose) (mmol/L) / (1.59 * HbA1c [%] - 2.59)]. Based on the presence or absence of CKD and SHR levels, patients were categorized into four groups. Long-term all-cause and cardiovascular mortality were the primary endpoints. The Kaplan-Meier method, restricted cubic spline (RCS), cox regression analysis, subgroups analysis, and sensitivity analysis were employed to estimate the connection between SHR and all-cause as well as cardiovascular mortality.

During a median follow-up of 5.2 years ( IQR 3.0-8.0), among 45,780 CAD patients (mean age [SD]: 62.8 ± 10.6 years; 23.9% female), the number of all-cause deaths was 7144(15.6%), and cardiovascular-related deaths was 3255 (7.1%). In cohorts with CKD, patients with high SHR had higher all-cause mortality (30.2% vs. 27.6%; adjusted hazard ratio HR 1.13, 95% CI 1.04-1.22; P = 0.003) and cardiovascular mortality (18.2% vs. 15.6%; HR adjusted 1.17, 95% CI 1.06-1.30; P = 0.002) compared to the individuals in low SHR. However, this was not the case in CAD cohorts without CKD [all-cause mortality (12.9% vs. 11.9%; HR adjusted 1.04, 95%CI 0.98-1.10, P = 0.206); cardiovascular mortality (5.1% vs. 4.4%; HR adjusted 1.09, 95%CI 0.99-1.20, P = 0.084)]. KM analysis revealed that high SHR is linked with all-cause mortality [CKD (log-rank P < 0.001); no-CKD (log-rank P = 0.024)] and cardiovascular mortality [CKD (log-rank P < 0.001); no-CKD (log-rank P = 0.01)] in CAD patients with or without CKD. RCS demonstrated that the relation between SHR and all-cause mortality was U-shaped after full modification, which was shown for CKD patients (P for non-linearity = 0.003) and also for patients without CKD (P for non-linearity = 0.001). Analogous effects were discovered for cardiovascular mortality, which was the case for CKD patients (P for non-linearity < 0.001) and also for patients without CKD (P for non-linearity = 0.001).

Among patients with CAD, an elevated stress hyperglycemia ratio (SHR) is implicated in a heightened risk of long-term outcomes, particularly in those with CKD. This signifies that SHR might have a latent function in the cardiovascular risk categorization of the CAD population.

In clinical practice, an increasing number of patients exhibit concurrent cardiac and renal dysfunction, known as "cardiorenal syndrome," where each condition exacerbates the other, resulting in poorer patient prognosis. Fluid and sodium retention can lead to excessive fluid overload in the body; therefore, correcting fluid and sodium metabolic disorders is crucial for alleviating patient symptoms. This study was to investigate the abnormalities in water and sodium metabolism, as well as the expression levels of arginine vasopressin receptor 1a (AVPR1a) and arginine vasopressin receptor 2 (AVPR2), in a rat model of chronic renal failure-chronic heart failure (CRF-CHF). One hundred male Sprague-Dawley rats were randomly assigned into four groups: the CG group (normal feeding), the CRF group (3/4 nephrectomy using a "two-step surgical method"), the CHF group (subcutaneous injection of isoproterenol at 100 mg/kg), and the CRF-CHF group (3/4 nephrectomy followed by a subcutaneous injection of isoproterenol at 100 mg/kg 1 week later). 4 weeks post-surgery, urine and blood samples were collected to measure 24 h urinary protein, sodium, and potassium levels. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were determined using assay kits. Left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP) were measured via left ventricular catheterization. The heart was weighed to calculate the left ventricular weight to body weight ratio (LVW/BW). The renal cortex and medulla were isolated to assess the relative mRNA and protein expression levels of AVPR1a and AVPR2. Compared to the CG group, the CRF and CRF-CHF groups exhibited significantly elevated levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla. The CHF and CRF-CHF groups showed significant increases in LVEDP and LVW/BW (P < 0.05). Additionally, compared to the CG group, the other three groups had significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Compared to the CRF and CHF groups, the CRF-CHF group exhibited significantly higher levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla, along with significantly increased LVEDP and LVW/BW, significantly reduced LVSP, significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Rats with CRF-CHF experienced exacerbated renal and cardiac failure, characterized by significant disturbances in water and sodium metabolism and abnormal expression of AVPR1a and AVPR2.

In response to hyperglycemia, endothelial cells (ECs) release exosomes with altered protein content and contribute to paracrine signalling, subsequently leading to vascular dysfunction in type 2 diabetes (T2D). High glucose reprograms DNA methylation patterns in various cell/tissue types, including ECs, resulting in pathologically relevant changes in cellular and extracellular proteome. However, DNA methylation-based proteome reprogramming in endothelial exosomes and associated pathological implications in T2D are not known. Hence, in the present study, we used Human umbilical vein endothelial cells (HUVECs), High Fat Diet (HFD) induced diabetic mice (C57BL/6) and clinical models to understand epigenetic basis of exosome proteome regulation in T2D pathogenesis . Exosomes were isolated by size exclusion chromatography and subjected to tandem mass tag (TMT) labelled quantitative proteomics and bioinformatics analysis. Immunoblotting was performed to validate exosome protein signature in clinically characterized individuals with T2D. We observed ECs cultured in high glucose and aortic ECs from HFD mouse expressed elevated DNA methyltransferase1 (DNMT1) levels. Quantitative proteomics of exosomes isolated from ECs treated with high glucose and overexpressing DNMT1 showed significant alterations in both protein levels and post translational modifications which were aligned to T2D associated vascular functions. Based on ontology and gene-function-disease interaction analysis, differentially expressed exosome proteins such as Thrombospondin1, Pentraxin3 and Cystatin C related to vascular complications were significantly increased in HUVECs treated with high glucose and HFD animals and T2D individuals with higher levels of glycated hemoglobin. These proteins were reduced upon treatment with 5-Aza-2'-deoxycytidine. Our study shows epigenetic regulation of exosome proteome in T2D associated vascular complications.

This study aimed to develop and validate a nomogram for predicting 28-day and 90-day mortality in intensive care unit (ICU) patients who have chronic obstructive pulmonary disease (COPD) coexisting with congestive heart failure (CHF).

An extensive analysis was conducted on clinical data from the Medical Information Mart for Intensive Care IV database, covering patients over 18 years old with both COPD and CHF, who were were first-time ICU admissions between 2008 and 2019. The least absolute shrinkage and selection operator (LASSO) regression method was employed to screen clinical features, with the final model being optimized using backward stepwise regression guided by the Akaike Information Criterion (AIC) to construct the nomogram. The predictive model's discrimination and clinical applicability were evaluated via receiver operating characteristic (ROC) curves, calibration curves, the C-index, and decision curve analysi s (DCA).

This analysis was comprised of a total of 1948 patients. Patients were separated into developing and validation cohorts in a 7:3 ratio, with similar baseline characteristics between the two groups. The ICU mortality rates for the developing and verification cohorts were 20.8 % and 19.5 % at 28 days, respectively, and 29.4 % and 28.3 % at 90 days, respectively. The clinical characteristics retained by the backward stepwise regression include age, weight, systolic blood pressure (SBP), respiratory rate (RR), oxygen saturation (SpO2), red blood cell distribution width (RDW), lactate, partial thrombosis time (PTT), race, marital status, type 2 diabetes mellitus (T2DM), malignant cancer, acute kidney failure (AKF), pneumonia, immunosuppressive drugs, antiplatelet agents, vasoactive agents, acute physiology score III (APS III), Oxford acute severity of illness score (OASIS), and Charlson comorbidity index (CCI). We developed two separate models by assigning weighted scores to each independent risk factor: nomogram A excludes CCI but includes age, T2DM, and malignant cancer, while nomogram B includes only CCI, without age, T2DM, and malignant cancer. Based on the results of the AUC and C-index, this study selected nomogram A, which demonstrated better predictive performance, for subsequent validation. The calibration curve, C-index, and DCA results indicate that nomogram A has good accuracy in predicting short-term mortality and demonstrates better discriminative ability than commonly used clinical scoring systems, making it more suitable for clinical application.

The nomogram developed in this study offers an effective assessment of short-term mortality risk for ICU patients with COPD and CHF, proving to be a superior tool for predicting their short-term prognosis.

The HeartLogic algorithm (Boston Scientific, St Paul, MN) integrates data from implantable cardioverter-defibrillator (ICD) sensors to predict heart failure (HF) decompensation: first (S1) and third (S3) heart sounds, intrathoracic impedance, respiration rate, ratio of respiration rate to tidal volume (RSBI), and night heart rate.

This study assessed the relative changes in ICD sensors at the onset of HeartLogic alerts, their association with patient characteristics, and outcomes.

The study included 568 patients with HF carrying ICDs (CRT-D, n = 410) across 26 centers, with a median follow-up of 26 months. HeartLogic alerts triggered patient contact and potential treatment.

A total of 1200 HeartLogic alerts were recorded in 370 patients. The sensor with the highest change at the alert's onset was S3 in 27% of alerts, followed by S3/S1 (25%). Patients with atrial fibrillation (AF) and chronic kidney disease (CKD) at implantation had higher prevalence of alerts (AF, 84% vs no AF, 58%; CKD, 72% vs no CKD, 59%; P < .05) and rate (AF, 1.51 per patient-year vs no AF, 0.88 per patient-year; CKD, 1.30 per patient-year vs no CKD, 0.89 per patient-year; P < .05). During follow-up, 247 patients experienced more than 1 alert; in 85%, the sensor with the highest change varied between successive alerts. Of the 88 (7%) alerts associated with HF hospitalization or death, respiration rate or RSBI (11%, P = .007 vs S3/S1) and night heart rate (11%, P = .031 vs S3/S1) were more commonly the sensors showing the highest change. Clinical events were more common with the first alert (12.6%) than subsequent alerts (5.2%, P < .001).

HeartLogic alerts are mostly triggered by changes in heart sounds, but clinical events are more linked to respiration rate, RSBI, and night heart rate. Recurrent alerts often involve different sensors, indicating diverse mechanisms of HF progression.

Diabetes is a major risk factor for cardiovascular diseases, and myocardial damage caused by hyperglycemia is the main cause of heart failure. However, there is still a lack of systematic understanding of myocardial damage caused by diabetes. At present, we believe that the cellular inflammatory damage caused by hyperglycemia is one of the causes of diabetic cardiomyopathy. Pyroptosis, as a proinflammatory form of cell death, is closely related to the occurrence and development of diabetic cardiomyopathy. Therefore, this paper focuses on the important role of inflammation in the occurrence and development of diabetic cardiomyopathy. From the perspective of pyroptosis, we summarize the pyroptosis of different types of cells in diabetic cardiomyopathy and its related signaling pathways. It also summarizes the treatment of diabetic cardiomyopathy, hoping to provide methods for the prevention and treatment of diabetic cardiomyopathy by inhibiting pyroptosis.

This study aimed to evaluate the burden of kidney dysfunction (KD), assess socioeconomic inequalities, and project trends in the future.

Data on deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) were from Global Burden of Disease Study 2019. The Joinpoint regression model was utilized to analyze the temporal trend by the annual percentage change (APC). The slope index and concentration index were employed to evaluate cross-country disparities. The future trend was predicted using an age-period-cohort analysis.

In the past three decades, the death numbers of KD increased from 1,571,720 to 3,161,552, DALYs from 42,090,331 to 76,486,945, YLDs from 5,003,267 to 11,282,484, and YLLs from 37,087,065 to 65,204,461, respectively. The age-standardized rate (ASR) of deaths, DALYs, and YLLs exhibited a declining trend. The ASR of YLDs increased until 2017, then decreased. The slope index and concentration index for DALYs increased from 248.1 to 351.9 and from 40.70 to 57.8. In the future, the ASR of deaths, DALYs, YLDs, and YLLs will remain stable, while their numbers will continue to rise, except for YLLs.

The disease burden of KD remained serious. Tailored interventions should be developed based on national contexts.

Current understanding of the prognosis for patients with chronic kidney disease (CKD) and overlapping cardio-renal-metabolic components, specifically heart failure (HF) and diabetes mellitus (DM), remains limited. While previous studies have explored the interactions between CKD, HF, and DM, they have predominantly focused on cohorts of HF or DM patients. This study aims to fill this gap by investigating the long-term outcomes and treatment patterns in a cohort of CKD patients, particularly those with coexisting HF and DM.

We analysed data from the Swedish national CKD patient cohort, the Swedish Renal Registry, with a follow-up period extending up to 10 years. The study examined the risks of all-cause mortality, major adverse cardiovascular events (MACE)-defined as a composite of non-fatal myocardial infarction, hospitalization for congestive HF, non-fatal stroke, or cardiovascular death-and the initiation of kidney replacement therapy (KRT). Analyses were conducted using Cox proportional hazards and competing risk models. Among the 27 647 patients, 48% had CKD alone, 12% had CKD with HF, 27% had CKD with DM, and 13% had CKD with both HF and DM. After 5 years, mortality rates were 23% for patients with CKD, 30% for those with CKD/DM, 54% for CKD/HF, and 55% for CKD/HF/DM. The 10 year absolute risk of MACE was 28% for CKD alone, 35% for CKD/DM, 67% for CKD/HF, and 73% for CKD/HF/DM. The adjusted hazard ratio (HR) for mortality was approximately three times higher in patients with any HF combination, with HRs of 2.57 [95% confidence interval (CI) 2.43-2.71] for CKD/HF and 3.22 (95% CI 3.05-3.39) for CKD/HF/DM, compared with CKD alone. The impact of HF on MACE prognosis was even more pronounced, with adjusted sub-hazard ratios (SHRs) of 3.33 (95% CI 3.14-3.53) for CKD/HF and 4.26 (95% CI 4.04-4.50) for CKD/HF/DM. Additionally, CKD patients diagnosed with HF were less likely to commence KRT, and the risk of death prior to KRT initiation was roughly twice as high for these groups, with SHRs of 2.05 (95% CI 1.93-2.18) for CKD + HF and 2.43 (95% CI 2.29-2.58) for CKD + HF + DM.

In a cohort of CKD patients, having HF contributes substantially to increased mortality and the risk of MACE, and these patients are less likely to start KRT. These findings highlight the urgent need for targeted therapeutic strategies and management plans for CKD patients, particularly those with concurrent HF, to enhance patient prognosis.

The management of patients with type 2 diabetes is asynchronous, i.e. not coordinated in time, resulting in delayed access to care and low use of guideline-directed medical therapy (GDMT).

We retrospectively analysed consecutive patients assessed in the 'synchronized' DECIDE-CV clinic. In this outpatient clinic, patients with type 2 diabetes and cardiovascular or chronic kidney disease are simultaneously assessed by an endocrinologist, cardiologist and nephrologist in the same visit. The primary outcome was use of GDMT before and after the assessment in the clinic, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, renin-angiotensin system blockers and mineralocorticoid receptor antagonists. Secondary outcomes included the baseline-to-last-visit change in surrogate laboratory biomarkers.

The first 232 patients evaluated in the clinic were included. The mean age was 67 ± 12 years, 69% were men and 92% had diabetes. In total, 73% of patients had atherosclerotic cardiovascular disease, 65% heart failure, 56% chronic kidney disease and 59% had a urinary albumin-to-creatinine ratio ≥30 mg/g. There was a significant increase in the use of GDMT:sodium-glucose cotransporter 2 inhibitors (from 44% to 87% of patients), glucagon-like peptide 1 receptor agonists (from 8% to 45%), renin-angiotensin system blockers (from 77% to 91%) and mineralocorticoid receptor antagonists (from 25% to 45%) (p < .01 for all). Among patients with paired laboratory data, glycated haemoglobin, urinary albumin-to-creatinine ratio and N-terminal proB-type natriuretic peptide levels significantly dropped from baseline (p < .05 for all).

Joint assessment of patients with diabetes in a synchronized cardiometabolic clinic holds promise for enhancing GDMT use and has led to significant reductions in surrogate cardiovascular and renal laboratory biomarkers.

Heart failure (HF) is a complex clinical syndrome caused by structural or functional dysfunction of the ventricular filling or blood supply. Diabetes mellitus (DM) is an independent predictor of mortality for HF. The increase in prevalence, co-morbidity and hospitalization rates of both DM and HF has further fueled the possibility of overlapping disease pathology between the two. For decades, antidiabetic drugs that are known to definitively increase the risk of HF are the thiazolidinediones (TZDs) and saxagliptin in the dipeptidyl peptidase-4 (DPP-4) inhibitor, and insulin, which causes sodium and water retention, and whether metformin is effective or safe for HF is not clear. Notably, sodium-glucose transporter 2 (SGLT2) inhibitors and partial glucagon-like peptide-1 receptor agonists (GLP-1 RA) all achieved positive results for HF endpoints, with SGLT2 inhibitors in particular significantly reducing the composite endpoint of cardiovascular mortality and hospitalization for heart failure (HHF). Further understanding of the mutual pathophysiological mechanisms between HF and DM may facilitate the detection of novel therapeutic targets to improve the clinical outcome. This review focuses on the association between HF and DM, emphasizing the efficacy and safety of antidiabetic drugs and HF treatment. In addition, recent therapeutic advances in HF and the important mechanisms by which SGLT2 inhibitors/mineralocorticoid receptor antagonist (MRA)/vericiguat contribute to the benefits of HF are summarized.

We aimed to analyze the trajectories of cognitive decline as a function of the presence of type 2 diabetes and glycemic control in analyzes stratified by sex in an 8-year follow-up period.

A total of 1 752 men and 2 232 women aged ≥50 years who participated in the English Longitudinal Study of Ageing (ELSA), conducted from 2004 to 2012, were analyzed. The outcomes of interest were performance on the cognitive domains of memory, executive function, and temporal orientation as well as the global cognition score. Cognitive performance was standardized in z-scores in strata based on schooling and age. The participants were classified as without diabetes, with controlled glycemia, and with uncontrolled glycemia, according to medical diagnosis, glucose-lowering medications use and HbA1c levels. Generalized linear mixed models controlled by sociodemographic, behavioral, and health-related characteristics were used for the trajectory analyses.

No differences in z-scores were found for global cognition or cognitive domains based on diabetes classification in men and women at baseline. More than 8 years of follow up, women with uncontrolled glycemia had a greater decline in z-scores for global cognition (-0.037 SD/year [95% CI: -0.073; -0.001]) and executive function (-0.049 SD/year [95% CI: -0.092; -0.007]) compared with those without diabetes. No significant difference in trajectories of global cognition or any cognitive domain was found in men as a function of diabetes classification.

Women with uncontrolled glycemia are at greater risk of a decline in global cognition and executive function than those without diabetes.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been studied in patients with heart failure, type 2 diabetes, chronic kidney disease, atherosclerotic cardiovascular disease, and acute myocardial infarction. Individual trials were powered to study composite outcomes in one disease state. We aimed to evaluate the treatment effect of SGLT2 inhibitors on specific clinical endpoints across multiple demographic and disease subgroups.

In this systematic review and meta-analysis, we queried online databases (PubMed, Cochrane CENTRAL, and SCOPUS) up to Feb 10, 2024, for primary and secondary analyses of large trials (n>1000) of SGLT2 inhibitors in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease (including acute myocardial infarction). Outcomes studied included composite of first hospitalisation for heart failure or cardiovascular death, first hospitalisation for heart failure, cardiovascular death, total (first and recurrent) hospitalisation for heart failure, and all-cause mortality. Effect sizes were pooled using random-effects models. This study is registered with PROSPERO, CRD42024513836.

We included 15 trials (N=100 952). Compared with placebo, SGLT2 inhibitors reduced the risk of first hospitalisation for heart failure by 29% in patients with heart failure (hazard ratio [HR] 0·71 [95% CI 0·67-0·77]), 28% in patients with type 2 diabetes (0·72 [0·67-0·77]), 32% in patients with chronic kidney disease (0·68 [0·61-0·77]), and 28% in patients with atherosclerotic cardiovascular disease (0·72 [0·66-0·79]). SGLT2 inhibitors reduced cardiovascular death by 14% in patients with heart failure (HR 0·86 [95% CI 0·79-0·93]), 15% in patients with type 2 diabetes (0·85 [0·79-0·91]), 11% in patients with chronic kidney disease (0·89 [0·82-0·96]), and 13% in patients with atherosclerotic cardiovascular disease (0·87 [0·78-0·97]). The benefit of SGLT2 inhibitors on both first hospitalisation for heart failure and cardiovascular death was consistent across the majority of the 51 subgroups studied. Notable exceptions included acute myocardial infarction (22% reduction in first hospitalisation for heart failure; no effect on cardiovascular death) and heart failure with preserved ejection fraction (26% reduction in first hospitalisation for heart failure; no effect on cardiovascular death).

SGLT2 inhibitors reduced heart failure events and cardiovascular death in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease. These effects were consistent across a wide range of subgroups within these populations. This supports the eligibility of a large population with cardiorenal-metabolic diseases for treatment with SGLT2 inhibitors.

None.

Background: Several studies have shown that sodium-dependent glucose transporter 2 inhibitors can be used in the treatment of heart failure. This article summarized systematic reviews of sodium-dependent glucose transporter 2 inhibitors in the treatment of heart failure in order to evaluate efficacy and safety. Methods: We systematically searched eight electronic databases from inception to July 2023. We used Assessment of Multiple Systematic Reviews 2 to evaluate the methodological quality, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 to assess report quality, Risk of Bias in Systematic Review to assess the risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation to rate the quality of evidence. Outcome: A total of 36 systematic reviews were included. Our results were classified as clear evidence of benefit: hospitalization for heart failure; possible benefit: cardiovascular death (mortality) and renal outcome composite; clear evidence of no effect or equivalence: atrial arrhythmias, ventricular arrhythmia, atrial fibrillation, and hypotension; possible harm: genital infection; insufficient evidence to draw a conclusion: atrial flutter, major adverse cardiovascular events, urinary tract infection, acute kidney injury, hypoglycemia, and bone fracture. Conclusions: Sodium-dependent glucose transporter 2 inhibitors are beneficial for the treatment of heart failure, especially in terms of heart failure hospitalization.

The study aimed to investigate the potential effect of Antithrombin III (ATIII) between chronic renal insufficiency and chronic coronary artery disease (chronic CAD) in type 2 diabetes mellitus (T2DM) patients.

T2DM patients hospitalized in ZhongDa Hospital from 2013 to 2018 were enrolled. Relationships between renal function, ATIII, and chronic CAD risk were explored using multivariate regression models. Multiplicative and additive interactions were investigated between ATIII and renal function for CAD risk, and the role of ATIII was determined by bootstrap mediation analysis in patients with chronic renal dysfunction.

A total of 4197 patients were included in the study, with a chronic CAD prevalence of 23.02%. Low ATIII level was statistically associated with chronic renal insufficiency and elevated CAD risk even after adjustments (P < 0.05). A positive correlation between renal function and ATIII was demonstrated, and each 1 SD increase in renal function, ATIII increased by 2.947% (2.406-3.488%, P < 0.001) and 0.969% (0.297-1.642%, P < 0.001) in crude and adjusted models respectively. Patients with decreased renal function and ATIII were at the highest chronic CAD risk (OR = 1.51, 95%CI:1.15-1.98, P < 0.05), while no multiplicative and additive interaction effects were significant. Bootstrap mediation analysis estimated that ATIII mediated approximately 4.27% of the effect of chronic renal insufficiency on chronic CAD risk.

ATIII may serve as a mediator between chronic renal insufficiency and chronic CAD, providing mechanistic clues for renal-heart association and new insight into clinical therapies.

This study aimed to evaluate the potential association between chewing areca nuts and the occurrence of type 2 diabetes and to investigate whether chewing status (current chewers or ex-chewers) affects this association.

We searched The Cochrane Library, PubMed, and EMBASE databases for relevant studies up to May 21, 2023, using predefined inclusion and exclusion criteria. Three population-based studies conducted in Taiwan were included in the systematic review and meta-analysis.

When combined current or ex-chewers were more likely to develop diabetes (Odds Ratio [OR] = 1.45; 95% confidence interval [CI]: 1.30-1.62) compared to the never chewers. Ex-chewers had a higher risk of diabetes (OR: 1.53, 95% CI: 1.45-1.62) compared to never chewers. However, there was no evidence that current chewers were associated with a higher risk of diabetes compared to never chewers. Male current and ex-chewers were associated with higher risk of diabetes compared with never chewers (OR: 1.55, 95% CI: 1.49-1.61). For females there was insufficient evidence.

Existing evidence suggests a link between chewing areca nuts and the development of type 2 diabetes. Therefore, areca chewers should monitor diabetes-related biomarkers.

The aim of the study was to evaluate renal function in three groups of precarious workers: garbage recyclers (REC), quarry workers (CAN), and brick makers (LAD). Samples of urine and blood were collected to evaluate clinical parameters and the metal levels in urine was measured using ICP-MS. REC group had the highest concentrations of chromium in urine (36.03 ± 27.2 µg/l) compared to CAN and LAD groups. Mercury concentrations were higher in the LAD group (3.7 ± 0.8 µg/l). Additionally, arsenic was detected in both CAN and REC groups (25.4 ± 26.2 and 19.09 ± 16.7 µg/l, respectively), while arsenic concentrations in LAD were higher (47.2 ± 30.8 µg/l). In kidney biomarkers, β2-microglobulin concentrations were higher in the REC group (87867 ± 115159.5 ng/g UCr). Similarly, cystatin-C concentrations were higher in the REC group (32795.61 ± 34965.8 ng/g UCr). The data suggests that precarious workers are exposed to heavy metals and have elevated protein levels that contribute to kidney damage.

To evaluate the prevalence of heart failure (HF) in patients with diabetes in tertiary care, and the implementation of sodium-glucose co-transporter 2 inhibitor (SGLT2i).

Between 28.09.2020 and 31.03.2022, patients enrolled in the Swiss Diabetes Registry at one study centre were screened for HF based on the recommendations by the European Society of Cardiology. Indicated patients were referred for echocardiography and a clinical evaluation of HF, further stratified by preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) left ventricular ejection fraction.

In total, 534 patients were screened (31.5%, type 1 diabetes (T1D); 59.7%, type 2 diabetes (T2D); 8.8%, other forms). Overall, HF was present in 11.2% (HFpEF, 56.7%; HFmrEF, 11.7%; HFrEF, 31.7%). Prevalence by diabetes type was 2.4%, T1D; 16.0%, T2D; and 10.6%, other forms. Of the identified cases, 40.0% were previously diagnosed and 60.0% were diagnosed as a result of the screening. Of the 24 patients with previously known HF, 50.0% were prescribed SGLT2i (including 2 out of 3 patients with HFrEF).

The fact that most cases of HF were previously undiagnosed and treatment with SGLT2i could be improved highlights the need to increase awareness of HF among healthcare professionals treating patients with diabetes.

Intervertebral disc degeneration (IVDD) contributes largely to low back pain. Recent studies have highlighted the exacerbating role of diabetes mellitus (DM) in IVDD, mainly due to the influence of hyperglycemia (HG) or the accumulation of advanced glycation end products (AGEs). Vascular endothelial growth factor A (VEGFA) newly assumed a distinct impact in nonvascular tissues through mitophagy regulation. However, the combined actions of HG and AGEs on IVDD and the involved role of VEGFA remain unclear. We confirmed the potential relation between VEGFA and DM through bioinformatics and biological specimen detection. Then we observed that AGEs induced nucleus pulposus (NP) cell degeneration by upregulating cellular reactive oxygen species (ROS), and HG further aggravated ROS level through breaking AGEs-induced protective mitophagy. Furthermore, this adverse effect could be strengthened by VEGFA knockdown. Importantly, we identified that the regulation of VEGFA and mitophagy were vital mechanisms in AGEs-HG-induced NP cell degeneration through Parkin/Akt/mTOR and AMPK/mTOR pathway. Additionally, VEGFA overexpression through local injection with lentivirus carrying VEGFA plasmids significantly alleviated NP degeneration and IVDD in STZ-induced diabetes and puncture rat models. In conclusion, the findings first confirmed that VEGFA protects against AGEs-HG-induced IVDD, which may represent a therapeutic strategy for DM-related IVDD.

Cervical cancer (CC) in Mexico is diagnosed mainly in locally advanced (LACC) and advanced (ACC) stages, where ureteral obstruction is more frequent. The standard treatment for this population is concurrent chemoradiotherapy (CCRT) with cisplatin, which is nephrotoxic and could lead to further deterioration of renal function in LACC patients with renal function decline. We aimed to evaluate the effect of CCRT with Gemcitabine on renal function in LACC patients.

This retrospective study included LACC patients treated with CCRT with Gemcitabine as a radiosensitizer from February 2003 to December 2018. Data were collected from medical archives and electronic records. We assessed renal function before and after CCRT treatment and analyzed the patient's response to treatment and survival.

351 LACC patients treated were included and stratified into two groups: 198 with Glomerular Filtration Rate (GFR) ≥60ml/min (group A) and 153 with GFR<60ml/min (group B). An improvement in GFR was observed after CCRT in patients in group B, from 33 ml/min to 57.5 ml/min (p<0.001). Complete response was observed in 64.1% of patients in Group A and 43.8% in Group B (p<0.0001). Factors associated with increased risk of death included having a GFR of 15-29 ml/min (HR: 2.17; 1.08-4.35), having GFR<15 ml/min (HR: 3.08; 1.63-5.79), and receiving Boost treatment (HR: 2.09; 1.18-3.69). On the other hand, receiving brachytherapy is a positive predictor for OS (HR:0.51; 0.31-0.84).

CCRT with gemcitabine is an appropriate treatment option for patients diagnosed with LACC who present impaired renal function due to the disease's obstructive nature or other comorbidities.

Heart failure (HF) affects an estimated 6 million American adults, and the prevalence continues to increase, driven in part by the aging of the population and by increases in the prevalence of diabetes. In recent decades, improvements in the survival of patients with HF have resulted in a growing number of individuals living longer with HF. HF and its comorbidities are associated with substantial impairments in physical functioning, emotional well-being, and quality of life, and also with markedly increased rates of morbidity and mortality. As a result, the management of patients with HF has a substantial economic impact on the health care system, with most costs arising from hospitalization. Clinicians have an important role in helping to reduce the burden of HF through timely diagnosis of HF as well as increasing access to effective treatments to minimize symptoms, delay progression, and reduce hospital admissions. Prevention and early diagnosis of HF will play a fundamental role in efforts to reduce the large and growing burden of HF. Recent advances in pharmacotherapies for HF have the potential to radically change the management of HF, offering the possibility of improved survival and quality of life for patients.

Mitochondrial-derived peptides (MDPs) are a novel class of bioactive microproteins encoded by short open-reading frames (sORF) in mitochondrial DNA (mtDNA). Currently, three types of MDPs have been identified: Humanin (HN), MOTS-c (Mitochondrial ORF within Twelve S rRNA type-c), and SHLP1-6 (small Humanin-like peptide, 1 to 6). The 12 S ribosomal RNA (MT-RNR1) gene harbors the sequence for MOTS-c, whereas HN and SHLP1-6 are encoded by the 16 S ribosomal RNA (MT-RNR2) gene. Special genetic codes are used in mtDNA as compared to nuclear DNA: (i) ATA and ATT are used as start codons in addition to the standard start codon ATG; (ii) AGA and AGG are used as stop codons instead of coding for arginine; (iii) the standard stop codon UGA is used to code for tryptophan. While HN, SHLP6, and MOTS-c are encoded by the H (heavy owing to high guanine + thymine base composition)-strand of the mtDNA, SHLP1-5 are encoded by the L (light owing to less guanine + thymine base composition)-strand. MDPs attenuate disease pathology including Type 1 diabetes (T1D), Type 2 diabetes (T2D), gestational diabetes, Alzheimer's disease (AD), cardiovascular diseases, prostate cancer, and macular degeneration. The current review will focus on the MDP regulation of T2D, T1D, and gestational diabetes along with an emphasis on the evolutionary pressures for conservation of the amino acid sequences of MDPs.

Background: To evaluate the efficacy and safety of Keluoxin (KLX) capsules and provide validated evidence for the application of KLX in the treatment of diabetic kidney disease (DKD). Methods: A multicenter, randomized, double-blind, placebo-controlled trial design was used to screen 129 patients with DKD (urinary albumin-to-creatinine ratio [UACR]: male, 2.5-30 mg/mmol; female, 3.5-30 mg/mmol) and with Qi and Yin deficiency and blood stasis symptoms. Written informed consent was obtained from all patients. The patients were randomly divided into KLX and control groups. The KLX group was orally administered KLX (6 g/day) and irbesartan tablets (150 mg/day), whereas the control group was administered KLX placebo (6 g/day) and irbesartan tablets (150 mg/day). Patients were observed for 24 weeks to evaluate the natural logarithm of the UACR (log-UACR), the odds ratio (OR) for a sustained increase in the UACR of at least 30% and 40%, estimated glomerular filtration rate (eGFR), changes in symptoms and quality-of-life scores, and adverse events. Results: The changes of the natural log-UACR during the 24 weeks compared with baseline in the KLX group were better than those in the control group (LS mean ± standard error, -0.26 ± 0.10 vs. 0.01 ± 0.09, p = 0.0292). The incidence of a sustained increase in the UACR of at least 30% and 40% was found to be significantly lower in the KLX group (OR, 0.26; 95% confidence interval [CI], 0.09-0.75; OR, 0.29; 95% CI, 0.10-0.82). Changes in symptoms and quality-of-life scores in the KLX group were better than those in the control group. There was no statistically significant difference in eGFR or the incidence of adverse events between the groups. Conclusions: Overall, these results suggest that KLX capsules combined with irbesartan can reduce microalbuminuria, relieve the symptoms, and improve the quality of life for patients with type 2 early DKD compared with the use of irbesartan alone. Trial registration: Chinese Clinical Trial Registry, registration number: ChiCTR2100052764.

Heart failure (HF) is a chronic disease characterized by high mortality and healthcare expenditures. Digital health solutions, including mobile health applications (apps), offer opportunities to enhance patients' self-care and quality of life. This qualitative study aimed to explore expectations, experiences, and usage behaviour of HF-patients regarding a self-care app (DoctorME app).

Semi-structured interviews were conducted at 2-3 weeks (initial: n = 38), and 4-6 months (post: n = 45) of app use across four European countries. Most patients were male (initial: 84%; post: 78%), aged 60-69 years (initial and post: 29%), with mild HF symptoms. Interviews were transcribed, pseudonymised, and analysed using qualitative content analysis.

Five key themes were identified: 1) expectations, 2) perceived usability and benefit, 3) usage behaviour and experiences, 4) self-care, and 5) social influences. Patients expected and valued continuous monitoring of vital signs and weight, early detection of deterioration, and quick feedback. The app was considered user-friendly, with most patients using it as recommended (eight times per month). Those reporting improved self-care attributed it to increased awareness and a sense of security. Patients with established self-care routines did not perceive any additional benefit. Patients' perceptions on the impact of healthcare professionals' and relatives opinions on app use were divided.

User-friendliness, continuous monitoring, rapid feedback, and e-learning modules are crucial for integrating self-care apps into daily HF care. While technical reliability and individualisation may enhance long-term use, most HF patients considered the app as a complement to, not a replacement for, professional healthcare guidance.

Limited data have examined the association between air pollution and the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We aimed to investigate whether long-term exposure to air pollutants is related to the development of ESRD among patients with T2DM and CKD. A total of 1,738 patients with T2DM and CKD hospitalized in Peking University Third Hospital from January 1, 2013, to December 31, 2021 were enrolled in this study. The outcome was defined as the occurrence of ESRD. Data on six air pollutants (PM2.5, PM10, CO, NO2, SO2, and O3) from 35 monitoring stations were obtained from the Beijing Municipal Ecological and Environmental Monitoring Center. Long-term exposure to air pollutants during the follow-up period was measured using the ordinary Kriging method. During a mean follow-up of 41 months, 98 patients developed ESRD. Multivariate logistic regression analysis showed that an increase of 10 μg/m3 in PM2.5 (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.03-1.36) and PM10 (OR 1.15, 95% CI 1.02-1.30) concentration were positively associated with ESRD. An increase of 1 mg/m3 in CO (2.80, 1.05-7.48) and an increase of 1 μg/m3 in SO2 (1.06, 1.00-1.13) concentration were also positively associated with ESRD. Apart from O3 and NO2, all the above air pollutants have additional predictive value for ESRD in patients with T2DM and CKD. The results of Bayesian kernel machine regression and the weighted quantile sum regression all showed that PM2.5 was the most important air pollutant. Backward stepwise logistic regression showed that PM2.5 was the only pollutant remaining in the prediction model. In patients with T2DM and CKD, long-term exposure to ambient PM2.5, PM10, CO, and SO2 was positively associated with the development of ESRD.