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1.
Artículo en Inglés | MEDLINE | ID: mdl-39047687

RESUMEN

INTRODUCTION: There was limited research on the epidemiology of hyperphosphatemia in early-stage chronic kidney disease (CKD) patients. We aimed to explore the clinical characteristics and prognostic value of hyperphosphatemia in patients with CKD stages 1-2. METHODS: We enrolled adult patients with CKD stages 1-2 from 24 regional central hospitals across China. Hyperphosphatemia was defined as a serum phosphate level exceeding 1.45 mmol/L. The study outcomes included all-cause and cardiovascular (CV) mortality. Cox proportional hazard models were used to investigate the association of hyperphosphatemia with all-cause and CV mortality. RESULTS: Among 99,266 patients with CKD stages 1-2 across China, the prevalence of hyperphosphatemia was 8.3%. The prevalence of hyperphosphatemia was increased with the level of urinary protein and was higher in younger and female patients. Among 63,121 patients with survival information, during a median of 5.2 years follow-up period, there were 436 (8.0%) and 4,695 (8.1%) deaths in those with and without hyperphosphatemia, respectively. After adjusting for potential confounders, compared with patients without hyperphosphatemia, patients with hyperphosphatemia was associated with a higher risk of all-cause mortality (HR, 1.28, 95% CI, 1.16-1.41). Although nearly 60.3% of hyperphosphatemia could be relieved without phosphate-lowering drug therapy among patients with CKD stages 1-2, transient hyperphosphatemia was also associated with an increased risk of all-cause mortality (P=0.048). CONCLUSIONS: Hyperphosphatemia was not rare in patients with CKD stages 1-2 and was associated with an increased risk of mortality. Clinicians should closely monitor serum phosphorus levels in patients with CKD, even in those with normal kidney function.

2.
Sci Rep ; 14(1): 16878, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043740

RESUMEN

Lipid peroxidation and mitochondrial damage impair insulin sensitivity in skeletal muscle. Sirtuin-1 (SIRT1) protects mitochondria and activates under energy restriction. Dapagliflozin (Dapa) is an antihyperglycaemic agent that belongs to the sodium-glucose cotransporter-2 (SGLT2) inhibitors. Evidence shows that Dapa can induce nutrient deprivation effects, providing additional metabolic benefits. This study investigates whether Dapa can trigger nutrient deprivation to activate SIRT1 and enhance insulin sensitivity in skeletal muscle. We treated diet-induced obese (DIO) mice with Dapa and measured metabolic parameters, lipid accumulation, oxidative stress, mitochondrial function, and glucose utilization in skeletal muscle. ß-hydroxybutyric acid (ß-HB) was intervened in C2C12 myotubes. The role of SIRT1 was verified by RNA interference. We found that Dapa treatment induced nutrient deprivation state and reduced lipid deposition and oxidative stress, improved mitochondrial function and glucose tolerance in skeletal muscle. The same positive effects were observed after ß-HB intervening for C2C12 myotubes, and the promoting effects on glucose utilization were diminished by SIRT1 RNA interference. Thus, Dapa promotes a nutrient deprivation state and enhances skeletal muscle insulin sensitivity via SIRT1 activation. In this study, we identified a novel hypoglycemic mechanism of Dapa and the potential mechanistic targets.


Asunto(s)
Compuestos de Bencidrilo , Glucósidos , Resistencia a la Insulina , Músculo Esquelético , Estrés Oxidativo , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Sirtuina 1/genética , Glucósidos/farmacología , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Ratones , Compuestos de Bencidrilo/farmacología , Estrés Oxidativo/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Masculino , Glucosa/metabolismo , Línea Celular , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Ratones Endogámicos C57BL , Ácido 3-Hidroxibutírico/farmacología , Ácido 3-Hidroxibutírico/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Hipoglucemiantes/farmacología
3.
Angew Chem Int Ed Engl ; : e202411871, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054405

RESUMEN

Advancing catalyst design is pivotal for the enhancement of photocatalytic processes in renewable energy conversion. The incorporation of structural chirality into conventional inorganic solar hydrogen nanocatalysts promises a significant transformation in catalysis, a feature absent in this field. Here we unveil the unexplored potential of geometric chirality by creating a chiral composite that integrates geometric chiral Au nanoparticles (NPs) with two-dimensional C3N4 nanosheets, significantly boosting photocatalytic H2 evolution beyond the achiral counterparts. The superior performance is driven by the geometric chirality of Au NPs, which facilitates efficient charge carrier separation through the favorable C3N4-chiral Au NP interface and chiral induced spin polarization, and exploits high-activity facets within the concave surfaces of chiral Au NPs. The resulting synergistic effect leads to a remarkable increase in photocatalytic H2 evolution, with an apparent quantum yield of 44.64% at 400 nm. Furthermore, we explore the selective polarized photo-induced carrier separation behavior, revealing a distinct chiral-dependent photocatalytic HER performance. Our work advances the design and utilization of chiral inorganic nanostructures for superior performance in energy conversion processes.

4.
medRxiv ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39006439

RESUMEN

Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.

5.
Trends Pharmacol Sci ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39019764

RESUMEN

Magnesium (Mg2+) is a commonly used dietary supplement for the prevention and treatment of diseases. However, the efficacy and mechanisms of action of Mg2+ in most diseases have been controversial because of conflicting findings in earlier studies. Recent clinical and preclinical studies provide novel insights into the use of Mg2+ for the treatment and prevention of diseases affecting different organ systems. In this review, we provide an overview of recent clinical evidence for, and controversies over, the medical benefits of Mg2+. In addition, we critically discuss recent advances in understanding the mechanisms of action of Mg2+, which could enable the development of novel targeted therapies.

7.
Water Sci Technol ; 90(1): 270-286, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39007319

RESUMEN

The completely autotrophic nitrogen removal over nitrite (CANON) process is significantly hindered by prolonged start-up periods and unstable nitrogen removal efficiency. In this study, a novel umbrella basalt fiber (BF) carrier with good biological affinity and adsorption performance was used to initiate the CANON process. The CANON process was initiated on day 64 in a sequencing batch reactor equipped with umbrella BF carriers. During this period, the influent NH4+-N concentration gradually increased from 100 to 200 mg·L-1, and the dissolved oxygen was controlled below 0.8 mg L-1. Consequently, an average ammonia nitrogen removal efficiency (ARE) and total nitrogen removal efficiency (TNRE) of ∼90 and 80% were achieved, respectively. After 130 days, ARE and TNRE remained stable at 92 and 81.1%, respectively. This indicates a reliable method for achieving rapid start-up and stable operation of the CANON process. Moreover, Candidatus Kuenenia and Candidatus Brocadia were identified as dominant anammox genera on the carrier. Nitrosomonas was the predominant genus among ammonia-oxidizing bacteria. Spatial differences were observed in the microbial population of umbrella BF carriers. This arrangement facilitated autotrophic nitrogen removal in a single reactor. This study indicates that the novel umbrella BF carrier is a highly suitable biocarrier for the CANON process.


Asunto(s)
Procesos Autotróficos , Reactores Biológicos , Nitritos , Nitrógeno , Nitrógeno/química , Nitritos/química , Eliminación de Residuos Líquidos/métodos , Bacterias/metabolismo
8.
Indian J Hematol Blood Transfus ; 40(3): 504-507, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39011245

RESUMEN

H-antigen deletion is often caused by FUT1 gene mutation, which is a very rare blood group. In this case, the H-antigen phenotype, FUT1, FUT2 sequences, and family genetic investigation of a 26-year-old patient (proband) and her three family members were studied. The results showed that the proband and little her brother were H-deficient phenotype, their ABO genotype of both was A/O1, her father was A/B, and her mother was O1/O1. The proband and her little brother's FUT1 phenotype were both h3|h3, with a homozygous mutation 658C > T in their FUT1 gene, and the FUT1 phenotype of their parents' were H|h3, with a heterozygous mutation (658C > T) in their FUT1 gene. The result of whole gene sequencing showed that the father of the proband had a deletion of CHR19.49,255,178-49,257,177 in the FUT1 gene (hg19 was used as the reference). The results of the family investigation showed that the mutation of site 658 in the FUT1 gene between offspring and parents was consistent with Mendelian inheritance law.

9.
Pharm Res ; 41(7): 1455-1473, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38955997

RESUMEN

PURPOSE: Polysorbates are among the most used surfactants in biopharmaceutical products containing proteins. Our work aims to develop a high-throughput fluorometric assay to further diversify the analytical toolbox for quantification of PSs. METHOD: The assay leverages the micelle activated fluorescence signal from N-Phenyl-1-Naphthylamine (NPN). The development and optimization of assay parameters were guided by the pre-defined analytical target profile. Furthermore, NMR was used to probe the interaction between protein, PS80 and NPN in the measurement system and understand protein interference. RESULTS: All assay parameters including excitation and emission wavelengths, standard curve, NPN concentration, and incubation time have been optimized and adapted to a microplate format, making it compatible with automated solutions that will be pursued in the near future to drive consistency and efficiency in our workflows. The specificity, accuracy, and precision of the assay have been demonstrated through a case study. Furthermore, NMR results provided additional insight into the change of the interaction dynamics between PS80 and NPN as the protein concentration increases. The results indicate minimal interaction between the protein and PS80 at lower concentration. However, when the concentration exceeds 75 mg/mL, there is a significant interaction between the protein and PS-80 micelle and monomer. CONCLUSION: A high-throughput fluorometric assay has been developed for quantification of polysorbates in biopharmaceutical samples including in-process samples, drug substance and drug product. The assay reported herein could serve as a powerful analytical tool for polysorbate quantification and control, complementing the widely used liquid chromatography with charged aerosol detection method.


Asunto(s)
Colorantes Fluorescentes , Fluorometría , Ensayos Analíticos de Alto Rendimiento , Micelas , Polisorbatos , Polisorbatos/química , Polisorbatos/análisis , Colorantes Fluorescentes/química , Ensayos Analíticos de Alto Rendimiento/métodos , Fluorometría/métodos , Tensoactivos/química , Tensoactivos/análisis , 1-Naftilamina/análogos & derivados , 1-Naftilamina/química , Productos Biológicos/análisis , Productos Biológicos/química , Espectroscopía de Resonancia Magnética/métodos
11.
Langmuir ; 40(29): 14941-14952, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38980061

RESUMEN

The objective of the current study is to prepare amorphous solid dispersions (ASDs) containing piperine (PIP) by utilizing organic acid glycyrrhizic acid (GA) and inorganic disordered mesoporous silica 244FP (MSN/244FP) as carriers and to investigate their dissolution mechanism. The physicochemical properties of ASDs were characterized with scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) and one-dimensional proton nuclear magnetic resonance (1H NMR) studies collectively proved that strong hydrogen-bonding interactions formed between PIP and the carriers in ASDs. Additionally, molecular dynamic (MD) simulation was conducted to simulate and predict the physical stability and dissolution mechanisms of the ASDs. Interestingly, it revealed a significant increase in the dissolution of amorphous PIP in ASDs in in vitro dissolution studies. Rapid dissolution of GA in pH 6.8 medium resulted in the immediate release of PIP drugs into a supersaturated state, acting as a dissolution-control mechanism. This exhibited a high degree of fitting with the pseudo-second-order dynamic model, with an R2 value of 0.9996. Conversely, the silanol groups on the outer surface of the MSN and its porous nanostructures enabled PIP to display a unique two-step drug release curve, indicating a diffusion-controlled mechanism. This curve conformed to the Ritger-Peppas model, with an R2 > 0.9. The results obtained provide a clear evidence of the proposed transition of dissolution mechanism within the same ASD system, induced by changes in the properties of carriers in a solution medium of varying pH levels.


Asunto(s)
Alcaloides , Benzodioxoles , Piperidinas , Alcamidas Poliinsaturadas , Dióxido de Silicio , Piperidinas/química , Benzodioxoles/química , Alcamidas Poliinsaturadas/química , Alcaloides/química , Porosidad , Dióxido de Silicio/química , Ácido Glicirrínico/química , Solubilidad , Simulación de Dinámica Molecular , Portadores de Fármacos/química , Tamaño de la Partícula
12.
J Biomed Mater Res A ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963690

RESUMEN

Approximately 5%-10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA-approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti-inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC-based therapies.

13.
ACS Appl Mater Interfaces ; 16(30): 39287-39294, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39026183

RESUMEN

In recent years, the triboelectric-electromagnetic hybrid generator (TEHG) has been widely studied. However, the problems of unsteady output and high starting wind speed of traditional TEHG in the wind energy environment have not been effectively solved. This work introduces an innovative solution in the form of a steady output triboelectric-electromagnetic hybrid generator (SO-TEHG) with variable drag turbine blades. The SO-TEHG integrates the energy management circuit to output steady electric energy under random wind conditions. In addition, the integration of variable drag turbine blades with the triboelectric nanogenerator (TENG) reduces the wind speed threshold required for SO-TEHG activation. In comparison to the traditional turbine blades, which necessitate a minimum wind speed of 3 m/s, the SO-TEHG's innovative design allows it to commence power generation at a lower 2 m/s wind speed, producing an additional output of 50 V. This enhanced starting capability in mild breezes positions the SO-TEHG as an ideal power source for applications. In practical farmland settings, experimental results conclusively demonstrate the SO-TEHG's ability to successfully activate soil hygrothermographs and hydrogen sensors. As a steady power source driven by gentle winds, the SO-TEHG holds tremendous promise for advancing smart agriculture.

14.
Front Bioeng Biotechnol ; 12: 1399689, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39045537

RESUMEN

Extracellular vesicles (EVs) are pivotal in intercellular communication, disease mechanisms. Despite numerous methods for EVs isolation, challenges persist in yield, purity, reproducibility, cost, time, and automation. We introduce a EVs isolation technique using Fe3O4@ZrO2 beads, leveraging ZrO2-phosphate interaction. The results indicated that EVs were efficiently separated from large volumes of samples in 30 minutes without preconcentration. Our method demonstrated capture efficiency (74%-78%) compared to ultracentrifugation, purity (97%), and reproducibility (0.3%-0.5%), with excellent linearity (R2 > 0.99). EVs from urine samples showed altered expression of miRNAs. The logistic regression model achieved an AUC of 0.961, sensitivity of 0.92, and specificity of 0.94. With potential for automation, this magnetic bead-based method holds promise for clinical applications, offering an efficient and reliable tool for EVs research and clinical studies.

15.
Bioessays ; : e2400117, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044599

RESUMEN

In cells, microtubules (MTs) assemble from α/ß-tubulin subunits at nucleation sites containing the γ-tubulin ring complex (γ-TuRC). Within the γ-TuRC, exposed γ-tubulin molecules act as templates for MT assembly by interacting with α/ß-tubulin. The vertebrate γ-TuRC is scaffolded by γ-tubulin-interacting proteins GCP2-6 arranged in a specific order. Interestingly, the γ-tubulin molecules in the γ-TuRC deviate from the cylindrical geometry of MTs, raising the question of how the γ-TuRC structure changes during MT nucleation. Recent studies on the structure of the vertebrate γ-TuRC attached to the end of MTs came to varying conclusions. In vitro assembly of MTs, facilitated by an α-tubulin mutant, resulted in a closed, cylindrical γ-TuRC showing canonical interactions between all γ-tubulin molecules and α/ß-tubulin subunits. Conversely, native MTs formed in a frog extract were capped by a partially closed γ-TuRC, with some γ-tubulin molecules failing to align with α/ß-tubulin. This review discusses these outcomes, along with the broader implications.

16.
J Xray Sci Technol ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38995761

RESUMEN

BACKGROUND: Chest X-rays (CXR) are widely used to facilitate the diagnosis and treatment of critically ill and emergency patients in clinical practice. Accurate hemi-diaphragm detection based on postero-anterior (P-A) CXR images is crucial for the diaphragm function assessment of critically ill and emergency patients to provide precision healthcare for these vulnerable populations. OBJECTIVE: Therefore, an effective and accurate hemi-diaphragm detection method for P-A CXR images is urgently developed to assess these vulnerable populations' diaphragm function. METHODS: Based on the above, this paper proposes an effective hemi-diaphragm detection method for P-A CXR images based on the convolutional neural network (CNN) and graphics. First, we develop a robust and standard CNN model of pathological lungs trained by human P-A CXR images of normal and abnormal cases with multiple lung diseases to extract lung fields from P-A CXR images. Second, we propose a novel localization method of the cardiophrenic angle based on the two-dimensional projection morphology of the left and right lungs by graphics for detecting the hemi-diaphragm. RESULTS: The mean errors of the four key hemi-diaphragm points in the lung field mask images abstracted from static P-A CXR images based on five different segmentation models are 9.05, 7.19, 7.92, 7.27, and 6.73 pixels, respectively. Besides, the results also show that the mean errors of these four key hemi-diaphragm points in the lung field mask images abstracted from dynamic P-A CXR images based on these segmentation models are 5.50, 7.07, 4.43, 4.74, and 6.24 pixels,respectively. CONCLUSION: Our proposed hemi-diaphragm detection method can effectively perform hemi-diaphragm detection and may become an effective tool to assess these vulnerable populations' diaphragm function for precision healthcare.

17.
Zookeys ; 1204: 223-240, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38882561

RESUMEN

In present study, a previously unidentified but frequently encountered species of deep-sea protobranch, Yoldiellahaimaensis sp. nov., is described new to science from the Haima Cold Seep on the northwestern slope of the South China Sea. A morphological analysis confirmed that this species belongs to a previously undescribed species of the genus Yoldiella A.E. Verrill & K.J. Bush, 1897. It differs morphologically from other known species within the genus in its shell shape, degree of inflation, beaks, and number of hinge teeth. Furthermore, we sequenced three gene segments of Y.haimaensis sp. nov., comprising a nuclear ribosomal gene (18S rRNA), a nuclear protein-coding gene (histone H3), and a mitochondrial gene (cytochrome c oxidase subunit I, COI). Our phylogenetic analysis performed on the superfamily Nuculanoidea and family Yoldiidae indicates that the genus Yoldiella is non-monophyletic, and the widely recognized families within the superfamily Nuculanoidea are also not monophyletic. Our results provide molecular insights into the Protobranchia and highlight the necessity for further samples and data to revise the classification of families and genera within the superfamily using an integrative approach that combines morphological analysis and molecular data.

18.
PLoS Negl Trop Dis ; 18(6): e0012151, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38843297

RESUMEN

BACKGROUND: Hemorrhagic Fever with Renal Syndrome (HFRS) continues to pose a significant public health threat to the well-being of the population. Given that the spread of HFRS is susceptible to meteorological factors, we aim to probe into the meteorological drivers of HFRS. Thus, novel techniques that can discern time-delayed non-linear relationships from nonlinear dynamical systems are compulsory. METHODS: We analyze the epidemiological features of HFRS in Weifang City, 2011-2020, via the employment of the Empirical Dynamic Modeling (EDM) method. Our analysis delves into the intricate web of time-delayed non-linear associations between meteorological factors and HFRS. Additionally, we investigate the repercussions of minor perturbations in meteorological variables on future HFRS incidence. RESULTS: A total of 2515 HFRS cases were reported in Weifang from 2011 to 2020. The number of cases per week was 4.81, and the average weekly incidence was 0.52 per 1,000,000. The propagation of HFRS is significantly impacted by the mean weekly temperature, relative humidity, cumulative rainfall, and wind speed, and the ρCCM converges to 0.55,0.48,0.38 and 0.39, respectively. The graphical representation of the relationship between temperature (lagged by 2 weeks) and the incidence of HFRS exhibits an inverted U-shaped curve, whereby the incidence of HFRS culminates as the temperature reaches 10 °C. Moreover, temperature, relative humidity, cumulative rainfall, and wind speed exhibit a positive correlation with HFRS incidence, with a time lag of 4-6 months. CONCLUSIONS: Our discoveries suggest that meteorological factors can drive the transmission of HFRS both at a macroscopic and microscopic scale. Prospective alterations in meteorological conditions, for instance, elevations in temperature, relative humidity, and precipitation will instigate an upsurge in the incidence of HFRS after 4-6 months, and thus, timely public health measures should be taken to mitigate these changes.


Asunto(s)
Fiebre Hemorrágica con Síndrome Renal , Conceptos Meteorológicos , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Humanos , China/epidemiología , Incidencia , Temperatura , Masculino , Femenino , Adulto , Persona de Mediana Edad , Humedad , Adulto Joven , Adolescente
19.
Diabetes Metab Syndr ; 18(6): 103043, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38908114

RESUMEN

AIMS: To assess the relationships between urate-lowering therapy (ULT) initiation with all-cause mortality in patients with asymptomatic hyperuricemia and Type 2 Diabetes (T2D). METHODS: This nationwide retrospective cohort study involved patients with T2D and asymptomatic hyperuricemia from 19 academic hospitals across China between 2000 and 2021. The primary exposure was ULT initiation, including allopurinol, febuxostat, or benzbromarone. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) and non-CV mortality. Propensity score matching was employed to create a 1:2 matched cohort with balanced likelihood of ULT initiation. Associations between ULT initiation with all-cause and CV mortality were assessed in the matched cohort. RESULTS: Among 42 507 patients, 5028 initiated ULT and 37 479 did not. In the matched cohort, comprising 4871 ULT initiators and 9047 noninitiators, ULT initiation was significantly associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.84), CV mortality (HR 0.86; 95% CI, 0.76-0.97), and non-CV mortality (HR 0.72; 95% CI, 0.64-0.80) over an average 3.0 years of follow-up. Among the ULT initiators, post-treatment SUA levels of 360-420 µmol/L was related to a significantly lower risk for all-cause mortality compared to levels >420 µmol/L (HR 0.74; 95% CI, 0.59-0.94) while levels ≤360 µmol/L did not (HR, 0.96; 95% CI, 0.81-1.14), suggesting a U-shaped relationship. CONCLUSIONS: Initiating ULT was associated with a significant reduction in all-cause mortality in patients with T2D and asymptomatic hyperuricemia. Notably, maintaining post-treatment SUA concentrations within 360-420 µmol/L could potentially enhance this reduced mortality.

20.
Cardiovasc Diabetol ; 23(1): 222, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926737

RESUMEN

BACKGROUND: Previous studies have shown that an elevated triglyceride-glucose (TyG) index was associated with all-cause mortality in both general adult individuals and critically ill adult patients. However, the relationship between the TyG index and clinical prognosis in pediatric patients admitted to the intensive care unit (ICU) remains unknown. We aimed to investigate the association of the TyG index with in-hospital all-cause mortality in critically ill pediatric patients. METHODS: A total of 5706 patients in the Pediatric Intensive Care database were enrolled in this study. The primary outcome was 30-day in-hospital all-cause mortality, and secondary outcome was 30-day in-ICU all-cause mortality. The restricted cubic spline (RCS) curves and two-piecewise multivariate Cox hazard regression models were performed to explore the relationship between the TyG index and outcomes. RESULTS: The median age of the study population was 20.5 [interquartile range (IQR): 4.8, 63.0] months, and 3269 (57.3%) of the patients were male. The mean TyG index level was 8.6 ± 0.7. A total of 244 (4.3%) patients died within 30 days of hospitalization during a median follow-up of 11 [7, 18] days, and 236 (4.1%) patients died in ICU within 30 days of hospitalization during a median follow-up of 6 [3, 11] days. The RCS curves indicated a U-shape association between the TyG index and 30-day in-hospital and in-ICU all-cause mortality (both P values for non-linear < 0.001). The risk of 30-day in-hospital all-cause mortality was negatively correlated with the TyG index until it bottoms out at 8.6 (adjusted hazard ratio [HR], 0.72, 95% confidence interval [CI] 0.55-0.93). However, when the TyG index was higher than 8.6, the risk of primary outcome increased significantly (adjusted HR, 1.51, 95% CI 1.16-1.96]). For 30-day in-ICU all-cause mortality, we also found a similar relationship (TyG < 8.6: adjusted HR, 0.75, 95% CI 0.57-0.98; TyG ≥ 8.6: adjusted HR, 1.42, 95% CI 1.08-1.85). Those results were consistent in subgroups and various sensitivity analysis. CONCLUSIONS: Our study showed that the association between the TyG index and 30-day in-hospital and in-ICU all-cause mortality was nonlinear U-shaped, with a cutoff point at the TyG index of 8.6 in critically ill pediatric patients. Our findings suggest that the TyG index may be a novel and important factor for the short-term clinical prognosis in pediatric patients.


Asunto(s)
Biomarcadores , Glucemia , Causas de Muerte , Enfermedad Crítica , Bases de Datos Factuales , Mortalidad Hospitalaria , Unidades de Cuidado Intensivo Pediátrico , Triglicéridos , Humanos , Masculino , Enfermedad Crítica/mortalidad , Femenino , Estudios Retrospectivos , Glucemia/metabolismo , Triglicéridos/sangre , Factores de Riesgo , Lactante , Preescolar , Factores de Tiempo , Medición de Riesgo , Biomarcadores/sangre , Pronóstico , Factores de Edad , Niño , Valor Predictivo de las Pruebas , Mortalidad del Niño
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