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JACC. Advances Feb 2024Treatment with vitamin K antagonists (VKAs) has been linked to worsening of kidney function in patients with atrial fibrillation (AF).
BACKGROUND
Treatment with vitamin K antagonists (VKAs) has been linked to worsening of kidney function in patients with atrial fibrillation (AF).
OBJECTIVES
XARENO (Factor XA-inhibition in RENal patients with non-valvular atrial fibrillation Observational registry; NCT02663076) is a prospective observational study comparing adverse kidney outcomes in patients with AF and advanced chronic kidney disease receiving rivaroxaban or VKA.
METHODS
Patients with AF and an estimated glomerular filtration rate (eGFR) of 15 to 49 mL/min/1.73 m were included. Blinded adjudicated outcome analysis evaluated adverse kidney outcomes (a composite of eGFR decline to <15 mL/min/1.73 m, need for chronic kidney replacement therapy, or development of acute kidney injury). A composite net clinical benefit outcome (stroke or systemic embolism, major bleeding, myocardial infarction, acute coronary syndrome, or cardiovascular death) was also analyzed. HRs with 95% CIs were calculated using propensity score overlap weighting Cox regression.
RESULTS
There were 1,455 patients (764 rivaroxaban; 691 VKA; mean age 78 years; 44% females). The mean eGFR was 37.1 ± 9.0 in those receiving rivaroxaban and 36.4 ± 10.1 mL/min/1.73 m in those receiving VKA. After a median follow-up of 2.1 years, rivaroxaban was associated with less adverse kidney outcomes (HR: 0.62; 95% CI: 0.43-0.88) and all-cause death (HR: 0.76, 95% CI: 0.59-0.98). No significant differences were observed in net clinical benefit.
CONCLUSIONS
In patients with AF and advanced chronic kidney disease, those receiving rivaroxaban had less adverse kidney events and lower all-cause mortality compared to those receiving VKA, supporting the use of rivaroxaban in this high-risk group of patients.
PubMed: 38939389
DOI: 10.1016/j.jacadv.2023.100813 -
JACC. Advances Feb 2024Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the...
BACKGROUND
Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the risk stratification and prognostication of heart failure (HF) patients. However, very few have been adopted clinically, owing to the lack of consistency.
OBJECTIVES
The authors aimed to study the association between cystatin C, NGAL, and KIM-1 and outcomes, mortality, hospitalizations, and worsening renal function (WRF) in patients with acute and chronic HF.
METHODS
We included peer-reviewed English-language articles from PubMed and EMBASE published up to December 2021. We analyzed the above associations using random-effects meta-analysis. Publication bias was assessed using funnel plots.
RESULTS
Among 2,631 articles, 100 articles, including 45,428 patients, met the inclusion criteria. Top-tertile of serum cystatin C, when compared to the bottom-tertile, carried a higher pooled hazard ratio (pHR) for mortality (pHR: 1.59, 95% CI: 1.42-1.77) and for the composite outcome of mortality and HF hospitalizations (pHR: 1.49, 95% CI: 1.23-1.75). Top-tertile of serum NGAL had a higher hazard for mortality (pHR: 2.91, 95% CI: 1.49-5.67) and composite outcome (HR: 4.11, 95% CI: 2.69-6.30). Serum and urine NGAL were significantly associated with WRF, with pHRs of 2.40 (95% CI: 1.48-3.90) and 2.01 (95% CI: 1.21-3.35). Urine KIM-1 was significantly associated with WRF (pHR: 1.60, 95% CI: 1.24-2.07) but not with other outcomes. High heterogeneity was noted between studies without an obvious explanation based on meta-regression.
CONCLUSIONS
Serum cystatin C and serum NGAL are independent predictors of adverse outcomes in HF. Serum and urine NGAL are important predictors of WRF in HF.
PubMed: 38939376
DOI: 10.1016/j.jacadv.2023.100765 -
JACC. Advances Feb 2024A blood multimarker approach may be useful to enhance risk stratification in patients undergoing TAVI.
BACKGROUND
A blood multimarker approach may be useful to enhance risk stratification in patients undergoing TAVI.
OBJECTIVES
The objective of this study was to determine the prognostic value of multiple blood biomarkers in transcatheter aortic valve implantation (TAVI) patients.
METHODS
In this prospective study, several blood biomarkers of cardiovascular function, inflammation, and renal function were measured in 362 patients who underwent TAVI. The cohort was divided into 3 groups according to the number of elevated blood biomarkers (ie, ≥ median value for the whole cohort) for each patient before the procedure. Survival analyses were conducted to evaluate the association between blood biomarkers and risk of adverse event following TAVI.
RESULTS
During a median follow-up of 2.5 (IQR: 1.9-3.2) years, 34 (9.4%) patients were rehospitalized for heart failure, 99 (27%) patients died, and 113 (31.2%) met the composite endpoint of all-cause mortality or heart failure rehospitalization. Compared to patients with 0 to 3 elevated biomarkers (referent group), those with 4 to 7 and 8 to 9 elevated biomarkers had a higher risk of all-cause mortality (HR: 1.54 [95% CI: 0.84-2.80], = 0.16, and HR: 2.81 [95% CI: 1.53-5.15], < 0.001, respectively) and of the composite endpoint (HR: 1.65 [95% CI: 0.95-2.84], = 0.07, and HR: 2.67 [95% CI: 1.52-4.70] < 0.001, respectively). Moreover, adding the number of elevated blood biomarkers into the clinical multivariable model provided significant incremental predictive value for all-cause mortality (Net Reclassification Index = 0.71, < 0.001).
CONCLUSIONS
An increasing number of elevated blood biomarkers is associated with higher risks of adverse clinical outcomes following TAVI. The blood multimarker approach may be helpful to enhance risk stratification in TAVI patients.
PubMed: 38939373
DOI: 10.1016/j.jacadv.2023.100761 -
Experimental and Therapeutic Medicine Aug 2024Triiodothyronine (T3) concentrations in plasma decrease during acute illness and it is unclear if this contributes to disease. Clinical and laboratory studies of T3...
Triiodothyronine (T3) concentrations in plasma decrease during acute illness and it is unclear if this contributes to disease. Clinical and laboratory studies of T3 supplementation in disease have revealed little or no effect. It is uncertain if short term supplementation of T3 has any discernible effect in a healthy animals. Observational study of intravenous T3 (1 µg/kg/h) for 24 h in a healthy sheep model receiving protocol-guided intensive care supports (T3 group, n=5). A total of 45 endpoints were measured including hemodynamic, respiratory, renal, hematological, metabolic and endocrine parameters. Data were compared with previously published studies of sheep subject to the same support protocol without administered T3 (No T3 group, n=5). Plasma free T3 concentrations were elevated 8-fold by the infusion (pmol/l at 24 h; T3 group 34.9±9.9 vs. No T3 group 4.4±0.3, P<0.01, reference range 1.6 to 6.8). There was no significant physiological response to administration of T3 over the study duration. Supplementation of intravenous T3 for 24 h has no physiological effect on relevant physiological endpoints in healthy sheep. Further research is required to understand if the lack of effect of short-term T3 may be related to kinetics of T3 cellular uptake, metabolism and action, or acute counterbalancing hormone resistance. This information may be helpful in design of clinical T3 supplementation trials.
PubMed: 38939174
DOI: 10.3892/etm.2024.12611 -
JACC. Advances Jul 2023Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients...
BACKGROUND
Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction.
OBJECTIVES
This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function.
METHODS
In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy.
RESULTS
Baseline eGFR <60 ml/min/1.73 m and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome ( interaction = 0.02) and death ( interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI.
CONCLUSIONS
In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.
PubMed: 38938997
DOI: 10.1016/j.jacadv.2023.100393 -
Mayo Clinic Proceedings. Digital Health Jun 2024This study aimed to review the application of natural language processing (NLP) in thyroid-related conditions and to summarize current challenges and potential future...
This study aimed to review the application of natural language processing (NLP) in thyroid-related conditions and to summarize current challenges and potential future directions. We performed a systematic search of databases for studies describing NLP applications in thyroid conditions published in English between January 1, 2012 and November 4, 2022. In addition, we used a snowballing technique to identify studies missed in the initial search or published after our search timeline until April 1, 2023. For included studies, we extracted the NLP method (eg, rule-based, machine learning, deep learning, or hybrid), NLP application (eg, identification, classification, and automation), thyroid condition (eg, thyroid cancer, thyroid nodule, and functional or autoimmune disease), data source (eg, electronic health records, health forums, medical literature databases, or genomic databases), performance metrics, and stages of development. We identified 24 eligible NLP studies focusing on thyroid-related conditions. Deep learning-based methods were the most common (38%), followed by rule-based (21%), and traditional machine learning (21%) methods. Thyroid nodules (54%) and thyroid cancer (29%) were the primary conditions under investigation. Electronic health records were the dominant data source (17/24, 71%), with imaging reports being the most frequently used (15/17, 88%). There is increasing interest in NLP applications for thyroid-related studies, mostly addressing thyroid nodules and using deep learning-based methodologies with limited external validation. However, none of the reviewed NLP applications have reached clinical practice. Several limitations, including inconsistent clinical documentation and model portability, need to be addressed to promote the evaluation and implementation of NLP applications to support patient care in thyroidology.
PubMed: 38938930
DOI: 10.1016/j.mcpdig.2024.03.007 -
Journal of Extracellular Biology Jan 2024Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV...
Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV long RNAs are among the critical cargos capable of providing unique transcriptome information of the source cells. However, consensus regarding ideal reference genes for relative long RNAs quantification in uEVs is not available as of date. Here we explored stable reference genes through profiling the long RNA expression by RNA-seq following unsupervised analysis and validation studies. Candidate reference genes were identified using four algorithms: NormFinder, GeNorm, BestKeeper and the Delta Ct method, followed by validation. RNA profile showed uEVs contained abundant long RNAs information and the core transcriptome was related to cellular structures, especially ribosome which functions mainly as translation, protein and RNA binding molecules. Analysis of RNA-seq data identified RPL18A, RPL11, RPL27, RACK1, RPSA, RPL41, H1-2, RPL4, GAPDH, RPS27A as candidate reference genes. RT-qPCR validation revealed that RPL41, RPSA and RPL18A were reliable reference genes for long RNA quantification in uEVs from patients with diabetes mellitus (DM), diabetic nephropathy (DN), IgA nephropathy (IgAN) and prostate cancer (PCA). Interestingly, RPL41 also outperformed traditional reference genes in renal tissues of DN and IgAN, as well as in plasma EVs of several types of cancers. The stable reference genes identified in this study may facilitate development of uEVs as novel biomarkers and increase the accuracy and comparability of biomarker studies.
PubMed: 38938675
DOI: 10.1002/jex2.136 -
Frontiers in Immunology 2024Nephritis is a frequent and severe complication of Systemic Lupus Erythematous (SLE). The clinical course of lupus nephritis (LN) is usually characterized by alternating... (Review)
Review
Nephritis is a frequent and severe complication of Systemic Lupus Erythematous (SLE). The clinical course of lupus nephritis (LN) is usually characterized by alternating phases of remission and exacerbation. Flares of LN can lead to deterioration of kidney function, necessitating timely diagnosis and therapy. The presence of autoantibodies against C1q (anti-C1qAb) in the sera of SLE patients has been reported in various studies. Some research suggests that the presence and changes in the titer of anti-C1qAb may be associated with the development of LN, as well as with LN activity and renal flares. However, the exact role of anti-C1qAb in LN remains a subject of debate. Despite variability in the results of published studies, anti-C1qAb hold promise as noninvasive markers for assessing LN activity in SLE patients. Measuring anti-C1qAb levels could aid in diagnosing and managing LN during periods of both inactive disease and renal flares. Nevertheless, larger controlled trials with standardized laboratory assays are necessary to further establish the utility of anti-C1qAb in predicting the reactivation and remission of LN and guiding treatment strategies.
Topics: Lupus Nephritis; Humans; Complement C1q; Biomarkers; Autoantibodies; Disease Management; Animals
PubMed: 38938561
DOI: 10.3389/fimmu.2024.1410032 -
Frontiers in Endocrinology 2024
Topics: Humans; Metabolic Syndrome; Renal Insufficiency, Chronic
PubMed: 38938518
DOI: 10.3389/fendo.2024.1442803 -
CHEST Critical Care Jun 2024A 48-year-old man with history of recent travel to central Mexico and immunosuppression sought treatment with a 1-month-long history of progressive headache, fatigue,...
A 48-year-old man with history of recent travel to central Mexico and immunosuppression sought treatment with a 1-month-long history of progressive headache, fatigue, word-finding difficulties, and night sweats. The patient had a history of end-stage renal disease; he had undergone a kidney transplantation 7 years prior with good graft function with immunosuppression with tacrolimus, everolimus, and low-dose prednisone. At an outside hospital, he recently had been treated with empiric antibiotics for meningitis, but these were discontinued given the low suspicion for a bacterial cause. After discharge, he continued to have headaches, limited oral intake, persistent nausea, urinary frequency, and falls, prompting him to seek treatment at the ED. Physical examination findings were benign aside from disorientation. Laboratory workup was significant for hyponatremia of 122 mM, creatinine of 1.4 mg/dL (baseline, 1.4-1.5 mg/dL), WBC count of 7.2 10/L, hemoglobin of 13 g/dL, and platelet count of 349 10/L. Neither tacrolimus nor everolimus levels were supratherapeutic.
PubMed: 38938509
DOI: 10.1016/j.chstcc.2024.100064